Effect of maximum-tolerated doses and low-dose metronomic chemotherapy on serum vascular endothelial growth factor and thrombospondin-1 levels in patients with advanced nonsmall cell lung cancer

Taş, Faruk; Duranyıldız, Derya; Soydinc, Hilal Oguz; Çiçin, İrfan; Selam, Meltem; Uygun, Kazım; Dişçi, Rian; Yasasever, Vildan; Topuz, Erkan

doi:10.1007/s00280-007-0526-4

Cited by 28 publications

(28 citation statements)

References 11 publications

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“…21,22 We also monitored serum levels of thrombospondin (TSP)-1, an endogenous anti-angiogenic factor produced by endothelial cells and whose levels have been found greatly increased in other trials testing metronomic chemotherapy. 23 It was observed a significant decrease in TSP-1 serum level in all of the patients. Its reduction was however maximal in the patients who did not receive bevacizumab (level 0 vs.…”

Section: Demographymentioning

confidence: 75%

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab in advanced non-small-cell-lung cancer patients

Correale¹,

Remondo²,

Carbone³

et al. 2010

Cancer Biology & Therapy

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Section: Demographymentioning

confidence: 75%

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab in advanced non-small-cell-lung cancer patients

Correale¹,

Remondo²,

Carbone³

et al. 2010

Cancer Biology & Therapy

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“…In another trial comparing metronomic versus MTD of cisplatin and docetaxel given i.v. in patients with lung cancer, no significant changes in VEGF, TSP1 and VEGFR1 levels were found in the group treated with MCT [50]. Recently it was shown a decrease in TSP-1 levels in patients receiving metronomic Cy a change that did not correlate to clinical benefit [51] The proportion of CEPs in NR patients showed a tendency to higher values during their time of permanence.…”

Section: Discussionmentioning

confidence: 96%

Safety and Therapeutic Effect of Metronomic Chemotherapy with Cyclophosphamide and Celecoxib in Advanced Breast Cancer Patients

et al. 2013

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“…DRs such as DR4, DR5, and Fas are increased by p53-dependent transcriptional activation (13). Interaction of tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor family of proteins, with DR4 and DR5 leads to recruitment of the adaptor protein FADD and initiator caspase-8 to the death-inducing signaling complex (14). This results in enzymatic activation of caspase-8, which in turn activates a downstream caspase cascade in the presence or absence of mitochondrial amplification machinery (15,16).…”

mentioning

confidence: 99%

CHM-1, a New Vascular Targeting Agent, Induces Apoptosis of Human Umbilical Vein Endothelial Cells via p53-mediated Death Receptor 5 Up-regulation

Tsai

Pan

Sun

et al. 2010

Journal of Biological Chemistry

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CHM-1 (2-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone) has been identified as a potent antitumor agent in human hepatocellular carcinoma; however, its role in tumor angiogenesis is unclear. This study investigated the effects of CHM-1 and the mechanisms by which it exerts its antiangiogenic and vascular disrupting properties. Using a xenograft model antitumor assay, we found that CHM-1 significantly inhibits tumor growth and microvessel formation. Flow cytometry, immunofluorescence microscopy, and cell death enzyme-linked immunosorbent assay kit revealed that CHM-1 inhibits growth of human umbilical vein endothelial cells (HUVEC) by induction of apoptotic cell death in a concentration-dependent manner. CHM-1 also suppresses HUVEC migration and capillary-like tube formation. We were able to correlate CHM-1-induced apoptosis in HUVEC with the cleavage of procaspase-3, -7, and -8, as well as with the cleavage of poly(ADP-ribose) polymerase by Western blotting assay. Such sensitization was achieved through up-regulation of death receptor 5 (DR5) but not DR4 or Fas. CHM-1 was also capable of increasing the expression level of p53, and most importantly, the induction of DR5 by CHM-1 was abolished by p53 small interfering RNA. Taken together, the results of this study indicate that CHM-1 exhibits vascular targeting activity associated with the induction of DR5-mediated endothelial cell apoptosis through p53 up-regulation, which suggests its potential as an antivascular and antitumor therapeutic agent.In neoplasm, malignant angiogenesis and tumor mortality are highly associated with each other. Almost every step of aggressive tumor growth and metastatic dissemination relies on a functional vascular network to provide tumor cells with oxygen and nutrients and to remove waste products associated with tumor metabolism, a crucial hallmark of cancer (1). Nowadays, several antiangiogenic strategies have been developed to inhibit tumor growth and metastasis. In addition to the indirect interference of proangiogenic communication between the tumor and endothelial cell compartments, several recent reports have suggested that the induction of apoptosis in proliferation of endothelial cells may represent a potential therapeutic strategy in the treatment of neovascularization-related diseases (2-4). For instance, numerous natural angiogenic inhibitors, such as endostatin, angiostatin, and thrombospondin-1, act in part through selective triggering apoptosis in endothelial cells, resulting in vascular regression (5, 6). Several antitubulin-binding agents (e.g. CA-4-phosphate, ZD6126, and TZT-1027) and flavonoids (5,6-dimethylxanthenone-4-acetic acid) have demonstrated the ability to induce apoptosis of tumor vascular endothelial cells, leading to the rapid collapse and obstruction of tumor vessels and ultimately causing a tumor vascular shutdown effect (7).Apoptosis is an intracellular suicide program possessing morphologic characteristics and biochemical features, including chromatin condensation, nuclear DNA fragmentation, cell s...

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Effect of maximum-tolerated doses and low-dose metronomic chemotherapy on serum vascular endothelial growth factor and thrombospondin-1 levels in patients with advanced nonsmall cell lung cancer

Abstract: The continuous/metronomic chemotherapy may not achieve a more pronounced antiangiogenic effect than MTD-scheduling chemotherapy. Future studies involving a larger number of patients are needed to confirm the present findings.

Cited by 28 publications

References 11 publications

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab in advanced non-small-cell-lung cancer patients

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab in advanced non-small-cell-lung cancer patients

Safety and Therapeutic Effect of Metronomic Chemotherapy with Cyclophosphamide and Celecoxib in Advanced Breast Cancer Patients

CHM-1, a New Vascular Targeting Agent, Induces Apoptosis of Human Umbilical Vein Endothelial Cells via p53-mediated Death Receptor 5 Up-regulation

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