Preclinical antitumor efficacy of S-1: a new oral formulation of 5-fluorouracil on human tumor xenografts.

Fukushima, Mitsuo; Satake, Hirofumi; Uchida, Junji; Shimamoto, Yuji; Kato, Tomoyuki; Takechi, Teiji; Okabe, Hidetoshi; Fujioka, Akio; Nakano, Koushi; Ohshimo, Hideyuki; Takeda, Setsuo; Shirasaka, Tetsuhiko

doi:10.3892/ijo.13.4.693

Cited by 54 publications

(52 citation statements)

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“…Briefly, the combined treatment of LNT and S-1 induced the down-regulation of TS protein and DPD protein and the up-regulation of OPRT protein level in KB tumors similarly to each gene expression (Table III). (4,(18)(19)(20)(21)(22)(23). It is thought that LNT have a lower incidence of side effect.…”

Section: Protein Levels Of Ts Dpd and Oprt In Nude Mouse Tumorsmentioning

confidence: 99%

“…Lentinan (LNT), ß-(1➝3)-D-glucan, an extract from the edible mushroom, Lentinus edodes, has been reported to show direct antitumor effects (5,17) and various immunomodulatory effects; for example, LNT is able to activate CTLs (18,19), LAK cells, NK cells and macrophages (20), and to improve Th1/Th2 cytokine balance (21). LNT has been used to treat cancer patients as a biological response modifier (BRM) with cancer chemotherapy, and has been reported to improve the quality of life of the patients and prolong their survival periods (22).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Protein Levels Of Ts Dpd and Oprt In Nude Mouse Tumorsmentioning

confidence: 99%

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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“…5-FU was administered intraperitoneally at a dose of 50mg/kg three times every 4 days. S-1 and UFT were administered orally at a dose of 10 mg/kg or 24mg/kg, respectively, once daily for 9 consecutive days [26]. The control group received 0.5% (w/v) HPMC solution orally once daily for 9 consecutive days.…”

Section: Antitumor Activity Of 5-fu In Human Gastric Cancer Xenograftsmentioning

confidence: 99%

Prediction of sensitivity to fluoropyrimidines by metabolic and target enzyme activities in gastric cancer

et al. 2003

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“…S-1 has also been shown to be a potent radiosensitizer in human solid tumour xenograft (Fukushima et al, 1998;Harada et al, 2004), which suggests that the combination of radiotherapy and S-1 may improve survival in patients with locally advanced pancreatic cancer. However, no previous reports have described the efficacy and safety of chemoradiation therapy with S-1 for the treatment of pancreatic cancer.…”

mentioning

confidence: 99%

Phase-I trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent radiotherapy in patients with unresectable pancreatic cancer

et al. 2007

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In this phase-I trial, we evaluated the safety of S-1, a novel oral fluoropyrimidine anticancer agent, combined with external-beam radiotherapy (EBRT) to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) in unresectable pancreatic cancer patients. Patients had histologically proven unresectable locally advanced or metastatic pancreatic cancer. S-1 was administered orally twice daily. External-beam radiotherapy was delivered in fractions of 1.25 Gy Â 2 per day, totalling 50 Gy per 40 fractions for 4 weeks. S-1 was given at five dose levels: 60 mg m -2 day -1 on days 1 -7 and 15 -21 (level 1), 1 -14 (level 2), and 1 -21 (level 3a) and 80 mg m -2 day -1 on days 1 -21 (level 3b) and 1 -28 (level 4). We studied 17 patients: dose levels 1 (four patients), 2 (four patients), 3a (three patients), 3b (three patients), and 4 (three patients). One patient in level 1 (grade 3 vomiting) and two patients in level 4 (grade 4 neutropenia and grade 3 anorexia) showed DLT. No DLT was seen for levels 2, 3a, and 3b. Clinical effects by computed tomography included 5 partial responses (35%), 11 cases of stable disease, and one case of progressive disease. CA19 -9 levels of less than half the starting values were observed in 8 of 16 (50%) patients. S-1 at a dose of 80 mg m -2 day -1 given on days 1 -21 is safe and recommended for phase-II study in patients with locally advanced and unresectable pancreatic cancer when given with EBRT.

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Preclinical antitumor efficacy of S-1: a new oral formulation of 5-fluorouracil on human tumor xenografts.

Cited by 54 publications

References 0 publications

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

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

Prediction of sensitivity to fluoropyrimidines by metabolic and target enzyme activities in gastric cancer

Phase-I trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent radiotherapy in patients with unresectable pancreatic cancer

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