S-1, an oral fluoropyrimidine anti-cancer agent, enhanced radiosensitivity in a human oral cancer cell line in vivo and in vitro: involvement possibility of inhibition of survival signal, Akt/PKB

Harada, Koji; Kawaguchi, Shinichi; Supriatno, .; Kawashima, Yuichiro; Yoshida, Hideo; Sato, Mitsunobu

doi:10.1016/j.canlet.2004.12.048

Cited by 29 publications

(21 citation statements)

References 20 publications

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“…Several reports have suggested that chemoradiotherapy using S-1 in combination with X-ray irradiation is fairly effective against various types of cancer xenografts, and its anticancer effects are mediated by mechanisms including induction of apoptosis, inhibition of survival signals or suppression of radiation-induced hypoxia-inducible factor-1 (HIF-1) activation (22)(23)(24)(25). Preliminary clinical studies have demonstrated the potential efficacy of chemoradiotherapy with S-1 and radiation in treating locally advanced head and neck and pancreatic cancers (26,27).…”

Section: Introductionmentioning

confidence: 99%

Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

Fukushima

Sakamoto²,

Sakata³

et al. 2010

Oncol Rep

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Abstract. Chemoradiotherapy is a useful treatment strategy in patients with locally advanced cancers. In particular, combination of 5-fluorouracil (5-FU) with X-ray irradiation is effective for the treatment of some types of gastrointestinal cancers. We investigated the antitumor effects of combination treatment with X-ray and S-1, a unique formulation of 5-FU, on human cancer xenografts in nude mice and compared the efficacy of this treatment to that of radiotherapy combined with cisplatin, UFT, another oral 5-FU prodrug, and intravenous 5-FU. Tumors implanted into the left hind legs of mice were treated with a dose of 2 or 5 Gy X-ray irradiation on days 1 and 8, and S-1, UFT and 5-FU were administered for 14 days. The efficacy of combined treatment with 8.3 mg/kg S-1 and 2 Gy X-ray irradiation in treating non-small cell lung cancer xenografts (Lu-99 and LC-11) was significantly higher than that of treatment with S-1 alone or 2 Gy X-ray irradiation alone, and the antitumor activity of combined treatment was similar to that of 5 Gy X-ray irradiation alone. Although 8.3 mg/kg S-1 and 17.5 mg/kg UFT had equivalent antitumor activity; the antitumor efficacy of combination treatment with S-1 and 2 Gy X-ray irradiation on LC-11 tumors was significantly higher than that of combination treatment with UFT and 2 Gy X-ray irradiation. Combination treatment with S-1 and X-ray irradiation was also more effective against pancreatic tumors than combination treatment with intravenous 5-FU and X-ray irradiation. To elucidate the reason for the increased antitumor efficacy of combination treatment with S-1 and X-ray irradiation, the antitumor effect of gimeracil, one of the components of S-1, was tested in combination with 2 Gy X-ray irradiation. These experiments demonstrated that gimeracil enhanced the efficacy of X-ray irradiation against lung as well as head and neck cancer xenografts in a dosedependent manner. Furthermore, we observed decreased expression of Á-H2AX protein, a marker of DNA repair, in LC-11 tumors treated with X-ray irradiation and gimeracil compared to that observed in tumors treated with X-ray irradiation alone, suggesting that gimeracil may inhibit rapid repair of X-ray-induced DNA damage in tumors. The present study suggests that chemoradiotherapy using S-1 acts through a novel mechanism and may prove useful in treating patients with locally advanced cancers whose disease progression is difficult to control using chemotherapy alone.

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Section: Introductionmentioning

confidence: 99%

Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

Fukushima

Sakamoto²,

Sakata³

et al. 2010

Oncol Rep

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“…In terms of the effect on primary foci, the CR rate was 37.5%, indicating a high rate of local tumor control. Additive effects of S-1 on tumor cell killing by irradiation were also confirmed by in vitro study (15)(16)(17). Of the 11 patients in whom cancer was not cured, 2 refused additional treatment, 8 underwent salvage surgery, and selective arterial infusion therapy was possible in the remaining Table II.…”

Section: Discussionmentioning

confidence: 73%

Effects of a concurrent chemoradiotherapy with S-1 for locally advanced oral cancer

et al. 2011

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Abstract.A number of regimens composed of concurrent chemoradiotherapy (CCRT) have been attempted as radical or adjuvant therapies for locally advanced oral cancer. CCRT with S-1 is considered promising due to its efficacy and simplicity of application. Patients (n=16) with locally advanced squamous cell carcinoma of the oral cavity were enrolled. Chemotherapy consisted of oral administration of S-1 (65 mg/m 2 ) for 14 consecutive days followed by a 1-week rest. Radiation treatment at a dose of 30 Gy in 15 fractions was administered concomitantly with S-1. A course schedule of 3 weeks of treatment was applied twice. The overall response rate was 87.5%. Median progression-free survival and median overall survival were 6.3 and 42.5 months, respectively. Although no grade 4 adverse events were observed, grade 3 adverse events, such as anemia (12.5%), stomatitis (25%) and anorexia (18.8%) were present. Thus, CCRT with S-1 is an effective modality that can be safely conducted with minimal burden on patients.

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“…However, continuous intravenous infusion of 5-FU can be replaced by long-term daily oral administration of S-1. As S-1 is administered orally, it is convenient for divided radiotherapy [10]. Further, a significant safety advantage was observed in the S-1 plus cisplatin regimen as compared to the 5-FU plus cisplatin regimen in advanced gastric or gastroesophageal adenocarcinoma studies [22].…”

Section: Discussionmentioning

confidence: 99%

“…Compared with 5-FU, the response rate (RR) in gastric cancer for S-1 was higher, while the incidence of toxicity was lower as compared with 5-FU [9]. Additionally, S-1 enhances radiotherapy and might prove to be an effective chemotherapeutic agent in a CRT setting [10].…”

mentioning

confidence: 99%

Split-course chemoradiotherapy with S-1, a novel oral fluorouracil, and cisplatin for distant metastases of oesophageal cancer stage IVb

Iwase¹,

Shimada²,

Hirashima³

et al. 2017

J Cancer Res Ther.

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S-1, an oral fluoropyrimidine anti-cancer agent, enhanced radiosensitivity in a human oral cancer cell line in vivo and in vitro: involvement possibility of inhibition of survival signal, Akt/PKB

Cited by 29 publications

References 20 publications

Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo

Effects of a concurrent chemoradiotherapy with S-1 for locally advanced oral cancer

Split-course chemoradiotherapy with S-1, a novel oral fluorouracil, and cisplatin for distant metastases of oesophageal cancer stage IVb

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