Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients

Loven, David; Beery, Einat; Yerushalmi, Rinat; Koren, Claude; Sulkes, Aarón; Lavi, Idit; Shaked, Yuval; Fenig, Eyal

doi:10.1080/02841860701472470

Cited by 17 publications

(11 citation statements)

References 18 publications

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“…However, combined chemoirradiation with or without multi-tyrosine kinase inhibitors against VEGF has also been shown to decrease circulating levels of PDGF-AA or PDGF-BB ( Loven et al , 2008 ; Inanc et al , 2012 ; Shin et al , 2012 ). Therefore, as in our study the first cycle of CRT was already started at T2, we have to be aware that the observed decline might be partly due to the CRT.…”

Section: Discussionmentioning

confidence: 99%

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

et al. 2015

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Background:This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT).Methods:From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with α-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for circulating angiogenic proteins. Markers were related with the pathological response of patients.Results:One dose of bevacizumab changed the expression of 14 genes and led to a significant decrease in microvessel density and in the proportion of pericyte-covered blood vessels, and a small but nonsignificant increase in hypoxia. Alterations in angiogenic processes after bevacizumab delivery were only detected in responding tumours. Lower PDGFA expression and PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression were found after bevacizumab treatment only in patients with pathological complete response.Conclusions:We could not support the ‘normalization hypothesis' and suggest a role for PDGFA, PDGF-BB, CA-IX and α-SMA. Validation in larger patient groups is needed.

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Section: Discussionmentioning

confidence: 99%

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

et al. 2015

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“…Concentrations of PDGF and FGF in serum or in plasma during anti-cancer treatment have not yet been fully investigated although a decline in serum PDGF-AA or PDGF-BB has been demonstrated in various cancer types during chemotherapy and/or radiotherapy [35-37], and when combined with multi-tyrosine kinase inhibitors (VEGFR-2, FGF and PDGF) [38]. Other reports suggest that plasma PDGF-AB, PDGF-BB, and VEGF may be stable during treatment with Imatinib Mesylate [33].…”

Section: Discussionmentioning

confidence: 99%

Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant ovarian cancer patients treated with bevacizumab

et al. 2012

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IntroductionAnti-VEGF treatment has proven effective in recurrent ovarian cancer. However, the identification of the patients most likely to respond is still pending. It is well known that the angiogenesis is regulated by several other pro-angiogenic proteins, e.g. the platelet - derived growth factor (PDGF) system and the fibroblast growth factor (FGF) system. These other signaling pathways may remain active or become upregulated during anti-VEGF treatment.The aim of the present study was to investigate if potential changes of PDGF-BB, PDGF-AA, and FGF2 before and during bevacizumab treatment had predictive value for early progression or survival. Furthermore, we wanted to investigate the importance of serum VEGF in the same cohort.MethodsThis study included 106 patients with chemotherapy-resistant epithelial ovarian cancer who were treated with single agent bevacizumab as part of a biomarker protocol. Patients were evaluated for response by the Response Evaluation Criteria In Solid Tumors (RECIST) and/ or Gynecologic Cancer Intergroup (GCIG) CA125 criteria. Serum samples were collected at baseline and prior to each treatment. FGF2, PDGF-BB, PDGF-AA were quantified simultaneously using the Luminex system, and VEGF-A was measured by ELISA. Eighty-eight baseline samples were avaliable for FGF2, PDGF-BB, PDGF-AA analysis, and 93 baseline samples for VEGF.ResultsHigh baseline serum VEGF was related to poor overall survival. Furthermore, high serum PDGF-BB and FGF2 was of prognostic significance. None of the markers showed predictive value, neither at baseline level nor during the treatment.

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“…Along the same lines, LDM chemotherapy has been shown to cause the decrease of proangiogenic factors, such as VEGF and platelet-derived growth factor-BB (PDGF-BB; ref. 125). PDGF-BB, depending on the context, may also have prometastatic properties.…”

Section: Low-dose Metronomic Chemotherapymentioning

confidence: 99%

Chemotherapy-Induced Metastasis: Molecular Mechanisms, Clinical Manifestations, Therapeutic Interventions

2019

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Chemotherapy offers long-term clinical benefits to many patients with advanced cancer. However, recent evidence has linked the cytotoxic effects of chemotherapy with the de novo elicitation of a prometastatic tumor microenvironment. This "modified" tumor microenvironment is triggered by a chemotherapy-driven cytokine storm or through direct effects of certain chemotherapeutics on stromal and/or immune cells, the most critical being tumor-associated macrophages. These chemotherapy-educated cells act as facilitators in tumor-host cell interactions promoting the establishment of distant metastasis. Certain clinical studies now offer substantial evidence that prometastatic changes are indeed identified in the tumor microenvironment of certain patient subpopulations, especially those that do not present with any pathologic response after neoadjuvant chemotherapy. Deciphering the exact contextual prerequisites for chemotherapy-driven metastasis will be paramount for designing novel mechanism-based treatments for circumventing chemotherapy-induced metastasis.

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Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients

Cited by 17 publications

References 18 publications

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial

Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant ovarian cancer patients treated with bevacizumab

Chemotherapy-Induced Metastasis: Molecular Mechanisms, Clinical Manifestations, Therapeutic Interventions

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