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Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition

Lynnette R. Ferguson, Helen Chen, Andrew R. Collins and 32 more

Seminars in Cancer Biology · 2015 · Review · CC BY

doi:10.1016/j.semcancer.2015.03.005

Abstract

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 19, 2026. Paragraph numbers are ours, so an answer can point at one.

Cellular mechanisms that prevent or promote genomic instability

Genomic instability plays critical roles in both cancer initiation and progression. This instability can manifest itself genetically on several different levels, ranging from simple deoxyribonucleic acid (DNA) sequence changes to structural and numerical abnormalities at the chromosomal level. This section will briefly outline the mechanisms that maintain the stability of nuclear and mitochondrial DNA and how these mechanisms may become corrupted in cancer cells.

Telomeres foster chromosomal stability and can inhibit or promote malignant transformation

The chromosome stabilizing role of intact telomeres was recognized as early as the 1930s from independent research by McClintock and Muller and more recent work has further strengthened the connection between telomere dysfunction and chromosomal instability (CIN),. Telomeres, which are located at the ends of each chromosome, consist of approximately 5–10 kbp of specialized, tandem repeat, noncoding DNA complexed with a variety of telomere associated proteins,. These elements create a protective cap that prevents the recognition of the chromosomal termini as DNA double strand breaks (DSBs) and their consequent aberrant repair via nonhomologous end joining (NHEJ) or homologous recombination (HR),,,. Due to the inability of DNA polymerase to fully replicate the ends of linear DNA molecules, in the absence of compensatory mechanisms, telomeric DNA is lost at the rate of approximately 100 base pairs (bp) per telomere per cell division,,,,,,. In normal somatic cells, this telomere erosion is used by the cell to monitor its division history, with moderate telomere shortening triggering either irreversible cell cycle arrest, termed replicative senescence, or apoptosis,,,. This block to continued proliferation is thought to have evolved to prevent the development of cancer in long-lived organisms by restricting the uncontrolled outgrowth of transformed cell clones, and also by preventing further telomere erosion which would accompany such abnormal growth and eventually destabilize the telomeres leading to CIN,.

A current popular model for the involvement of telomere shortening in carcinogenesis posits that increasing numbers of cells experience telomere shortening as a person ages, which increases the pool size of cells that are in danger of experiencing eventual telomere dysfunction and prooncogenic CIN. In the vast majority of such cells, the senescence and apoptotic blocks are strictly enforced,,,,,. However, this process eventually fails in rare cells which continue to replicate and eventually experience CIN due to critical telomere shortening,,,,,,,,,. Notably, such cells may be more tolerant of rampant genomic instability due to their previous abrogation of the tumor suppressive telomere length checkpoints. However, if left unchecked, this instability will eventually reach lethal levels in the transforming cells, thereby presenting a second block to the development of cancer,,,. This escalating telomere driven CIN creates a strong selective pressure for telomere maintenance in incipient cancer cell populations; a problem that is solved in one of two ways: activation of telomerase or alternative lengthening of telomeres (ALT). In the majority of human cancers, the telomere specific reverse transcriptase telomerase, which is stringently repressed in normal somatic cells, is activated, thereby restabilizing the telomeres, although cancer telomeres on average seem to remain very short,,,,,. Whereas most cancers use telomerase to maintain telomere length, a significant minority of cancers (typically non-carcinomas) utilize ALT, a telomerase independent, homologous recombination based mechanism,,. This mode of telomere maintenance results in extreme telomere length heterogeneity and, interestingly, better patient survival compared to their telomerase positive counterparts in several tumor types,,,. These observations suggest that cancer cells utilizing ALT may have compromised their vitality in exchange for the unlimited replicative potential conferred by this telomere maintenance mechanism.

Centrosomes, the spindle assembly checkpoint, and tumorigenesis

The centrosome is the primary microtubule organizing center in dividing mammalian cells and is composed of a pair of centrioles surrounded by a cloud of proteins that promote microtubule nucleation,. The centrosome is duplicated in a semiconservative fashion with one daughter centriole formed next to a preexisting mother centriole, and this process only occurs once in every cell cycle,. Centrosome amplification, the presence of greater than two centrosomes during mitosis, is a common characteristic of most solid and hematological tumors that may induce multipolar mitoses, chromosome missegregation, and subsequent genetic imbalances that promote tumorigenesis,.

Centrosome amplification may be caused by diverse mechanisms, including centrosome overduplication,,,, de novo assembly,,, and mitotic failure downstream from mono- or multipolar division,,,,,. The end result of these structural abnormalities is often cytokinesis failure, which can give rise to tetraploid binucleated cells and genome instability downstream. Over time, the net result is a small population of cells that harbor the ability to manage extra centrosomes, which could account for the accumulation of cancer cells with centrosome amplification and aneuploidy.

Catastrophic aneuploidy and nonviable daughter cells are a possible tumor suppressive consequence for centrosome abnormalities. However, cancer cells have developed mechanisms that overcome this fate by clustering multiple centrosomes into a “pseudobipolar” state,,,. Cancer cells may utilize this mechanism to dampen high level aneuploidy and extreme CIN, leading to better prognostic outcomes,. Centrosome clustering in tumor cells is not completely understood, but it is likely to rely on microtubule associated proteins and motor proteins that bundle together microtubules and centrosomes. Given that centrosome clustering may be advantageous for cancer cell survival, this process may be an attractive and specific therapeutic target,,. In theory, the induction of multipolarity through declustering of supernumerary centrosomes will selectively target cancer cells without affecting healthy cells,,,.

Bipolar chromosome attachment during mitosis is ensured by a quality control mechanism known as the spindle assembly checkpoint. The assembly checkpoint senses tension across kinetochores as a measure of bipolar attachment of chromosomes, and prevents the onset of anaphase in the presence of unattached and/or misattached chromosomes. Any failures to sense errors will compromise the checkpoint and, potentially, induce instability.

The assembly checkpoint relies upon kinase signaling to delay cell cycle progression and correct attachment errors. Aurora kinase B, for example, detects misattached chromosomes, and overexpression of the kinase is sufficient to disrupt the checkpoint and promote tetraploidy. Moreover, mutations or expression changes in other checkpoint gene products may compromise the checkpoint and favor tumorigenesis,,,. Lastly, oncogenic cues, such as overexpression of Aurora kinase A, may override a functioning checkpoint and enable cells to enter anaphase despite misattached chromosomes. Cancer cells may take advantage of the checkpoint for their own benefit. For example, checkpoint mediated delay provides time for centrosome clustering, which can be manipulated by disabling or restoring assembly checkpoint function. The ability to manipulate or hijack the cell's innate quality control mechanism may act as a selection pressure, and cancer cells that possess this ability may have a growth advantage over others.

Correlation between aberrant centrosome numbers and aberrant chromosome numbers dates back over 100 years, yet there is still a debate whether supernumerary centrosomes are the cause or the result of genomic instability, or vice versa. One interesting phenomenon that may shed light on this debate is the presence of a transient tetraploid state during tumorigenesis.

Tetraploidy arises after cytokinesis failure following prolonged activation of the assembly checkpoint, regardless of the reason for checkpoint activation. Depending on the status of tumor protein 53 (TP53), a tumor suppressor, the aborted postmitotic cells will either undergo apoptosis after prolonged cell cycle arrest or continue to cycle,,,,. In p53 null cells, a postmitotic checkpoint is compromised, which enables the cell to progress through a subsequent cell cycle with double the amount of centrosomes and genetic material,. Consequently, each subsequent division for these tetraploid cells will be more error prone, generating more unstable and detrimental aneuploidy. A TP53-dependent postmitotic checkpoint is frequently mutated during early stages of tumorigenesis,,,, which suggests that the tetraploid state serves as an intermediate for the aneuploid state observed in cancer cells. In patients with Barrett's oesophagus, the presence of tetraploid cells is detected before aneuploid cells and correlates with early loss of TP53. Tetraploid cells were also isolated from p53-/− mouse mammary epithelial cells, and these cells formed tumors in nude mice and showed increased aberrant mitoses and genomic instability in culture. Therefore, regardless of how centrosome amplification or genomic instability occurs in this “chicken or egg” argument, it is clear that either event is positively enhanced by the other in promoting tumorigenesis.

Epigenetic mechanisms contributing to genomic instability

A plethora of studies, including more recent genome-wide profiling, have demonstrated that epigenetic changes direct different cellular phenotypes in both normal and cancer cells,,. Epigenetics refer to all heritable changes that may modify gene expression without changing the primary DNA sequence, such as DNA methylation and chromatin remodelling. Epigenetic modifications are established during differentiation and are stably inherited and maintained through multiple rounds of cell division. Epigenetic processes that lead to genomic instability and ultimately malignant transformation constitute heritable changes that modulate gene expression and can also affect DNA repair dynamics,,.

DNA methylation consists of the addition of a methyl group at the carbon 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring,. Most cytosine methylation occurs in the context of cytosine-phosphate-guanine (CpG) dinucleotides, and occurs via a group of DNA methyltransferase enzymes resulting in silencing of gene transcription,. Aberrant changes in DNA methylation were among the first events to be recognized in cancer. Global hypomethylation in repetitive sequences of the genome can occur early during tumorigenesis and may initially predispose premalignant cells to repetitive sequence genomic instability. Furthermore, hypomethylation of the promoter of oncogenes can increase their expression and lead to genomic instability,. Similarly, aberrant sequence specific hypermethylation in cancer cells can lead to further genomic instability by the silencing of genes involved in cell cycle regulation and DNA repair. A prominent example is the aberrant methylation of CpG islands in the promoter regions of DNA mismatch repair (MMR) genes that result in cancer cells with a “mutator phenotype”,.

In addition to DNA methylation, histone molecules that form the primary protein component of chromatin also regulate genome stability as well as gene transcription. A number of posttranslational modifications such as acetylation, deacetylation, methylation, phosphorylation and ubiquitination have been identified that alter the function of histones. Various combinations of these posttranslational histone modifications have been hypothesized to form a “histone code” that dictate distinct chromatin structures that can affect genome stability pathways and transcription,,,. Acetylation of the lysine residues at the amino (N) terminus of histone proteins removes positive charges, thereby reducing the affinity between histones and DNA to facilitate access by ribonucleic acid (RNA) polymerase and transcription factors to gene promoter regions. Therefore, in most cases, histone acetylation enhances transcription while histone deacetylation represses transcription. In addition, histone acetylation can affect DNA repair by promoting histone dynamics that stimulate a DNA damage response in response to ionizing radiation,,,,,. Similarly, histone ubiquitination can also modify DNA repair capacity,,,,. Briefly, ubiquitinated histones can lead to chromatin structures that are conducive to the assembly of nucleotide excision repair complexes on damaged DNA, as well as both types of DSB repair pathways and cell cycle checkpoint factors critical for the DNA damage response,,,,,,,. Monoubiquitination of histones H2A and H2B prevents chromatin compaction and facilitates assembly of the repair machinery at the damaged sites. Polyubiquitination of histone H2A and H2AX is important for the retention of repair proteins, such as TP53 binding protein 1 (53BP1) and breast cancer 1 (BRCA1), at damaged loci,. Finally, histone phosphorylation is an early event following DNA damage and required for efficient DNA repair. Upon introduction of a DSB, hundreds of histone molecules become phosphorylated within minutes at the chromatin flanking the break site, thus providing a rapid and highly amplified detection system and a focus for the accumulation of many other proteins involved in DNA repair and chromatin remodelling. These examples, and numerous other observations, suggest that a vast array of epigenetic mechanisms contribute to the genomic instability in cancer cells.

Mitochondrial DNA alteration in human cancers

Mitochondrial genetic reprogramming and energy balance within cancer cells play a pivotal role in tumorigenesis and are duly regarded as one of the hallmarks of human cancer. In 1927, Otto Warburg, identified mitochondrial dysfunction as a key component of tumorigenesis and numerous studies have since elaborated upon the role of mitochondrial DNA (mtDNA) alterations in different human cancers.

Mitochondria are the key component of the oxidative phosphorylation system to generate cellular adenosine triphosphate. They uniquely possess their own DNA and generate reactive oxygen species (ROS). Most human cells contain hundreds of nearly homoplasmic (identical) copies of mtDNA, which are maternally inherited. Compared to the nuclear DNA, the mutation rate of mtDNA is nearly 10 times higher and alterations are much easier to detect due to their high copy number in cancer cells.

A substantial number of studies identified somatic mtDNA mutations involving coding and noncoding mtDNA regions in various cancers,,,,. Among the noncoding mtDNA mutations, a poly C mononucleotide repeat (known as D310) was frequently altered in numerous cancers and appeared to be a mutational hot spot. Notably, coding mtDNA mutations targeting respiratory complex I, III, IV or V were frequent in a variety of human cancers,,,,,,. Moreover, alteration of mtDNA copy number could potentially be associated with mitochondrial dysfunction leading to disease progression,. In recent studies, a correlation between mutations in mtDNA and epidermal growth factor receptor, or prostate-specific antigen expression, was established in lung and prostate cancer, respectively,. These results suggest cross talk between mitochondria and nuclear genomes maintain tumor growth.

In order to understand their role, a number of studies introduced mtDNA mutations in cancer cells. Introduction of a mitochondrial mutant adenosine triphosphate 6 (ATP6) (complex V) or cyclooxygenase 1 (COXI) (complex IV) increased the growth of prostate cancer cells, or induced cancer cell proliferation and altered reactive oxygen and nitrogen species, respectively. In a bladder cancer study, introduction of a mutant mitochondria encoded cytochrome B (CYTB) induced bladder cancer growth and invasion, accompanied with increased ROS, lactate production and oxygen consumption. Moreover, the ROS-producing CYTB mutant tumor cells efficiently killed normal splenic immune effector cells, which may provide tumor cells with an immune evasion mechanism. In addition, mutant CYTB overexpression in nontumorigenic bladder epithelial cells triggered an increased mitochondrial proliferation and inhibition of apoptosis. As these mutations in mtDNA were detected in human patients, the preceding studies suggest a causative role for mtDNA alterations in tumorigenesis.

Repair pathways responsible for genetic fidelity and tumor suppression

DNA is replicated with extreme fidelity in normal cells with a mutation rate of 10−10 per base pair per cell division. DNA damage typically occurs through the following: (1) exposure to agents such as ultraviolet irradiation, genotoxic chemicals, and ionizing radiation; (2) spontaneous DNA damaging events, such as a basic site formation; and (3) failure in normal cellular DNA processing and replication events, such as stalled replication forks. These processes induce oxidation, alkylation, crosslinking, dimerization, and strand breaks in DNA, which must be resolved. As such, repair of this DNA damage is essential to preserving genome integrity and preventing cancer.

Excision repair pathways

Three excision repair pathways can repair single stranded DNA damage: nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR).

Nucleotide excision repair

Fidelity of genetic information transmission depends on NER, which serves to repair DNA damage caused by ultraviolet irradiation, alkylating and oxidizing agents, or chemotherapeutic drugs that form bulky, helix distorting adducts. Two sub-pathways have been identified. Global genome NER repairs damage in both strands of the DNA regardless of whether the gene is being actively transcribed,,. Transcriptionally coupled NER, however, repairs transcriptionally active genes,,. The two pathways are similar in that they use many of the same pathways, but global genome NER uses xeroderma pigmentosum complementation group C (XPC)-RAD23 homolog B (HR23B) and DNA damage binding protein 1 (DDB1)-DDB2/XPE proteins to recognize distortions in the double helix while transcriptionally coupled NER occurs at regions where RNA Polymerase II has stalled,,,,. Genetic polymorphisms of NER gene products associate with human diseases, including xeroderma pigmentosum, which can lead to severe cases of skin cancer.

Base excision repair

The BER pathway fixes damaged DNA bases (reviewed in ). These lesions are recognized and removed by specific DNA glycosylases, which cleave the glycosidic bond between the damaged base and the sugar of the DNA backbone. In more complex lesions, proliferating cell nuclear antigen (PCNA), flap endonuclease 1 (FEN1), and DNA polymerase (POL) β, with or without POLδ/ɛ, act to repair the lesion. This complex set of events in BER is facilitated by poly (ADP-ribose) polymerase 1 (PARP1), which recruits proteins involved in the DNA repair response, such as X-ray repair cross-complementing protein (XRCC)1, DNA ligase, and DNA polymerase,.

Because cells are constantly subjected to DNA damaging conditions, the BER pathway is crucial to preserving genome integrity. This is exemplified by the embryonic lethality of mice that possess knockouts of key components of this pathway,,. A biallelic germline defect within a DNA glycosylase, mutY Homology (MUTYH), was initially found in families that had excess colorectal tumors with somatic mutations in the adenomatous polyposis coli gene. A subsequent larger study revealed that biallelic germline MUTYH defects conferred 93 fold excess risk of colon cancer with penetrance by age 60, and may also confer increased risk for endometrial cancer. Mutations in another glycosylase, 8 Oxoguanine (OGG1), have been associated with laryngeal cancers while gastric cancers harbor inactivating mutations in glycosylase nei endonuclease VIII-like 1 (NEIL1). Taken together, these studies confirm the importance of BER in the suppression of carcinogenesis.

DNA mismatch repair

Some evidence suggests that proofreading activity of replicative DNA polymerases and MMR machinery act in series in mammalian cells,,,. MMR targets could generally be classified into base/base mispairs and large insertion–deletion loops. At the forefront of error recognition, MutS protein homolog (Msh) 2 pairs with Msh6 or Msh3, to form MutSα (Msh2/Msh6) and MutSβ (Msh2/Msh3). Whereas the former is mostly responsible for base/base mispairs, the latter targets large insertion–deletion loops. To initiate the repair process, MutL homolog 1(Mlh1)/Pms2 heterodimers (MutL homologues), in the presence of exonuclease1, interact with MutS complexes to create nicks in the 3′ and 5′ of the nascent strand containing the mismatch. Following nick creation, enzymes required to repair the damage site are recruited and resynthesis of the DNA is carried out by POLδ/ɛ. As a nexus for DNA damage sensing and cell death, MMR machinery play an important role in recognizing damaged DNA and relaying signals downstream to activate a G2/M cell cycle checkpoint.

Double strand break repair and cancer predisposition

The DSB is the most lethal form of DNA damage, as it can lead to significant DNA damage by multiple genomic changes, including translocation formation, deletions, and amplifications, resulting in heritable cellular genomic instability/damage that can lead to malignancy,,. DSBs are repaired by both HR and NHEJ repair pathways. NHEJ repair occurs throughout the cell cycle, while HR prevails in S and G2 phase cells (reviewed,,, ). NHEJ repair joins broken DNA ends without identifying DNA sequence homology and is therefore highly error prone. HR repair is dependent upon DNA sequence homology and therefore is relatively error free,,.

Errors in the NHEJ pathway may generate inappropriate dicentric chromosomes that are covalently joined (reviewed,, ). These dicentric chromosomes may break during anaphase, producing new dicentric chromosomes through further NHEJ,. This process is known as the breakage fusion bridge (BFB) cycle, which is important in telomere related genome instability. Damaged telomeres will be processed by NHEJ, unless the broken ends are healed by a new telomere, and continuation of the BFB cycle can result in complex chromosomal rearrangements that include gene loss, gene amplification and unbalanced translocations,. BFB cycles are self-perpetuating and result in genetic heterogeneity in a variety of cancers.

HR repair involves multiple gene products some of which are involved in repair of stalled replication forks. The DSB is recognized by a Mre11-Rad50-NBS1 complex which recruits many different proteins, including proteins with topoisomerase, endonuclease, and helicase activity. Eventually a “synaptic complex” is formed which allows homologous single strand DNA (ssDNA) to invade and anneal to complementary DNA. DNA polymerase then fills in the ssDNA gap and the synaptic complex is resolved. Both crossover and non-crossover products can be created by this process,,,. Interestingly, loss or mutation of many of these gene products is associated with specific cancer prone diseases.

BRCA1 and BRCA2 are key players in the HR repair pathway and act as tumor suppressors by maintaining genome stability. Linkage studies in families with early onset breast cancer detected the presence of a breast cancer susceptibility gene, BRCA1. Subsequently, mutations in BRCA1 were confirmed in families with early onset breast and ovarian cancer,,,. Later, a novel locus, encoding BRCA2, was discovered and linked to breast cancer susceptibility,,. In one meta-analysis, cumulative breast and ovarian cancer risks for BRCA1 mutation carriers are 57 and 40%, respectively, while, for carriers of BRCA2 mutations, these risks are 49 and 18%, respectively. Furthermore, hereditary BRCA mutations have been also linked to pancreatic, prostate, and colon cancers. Of interest, germline mutations in BRCA1 versus BRCA2 associate with different subtypes of breast cancer. BRCA1 associated cancers are of the more aggressive triple negative subtype and appear at an earlier age than sporadic tumors. In contrast, BRCA2-associated tumors relate mostly with hormone receptor positive breast cancers.

Like BRCA1 and BRCA2, partner and localizer of BRCA1 (PALB2) promotes genome integrity through its role in DSB repair. It binds and colocalizes with BRCA2 in the nucleus to stabilize BRCA2 foci and facilitate the intra S phase checkpoint and HR repair. Germline mutations in PALB2 confer a 2–5 fold increase in breast cancer risk, and germline mutations have been recently found in African American breast cancer patients,. PALB2 mutations have also been observed in 1% of Chinese women with early onset breast cancer. Interestingly, exome sequencing identified PALB2 as a pancreatic cancer susceptibility gene and PALB2 mutations have been found in patients with familial pancreatic cancers,.

Fanconi anemia (FA) is an autosomal recessive disorder characterized by congenital defects, CIN, hypersensitivity to DNA crosslinks, bone marrow failure, and predisposition to cancer,. Fifteen FA or FA-like genes have been identified, all of which are involved in coordinating DNA repair through the FA/BRCA pathway. Interestingly, two of these genes are BRCA2 (FANCD1) and PALB2 (FANCN), thus revealing interplay between FA and HR,. Patients with FA have increased susceptibility to breast, ovarian, and oral cancers. Additionally, heterozygote carriers of germline mutations in FA genes may also harbor an increased risk to develop cancer. Importantly, unlike the BRCA-associated cancers, tumors from FA patients, or with acquired FA defects, may be hypersensitive to crosslinking agents such as cisplatin and mitomycin C, and also are hypersensitive to radiation,,. Finally, biallelic loss of ataxia telangiectasia mutated (ATM) results in ataxia telangiectasia, a disease characterized by a roughly 1000 fold increased lymphoma incidence,.

Therapeutic targeting of genomic instability

Current standard therapies for cancer often involve agents or strategies that damage the DNA, which can also damage noncancerous tissues. New treatments that target genomic instability (Fig. 1) may minimize these off target toxicities to normal tissues.

Targeting DNA repair pathways in cancer therapy

Drugs that target DNA repair proteins have shown preclinical and/or clinical efficacy in potentiating DNA damage (reviewed in ). Synthetic lethality, whereby deficiencies in parallel pathways are only cytotoxic when both pathways are defective, is a novel strategy that may selectively target cancerous cells defective in DNA repair. Synthetic lethality was illustrated in BRCA deficient cells, which exhibited profound sensitivity to inhibition of PARP,. This was due to conversion of unrepaired single strand breaks into DSBs during DNA replication due to the BRCA deficiency. Persistence of the unrepaired DSBs led to profound cellular cytotoxicity. The potential efficacy of PARP inhibitors in patients with BRCA-associated cancers has been reported in multiple clinical trials,,,,,. Perhaps more important is the high therapeutic index of these compounds, since noncancerous cells in this patient population still maintain one wild type allele and thus remain HR proficient. Natural products have also been shown to act on PARP, such as isothiocyanates, which are found in Brassica vegetables. Isothiocyanates stimulate the proteolytic cleavage of PARP. Recent work implicates vitamin D as a possible treatment mechanism to supplement PARP treatment. BRCA1-deficient cells bypass growth arrest by activating cathepsin L (CTSL)-mediated degradation of 53BP1. Vitamin D depletes or inhibits CTSL leading to increased genomic instability and compromised cancer cell proliferation after irradiation and treatment with PARP inhibitors. Selenocysteine can induce ROS formation, which can lead to DSBs in cancer cells but not in normal human fibroblasts. Thus, DSB repair deficient cancers may be sensitive to treatment with selenium compounds.

In addition to defective DSB repair, inappropriate HR often results in a significant predisposition to cancer development,. Many human malignancies with HR deficiency show increased sensitivity to chemotherapy agents that cause DSBs, such as ionizing radiation, bleomycin, and cisplatin. Additionally, agents which inhibit DNA replication, such as bifunctional alkylating agents and topoisomerase inhibitors, also preferentially inhibit the growth of HR deficient malignant cells,,. There has been intense interest in identifying HR deficiencies in human tumors and targeting these tumors with DSB-inducing chemotherapeutic agents. Since ∼25% of human malignancies show HR defects, targeted treatment could eventually play a significant role in chemotherapy. As tumors often overexpress specific proteins involved in HR, this approach might also preferentially target tumor over normal tissue,,,. A major challenge in this area is the efficient and accurate identification of HR deficiency in human malignancies.

Some of the proteins that have been proposed as useful targets to inhibit HR include ATM, checkpoint kinase (CHK)1&2, ataxia telangiectasia and Rad3 related (ATR), and the FA pathway proteins. Many inhibitors that target these enzymes are either in preclinical development or in the early phases of clinical development,. Resveratrol may activate sirtuin 1 (Sirt1) activity, which is a nicotinamide adenine dinucleotide-dependent deacetylase that is known to activate DNA repair. Studies in mice have shown that Sirt1+/−; p53+/− mice develop tumors in many different tissue types but mice treated with resveratrol display a reduced amount of tumorigenesis, indicating that resveratrol could act to prevent and/or treat cancers in patients that have reduced Sirt1 function. Although in early development, therapies that specifically alter HR are a promising area of research and may contribute to targeted chemotherapy regimens that are more personalized and effective.

Targeting microsatellite instability

MMR inactivation is associated with the lack of repair of replication errors leading to an increase in spontaneous mutation rate. A marker of defective MMR is microsatellite instability (MSI), or numerous alterations in the lengths of microsatellites,. Tumors displaying MSI are said to exhibit a “mutator phenotype”, with a dramatic predisposition to somatic mutations.

The critical role of MMR pathways in tumorigenesis is exemplified by the fact that germline mutations in the genes involved in MMR predispose to cancer development. In the case of colorectal cancer (CRC), MMR deficiency is estimated to be present in 15 to 17% of all primary cancers, including both sporadic CRC and Lynch syndrome (then called hereditary nonpolyposis colorectal cancer), though through different mechanisms,,. Lynch syndrome is characterized by inactivating germline mutations to MSH2, MSH6, PMS2, or MLH1, whereas MLH1 expression is silenced due to biallelic hypermethylation in sporadic CRC,,,,. MLH1 methylation results from extensive aberrant promoter methylation,. The 3′ end of the MLH1 promoter, proximal to the start codon, is most commonly methylated. Methylation of the 5′ end of the MLH1 promoter can also occur, however, the methylation pattern must extends to the 3′ end to be deleterious. Loss of MLH1 expression increases with age and protein expression is lost by ∼50% in patients who are 90 years or older. The exact mechanism(s) behind MLH1 silencing remain unknown, but may result from abnormal methylation, structural chromatin changes that increase accessibility to promoter regions, or genomic damage. Tumors with mutations in the MLH1 gene are rare, which suggests that hypermethylation of the MLH1 promoter is an important event in neoplastic transformation in sporadic CRC.

The extent of MSI in CRC has been classified as MSS (microsatellite–stable), MSI-H (with high level of instability), and MSI-L (with low level of instability). Classification between MSI-H and MSI-L depends on which MSI markers are present and their proportions. These markers include mononucleotide repeats, such as BAT25, BAT26, and BAT40, and the dinucleotide repeats D5S346, D2S123, and D17S250,,,. Dinucleotide markers are present in both MSI-H and MSI-L cancers, whereas mononucleotide markers are specific for MSI-H cancers. In MSI-H tumors, more than 30% of these markers are unstable, while in MSH-L tumors, 10–40% of these markers are unstable, and MSS tumors demonstrate no unstable markers,,,,. MSI-L and MSS tumors are frequently grouped together due to similarities in their clinical features and gross abnormalities. MSI-H is most prevalent in sporadic CRC, observed in 10–15% of all cases,.

The predictive value of MMR status as a marker of response to 5 fluorouracil, irinotecan and other drugs is still controversial. Recently, two large retrospective analyses from several randomized trials confirmed the detrimental effect of a 5 fluorouracil-based adjuvant therapy in stage II colorectal patients, not applicable to stage III patients. These latter authors, however, reported that MSI stage III tumors harboring genetic mutation in the MMR genes seem to benefit from the 5 fluorouracil adjuvant therapy. These data imply that molecular differences within the MSI subgroup influence the response to 5 fluorouracil.

The CRC MSI subgroup represents a cancer with a defined molecular etiology, a characterized mutational profile and an established genotype–phenotype relationship, which may enable synthetic lethal approaches that target MMR deficiency. High throughput experiments revealed synthetic lethal interactions between MSH2 and POLB, between MLH1 and Polymerase G gene, between RAD54B and FEN1,, between MLH1/MSH2 and PTEN-induced putative kinase 1 gene, and the preferential effect of methotrexate in MMR deficient systems. These synthetic interactions may induce or accumulate ROS,. A phase II randomized clinical trial in MLH2-deficient metastatic CRC (NTC00952016) is currently underway. Combination therapy with methotrexate and PARP inhibitors may be effective against tumors with MMR mutations. Methotrexate elevates ROS and DSBs and the combination of MMR mutation and PARP inhibition may attenuate repair and induce growth arrest or apoptosis,,.

Targeting gene expression of cell cycle and DNA repair components

RNA interference (RNAi) may enable personalized antitumor therapies. A number of RNAi-based studies have silenced genes responsible for tumor cell growth, metastasis, angiogenesis, and chemoresistance. For example, siRNA targeting of Cyclin E suppressed tumor development. Epigenetic regulation of gene expression is an alternative approach. Resveratrol, a phytoalexin produced by plants such as the Japanese knotweed, prevents hypermethylation of the BRCA1 promoter, and may be effective for triple negative or basal subtype breast cancers. Other natural compounds, like genistein and lycopene, can alter DNA methylation of the glutathione S transferase p1 (GSTP1) tumor suppressor gene.

Targeting centrosome abnormalities

Centrosome amplification is an important process during early stages of cancer development (see Section 1.2). Though the mechanism(s) behind centrosome amplification remain elusive, TP53 negatively regulates centrosome amplification through a TP53-p21-CDK2 signaling loop,. Moreover, TP53 induces apoptosis through transactivation of proapoptotic genes and transrepression of antiapoptotic genes. Thus, TP53 provides an interesting link between two major cancer processes, centrosome amplification and apoptosis dysregulation. In one study, the loss of TP53, or treatment with 5 fluorouracil, promoted centrosome amplification in HCT116 cells and those cells with supernumerary centrosomes were more acutely sensitive to resveratrol. However, TP53 defective cancer cells that resist 5 fluorouracil treatment are prone to centrosome amplification and downstream genome instability. The presence of supernumerary centrosome can also be problematic for cancer cells. Clustering excess centrosomes may be a necessary prosurvival pathway for cancer cells and thus an attractive target. Griseofulvin, an antifungal drug that suppresses proliferation in tumor cells without affecting non-transformed cells, declusters centrosome, although the precise mechanisms behind the drug's action remain unknown. In a similar fashion, depletion of a kinesin-like motor protein can selectively kill tumor cells with supernumerary centrosomes. Finally, the PARP inhibitor PJ34 also declusters supernumerary centrosomes without deleterious effects on spindle morphology, centrosome integrity, mitosis, or cell viability in normal cells.

Prevention of genomic instability and human cancer

There is no question that optimizing nutrient intake plays a significant role in stabilizing the genome. In recent years, an increasing number of biomarkers of genome integrity, including telomere length and mtDNA deletions, have been utilized in establishing recommended daily intakes for nutrients. In several cases, such an approach has led to substantial changes in the levels of various nutrients that populations had been previously advised to consume. These findings highlight the need to better optimize an individual's diet to their personal genetic makeup, which in turn has prompted the emergence of nutrigenomics, a new field that aims to determine how a particular genotype or expression profile correlates to nutrient metabolism, absorption, etc. (reviewed in, ).

Vitamins–carotenoids

Since Peto et al. concluded that the evidence pointed to a cancer preventive role for β carotene, many placebo-controlled carotenoid intervention trials have been carried out with disease and mortality as outcomes. Early findings were that, in subjects who were smokers and/or asbestos workers, there was a significant increase in lung cancer incidence. A recent meta-analysis confirmed that a significant increase in mortality is associated with vitamin A, β carotene or vitamin E supplements. When determining the effects that dietary supplements and other compounds have on cancer prevention, it is important to take into account the different types of data: conventional intervention studies, animal experiments, cell culture studies, or human intervention trials based on biomarkers. This is important because of the nature of each type of experiment and the information that can be obtained from them.

Human biomarker trials with molecular endpoints

Human trials with carotenoids,,,,,,,,, were mostly cross sectional or case control studies, with a few intervention trials. In general, a negative correlation was seen between blood carotenoid levels and various biomarkers of DNA damage, and intervention trials tended to show a decrease in DNA damage or no effect.

Animal experiments

Most animal experiments,,,,,,,,,,,,, involved treatment of rats or ferrets with genotoxic agents during or after carotenoid supplementation, and generally decreased levels of DNA damage were reported. Another study looked at base oxidation in leukocytes and oxidation products in urine, reporting a carotenoid-induced decrease in the former (but no effect on urinary biomarkers). There was a decrease in endogenous DNA oxidation in liver of mice fed tomato paste (rich in lycopene).

Cell culture experiments

We found eleven cell culture studies,,,,,,,,,, with provitamin A carotenoids (α and β carotene, β cryptoxanthin, retinoic acid, retinal and retinol), and eight with nonvitamin A carotenoids (lycopene, lutein, astaxanthin or zeaxanthin),,,,,,,. Experiments in most cases involved cotreatment with DNA damaging agent and carotenoid. Concentrations of carotenoid varied widely, from less than 1–100 μM. Here we found a very clear pattern in the results, depending on the type of carotenoid and the concentration: while the non-vitamin A carotenoids invariably resulted in a decrease in DNA damage, the provitamin A carotenoids at low concentrations either had no effect or decreased DNA damage, while at concentrations above about 5 μM, increases in damage were the norm. Potential prooxidant effects of carotenoids can probably be ruled out as a cause of this DNA damage, since there is no obvious reason why provitamin A carotenoids should be more likely to act as prooxidants. Instead, we should perhaps be looking at downstream effects of vitamin A itself, on transcription, via retinoic acid and retinoic acid receptors binding to retinoic acid response elements present in the regulatory sequence of many genes.

In a review of effects of carotenoids on DNA repair, we found relatively few reports. Cells from the spleen of rats supplemented with carotenoids (plus nicotinamide and zinc) showed accelerated repair of DSBs induced by radiation, and lymphocytes from human subjects given the same supplement mix were faster at rejoining hydrogen peroxide induced breaks. Mixed carotenes plus α tocopherol as a supplement in humans had no effect on DNA repair. DSB rejoining was faster in Molt 17 cells in the presence of β carotene, lutein or β cryptoxanthin, and in HeLa and Caco2 cells with β cryptoxanthin; but no effect was seen in lymphocytes incubated with β carotene or lycopene or with vitamin A.

Lung cells from ferrets supplemented with β carotene were tested for BER capacity with an in vitro comet-based assay, and showed an increase in activity. B cryptoxanthin enhanced BER of 8 oxoguanine in HeLa and Caco2 cells, but no effect of carotenoids was seen in Molt 17 cells or lymphocytes.

The pattern that emerges from this survey of carotenoid effects on DNA damage is that, in cell culture at least, while nonvitamin A carotenoids tend to decrease damage (whether endogenous or induced), at whatever concentration, the provitamin A carotenoids show a clear tendency to cause or increase damage at high concentrations. Whether this can account for the apparent harmful effects of β carotene as seen in the human clinical trials is not possible to answer at present.

Glutathione is another important antioxidant that can improve outcomes for patients with cancer and can help reduce treatment toxicity. Some studies have shown that supplementation with glutathione can reduce the toxicity of chemotherapy agents such as cisplatin and cyclophosphamide during treatment,. Interestingly, while the antioxidant properties of glutathione may reduce treatment toxicity, the same properties can make tumor cells resistant to chemotherapy when glutathione is present in high levels in the cells,. A GSTP1 polymorphism (GSTP1 Ile105Val), which has a seven fold higher efficiency, has been linked to a reduced survival rate in cancer patients further emphasizing that while glutathione may be able to reduce treatment toxicity, it can potentially also confer an advantage to the tumor cells as well,.

An additional aspect that may lead to conflicting results regarding the efficacy of antioxidants in cancer treatment is the oxidative stress that tumor cells experience in their microenvironment. Tumor cells have been shown to undergo the Warburg effect, which is where they produce energy primarily through glycolysis rather than through aerobic respiration (; reviewed in ). The production of lactate in tumor cells rather than pyruvate, an antioxidant, increases the load of ROS and increases oxidative stress in the cancer cells. Recent work has suggested that cancer cells might be targeted by using 3 bromopyruvate, an inhibitor of the glycolysis enzyme hexokinase II, to amplify the Warburg effect in cells.

Other vitamins

A range of B vitamins, including niacin (vitamin B3), folate (vitamin B9), and vitamin B12, significantly interact to maintain the stability of both nuclear and mitochondrial genomes. For example, a niacin deficiency, common in certain populations, impairs the function of the PARP family of enzymes, identified above as critical to DNA repair. A folate deficiency, especially in the presence of suboptimal levels of vitamin B6 and vitamin B12, may have significant effects on the expression of chromosomal fragile sites, leading to chromosome breaks, micronuclei and deletions of mtDNA. It may also lead to reduced telomere length. There are considerable interindividual differences in people's capacity to absorb and metabolize these vitamins, dependent upon genotype and epigenotype.

Vitamin C is considered an antioxidant, and is present at high concentrations (mM) in certain tissues such as the eye. Effects on various markers of genome stability were shown to depend on individual diet-derived vitamin C concentrations, and also on exposure to xenobiotics or oxidative stress. Vitamin D is also critical in the maintenance of genome stability, possibly through protection against oxidative stress, chromosomal aberrations, telomere shortening and inhibition of telomerase activity.

Minerals

While a number of minerals are typically considered as toxicants, there are several that are essential micronutrients, albeit usually with a narrow window of efficacy as compared with toxicity. These include iron, selenium, and zinc.

Selenium provides a useful illustration of the complexities of reaching agreement on optimal population levels. The population as a whole shows a “U” shaped curve for functionality, where low and high selenium levels both increase genomic instability. Optimal levels of selenium may protect against DNA or chromosome breakage, chromosome gain or loss, damage to mtDNA, and detrimental effects on telomere length and function. One example of how selenium can function is by protecting genome stability through a BRCA1-dependent mechanism. When cells are supplemented with selenium, there is reduced DNA breakage and the number of aneuploid cells is reduced when compared to control cells. Unfortunately, these optima differ among individuals and according to the form of selenium in the diet,. Various genetic polymorphisms have been shown to affect the uptake and utilization of selenium among individuals.

Other dietary factors

Diets high in plant-based foods have been associated with decreased cancer risks. Lim and Song discuss how certain dietary components, common in plant foods, can alter DNA methylation levels, affecting genome stability and transcription of tumor suppressors and oncogenes. Much of the available data exist for folate, since this is a well-recognized nutritional factor in one-carbon metabolism, acting to supply the methyl units for DNA methylation. This has been shown to be especially important in the maternal diet as a lack of folate can lead to hypomethylation of some genes in their offspring. One well studied example of this is the Agouti mutation in mice, which affects coat color, as well as making the offspring more susceptible to cancer and obesity,. The Agouti mutation has been shown to be a lack of methylation at the promoter of the Agouti gene. Pregnant mice that were fed bisphenol A had offspring that exhibited hypomethylation of the Agouti gene but, by feeding them dietary supplements of folate, methylation status was rescued. This data demonstrates the importance of the maternal diet during development to outcomes even later in life for their offspring. In other systems, folate supplements during pregnancy have also been shown to be protective against neuroectodermal brain tumors.

Alcohol, various polyphenols, phytoestrogens and lycopene also have demonstrable effects. Indeed, there is compelling evidence that a considerable range of plant polyphenols may stabilize genomic DNA, through various processes, including effects on DNA methylation. Duthie suggested that the evidence is particularly strong for berry phytochemicals, specifically anthocyanins (a class of flavonoids), which modulate various biomarkers of DNA damage and carcinogenesis, in both in vitro and in vivo animal studies. However, evidence for cancer preventive effects in human studies is currently weak.

Accumulating evidence shows that genome integrity is highly sensitive to nutrient status, and that optimal levels may differ among individuals. Many investigations to date are limited by considering only the effects of single nutrients, without looking at the potential interactions among these, and of nutrients with toxicants in the diet. Many currently available studies also suffer from a failure to consider the effects of genetic susceptibility. In subsequent work, it will be critical to consider modifying and interactive effects with deficiencies in nutrients required for effective DNA damage response, and DNA repair.

Hyperglycemia and a high fat diet have been shown to be positively correlated with an increased risk of cancers, such as breast and endometrial cancers. Hyperglycemic diets have been shown to increase the levels of many signaling molecules. Rats that were fed high fat diets had an increased risk of breast cancer in their progeny. These results were similar to those seen when mice are treated with estradiol. In addition to an increased risk of developing cancer, hyperglycemia, diabetes, and obesity have been linked to a worse prognosis. Advanced breast cancer patients with high blood glucose levels had a lower rate of survival than those with normal sugar levels and obese adolescents with pediatric acute lymphoblastic leukemia had a higher likelihood of relapse than a normal cohort.

Complementary effects on the enabling characteristics of cancer while targeting genomic instability

Treatments that are less cytotoxic but can also act on multiple different cancers and pathways that contribute to cancer formation is an important goal (Table 1). Work focusing on the effects of vitamin D, vitamin B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates has shown promising results (Table 2).

During cancer formation, genetic instability interacts with many other pathways that are integral to the survival and proliferation of the cancer cells, such as inflammation, immune system evasion, or apoptosis resistance. Preventing and/or treating genomic instability can cause tumor cells to lose: (1) their replicative immortality; (2) their ability to evade the immune system; and/or, (3) their ability to evade antigrowth signaling (Table 1). For example, in MSI-H CRCs, the immune response can be evaded by mutations in the neoantigens caused by defects in DNA repair machinery. In this case, by preventing genomic instability, it could be possible to minimize the mutations that lead to immune system evasion.

Sustained proliferative signaling is required for cancer cell growth and vitamin D and resveratrol are able to inhibit this signaling,,. There are no known interactions for the other compounds, except selenium, which inhibits growth in some cases while inducing it in others,. In a related characteristic of cancer cells, evasion of antigrowth signaling, all compounds are able to inhibit growth except vitamin B, which shows no relationship, and carotenoids, which have mixed results,,,,,,,,,. Similarly, all of the compounds are able to prevent replicative immortality by impairing telomerase activity or inducing senescence,,,,,,,,,, and increasing cell death except for vitamin B, which has no known relationship to apoptosis,,,,,. Dysregulated metabolism also contributes to cancer cell growth and all of the compounds had complementary effects on metabolic pathways except vitamin D and PARP inhibitors, which have no known link,,,,,,.

Cancer cells use inflammatory agents in the microenvironment to promote their proliferation and survival. One important inflammatory signaling molecule is nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), a transcription factor whose aberrant regulation has been linked to cancer,. Inflammatory signaling, including that of NFκB, can be affected by the diet. It has been shown that compounds found in cruciferous vegetables can reduce NFκB signaling in pancreatic cancer cells. Polyphenols have also been shown to suppress transcription factors upstream of NFκB. Inflammation, in general, is also inhibited by all of the compounds, except vitamin B,,,,,,,,,,,,,,, while only vitamin D, carotenoids, and resveratrol prevent the tumor cells from evading the immune system,,.

Tumors need specialized environments to grow and thrive in. As the tumor grows, new blood vessels need to form to provide the cells with oxygen and all of the treatment options selected are able to inhibit angiogenesis, except vitamin B and selenium, both of which show mixed results,,,,,,,,,,,. Interestingly though, in regards to other factors that contribute to the tumor microenvironment, all compounds are able to provide therapeutic value,,,,,.

Effective treatments to prevent tissue invasion and metastasis are important as these stages of cancer are associated with poor outcomes. It has been found that all of the targeted treatments are able to inhibit/prevent these pathways except for resveratrol and PARP inhibitors, which have no known relationship,,,,,,,,,. Further work and clinical trials will have to be performed to understand the full benefit of these compounds in regards to cancer treatment.

Conclusion

Genomic instability plays a critical role in cancer initiation and progression. The fidelity of the genome is protected at every stage of the cell cycle. In cancer, the presence of aneuploid or tetraploid cells indicates the failure of one or many of these safety nets. The resultant genomic heterogeneity may offer the cancer “tissue” a selection advantage against standard of care and emerging therapies. Understanding these safety nets, and how they are bypassed in cancer cells, may highlight new and more specific mechanisms for cancer prevention or therapeutic attack.

The therapeutic targeting of genomic instability may dampen other enabling characteristic of tumors cells, such as replicative immortality, evasion of antigrowth signaling, and tumor promoting inflammation. To this end, vitamins, minerals, and antioxidants, such as vitamin D, vitamin B, selenium, and carotenoids, as well as nutraceuticals, such as resveratrol, have shown remarkable plasticity in elucidating antitumor responses. In addition to alleviating genomic instability, these compounds are known to inhibit proliferative signaling,,, attenuate oncogenic metabolism,,,,,,, and block inflammation,,,,,,,,,,,,,,. However, caution must be applied as certain antioxidants, such β carotene, may promote carcinogenic processes in a dose- and context-dependent manner.

While mortality rates associated with heart disease and stroke have been reduced ∼70% in the last 50 years, mortality rates associated with cancer remain largely unchanged. This is likely due to our ability to manage the risk factors for heart disease and stroke and our inability to detect and prevent genomic instability and cancer. However, diet and lifestyle are two of our great hopes in this area. In particular, antioxidants are critical for the prevention of DNA damage that enables cancer initiation and growth. Growing evidence shows that vitamins, minerals, and other dietary factors have profound and protective effects against cancer cells, whether they are grown in the lab, in animals, or studied in human populations. A better understanding of the effects and synergy of these dietary factors in the prevention and treatment of genomic instability is critical to the future reduction of mortality associated with cancer.

Author's contributions

The following authors composed the indicated sections: HC, CAM, AKM (Mechanisms underlying genomic instability), PTT (epigenetic mechanisms), SD and DS (Mitochondrial genetics), GD, ESY, SR (DNA repair pathways), ARC and LRF (cancer prevention), SP and MM (targeting with RNAi). AA, AA, SSA, KA, ASA, DB, AB, CSB, SC, MC, MRC, HJ, GG, DH, BH, WNK, SM, EN, XY and KH (cross validation in Table 1, Table 2). LRF, MC, and CAM integrated and edited the sections.

Conflict of interest statement

The following authors declare that there are no conflicts of interest: LRF, HC, ARC, MC, GD, SD, MM, AKM, AA, AA, SSA, KA, ASA, DB, AB, CSB, SC, MRC, HF, GG, DH, WGH, WNK, SIM, EN, XY, KH, VRP, PR, SR, RS, DS, PTT, and CAM. ESY has material transfer agreements with AbbVie, Eli Lilly, Bristol Myers Squibb, and Cerion NRx.

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    Glover D.M., Leibowitz M.H., McLean D.A., Parry H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell. 1995;891:95-105.

    Not in our library10.1016/0092-8674(95)90374-7

  64. 64.
    NuMA is required for proper spindle assembly and chromosome alignment in prometaphase · 2009
    Not checked
  65. 65.

    Luca M.D., Lavia P., Guarguaglini G. A functional interplay between Aurora-A, Plk1 and TPX2 at the spindle poles. Cell Cycle. 2006;5.

    Not in our library10.4161/cc.5.3.2392

  66. 66.

    Maxwell C.A., Keats J.J., Belch A.R., Pilarski L.M., Reiman T. Receptor for hyaluronan-mediated motility correlates with centrosome abnormalities in multiple myelomana nd maintains mitotic integrity. Cancer Res. 2005;56:850-860.

    Not in our library

  67. 67.

    Maxwell C.A., Keats J.J., Crainie M., Sun X., Yen T., Shibuya E. RHAMM is a centrosomal protein that interacts with dynein and maintains spindle pole stability. Mol Biol Cell. 2003;14:2262-2276.

    Not in our library10.1091/mbc.e02-07-0377

  68. 68.

    Merdes A., Ramyar K., Vechio D., Cleveland D.W. A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. Cell. 1996;87:447-458.

    Not in our library10.1016/s0092-8674(00)81365-3

  69. 69.

    Silk A.D., Holland A.J., Cleveland D.W. Requirements for NuMA in maintenance and establishment of mammalian spindle poles. J Cell Biol. 2009;184:677-690.

    Not in our library10.1083/jcb.200810091

  70. 70.

    Kramer A., Maier B., Bartek J. Centrosome clustering and chromosomal (in)stability: a matter of life and death. Mol Oncol. 2011;5:324-335.

    Not in our library10.1016/j.molonc.2011.05.003

  71. 71.

    Ogden A., Rida P.C., Aneja R. Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy. Cell Death Differ. 2012;19:1255-1267.

    Not in our library10.1038/cdd.2012.61

  72. 72.

    Quintyne N.J., Reing J.E., Hoffelder D.R., Gollin S.M., Saunders W.S. Spindle multipolarity is prevented by centrosomal clustering. Science. 2005;307:127-129.

    Not in our library10.1126/science.1104905

  73. 73.

    Birkbak N.J., Eklund A.C., Li Q., McClelland S.E., Endesfelder D., Tan P. Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res. 2011;71:3447-3452.

    Not in our library10.1158/0008-5472.can-10-3667

  74. 74.

    Weaver B.A., Silk A.D., Montagna C., Verdier-Pinard P., Cleveland D.W. Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell. 2007;11:25-36.

    Not in our library10.1016/j.ccr.2006.12.003

  75. 75.

    Gergely F., Basto R. Multiple centrosomes: together they stand, divided they fall. Genes Dev. 2008;22:2291-2296.

    Not in our library10.1101/gad.1715208

  76. 76.

    Marthien V., Piel M., Basto R. Never tear us apart – the importance of centrosome clustering. J Cell Sci. 2012;125:3281-3292.

    Not in our library10.1242/jcs.094797

  77. 77.

    Kwon M., Godinho S.A., Chandhok N.S., Ganem N.J., Azioune A., Thery M. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev. 2008;22:2189-2203.

    Not in our library10.1101/gad.1700908

  78. 78.

    Lara-Gonzalez P., Westhorpe F.G., Taylor S.S. The spindle assembly checkpoint. Curr Biol. 2012;22:R966-R980.

    Not in our library10.1016/j.cub.2012.10.006

  79. 79.

    Foley E.A., Kapoor T.M. Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat Rev Mol Cell Biol. 2013;14:25-37.

    Not in our library10.1038/nrm3494

  80. 80.

    Lens S.M., Voest E.E., Medema R.H. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer. 2010;10:825-841.

    Not in our library10.1038/nrc2964

  81. 81.

    Nguyen H.G., Makitalo M., Yang D., Chinnappan D., St Hilaire C., Ravid K. Deregulated Aurora-B induced tetraploidy promotes tumorigenesis. FASEB J. 2009;23:2741-2748.

    Not in our library10.1096/fj.09-130963

  82. 82.

    Chan L.Y., Amon A. The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4. Genes Dev. 2009;23:1639-1649.

    Not in our library10.1101/gad.1804609

  83. 83.

    Fang X., Zhang R. Aneuploidy and tumourigenesis. Semin Cell Dev Biol. 2011;22:595-601.

    Not in our library10.1016/j.semcdb.2011.03.002

  84. 84.

    Grabsch H., Takeno S., Parsons W.J., Pomjanski N., Boecking A., Gabbert H.E. Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer – association with tumour cell proliferation. J Pathol. 2003;200:16-22.

    Not in our library10.1002/path.1324

  85. 85.

    Hanks S., Coleman K., Reid S., Plaja A., Firth H., Fitzpatrick D. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004;36:1159-1161.

    Not in our library10.1038/ng1449

  86. 86.

    Anand P., Lowe V. AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell. 2003;3:51-62.

    Not in our library10.1016/s1535-6108(02)00235-0

  87. 87.

    Hardy P.A., Zacharias H. Reappraisal of the Hansemann–Boveri hypothesis on the origin of tumors. Cell Biol Int. 2005;29:983-992.

    Not in our library10.1016/j.cellbi.2005.10.001

  88. 88.

    Shackney S.E., Smith C.A., Miller B.W., Burholt D.R., Murtha K., Giles H.R. Model for the genetic evolution of human solid tumors. Cancer Res. 1989;49:3344-3354.

    Not in our library

  89. 89.

    Andreassen P.R., Lohez O.D., Lacroix F.B., Margolis R.L. Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell. 2001;12:1315-1328.

    Not in our library10.1091/mbc.12.5.1315

  90. 90.

    Borel F., Lohez O.D., Lacroix F.B., Margolis R.L. Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells. Proc Natl Acad Sci U S A. 2002;99:9819-9824.

    Not in our library10.1073/pnas.152205299

  91. 91.

    Lanni J.S., Jacks T. Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol Cell Biol. 1998;18.

    Not in our library10.1128/mcb.18.2.1055

  92. 92.

    Livingstone L.R., White A., Sprouse J., Livanos E., Jacks T., Tlsty T.D. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell. 1992;70:923-935.

    Not in our library10.1016/0092-8674(92)90243-6

  93. 93.

    Galipeau P.C., Cowan D.S., Sanchez C.A., Barretr M.T., Emondt M.J., Levinet D.S. Progression to aneuploidy in Barrett’ s esophagus. Cell. 1996;93:7081-7084.

    Not in our library10.1073/pnas.93.14.7081

  94. 94.

    Fujiwara T., Bandi M., Nitta M., Ivanova E.V., Bronson R.T., Pellman D. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 2005;437:1043-1047.

    Not in our library10.1038/nature04217

  95. 95.

    Sharma S., Kelly T.K., Jones P.A. Epigenetics in cancer. Carcinogenesis. 2010;31:27-36.

    Not in our library10.1093/carcin/bgp220

  96. 96.

    Berger S.L., Kouzarides T., Shiekhattar R., Shilatifard A. An operational definition of epigenetics. Genes Dev. 2009;23:781-783.

    Not in our library10.1101/gad.1787609

  97. 97.

    Nowsheen S., Aziz K., Tran P.T., Gorgoulis V.G., Yang E.S., Georgakilas A.G. Epigenetic inactivation of DNA repair in breast cancer. Cancer Lett. 2012.

    Not in our library10.1016/j.canlet.2012.05.015

  98. 98.

    Cedar H., Bergman Y. Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009;10:295-304.

    Not in our library10.1038/nrg2540

  99. 99.

    Robertson K.D. DNA methylation and chromatin – unraveling the tangled web. Oncogene. 2002;21:5361-5379.

    Not in our library10.1038/sj.onc.1205609

  100. 100.

    Das P.M., Singal R. DNA methylation and cancer. J Clin Oncol. 2004;22:4632-4642.

    Not in our library10.1200/jco.2004.07.151

  101. 101.

    Baylin S.B., Esteller M., Rountree M.R., Bachman K.E., Schuebel K., Herman J.G. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet. 2001;10:687-692.

    Not in our library10.1093/hmg/10.7.687

  102. 102.

    Feinberg A.P., Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983;301:89-92.

    Not in our library10.1038/301089a0

  103. 103.

    Robertson K.D. DNA methylation and human disease. Nat Rev Genet. 2005;6:597-610.

    Not in our library10.1038/nrg1655

  104. 104.

    Baylin S.B., Ohm J.E. Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction. Nat Rev Cancer. 2006;6:107-116.

    Not in our library10.1038/nrc1799

  105. 105.

    Felsher D.W., Bishop J.M. Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc Natl Acad Sci. 1999;96:3940-3944.

    Not in our library10.1073/pnas.96.7.3940

  106. 106.

    Denko N.C., Giaccia A.J., Stringer J.R., Stambrook P.J. The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle. Proc Natl Acad Sci. 1994;91:5124-5128.

    Not in our library10.1073/pnas.91.11.5124

  107. 107.

    Jin B., Robertson K.D. DNA methyltransferases, DNA damage repair and cancer. Adv Exp Med Biol. 2013;754:3-29.

    Not in our library10.1007/978-1-4419-9967-2_1

  108. 108.

    Hitchins M.P. Inheritance of epigenetic aberrations (constitutional epimutations) in cancer susceptibility. Adv Genet. 2010;70:201-243.

    Not in our library10.1016/b978-0-12-380866-0.60008-3

  109. 109.

    Goel A., Nagasaka T., Arnold C.N., Inoue T., Hamilton C., Niedzwiecki D. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology. 2007;132:127-138.

    Not in our library10.1053/j.gastro.2006.09.018

  110. 110.

    Sproul D., Gilbert N., Bickmore W.A. The role of chromatin structure in regulating the expression of clustered genes. Nat Rev Genet. 2005;6:775-781.

    Not in our library10.1038/nrg1688

  111. 111.

    Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693-705.

    Not in our library10.1016/j.cell.2007.02.005

  112. 112.

    Turner B.M. Histone acetylation and an epigenetic code. Bioessays. 2000;22:836-845.

    Not in our library10.1002/1521-1878(200009)22:9<836::aid-bies9>3.0.co;2-x

  113. 113.

    Gorrini C., Squatrito M., Luise C., Syed N., Perna D., Wark L. Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature. 2007;448.

    Not in our library10.1038/nature06055

  114. 114.

    Tang Y., Luo J.Y., Zhang W.Z., Gu W. Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell. 2006;24:827-839.

    Not in our library10.1016/j.molcel.2006.11.021

  115. 115.

    Ikura T., Tashiro S., Kakino A., Shima H., Jacob N., Amunugarna R. DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. Mol Cell Biol. 2007;27:7028-7040.

    Not in our library10.1128/mcb.00579-07

  116. 116.

    Sun Y.L., Jiang X.F., Chen S.J., Fernandes N., Price B.D. A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci U S A. 2005;102:13182-13187.

    Not in our library10.1073/pnas.0504211102

  117. 117.

    Xie W., Song C.Y., Young N.L., Sperling A.S., Xu F., Sridharan R. Histone H3 lysine 56 acetylation is linked to the core transcriptional network in human embryonic stem cells. Mol Cell. 2009;33:417-427.

    Not in our library10.1016/j.molcel.2009.02.004

  118. 118.

    Das C., Lucia M.S., Hansen K.C., Tyler J.K. CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature. 2009;459.

    Not in our library10.1038/nature07861

  119. 119.

    Osley M.A. Regulation of histone H2A and H2B ubiquitylation. Brief Funct Genomic Proteomic. 2006;5:179-189.

    Not in our library10.1093/bfgp/ell022

  120. 120.

    Mailand N., Bekker-Jensen S., Faustrup H., Melander F., Bartek J., Lukas C. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell. 2007;131:887-900.

    Not in our library10.1016/j.cell.2007.09.040

  121. 121.

    Huen M.S.Y., Grant R., Manke I., Minn K., Yu X.C., Yaffe M.B. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell. 2007;131:901-914.

    Not in our library10.1016/j.cell.2007.09.041

  122. 122.

    Kao C.F., Hillyer C., Tsukuda T., Henry K., Berger S., Osley M.A. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev. 2004;18:184-195.

    Not in our library10.1101/gad.1149604

  123. 123.

    Turner S.D., Ricci A.R., Petropoulos H., Genereaux J., Skerjanc I.S., Brandl C.J. The E2 ubiquitin conjugase Rad6 is required for the ArgR/Mcm1 repression of ARG1 transcription. Mol Cell Biol. 2002;22:4011-4019.

    Not in our library10.1128/mcb.22.12.4011-4019.2002

  124. 124.

    Luijsterburg M.S., Goedhart J., Moser J., Kool H., Geverts B., Houtsmuller A.B. Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC. J Cell Sci. 2007;120:2706-2716.

    Not in our library10.1242/jcs.008367

  125. 125.

    Nicassio F., Corrado N., Vissers J.H.A., Areces L.B., Bergink S., Marteijn J.A. Human USP3 is a chromatin modifier required for S phase progression and genome stability. Curr Biol. 2007;17:1972-1977.

    Not in our library10.1016/j.cub.2007.10.034

  126. 126.

    Moyal L., Lerenthal Y., Gana-Weisz M., Mass G., So S., Wang S.Y. Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Mol Cell. 2011;41:529-542.

    Not in our library10.1016/j.molcel.2011.02.015

  127. 127.

    Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K., Miller E.S. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell. 2009;136:420-434.

    Not in our library10.1016/j.cell.2008.12.042

  128. 128.

    Bonner W.M., Redon C.E., Dickey J.S., Nakamura A.J., Sedelnikova O.A., Solier S. OPINION gamma H2AX and cancer. Nat Rev Cancer. 2008;8:957-967.

    Not in our library10.1038/nrc2523

  129. 129.

    Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.

    Not in our library10.1016/j.cell.2011.02.013

  130. 130.

    Warburg O., Wind F., Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519-530.

    Not in our library10.1085/jgp.8.6.519

  131. 131.

    Warburg O. On the origin of cancer cells. Science. 1956;123:309-314.

    Not in our library10.1126/science.123.3191.309

  132. 132.

    Chatterjee A., Dasgupta S., Sidransky D. Mitochondrial subversion in cancer. Cancer Prev Res (Phila). 2011;4:638-654.

    Not in our library10.1158/1940-6207.capr-10-0326

  133. 133.

    Dasgupta S., Shao C., Keane T.E., Duberow D.P., Mathies R.A., Fisher P.B. Detection of mitochondrial deoxyribonucleic acid alterations in urine from urothelial cell carcinoma patients. Int J Cancer. 2012;131:158-164.

    Not in our library10.1002/ijc.26357

  134. 134.

    Dasgupta S., Soudry E., Mukhopadhyay N., Shao C., Yee J., Lam S. Mitochondrial DNA mutations in respiratory complex-I in never-smoker lung cancer patients contribute to lung cancer progression and associated with EGFR gene mutation. J Cell Physiol. 2012;227:2451-2460.

    Not in our library10.1002/jcp.22980

  135. 135.

    Kloss-Brandstatter A., Schafer G., Erhart G., Huttenhofer A., Coassin S., Seifarth C. Somatic mutations throughout the entire mitochondrial genome are associated with elevated PSA levels in prostate cancer patients. Am J Hum Genet. 2010;87:802-812.

    Not in our library10.1016/j.ajhg.2010.11.001

  136. 136.

    Petros J.A., Baumann A.K., Ruiz-Pesini E., Amin M.B., Sun C.Q., Hall J. mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci U S A. 2005;102:719-724.

    Not in our library10.1073/pnas.0408894102

  137. 137.

    Dasgupta S., Yung R.C., Westra W.H., Rini D.A., Brandes J., Sidransky D. Following mitochondrial footprints through a long mucosal path to lung cancer. PLoS ONE. 2009;4:e6533.

    Not in our library10.1371/journal.pone.0006533

  138. 138.

    Dasgupta S., Koch R., Westra W.H., Califano J.A., Ha P.K., Sidransky D. Mitochondrial DNA mutation in normal margins and tumors of recurrent head and neck squamous cell carcinoma patients. Cancer Prev Res (Phila). 2010;3:1205-1211.

    Not in our library10.1158/1940-6207.capr-10-0018

  139. 139.

    Cook C.C., Kim A., Terao S., Gotoh A., Higuchi M. Consumption of oxygen: a mitochondrial-generated progression signal of advanced cancer. Cell Death Dis. 2012;3:e258.

    Not in our library10.1038/cddis.2011.141

  140. 140.

    Arnold R.S., Sun C.Q., Richards J.C., Grigoriev G., Coleman I.M., Nelson P.S. Mitochondrial DNA mutation stimulates prostate cancer growth in bone stromal environment. Prostate. 2009;69:1-11.

    Not in our library10.1002/pros.20854

  141. 141.

    Arnold R.S., Sun Q., Sun C.Q., Richards J.C., O’Hearn S., Osunkoya A.O. An inherited heteroplasmic mutation in mitochondrial gene COI in a patient with prostate cancer alters reactive oxygen, reactive nitrogen and proliferation. Biomed Res Int. 2013;2013:239257.

    Not in our library10.1155/2013/239257

  142. 142.

    Dasgupta S., Hoque M.O., Upadhyay S., Sidransky D. Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer. Cancer Res. 2008;68:700-706.

    Not in our library10.1158/0008-5472.can-07-5532

  143. 143.

    Aguilera A., Gomez-Gonzalez B. Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet. 2008;9:204-217.

    Not in our library10.1038/nrg2268

  144. 144.

    Houtgraaf J.H., Versmissen J., van der Giessen W.J. A concise review of DNA damage checkpoints and repair in mammalian cells. Cardiovasc Revasc Med. 2006;7:165-172.

    Not in our library10.1016/j.carrev.2006.02.002

  145. 145.

    Sancar A., Lindsey-Boltz L.A., Unsal-Kacmaz K., Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39-85.

    Not in our library10.1146/annurev.biochem.73.011303.073723

  146. 146.

    Hanawalt P.C., Spivak G. Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol. 2008;9:958-970.

    Not in our library10.1038/nrm2549

  147. 147.

    Wei K., Kucherlapati R., Edelmann W. Mouse models for human DNA mismatch-repair gene defects. Trends Mol Med. 2002;8:346-353.

    Not in our library10.1016/s1471-4914(02)02359-6

  148. 148.

    Taketo M.M., Edelmann W. Mouse models of colon cancer. Gastroenterology. 2009;136:780-798.

    Not in our library10.1053/j.gastro.2008.12.049

  149. 149.

    Hollander M.C., Philburn R.T., Patterson A.D., Velasco-Miguel S., Friedberg E.C., Linnoila R.I. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proc Natl Acad Sci U S A. 2005;102:13200-13205.

    Not in our library10.1073/pnas.0503133102

  150. 150.

    Thoms K.M., Kuschal C., Emmert S. Lessons learned from DNA repair defective syndromes. Exp Dermatol. 2007;16:532-544.

    Not in our library10.1111/j.1600-0625.2007.00559.x

  151. 151.

    Maynard S., Schurman S.H., Harboe C., de Souza-Pinto N.C., Bohr V.A. Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis. 2009;30:2-10.

    Not in our library10.1093/carcin/bgn250

  152. 152.

    Rouleau M., Patel A., Hendzel M.J., Kaufmann S.H., Poirier G.G. PARP inhibition: PARP1 and beyond. Nat Rev Cancer. 2010;10:293-301.

    Not in our library10.1038/nrc2812

  153. 153.

    Hassa P.O., Hottiger M.O. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci. 2008;13:3046-3082.

    Not in our library10.2741/2909

  154. 154.

    Larsen E., Gran C., Saether B.E., Seeberg E., Klungland A. Proliferation failure and gamma radiation sensitivity of Fen1 null mutant mice at the blastocyst stage. Mol Cell Biol. 2003;23:5346-5353.

    Not in our library10.1128/mcb.23.15.5346-5353.2003

  155. 155.

    Sobol R.W., Horton J.K., Kuhn R., Gu H., Singhal R.K., Prasad R. Requirement of mammalian DNA polymerase-beta in base-excision repair. Nature. 1996;379:183-186.

    Not in our library10.1038/379183a0

  156. 156.

    Tebbs R.S., Flannery M.L., Meneses J.J., Hartmann A., Tucker J.D., Thompson L.H. Requirement for the Xrcc1 DNA base excision repair gene during early mouse development. Dev Biol. 1999;208:513-529.

    Not in our library10.1006/dbio.1999.9232

  157. 157.

    Al-Tassan N., Chmiel N.H., Maynard J., Fleming N., Livingston A.L., Williams G.T. Inherited variants of MYH associated with somatic G:C → T:A mutations in colorectal tumors. Nat Genet. 2002;30:227-232.

    Not in our library10.1038/ng828

  158. 158.

    Farrington S.M., Tenesa A., Barnetson R., Wiltshire A., Prendergast J., Porteous M. Germline susceptibility to colorectal cancer due to base-excision repair gene defects. Am J Hum Genet. 2005;77:112-119.

    Not in our library10.1086/431213

  159. 159.

    Tenesa A., Farrington S.M., Dunlop M.G. Re: association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk. J Natl Cancer Inst. 2005;97:320-321.

    Not in our library10.1093/jnci/dji051

  160. 160.

    Barnetson R.A., Devlin L., Miller J., Farrington S.M., Slater S., Drake A.C. Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer. Clin Genet. 2007;72:551-555.

    Not in our library10.1111/j.1399-0004.2007.00900.x

  161. 161.

    Mahjabeen I., Masood N., Baig R.M., Sabir M., Inayat U., Malik F.A. Novel mutations of OGG1 base excision repair pathway gene in laryngeal cancer patients. Fam Cancer. 2012;11:587-593.

    Not in our library10.1007/s10689-012-9554-2

  162. 162.

    Shinmura K., Tao H., Goto M., Igarashi H., Taniguchi T., Maekawa M. Inactivating mutations of the human base excision repair gene NEIL1 in gastric cancer. Carcinogenesis. 2004;25:2311-2317.

    Not in our library10.1093/carcin/bgh267

  163. 163.

    Kunkel T.A. Evolving views of DNA replication (in)fidelity. Cold Spring Harb Symp Quant Biol. 2009;74:91-101.

    Not in our library10.1101/sqb.2009.74.027

  164. 164.

    Morrison A., Johnson A.L., Johnston L.H., Sugino A. Pathway correcting DNA replication errors in Saccharomyces cerevisiae. EMBO J. 1993;12:1467-1473.

    Not in our library10.1002/j.1460-2075.1993.tb05790.x

  165. 165.

    Albertson T.M., Ogawa M., Bugni J.M., Hays L.E., Chen Y., Wang Y. DNA polymerase epsilon and delta proofreading suppress discrete mutator and cancer phenotypes in mice. Proc Natl Acad Sci U S A. 2009;106:17101-17104.

    Not in our library10.1073/pnas.0907147106

  166. 166.

    Kolodner R.D., Marsischky G.T. Eukaryotic DNA mismatch repair. Curr Opin Genet Dev. 1999;9:89-96.

    Not in our library10.1016/s0959-437x(99)80013-6

  167. 167.

    Ciccia A., Elledge S.J. The DNA damage response: making it safe to play with knives. Mol Cell. 2010;40:179-204.

    Not in our library10.1016/j.molcel.2010.09.019

  168. 168.

    Helleday T., Lo J., van Gent D.C., Engelward B.P. DNA double-strand break repair: from mechanistic understanding to cancer treatment. DNA Rep. 2007;6:923-935.

    Not in our library10.1016/j.dnarep.2007.02.006

  169. 169.

    Moynahan M.E., Jasin M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol. 2010;11:196-207.

    Not in our library10.1038/nrm2851

  170. 170.

    Willers H., Pfäffle H.N., Zou L., Kelley M.R. Targeting homologous recombination repair in cancer: molecular targets and clinical applications. 2011;119-160.

    Not in our library

  171. 171.

    Riha K., Heacock M.L., Shippen D.E. The role of the nonhomologous end-joining DNA double-strand break repair pathway in telomere biology. Annu Rev Genet. 2006;40:237-277.

    Not in our library10.1146/annurev.genet.39.110304.095755

  172. 172.

    De Lange T. Telomere-related genome instability in cancer. Cold Spring Harb Symp Quant Biol. 2005;70:197-204.

    Not in our library10.1101/sqb.2005.70.032

  173. 173.

    McClintock B. The behavior in successive nuclear divisions of a chromosome broken at meiosis. Proc Natl Acad Sci U S A. 1939;25:405-416.

    Not in our library10.1073/pnas.25.8.405

  174. 174.

    Hall J.M., Lee M.K., Newman B., Morrow J.E., Anderson L.A., Huey B. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990;250:1684-1689.

    Not in our library10.1126/science.2270482

  175. 175.

    Friedman L.S., Ostermeyer E.A., Szabo C.I., Dowd P., Lynch E.D., Rowell S.E. Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nat Genet. 1994;8:399-404.

    Not in our library10.1038/ng1294-399

  176. 176.

    Castilla L.H., Couch F.J., Erdos M.R., Hoskins K.F., Calzone K., Garber J.E. Mutations in the BRCA1 gene in families with early-onset breast and ovarian cancer. Nat Genet. 1994;8:387-391.

    Not in our library10.1038/ng1294-387

  177. 177.

    Futreal P.A., Liu Q., Shattuck-Eidens D., Cochran C., Harshman K., Tavtigian S. BRCA1 mutations in primary breast and ovarian carcinomas. Science. 1994;266:120-122.

    Not in our library10.1126/science.7939630

  178. 178.

    Ford D., Easton D.F., Bishop D.T., Narod S.A., Goldgar D.E. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994;343:692-695.

    Not in our library10.1016/s0140-6736(94)91578-4

  179. 179.

    Wooster R., Neuhausen S.L., Mangion J., Quirk Y., Ford D., Collins N. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994;265:2088-2090.

    Not in our library10.1126/science.8091231

  180. 180.

    Wooster R., Bignell G., Lancaster J., Swift S., Seal S., Mangion J. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789-792.

    Not in our library10.1038/378789a0

  181. 181.

    Collins N., McManus R., Wooster R., Mangion J., Seal S., Lakhani S.R. Consistent loss of the wild type allele in breast cancers from a family linked to the BRCA2 gene on chromosome 13q12-13. Oncogene. 1995;10:1673-1675.

    Not in our library

  182. 182.

    Chen S., Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25:1329-1333.

    Not in our library10.1200/jco.2006.09.1066

  183. 183.

    Friedenson B. BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. MedGenMed. 2005;7:60.

    Not in our library

  184. 184.

    Xia B., Sheng Q., Nakanishi K., Ohashi A., Wu J., Christ N. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell. 2006;22:719-729.

    Not in our library10.1016/j.molcel.2006.05.022

  185. 185.

    Tischkowitz M., Capanu M., Sabbaghian N., Li L., Liang X., Vallee M.P. Rare germline mutations in PALB2 and breast cancer risk: a population-based study. Hum Mutat. 2012;33:674-680.

    Not in our library10.1002/humu.22022

  186. 186.

    Rahman N., Seal S., Thompson D., Kelly P., Renwick A., Elliott A. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007;39:165-167.

    Not in our library10.1038/ng1959

  187. 187.

    Zheng Y., Zhang J., Niu Q., Huo D., Olopade O.I. Novel germline PALB2 truncating mutations in African American breast cancer patients. Cancer. 2012;118:1362-1370.

    Not in our library10.1002/cncr.26388

  188. 188.

    Ding Y.C., Steele L., Chu L.H., Kelley K., Davis H., John E.M. Germline mutations in PALB2 in African-American breast cancer cases. Breast Cancer Res Treat. 2011;126:227-230.

    Not in our library10.1007/s10549-010-1271-7

  189. 189.

    Cao A.Y., Huang J., Hu Z., Li W.F., Ma Z.L., Tang L.L. The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast Cancer Res Treat. 2009;114:457-462.

    Not in our library10.1007/s10549-008-0036-z

  190. 190.

    Jones S., Hruban R.H., Kamiyama M., Borges M., Zhang X., Parsons D.W. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009;324:217.

    Not in our library10.1126/science.1171202

  191. 191.

    Tischkowitz M.D., Sabbaghian N., Hamel N., Borgida A., Rosner C., Taherian N. Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology. 2009;137:1183-1186.

    Not in our library10.1053/j.gastro.2009.06.055

  192. 192.

    Slater E.P., Langer P., Niemczyk E., Strauch K., Butler J., Habbe N. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010;78:490-494.

    Not in our library10.1111/j.1399-0004.2010.01425.x

  193. 193.

    Kee Y., D’Andrea A.D. Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes Dev. 2010;24:1680-1694.

    Not in our library10.1101/gad.1955310

  194. 194.

    D’Andrea A.D. Susceptibility pathways in Fanconi's anemia and breast cancer. New Engl J Med. 2010;362:1909-1919.

    Not in our library10.1056/nejmra0809889

  195. 195.

    Tischkowitz M., Xia B. PALB2/FANCN: recombining cancer and Fanconi anemia. Cancer Res. 2010;70:7353-7359.

    Not in our library10.1158/0008-5472.can-10-1012

  196. 196.

    Reid S., Schindler D., Hanenberg H., Barker K., Hanks S., Kalb R. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007;39:162-164.

    Not in our library10.1038/ng1947

  197. 197.

    Chirnomas D., Taniguchi T., de la Vega M., Vaidya A.P., Vasserman M., Hartman A.R. Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway. Mol Cancer Ther. 2006;5:952-961.

    Not in our library10.1158/1535-7163.mct-05-0493

  198. 198.

    Alter B.P. Radiosensitivity in Fanconi's anemia patients. Radiother Oncol. 2002;62:345-347.

    Not in our library10.1016/s0167-8140(01)00474-1

  199. 199.

    Otsuki T., Wang J., Demuth I., Digweed M., Liu J.M. Assessment of mitomycin C sensitivity in Fanconi anemia complementation group C gene (Fac) knock-out mouse cells. Int J Hematol. 1998;67:243-248.

    Not in our library10.1016/s0925-5710(98)00012-7

  200. 200.
    The ATM signaling network in development and disease · 2013
    No notice
  201. 201.

    Kobayashi H., Ohno S., Sasaki Y., Matsuura M. Hereditary breast and ovarian cancer susceptibility genes (review). Oncol Rep. 2013.

    Not in our library10.3892/or.2013.2541

  202. 202.

    Helleday T., Petermann E., Lundin C., Hodgson B., Sharma R.A. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 2008;8:193-204.

    Not in our library10.1038/nrc2342

  203. 203.

    Sajesh B.V., Guppy B.J., McManus K.J. Synthetic genetic targeting of genome instability in cancer. Cancers. 2013;5:739-761.

    Not in our library10.3390/cancers5030739

  204. 204.

    Bryant H.E., Schultz N., Thomas H.D., Parker K.M., Flower D., Lopez E. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913-917.

    Not in our library10.1038/nature03443

  205. 205.

    Farmer H., McCabe N., Lord C.J., Tutt A.N., Johnson D.A., Richardson T.B. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917-921.

    Not in our library10.1038/nature03445

  206. 206.

    Fong P.C., Boss D.S., Yap T.A., Tutt A., Wu P., Mergui-Roelvink M. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. New Engl J Med. 2009;361:123-134.

    Not in our library10.1056/nejmoa0900212

  207. 207.

    Fong P.C., Yap T.A., Boss D.S., Carden C.P., Mergui-Roelvink M., Gourley C. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol. 2010;28:2512-2519.

    Not in our library10.1200/jco.2009.26.9589

  208. 208.

    Irshad S., Ashworth A., Tutt A. Therapeutic potential of PARP inhibitors for metastatic breast cancer. Expert Rev Anticancer Ther. 2011;11:1243-1251.

    Not in our library10.1586/era.11.52

  209. 209.

    Sessa C. Update on PARP1 inhibitors in ovarian cancer. Ann Oncol. 2011;22(Suppl. 8):viii72-viii76.

    Not in our library10.1093/annonc/mdr528

  210. 210.

    Telli M.L., Ford J.M. PARP inhibitors in breast cancer. Clin Adv Hematol Oncol. 2010;8:629-635.

    Not in our library

  211. 211.

    Tutt A., Robson M., Garber J.E., Domchek S.M., Audeh M.W., Weitzel J.N. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376:235-244.

    Not in our library10.1016/s0140-6736(10)60892-6

  212. 212.

    Fowke J.H., Gao Y.T., Chow W.H., Cai Q., Shu X.O., Li H.L. Urinary isothiocyanate levels and lung cancer risk among non-smoking women: a prospective investigation. Lung Cancer. 2011;73:18-24.

    Not in our library10.1016/j.lungcan.2010.10.024

  213. 213.

    Grotsky D.A., Gonzalez-Suarez I., Novell A., Neumann M.A., Yaddanapudi S.C., Croke M. BRCA1 loss activates cathepsin l-mediated degradation of 53BP1 in breast cancer cells. J Cell Biol. 2013;200:187-202.

    Not in our library10.1083/jcb.201204053

  214. 214.

    Chen T., Wong Y.S. Selenocystine induces caspase-independent apoptosis in MCF-7 human breast carcinoma cells with involvement of p53 phosphorylation and reactive oxygen species generation. Int J Biochem Cell Biol. 2009;41:666-676.

    Not in our library10.1016/j.biocel.2008.07.014

  215. 215.

    Taniguchi T., Tischkowitz M., Ameziane N., Hodgson S.V., Mathew C.G., Joenje H. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med. 2003;9:568-574.

    Not in our library10.1038/nm852

  216. 216.

    Swisher E.M., Sakai W., Karlan B.Y., Wurz K., Urban N., Taniguchi T. Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance. Cancer Res. 2008;68:2581-2586.

    Not in our library10.1158/0008-5472.can-08-0088

  217. 217.

    Tennstedt P., Fresow R., Simon R., Marx A., Terracciano L., Petersen C. RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma. Int J Cancer. 2013;132:2118-2126.

    Not in our library10.1002/ijc.27907

  218. 218.

    Hickson I., Zhao Y., Richardson C.J., Green S.J., Martin N.M., Orr A.I. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res. 2004;64:9152-9159.

    Not in our library10.1158/0008-5472.can-04-2727

  219. 219.

    Dent P., Tang Y., Yacoub A., Dai Y., Fisher P.B., Grant S. CHK1 inhibitors in combination chemotherapy: thinking beyond the cell cycle. Mol Interv. 2011;11:133-140.

    Not in our library10.1124/mi.11.2.11

  220. 220.

    Poulsen M.M., Jorgensen J.O., Jessen N., Richelsen B., Pedersen S.B. Resveratrol in metabolic health: an overview of the current evidence and perspectives. Ann N Y Acad Sci. 2013;1290:74-82.

    Not in our library10.1111/nyas.12141

  221. 221.

    Wang R.H., Zheng Y., Kim H.S., Xu X., Cao L., Luhasen T. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol Cell. 2008;32:11-20.

    Not in our library10.1016/j.molcel.2008.09.011

  222. 222.

    Hoeijmakers J.H. DNA damage, aging, and cancer. New Engl J Med. 2009;361:1475-1485.

    Not in our library10.1056/nejmra0804615

  223. 223.

    Imai K., Yamamoto H. Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis. 2008;29:673-680.

    Not in our library10.1093/carcin/bgm228

  224. 224.

    Jiricny J. The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol. 2006;7:335-346.

    Not in our library10.1038/nrm1907

  225. 225.

    Vilar E., Gruber S.B. Microsatellite instability in colorectal cancer – the stable evidence. Nat Rev Clin Oncol. 2010;7:153-162.

    Not in our library10.1038/nrclinonc.2009.237

  226. 226.

    Popat S., Hubner R., Houlston R.S. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609-618.

    Not in our library10.1200/jco.2005.01.086

  227. 227.

    Boland C.R., Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138:2073-2087.e3.

    Not in our library10.1053/j.gastro.2009.12.064

  228. 228.

    Papadopoulos N., Nicolaides N.C., Wei Y.F., Ruben S.M., Carter K.C., Rosen C.A. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994;263:1625-1629.

    Not in our library10.1126/science.8128251

  229. 229.

    Nicolaides N.C., Papadopoulos N., Liu B., Wei Y.F., Carter K.C., Ruben S.M. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature. 1994;371:75-80.

    Not in our library10.1038/371075a0

  230. 230.

    Bronner C.E., Baker S.M., Morrison P.T., Warren G., Smith L.G., Lescoe M.K. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994;368:258-261.

    Not in our library10.1038/368258a0

  231. 231.

    Leach F.S., Nicolaides N.C., Papadopoulos N., Liu B., Jen J., Parsons R. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993;75:1215-1225.

    Not in our library10.1016/0092-8674(93)90330-s

  232. 232.

    Fishel R., Lescoe M.K., Rao M.R., Copeland N.G., Jenkins N.A., Garber J. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1994;77.

    Not in our library

  233. 233.
    CpG island methylator phenotype in colorectal cancer · 1999
    Not checked
  234. 234.

    Cunningham J.M., Christensen E.R., Tester D.J., Kim C.Y., Roche P.C., Burgart L.J. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res. 1998;58:3455-3460.

    Not in our library

  235. 235.

    Kakar S., Burgart L.J., Thibodeau S.N., Rabe K.G., Petersen G.M., Goldberg R.M. Frequency of loss of hMLH1 expression in colorectal carcinoma increases with advancing age. Cancer. 2003;97:1421-1427.

    Not in our library10.1002/cncr.11206

  236. 236.

    Baylin S.B., Herman J.G., Graff J.R., Vertino P.M., Issa J.P. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res. 1998;72:141-196.

    Not in our library

  237. 237.

    Pfeifer G.P., Steigerwald S.D., Hansen R.S., Gartler S.M., Riggs A.D. Polymerase chain reaction-aided genomic sequencing of an X chromosome-linked CpG island: methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability. Proc Natl Acad Sci U S A. 1990;87:8252-8256.

    Not in our library10.1073/pnas.87.21.8252

  238. 238.

    Wachsman J.T. DNA methylation and the association between genetic and epigenetic changes: relation to carcinogenesis. Mutat Res. 1997;375:1-8.

    Not in our library10.1016/s0027-5107(97)00003-1

  239. 239.

    Umar A., Boland C.R., Terdiman J.P., Syngal S., de la Chapelle A., Ruschoff J. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261-268.

    Not in our library10.1093/jnci/djh034

  240. 240.

    Pawlik T.M., Raut C.P., Rodriguez-Bigas M.A. Colorectal carcinogenesis: MSI-H versus MSI-L. Dis Markers. 2004;20:199-206.

    Not in our library10.1155/2004/368680

  241. 241.

    Dietmaier W., Wallinger S., Bocker T., Kullmann F., Fishel R., Ruschoff J. Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res. 1997;57:4749-4756.

    Not in our library

  242. 242.

    Stone J.G., Tomlinson I.P., Houlston R.S. Optimising methods for determining RER status in colorectal cancers. Cancer Lett. 2000;149:15-20.

    Not in our library10.1016/s0304-3835(99)00324-9

  243. 243.

    Zhou X.P., Hoang J.M., Cottu P., Thomas G., Hamelin R. Allelic profiles of mononucleotide repeat microsatellites in control individuals and in colorectal tumors with and without replication errors. Oncogene. 1997;15:1713-1718.

    Not in our library10.1038/sj.onc.1201337

  244. 244.

    Hoang J.M., Cottu P.H., Thuille B., Salmon R.J., Thomas G., Hamelin R. BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. Cancer Res. 1997;57:300-303.

    Not in our library

  245. 245.

    Boland C.R., Thibodeau S.N., Hamilton S.R., Sidransky D., Eshleman J.R., Burt R.W. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248-5257.

    Not in our library

  246. 246.

    Gryfe R., Kim H., Hsieh E.T., Aronson M.D., Holowaty E.J., Bull S.B. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. New Engl J Med. 2000;342:69-77.

    Not in our library10.1056/nejm200001133420201

  247. 247.

    Tomlinson I., Halford S., Aaltonen L., Hawkins N., Ward R. Does MSI-low exist? J Pathol. 2002;197:6-13.

    Not in our library10.1002/path.1071

  248. 248.

    Watson M.M., Berg M., Soreide K. Prevalence and implications of elevated microsatellite alterations at selected tetranucleotides in cancer. Br J Cancer. 2014.

    Not in our library10.1038/bjc.2014.167

  249. 249.

    Vilar E., Tabernero J. Molecular dissection of microsatellite instable colorectal cancer. Cancer Discov. 2013;3:502-511.

    Not in our library10.1158/2159-8290.cd-12-0471

  250. 250.

    Sargent D.J., Marsoni S., Monges G., Thibodeau S.N., Labianca R., Hamilton S.R. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28:3219-3226.

    Not in our library10.1200/jco.2009.27.1825

  251. 251.

    Sinicrope F.A., Foster N.R., Thibodeau S.N., Marsoni S., Monges G., Labianca R. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst. 2011;103:863-875.

    Not in our library10.1093/jnci/djr153

  252. 252.

    Martin S.A., McCabe N., Mullarkey M., Cummins R., Burgess D.J., Nakabeppu Y. DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1. Cancer Cell. 2010;17:235-248.

    Not in our library10.1016/j.ccr.2009.12.046

  253. 253.

    van Pel D.M., Barrett I.J., Shimizu Y., Sajesh B.V., Guppy B.J., Pfeifer T. An evolutionarily conserved synthetic lethal interaction network identifies FEN1 as a broad-spectrum target for anticancer therapeutic development. PLOS Genet. 2013;9:e1003254.

    Not in our library10.1371/journal.pgen.1003254

  254. 254.

    McManus K.J., Barrett I.J., Nouhi Y., Hieter P. Specific synthetic lethal killing of RAD54B-deficient human colorectal cancer cells by FEN1 silencing. Proc Natl Acad Sci U S A. 2009;106:3276-3281.

    Not in our library10.1073/pnas.0813414106

  255. 255.

    Martin S.A., Hewish M., Sims D., Lord C.J., Ashworth A. Parallel high-throughput RNA interference screens identify PINK1 as a potential therapeutic target for the treatment of DNA mismatch repair-deficient cancers. Cancer Res. 2011;71:1836-1848.

    Not in our library10.1158/0008-5472.can-10-2836

  256. 256.

    Martin S.A., McCarthy A., Barber L.J., Burgess D.J., Parry S., Lord C.J. Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the DNA mismatch repair gene MSH2. EMBO Mol Med. 2009;1:323-337.

    Not in our library10.1002/emmm.200900040

  257. 257.

    Martin S.A., Lord C.J., Ashworth A. Therapeutic targeting of the DNA mismatch repair pathway. Clin Cancer Res. 2010;16:5107-5113.

    Not in our library10.1158/1078-0432.ccr-10-0821

  258. 258.

    Sajesh B.V., Bailey M., Lichtensztejn Z., Hieter P., McManus K.J. Synthetic lethal targeting of superoxide dismutase 1 selectively kills RAD54B-deficient colorectal cancer cells. Genetics. 2013;195:757-767.

    Not in our library10.1534/genetics.113.156836

  259. 259.

    McCabe N., Turner N.C., Lord C.J., Kluzek K., Bialkowska A., Swift S. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. 2006;66:8109-8115.

    Not in our library10.1158/0008-5472.can-06-0140

  260. 260.

    Vilar E., Bartnik C.M., Stenzel S.L., Raskin L., Ahn J., Moreno V. MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. Cancer Res. 2011;71:2632-2642.

    Not in our library10.1158/0008-5472.can-10-1120

  261. 261.

    Miquel C., Jacob S., Grandjouan S., Aime A., Viguier J., Sabourin J.C. Frequent alteration of DNA damage signalling and repair pathways in human colorectal cancers with microsatellite instability. Oncogene. 2007;26:5919-5926.

    Not in our library10.1038/sj.onc.1210419

  262. 262.

    Phalon C., Rao D.D., Nemunaitis J. Potential use of RNA interference in cancer therapy. Expert Rev Mol Med. 2010;2010.

    Not in our library10.1017/s1462399410001584

  263. 263.

    Liang Y., Gao H., Lin S.Y., Goss J.A., Brunicardi F.C., Li K. siRNA-based targeting of cyclin E overexpression inhibits breast cancer cell growth and suppresses tumor development in breast cancer mouse model. PLoS ONE. 2010;5:e12860.

    Not in our library10.1371/journal.pone.0012860

  264. 264.

    Papoutsis A.J., Borg J.L., Selmin O.I., Romagnolo D.F. BRCA-1 promoter hypermethylation and silencing induced by the aromatic hydrocarbon receptor-ligand TCDD are prevented by resveratrol in MCF-7 cells. J Nutr Biochem. 2012;23:1324-1332.

    Not in our library10.1016/j.jnutbio.2011.08.001

  265. 265.

    King-Batoon A., Leszczynska J.M., Klein C.B. Modulation of gene methylation by genistein or lycopene in breast cancer cells. Environ Mol Mutagen. 2008;49:36-45.

    Not in our library10.1002/em.20363

  266. 266.

    Fukasawa K. P53, cyclin-dependent kinase and abnormal amplification of centrosomes. Biochim Biophys Acta. 2008;1786:15-23.

    Not in our library10.1016/j.bbcan.2008.04.002

  267. 267.
    Cyclin-dependent kinase control of centrosome duplication · 1999
    Not checked
  268. 268.

    Lee S.C., Chan J.Y., Pervaiz S. Spontaneous and 5-fluorouracil-induced centrosome amplification lowers the threshold to resveratrol-evoked apoptosis in colon cancer cells. Cancer Lett. 2010;288:36-41.

    Not in our library10.1016/j.canlet.2009.06.020

  269. 269.

    Fukasawa K. Centrosome amplification, chromosome instability and cancer development. Cancer Lett. 2005;230:6-19.

    Not in our library10.1016/j.canlet.2004.12.028

  270. 270.

    Castiel A., Visochek L., Mittelman L., Dantzer F., Izraeli S., Cohen-Armon M. A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent exclusively eradicating human cancer cells. BMC Cancer. 2011;11:412.

    Not in our library10.1186/1471-2407-11-412

  271. 271.

    Otten J.J., Hellwig J.P., Meyers L.D. DRI, dietary reference intakes: the essential guide to nutrient requirements. 2006.

    Not in our library

  272. 272.

    Neeha V.S., Kinth P. Nutrigenomics research: a review. J Food Sci Technol. 2013;50:415-428.

    Not in our library10.1007/s13197-012-0775-z

  273. 273.

    German J.B., Zivkovic A.M., Dallas D.C., Smilowitz J.T. Nutrigenomics and personalized diets: what will they mean for food? Ann Rev Food Sci Technol. 2011;2:97-123.

    Not in our library10.1146/annurev.food.102308.124147

  274. 274.

    Peto R., Doll R., Buckley J.D., Sporn M. Can dietary beta-carotene materially reduce human cancer rates. Nature. 1981;290:201-208.

    Not in our library10.1038/290201a0

  275. 275.

    Omenn G.S., Goodman G.E., Thornquist M.D., Balmes J., Cullen M.R., Glass A. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996;88:1550-1559.

    Not in our library10.1093/jnci/88.21.1550

  276. 276.

    Bjelakovic G., Nikolova D., Gluud L.L., Simonetti R.G., Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297:842-857.

    Not in our library10.1001/jama.297.8.842

  277. 277.

    Foksinski M., Gackowski D., Rozalski R., Siomek A., Guz J., Szpila A. Effects of basal level of antioxidants on oxidative DNA damage in humans. Eur J Nutr. 2007;46:174-180.

    Not in our library10.1007/s00394-006-0642-7

  278. 278.

    Çalışkan-Can E., Fırat H., Ardıç S., Şimşek B., Torun M., Yardim-Akaydin S. Increased levels of 8-hydroxydeoxyguanosine and its relationship with lipid peroxidation and antioxidant vitamins in lung cancer. Clin Chem Lab Med. 2008;46:107-112.

    Not in our library10.1515/cclm.2008.010

  279. 279.

    Sram R., Farmer P., Singh R., Garte S., Kalina I., Popov T. Effect of vitamin levels on biomarkers of exposure and oxidative damage – the EXPAH study. Mutat Res. 2009;672:129-134.

    Not in our library10.1016/j.mrgentox.2008.11.005

  280. 280.

    Kelvin E.A., Edwards S., Jedrychowski W., Schleicher R.L., Camann D., Tang D. Modulation of the effect of prenatal PAH exposure on PAH-DNA adducts in cord blood by plasma antioxidants. Cancer Epidemiol Biomark. 2009;18:2262-2268.

    Not in our library10.1158/1055-9965.epi-09-0316

  281. 281.

    Park E., Park Y.K., Kim S.-M., Lee H.-J., Kang M.-H. Susceptibility to oxidative stress is greater in Korean Patients with Coronary Artery Disease than Healthy Subjects. J Clin Biochem Nutr. 2009;45:341.

    Not in our library10.3164/jcbn.09-44

  282. 282.
    8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker of oxidative damage in oesophageal cancer patients: lack of association with antioxidant vitamins and polymorphism of <it>hOGG1 </it>and <it>GST</it> · 2010
    Not checked
  283. 283.

    Briviba K., Bub A., Möseneder J., Schwerdtle T., Hartwig A., Kulling S. No differences in DNA damage and antioxidant capacity between intervention groups of healthy, nonsmoking men receiving 2, 5, or 8 servings/day of vegetables and fruit. Nutr Cancer. 2008;60:164-170.

    Not in our library10.1080/01635580701621346

  284. 284.

    Cho S., Lee D.H., Won C.-H., Kim S.M., Lee S., Lee M.-J. Differential effects of low-dose and high-dose beta-carotene supplementation on the signs of photoaging and type I procollagen gene expression in human skin in vivo. Dermatology. 2010;221:160-171.

    Not in our library10.1159/000305548

  285. 285.

    Devaraj S., Mathur S., Basu A., Aung H.H., Vasu V.T., Meyers S. A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr. 2008;27:267-273.

    Not in our library10.1080/07315724.2008.10719699

  286. 286.
    Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans · 2010
    No notice
  287. 287.

    van Helden Y.G., Keijer J., Heil S.G., Picó C., Palou A., Oliver P. Beta-carotene affects oxidative stress-related DNA damage in lung epithelial cells and in ferret lung. Carcinogenesis. 2009;30:2070-2076.

    Not in our library10.1093/carcin/bgp186

  288. 288.

    Velanganni A., Dharaneedharan S., Geraldine P., Balasundram C. Dietary supplementation of vitamin A, C and E prevents p-dimethylamino-azobenzene induced hepatic DNA damage in rats. Indian J Biochem Biophys. 2007;44:157.

    Not in our library

  289. 289.

    Liu C., Bronson R.T., Russell R.M., Wang X.-D. β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage, and squamous metaplasia in ferrets. Cancer Prev Res. 2011;4:1255-1266.

    Not in our library10.1158/1940-6207.capr-10-0384

  290. 290.

    Moreno F.S., Toledo L.P., de Conti A., Heidor R., Jordão A., Vannucchi H. Lutein presents suppressing but not blocking chemopreventive activity during diethylnitrosamine-induced hepatocarcinogenesis and this involves inhibition of DNA damage. Chem Biol Interact. 2007;168:221-228.

    Not in our library10.1016/j.cbi.2007.04.011

  291. 291.

    Ferreira A.L.A., Salvadori D.M.F., Nascimento M.C.M.O., Rocha N.S., Correa C.R., Pereira E.J. Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats. Mutat Res. 2007;631:26-35.

    Not in our library10.1016/j.mrgentox.2007.04.003

  292. 292.

    Tripathi D., Jena G. Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology. 2008;248:96-103.

    Not in our library10.1016/j.tox.2008.03.015

  293. 293.

    Nakajima Y., Inokuchi Y., Shimazawa M., Otsubo K., Ishibashi T., Hara H. Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivo. J Pharm Pharmacol. 2008;60:1365-1374.

    Not in our library10.1211/jpp/60.10.0013

  294. 294.

    Scolastici C., Lopes G.A., Barbisan L.F., Salvadori D.M. Tomato oleoresin inhibits DNA damage but not diethylnitrosamine-induced rat hepatocarcinogenesis. Exp Toxicol Pathol. 2008;60:59-68.

    Not in our library10.1016/j.etp.2008.01.010

  295. 295.

    Tripathi D., Jena G. Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact. 2009;180:398-406.

    Not in our library10.1016/j.cbi.2009.03.017

  296. 296.

    Serpeloni J.M., Grotto D., Mercadante A.Z., de Lourdes Pires Bianchi M., Antunes L.M.G. Lutein improves antioxidant defense in vivo and protects against DNA damage and chromosome instability induced by cisplatin. Arch Toxicol. 2010;84:811-822.

    Not in our library10.1007/s00204-010-0576-y

  297. 297.

    Sasaki M., Yuki K., Kurihara T., Miyake S., Noda K., Kobayashi S. Biological role of lutein in the light-induced retinal degeneration. J Nutr Biochem. 2012;23:423-429.

    Not in our library10.1016/j.jnutbio.2011.01.006

  298. 298.

    Chew B.P., Mathison B.D., Hayek M.G., Massimino S., Reinhart G.A., Park J.S. Dietary astaxanthin enhances immune response in dogs. Vet Immunol Immunopathol. 2011;140:199-206.

    Not in our library10.1016/j.vetimm.2010.12.004

  299. 299.

    Tripathi D., Jena G. Astaxanthin intervention ameliorates cyclophosphamide-induced oxidative stress, DNA damage and early hepatocarcinogenesis in rat: role of Nrf2, p53, p38 and phase-II enzymes. Mutat Res. 2010;696:69-80.

    Not in our library10.1016/j.mrgentox.2009.12.014

  300. 300.

    Huang C.-S., Hu M.-L. Lycopene inhibits DNA damage and reduces hMTH1 mRNA expression in the liver of Mongolian gerbils treated with ferric nitrilotriacetate. Food Chem Toxicol. 2011;49:1381-1386.

    Not in our library10.1016/j.fct.2011.03.023

  301. 301.

    Morin B., Narbonne J.-F., Ribera D., Badouard C., Ravanat J.-L. Effect of dietary fat-soluble vitamins A and E and proanthocyanidin-rich extract from grape seeds on oxidative DNA damage in rats. Food Chem Toxicol. 2008;46:787-796.

    Not in our library10.1016/j.fct.2007.10.011

  302. 302.

    Konijeti R., Henning S., Moro A., Sheikh A., Elashoff D., Shapiro A. Chemoprevention of prostate cancer with lycopene in the TRAMP model. Prostate. 2010;70:1547-1554.

    Not in our library10.1002/pros.21190

  303. 303.

    Zhou G.-D., Richardson M., Fazili I.S., Wang J., Donnelly K.C., Wang F. Role of retinoic acid in the modulation of benzo (a) pyrene-DNA adducts in human hepatoma cells: implications for cancer prevention. Toxicol Appl Pharm. 2010;249:224-230.

    Not in our library10.1016/j.taap.2010.09.019

  304. 304.

    Reddy L., Odhav B., Bhoola K. Aflatoxin B1-induced toxicity in HepG2 cells inhibited by carotenoids: morphology, apoptosis and DNA damage. Biol Chem. 2006;387:87-93.

    Not in our library10.1515/bc.2006.012

  305. 305.

    Bergström T., Bergman J., Möller L. Vitamin A and C compounds permitted in supplements differ in their abilities to affect cell viability, DNA and the DNA nucleoside deoxyguanosine. Mutagenesis. 2011;26:735-744.

    Not in our library10.1093/mutage/ger041

  306. 306.

    Lorenzo Y., Azqueta A., Luna L., Bonilla F., Domínguez G., Collins A.R. The carotenoid β-cryptoxanthin stimulates the repair of DNA oxidation damage in addition to acting as an antioxidant in human cells. Carcinogenesis. 2009;30:308-314.

    Not in our library10.1093/carcin/bgn270

  307. 307.

    Rosignoli P., Fabiani R., De Bartolomeo A., Fuccelli R., Pelli M.A., Morozzi G. Genotoxic effect of bile acids on human normal and tumour colon cells and protection by dietary antioxidants and butyrate. Eur J Nutr. 2008;47:301-309.

    Not in our library10.1007/s00394-008-0725-8

  308. 308.

    Yurtcu E., Iseri O.D., Sahin F.I. Effects of ascorbic acid and β-carotene on HepG2 human hepatocellular carcinoma cell line. Mol Biol Rep. 2011;38:4265-4272.

    Not in our library10.1007/s11033-010-0549-5

  309. 309.

    van Helden Y.G., Keijer J., Knaapen A.M., Heil S.G., Briedé J.J., Van Schooten F.J. β-Carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells. Free Rad Biol Med. 2009;46:299-304.

    Not in our library10.1016/j.freeradbiomed.2008.10.038

  310. 310.

    Shiau R.-J., Chen K.-Y., Wen Y.-D., Chuang C.-H., Yeh S.-L. Genistein and β-carotene enhance the growth-inhibitory effect of trichostatin A in A549 cells. Eur J Nutr. 2010;49:19-25.

    Not in our library10.1007/s00394-009-0044-8

  311. 311.

    Kontek R., Drozda R., Śliwiński M., Grzegorczyk K. Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients. Toxicol In Vitro. 2010;24:417-424.

    Not in our library10.1016/j.tiv.2009.10.013

  312. 312.

    Jang S.H., Lim J.W., Kim H. Mechanism of β-carotene-induced apoptosis of gastric cancer cells: involvement of ataxia-telangiectasia-mutated. Ann N Y Acad Sci. 2009;1171:156-162.

    Not in our library10.1111/j.1749-6632.2009.04711.x

  313. 313.

    Santocono M., Zurria M., Berrettini M., Fedeli D., Falcioni G. Lutein, zeaxanthin and astaxanthin protect against DNA damage in SK-N-SH human neuroblastoma cells induced by reactive nitrogen species. J Photochem Photobiol B: Biol. 2007;88:1-10.

    Not in our library10.1016/j.jphotobiol.2007.04.007

  314. 314.

    Scolastici C., de Lima R., Barbisan L., Ferreira A., Ribeiro D., Salvadori D. Lycopene activity against chemically induced DNA damage in Chinese hamster ovary cells. Toxicol In Vitro. 2007;21:840-845.

    Not in our library10.1016/j.tiv.2007.01.020

  315. 315.

    Srinivasan M., Sudheer A.R., Pillai K.R., Kumar P.R., Sudhakaran P., Menon V. Lycopene as a natural protector against γ-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes in vitro. Biochim Biophys Acta. 2007;1770:659-665.

    Not in our library10.1016/j.bbagen.2006.11.008

  316. 316.

    Srinivasan M., Devipriya N., Kalpana K., Menon V.P. Lycopene: an antioxidant and radioprotector against γ-radiation-induced cellular damages in cultured human lymphocytes. Toxicology. 2009;262:43-49.

    Not in our library10.1016/j.tox.2009.05.004

  317. 317.

    Kowalczyk M.C., Walaszek Z., Kowalczyk P., Kinjo T., Hanausek M., Slaga T.J. Differential effects of several phytochemicals and their derivatives on murine keratinocytes in vitro and in vivo: implications for skin cancer prevention. Carcinogenesis. 2009;30:1008-1015.

    Not in our library10.1093/carcin/bgp069

  318. 318.

    Zini A., San Gabriel M., Libman J. Lycopene supplementation in vitro can protect human sperm deoxyribonucleic acid from oxidative damage. Fertil Steril. 2010;94:1033-1036.

    Not in our library10.1016/j.fertnstert.2009.04.004

  319. 319.

    Collins A.R., Azqueta A., Langie S.A. Effects of micronutrients on DNA repair. Eur J Nutr. 2012;51:261-279.

    Not in our library10.1007/s00394-012-0318-4

  320. 320.

    Astley S.B., Elliott R.M., Archer D.B., Susan Southon S. Evidence that dietary supplementation with carotenoids and carotenoid-rich foods modulates the DNA damage:repair balance in human lymphocytes. Br J Nutr. 2004;91:63-72.

    Not in our library10.1079/bjn20031001

  321. 321.

    Astley S.B., Elliott R.M., Archer D.B., Southon S. Increased cellular carotenoid levels reduce the persistence of DNA single-strand breaks after oxidative challenge. Nutr Cancer. 2002;43:202-213.

    Not in our library10.1207/s15327914nc432_11

  322. 322.

    Glei M., Liegibel U.M., Ebert M.N., Böhm V., Pool-Zobel B.L. β-Carotene reduces bleomycin-induced genetic damage in human lymphocytes. Toxicol Appl Pharm. 2002;179:65-73.

    Not in our library10.1006/taap.2001.9329

  323. 323.

    van Helden Y.G., Keijer J., Heil S.G., Pico C., Palou A., Oliver P. Beta-carotene affects oxidative stress-related DNA damage in lung epithelial cells and in ferret lung. Carcinogenesis. 2009;30:2070-2076.

    Not in our library10.1093/carcin/bgp186

  324. 324.

    Di Re F., Bohm S., Oriana S., Spatti G.B., Zunino F. Efficacy and safety of high-dose cisplatin and cyclophosphamide with glutathione protection in the treatment of bulky advanced epithelial ovarian cancer. Cancer Chemother Pharmacol. 1990;25:355-360.

    Not in our library10.1007/bf00686237

  325. 325.

    Smyth J.F., Bowman A., Perren T., Wilkinson P., Prescott R.J., Quinn K.J. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Ann Oncol. 1997;8:569-573.

    Not in our library10.1023/a:1008211226339

  326. 326.

    Calvert P., Yao K.S., Hamilton T.C., O’Dwyer P.J. Clinical studies of reversal of drug resistance based on glutathione. Chem Biol Interact. 1998;111–112:213-224.

    Not in our library10.1016/s0009-2797(98)00008-8

  327. 327.

    Estrela J.M., Ortega A., Obrador E. Glutathione in cancer biology and therapy. Crit Rev Clin Labor Sci. 2006;43:143-181.

    Not in our library10.1080/10408360500523878

  328. 328.

    Ali-Osman F., Akande O., Antoun G., Mao J.X., Buolamwini J. Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem. 1997;272:10004-10012.

    Not in our library10.1074/jbc.272.15.10004

  329. 329.

    Stoehlmacher J., Park D.J., Zhang W., Groshen S., Tsao-Wei D.D., Yu M.C. Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst. 2002;94:936-942.

    Not in our library10.1093/jnci/94.12.936

  330. 330.

    Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.

    Not in our library10.1126/science.1160809

  331. 331.

    El Sayed S.M., Mahmoud A.A., El Sawy S.A., Abdelaal E.A., Fouad A.M., Yousif R.S. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect). Med Hypotheses. 2013;81:866-870.

    Not in our library10.1016/j.mehy.2013.08.024

  332. 332.

    van Ommen B., El-Sohemy A., Hesketh J., Kaput J., Fenech M., Evelo C.T. The Micronutrient Genomics Project: a community-driven knowledge base for micronutrient research. Genes Nutr. 2010;5:285-296.

    Not in our library10.1007/s12263-010-0192-8

  333. 333.

    Sram R.J., Binkova B., Rossner P. Vitamin C for DNA damage prevention. Mutat Res. 2012;733:39-49.

    Not in our library10.1016/j.mrfmmm.2011.12.001

  334. 334.

    Nair-Shalliker V., Armstrong B.K., Fenech M. Does vitamin D protect against DNA damage? Mutat Res. 2012;733:50-57.

    Not in our library10.1016/j.mrfmmm.2012.02.005

  335. 335.

    Prá D., Franke S.I.R., Henriques J.A.P., Fenech M. Iron and genome stability: an update. Mutat Res. 2012;733:92-99.

    Not in our library10.1016/j.mrfmmm.2012.02.001

  336. 336.

    Ferguson L.R., Karunasinghe N., Zhu S., Wang A.H. Selenium and its’ role in the maintenance of genomic stability. Mutat Res. 2012;733:100-110.

    Not in our library10.1016/j.mrfmmm.2011.12.011

  337. 337.

    Sharif R., Thomas P., Zalewski P., Fenech M. The role of zinc in genomic stability. Mutat Res. 2012;733:111-121.

    Not in our library10.1016/j.mrfmmm.2011.08.009

  338. 338.

    Ferguson L., Schlothauer R. The potential role of nutritional genomics tools in validating high health foods for cancer control: broccoli as example. Mol Nutr Food Res. 2012;56:126-146.

    Not in our library10.1002/mnfr.201100507

  339. 339.

    Karunasinghe N., Han D.Y., Zhu S., Yu J., Lange K., Duan H. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 2012;7:179-190.

    Not in our library10.1007/s12263-011-0259-1

  340. 340.

    Duthie S.J. Berry phytochemicals, genomic stability and cancer: evidence for chemoprotection at several stages in the carcinogenic process. Mol Nutr Food Res. 2007;51:665-674.

    Not in our library10.1002/mnfr.200600257

  341. 341.

    Lim U., Song M.-A. Dietary and lifestyle factors of DNA methylation. Cancer epigenetics. 2012;359-376.

    Not in our library10.1007/978-1-61779-612-8_23

  342. 342.

    Hansen L.A., Malarkey D.E., Wilkinson J.E., Rosenberg M., Woychik R.E., Tennant R.W. Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice. Carcinogenesis. 1998;19:1837-1845.

    Not in our library10.1093/carcin/19.10.1837

  343. 343.

    Kuklin A.I., Mynatt R.L., Klebig M.L., Kiefer L.L., Wilkison W.O., Woychik R.P. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes. Mol Cancer. 2004;3:17.

    Not in our library10.1186/1476-4598-3-17

  344. 344.

    Morgan H.D., Sutherland H.G., Martin D.I., Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23:314-318.

    Not in our library10.1038/15490

  345. 345.

    Dolinoy D.C., Huang D., Jirtle R.L. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A. 2007;104:13056-13061.

    Not in our library10.1073/pnas.0703739104

  346. 346.

    Bunin G.R., Kuijten R.R., Buckley J.D., Rorke L.B., Meadows A.T. Relation between maternal diet and subsequent primitive neuroectodermal brain tumors in young children. New Engl J Med. 1993;329:536-541.

    Not in our library10.1056/nejm199308193290804

  347. 347.

    Ferguson L.R. Role of plant polyphenols in genomic stability. Mutat Res. 2001;475:89-111.

    Not in our library10.1016/s0027-5107(01)00073-2

  348. 348.

    Lopez R., Arumugam A., Joseph R., Monga K., Boopalan T., Agullo P. Hyperglycemia enhances the proliferation of non-tumorigenic and malignant mammary epithelial cells through increased leptin/IGF1R signaling and activation of AKT/mTOR. PLOS ONE. 2013;8:e79708.

    Not in our library10.1371/journal.pone.0079708

  349. 349.

    Hilakivi-Clarke L., Clarke R., Onojafe I., Raygada M., Cho E., Lippman M. A maternal diet high in n-6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring. Proc Natl Acad Sci U S A. 1997;94:9372-9377.

    Not in our library10.1073/pnas.94.17.9372

  350. 350.

    Villarreal-Garza C., Shaw-Dulin R., Lara-Medina F., Bacon L., Rivera D., Urzua L. Impact of diabetes and hyperglycemia on survival in advanced breast cancer patients. Exp Diabetes Res. 2012;2012:732027.

    Not in our library10.1155/2012/732027

  351. 351.

    Butturini A.M., Dorey F.J., Lange B.J., Henry D.W., Gaynon P.S., Fu C. Obesity and outcome in pediatric acute lymphoblastic leukemia. J Clin Oncol. 2007;25:2063-2069.

    Not in our library10.1200/jco.2006.07.7792

  352. 352.

    Kloor M., Michel S., von Knebel Doeberitz M. Immune evasion of microsatellite unstable colorectal cancers. Int J Cancer. 2010;127:1001-1010.

    Not in our library10.1002/ijc.25283

  353. 353.

    Liu W., Asa S.L., Fantus I.G., Walfish P.G., Ezzat S. Vitamin D arrests thyroid carcinoma cell growth and induces p27 dephosphorylation and accumulation through PTEN/akt-dependent and -independent pathways. Am J Pathol. 2002;160:511-519.

    Not in our library10.1016/s0002-9440(10)64870-5

  354. 354.

    Zhang M., Zhou X., Zhou K. Resveratrol inhibits human nasopharyngeal carcinoma cell growth via blocking pAkt/p70S6K signaling pathways. Int J Mol Med. 2013;31:621-627.

    Not in our library10.3892/ijmm.2013.1237

  355. 355.

    Amiri F., Zarnani A.H., Zand H., Koohdani F., Jeddi-Tehrani M., Vafa M. Synergistic anti-proliferative effect of resveratrol and etoposide on human hepatocellular and colon cancer cell lines. Eur J Pharmacol. 2013;718:34-40.

    Not in our library10.1016/j.ejphar.2013.09.020

  356. 356.
    Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium. · 2013
    Not checked
  357. 357.

    Lee Y.C., Tang Y.C., Chen Y.H., Wong C.M., Tsou A.P. Selenite-induced survival of HuH7 hepatoma cells involves activation of focal adhesion kinase-phosphatidylinositol 3-kinase-Akt pathway and Rac1. J Biol Chem. 2003;278:39615-39624.

    Not in our library10.1074/jbc.m304095200

  358. 358.

    Chuang H.-C., Kapuriya N., Kulp S., Chen C.-S., Shapiro C. Differential anti-proliferative activities of poly(ADP-ribose) polymerase (PARP) inhibitors in triple-negative breast cancer cells. Br Cancer Res Treat. 2012;134:649-659.

    Not in our library10.1007/s10549-012-2106-5

  359. 359.

    Chun J., Nadiminty N., Lee S., Onate S., Lou W., Gao A. Mechanisms of selenium down-regulation of androgen receptor signaling in prostate cancer. Mol Cancer Ther. 2006;5:913-918.

    Not in our library10.1158/1535-7163.mct-05-0389

  360. 360.

    Jakubikova J., Cervi D., Ooi M., Kim K., Nahar S., Klippel S. Anti-tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma. Haematologica. 2011;96:1170-1179.

    Not in our library10.3324/haematol.2010.029363

  361. 361.

    Kang L., Wang Z.-Y. Breast cancer cell growth inhibition by phenethyl isothiocyanate is associated with down-regulation of oestrogen receptor-alpha36. J Cell Mol Med. 2010;14:1485-1493.

    Not in our library10.1111/j.1582-4934.2009.00877.x

  362. 362.

    Keith M., Laporta E., Welsh J. Stable expression of human VDR in murine VDR-null cells recapitulates vitamin D mediated anti-cancer signaling. Mol Carcinog. 2013.

    Not in our library10.1002/mc.21975

  363. 363.

    Kim S.-H., Nagalingam A., Saxena N., Singh S., Sharma D. Benzyl isothiocyanate inhibits oncogenic actions of leptin in human breast cancer cells by suppressing activation of signal transducer and activator of transcription 3. Carcinogenesis. 2011;32:359-367.

    Not in our library10.1093/carcin/bgq267

  364. 364.

    Lamy E., Herz C., Lutz-Bonengel S., Hertrampf A., Márton M.-R., Mersch-Sundermann V. The MAPK pathway signals telomerase modulation in response to isothiocyanate-induced DNA damage of human liver cancer cells. PLOS ONE. 2013;8.

    Not in our library10.1371/journal.pone.0053240

  365. 365.

    Lowe L., Hansen C., Senaratne S., Colston K. Mechanisms implicated in the growth regulatory effects of vitamin D compounds in breast cancer cells. Recent Results Cancer Res. 2003;164:99-110.

    Not in our library10.1007/978-3-642-55580-0_6

  366. 366.

    Palozza P., Serini S., Di Nicuolo F., Calviello G. Mitogenic and apoptotic signaling by carotenoids: involvement of a redox mechanism. IUBMB Life. 2001;52:77-81.

    Not in our library10.1080/15216540252774810

  367. 367.

    Błasiak J., Kadłubek M., Kowalik J., Romanowicz-Makowska H., Pertyński T. Inhibition of telomerase activity in endometrial cancer cells by selenium-cisplatin conjugate despite suppression of its DNA-damaging activity by sodium ascorbate. Teratog Carcinog Mutagen. 2002;22:73-82.

    Not in our library10.1002/tcm.1040

  368. 368.

    Efimova E., Mauceri H., Golden D., Labay E., Bindokas V., Darga T. Poly(ADP-ribose) polymerase inhibitor induces accelerated senescence in irradiated breast cancer cells and tumors. Cancer Res. 2010;70:6277-6282.

    Not in our library10.1158/0008-5472.can-09-4224

  369. 369.

    Ikeda N., Uemura H., Ishiguro H., Hori M., Hosaka M., Kyo S. Combination treatment with 1alpha,25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells. Mol Cancer Ther. 2003;2:739-746.

    Not in our library

  370. 370.

    Kasiappan R., Shen Z., Tse A., Jinwal U., Tang J., Lungchukiet P. 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498. J Biol Chem. 2012;287:41297-41309.

    Not in our library10.1074/jbc.m112.407189

  371. 371.

    Lamy E., Oey D., Eißmann F., Herz C., Münstedt K., Tinneberg H.-R. Erucin and benzyl isothiocyanate suppress growth of late stage primary human ovarian carcinoma cells and telomerase activity in vitro. Phytother Res. 2013;27:1036-1041.

    Not in our library10.1002/ptr.4798

  372. 372.

    Liu L., Berletch J.B., Green J.G., Pate M.S., Andrews L.G., Tollefsbol T.O. Telomerase inhibition by retinoids precedes cytodifferentiation of leukemia cells and may contribute to terminal differentiation. Mol Cancer Ther. 2004;3:1003-1009.

    Not in our library

  373. 373.

    Love W., Berletch J., Andrews L., Tollefsbol T. Epigenetic regulation of telomerase in retinoid-induced differentiation of human leukemia cells. Int J Oncol. 2008;32:625-631.

    Not in our library

  374. 374.

    Zhang X., Nicosia S.V., Bai W. Vitamin D receptor is a novel drug target for ovarian cancer treatment. Curr Cancer Drug Targets. 2006;6:229-244.

    Not in our library10.2174/156800906776842939

  375. 375.

    Fuggetta M.P., Lanzilli G., Tricarico M., Cottarelli A., Falchetti R., Ravagnan G. Effect of resveratrol on proliferation and telomerase activity of human colon cancer cells in vitro. J Exp Clin Cancer Res. 2006;25:189-193.

    Not in our library

  376. 376.

    Lanzilli G., Fuggetta M.P., Tricarico M., Cottarelli A., Serafino A., Falchetti R. Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro. Int J Oncol. 2006;28:641-648.

    Not in our library

  377. 377.

    Rengarajan T., Rajendran P., Nandakumar N., Balasubramanian M., Nishigaki I. Cancer preventive efficacy of marine carotenoid fucoxanthin: cell cycle arrest and apoptosis. Nutrients. 2013;5:4978-4989.

    Not in our library10.3390/nu5124978

  378. 378.
    Selenium Compounds, Apoptosis and Other Types of Cell Death: An Overview for Cancer Therapy · 2012
    No notice
  379. 379.

    Thomson S., Brown K., Pullar J., Hampton M. Phenethyl isothiocyanate triggers apoptosis in Jurkat cells made resistant by the overexpression of Bcl-2. Cancer Res. 2006;66:6772-6777.

    Not in our library10.1158/0008-5472.can-05-3809

  380. 380.

    Ting H.-J., Hsu J., Bao B.-Y., Lee Y.-F. Docetaxel-induced growth inhibition and apoptosis in androgen independent prostate cancer cells are enhanced by 1alpha,25-dihydroxyvitamin D3. Cancer Lett. 2007;247:122-129.

    Not in our library10.1016/j.canlet.2006.03.025

  381. 381.

    Zhang J., Kan Y., Tian Y., Wang Z., Zhang J. Effects of poly (ADP-ribosyl) polymerase (PARP) inhibitor on cisplatin resistance & proliferation of the ovarian cancer C13* cells. Indian J Med Res. 2013;137:527-532.

    Not in our library

  382. 382.

    Wesolowska O., Wisniewski J., Bielawska-Pohl A., Paprocka M., Duarte N., Ferreira M.J. Stilbenes as multidrug resistance modulators and apoptosis inducers in human adenocarcinoma cells. Anticancer Res. 2010;30:4587-4593.

    Not in our library

  383. 383.

    Chen H., Landen C., Li Y., Alvarez R., Tollefsbol T. Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation. Exp Cell Res. 2013;319:697-706.

    Not in our library10.1016/j.yexcr.2012.12.026

  384. 384.

    El-Bayoumy K. The protective role of selenium on genetic damage and on cancer. Mutat Res. 2001;475:123-139.

    Not in our library10.1016/s0027-5107(01)00075-6

  385. 385.

    Moon D.-O., Kang S.-H., Kim K.-C., Kim M.-O., Choi Y., Kim G.-Y. Sulforaphane decreases viability and telomerase activity in hepatocellular carcinoma Hep3B cells through the reactive oxygen species-dependent pathway. Cancer Lett. 2010;295:260-266.

    Not in our library10.1016/j.canlet.2010.03.009

  386. 386.

    Donkena K.V., Yuan H., Young C.Y. Vitamin Bs, one carbon metabolism and prostate cancer. Mini Rev Med Chem. 2010;10:1385-1392.

    Not in our library10.2174/138955710793564106

  387. 387.

    Rayet B., Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18:6938-6947.

    Not in our library10.1038/sj.onc.1203221

  388. 388.
    NF-kappa B genes have a major role in Inflammatory Breast Cancer · 2008
    No notice
  389. 389.

    Batra S., Sahu R.P., Kandala P.K., Srivastava S.K. Benzyl isothiocyanate-mediated inhibition of histone deacetylase leads to NF-kappaB turnoff in human pancreatic carcinoma cells. Mol Cancer Ther. 2010;9:1596-1608.

    Not in our library10.1158/1535-7163.mct-09-1146

  390. 390.

    Choi K.C., Jung M.G., Lee Y.H., Yoon J.C., Kwon S.H., Kang H.B. Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Res. 2009;69:583-592.

    Not in our library10.1158/0008-5472.can-08-2442

  391. 391.

    Hopkins M.H., Owen J., Ahearn T., Fedirko V., Flanders W.D., Jones D.P. Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorectal adenoma patients: a randomized, controlled clinical trial. Cancer Prev Res. 2011;4:1645-1654.

    Not in our library10.1158/1940-6207.capr-11-0105

  392. 392.

    Krishnan A.V., Moreno J., Nonn L., Swami S., Peehl D.M., Feldman D. Calcitriol as a chemopreventive and therapeutic agent in prostate cancer: role of anti-inflammatory activity. J Bone Miner Res. 2007;22(Suppl 2):V74-V80.

    Not in our library10.1359/jbmr.07s213

  393. 393.

    Zhang X.-H., Ma J., Smith-Warner S., Lee J., Giovannucci E. Vitamin B6 and colorectal cancer: current evidence and future directions. World J Gastroenterol. 2013;19:1005-1010.

    Not in our library10.3748/wjg.v19.i7.1005

  394. 394.

    Sharp L., Carsin A.E., Cantwell M.M., Anderson L.A., Murray L.J., Group F.S. Intakes of dietary folate and other B vitamins are associated with risks of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. J Nutr. 2013;143:1966-1973.

    Not in our library10.3945/jn.113.174664

  395. 395.

    Barrett C., Singh K., Motley A., Lintel M., Matafonova E., Bradley A. Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis. PLOS ONE. 2013;8.

    Not in our library10.1371/journal.pone.0067845

  396. 396.

    Kristal A., Arnold K., Neuhouser M., Goodman P., Platz E., Albanes D. Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol. 2010;172:566-577.

    Not in our library10.1093/aje/kwq148

  397. 397.

    Ozten N., Horton L., Lasano S., Bosland M. Selenomethionine and alpha-tocopherol do not inhibit prostate carcinogenesis in the testosterone plus estradiol-treated NBL rat model. Cancer Prev Res (Phila). 2010;3:371-380.

    Not in our library10.1158/1940-6207.capr-09-0152

  398. 398.

    Trejo-Solís C., Pedraza-Chaverrí J., Torres-Ramos M., Jiménez-Farfán D., Cruz Salgado A., Serrano-García N. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid Based Complement Alternat Med. 2013;2013:705121.

    Not in our library10.1155/2013/705121

  399. 399.

    Wertz K. Lycopene effects contributing to prostate health. Nutr Cancer. 2009;61:775-783.

    Not in our library10.1080/01635580903285023

  400. 400.

    Swindall A., Stanley J., Yang E. PARP-1: friend or foe of DNA damage and repair in tumorigenesis. Cancers. 2013;5:943-958.

    Not in our library10.3390/cancers5030943

  401. 401.

    Masutani M., Fujimori H. Poly(ADP-ribosyl)ation in carcinogenesis. Mol Asp Med. 2013;34:1202-1216.

    Not in our library10.1016/j.mam.2013.05.003

  402. 402.

    Chen M.C., Chang W.W., Kuan Y.D., Lin S.T., Hsu H.C., Lee C.H. Resveratrol inhibits LPS-induced epithelial–mesenchymal transition in mouse melanoma model. Innate Immun. 2012;18:685-693.

    Not in our library10.1177/1753425912436589

  403. 403.

    Fahey J., Wehage S., Holtzclaw W., Kensler T., Egner P., Shapiro T. Protection of humans by plant glucosinolates: efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora. Cancer Prev Res (Phila). 2012;5:603-611.

    Not in our library10.1158/1940-6207.capr-11-0538

  404. 404.

    Li R., Li C., Wang T. Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate. Mol Carcinog. 2013;52:426-437.

    Not in our library10.1002/mc.21873

  405. 405.

    Kusmartsev S., Cheng F., Yu B., Nefedova Y., Sotomayor E., Lush R. All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res. 2003;63:4441-4449.

    Not in our library

  406. 406.
    Clinical Perspectives on Targeting of Myeloid Derived Suppressor Cells in the Treatment of Cancer · 2013
    No notice
  407. 407.

    Sayeed A., Luciani-Torres G., Meng Z., Bennington J.L., Moore D.H., Dairkee S.H. Aberrant regulation of the BST2 (Tetherin) promoter enhances cell proliferation and apoptosis evasion in high grade breast cancer cells. PLOS ONE. 2013;8:e67191.

    Not in our library10.1371/journal.pone.0067191

  408. 408.

    Aroni K., Anagnostopoulou K., Tsagroni E., Ioannidis E. Skin hyperpigmentation and increased angiogenesis secondary to vitamin B12 deficiency in a young vegetarian woman. Acta Derm Venereol. 2008;88:191-192.

    Not in our library10.2340/00015555-0377

  409. 409.

    Gadau S., Emanueli C., Van Linthout S., Graiani G., Todaro M., Meloni M. Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Diabetologia. 2006;49:405-420.

    Not in our library10.1007/s00125-005-0103-5

  410. 410.

    Huang P.H., Lin C.P., Wang C.H., Chiang C.H., Tsai H.Y., Chen J.S. Niacin improves ischemia-induced neovascularization in diabetic mice by enhancement of endothelial progenitor cell functions independent of changes in plasma lipids. Angiogenesis. 2012;15:377-389.

    Not in our library10.1007/s10456-012-9267-z

  411. 411.

    Jiang C., Jiang W., Ip C., Ganther H., Lu J. Selenium-induced inhibition of angiogenesis in mammary cancer at chemopreventive levels of intake. Mol Carcinog. 1999;26:213-225.

    Not in our library10.1002/(sici)1098-2744(199912)26:4<213::aid-mc1>3.0.co;2-z

  412. 412.

    Lin S.Y., Lee W.R., Su Y.F., Hsu S.P., Lin H.C., Ho P.Y. Folic acid inhibits endothelial cell proliferation through activating the cSrc/ERK 2/NF-kappaB/p53 pathway mediated by folic acid receptor. Angiogenesis. 2012;15:671-683.

    Not in our library10.1007/s10456-012-9289-6

  413. 413.

    McAuslan B.R., Reilly W. Selenium-induced cell migration and proliferation: relevance to angiogenesis and microangiopathy. Microvasc Res. 1986;32:112-120.

    Not in our library10.1016/0026-2862(86)90047-6

  414. 414.

    Premkumar V.G., Yuvaraj S., Sathish S., Shanthi P., Sachdanandam P. Anti-angiogenic potential of CoenzymeQ10, riboflavin and niacin in breast cancer patients undergoing tamoxifen therapy. Vasc Pharmacol. 2008;48:191-201.

    Not in our library10.1016/j.vph.2008.02.003

  415. 415.

    Sun D., Liu Y., Yu Q., Zhou Y., Zhang R., Chen X. The effects of luminescent ruthenium(II) polypyridyl functionalized selenium nanoparticles on bFGF-induced angiogenesis and AKT/ERK signaling. Biomaterials. 2013;34:171-180.

    Not in our library10.1016/j.biomaterials.2012.09.031

  416. 416.

    Arensman R.M., Stolar C.J. Vitamin A effect on tumor angiogenesis. J Pediatr Surg. 1979;14:809-813.

    Not in our library10.1016/s0022-3468(79)80271-7

  417. 417.

    Bajpai S., Mishra M., Kumar H., Tripathi K., Singh S., Pandey H. Effect of selenium on connexin expression, angiogenesis, and antioxidant status in diabetic wound healing. Biol Trace Elem Res. 2011;144:327-338.

    Not in our library10.1007/s12011-011-9097-7

  418. 418.

    Rajesh M., Mukhopadhyay P., Bátkai S., Godlewski G., Haskó G., Liaudet L. Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis. Biochem Biophys Res Commun. 2006;350:352-357.

    Not in our library10.1016/j.bbrc.2006.09.049

  419. 419.

    Thejass P., Kuttan G. Allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) inhibit tumour-specific angiogenesis by downregulating nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) production. Nitric Oxide. 2007;16:247-257.

    Not in our library10.1016/j.niox.2006.09.006

  420. 420.

    Boreddy S., Sahu R., Srivastava S. Benzyl isothiocyanate suppresses pancreatic tumor angiogenesis and invasion by inhibiting HIF-α/VEGF/Rho-GTPases: pivotal role of STAT-3. PLoS ONE. 2011;6.

    Not in our library10.1371/journal.pone.0025799

  421. 421.

    Krishnan A., Swami S., Feldman D. Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention. J Steroid Biochem Mol Biol. 2013;136:289-295.

    Not in our library10.1016/j.jsbmb.2012.08.005

  422. 422.

    Puduvalli V., Sampath D., Bruner J., Nangia J., Xu R., Kyritsis A. TRAIL-induced apoptosis in gliomas is enhanced by Akt-inhibition and is independent of JNK activation. Apoptosis. 2005;10:233-243.

    Not in our library10.1007/s10495-005-6078-3

  423. 423.

    Soares N., Teodoro A., Oliveira F., Santos C., Takiya C., Junior O. Influence of lycopene on cell viability, cell cycle, and apoptosis of human prostate cancer and benign hyperplastic cells. Nutr Cancer. 2013;65:1076-1085.

    Not in our library10.1080/01635581.2013.812225

  424. 424.

    Zastre J., Sweet R., Hanberry B., Ye S. Linking vitamin B1 with cancer cell metabolism. Cancer Metab. 2013;1:16.

    Not in our library10.1186/2049-3002-1-16

  425. 425.

    Park E., Wilder E., Lane M. Retinol inhibits the invasion of retinoic acid-resistant colon cancer cells in vitro and decreases matrix metalloproteinase mRNA, protein, and activity levels. Nutr Cancer. 2007;57:66-77.

    Not in our library10.1080/01635580701268238

  426. 426.

    Park E.Y., Pinali D., Lindley K., Lane M.A. Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in a mouse xenograft model. Nutr Cancer. 2012;64:732-740.

    Not in our library10.1080/01635581.2012.687425

  427. 427.

    Raffoul J., Heydari A., Hillman G., DNA repair and cancer therapy. Targeting APE1/Ref-1 using dietary agents. J Oncol. 2012;2012:370481.

    Not in our library10.1155/2012/370481

  428. 428.

    Rao L., Puschner B., Prolla T.A. Gene expression profiling of low selenium status in the mouse intestine: transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress. J Nutr. 2001;131:3175-3181.

    Not in our library10.1093/jn/131.12.3175

  429. 429.

    Storz P. Reactive oxygen species in tumor progression. Front Biosci. 2005;10:1881-1896.

    Not in our library10.2741/1667

  430. 430.

    Yang M.-D., Lai K.-C., Lai T.-Y., Hsu S.-C., Kuo C.-L., Yu C.-S. Phenethyl isothiocyanate inhibits migration and invasion of human gastric cancer AGS cells through suppressing MAPK and NF-kappaB signal pathways. Anticancer Res. 2010;30:2135-2143.

    Not in our library

  431. 431.

    Nishino H., Murakosh M., Ii T., Takemura M., Kuchide M., Kanazawa M. Carotenoids in cancer chemoprevention. Cancer Metastasis Rev. 2002;21:257-264.

    Not in our library10.1023/a:1021206826750

  432. 432.

    Damm K., Hemmann U., Garin-Chesa P., Hauel N., Kauffmann I., Priepke H. A highly selective telomerase inhibitor limiting human cancer cell proliferation. EMBO J. 2001;20:6958-6968.

    Not in our library10.1093/emboj/20.24.6958

  433. 433.

    Deeb D., Gao X., Liu Y., Kim S.H., Pindolia K.R., Arbab A.S. Inhibition of cell proliferation and induction of apoptosis by oleanane triterpenoid (CDDO-Me) in pancreatic cancer cells is associated with the suppression of hTERT gene expression and its telomerase activity. Biochem Biophys Res Commun. 2012;422:561-567.

    Not in our library10.1016/j.bbrc.2012.05.024

  434. 434.

    Ermolaeva M.A., Schumacher B. Systemic DNA damage responses: organismal adaptations to genome instability. Trends Genet. 2014;30:95-102.

    Not in our library10.1016/j.tig.2013.12.001

  435. 435.

    Etchegaray J.P., Zhong L., Mostoslavsky R. The histone deacetylase SIRT6: at the crossroads between epigenetics, metabolism and disease. Curr Top Med Chem. 2013;13:2991-3000.

    Not in our library10.2174/15680266113136660213

  436. 436.

    Szabo G., Lippai D. Molecular hepatic carcinogenesis: impact of inflammation. Dig Dis. 2012;30:243-248.

    Not in our library10.1159/000336913

  437. 437.

    Xia X., Liu S., Xiao Z., Zhu F., Song N.Y., Zhou M. An IKKalpha-nucleophosmin axis utilizes inflammatory signaling to promote genome integrity. Cell Rep. 2013;5:1243-1255.

    Not in our library10.1016/j.celrep.2013.10.046

  438. 438.

    Mishra A., Liu S., Sams G.H., Curphey D.P., Santhanam R., Rush L.J. Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation. Cancer Cell. 2012;22:645-655.

    Not in our library10.1016/j.ccr.2012.09.009

  439. 439.

    Ghosh A., Saginc G., Leow S.C., Khattar E., Shin E.M., Yan T.D. Telomerase directly regulates NF-kappaB-dependent transcription. Nat Cell Biol. 2012;14:1270-1281.

    Not in our library10.1038/ncb2621

  440. 440.

    Nassani N., Khayat G., Raad I., Jiang Y., Alaaeddine N., Hilal G. Telomerase as a potential marker for inflammation and cancer detection in bronchial washing: a prospective study. Clin Biochem. 2013;46:1701-1704.

    Not in our library10.1016/j.clinbiochem.2013.07.018

  441. 441.

    Negrini S., Gorgoulis V.G., Halazonetis T.D. Genomic instability – an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010;11:220-228.

    Not in our library10.1038/nrm2858

  442. 442.

    Yun U.J., Park S.E., Jo Y.S., Kim J., Shin D.Y. DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors. Cancer Lett. 2012;323:155-160.

    Not in our library10.1016/j.canlet.2012.04.003

  443. 443.

    Nishikawa K., Rosenblum M.G., Newman R.A., Pandita T.K., Hittelman W.N., Donato N.J. Resistance of human cervical carcinoma cells to tumor necrosis factor correlates with their increased sensitivity to cisplatin: evidence of a role for DNA repair and epidermal growth factor receptor. Cancer Res. 1992;52:4758-4765.

    Not in our library

  444. 444.

    Shen S., Mao C.Q., Yang X.Z., Du X.J., Liu Y., Zhu Y.H. Cationic lipid-assisted polymeric nanoparticle mediated GATA2 siRNA delivery for synthetic lethal therapy of KRAS mutant non-small-cell lung carcinoma. Mol Pharm. 2014.

    Not in our library10.1021/mp400714z

  445. 445.

    Nam H.J., Chae S., Jang S.H., Cho H., Lee J.H. The PI3K-Akt mediates oncogenic Met-induced centrosome amplification and chromosome instability. Carcinogenesis. 2010;31:1531-1540.

    Not in our library10.1093/carcin/bgq133

  446. 446.

    Xu X., Weaver Z., Linke S.P., Li C., Gotay J., Wang X.W. Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. Mol Cell. 1999;3:389-395.

    Not in our library10.1016/s1097-2765(00)80466-9

  447. 447.

    Shay J.W. Telomerase therapeutics: telomeres recognized as a DNA damage signal: commentary re: K. Kraemer et al., antisense-mediated hTERT inhibition specifically reduces the growth of human bladder cancer cells. Clin. Cancer Res., 9: 3794–3800, 2003. Clin Cancer Res. 2003;9:3521-3525.

    Not in our library

  448. 448.

    Ghosal G., Chen J. DNA damage tolerance: a double-edged sword guarding the genome. Transl Cancer Res. 2013;2:107-129.

    Not in our library10.3978/j.issn.2218-676x.2013.04.01

  449. 449.

    Poynter K.R., Sachs P.C., Bright A.T., Breed M.S., Nguyen B.N., Elmore L.W. Genetic inhibition of telomerase results in sensitization and recovery of breast tumor cells. Mol Cancer Ther. 2009;8:1319-1327.

    Not in our library10.1158/1535-7163.mct-08-0849

  450. 450.

    Aguilera A., Garcia-Muse T. Causes of genome instability. Annu Rev Genet. 2013;47:1-32.

    Not in our library10.1146/annurev-genet-111212-133232

  451. 451.

    Cha H.J., Yim H. The accumulation of DNA repair defects is the molecular origin of carcinogenesis. Tumour Biol. 2013;34:3293-3302.

    Not in our library10.1007/s13277-013-1038-y

  452. 452.

    Ohshima S. Centrosome aberrations associated with cellular senescence and p53 localization at supernumerary centrosomes. Oxid Med Cell Longev. 2012;2012:217594.

    Not in our library10.1155/2012/217594

  453. 453.

    Tamae D., Lim P., Wuenschell G.E., Termini J. Mutagenesis and repair induced by the DNA advanced glycation end product N2-1-(carboxyethyl)-2’-deoxyguanosine in human cells. Biochemistry. 2011;50:2321-2329.

    Not in our library10.1021/bi101933p

  454. 454.

    Dai C., Sun F., Zhu C., Hu X. Tumor environmental factors glucose deprivation and lactic acidosis induce mitotic chromosomal instability – an implication in aneuploid human tumors. PLOS ONE. 2013;8:e63054.

    Not in our library10.1371/journal.pone.0063054

  455. 455.

    Li Y., Liu L., Tollefsbol T.O. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J. 2010;24:1442-1453.

    Not in our library10.1096/fj.09-149328

  456. 456.

    Mai W., Kawakami K., Shakoori A., Kyo S., Miyashita K., Yokoi K. Deregulated GSK3{beta} sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase. Clin Cancer Res. 2009;15:6810-6819.

    Not in our library10.1158/1078-0432.ccr-09-0973

  457. 457.

    Chavakis T., Orlova V.V., Langer H.F. A possible crosstalk between DNA repair pathways and angiogenesis. Cell Cycle. 2009;8:3438-3439.

    Not in our library10.4161/cc.8.21.9750

  458. 458.

    Rankin E.B., Giaccia A.J., Hammond E.M. Bringing H2AX into the angiogenesis family. Cancer Cell. 2009;15:459-461.

    Not in our library10.1016/j.ccr.2009.05.004

  459. 459.

    Celeste A., Petersen S., Romanienko P.J., Fernandez-Capetillo O., Chen H.T., Sedelnikova O.A. Genomic instability in mice lacking histone H2AX. Science. 2002;296:922-927.

    Not in our library10.1126/science.1069398

  460. 460.

    Economopoulou M., Langer H.F., Celeste A., Orlova V.V., Choi E.Y., Ma M. Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med. 2009;15:553-558.

    Not in our library10.1038/nm.1947

  461. 461.

    Coleman M.L., Ratcliffe P.J. Angiogenesis: escape from hypoxia. Nat Med. 2009;15:491-493.

    Not in our library10.1038/nm0509-491

  462. 462.

    Taylor S.M., Nevis K.R., Park H.L., Rogers G.C., Rogers S.L., Cook J.G. Angiogenic factor signaling regulates centrosome duplication in endothelial cells of developing blood vessels. Blood. 2010;116:3108-3117.

    Not in our library10.1182/blood-2010-01-266197

  463. 463.

    Kim Y.M., Yang S., Xu W., Li S., Yang X. Continuous in vitro exposure to low-dose genistein induces genomic instability in breast epithelial cells. Cancer Genet Cytogen. 2008;186:78-84.

    Not in our library10.1016/j.cancergencyto.2008.06.010

  464. 464.

    Li Y., Liu L., Andrews L.G., Tollefsbol T.O. Genistein depletes telomerase activity through cross-talk between genetic and epigenetic mechanisms. Int J Cancer. 2009;125:286-296.

    Not in our library10.1002/ijc.24398

  465. 465.

    Holysz H., Lipinska N., Paszel-Jaworska A., Rubis B. Telomerase as a useful target in cancer fighting-the breast cancer case. Tumour Biol. 2013;34:1371-1380.

    Not in our library10.1007/s13277-013-0757-4

  466. 466.

    LaTulippe E., Satagopan J., Smith A., Scher H., Scardino P., Reuter V. Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res. 2002;62:4499-4506.

    Not in our library

  467. 467.

    Olaussen K.A., Dunant A., Fouret P., Brambilla E., Andre F., Haddad V. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983-991.

    Not in our library10.1056/nejmoa060570

  468. 468.

    Ghadimi B.M., Sackett D.L., Difilippantonio M.J., Schrock E., Neumann T., Jauho A. Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and correlates with numerical chromosomal aberrations. Genes Chromosom Cancer. 2000;27:183-190.

    Not in our library

  469. 469.

    Lingle W.L., Barrett S.L., Negron V.C., D’Assoro A.B., Boeneman K., Liu W. Centrosome amplification drives chromosomal instability in breast tumor development. Proc Natl Acad Sci U S A. 2002;99:1978-1983.

    Not in our library10.1073/pnas.032479999

  470. 470.

    Chen L., Lu M.H., Zhang D., Hao N.B., Fan Y.H., Wu Y.Y. miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase. Cell Death Dis. 2014;5:e1034.

    Not in our library10.1038/cddis.2013.553

  471. 471.

    Chen P.C., Peng J.R., Huang L., Li W.X., Wang W.Z., Cui Z.Q. Overexpression of human telomerase reverse transcriptase promotes the motility and invasiveness of HepG2 cells in vitro. Oncol Rep. 2013;30:1157-1164.

    Not in our library10.3892/or.2013.2563

  472. 472.

    Dikmen Z.G., Ozgurtas T., Gryaznov S.M., Herbert B.S. Targeting critical steps of cancer metastasis and recurrence using telomerase template antagonists. Biochim Biophys Acta. 2009;1792:240-247.

    Not in our library10.1016/j.bbadis.2009.01.018

  473. 473.

    Griffith J.K., Bryant J.E., Fordyce C.A., Gilliland F.D., Joste N.E., Moyzis R.K. Reduced telomere DNA content is correlated with genomic instability and metastasis in invasive human breast carcinoma. Breast Cancer Res Treat. 1999;54:59-64.

    Not in our library10.1023/a:1006128228761

  474. 474.

    Heaphy C.M., Baumgartner K.B., Bisoffi M., Baumgartner R.N., Griffith J.K. Telomere DNA content predicts breast cancer-free survival interval. Clin Cancer Res. 2007;13:7037-7043.

    Not in our library10.1158/1078-0432.ccr-07-0432

  475. 475.

    Alderton G.K. Microenvironment secreted DNA damage? Nat Rev Cancer. 2013;13:77.

    Not in our library10.1038/nrc3455

  476. 476.

    Chan N., Pires I.M., Bencokova Z., Coackley C., Luoto K.R., Bhogal N. Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Cancer Res. 2010;70:8045-8054.

    Not in our library10.1158/0008-5472.can-10-2352

  477. 477.

    Falchetti M.L., Mongiardi M.P., Fiorenzo P., Petrucci G., Pierconti F., D’Agnano I. Inhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenografts. Int J Cancer. 2008;122:1236-1242.

    Not in our library10.1002/ijc.23193

  478. 478.

    Liu W., Asa S., Fantus I., Walfish P., Ezzat S. Vitamin D arrests thyroid carcinoma cell growth and induces p27 dephosphorylation and accumulation through PTEN/akt-dependent and-independent pathways. Am J Pathol. 2002.

    Not in our library10.1016/s0002-9440(10)64870-5

  479. 479.
    Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium. · 2013
    Not checked
  480. 480.
    Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells. · 2013
    Not checked
  481. 481.

    Yang E.S., Nowsheen S., Rahman M.A., Cook R.S., Xia F. Targeting BRCA1 localization to augment breast tumor sensitivity to poly(ADP-Ribose) polymerase inhibition. Cancer Res. 2012;72:5547-5555.

    Not in our library10.1158/0008-5472.can-12-0934

  482. 482.

    Yang C.M., Lu Y.L., Chen H.Y., Hu M.L. Lycopene and the LXRalpha agonist T0901317 synergistically inhibit the proliferation of androgen-independent prostate cancer cells via the PPARgamma-LXRalpha-ABCA1 pathway. J Nutr Biochem. 2012;23:1155-1162.

    Not in our library10.1016/j.jnutbio.2011.06.009

  483. 483.

    Cardnell R.J., Feng Y., Diao L., Fan Y.H., Masrorpour F., Wang J. Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer. Clin Cancer Res. 2013;19:6322-6328.

    Not in our library10.1158/1078-0432.ccr-13-1975

  484. 484.

    Wang Z., Li Y., Lv S., Tian Y. Inhibition of proliferation and invasiveness of ovarian cancer C13* cells by a poly(ADP-ribose) polymerase inhibitor and the role of nuclear factor-kappaB. J Int Med Res. 2013;41:1577-1585.

    Not in our library10.1177/0300060513480913

  485. 485.

    Melchini A., Traka M.H., Catania S., Miceli N., Taviano M.F., Maimone P. Antiproliferative activity of the dietary isothiocyanate erucin, a bioactive compound from cruciferous vegetables, on human prostate cancer cells. Nutr Cancer. 2013;65:132-138.

    Not in our library10.1080/01635581.2013.741747

  486. 486.

    Stan S.D., Singh S.V., Whitcomb D.C., Brand R.E. Phenethyl isothiocyanate inhibits proliferation and induces apoptosis in pancreatic cancer cells in vitro and in a MIAPaca2 xenograft animal model. Nutr Cancer. 2013.

    Not in our library10.1080/01635581.2013.795979

  487. 487.

    Hopkins M., Owen J., Ahearn T., Fedirko V., Flanders W., Jones D. Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorectal adenoma patients: a randomized, controlled clinical trial. Cancer Prev Res (Phila). 2011;4:1645-1654.

    Not in our library10.1158/1940-6207.capr-11-0105

  488. 488.

    Krishnan A., Moreno J., Nonn L., Swami S., Peehl D., Feldman D. Calcitriol as a chemopreventive and therapeutic agent in prostate cancer: role of anti-inflammatory activity. J Bone Min Res. 2007;22(Suppl. 2):80.

    Not in our library10.1359/jbmr.07s213

  489. 489.

    Gatz S.A., Wiesmuller L. Take a break – resveratrol in action on DNA. Carcinogenesis. 2008;29:321-332.

    Not in our library10.1093/carcin/bgm276

  490. 490.

    Hager G., Formanek M., Gedlicka C., Thurnher D., Knerer B., Kornfehl J. 1,25(OH)2 vitamin D3 induces elevated expression of the cell cycle-regulating genes P21 and P27 in squamous carcinoma cell lines of the head and neck. Acta Otolaryngol. 2001;121:103-109.

    Not in our library10.1080/000164801300006353

  491. 491.

    Hager G., Kornfehl J., Knerer B., Weigel G., Formanek M. Molecular analysis of p21 promoter activity isolated from squamous carcinoma cell lines of the head and neck under the influence of 1,25(OH)2 vitamin D3 and its analogs. Acta Otolaryngol. 2004;124:90-96.

    Not in our library10.1080/00016480310015353

  492. 492.

    Wong G., Gupta R., Dixon K.M., Deo S.S., Choong S.M., Halliday G.M. 1,25-Dihydroxyvitamin D and three low-calcemic analogs decrease UV-induced DNA damage via the rapid response pathway. J Steroid Biochem Mol Biol. 2004;89-90:567-570.

    Not in our library10.1016/j.jsbmb.2004.03.072

  493. 493.

    Bera S., De Rosa V., Rachidi W., Diamond A.M. Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention. Mutagenesis. 2013;28:127-134.

    Not in our library10.1093/mutage/ges064

  494. 494.

    Hamilton E.E., Fanwick P.E., Wilker J.J. Alkylation of inorganic oxo compounds and insights on preventing DNA damage. J Am Chem Soc. 2006;128:3388-3395.

    Not in our library10.1021/ja056568v

  495. 495.

    Collins A.R., Harrington V., Drew J., Melvin R. Nutritional modulation of DNA repair in a human intervention study. Carcinogenesis. 2003;24:511-515.

    Not in our library10.1093/carcin/24.3.511

  496. 496.

    He X., Wang Y., Zhu J., Orloff M., Eng C. Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011;301:168-176.

    Not in our library10.1016/j.canlet.2010.11.012

  497. 497.

    Kim K.H., Back J.H., Zhu Y., Arbesman J., Athar M., Kopelovich L. Resveratrol targets transforming growth factor-beta2 signaling to block UV-induced tumor progression. J Investig Dermatol. 2011;131:195-202.

    Not in our library10.1038/jid.2010.250

  498. 498.

    Zhang J., Kan Y., Tian Y., Wang Z., Zhang J. Effects of poly (ADP-ribosyl) polymerase (PARP) inhibitor on cisplatin resistance & proliferation of the ovarian cancer C13* cells. Indian J Med Res. 2013;137:527-532.

    Not in our library

  499. 499.
    P21-PARP-1 pathway is involved in cigarette smoke-induced lung DNA damage and cellular senescence. · 2013
    Not checked
  500. 500.

    Schabath M.B., Grossman H.B., Delclos G.L., Hernandez L.M., Day R.S., Davis B.R. Dietary carotenoids and genetic instability modify bladder cancer risk. J Nutr. 2004;134:3362-3369.

    Not in our library10.1093/jn/134.12.3362

  501. 501.

    Ren Z., Wang L., Cui J., Huoc Z., Xue J., Cui H. Resveratrol inhibits NF-kB signaling through suppression of p65 and IkappaB kinase activities. Pharmazie. 2013;68:689-694.

    Not in our library

  502. 502.

    Khuda-Bukhsh A.R., Das S., Saha S.K. Molecular approaches toward targeted cancer prevention with some food plants and their products: inflammatory and other signal pathways. Nutr Cancer. 2014;66:194-205.

    Not in our library10.1080/01635581.2014.864420

  503. 503.

    Rayalam S., Della-Fera M.A., Yang J.Y., Park H.J., Ambati S., Baile C.A. Resveratrol potentiates genistein's antiadipogenic and proapoptotic effects in 3T3-L1 adipocytes. J Nutr. 2007;137:2668-2673.

    Not in our library10.1093/jn/137.12.2668

  504. 504.

    Gomez L.S., Zancan P., Marcondes M.C., Ramos-Santos L., Meyer-Fernandes J.R., Sola-Penna M. Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase. Biochimie. 2013;95:1336-1343.

    Not in our library10.1016/j.biochi.2013.02.013

  505. 505.

    Fouad M.A., Agha A.M., Merzabani M.M., Shouman S.A. Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: calorie restriction is the force to the cytotoxicity. Hum Exp Toxicol. 2013;32:1067-1080.

    Not in our library10.1177/0960327113475679

  506. 506.

    Filomeni G., Graziani I., Rotilio G., Ciriolo M.R. trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways. Genes Nutr. 2007;2:295-305.

    Not in our library10.1007/s12263-007-0059-9

  507. 507.

    Kang N.H., Hwang K.A., Lee H.R., Choi D.W., Choi K.C. Resveratrol regulates the cell viability promoted by 17beta-estradiol or bisphenol A via down-regulation of the cross-talk between estrogen receptor alpha and insulin growth factor-1 receptor in BG-1 ovarian cancer cells. Food Chem Toxicol. 2013;59:373-379.

    Not in our library10.1016/j.fct.2013.06.029

  508. 508.
    Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways · 2010
    No notice
  509. 509.

    Moon A.F., Garcia-Diaz M., Batra V.K., Beard W.A., Bebenek K., Kunkel T.A. The X family portrait: structural insights into biological functions of X family polymerases. DNA Repair (Amst). 2007;6:1709-1725.

    Not in our library10.1016/j.dnarep.2007.05.009

  510. 510.

    Lee-Chang C., Bodogai M., Martin-Montalvo A., Wejksza K., Sanghvi M., Moaddel R. Inhibition of breast cancer metastasis by resveratrol-mediated inactivation of tumor-evoked regulatory B cells. J Immunol. 2013;191:4141-4151.

    Not in our library10.4049/jimmunol.1300606

  511. 511.

    Iwasaki K., Ray P.D., Huang B.W., Sakamoto K., Kobayashi T., Tsuji Y. Role of AMP-activated protein kinase in ferritin H gene expression by resveratrol in human T cells. Biochemistry. 2013;52:5075-5083.

    Not in our library10.1021/bi400399f

  512. 512.

    Noh K.T., Chae S.H., Chun S.H., Jung I.D., Kang H.K., Park Y.M. Resveratrol suppresses tumor progression via the regulation of indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun. 2013;431:348-353.

    Not in our library10.1016/j.bbrc.2012.12.093

  513. 513.

    Buttari B., Profumo E., Facchiano F., Ozturk E.I., Segoni L., Saso L. Resveratrol prevents dendritic cell maturation in response to advanced glycation end products. Oxid Med Cell Longev. 2013;2013:574029.

    Not in our library10.1155/2013/574029

  514. 514.

    Oikawa T., Hirotani K., Ogasawara H., Katayama T., Nakamura O., Iwaguchi T. Inhibition of angiogenesis by vitamin D3 analogues. Eur J Pharmacol. 1990;178:247-250.

    Not in our library10.1016/0014-2999(90)90483-m

  515. 515.

    Chen Y., Tseng S.H. Review. Pro- and anti-angiogenesis effects of resveratrol. In Vivo. 2007;21:365-370.

    Not in our library

  516. 516.
    Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients · 2009
    No notice
  517. 517.

    Bao B.-Y., Yeh S.-D., Lee Y.-F. 1α,25-Dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases. Carcinogenesis. 2006;27:32-42.

    Not in our library10.1093/carcin/bgi170

  518. 518.

    Zhu W.Y., Zheng J., Fang W.G. The inhibition effect of retinoic acid on the invasion and metastasis abilities of metastatic human lung cancer cell subline. Zhonghua Bing Li Xue Za Zhi. 1994;23:347-350.

    Not in our library

  519. 519.
    Resveratrol Inhibits Invasion and Metastasis of Colorectal Cancer Cells via MALAT1 Mediated Wnt/β-Catenin Signal Pathway · 2013
    Retracted
  520. 520.

    Ooi L.L., Zhou H., Kalak R., Zheng Y., Conigrave A.D., Seibel M.J. Vitamin D deficiency promotes human breast cancer growth in a murine model of bone metastasis. Cancer Res. 2010;70:1835-1844.

    Not in our library10.1158/0008-5472.can-09-3194

  521. 521.
    Lycopene inhibits NF-kB-mediated IL-8 expression and changes redox and PPARγ signalling in cigarette smoke-stimulated macrophages. · 2011
    Not checked
  522. 522.

    Shamim U., Hanif S., Albanyan A., Beck F.W., Bao B., Wang Z. Resveratrol-induced apoptosis is enhanced in low pH environments associated with cancer. J Cell Physiol. 2012;227:1493-1500.

    Not in our library10.1002/jcp.22865

  523. 523.
    Metastasis of Breast Tumor Cells to Brain Is Suppressed by Phenethyl Isothiocyanate in a Novel In Vivo Metastasis Model. · 2013
    Not checked

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