No retraction, correction or concern found when last checked on Oct 17, 2026.

Targeting the PDGF signaling pathway in tumor treatment

Carl-Henrik Heldin

Cell Communication and Signaling · 2013 · Review

Abstract

Platelet-derived growth factor (PDGF) isoforms and PDGF receptors have important functions in the regulation of growth and survival of certain cell types during embryonal development and e.g. tissue repair in the adult. Overactivity of PDGF receptor signaling, by overexpression or mutational events, may drive tumor cell growth. In addition, pericytes of the vasculature and fibroblasts and myofibroblasts of the stroma of solid tumors express PDGF receptors, and PDGF stimulation of such cells promotes tumorigenesis. Inhibition of PDGF receptor signaling has proven to useful for the treatment of patients with certain rare tumors. Whether treatment with PDGF/PDGF receptor antagonists will be beneficial for more common malignancies is the subject for ongoing studies.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 17, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

1Platelet-derived growth factor (PDGF) isoforms stimulate growth, survival and motility of mesenchymal cells and certain other cell types. They have important functions during embryonal development and in the control of tissue homeostasis in the adult. Overactivity of PDGF signaling is associated with the development of certain malignant diseases, as well as non-malignant diseases characterized by excessive cell proliferation. The involvement of PDGF overactivity in non-malignant diseases has been discussed in a recent review. The present review will focus on the role of PDGF signaling in tumor development, and on the use of PDGF antagonists in tumor treatment.

PDGF isoforms

2The PDGF family consists of disulphide-bonded homodimers of A-, B-, C- and D-polypeptide chains, and the heterodimer PDGF-AB. The PDGF isoforms are synthesized as precursor molecules. PDGF-AA, -AB and –BB are cleaved already inside the producer cells in secretory vesicles. In contrast, PDGF-CC and –DD are secreted as inactive precursor molecules; N-terminal CUB-domains need to be cleaved off to activate the growth factors. This cleavage serves an important regulatory role, and is performed by tissue-type plasminogen activator (tPA) or plasmin in the case of PDGF-CC, and by urokinase-type PA (uPA) or matriptase (MT-Sp1) in the case of PDGF-DD (Figure 1).

Signaling via PDGF receptors

3PDGF isoforms exert their cellular effects by binding to α- and β-tyrosine kinase receptors (PDGFRα and PDGFRβ, respectively). The two PDGF receptors are structurally similar and consist of extracellular domains with five immunoglobulin (Ig) - like domains and intracellular parts with kinase domains which contain characteristic inserts of about 100 amino acid residues without homology to kinases. Ligand binding occurs mainly to Ig-like domains 2 and 3, and causes dimerization of the receptors, which is further stabilized by direct receptor-receptor interactions involving Ig-like domain 4. The dimerization is a key event in activation since it brings the intracellular parts of the receptors close to each other promoting autophosphorylation in trans between the receptors. The PDGF polypeptide chains bind to the receptors with different affinities. Thus, PDGF-AA, -AB, -BB and -CC induce αα receptor homodimers, PDGF-BB and PDGF-DD ββ receptor homodimers, and PDGF-AB, -BB, -CC and –DD αβ receptor heterodimers Figure 1;.

4The autophosphorylation serves two important functions. First, it changes the conformation of the intracellular part of the receptor so that the kinase is activated. There is no 3-dimensional structure yet for PDGF receptors, so precise information about mechanisms that control the kinase is not available. However, it is likely that in the resting state, the kinase is kept inactive by at least three mechanisms: i) The activation loop in the kinase domain is likely to be folded over the catalytic cleft; autophosphorylation of a conserved tyrosine residue in this region causes the loop to move away from the active site. ii) The juxtamembrane part of the receptor is likely to be folded in a loop which restricts the access to the active site; autophosphorylation of two tyrosine residues in this region changes the conformation and enhances the kinase activity. iii) The C-terminal tail of the receptor is most likely folded over the kinase domain; autophosphorylation of two C-terminally located tyrosine residues relieves the kinase of this inhibition. Similar regulatory mechanisms have been observed in the structurally related colony stimulating factor-1 receptor (CSF1R) and FLT3.

5Second, autophosphorylation creates docking sites for SH2-domain-containing signaling molecules. The α- and β-receptors contain 10 and 11 known autophosphorylated tyrosine residues, respectively. About 10 different families of SH2-domain-containing molecules have been shown to selectively bind to different phosphorylated residues in the PDGF receptors. These include signaling molecules with intrinsic enzymatic activities, such as tyrosine kinases of the Src family, the SHP-2 tyrosine phosphatase, phospholipase C-γ (PLC-γ) and the GTPase activating protein (GAP) for Ras. Moreover, the receptors bind and activate signal transducers and activators of transcription (STATs), which after activation are translocated to the nucleus where they act as transcription factors. Finally, the receptors bind adaptor molecules which lack intrinsic enzymatic activities, but can form complexes with other signaling molecules. Examples include the regulatory subunit p85 of the phosphatidylinositol 3′-kinase (PI3K), which forms complex with the p110 catalytic subunit, and Grb2 which binds the nucleotide exchange molecule SOS1, activating Ras and the Erk MAP-kinase pathway (Figure 1). In addition, the PDGF receptors bind other adaptors, e.g. Shc, Nck, Crk and GAB, which mediate interactions with a plethora of different downstream signaling molecules. The activation of these signaling pathways leads to cell proliferation and survival, as well as to actin reorganization and cell migration. The extensive cross-talk between the different signaling pathways makes it difficult to assign individual pathways to specific responses; in a cell-type- and context-dependent manner, several signaling pathways contribute to each of the cellular responses.

Modulation and termination of PDGF receptor signaling

6Signaling via PDGF receptors is carefully controlled and modulated. In the early phase of signaling different mechanisms assure that the signal rapidly reaches sufficient strength. For instance, in PDGF stimulated cells reactive oxygen species are produced in a PI3-kinase-dependent pathway, which inhibit tyrosine phosphatases by reacting with a cysteine residue in their active site. Another mechanism that amplifies the signaling is the ubiquitination and degradation of MAP-kinase phosphatase 3, which dephosphorylates and inactivates Erk MAP-kinase; removal of this phosphatase enhances Erk MAP-kinase activation.

7There are also mechanisms that negatively modulate PDGF signaling. One example is the docking of Ras-GAP to the activated PDGFRβ; this counteracts the activation of Ras which occurs by the simultaneous docking of the Grb2-SOS1 complex. Interestingly, PDGFRα does not bind Ras-GAP and therefore activates Erk MAP-kinase more efficiently than PDGFRβ.

8Negative modulatory effects are also exerted by tyrosine phosphatases which dephosphorylate and inactivate PDGF receptors. Examples of such phosphatases include PTP1B, TC-PTP and PTPRJ/DEP-1. In addition, the tyrosine phosphatase SHP-2 binds to PDGF receptors and dephosphorylates the receptors and their substrates. However, SHP-2 also positively modulates signaling, e.g. via dephosphorylation of a C-terminal inhibitory phosphorylation site in Src family members, thereby activating them, or by acting as an adaptor for binding of the Grb2-SOS1 complex, thus promoting Ras activation.

9Other mechanisms of modulation of PDGF receptor signaling are exerted by interactions with other cell surface receptors. Thus, PDGF receptor interaction with other tyrosine kinase receptors, such as the EGF receptor, has been observed. Moreover, PDGF receptors have been shown to interact with non-kinase receptors; thus, integrins and the low density lipoprotein receptor-related protein enhance signaling, whereas interaction with the hyaluronan receptor CD44 suppresses signaling.

10Activation of PDGF receptors triggers internalization of the receptors in a clathrin- and dynamin-dependent manner. Internalization is promoted by ubiquitination of the receptors by the ubiquitin ligase Cbl. Signaling continues in endosomes until the receptors are degraded in proteasomes and lysosomes. Alternatively, receptors can be sorted to recycling vesicles whereby they reappear at the plasma membrane where they can signal again. One mechanism which promotes sorting of receptors to recycling is exerted by activation of PLCγ and the downstream protein kinase C (PKC), another involves PI3-kinase-mediated uptake of the receptor via an alternative internalization route, i.e. macropinocytosis. Increased receptor recycling is accompanied by an increased amplitude and duration of signaling.

Normal function of PDGF isoforms and receptors

11The physiological functions of PDGF have been analyzed using mice with the genes for PDGF isoforms or receptors knocked-out. These studies have elucidated important roles for PDGF isoforms in the development of mesenchymal cell types of different organs reviewed in. Often PDGF isoforms are produced by epithelial or endothelial cells and act in a paracrine manner on nearby mesenchymal cells, such as fibroblasts, pericytes and smooth muscle cells. Thus, signaling via PDGFRα is important for the development of the facial skeleton, hair follicles, spermatogenesis oligodendrocytes and astrocytes, as well as for the development of the lung and intestinal villi. Signaling via PDGFRβ is important for the development of blood vessels, kidneys and white adipocytes.

12In the adult, PDGF stimulates wound healing. It also regulates the intestinal fluid pressure in tissues and thereby counteracts edema formation.

PDGF signaling antagonists

13The involvement of PDGF overactivity in malignant diseases (see further below), as well as certain non-malignant diseases, has led to the development of different types of antagonists of PDGF signaling that now are under preclinical and clinical evaluation.

14The developed inhibitors include antibodies, DNA aptamers or soluble extracellular parts of the receptors that bind PDGF isoforms and thus prevent their binding to signaling receptors. Alternatively, antibodies or other binders can target the receptors and prevent their activation or promote their degradation. These types of antagonists have the advantage of being reasonably specific, however, they are expensive and cumbersome to administer. Another type of antagonists are low molecular inhibitors of the receptor kinases (Table 1). Several potent inhibitors of PDGF receptor kinases have been developed, including imatinib, sunitinib, sorafenib, pazopanib and nilotinib. None of these inhibitors are specific; they all have their characteristic profiles of inhibition of different other kinases. Thus, imatinib, in addition to inhibiting PDGF receptor kinases, inhibits the stem cell receptor (Kit) and Abl kinases, and sunitinib inhibits vascular endothelial cell growth factor (VEGF) receptors and Flt3; sorafenib has an inhibitory profile similar to sunitinib, but also inhibits the serine/threonine kinase Raf. Although the lack of specificity contributes to side effects and can be seen as a disadvantage, experience has shown that it is often advantageous to hit more than one kinase in tumor treatment.

PDGF signaling in malignant diseases

15There are several observations supporting the notion that overactivity of PDGF signaling can drive tumorigenesis. In certain tumors, PDGF or PDGF receptor genes are mutated, alternatively, their expressions are increased. Thus, in the rare skin tumor dermatofibrosarcoma protuberance (DFSP), the gene encoding PDGF-B is fused to the gene encoding collagen 1A1. This leads to the production of large amounts of a fusion protein consisting of N-terminal collagen sequence and C-terminal PDGF-B sequence. After processing, a PDGF-BB-like protein is released which stimulates the growth and survival of the producer fibroblasts in an autocrine manner.

16The PDGF receptor genes have also been found to be mutated in certain malignancies. Point mutations in the PDGFRα gene occur in about 5% of gastrointestinal stromal tumors (GIST); these mutations lead to amino acid residue replacements in critical regions of the receptor causing activation of the kinase. In GIST, similar mutations in the structurally related receptor Kit, is even more common. PDGF receptor genes have been found involved in gene rearrangements in certain leukemias. Thus, the intracellular parts of both PDGFRα and PDGFβ genes have been found to be fused to different partner genes that encode molecules that can oligomerize; the combination of loss of regulatory sequences in the juxtamembrane and transmembrane parts of the receptors and their oligomerization activate the receptor kinases. Moreover, in 5-10% of glioblastoma multiforme cases, the α-receptor gene is amplified resulting in expression of a high number of receptors. Amplification of PDGFRα has also been observed in oligodendrogliomas, esophageal squamous cell carcinoma, and artery intimal sarcomas. This makes the cells susceptible to stimulation by lowered amounts of PDGF, or if the number of receptors become high enough, signaling may occur in a PDGF-independent manner. An activating deletion mutation in the PDGFRα gene has also been detected in a human glioblastoma.

17During tumorigenesis, epithelial tumors may undergo epithelial-mesenchymal transition (EMT), which is associated with increased invasiveness and metastasis. During EMT, PDGF receptor expression by the tumor cells increases, so that epithelial tumors that initially did not respond to PDGF may become responsive to PDGF stimulation. The expression of PDGF isoforms are also part of the EMT program, which may enhance PDGF receptor signaling by autocrine stimulation.

18PDGF produced by tumor cells or non-tumorigenic cells, such as endothelial cells and macrophages, also acts on non-tumor cells in solid tumors. Thus, pericytes around blood vessels, and fibroblasts and myofibroblasts in the stroma, carry PDGF receptors and respond to PDGF. Pericytes are dependent on PDGF produced by endothelial cells and have an important role during angiogenesis. PDGF stimulation of fibroblasts and myofibroblasts in the stroma contributes to the increased interstitial fluid pressure (IFP) in solid tumors. The increased IFP is an obstacle in chemotherapeutic treatment of tumors, since it decreases the transcapillar flow and decreases drug uptake reviewed by.

19The fact that PDGF receptor signaling is often overactive in tumors has prompted attempts to treat patients with various malignancies with PDGF/PDGF receptor antagonists. During tumor progression, tumor cells acquire a number of mutations, some of which drive tumorigenesis. It has been observed that tumor cells often become “addicted” to the signaling pathways that are activated by mutational events, and that inhibition of such pathways induces apoptosis of the tumor cells. On the other hand, after some time re-growth of the tumor often occurs, due to the appearance of various types of resistance mechanisms. The involvement of PDGF signaling in specific tumor types and the possible usefulness of PDGF antagonists in tumor treatment (Table 2), are discussed in the following sections. First, mechanisms operating in the tumor cells themselves are discussed; the involvement of PDGF stimulation in the stroma compartment is discussed in a later chapter.

Brain tumors

20A clear demonstration that autocrine stimulation by PDGF can drive the development of glioblastoma multiforme (GBM) was the finding that simian sarcoma virus (SSV) induces brain tumors in marmoset monkeys; the transforming oncogene of SSV, v-sis, encodes a PDGF-B-like molecule. In human material, increased expression of PDGF isoforms and PDGF receptors have been demonstrated in GBM cell lines and in tumor tissue. Notably, a malignancy-dependent increased expression was noticed where the α-receptor was primarily expressed in the tumor cells, and the β-receptor in the stromal cells. Amplification of the PDGF α-receptor has been demonstrated, but is not as common as amplification of the EGF receptor. Mutations in the PDGFRα gene, in the parts encoding the extracellular as well as the intracellular domains, have been observed; in addition, a fusion with the VEGFR2 gene has been found.

21The importance of autocrine stimulation by PDGF has been verified in animal models, in which a retrovirus encoding PDGF-B was injected in newborn mice. PDGF-induced transformation was found to be enhanced by mutations in certain tumor suppressor genes, such as Ink4/Arf, TP53 and PTEN. In cells with Ink4a/Arf deficiency, PDGFRα promotes tumorigenesis via the SHP2/PI3K/Akt/mTOR pathway.

22PDGF overexpression forces differentiation of glial cells to the oligodendrocyte lineage and promotes the development of highly malignant oligodendroglial tumors in mice. The transforming efficiency of PDGF stimulation is illustrated by the fact that overexpression of PDGF-B in corpus callosum causes GBM also in adult rats. Overexpression of the long isoforms of PDGF-A, which has a retention motif enhancing its autocrine stimulatory effect, was also found to efficiently promote GBM development.

23Glioma stem cells preferentially express PDGFRβ and its activation promotes glioma stem cell self-renewal, suggesting that targeting of this receptor can be beneficial in treatment of glioma patients. PDGF-B depletion completely abrogated the tumor initiating capacity of glioma stem cells.

24Despite the finding that the PDGF receptor kinase inhibitor imatinib enhances the cytotoxicity of radiation in a mouse glioma model, only limited effects were recorded by imatinib treatment in Phase II clinical trials in glioblastoma patients. Subsequent Phase II and Phase III studies explored the combination between imatinib and hydroxyurea in the treatment of recurrent glioblastoma, but no clinically meaningful antitumor effect was observed.

25In addition to glioblastoma, PDGF overactivity has been implicated also in other types of brain tumors. PDGFRα and β have been shown to be overexpressed in ependymoma of children and expression of PDGFα was found to correlate to poor prognosis.

26Chordoma is a rare slow-growing tumor arising from remnants of the notochord, which often expresses PDGFRβ. Following encouraging treatment results of occasional patients with imatinib, a Phase II clinical study was organized. Among 50 patients treated, one partial response and 35 patients with stable disease were recorded.

27Meningeomas are mostly benign tumors with good prognosis that are treated with surgery, but some are inoperable and requires other treatment. Since meningiomas often express PDGF receptors, treatments of recurrent meningeomas with single-agent imatinib or with imatinib plus hydroxyurea have been tried; however, no or only modest effect was recorded. On the other hand, more encouraging results were obtained in a small study with preselected patients with recurrent meningeomas with expression of at least one of the PDGF receptors; whereas no complete or partial responses were seen, seven out of nine patients showed stable disease after imatinib treatment.

28PDGF receptors, as well as c-Kit, have been found to be overexpressed and overactivated in peripheral and vestibular schwannomas. Treatment of vestibular schwannoma cells or other types of primary schwannoma cells, lacking the tumor suppressor NF2, with nilotinib inhibited the growth of the cells in vitro.

Sarcomas

29Like in the case of glioblastomas, the normal counterpart cells of sarcomas express PDGF receptors. Overexpression of PDGF isoforms may then stimulate cell growth and survival in autocrine and paracrine manners. The clearest example that such mechanisms can drive tumorigenesis is the rare skin tumor DFSP, which is characterized by a gene rearrangement placing the collagen 1A1 gene upstream of the PDGF-B gene. This leads to the production of a fusion protein which is processed to a molecule similar to mature PDGF-BB and causes autocrine stimulation of growth.

30Inhibition of PDGF receptor signaling by the kinase inhibitor imatinib inhibits the growth and promotes apoptosis of DFSP cells. Treatment with imatinib has also shown beneficial effects for individual patients with DFSP. These encouraging findings prompted a multicenter Phase II trial; out of 12 patients with DFSP, 4 showed complete and 4 partial responses. The median time to progression was 24 months. Additional Phase II trials showed partial responses in about half of the cases; however, the response were rather short-lived whereafter resistance mechanisms occurred.

31In about 5% of patients with GIST, PDGFRα is activated by point mutations. Treatment with imatinib has been shown to improve the outcome for GIST patients. Upon development of resistance to imatinib, other kinase inhibitors, such as sunitinib and nilotinib have shown efficacy.

32PDGF and PDGF receptors are also expressed in other types of sarcomas. Early studies revealed that a human osteosarcoma cell line, U-2OS, secretes a PDGF-like growth factor and shows autocrine receptor activation by this factor. Malignancy-dependent co-expression of PDGF and PDGF receptors have also been observed in biopsies of soft tissue sarcoma, osteosarcoma and synovial sarcoma. Nearly all cases of Ewing’s sarcoma show the presence of the chimeric transcription factor EWS/ETS which causes upregulation of PDGF-C; treatment of a cell line from a Ewing’s sarcoma with a PDGFR kinase inhibitor was shown to inhibit its anchorage-independent growth.

33Whereas treatment of osteosarcoma patients with imatinib did not show any advantage as a single agent, the combination of the mTOR inhibitor everolimus and imatinib may be useful in the treatment of synovial sarcoma.

34PDGFRα is selectively upregulated in rhabdomyosarcoma, and PDGFRα expression is associated with poor prognosis. Treatment with imatinib or a neutralizing PDGFRα antibody inhibited growth of alveolar rhabdomyosarcoma in a mouse model.

35In a large randomized, double-blind, placebo-controlled Phase III trial, 369 patients with metastatic non-adipocytic soft tissue sarcoma who had failed on standard therapy, were subjected to treatment with pazopanib or not. A median progression-free survival of 4.6 months and an overall survival of 12.5 months were recorded for the pazopanib treated patients, compared to 1.6 and 10.7 months, respectively for untreated patients. This study thus showed that treatment with pazopanib is of some advantage for these patients with sarcomas.

36PDGF and PDGF receptors are also overexpressed in dog hemangiosarcoma, a malignant neoplasia of vascular endothelial cells. Treatment of hemangiosarcoma in dogs with imatinib and dasatinib augmented the response to doxorubicin; however, dasatinib, which inhibits Src in addition to PDGF receptor kinases, was more efficient.

Leukemias and lymphomas

37Activating mutations in the Abl and JAK2 genes, encoding tyrosine kinases, are common in myeloproliferative diseases; in some cases mutations are also seen in the PDGFRα and PDGFRβ genes.

38In chronic monomyelocytic leukemia (CMML) the PDGFRβ gene has been found to be fused with the gene encoding the transcription factor TEL; the N-terminal of the fusion protein contains sequences from TEL which is followed by the intracellular part of the receptor containing the kinase domain (Figure 2). There are also other fusion partners, including Rabaptin 5, HIP1 and H4. In a case of thrombocythemia, the tumor suppressor gene KANK1 was found to be fused with the PDGFRβ gene.

39PDGFRα are also rearranged in certain malignancies. Thus, in hypereosinophilic syndrome (HES), the α-receptor gene is fused to the FIP1L1 gene (Figure 2). Activating point mutations in the PDGF α-receptor have also been seen.

40These proteins all have the ability to oligomerize and thus cause clustering of the receptor kinase; the juxtaposition of the kinase domains, as well as the loss of inhibitory transmembrane and juxtamembrane sequences, cause activation of the kinase. Moreover, escape of ubiquitin-mediated degradation causing accumulation of large amounts of the fusion proteins may also contribute to the transformation.

41Activation of the PDGFRβ kinase through gene rearrangements leads to chronic myeologenous leukemia (CML) or CMML, whereas activation of the PDGFRα kinase causes HES or chronic eosinophilic leukemia. Interestingly, activation of yet other tyrosine kinases is associated with other types of leukemia, i.e. activation of the FLT3 kinase with acute myelocytic leukemia (AML) or myelodysplastic syndrome, and activation of the Kit kinase with aggressive mastocytosis, myelodysplastic syndrome and AML for references see. It is likely that these differences reflect differences in the activation of signaling pathways. FIP1L1-PDGFRα activates STAT5, PI3-kinase and the Ras-Erk and p38 MAP-kinase pathways; particularly, the stronger activation of Erk and p38 MAP-kinases by FIP1L1-PDGFRα, compared to TEL-PDGFRβ, could be linked to eosinophilic differentiation. Both TEL-PDGFRα and FIP1L1-PDGFRα fusion proteins activate the transcription factors STAT1, 3 and 5, and nuclear factor-κB (NFκB), and cause proliferation and differentiation towards the eosinophilic lineage.

42Patients with CMML have been successfully treated with imatinib, as have patients with HES. Point mutations conferring imatinib resistance have been described both for TEL-PDGFRβ and FIP1L1-PDGFRα. Other kinase inhibitors, such as nilotinib or sorafenib, or midostaurin (PKC412), could inhibit some of the resistant kinase mutants, and offers alternative treatments. Interestingly, only few cases of resistance due to point mutations in the PDGFR kinase domains have been reported, in contrast to the situation for the treatment of chronic myeloic leukemia in which such mutations in the kinase domain of Brc-Abl are very common; it has been suggested that this is because the PDGFRα kinase domain contains only few residues which can be exchanged resulting in interference with inhibitor binding, without loss of kinase activity.

43Large granular lymphocyte leukemia results from the expansion of cytotoxic T cells or natural killer cells, cell types that have been shown to express PDGF receptors. Together with stimulation by IL-15, autocrine stimulation by PDGF-BB drives the development of this rare leukemia, and a PDGF-BB neutralizing antibody was found to inhibit growth and survival of the leukemia cells.

44Anaplastic large cell lymphoma is an aggressive non-Hodgkin’s lymphoma, which is characterized by the occurrence of a fusion between nucleophosmin and the tyrosine kinase ALK. In a mouse model of this disease, the AP-1 members Jun and JunB were found to promote the expression of PDGF-B in the lymphoma cells. The importance of the autocrine PDGF stimulation for tumorigenesis is illustrated by the finding that treatment of the transgenic mice with imatinib significantly prolonged their life. Moreover, treatment of a patient with anaplastic large cell lymphoma with imatinib resulted in rapid, complete and sustained remission.

Prostate cancer

45Immunohistochemical stainings have revealed that PDGFRβ is upregulated in most primary and metastatic prostate cancer cells. Moreover, PDGFRβ mRNA expression was identified by microarray analyses as one of five mRNAs that predict prostate cancer recurrence, the other four being chromogranin A, HOXC6, IPTR3 and sialyltransferase-1. Whereas the PDGFRβ ligand PDGF-B has not been found to be overexpressed in prostate tumors, the other PDGFRβ ligand, PDGF-D, is often expressed at high levels and its expression correlates to the degree of malignancy. Overexpression of PDGF-D in a mouse model significantly enhanced prostate carcinoma onset and invasiveness. Loss of PTEN, which enhances PI3-kinase signaling, promotes production of PDGF-D, whereas the AMP-activated kinase (AMPK) regulates PDGF-B expression. Overexpression of PDGF-D in PC3 prostate cancer cells was found to promote EMT and a stem cell phenotype, which may explain the increased invasiveness. When PDGF-B and PDGF-D were transfected into non-malignant prostate epithelial cells, PDGF-D was found to induce cell migration and invasion more efficiently than PDGF-B. The stronger effect of PDGF-D was dependent of the Jun MAP-kinase and involved shedding and activation of the serine protease matriptase. The mechanism behind the stronger tumorigenic effect of PDGF-D, compared to PDGF-B that binds to the same receptor, remains to be elucidated.

46Interestingly, PDGF-D, but not PDGF-B, was able to induce osteoclast differentiation, and to upregulate the expression and nuclear translocation of nuclear factor of activated T cells 1 (NFAT-1), a master regulator of osteoclastogenesis. This production of PDGF-D by prostate cancer cells is likely to be of importance for the establishment of bone metastases.

47PDGFRα has also been implicated in prostate cancer. In a preclinical model of disseminated prostate cancer, it was shown that treatment with a neutralizing antibody against PDGFRα inhibited the growth of skeletal metastases. Moreover, knock-down of PDGFRα, as well as PDGFRβ, by siRNA suppressed growth of prostate cancer cells in mice and suppressed tumor angiogenesis. Interestingly, evidence have been presented that a soluble component of the bone marrow can activate PDGFRα, and promote bone metastasis of prostate cancer cells, through a mechanism that does not require ligand-binding or receptor dimerization.

48Preclinical studies have demonstrated potential benefit of inhibition of PDGFRβ signaling by imatinib in prostate cancer. Whereas a Phase I clinical trial with imatinib combined with docetaxel showed some benefit, placebo-controlled clinical trials did not show any significantly increased progression free or overall survival. Further clinical trials were halted because of excessive side effects; possibly, other PDGF receptor kinase inhibitors would be more useful. An interesting candidate is cediranib, which inhibits PDGF and VEGF receptor kinases and has been shown to inhibit intraosseous growth of PDGF-D positive prostate cancer cells in a mouse model.

Liver cancer

49During the progression of hepatocellular carcinoma, and in conjunction with epithelial-mesenchymal transition (EMT), PDGF-A as well as PDGFRα and β are induced. Inhibition of PDGF receptor signaling was found to decrease cell migration in vitro and tumor growth in vivo, in a β-catenin-dependent manner, indicating an important role for PDGF signaling in hepatocyte tumor progression. Sorafenib, which in addition to PDGFR inhibits Raf, VEGFR and Kit, is now standard treatment for patients with hepatocellular carcinoma. However, it is not clear how important PDGFR kinase inhibition is for the beneficial effects.

50PDGF-A and PDGFRα mRNA and protein are often overexpressed in patients with cholangiocarcinoma; treatment of cholangiocarcinoma cell lines with the PDGF receptor kinase inhibitors imatinib or sunitinib suppressed cell viability and migration. Sorafenib also inhibited cholangiocarcinoma cell growth and survival in vitro and in vivo. In another study, myofibroblast-derived PDGF-BB was shown to provide survival signals for cholangiocarcinoma cells, thus protecting them from TRAIL-mediated cytotoxicity by enhancing Hedgehog signaling. Targeting PDGFRα by imatinib sensitized cholangiocarcinoma cells to apoptotic stimuli in vitro and in vivo.

Non-small cell lung cancer

51PDGF receptors are not expressed, or expressed at low levels, in normal lung epithelial cells, however, expression of PDGFRα has been reported in lung cancer cell lines and tumor tissue. Expression of PDGFRβ was also seen, but mainly in the stromal cells. Increased expression of PDGFRβ was seen in the rare sarcomatoid type of non-small cell lung cancer. Expression of PDGF and PDGF receptors in lung cancer was found to be associated with poor prognosis. Inhibition of PDGF in preclinical models of non-small cell lung cancer by treatment with a neutralizing PDGFRα antibody (MEDI-575) caused a significant decrease in stromal fibroblast content but had only minor effect on tumor cell proliferation. In addition, transfection of a non-receptor binding mutant of PDGF-A (PDGF-0) in A549 lung cancer cells, which inactivates the PDGF produced by these cells, led to a markedly decreased tumor growth in vivo because of impaired recruitment of peri-endothelial cells.

52A Phase II clinical study explored the effect of imatinib combined with docetaxel for the treatment of recurrent non-small cell lung cancer, however, only one partial response and 4 stable disease out of 23 treated patients were seen; thus, the study did not reach its objective. Another study focused on Asian patients who were treated with sunitinib; two partial responses and 7 stable disease were observed out of 18 patients treated. Larger studies need to be conducted before it is possible to determine whether inhibition of PDGF receptors, with or without inhibition of VEGF receptors, is of any benefit for lung cancer patients.

Breast cancer

53In breast cancer, expression of PDGF in tumor cells and PDGF receptors in stromal cells have been reported. PDGF receptors are also expressed in the tumor cells, which correlate with tumor progression and invasion. PDGF receptors have been observed to be upregulated upon IGF1 receptor independence in an animal model.

54Combining imatinib treatment with radiotherapy showed a significantly stronger inhibition of cell proliferation compared to radiotherapy alone in a mouse model for breast cancer.

55PDGF-D produced by cells in the stroma of breast cancers, e.g. adipose tissue-derived stem cells, was found to induce EMT of the cancer cells in a paracrine manner, thereby promoting the formation of cancer stem cells and tumorigenesis.

56It remains to be determined whether inhibition of PDGF receptor signaling is of benefit for breast cancer patients. A possible subgroup that could benefit is patients with estrogen receptor positive tumors undergoing aromatase inhibition therapy, since this treatment has been found to be associated with an upregulation of PDGFRβ on the tumor cells.

Colorectal cancer

57In colorectal cancers PDGF receptors are mainly expressed by stromal cells and pericytes, but PDGF receptor expression has also been noted on colorectal carcinoma cell lines. Expression of PDGF receptors is associated with poor prognosis for patients with colorectal cancer. Studies using preclinical models have shown that colorectal cancer cells can acquire PDGFRβ in conjunction with EMT, and that activation of this receptor promotes metastasis.

Other tumors

58Several other tumor types have been reported to involve overactive PDGF signaling in the tumor cells. Thus, PDGF-D and PDGFRβ were found to be co-expressed in several mesothelioma cell lines, resulting in autocrine stimulation of cell proliferation.

59In Wilms’ tumor of the kidney, PDGF-A and PDGFRα was expressed in 50% and 55% of the cases, respectively, in a cohort of 62 patients; interestingly, expression of PDGF-A and PDGFRα correlated with good prognosis. It is possible that expression of PDGF-A and PDGFRα reflect a differentiated phenotype and therefore correlates to favorable prognosis. This is in contrast to breast, ovarian and lung carcinomas, in which cases PDGF and PDGF receptor expression correlate to poor prognosis.

60The childhood tumor neuroblastoma arises from the neural crest remnants of the sympathetic nervous system, and has been shown to express PDGF receptors, as well as c-Kit. Whereas imatinib inhibited neuroblastoma cells in vitro and in xenografts, little or no treatment effect as single agent was seen in children with relapsed or refractory neuroblastoma.

61Activation of the hedgehog pathway occurs frequently in basal cell carcinoma of the skin. The transcription factor Gli1, which is activated in the hedgehog pathway, activates the promoter of the PDGFRα gene and thus promotes PDGFRα expression; this is an important mechanism by which hedgehog signaling promotes tumorigenesis, and suggests that PDGF inhibition could be beneficial in skin tumor treatment.

62Leydig cell tumors of the testis express high levels of PDGF isoforms and PDGF receptors. However, treatment of a patient with imatinib was not successful. On the other hand, human testicular germ tumors also express PDGF receptors, and treatment with sunitinib as single agent showed beneficial effects even in cisplatin-resistant tumors in a mouse model.

63Overexpression of PDGF-A, -B and –C isoforms and both PDGF receptors were found to be crucial for the development of thyroid nodules and recurrent goitre.

Targeting PDGF in tumor stroma

64In addition to tumor cells, non-tumor cells in solid tumors, such as macrophages and endothelial cells, produce PDGF isoforms. PDGF receptors are expressed on pericytes and smooth muscle cells of vessels, as well as on fibroblasts and myofibroblasts. Recent studies have shown that targeting of cells in tumor stroma can be beneficial in tumor treatment, particularly if combined with targeting of the tumor cells directly.

Anti-angiogenic treatment

65Angiogenesis is promoted by several different factors, including VEGF, FGF, TGFβ, angiopoietins and PDGF. A monoclonal antibody against VEGF, bevacizumab, is already used clinically. PDGF has an accessory role in angiogenesis and, in particular, promotes pericyte recruitment to vessels. Studies using different mouse models have shown that anti-angiogenic therapy can be more efficient by combination of inhibition of VEGF signaling, targeting endothelial cells, and PDGF signaling, targeting pericytes. Combination therapy probably interrupts the trophic relationship between endothelial cells and pericytes. Simultaneous inhibition of fibroblast growth factor (FGF) may be even more beneficial. Interestingly, resistance to anti-VEGF treatment has been shown to involve increased expression of PDGF-C. However, the effect of anti-PDGF treatment may be context-dependent. Thus, no synergistic effect was seen by the combination of anti-VEGF and anti-PDGF treatment in mouse models of colorectal and pancreatic cancer; in fact PDGF overexpression was found to inhibit endothelial cells and angiogenesis by intensive pericyte recruitment. Another complication was reported from a clinical study in which CDP860, an engineered Fab’ fragment inhibiting PDGFRβ, was used; the study had to be interrupted since seven of eight patients developed fluid retention and three significant ascites upon treatment.

66Bone-marrow-derived mesenchymal stem cells have been shown to exert an anti-angiogenic effect in preclinical models of glioma by inhibiting the recruitment of endothelial progenitor cells through decreased expression of PDGF-BB and other angiogenic factors.

67A mechanism whereby PDGF-BB promotes tumor angiogenesis and tumor growth was recently presented; by induction of erythropoietin, PDGF-BB promotes endothelial cell proliferation, migration, sprouting and tube formation, and promotes extramodullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Another mechanism was unraveled by studies of chronic lymphocytic leukemia; PDGF secreted by these tumor cells stimulated mesenchymal stromal cells to produce VEGF.

68PDGF-BB has also been shown to stimulate lymphangiogenesis, and to promote lymphatic metastasis in gastric carcinoma. In papillary thyroid cancer, expression of PDGFRα correlated with lymphatic metastases.

Cancer-associated fibroblasts

69It has become increasingly appreciated that stromal cells of solid tumors contribute to tumorigenesis. Such cells include, in addition to vascular cells, e.g. macrophages and cancer-associated fibroblasts (CAFs). The latter cell type is heterogeneous and may derive from tissue fibroblasts, bone-marrow-derived progenitor cells or transdifferentiating epithelial cells. The various cell types of the stromal compartment contribute to tumorigenesis by secreting various growth factors and cytokines which promotes growth, survival and migration of the tumor cells, as well as epithelial-mesenchymal transition and tumor angiogenesis.

70PDGF receptors are expressed on CAFs and there are several reports that PDGF stimulation affects CAF function. Thus, ectopic expression of PDGF-BB was found to promote stroma formation and tumor growth of melanoma, tumorigenesis of immortalized keratinocytes and growth of prostate cancer. Tumor cell-derived PDGF-AA was found to recruit CAFs in xenograft studies of breast and lung carcinomas. Transgenic expression of PDGF-CC in mouse liver cells resulted in tissue fibrosis and promoted development of hepatocellular carcinoma. Moreover, expression of PDGF-CC in mouse models promoted recruitment of CAFs and growth of malignant melanoma and liver metastasis of colorectal cancer. Finally, ectopic expression of PDGF-DD was found to promote tumorigenesis and angiogenesis. Stromal PDGF receptor expression has been shown to be associated with poor prognosis in breast and prostate cancer, in colorectal cancer and in pancreatic carcinoma.

71CAFs and myofibroblasts make contacts with collagen fibers of the extracellular matrix. PDGF stimulation of these cells causes cell contraction leading to an increased tumor interstitial pressure. This is an obstacle in treatment of tumor patients with chemotherapy, since it decreases transcapillary transport and drug uptake. Treatment of mice with different types of solid tumors with PDGF antagonists was found to decrease IFP, to increase drug uptake, and to improve the efficiency of treatment with chemotherapeutic drugs. In addition, treatment with VEGF antagonists was also found to decrease tumor IFP, and the combination of PDGF and VEGF antagonists gave an additive effect.

72Targeting PDGF receptors in the stroma has been found to inhibit lung cancer growth and bone metastasis, and colon cancer growth and metastasis in mouse models.

Future perspectives

73The fact that PDGF and/or PDGF receptors are overexpressed or mutated in different tumors makes it desirable to investigate whether PDGF or PDGF receptor antagonists can be used to treat patients with these diseases. Some encouraging results have already been obtained by treatment of some rather rare tumors driven by overactive PDGF receptor signaling due to mutations of either PDGF or PDGF receptor genes. However, resistance mechanisms limit the success of such treatments, and anti-PDGF receptor treatment most likely will have to be combined with other signal transduction inhibitors, chemotherapeutical agents or other treatments, in order to achieve long lasting remissions.

74In solid tumors PDGF receptors are expressed on pericytes of vessels and on fibroblasts and myofibroblasts of the stroma. Tumor cells are dependent on their environment for their proliferation and survival, making non-malignant PDGF receptor expressing cells interesting targets in tumor treatment. Further studies are needed in order to explore whether anti-PDGF receptor treatment targeting non-malignant cells in the tumor, in combination with anti-tumor cell treatment, will be of benefit for patients. It also remains to be determined whether selective inhibition of PDGF or PDGF receptors by e.g. monoclonal antibodies or ligand traps, or more unspecific inhibition of PDGF receptor kinases by low molecular weight inhibitors, will give the best clinical results.

Competing interest

75The author declare that he has no competing interests.

References 283

1.
Heldin C-H Westermark B Mechanism of action and in vivo role of platelet-derived growth factorPhysiol Rev1999 1112831316
Not in our library10.1152/physrev.1999.79.4.1283
2.
Andrae J Gallini R Betsholtz C Role of platelet-derived growth factors in physiology and medicineGenes Dev2008 1112761312
Not in our library10.1101/gad.1653708
3.
Heldin C-H Targeting the PDGF signaling pathway in the treatment of non-malignant diseasesJ Neuroimmune Pharmacol2013 in press
Not in our library10.1007/s11481-013-9484-2
4.
Fredriksson L Li H Fieber C Li X Eriksson U Tissue plasminogen activator is a potent activator of PDGF-CCEMBO J2004 1137933802
Not in our library10.1038/sj.emboj.7600397
5.
Fredriksson L Li H Eriksson U The PDGF family: four gene products form five dimeric isoformsCytokine Growth Factor Rev2004 11197204
Not in our library10.1016/j.cytogfr.2004.03.007
6.
Ustach CV Kim HR Platelet-derived growth factor D is activated by urokinase plasminogen activator in prostate carcinoma cellsMol Cell Biol2005 1162796288
Not in our library10.1128/mcb.25.14.6279-6288.2005
7.
Ustach CV Huang W Conley-LaComb MK Lin CY Che M Abrams J Kim HR A novel signaling axis of matriptase/PDGF-D/β-PDGFR in human prostate cancerCancer Res2010 1196319640
Not in our library10.1158/0008-5472.can-10-0511
8.
Omura T Heldin C-H Östman A Immunoglobulin-like domain 4-mediated receptor-receptor interactions contribute to platelet-derived growth factor-induced receptor dimerizationJ Biol Chem1997 111267612682
Not in our library10.1074/jbc.272.19.12676
9.
Yang Y Yuzawa S Schlessinger J Contacts between membrane proximal regions of the PDGF receptor ectodomain are required for receptor activation but not for receptor dimerizationProc Natl Acad Sci USA2008 1176817686
Not in our library10.1073/pnas.0802896105
10.
Baxter RM Secrist JP Vaillancourt RR Kazlauskas A Full activation of the platelet-derived growth factor beta-receptor kinase involves multiple eventsJ Biol Chem1998 111705017055
Not in our library10.1074/jbc.273.27.17050
11.
Irusta PM Luo Y Bakht O Lai CC Smith SO DiMaio D Definition of an inhibitory juxtamembrane WW-like domain in the platelet-derived growth factor beta receptorJ Biol Chem2002 113862738634
Not in our library10.1074/jbc.m204890200
12.
Chiara F Bishayee S Heldin C-H Demoulin J-B Autoinhibition of the platelet-derived growth factor β receptor tyrosine kinase by its C-terminal tailJ Biol Chem2004 111973219738
Not in our library10.1074/jbc.m314070200
13.
Heldin C-H Östman A Rönnstrand L Signal transduction via platelet-derived growth factor receptorsBiochim Biophys Acta1998 11F79F113
Not in our library10.1016/s0304-419x(98)00015-8
14.
Bae YS Sung J-Y Kim O-S Kim YJ Hur KC Kazlauskas A Rhee SG Platelet-derived growth factor-induced H2O2 production requires the activation of phosphatidylinositol 3-kinaseJ Biol Chem2000 111052710531
Not in our library10.1074/jbc.275.14.10527
15.
Sundaresan M Yu ZX Ferrans VJ Irani K Finkel T Requirement for generation of H2O2 for platelet-derived growth factor signal transductionScience1995 11296299
Not in our library10.1126/science.270.5234.296
16.
Jurek A Amagasaki K Gembarska A Heldin C-H Lennartsson J Negative and positive regulation of MAPK phosphatase 3 controls platelet-derived growth factor-induced Erk activationJ Biol Chem2009 1146264634
Not in our library10.1074/jbc.m808490200
17.
Fantl WJ Escobedo JA Martin GA Turck CW del Rosario M McCormick F Williams LT Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathwaysCell1992 11413423
Not in our library10.1016/0092-8674(92)90444-h
18.
Jurek A Heldin C-H Lennartsson J Platelet-derived growth factor-induced signaling pathways interconnect to regulate the temporal pattern of Erk1/2 phosphorylationCell Signal2011 11280287
Not in our library10.1016/j.cellsig.2010.09.013
19.
Haj FG Markova B Klaman LD Bohmer FD Neel BG Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1BJ Biol Chem2003 11739744
Not in our library10.1074/jbc.m210194200
20.
Persson C Sävenhed C Bourdeau A Tremblay ML Markova B Böhmer FD Haj FG Neel BG Elson A Heldin C-H Site-selective regulation of platelet-derived growth factor β receptor tyrosine phosphorylation by T-cell protein tyrosine phosphataseMol Cell Biol2004 1121902201
Not in our library10.1128/mcb.24.5.2190-2201.2004
21.
Kovalenko M Denner K Sandström J Persson C Groß S Jandt E Vilella R Böhmer F Östman A Site-selective dephosphorylation of the platelet-derived growth factor β-receptor by the receptor-like protein-tyrosine phosphatase DEP-1J Biol Chem2000 111621916226
Not in our library10.1074/jbc.275.21.16219
22.
Kappert K Paulsson J Sparwel J Leppänen O Hellberg C Östman A Micke P Dynamic changes in the expression of DEP-1 and other PDGF receptor-antagonizing PTPs during onset and termination of neointima formationFASEB J2007 11523534
Not in our library10.1096/fj.06-6219com
23.
Peng Z-Y Cartwright CA Regulation of the Src tyrosine kinase and Syp tyrosine phosphatase by their cellular associationOncogene1995 1119551962
Not in our library
24.
Dance M Montagner A Salles JP Yart A Raynal P The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathwayCell Signal2008 11453459
Not in our library10.1016/j.cellsig.2007.10.002
25.
Saito Y Haendeler J Hojo Y Yamamoto K Berk BC Receptor heterodimerization: essential mechanism for platelet-derived growth factor-induced epidermal growth factor receptor transactivationMol Cell Biol2001 1163876394
Not in our library10.1128/mcb.21.19.6387-6394.2001
26.
Sundberg C Rubin K Stimulation of β1 integrins on fibroblasts induces PDGF independent tyrosine phosphorylation of PDGF β-receptorsJ Cell Biol1996 11741752
Not in our library10.1083/jcb.132.4.741
27.
Loukinova E Ranganathan S Kuznetsov S Gorlatova N Migliorini MM Loukinov D Ulery PG Mikhailenko I Lawrence DA Strickland DK Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of the low density lipoprotein receptor-related protein (LRP). Evidence for integrated co-receptor function between LRP and the PDGFJ Biol Chem2002 111549915506
Not in our library10.1074/jbc.m200427200
28.
Boucher P Liu P Gotthardt M Hiesberger T Anderson RG Herz J Platelet-derived growth factor mediates tyrosine phosphorylation of the cytoplasmic domain of the low density lipoprotein receptor-related protein in caveolaeJ Biol Chem2002 111550715513
Not in our library10.1074/jbc.m200428200
29.
Newton CS Loukinova E Mikhailenko I Ranganathan S Gao Y Haudenschild C Strickland DK Platelet-derived growth factor receptor-β (PDGFR-β) activation promotes its association with the low density lipoprotein receptor-related protein (LRP). Evidence for co-receptor functionJ Biol Chem2005 112787227878
Not in our library10.1074/jbc.m505410200
30.
Li L Heldin C-H Heldin P Inhibition of platelet-derived growth factor-BB-induced receptor activation and fibroblast migration by hyaluronan activation of CD44J Biol Chem2006 112651226519
Not in our library10.1074/jbc.m605607200
31.
Miyake S Mullane-Robinson KP Lill NL Douillard P Band H Cbl-mediated negative regulation of platelet-derived growth factor receptor-dependent cell proliferation - a critical role for Cbl tyrosine kinase-binding domainJ Biol Chem1999 111661916628
Not in our library10.1074/jbc.274.23.16619
32.
Wang Y Pennock SD Chen X Kazlauskas A Wang Z Platelet-derived growth factor receptor-mediated signal transduction from endosomesJ Biol Chem2004 1180388046
Not in our library10.1074/jbc.m311494200
33.
Hellberg C Schmees C Karlsson S Åhgren A Heldin C-H Activation of protein kinase C α is necessary for sorting the PDGF β-receptor to Rab4a-dependent recyclingMol Biol Cell2009 1128562863
Not in our library10.1091/mbc.e08-12-1228
34.
Schmees C Villaseñor R Zheng W Ma H Zerial M Heldin C-H Hellberg C Macropinocytosis of the PDGF β-receptor promotes fibroblast transformation by H-RasG12VMol Biol Cell2012 1125712582
Not in our library10.1091/mbc.e11-04-0317
35.
Soriano P The PDGFα receptor is required for neural crest cell development and for normal patterning of the somitesDevelopment1997 1126912700
Not in our library10.1242/dev.124.14.2691
36.
Boström H Willetts K Pekny M Levéen P Lindahl P Hedstrand H Pekna M Hellström M Gebre-Medhin S Schalling M PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesisCell1996 11863873
Not in our library10.1016/s0092-8674(00)81270-2
37.
Karlsson L Lindahl P Heath JK Betsholtz C Abnormal gastrointestinal development in PDGF-A and PDGFR-α deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesisDevelopment2000 1134573466
Not in our library10.1242/dev.127.16.3457
38.
Soriano P Abnormal kidney development and hematological disorders in PDGF β-receptor mutant miceGenes Dev1994 1118881896
Not in our library10.1101/gad.8.16.1888
39.
Levéen P Pekny M Gebre-Medhin S Swolin B Larsson E Betsholtz C Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalitiesGenes Dev1994 1118751887
Not in our library10.1101/gad.8.16.1875
40.
Lindahl P Johansson BR Levéen P Betsholtz C Pericyte loss and microaneurysm formation in PDGF-B-deficient miceScience1997 11242245
Not in our library10.1126/science.277.5323.242
41.
Lindahl P Karlsson L Hellström M Gebre-Medhin S Willetts K Heath JK Betsholtz C Alveogenesis failure in PDGF-A-deficient mice is coupled to lack of distal spreading of alveolar smooth muscle cell progenitors during lung developmentDevelopment1997 1139433953
Not in our library10.1242/dev.124.20.3943
42.
Ohashi S Natsuizaka M Naganuma S Kagawa S Kimura S Itoh H Kalman RA Nakagawa M Darling DS Basu D A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT-competent cells that express the ZEB transcription factorsCancer Res2011 1168366847
Not in our library10.1158/0008-5472.can-11-0846
43.
Robson MC Phillips LG Thomason A Robson LE Pierce GF Platelet-derived growth factor BB for the treatment of chronic pressure ulcersLancet1992 112325
Not in our library10.1016/0140-6736(92)90143-q
44.
Rodt SÅ Åhlén K Berg A Rubin K Reed RK A novel physiological function for platelet-derived growth factor-BB in rat dermisJ Physiol1996 11193200
Not in our library10.1113/jphysiol.1996.sp021584
45.
Green LS Jellinek D Jenison R Östman A Heldin C-H Janjic N Inhibitory DNA ligands to platelet-derived growth factor B-chainBiochem1996 111441314424
Not in our library10.1021/bi961544+
46.
Hawthorne T Giot L Blake L Kuang B Gerwien R Smithson G Hahne W Mansfield T Starling GC Pochart P A phase I study of CR002, a fully-human monoclonal antibody against platelet-derived growth factor-DInt J Clin Pharmacol Ther2008 11236244
Not in our library10.5414/cpp46236
47.
Jayson GC Parker GJ Mullamitha S Valle JW Saunders M Broughton L Lawrance J Carrington B Roberts C Issa B Blockade of platelet-derived growth factor receptor-beta by CDP860, a humanized, PEGylated di-Fab’, leads to fluid accumulation and is associated with increased tumor vascularized volumeJ Clin Oncol2005 11973981
Not in our library10.1200/jco.2005.01.032
48.
Shen J Vil MD Zhang H Tonra JR Rong LL Damoci C Prewett M Deevi DS Kearney J Surguladze D An antibody directed against PDGF receptor β enhances the antitumor and the anti-angiogenic activities of an anti-VEGF receptor 2 antibodyBiochem Biophys Res Commun2007 1111421147
Not in our library10.1016/j.bbrc.2007.04.075
49.
Shen J Vil MD Prewett M Damoci C Zhang H Li H Jimenez X Deevi DS Iacolina M Kayas A Development of a fully human anti-PDGFRβ antibody that suppresses growth of human tumor xenografts and enhances antitumor activity of an anti-VEGFR2 antibodyNeoplasia2009 11594604
Not in our library10.1593/neo.09278
50.
Socinski MA Multitargeted receptor tyrosine kinase inhibition: an antiangiogenic strategy in non-small cell lung cancerCancer Treat Rev2011 11611617
Not in our library10.1016/j.ctrv.2011.04.003
51.
Chao Q Sprankle KG Grotzfeld RM Lai AG Carter TA Velasco AM Gunawardane RN Cramer MD Gardner MF James J Identification of N-(5-tert-butyl-isoxazol-3-yl)-N’-{4-[7-(2-morpholin-4-yl-ethoxy) imidazo [2,1-b] [1,3] benzothiazol-2-yl] phenyl} urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitorJ Med Chem2009 1178087816
Not in our library10.1021/jm9007533
52.
Kampa-Schittenhelm KM Heinrich MC Akmut F Dohner H Dohner K Schittenhelm MM Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoformsMol Cancer2013 1119
Not in our library10.1186/1476-4598-12-19
53.
Huang WS Metcalf CA Sundaramoorthi R Wang Y Zou D Thomas RM Zhu X Cai L Wen D Liu S Discovery of 3-[2-(imidazo [1,2-b] \pyridazin-3-yl) ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl) methyl]-3-(trifluoromethyl) phenyl} benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutantJ Med Chem2010 1147014719
Not in our library10.1021/jm100395q
54.
De Falco V Buonocore P Muthu M Torregrossa L Basolo F Billaud M Gozgit JM Carlomagno F Santoro M Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancerJ Clin Endocrinol Metab2013 11E811E819
Not in our library10.1210/jc.2012-2672
55.
Pietras K Sjöblom T Rubin K Heldin C-H Östman A PDGF receptors as cancer drug targetsCancer Cell2003 11439443
Not in our library10.1016/s1535-6108(03)00089-8
56.
O’Brien KP Seroussi E Dal Cin P Sciot R Mandahl N Fletcher JA Turc-Carel C Dumanski JP Various regions within the α-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomasGene Chrom Cancer1998 11187193
Not in our library
57.
Simon M-P Pedeutour F Sirvent N Grosgeorge J Minoletti F Coindre J-M Terrier-Lacombe M-J Mandahl N Craver RD Blin N Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastomaNature Genet1997 119598
Not in our library10.1038/ng0197-95
58.
Shimizu A O’Brien KP Sjöblom T Pietras K Buchdunger E Collins VP Heldin C-H Dumanski JP Östman A The dermatofibrosarcoma protuberans-associated collagen type Iα1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BBCancer Res1999 1137193723
Not in our library
59.
Heinrich MC Corless CL Duensing A McGreevey L Chen CJ Joseph N Singer S Griffith DJ Haley A Town A PDGFRA activating mutations in gastrointestinal stromal tumorsScience2003 11708710
Not in our library10.1126/science.1079666
60.
Toffalini F Demoulin JB New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinasesBlood2010 1124292437
Not in our library10.1182/blood-2010-04-279752
61.
Fleming TP Saxena A Clark WC Robertson JT Oldfield EH Aaronson SA Ali IU Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumorsCancer Res1992 1145504553
Not in our library
62.
Kumabe T Sohma Y Kayama T Yoshimoto T Yamamoto T Amplification of α-platelet-derived growth factor receptor gene lacking an exon coding for a portion of the extracellular region in a primary brain tumor of glial originOncogene1992 11627633
Not in our library
63.
Puputti M Tynninen O Sihto H Blom T Maenpaa H Isola J Paetau A Joensuu H Nupponen NN Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomasMol Cancer Res2006 11927934
Not in our library10.1158/1541-7786.mcr-06-0085
64.
Smith JS Wang XY Qian J Hosek SM Scheithauer BW Jenkins RB James CD Amplification of the platelet-derived growth factor receptor-A (PDGFRA) gene occurs in oligodendrogliomas with grade IV anaplastic featuresJ Neuropathol Exp Neurol2000 11495503
Not in our library10.1093/jnen/59.6.495
65.
Arai H Ueno T Tangoku A Yoshino S Abe T Kawauchi S Oga A Furuya T Oka M Sasaki K Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma: comparison with conventional comparative genomic hybridization analysisCancer Genet Cytogenet2003 111621
Not in our library10.1016/s0165-4608(03)00106-7
66.
Zhao J Roth J Bode-Lesniewska B Pfaltz M Heitz PU Komminoth P Combined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumorsGenes Chromosomes Cancer2002 114857
Not in our library10.1002/gcc.10035
67.
Dewaele B Floris G Finalet-Ferreiro J Fletcher CD Coindre JM Guillou L Hogendoorn PC Wozniak A Vanspauwen V Schoffski P Coactivated platelet-derived growth factor receptor α and epidermal growth factor receptor are potential therapeutic targets in intimal sarcomaCancer Res2010 1173047314
Not in our library10.1158/0008-5472.can-10-1543
68.
Clarke ID Dirks PB A human brain tumor-derived PDGFR-α deletion mutant is transformingOncogene2003 11722733
Not in our library10.1038/sj.onc.1206160
69.
Thiery JP Acloque H Huang RY Nieto MA Epithelial-mesenchymal transitions in development and diseaseCell2009 11871890
Not in our library10.1016/j.cell.2009.11.007
70.
Jechlinger M Sommer A Moriggl R Seither P Kraut N Capodiecci P Donovan M Cordon-Cardo C Beug H Grunert S Autocrine PDGFR signaling promotes mammary cancer metastasisJ Clin Invest2006 1115611570
Not in our library10.1172/jci24652
71.
Heldin C-H Rubin K Pietras K Östman A High interstitial fluid pressure - an obstacle in cancer therapyNat Rev Cancer2004 11806813
Not in our library10.1038/nrc1456
72.
Weinstein IB Joe A Oncogene addictionCancer Res2008 1130773080
Not in our library10.1158/0008-5472.can-07-3293
73.
Deinhardt F Klein GThe biology of primate retrovirusViral oncology1980 New York: Raven Press359398
Not in our library
74.
Waterfield MD Scrace GT Whittle N Stroobant P Johnsson A Wasteson Å Westermark B Heldin C-H Huang JS Deuel TF Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virusNature (London)1983 113539
Not in our library10.1038/304035a0
75.
Doolittle RF Hunkapiller MW Hood LE Devare SD Robbins KC Aaronson SA Antoniades HN Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factorScience1983 11275277
Not in our library10.1126/science.6304883
76.
Nistér M Libermann TA Betsholtz C Pettersson M Claesson-Welsh L Heldin C-H Schlessinger J Westermark B Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-α and their receptors in human malignant glioma cell linesCancer Res1988 1139103918
Not in our library
77.
Lokker NA Sullivan CM Hollenbach SJ Israel MA Giese NA Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumorsCancer Res2002 1137293735
Not in our library
78.
Hermanson M Funa K Hartman M Claesson-Welsh L Heldin C-H Westermark B Nistér M Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loopsCancer Res1992 1132133219
Not in our library
79.
Di Rocco F Carroll RS Zhang JP Black PM Platelet-derived growth factor and its receptor expression in human oligodendrogliomasNeurosurgery1998 11341346
Not in our library10.1097/00006123-199802000-00080
80.
Martinho O Longatto-Filho A Lambros MB Martins A Pinheiro C Silva A Pardal F Amorim J Mackay A Milanezi F Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomasBr J Cancer2009 11973982
Not in our library10.1038/sj.bjc.6605225
81.
Hermanson M Funa K Koopmann J Maintz D Waha A Westermark B Heldin C-H Wiestler OD Louis DN von Deimling A Nistér M Association of loss of heterozygosity on chromosome 17p with high platelet-derived growth factor α receptor expression in human malignant gliomasCancer Res1996 11164171
Not in our library
82.
Guha A Dashner K Black PM Wagner JA Stiles CD Expression of PDGF and PDGF receptors in human astrocytoma operation specimens supports the existence of an autocrine loopInt J Cancer1995 11168173
Not in our library10.1002/ijc.2910600206
83.
Maxwell M Naber SP Wolfe HJ Galanopoulos T Hedley-Whyte ET Black PM Antoniades HN Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenanceJ Clin Invest1990 11131140
Not in our library10.1172/jci114675
84.
Plate KH Breier G Farrell CL Risau W Platelet-derived growth factor receptor-β is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomasLab Invest1992 11529534
Not in our library
85.
Rand V Huang J Stockwell T Ferriera S Buzko O Levy S Busam D Li K Edwards JB Eberhart C Sequence survey of receptor tyrosine kinases reveals mutations in glioblastomasProc Natl Acad Sci U S A2005 111434414349
Not in our library10.1073/pnas.0507200102
86.
Kumabe T Sohma Y Kayama T Yoshimoto T Yamamoto T Overexpression and amplification of alpha-PDGF receptor gene lacking exons coding for a portion of the extracellular region in a malignant gliomaTohoku J Exp Med1992 11265269
Not in our library10.1620/tjem.168.265
87.
Verhaak RG Hoadley KA Purdom E Wang V Qi Y Wilkerson MD Miller CR Ding L Golub T Mesirov JP Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1Cancer Cell2010 1198110
Not in our library10.1016/j.ccr.2009.12.020
88.
Paugh BS Zhu X Qu C Endersby R Diaz AK Zhang J Bax DA Carvalho D Reis RM Onar-Thomas A Novel oncogenic PDGFRA mutations in pediatric high-grade gliomasCancer Res2013 1162196229
Not in our library10.1158/0008-5472.can-13-1491
89.
Ozawa T Brennan CW Wang L Squatrito M Sasayama T Nakada M Huse JT Pedraza A Utsuki S Yasui Y PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomasGenes Dev2010 1122052218
Not in our library10.1101/gad.1972310
90.
Uhrbom L Hesselager G Nistér M Westermark B Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirusCancer Res1998 1152755279
Not in our library
91.
Uhrbom L Hesselager G Östman A Nistér M Westermark B Dependence of autocrine growth factor stimulation in platelet-derived growth factor-B-induced mouse brain tumor cellsInt J Cancer2000 11398406
Not in our library10.1002/(sici)1097-0215(20000201)85:3<398::aid-ijc17>3.0.co;2-l
92.
Hesselager G Uhrbom L Westermark B Nister M Complementary effects of platelet-derived growth factor autocrine stimulation and p53 or Ink4a-Arf deletion in a mouse glioma modelCancer Res2003 1143054309
Not in our library
93.
See WL Miller JP Squatrito M Holland E Resh MD Koff A Defective DNA double-strand break repair underlies enhanced tumorigenesis and chromosomal instability in p27-deficient mice with growth factor-induced oligodendrogliomasOncogene2010 1117201731
Not in our library10.1038/onc.2009.465
94.
Tchougounova E Kastemar M Brasater D Holland EC Westermark B Uhrbom L Loss of Arf causes tumor progression of PDGFB-induced oligodendrogliomaOncogene2007 1162896296
Not in our library10.1038/sj.onc.1210455
95.
Liu KW Feng H Bachoo R Kazlauskas A Smith EM Symes K Hamilton RL Nagane M Nishikawa R Hu B Cheng SY SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humansJ Clin Invest2011 11905917
Not in our library10.1172/jci43690
96.
Appolloni I Calzolari F Tutucci E Caviglia S Terrile M Corte G Malatesta P PDGF-B induces a homogeneous class of oligodendrogliomas from embryonic neural progenitorsInt J Cancer2009 1122512259
Not in our library10.1002/ijc.24206
97.
Tumor Progression and Oncogene Addiction in a PDGF-B-Induced Model of Gliomagenesis · 2008
Not checked
98.
Dai C Celestino JC Okada Y Louis DN Fuller GN Holland EC PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivoGenes Dev2001 1119131925
Not in our library10.1101/gad.903001
99.
Assanah M Lochhead R Ogden A Bruce J Goldman J Canoll P Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retrovirusesJ Neurosci2006 1167816790
Not in our library10.1523/jneurosci.0514-06.2006
100.
Nazarenko I Hedren A Sjodin H Orrego A Andrae J Afink GB Nister M Lindstrom MS Brain abnormalities and glioma-like lesions in mice overexpressing the long isoform of PDGF-A in astrocytic cellsPLoS One2011 11e18303
Not in our library10.1371/journal.pone.0018303
101.
Kim Y Kim E Wu Q Guryanova O Hitomi M Lathia JD Serwanski D Sloan AE Weil RJ Lee J Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneityGenes Dev2012 1112471262
Not in our library10.1101/gad.193565.112
102.
PDGF-B Can Sustain Self-renewal and Tumorigenicity of Experimental Glioma-Derived Cancer-Initiating Cells by Preventing Oligodendrocyte Differentiation · 2011
Not checked
103.
Holdhoff M Kreuzer KA Appelt C Scholz R Na IK Hildebrandt B Riess H Jordan A Schmidt CA Van Etten RA Imatinib mesylate radiosensitizes human glioblastoma cells through inhibition of platelet-derived growth factor receptorBlood Cells Mol Dis2005 11181185
Not in our library10.1016/j.bcmd.2004.11.006
104.
Wen PY Yung WK Lamborn KR Dahia PL Wang Y Peng B Abrey LE Raizer J Cloughesy TF Fink K Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American brain tumor consortium study 99–08Clin Cancer Res2006 1148994907
Not in our library10.1158/1078-0432.ccr-06-0773
105.
Raymond E Brandes AA Dittrich C Fumoleau P Coudert B Clement PM Frenay M Rampling R Stupp R Kros JM Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European organisation for research and treatment of cancer brain tumor group studyJ Clin Oncol2008 1146594665
Not in our library10.1200/jco.2008.16.9235
106.
Reardon DA Dresemann G Taillibert S Campone M van den Bent M Clement P Blomquist E Gordower L Schultz H Raizer J Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastomaBr J Cancer2009 1119952004
Not in our library10.1038/sj.bjc.6605411
107.
Dresemann G Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient seriesAnn Oncol2005 1117021708
Not in our library10.1093/annonc/mdi317
108.
Dresemann G Weller M Rosenthal MA Wedding U Wagner W Engel E Heinrich B Mayer-Steinacker R Karup-Hansen A Fluge O Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomideJ Neurooncol2010 11393402
Not in our library10.1007/s11060-009-9976-3
109.
Moreno L Popov S Jury A Al Sarraj S Jones C Zacharoulis S Role of platelet derived growth factor receptor (PDGFR) over-expression and angiogenesis in ependymomaJ Neurooncol2013 11169176
Not in our library10.1007/s11060-012-0996-z
110.
Tamborini E Miselli F Negri T Lagonigro MS Staurengo S Dagrada GP Stacchiotti S Pastore E Gronchi A Perrone F Molecular and biochemical analyses of platelet-derived growth factor receptor (PDGFR) B, PDGFRA, and KIT receptors in chordomasClin Cancer Res2006 1169206928
Not in our library10.1158/1078-0432.ccr-06-1584
111.
Stacchiotti S Longhi A Ferraresi V Grignani G Comandone A Stupp R Bertuzzi A Tamborini E Pilotti S Messina A Phase II study of imatinib in advanced chordomaJ Clin Oncol2012 11914920
Not in our library10.1200/jco.2011.35.3656
112.
Wen PY Yung WK Lamborn KR Norden AD Cloughesy TF Abrey LE Fine HA Chang SM Robins HI Fink K Phase II study of imatinib mesylate for recurrent meningiomas (North American brain tumor consortium study 01–08)Neuro Oncol2009 11853860
Not in our library10.1215/15228517-2009-010
113.
Reardon DA Norden AD Desjardins A Vredenburgh JJ Herndon JE 2nd Coan A Sampson JH Gururangan S Peters KB McLendon RE Phase II study of Gleevec (R) plus hydroxyurea (HU) in adults with progressive or recurrent meningiomaJ Neurooncol2012 11409415
Not in our library10.1007/s11060-011-0687-1
114.
Horak P Wohrer A Hassler M Hainfellner J Preusser M Marosi C Imatinib mesylate treatment of recurrent meningiomas in preselected patients: a retrospective analysisJ Neurooncol2012 11323330
Not in our library10.1007/s11060-012-0896-2
115.
Mukherjee J Kamnasaran D Balasubramaniam A Radovanovic I Zadeh G Kiehl TR Guha A Human schwannomas express activated platelet-derived growth factor receptors and c-kit and are growth inhibited by Gleevec (Imatinib Mesylate)Cancer Res2009 1150995107
Not in our library10.1158/0008-5472.can-08-4475
116.
Sabha N Au K Agnihotri S Singh S Mangat R Guha A Zadeh G Investigation of the in vitro therapeutic efficacy of nilotinib in immortalized human NF2-null vestibular schwannoma cellsPLoS One2012 11e39412
Not in our library10.1371/journal.pone.0039412
117.
Ammoun S Schmid MC Triner J Manley P Hanemann CO Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2Neuro Oncol2011 11759766
Not in our library10.1093/neuonc/nor056
118.
Malhotra B Schuetze SM Dermatofibrosarcoma protruberans treatment with platelet-derived growth factor receptor inhibitor: a review of clinical trial resultsCurr Opin Oncol2012 11419424
Not in our library10.1097/cco.0b013e328353d78d
119.
Patel KU Szabo SS Hernandez VS Prieto VG Abruzzo LV Lazar AJ Lopez-Terrada D Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assaysHum Pathol2008 11184193
Not in our library10.1016/j.humpath.2007.06.009
120.
Greco A Roccato E Miranda C Cleris L Formelli F Pierotti MA Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangementInt J Cancer2001 11354360
Not in our library10.1002/ijc.1190
121.
Sjöblom T Shimizu A O’Brien KP Pietras K Dal Cin P Buchdunger E Dumanski JP Östman A Heldin C-H Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosisCancer Res2001 1157785783
Not in our library
122.
Rubin BP Schuetze SM Eary JF Norwood TH Mirza S Conrad EU Bruckner JD Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberansJ Clin Oncol2002 1135863591
Not in our library10.1200/jco.2002.01.027
123.
Price VE Fletcher JA Zielenska M Cole W Viero S Manson DE Stuart M Pappo AS Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberansPediatr Blood Cancer2005 11511515
Not in our library10.1002/pbc.20249
124.
Maki RG Awan RA Dixon RH Jhanwar S Antonescu CR Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberansInt J Cancer2002 11623626
Not in our library10.1002/ijc.10535
125.
Labropoulos SV Fletcher JA Oliveira AM Papadopoulos S Razis ED Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylateAnti-cancer drugs2005 11461466
Not in our library10.1097/00001813-200504000-00014
126.
Mizutani K Tamada Y Hara K Tsuzuki T Saeki H Tamaki K Matsumoto Y Imatinib mesylate inhibits the growth of metastatic lung lesions in a patient with dermatofibrosarcoma protuberansBr J Dermatol2004 11235237
Not in our library10.1111/j.1365-2133.2004.06024.x
127.
McArthur GA Demetri GD van Oosterom A Heinrich MC Debiec-Rychter M Corless CL Nikolova Z Dimitrijevic S Fletcher JA Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: imatinib target exploration consortium study B2225J Clin Oncol2005 11866873
Not in our library10.1200/jco.2005.07.088
128.
Heinrich MC Joensuu H Demetri GD Corless CL Apperley J Fletcher JA Soulieres D Dirnhofer S Harlow A Town A Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinasesClin Cancer Res2008 1127172725
Not in our library10.1158/1078-0432.ccr-07-4575
129.
Rutkowski P Van Glabbeke M Rankin CJ Ruka W Rubin BP Debiec-Rychter M Lazar A Gelderblom H Sciot R Lopez-Terrada D Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trialsJ Clin Oncol2010 1117721779
Not in our library10.1200/jco.2009.25.7899
130.
Stacchiotti S Pedeutour F Negri T Conca E Marrari A Palassini E Collini P Keslair F Morosi C Gronchi A Dermatofibrosarcoma protuberans-derived fibrosarcoma: clinical history, biological profile and sensitivity to imatinibInt J Cancer2011 1117611772
Not in our library10.1002/ijc.25826
131.
Kerob D Porcher R Verola O Dalle S Maubec E Aubin F D’Incan M Bodokh I Boulinguez S Madelaine-Chambrin I Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: results of a multicenter phase II study on 25 patientsClin Cancer Res2010 1132883295
Not in our library10.1158/1078-0432.ccr-09-3401
132.
Heinrich MC Corless CL Demetri GD Blanke CD von Mehren M Joensuu H McGreevey LS Chen CJ Van den Abbeele AD Druker BJ Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumorJ Clin Oncol2003 1143424349
Not in our library10.1200/jco.2003.04.190
133.
Demetri GD von Mehren M Blanke CD Van den Abbeele AD Eisenberg B Roberts PJ Heinrich MC Tuveson DA Singer S Janicek M Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumorsThe New England journal of medicine2002 11472480
Not in our library10.1056/nejmoa020461
134.
Verweij J Casali PG Zalcberg J LeCesne A Reichardt P Blay JY Issels R van Oosterom A Hogendoorn PC Van Glabbeke M Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trialLancet2004 1111271134
Not in our library10.1016/s0140-6736(04)17098-0
135.
Demetri GD van Oosterom AT Garrett CR Blackstein ME Shah MH Verweij J McArthur G Judson IR Heinrich MC Morgan JA Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trialLancet2006 1113291338
Not in our library10.1016/s0140-6736(06)69446-4
136.
Demetri GD Casali PG Blay JY von Mehren M Morgan JA Bertulli R Ray-Coquard I Cassier P Davey M Borghaei H A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumorsClin Cancer Res2009 1159105916
Not in our library10.1158/1078-0432.ccr-09-0542
137.
Montemurro M Schoffski P Reichardt P Gelderblom H Schutte J Hartmann JT von Moos R Seddon B Joensuu H Wendtner CM Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinibEur J Cancer2009 1122932297
Not in our library10.1016/j.ejca.2009.04.030
138.
Saglio G Kim DW Issaragrisil S le Coutre P Etienne G Lobo C Pasquini R Clark RE Hochhaus A Hughes TP Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemiaN Engl J Med2010 1122512259
Not in our library10.1056/nejmoa0912614
139.
Betsholtz C Westermark B Ek B Heldin C-H Coexpression of a PDGF-like growth factor and PDGF receptors in a human osteosarcoma cell line: Implications for autocrine receptor activationCell1984 11447457
Not in our library10.1016/0092-8674(84)90452-5
140.
Smits A Funa K Vassbotn FS Beausang-Linder M af Ekenstam F Heldin C-H Westermark B Nistér M Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic originAm J Pathol1992 11639648
Not in our library
141.
Wang J Coltrera MD Gown AM Cell proliferation in human soft tissue tumors correlates with platelet-derived growth factor B chain expression: an immunohistochemical and in situ hybridization studyCancer Res1994 11560564
Not in our library
142.
Kubo T Piperdi S Rosenblum J Antonescu CR Chen W Kim HS Huvos AG Sowers R Meyers PA Healey JH Gorlick R Platelet-derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcomaCancer2008 1121192129
Not in our library10.1002/cncr.23437
143.
Ho AL Vasudeva SD Lae M Saito T Barbashina V Antonescu CR Ladanyi M Schwartz GK PDGF receptor alpha is an alternative mediator of rapamycin-induced Akt activation: implications for combination targeted therapy of synovial sarcomaCancer Res2012 1145154525
Not in our library10.1158/0008-5472.can-12-1319
144.
Zwerner JP May WA Dominant negative PDGF-C inhibits growth of Ewing family tumor cell linesOncogene2002 1138473854
Not in our library10.1038/sj.onc.1205486
145.
Ehnman M Missiaglia E Folestad E Selfe J Strell C Thway K Brodin B Pietras K Shipley J Ostman A Eriksson U Distinct effects of ligand-induced PDGFRα and PDGFRβ signaling in the human rhabdomyosarcoma tumor cell and stroma cell compartmentsCancer Res2013 1121392149
Not in our library10.1158/0008-5472.can-12-1646
146.
Taniguchi E Nishijo K McCleish AT Michalek JE Grayson MH Infante AJ Abboud HE Legallo RD Qualman SJ Rubin BP Keller C PDGFR-A is a therapeutic target in alveolar rhabdomyosarcomaOncogene2008 1165506560
Not in our library10.1038/onc.2008.255
147.
Blandford MC Barr FG Lynch JC Randall RL Qualman SJ Keller C Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: a report from the children’s oncology groupPediatr Blood Cancer2006 11329338
Not in our library10.1002/pbc.20466
148.
Armistead PM Salganick J Roh JS Steinert DM Patel S Munsell M El-Naggar AK Benjamin RS Zhang W Trent JC Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma: correlation with overall survival in 105 patientsCancer2007 1122932303
Not in our library10.1002/cncr.23038
149.
van der Graaf WT Blay JY Chawla SP Kim DW Bui-Nguyen B Casali PG Schoffski P Aglietta M Staddon AP Beppu Y Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trialLancet2012 1118791886
Not in our library10.1016/s0140-6736(12)60651-5
150.
Asa SA Murai A Murakami M Hoshino Y Mori T Maruo K Khater A El-Sawak A El-Aziz EA Yanai T Sakai H Expression of platelet-derived growth factor and its receptors in spontaneous canine hemangiosarcoma and cutaneous hemangiomaHistol Histopathol2012 11601607
Not in our library10.14670/hh-27.601
151.
Dickerson EB Marley K Edris W Tyner JW Schalk V Macdonald V Loriaux M Druker BJ Helfand SC Imatinib and dasatinib inhibit hemangiosarcoma and implicate PDGFR-β and Src in tumor growthTransl Oncol2013 11158168
Not in our library10.1593/tlo.12307
152.
Golub TR Barker GF Lovett M Gilliland DG Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t (5;12) chromosomal translocationCell1994 11307316
Not in our library10.1016/0092-8674(94)90322-0
153.
Magnusson MK Meade KE Brown KE Arthur DC Krueger LA Barrett AJ Dunbar CE Rabaptin-5 is a novel fusion partner to platelet-derived growth factor β receptor in chronic myelomonocytic leukemiaBlood2001 1125182525
Not in our library10.1182/blood.v98.8.2518
154.
Ross TS Gilliland DG Transforming properties of the Huntingtin interacting protein 1/platelet-derived growth factor beta receptor fusion proteinJ Biol Chem1999 112232822336
Not in our library10.1074/jbc.274.32.22328
155.
Schwaller J Anastasiadou E Cain D Kutok J Wojiski S Williams IR LaStarza R Crescenzi B Sternberg DW Andreasson P H4(D10S170), a gene frequently rearranged in papillary thyroid carcinoma, is fused to the platelet-derived growth factor receptor β gene in atypical chronic myeloid leukemia with t (5;10) (q33; q22)Blood2001 1139103918
Not in our library10.1182/blood.v97.12.3910
156.
Medves S Duhoux FP Ferrant A Toffalini F Ameye G Libouton JM Poirel HA Demoulin JB KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemiaLeukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, UK2010 1110521055
Not in our library10.1038/leu.2010.13
157.
Cools J DeAngelo DJ Gotlib J Stover EH Legare RD Cortes J Kutok J Clark J Galinsky I Griffin JD A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndromeN Engl J Med2003 1112011214
Not in our library10.1056/nejmoa025217
158.
Griffin JH Leung J Bruner RJ Caligiuri MA Briesewitz R Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndromeProc Natl Acad Sci USA2003 1178307835
Not in our library10.1073/pnas.0932698100
159.
Pardanani A Ketterling RP Brockman SR Flynn HC Paternoster SF Shearer BM Reeder TL Li CY Cross NC Cools J CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapyBlood2003 1130933096
Not in our library10.1182/blood-2003-05-1627
160.
Elling C Erben P Walz C Frickenhaus M Schemionek M Stehling M Serve H Cross NC Hochhaus A Hofmann WK Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like diseaseBlood2011 1129352943
Not in our library10.1182/blood-2010-05-286757
161.
Toffalini F Hellberg C Demoulin J-B Critical role of the platelet-derived growth factor receptor (PDGFR) β transmembrane domain in the TEL-PDGFRβ cytosolic oncoproteinJ Biol Chem2010 111226812278
Not in our library10.1074/jbc.m109.076638
162.
Stover EH Chen J Folens C Lee BH Mentens N Marynen P Williams IR Gilliland DG Cools J Activation of FIP1L1-PDGFRα requires disruption of the juxtamembrane domain of PDGFRα and is FIP1L1-independentProc Natl Acad Sci USA2006 1180788083
Not in our library10.1073/pnas.0601192103
163.
Toffalini F Kallin A Vandenberghe P Pierre P Michaux L Cools J Demoulin JB The fusion proteins TEL-PDGFRβ and FIP1L1-PDGFRα escape ubiquitination and degradationHaematologica2009 1110851093
Not in our library10.3324/haematol.2008.001149
164.
Cools J Stover EH Boulton CL Gotlib J Legare RD Amaral SM Curley DP Duclos N Rowan R Kutok JL PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRα-induced myeloproliferative diseaseCancer Cell2003 11459469
Not in our library10.1016/s1535-6108(03)00108-9
165.
Klion AD Noel P Akin C Law MA Gilliland DG Cools J Metcalfe DD Nutman TB Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsivenessBlood2003 1146604666
Not in our library10.1182/blood-2003-01-0006
166.
Fukushima K Matsumura I Ezoe S Tokunaga M Yasumi M Satoh Y Shibayama H Tanaka H Iwama A Kanakura Y FIP1L1-PDGFRα imposes eosinophil lineage commitment on hematopoietic stem/progenitor cellsJ Biol Chem2009 1177197732
Not in our library10.1074/jbc.m807489200
167.
Buitenhuis M Verhagen LP Cools J Coffer PJ Molecular mechanisms underlying FIP1L1-PDGFRA-mediated myeloproliferationCancer Res2007 1137593766
Not in our library10.1158/0008-5472.can-06-4183
168.
Montano-Almendras CP Essaghir A Schoemans H Varis I Noel LA Velghe AI Latinne D Knoops L Demoulin JB ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κBHaematologica2012 1110641072
Not in our library10.3324/haematol.2011.047530
169.
Apperley JF Gardembas M Melo JV Russell-Jones R Bain BJ Baxter EJ Chase A Chessells JM Colombat M Dearden CE Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor betaN Engl J Med2002 11481487
Not in our library10.1056/nejmoa020150
170.
Gleich GJ Leiferman KM Pardanani A Tefferi A Butterfield JH Treatment of hypereosinophilic syndrome with imatinib mesilateLancet2002 1115771578
Not in our library10.1016/s0140-6736(02)08505-7
171.
Cortes J Ault P Koller C Thomas D Ferrajoli A Wierda W Rios MB Letvak L Kaled ES Kantarjian H Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndromeBlood2003 1147144716
Not in our library10.1182/blood-2003-01-0081
172.
Ault P Cortes J Koller C Kaled ES Kantarjian H Response of idiopathic hypereosinophilic syndrome to treatment with imatinib mesylateLeuk Res2002 11881884
Not in our library10.1016/s0145-2126(02)00046-2
173.
Pardanani A Reeder T Porrata LF Li CY Tazelaar HD Baxter EJ Witzig TE Cross NC Tefferi A Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disordersBlood2003 1133913397
Not in our library10.1182/blood-2002-10-3103
174.
Chen J Wall NR Kocher K Duclos N Fabbro D Neuberg D Griffin JD Shi Y Gilliland DG Stable expression of small interfering RNA sensitizes TEL-PDGFβR to inhibition with imatinib or rapamycinJ Clin Invest2004 1117841791
Not in our library10.1172/jci20673
175.
Lierman E Folens C Stover EH Mentens N Van Miegroet H Scheers W Boogaerts M Vandenberghe P Marynen P Cools J Sorafenib is a potent inhibitor of FIP1L1-PDGFRα and the imatinib-resistant FIP1L1-PDGFRα T674I mutantBlood2006 1113741376
Not in our library10.1182/blood-2006-02-004457
176.
Stover EH Chen J Lee BH Cools J McDowell E Adelsperger J Cullen D Coburn A Moore SA Okabe R The small molecule tyrosine kinase inhibitor AMN107 inhibits TEL-PDGFRβ and FIP1L1-PDGFRα in vitro and in vivoBlood2005 1132063213
Not in our library10.1182/blood-2005-05-1932
177.
von Bubnoff N Gorantla SP Engh RA Oliveira TM Thone S Aberg E Peschel C Duyster J The low frequency of clinical resistance to PDGFR inhibitors in myeloid neoplasms with abnormalities of PDGFRA might be related to the limited repertoire of possible PDGFRA kinase domain mutations in vitroOncogene2011 11933943
Not in our library10.1038/onc.2010.476
178.
Daynes RA Dowell T Araneo BA Platelet-derived growth factor is a potent biologic response modifier of T cellsJ Exp Med1991 1113231333
Not in our library10.1084/jem.174.6.1323
179.
Gersuk GM Westermark B Mohabeer AJ Challita PM Pattamakom S Pattengale PK Inhibition of human natural killer cell activity by platelet-derived growth factor (PDGF): III membrane binding studies and differential biological effect of recombinant PDGF isoformsScand J Immunol1991 11521532
Not in our library10.1111/j.1365-3083.1991.tb02522.x
180.
Yang J Liu X Nyland SB Zhang R Ryland LK Broeg K Baab KT Jarbadan NR Irby R Loughran TP Jr Platelet-derived growth factor mediates survival of leukemic large granular lymphocytes via an autocrine regulatory pathwayBlood2010 115160
Not in our library10.1182/blood-2009-06-223719
181.
Laimer D Dolznig H Kollmann K Vesely PW Schlederer M Merkel O Schiefer AI Hassler MR Heider S Amenitsch L PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomasNat Med2012 1116991704
Not in our library10.1038/nm.2966
182.
Ko YJ Small EJ Kabbinavar F Chachoua A Taneja S Reese D DePaoli A Hannah A Balk SP Bubley GJ A multi-institutional phase ii study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancerClin Cancer Res2001 11800805
Not in our library
183.
Singh D Febbo PG Ross K Jackson DG Manola J Ladd C Tamayo P Renshaw AA D’Amico AV Richie JP Gene expression correlates of clinical prostate cancer behaviorCancer Cell2002 11203209
Not in our library10.1016/s1535-6108(02)00030-2
184.
Ustach CV Taube ME Hurst NJ Jr Bhagat S Bonfil RD Cher ML Schuger L Kim HR A potential oncogenic activity of platelet-derived growth factor D in prostate cancer progressionCancer Res2004 1117221729
Not in our library10.1158/0008-5472.can-03-3047
185.
Conley-LaComb MK Huang W Wang S Shi D Jung YS Najy A Fridman R Bonfil RD Cher ML Chen YQ Kim HR PTEN regulates PDGF ligand switch for beta-PDGFR signaling in prostate cancerAm J Pathol2012 1110171027
Not in our library10.1016/j.ajpath.2011.11.021
186.
Epithelial to Mesenchymal Transition Is Mechanistically Linked with Stem Cell Signatures in Prostate Cancer Cells · 2010
No notice
187.
Najy AJ Won JJ Movilla LS Kim HR Differential tumorigenic potential and matriptase activation between PDGF B versus PDGF D in prostate cancerMol Cancer Res2012 1110871097
Not in our library10.1158/1541-7786.mcr-12-0071
188.
Huang W Fridman Y Bonfil RD Ustach CV Conley-LaComb MK Wiesner C Saliganan A Cher ML Kim HR A novel function for platelet-derived growth factor D: induction of osteoclastic differentiation for intraosseous tumor growthOncogene2012 1145274535
Not in our library10.1038/onc.2011.573
189.
Dolloff NG Russell MR Loizos N Fatatis A Human bone marrow activates the Akt pathway in metastatic prostate cells through transactivation of the alpha-platelet-derived growth factor receptorCancer Res2007 11555562
Not in our library10.1158/0008-5472.can-06-2593
190.
Russell MR Jamieson WL Dolloff NG Fatatis A The α-receptor for platelet-derived growth factor as a target for antibody-mediated inhibition of skeletal metastases from prostate cancer cellsOncogene2009 11412421
Not in our library10.1038/onc.2008.390
191.
Park YH Seo SY Ha M Ku JH Kim HH Kwak C Inhibition of prostate cancer using RNA interference-directed knockdown of platelet-derived growth factor receptorUrology2011 111509e1509-1515
Not in our library10.1016/j.urology.2011.01.050
192.
Russell MR Liu Q Lei H Kazlauskas A Fatatis A The α-receptor for platelet-derived growth factor confers bone-metastatic potential to prostate cancer cells by ligand- and dimerization-independent mechanismsCancer Res2010 1141954203
Not in our library10.1158/0008-5472.can-09-4712
193.
Uehara H Kim SJ Karashima T Shepherd DL Fan D Tsan R Killion JJ Logothetis C Mathew P Fidler IJ Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastasesJ Natl Cancer Inst2003 11458470
Not in our library10.1093/jnci/95.6.458
194.
Kim SJ Uehara H Yazici S Langley RR He J Tsan R Fan D Killion JJ Fidler IJ Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude miceCancer Res2004 1142014208
Not in our library10.1158/0008-5472.can-03-3763
195.
Mathew P Thall PF Jones D Perez C Bucana C Troncoso P Kim SJ Fidler IJ Logothetis C Platelet-derived growth factor receptor inhibitor imatinib mesylate and docetaxel: a modular phase I trial in androgen-independent prostate cancerJ Clin Oncol2004 1133233329
Not in our library10.1200/jco.2004.10.116
196.
Mathew P Thall PF Bucana CD Oh WK Morris MJ Jones DM Johnson MM Wen S Pagliaro LC Tannir NM Platelet-derived growth factor receptor inhibition and chemotherapy for castration-resistant prostate cancer with bone metastasesClin Cancer Res2007 1158165824
Not in our library10.1158/1078-0432.ccr-07-1269
197.
Mathew P Thall PF Wen S Bucana C Jones D Horne E Oh WK Morris MJ Lee YC Logothetis CJ Dynamic change in phosphorylated platelet-derived growth factor receptor in peripheral blood leukocytes following docetaxel therapy predicts progression-free and overall survival in prostate cancerBr J Cancer2008 1114261432
Not in our library10.1038/sj.bjc.6604706
198.
Najy AJ Jung YS Won JJ Conley-LaComb MK Saliganan A Kim CJ Heath E Cher ML Bonfil RD Kim HR Cediranib inhibits both the intraosseous growth of PDGF D-positive prostate cancer cells and the associated bone reactionProstate2012 1113281338
Not in our library10.1002/pros.22481
199.
Gotzmann J Fischer AN Zojer M Mikula M Proell V Huber H Jechlinger M Waerner T Weith A Beug H Mikulits W A crucial function of PDGF in TGF-β-mediated cancer progression of hepatocytesOncogene2006 1131703185
Not in our library10.1038/sj.onc.1209083
200.
Fischer AN Fuchs E Mikula M Huber H Beug H Mikulits W PDGF essentially links TGF-β signaling to nuclear β-catenin accumulation in hepatocellular carcinoma progressionOncogene2007 1133953405
Not in our library10.1038/sj.onc.1210121
201.
Llovet JM Ricci S Mazzaferro V Hilgard P Gane E Blanc JF de Oliveira AC Santoro A Raoul JL Forner A Sorafenib in advanced hepatocellular carcinomaN Engl J Med2008 11378390
Not in our library10.1056/nejmoa0708857
202.
Cheng AL Kang YK Chen Z Tsao CJ Qin S Kim JS Luo R Feng J Ye S Yang TS Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trialLancet Oncol2009 112534
Not in our library10.1016/s1470-2045(08)70285-7
203.
Boonjaraspinyo S Boonmars T Wu Z Loilome W Sithithaworn P Nagano I Pinlaor S Yongvanit P Nielsen PS Pairojkul C Khuntikeo N Platelet-derived growth factor may be a potential diagnostic and prognostic marker for cholangiocarcinomaTumour Biol2012 1117851802
Not in our library10.1007/s13277-012-0438-8
204.
Sugiyama H Onuki K Ishige K Baba N Ueda T Matsuda S Takeuchi K Onodera M Nakanuma Y Yamato M Potent in vitro and in vivo antitumor activity of sorafenib against human intrahepatic cholangiocarcinoma cellsJ Gastroenterol2011 11779789
Not in our library10.1007/s00535-011-0380-3
205.
Fingas CD Bronk SF Werneburg NW Mott JL Guicciardi ME Cazanave SC Mertens JC Sirica AE Gores GJ Myofibroblast-derived PDGF-BB promotes Hedgehog survival signaling in cholangiocarcinoma cellsHepatology2011 1120762088
Not in our library10.1002/hep.24588
206.
Fingas CD Mertens JC Razumilava N Bronk SF Sirica AE Gores GJ Targeting PDGFR-β in cholangiocarcinomaLiver Int2012 11400409
Not in our library10.1111/j.1478-3231.2011.02687.x
207.
Kawai T Hiroi S Torikata C Expression in lung carcinomas of platelet-derived growth factor and its receptorsLab Invest1997 11431436
Not in our library
208.
Fitzer-Attas C Feldman M Eisenbach L Expression of functionally intact PDGF-α receptors in highly metastatic 3LL Lewis lung carcinoma cellsInt J Cancer1993 11315322
Not in our library10.1002/ijc.2910530224
209.
Antoniades HN Galanopoulos T Neville-Golden J O’Hara CJ Malignant epithelial cells in primary human lung carcinomas coexpress in vivo platelet-derived growth factor (PDGF) and PDGF receptor mRNAs and their protein productsProc Natl Acad Sci USA1992 1139423946
Not in our library10.1073/pnas.89.9.3942
210.
Tsao AS Wei W Kuhn E Spencer L Solis LM Suraokar M Lee JJ Hong WK Wistuba II Immunohistochemical overexpression of platelet-derived growth factor receptor-beta (PDGFR-β) is associated with PDGFRB gene copy number gain in sarcomatoid non-small-cell lung cancerClin Lung Cancer2011 11369374
Not in our library10.1016/j.cllc.2011.02.002
211.
Donnem T Al-Saad S Al-Shibli K Andersen S Busund LT Bremnes RM Prognostic impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cellsJ Thorac Oncol2008 11963970
Not in our library10.1097/jto.0b013e3181834f52
212.
Laing N McDermott B Wen S Yang D Lawson D Collins M Reimer C Hall PA Andersen H Snaith M Inhibition of platelet-derived growth factor receptor α by MEDI-575 reduces tumor growth and stromal fibroblast content in a model of non-small cell lung cancerMol Pharmacol2013 1112471256
Not in our library10.1124/mol.112.084079
213.
Reinmuth N Liersch R Raedel M Fehrmann F Fehrmann N Bayer M Schwoeppe C Kessler T Berdel W Thomas M Mesters RM Combined anti-PDGFRα and PDGFRβ targeting in non-small cell lung cancerInt J Cancer2009 1115351544
Not in our library10.1002/ijc.24109
214.
Huang CH Williamson SK Van Veldhuizen PJ Hsueh CT Allen A Tawfik O Wick J Smith H Uypeckcuat AM Mayo M Kelly K Potential role of platelet-derived growth factor receptor inhibition using imatinib in combination with docetaxel in the treatment of recurrent non-small cell lung cancerJ Thorac Oncol2011 11372377
Not in our library10.1097/jto.0b013e318200f9ad
215.
Ping G Hui-Min W Wei-Min W Bao-Hui H Sunitinib in pretreated advanced non-small-cell lung carcinoma: a primary result from Asian populationMed Oncol2011 11578583
Not in our library10.1007/s12032-010-9500-9
216.
Bhardwaj B Klassen J Cossette N Sterns E Tuck A Deeley R Sengupta S Elliott B Localization of platelet-derived growth factor β receptor expression in the periepithelial stroma of human breast carcinomaClin Cancer Res1996 11773782
Not in our library
217.
Coltrera MD Wang J Porter PL Gown AM Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor β subunit in human breast tissue and breast carcinomaCancer Res1995 1127032708
Not in our library
218.
Seymour L Bezwoda WR Positive immunostaining for platelet derived growth factor (PDGF) is an adverse prognostic factor in patients with advanced breast cancerBreast Cancer Res Treat1994 11229233
Not in our library10.1007/bf00665774
219.
Overexpression of platelet-derived growth factor receptor α in breast cancer is associated with tumour progression · 2005
No notice
220.
Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors · 2011
Not checked
221.
Weigel MT Dahmke L Schem C Bauerschlag DO Weber K Niehoff P Bauer M Strauss A Jonat W Maass N Mundhenke C In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cellsBMC cancer2010 11412
Not in our library10.1186/1471-2407-10-412
222.
Devarajan E Song YH Krishnappa S Alt E Epithelial-mesenchymal transition in breast cancer lines is mediated through PDGF-D released by tissue-resident stem cellsInt J Cancer2012 1110231031
Not in our library10.1002/ijc.26493
223.
Weigel MT Ghazoui Z Dunbier A Pancholi S Dowsett M Martin LA Preclinical and clinical studies of estrogen deprivation support the PDGF/Abl pathway as a novel therapeutic target for overcoming endocrine resistance in breast cancerBreast Cancer Res2012 11R78
Not in our library10.1186/bcr3191
224.
Lindmark G Sundberg C Glimelius B Påhlman L Rubin K Gerdin B Stromal expression of platelet-derived growth factor β-receptor and platelet-derived growth factor B-chain in colorectal cancerLab Invest1993 11682689
Not in our library
225.
Sundberg C Ljungström M Lindmark G Gerdin B Rubin K Microvascular pericytes express platelet-derived growth factor-β receptors in human healing wounds and colorectal adenocarcinomaAm J Pathol1993 1113771388
Not in our library
226.
Steller EJ Ritsma L Raats DA Hoogwater FJ Emmink BL Govaert KM Laoukili J Rinkes IH van Rheenen J Kranenburg O The death receptor CD95 activates the cofilin pathway to stimulate tumour cell invasionEMBO Rep2011 11931937
Not in our library10.1038/embor.2011.129
227.
Wehler TC Frerichs K Graf C Drescher D Schimanski K Biesterfeld S Berger MR Kanzler S Junginger T Galle PR PDGFRα/β expression correlates with the metastatic behavior of human colorectal cancer: a possible rationale for a molecular targeting strategyOncol Rep2008 11697704
Not in our library
228.
Kitadai Y Sasaki T Kuwai T Nakamura T Bucana CD Hamilton SR Fidler IJ Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potentialInt J Cancer2006 1125672574
Not in our library10.1002/ijc.22229
229.
Steller EJ Raats DA Koster J Rutten B Govaert KM Emmink BL Snoeren N van Hooff SR Holstege FC Maas C PDGFRB promotes liver metastasis formation of mesenchymal-like colorectal tumor cellsNeoplasia2013 11204217
Not in our library10.1593/neo.121726
230.
Honda M Kanno T Fujita Y Gotoh A Nakano T Nishizaki T Mesothelioma cell proliferation through autocrine activation of PDGF-ββ receptorCell Physiol Biochem2012 11667674
Not in our library10.1159/000176386
231.
Ghanem M Nijman R Safan M van der Kwast T Vansteenbrugge G Expression and prognostic value of platelet-derived growth factor-AA and its receptor α in nephroblastomaBJU Int2010 1113891393
Not in our library10.1111/j.1464-410x.2010.09211.x
232.
Seymour L Dajee D Bezwoda WR Tissue platelet derived-growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancerBreast Cancer Res Treat1993 11247252
Not in our library10.1007/bf00665802
233.
Henriksen R Funa K Wilander E Bäckström T Ridderheim M Öberg K Expression and prognostic significance of platelet-derived growth factor and its receptors in epithelial ovarian neoplasmsCancer Res1993 1145504554
Not in our library
234.
Takanami I Imamura T Yamamoto Y Kodaira S Usefulness of platelet-derived growth factor as a prognostic factor in pulmonary adenocarcinomaJ Surg Oncol1995 114043
Not in our library10.1002/jso.2930580109
235.
Matsui T Sano K Tsukamoto T Ito M Takaishi T Nakata H Nakamura H Chihara K Human neuroblastoma cells express α and β platelet-derived growth factor receptors coupling with neurotrophic and chemotactic signalingJ Clin Invest1993 1111531160
Not in our library10.1172/jci116684
236.
Uccini S Mannarino O McDowell HP Pauser U Vitali R Natali PG Altavista P Andreano T Coco S Boldrini R Clinical and molecular evidence for c-kit receptor as a therapeutic target in neuroblastic tumorsClin Cancer Res2005 11380389
Not in our library
237.
Bond M Bernstein ML Pappo A Schultz KR Krailo M Blaney SM Adamson PC A phase II study of imatinib mesylate in children with refractory or relapsed solid tumors: a children’s oncology group studyPediatr Blood Cancer2008 11254258
Not in our library10.1002/pbc.21132
238.
Xie J Aszterbaum M Zhang X Bonifas JM Zachary C Epstein E McCormick F A role of PDGFRα in basal cell carcinoma proliferationProc Natl Acad Sci U S A2001 1192559259
Not in our library10.1073/pnas.151173398
239.
Basciani S De Luca G Dolci S Brama M Arizzi M Mariani S Rosano G Spera G Gnessi L Platelet-derived growth factor receptor β-subtype regulates proliferation and migration of gonocytesEndocrinology2008 1162266235
Not in our library10.1210/en.2008-0349
240.
Froehner M Beuthien-Baumann B Dittert DD Schuler U Wirth MP Lack of efficacy of imatinib in a patient with metastatic leydig cell tumorCancer Chemother Pharmacol2006 11716718
Not in our library10.1007/s00280-005-0181-6
241.
Castillo-Avila W Piulats JM Garcia Del Muro X Vidal A Condom E Casanovas O Mora J Germa JR Capella G Villanueva A Vinals F Sunitinib inhibits tumor growth and synergizes with cisplatin in orthotopic models of cisplatin-sensitive and cisplatin-resistant human testicular germ cell tumorsClin Cancer Res2009 1133843395
Not in our library10.1158/1078-0432.ccr-08-2170
242.
Malkomes P Oppermann E Bechstein WO Holzer K Significantly high expression of platelet-derived growth factor (PDGF) in benign nodules of the thyroid: relevance in the development of goitre recurrence?Langenbecks Arch Surg2011 1111651172
Not in our library10.1007/s00423-011-0799-2
243.
Kerbel RS Tumor angiogenesisN Engl J Med2008 1120392049
Not in our library10.1056/nejmra0706596
244.
Sennino B Falcon BL McCauley D Le T McCauley T Kurz JC Haskell A Epstein DM McDonald DM Sequential loss of tumor vessel pericytes and endothelial cells after inhibition of platelet-derived growth factor B by selective aptamer AX102Cancer Res2007 1173587367
Not in our library10.1158/0008-5472.can-07-0293
245.
Kuhnert F Tam BY Sennino B Gray JT Yuan J Jocson A Nayak NR Mulligan RC McDonald DM Kuo CJ Soluble receptor-mediated selective inhibition of VEGFR and PDGFRβ signaling during physiologic and tumor angiogenesisProc Natl Acad Sci USA2008 111018510190
Not in our library10.1073/pnas.0803194105
246.
Erber R Thurnher A Katsen AD Groth G Kerger H Hammes HP Menger MD Ullrich A Vajkoczy P Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanismsFaseb J2004 11338340
Not in our library10.1096/fj.03-0271fje
247.
Hasumi Y Klosowska-Wardega A Furuhashi M Östman A Heldin C-H Hellberg C Identification of a subset of pericytes that respond to combination therapy targeting PDGF and VEGF signalingInt J Cancer2007 1126062614
Not in our library10.1002/ijc.22999
248.
Bergers G Song S Meyer-Morse N Bergsland E Hanahan D Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitorsJ Clin Invest2003 1112871295
Not in our library10.1172/jci17929
249.
Taeger J Moser C Hellerbrand C Mycielska ME Glockzin G Schlitt HJ Geissler EK Stoeltzing O Lang SA Targeting FGFR/PDGFR/VEGFR impairs tumor growth, angiogenesis, and metastasis by effects on tumor cells, endothelial cells, and pericytes in pancreatic cancerMol Cancer Ther2011 1121572167
Not in our library10.1158/1535-7163.mct-11-0312
250.
Crawford Y Kasman I Yu L Zhong C Wu X Modrusan Z Kaminker J Ferrara N PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatmentCancer Cell2009 112134
Not in our library10.1016/j.ccr.2008.12.004
251.
McCarty MF Somcio RJ Stoeltzing O Wey J Fan F Liu W Bucana C Ellis LM Overexpression of PDGF-BB decreases colorectal and pancreatic cancer growth by increasing tumor pericyte contentJ Clin Invest2007 1121142122
Not in our library10.1172/jci31334
252.
Ho IA Toh HC Ng WH Teo YL Guo CM Hui KM Lam PY Human bone marrow-derived mesenchymal stem cells suppress human glioma growth through inhibition of angiogenesisStem Cells2013 11146155
Not in our library10.1002/stem.1247
253.
Xue Y Lim S Yang Y Wang Z Jensen LD Hedlund EM Andersson P Sasahara M Larsson O Galter D PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cellsNat Med2012 11100110
Not in our library10.1038/nm.2575
254.
Ding W Knox TR Tschumper RC Wu W Schwager SM Boysen JC Jelinek DF Kay NE Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia: implications for an angiogenic switchBlood2010 1129842993
Not in our library10.1182/blood-2010-02-269894
255.
Cao R Björndahl MA Religa P Clasper S Garvin S Galter D Meister B Ikomi F Tritsaris K Dissing S PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasisCancer Cell2004 11333345
Not in our library10.1016/j.ccr.2004.08.034
256.
Kodama M Kitadai Y Sumida T Ohnishi M Ohara E Tanaka M Shinagawa K Tanaka S Yasui W Chayama K Expression of platelet-derived growth factor (PDGF)-B and PDGF-receptor β is associated with lymphatic metastasis in human gastric carcinomaCancer Sci2010 1119841989
Not in our library10.1111/j.1349-7006.2010.01639.x
257.
Zhang J Wang P Dykstra M Gelebart P Williams D Ingham R Adewuyi EE Lai R McMullen T Platelet-derived growth factor receptor-α promotes lymphatic metastases in papillary thyroid cancerJ Pathol2012 11241250
Not in our library10.1002/path.4069
258.
Pietras K Östman A Hallmarks of cancer: interactions with the tumor stromaExp Cell Res2010 1113241331
Not in our library10.1016/j.yexcr.2010.02.045
259.
Hanahan D Coussens LM Accessories to the crime: functions of cells recruited to the tumor microenvironmentCancer Cell2012 11309322
Not in our library10.1016/j.ccr.2012.02.022
260.
Forsberg K Valyi-Nagy I Heldin C-H Herlyn M Westermark B Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BBProc Natl Acad Sci U S A1993 11393397
Not in our library10.1073/pnas.90.2.393
261.
Tumorigenic conversion of immortal human keratinocytes through stromal cell activation · 1998
Not checked
262.
Cheng J Ye H Liu Z Xu C Zhang Z Liu Y Sun Y Platelet-derived growth factor-BB accelerates prostate cancer growth by promoting the proliferation of mesenchymal stem cellsJ Cell Biochem2013 1115101518
Not in our library10.1002/jcb.24492
263.
Shao Z-M Nguyen M Barsky SH Human breast carcinoma desmoplasia is PDGF initiatedOncogene2000 1143374345
Not in our library10.1038/sj.onc.1203785
264.
Tejada ML Yu L Dong J Jung K Meng G Peale FV Frantz GD Hall L Liang X Gerber HP Ferrara N Tumor-driven paracrine platelet-derived growth factor receptor α signaling is a key determinant of stromal cell recruitment in a model of human lung carcinomaClin Cancer Res2006 1126762688
Not in our library10.1158/1078-0432.ccr-05-1770
265.
Campbell JS Hughes SD Gilbertson DG Palmer TE Holdren MS Haran AC Odell MM Bauer RL Ren HP Haugen HS Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinomaProc Natl Acad Sci U S A2005 1133893394
Not in our library10.1073/pnas.0409722102
266.
Anderberg C Li H Fredriksson L Andrae J Betsholtz C Li X Eriksson U Pietras K Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblastsCancer Res2009 11369378
Not in our library10.1158/0008-5472.can-08-2724
267.
Bandapalli OR Macher-Goeppinger S Schirmacher P Brand K Paracrine signalling in colorectal liver metastases involving tumor cell-derived PDGF-C and hepatic stellate cell-derived PAK-2Clin Exp Metastasis2012 11409417
Not in our library10.1007/s10585-012-9459-3
268.
Li H Fredriksson L Li X Eriksson U PDGF-D is a potent transforming and angiogenic growth factorOncogene2003 1115011510
Not in our library10.1038/sj.onc.1206223
269.
Furuhashi M Sjöblom T Abramsson A Ellingsen J Micke P Li H Bergsten-Folestad E Eriksson U Heuchel R Betsholtz C Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rateCancer Res2004 1127252733
Not in our library10.1158/0008-5472.can-03-1489
270.
Stromal PDGFRbeta expression in prostate tumors and non-malignant prostate tissue predicts prostate cancer survival. · 2010
Not checked
271.
Paulsson J Sjöblom T Micke P Pontén F Landberg G Heldin C-H Bergh J Brennan DJ Jirström K Östman A Prognostic significance of stromal platelet-derived growth factor β-receptor expression in human breast cancerAm J Pathol2009 11334341
Not in our library10.2353/ajpath.2009.081030
272.
Kitadai Y Sasaki T Kuwai T Nakamura T Bucana CD Fidler IJ Targeting the expression of platelet-derived growth factor receptor by reactive stroma inhibits growth and metastasis of human colon carcinomaAm J Pathol2006 1120542065
Not in our library10.2353/ajpath.2006.060653
273.
Yuzawa S Kano MR Einama T Nishihara H PDGFRβ expression in tumor stroma of pancreatic adenocarcinoma as a reliable prognostic markerMed Oncol2012 1128242830
Not in our library10.1007/s12032-012-0193-0
274.
Pietras K Östman A Sjöquist M Buchdunger E Reed RK Heldin C-H Rubin K Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumorsCancer Res2001 1129292934
Not in our library
275.
Pietras K Rubin K Sjöblom T Buchdunger E Sjöquist M Heldin C-H Östman A Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapyCancer Res2002 1154765484
Not in our library
276.
Falcon BL Pietras K Chou J Chen D Sennino B Hanahan D McDonald DM Increased vascular delivery and efficacy of chemotherapy after inhibition of platelet-derived growth factor-BAm J Pathol2011 1129202930
Not in our library10.1016/j.ajpath.2011.02.019
277.
Tong RT Boucher Y Kozin SV Winkler F Hicklin DJ Jain RK Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumorsCancer Res2004 1137313736
Not in our library10.1158/0008-5472.can-04-0074
278.
Willett CG Boucher Y Di Tomaso E Duda DG Munn LL Tong RT Chung DC Sahani DV Kalva SP Kozin SV Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancerNat Med2004 11145147
Not in our library10.1038/nm988
279.
Combined anti-angiogenic therapy targeting PDGF and VEGF receptors lowers the interstitial fluid pressure in a murine experimental carcinoma. · 2009
Not checked
280.
Gerber DE Gupta P Dellinger MT Toombs JE Peyton M Duignan I Malaby J Bailey T Burns C Brekken RA Loizos N Stromal platelet-derived growth factor receptor α (PDGFRα) provides a therapeutic target independent of tumor cell PDGFRα expression in lung cancer xenograftsMol Cancer Ther2012 1124732482
Not in our library10.1158/1535-7163.mct-12-0431
281.
Kinoshita K Nakagawa K Hamada J Hida Y Tada M Kondo S Moriuchi T Imatinib mesylate inhibits the proliferation-stimulating effect of human lung cancer-associated stromal fibroblasts on lung cancer cellsInt J Oncol2010 11869877
Not in our library10.3892/ijo_00000738
282.
Catena R Luis-Ravelo D Anton I Zandueta C Salazar-Colocho P Larzabal L Calvo A Lecanda F PDGFR signaling blockade in marrow stroma impairs lung cancer bone metastasisCancer Res2010 11164174
Not in our library10.1158/0008-5472.can-10-1708
283.
Shinagawa K Kitadai Y Tanaka M Sumida T Onoyama M Ohnishi M Ohara E Higashi Y Tanaka S Yasui W Chayama K Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancerInt J Cancer2013 11813823
Not in our library10.1002/ijc.27735

Cited by papers we hold 12

Molecular targeted therapy for anticancer treatment · 2022
No notice
CD146, from a melanoma cell adhesion molecule to a signaling receptor · 2020
No notice
Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions · 2020
No notice
Resistance Mechanisms to Anti-angiogenic Therapies in Cancer · 2020
No notice
Blockade of PDGFRβ circumvents resistance to MEK-JAK inhibition via intratumoral CD8+ T-cells infiltration in triple-negative breast cancer · 2019
Not checked
Resistance to Anti-Angiogenic Therapy in Cancer—Alterations to Anti-VEGF Pathway · 2018
No notice
A proteomic landscape of diffuse-type gastric cancer · 2018
Corrected
Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges · 2018
No notice
Use of multitarget tyrosine kinase inhibitors to attenuate platelet-derived growth factor signalling in lung disease · 2017
Not checked
Pericytes, an overlooked player in vascular pathobiology · 2017
No notice
A Review of Anti-Angiogenic Targets for Monoclonal Antibody Cancer Therapy · 2017
No notice
The host microenvironment influences prostate cancer invasion, systemic spread, bone colonization, and osteoblastic metastasis · 2014
Not checked

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.