Expression of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyl transferase in prostate cancer

Miyoshi, Yoshiko; Uemura, Hiroji; Ishiguro, Hitoshi; Kitamura, Hitoshi; Nomura, Naruo; Danenberg, Peter V.; Kubota, Yoshinobu

doi:10.1038/sj.pcan.4500817

Cited by 19 publications

(13 citation statements)

References 27 publications

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“…The main feature of this method is the measurement of gene expression by real-time technology combined with LCM. 5,6 This technique allows the extraction of cancer cells from a small sample and the possibility of quantitative analysis. We analyzed gene expressions in samples of gallbladder cancer from our patient using this method.…”

Section: Discussionmentioning

confidence: 99%

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Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene

et al. 2008

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While surgical resection is the most effective treatment for gallbladder cancer, most of these cancers are not resectable at the time of diagnosis, and therefore, chemotherapy serves as the primary therapy in many cases. However, to date, there is no standard chemotherapy for this cancer. We report a case of advanced gallbladder cancer for which the anticancer drug S-1 was effective. The patient was a 53-year-old woman who presented with a huge ovarian tumor. On workup, all abdominal images revealed the presence of advanced gallbladder cancer that had invaded the liver. Because the gallbladder formed a relatively hard and swollen mass involving the omentum, as revealed during exploration, the surgical resection of the gallbladder was not possible at that time, and only hysterectomy and bilateral salpingo-oophorectomy were performed. She started on the anticancer drug S-1 just after this operation. S-1 is a prodrug of 5-fluorouracil (5-FU), and contains 5-chloro-2-4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase (DPD) that rapidly degrades 5-FU. Eight months after the first operation, radical cholecystectomy was performed. Pathologically, the tumor was diagnosed as an adenocarcinoma of the gallbladder, and no evidence of liver invasion was found. Intratumoral gene expression analysis of the resected gallbladder revealed significantly elevated DPD expression. We suggest that the rapid degradation of 5-FU mediated by this high DPD in our patient was significantly blocked by the CDHP in S-1, and that the efficacy of 5-FU was consequently maintained at the maximum level.

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Section: Discussionmentioning

confidence: 99%

“…These enzymes were all measured by Response Genetic (Los Angeles, CA, USA), according to the DTP method, with laser-capture microdissection (LCM), as previously described. 5,6 Intratumoral DPD and OPRT gene expressions were high. On the other hand, TS gene expression was lower than that found in normal tissue (Table 1).…”

Section: Case Reportmentioning

confidence: 97%

Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene

et al. 2008

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“…The degree of thymidylate synthase (TS), DPD and OPRT protein expression is thought to be one of the most reliable factors. Many studies have reported that various carcinomas with higher expression of TS, DPD and lower expression of OPRT may resist 5-FUbased chemotherapy (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Effects of Lentinan alone and in combination with fluoropyrimidine anticancer agent on growth of human oral squamous cell carcinoma in vitro and in vivo

Harada

Itashiki²,

Takenawa³

et al. 2010

Int J Oncol

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Abstract. Chemotherapy has shown little antitumor activity against advanced oral squamous cell carcinoma (OSCC) patients. Therefore, there is an urgent need to develop more effective therapeutic methods for patients with advanced OSCC. Lentinan, ß-(1➝3)-D-glucan, an extract from the edible mushroom, Lentinus edodes, has been reported to show direct antitumor effects and various immunomodulatory effects. S-1 is an oral antineoplastic agent that can induce apoptosis in various types of cancer cells, including OSCC. Hence, combined treatment of cancer cells with Lentinan and S-1 might exert dramatic antitumor effects on OSCC cells. In this study, the response of human OSCC cells to Lentinan alone and in combination with S-1 was examined using nude mouse xenograft models. S-1 (6.9 mg/kg/day, 7 times/week) was administered orally and Lentinan (0.1 mg/kg/day, 2 times/ week) was injected into peritumoral tissue for three weeks. Apoptotic cells were detected by a TUNEL method. The gene expression level of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) was determined using microdissection and RT-PCR, and their protein levels were determined using ELISA. Combined therapy of Lentinan and S-1 markedly exerted antitumor effects on human OSCC xenografts and significantly induced apoptotic cells in tumors treated with Lentinan plus S-1. Microdissection and RT-PCR revealed that the expression of TS and DPD mRNA was downregulated and that expression of OPRT mRNA was upregulated in tumors administered the combined treatment. Moreover, ELISA indicated that the protein levels of TS and DPD were down-regulated, and that OPRT was up-regulated in tumors treated with the combined therapy. During the experimental period, no loss of body weight was observed in mice treated with the combined therapy. These findings demonstrate that the combination of Lentinan and S-1 is effective against OSCC and has the potential of being a new therapeutic tool for future treatment of these tumors.

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“…[11][12][13] Microdissection A representative formalin-fi xed, paraffi n-embedded tumor specimen was selected by a pathologist after the examination of hematoxylin and eosin-stained slides. Ten-micronthick sections were stained with neutral fast red to enable visualization of histology for laser capture microdissection (P.A.L.M.…”

Section: Measurement Of Tp Gene Expressionmentioning

confidence: 99%

Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase

et al. 2008

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Expression of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyl transferase in prostate cancer

Cited by 19 publications

References 27 publications

Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene

Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene

Effects of Lentinan alone and in combination with fluoropyrimidine anticancer agent on growth of human oral squamous cell carcinoma in vitro and in vivo

Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase

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