Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment

Toi, Masakazu; Rahman, Mohammad Atiqur; Bando, Hiroko; Chow, Louis W C

doi:10.1016/s1470-2045(05)01766-3

Cited by 135 publications

(105 citation statements)

References 58 publications

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“…26 Meanwhile, preclinical studies suggested that TP was often up-regulated by stress such as hypoxia, radiation and chemotherapy agents, 27 which included anthracyclines, taxanes, cyclophosphamide, and platinum compounds. 28 Furthermore, given the synergistic effect between cisplatin and 5-FU, 12,13 it is reasonable to expect an enhanced activity of capecitabine when administered in combination with cisplatin.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes

Zhang

et al. 2015

Cancer Biology & Therapy

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Background: Cisplatin is an effective agent for triple-negative breast cancer (TNBC) and synergistic activity between cisplatin and capecitabine has been demonstrated by in vitro and in vivo studies. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of capecitabine plus cisplatin (XP) regimen in metastatic TNBC patients pretreated with anthracyclines and taxanes. Patients and Methods: Thirty-three patients with metastatic TNBC who had anthracyclines and taxanes as prior therapy were treated with capecitabine 2000 mg/m 2 orally on day 1 through 14 plus cisplatin 75mg/m 2 intravenously on day 1 of a 21-day cycle, followed by capecitabine maintenance medications after a maximum of 6 cycles. The primary end point was objective response rate (ORR) and the secondary end points included progression-free survival (PFS), overall survival (OS) and toxicity profiles. Results: A total of 162 cycles was given. ORR was 63.6%. Median PFS was 8.2 (95%CI: 4.8-11.6) months in the entire population and 10.8 (95%CI: 6.5-15.1) months in responding patients. Median OS was 17.8 (95%CI: 14.4-21.2) months in all enrolled patients and 25.8 (95%CI: 14.6-37.0) months in responding patients. Most adverse events were mild and manageable, with neutropenia and nausea/vomiting as the most common toxicities. Grade 3/4 toxicities included leukopenia (10, 30.3%), neutropenia (10, 30.3%), anemia (2, 6.1%), thrombocytopenia (1, 3.0%), nausea/vomiting (3, 9.1%), hand-foot syndrome (HFS; 1, 3.0%), and sensory neuropathy (1, 3.0%). Conclusions: Capecitabine plus cisplatin demonstrated an excellent activity and an acceptable safety profile in metastatic TNBC patients pretreated with anthracyclines and taxanes.

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Section: Discussionmentioning

confidence: 99%

A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes

Zhang

et al. 2015

Cancer Biology & Therapy

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“…tp induces cell proliferation, endothelial cell chemotaxis in vitro and angiogenesis in vivo (2,3). tp is detectable in healthy and tumor tissues, yet tp expression in solid tumors appears to be increased 3-to 10-fold with respect to healthy adjacent tissues (4,5). In the last few years, it has been shown that TP may have multiple roles in human cancer.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors induce thymidine phosphorylase expression in cultured breast cancer cell lines

Puppin

Puglisi²,

Pandolfi³

et al. 2011

Oncol Rep

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Abstract. thymidine phosphorylase (tp) is an enzyme involved in thymidine synthesis and degradation. the expression of this enzyme has been proposed as a predictive factor for the therapeutic benefit of capecitabine, which is a precursor of the drug 5'-fluorouracil. In fact, TP is the rate-limiting enzyme in the activation of capecitabine. therefore, higher levels of tp are expected to sensitize cancer cells to capecitabine treatment. In the present study, using breast cancer cell lines, we found a correlation between TP mRNA and protein levels, suggesting that compounds able to increase tp gene expression also increase protein levels. Accordingly, we demonstrated that treatment of breast cancer MCF7 and MDA231 cell lines with histone deacetylase inhibitors, tricostatin A and suberoylanilide hydroxamic acid, increased TP both at the mRNA and protein level. The effects of histone deacetylase inhibitors were not found to occur via the cytokine tnFα, a known inducer of TP expression. Our findings suggest a strategy to sensitize breast cancer cells to capecitabine treatment.

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“…Bevacizumab, a VEGF-neutralising antibody has been shown to improve survival in advanced colorectal cancer (Kabbinavar et al, 2005). Thymidine phosphorylase (TP) is often induced in the tumour microenvironment by physiological and chemical stress where it protects cells from apoptosis and helps cell survival by stimulating nucleoside metabolism and angiogenesis (Toi et al, 2005). The degree of angiogenesis of a tumour as measured by vascular density has emerged as a powerful candidate for prognosis and as a predictive tool in breast cancer and melanomas (Bamberger and Perrett, 2002;Uzzan et al, 2004).…”

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confidence: 99%

Role of lymphangiogenesis in epithelial ovarian cancer

et al. 2006

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We investigated the significance of lymphatic count, vascular count and angiogenic growth factors using immunohistochemistry in 108 tumour specimens of epithelial ovarian cancer with antibodies to lymphatic vessel endothelial hyaluronan receptor (LYVE-1), platelet endothelial cell adhesion molecule CD31, vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) in epithelial ovarian cancer to understand the pathogenesis of metastasis in ovarian cancer. The effect of prognostic variables on progression-free and overall survival was assessed. On multivariate analysis, bulky residual disease after surgery was the best prognostic indicator (Po0.001) for progression-free and overall survival (Po0.001). Lymphatic count was statistically significant as a prognostic factor for progression-free (P ¼ 0.05) and overall survival (P ¼ 0.04). However, lymphatic count did not impact on survival curves. No correlation was found between lymphatic count and age, histological subtype, FIGO stage or residual disease. Vascular count, VEGF or TP expressions were not significant in either analysis. Lymphatic spread may be significant in aiding metastases in ovarian cancer but requires other biological factors to act in conjunction, as it does not have clearcut prognostic significance. Dissemination of ovarian cancer does not occur primarily through vascular or lymphatic routes but may occur through direct intraperitoneal spread of disease.

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Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment

Cited by 135 publications

References 58 publications

A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes

A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes

Histone deacetylase inhibitors induce thymidine phosphorylase expression in cultured breast cancer cell lines

Role of lymphangiogenesis in epithelial ovarian cancer

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