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Eun-so Lee - One of the best experts on this subject based on the ideXlab platform.
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Acral lentiginosis associated with tegafur/Gimeracil/oteracil (TS-1).
European journal of dermatology : EJD, 2017Co-Authors: Young Joon Park, Byoung Woo Soh, Eun-so LeeAbstract:Acral lentiginosis refers to an outbreak of multiple lentigines confined to acral sites, e.g. hands and feet. It is known to be associated with immunodeficiency conditions, such as acquired immunodeficiency syndrome (AIDS) or immunosuppressive treatments [1-3]. Some authors consider the condition as a paraneoplastic syndrome [1].Tegafur/Gimeracil/oteracil (TS-1) is a combined oral chemotherapeutic agent containing 20 mg of tegafur, a prodrug converted by cells to fluorouracil (FU) and other components [...]
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acral lentiginosis associated with tegafur Gimeracil oteracil ts 1
European Journal of Dermatology, 2017Co-Authors: Young Joon Park, Byoung Woo Soh, Eun-so LeeAbstract:Acral lentiginosis refers to an outbreak of multiple lentigines confined to acral sites, e.g. hands and feet. It is known to be associated with immunodeficiency conditions, such as acquired immunodeficiency syndrome (AIDS) or immunosuppressive treatments [1-3]. Some authors consider the condition as a paraneoplastic syndrome [1].Tegafur/Gimeracil/oteracil (TS-1) is a combined oral chemotherapeutic agent containing 20 mg of tegafur, a prodrug converted by cells to fluorouracil (FU) and other components [...]
Masafumi Kawamura - One of the best experts on this subject based on the ideXlab platform.
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spinal infarction related to the adjuvant chemotherapy for surgically resected non small cell lung cancer report of a case
Japanese Journal of Clinical Oncology, 2013Co-Authors: Noriyuki Matsutani, Masafumi KawamuraAbstract:We report the development of spinal infarction during adjuvant chemotherapy with tegafur, Gimeracil and oteracil (TS-1) after surgery for lung adenocarcinoma. A 69-year-old female had a left upper lobectomy for pulmonary adenocarcinoma, T2aN0M0. Six weeks after the surgery, tegafur, Gimeracil and oteracil were administered orally as adjuvant chemotherapy for 1 year. After 10 months of adjuvant chemotherapy, the patient suddenly showed signs of numbness and weakness in both lower limbs. The patient did not have a previous medical history, and was receiving only tegafur, Gimeracil and oteracil with the stomach medication. Neurological findings showed muscle weakness, numbness and a loss of tendon reflex in both lower limbs, as well as bladder and rectal disturbance. Blood tests, brain magnetic resonance imaging and chest computed tomography showed no signs of abnormalities or metastasis. Magnetic resonance imaging of the spine showed a hyperintense lesion between the Th12 and L1 spinal levels by T2-weighted image. A spinal fluid test indicated no abnormalities, and cytological diagnosis was class II. Anti-aquaporin 4, anti-ganglioside and anti-neuronal autoantibodies were all negative. These results indicated that the patient had a spinal infarction, rather than myelitis or paraneoplastic neurological syndrome. The patient was treated with heparin and steroid pulse treatment followed by rehabilitation, and recovered sufficiently to be able to walk using a cane after 2 months. The development of spinal infarction during anti-cancer chemotherapy has not been previously reported. In this case, an association of spinal infarction with the use of adjuvant chemotherapy was strongly indicated due to the lack of abnormalities in coagulability, atherosclerotic lesions and aortic disease.
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Spinal Infarction Related to the Adjuvant Chemotherapy for Surgically Resected Non-small Cell Lung Cancer: Report of a Case
2012Co-Authors: Noriyuki Matsutani, Masafumi KawamuraAbstract:We report the development of spinal infarction during adjuvant chemotherapy with tegafur, Gimeracil and oteracil (TS-1) after surgery for lung adenocarcinoma. A 69-year-old female had a left upper lobectomy for pulmonary adenocarcinoma, T2aN0M0. Six weeks after the surgery, tegafur, Gimeracil and oteracil were administered orally as adjuvant chemotherapy for 1 year. After 10 months of adjuvant chemotherapy, the patient suddenly showed signs of numbness and weakness in both lower limbs. The patient did not have a previous medical history, and was receiving only tegafur, Gimeracil and oteracil with the stomach medication. Neurological findings showed muscle weakness, numbness and a loss of tendon reflex in both lower limbs, as well as bladder and rectal disturbance. Blood tests, brain magnetic res-onance imaging and chest computed tomography showed no signs of abnormalities or metas-tasis. Magnetic resonance imaging of the spine showed a hyperintense lesion between the Th12 and L1 spinal levels by T2-weighted image. A spinal fluid test indicated no abnormal-ities, and cytological diagnosis was class II. Anti-aquaporin 4, anti-ganglioside and anti-neur-onal autoantibodies were all negative. These results indicated that the patient had a spinal infarction, rather than myelitis or paraneoplastic neurological syndrome. The patient wa
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Case Report Spinal Infarction Related to the Adjuvant Chemotherapy for Surgically Resected Non-small Cell Lung Cancer: Report of a Case
2012Co-Authors: Noriyuki Matsutani, Masafumi KawamuraAbstract:We report the development of spinal infarction during adjuvant chemotherapy with tegafur, Gimeracil and oteracil (TS-1) after surgery for lung adenocarcinoma. A 69-year-old female had a left upper lobectomy for pulmonary adenocarcinoma, T2aN0M0. Six weeks after the surgery, tegafur, Gimeracil and oteracil were administered orally as adjuvant chemotherapy for 1 year. After 10 months of adjuvant chemotherapy, the patient suddenly showed signs of numbness and weakness in both lower limbs. The patient did not have a previous medical history, and was receiving only tegafur, Gimeracil and oteracil with the stomach medication. Neurological findings showed muscle weakness, numbness and a loss of tendon reflex in both lower limbs, as well as bladder and rectal disturbance. Blood tests, brain magnetic res-onance imaging and chest computed tomography showed no signs of abnormalities or metas-tasis. Magnetic resonance imaging of the spine showed a hyperintense lesion between the Th12 and L1 spinal levels by T2-weighted image. A spinal fluid test indicated no abnormal-ities, and cytological diagnosis was class II. Anti-aquaporin 4, anti-ganglioside and anti-neur-onal autoantibodies were all negative. These results indicated that the patient had a spinal infarction, rather than myelitis or paraneoplastic neurological syndrome. The patient wa
Shinobu Hosokawa - One of the best experts on this subject based on the ideXlab platform.
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A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small cell lung cancer with wild type EGFR (OLCSG1202).
Journal of Clinical Oncology, 2017Co-Authors: Akihiro Bessho, Nobuaki Ochi, Shoichi Kuyama, Nobukazu Fujimoto, Takahiro Umeno, Kiichiro Ninomiya, Genyo Ikeda, Daijiro Harada, Daizo Kishino, Shinobu HosokawaAbstract:e20614Background: S-1 is an oral fluoropyrimidine anticancer agent that combines tegafur, Gimeracil, and oteracil potassium. Two phase III trials in advanced non-small cell lung cancer (NSCLC) show...
Masakazu Fukushima - One of the best experts on this subject based on the ideXlab platform.
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Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA
2016Co-Authors: Masanori Someya, Koh-ichi Sakata, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Masato Hareyama, Masakazu FukushimaAbstract:Dihydropyrimidine dehydrogenase/Radiation induced focus/RPA phosphorylation/Camptothecin. Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothe-cin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mecha-nisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA signif-icantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD deple-tion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization
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The combination of hyperthermia or chemotherapy with Gimeracil for effective radiosensitization.
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al], 2012Co-Authors: Masaru Takagi, Koh-ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Hiroshi Tauchi, Masato Hareyama, Masakazu FukushimaAbstract:5-chloro-2,4-dihydroxypyridine (Gimeracil) is a component of the oral fluoropyrimidine derivative S-1. Gimeracil was originally added to S-1 to yield prolonged 5-fluorouracil (5-FU) concentrations in serum and tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We previously demonstrated that Gimeracil enhances the efficacy of radiotherapy through the suppression of homologous recombination (HR) in DNA double strand repair. The goal of this paper was to examine the effects of Gimeracil on the sensitivity of anticancer drugs and hyperthermia in order to obtain effective radiosensitization. Various cell lines, including DLD 1 (human colon carcinoma cells) and cells deficient in HR or nonhomologous end-joining (NHEJ), were used in clonogenic assays. The survival of these cells after various treatments (e.g., drug treatment, heat treatment, and radiation) was determined based on their colony-forming ability. Gimeracil enhanced cell-killing effects of camptothecin (CPT), 5-FU, and hydroxyurea. Gimeracil sensitized effects of CPT or 5-FU to cells deficient in HR or NHEJ to a similar extent as in other cells (DLD1 and a parent cell), indicating that its sensitizing mechanisms may be different from inhibition of HR or NHEJ. Combination of Gimeracil and CPT or 5-FU sensitized radiation more effectively than each modality alone. Gimeracil also enhanced heat sensitivity at 42°C or more. The degree of heat sensitization with Gimeracil increased as the temperature increased, and the combination of Gimeracil and heat-sensitized radiation was more effective than each modality alone. Gimeracil enhanced sensitivity of CPT, 5-FU, and hyperthermia. Combination of these modalities sensitized radiation more efficiently than each modality alone.
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Effects of Depletion of Dihydropyrimidine Dehydrogenase on Focus Formation and RPA Phosphorylation
Journal of Radiation Research, 2012Co-Authors: Masanori Someya, Koh-ichi Sakata, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Masato Hareyama, Masakazu FukushimaAbstract:Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.
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Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination
Cancer science, 2011Co-Authors: Koh-ichi Sakata, Masanori Someya, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Minoru Toyota, Masaru Takagi, Masato Hareyama, Masakazu FukushimaAbstract:Gimeracil (5-chloro-2, 4-dihydroxypyridine) is an inhibitor of dihydropyrimidine dehydrogenase (DPYD), which degrades pyrimidine including 5-fluorouracil in the blood. Gimeracil was originally added to an oral fluoropyrimidine derivative S-1 to yield prolonged 5-fluorouracil concentrations in serum and tumor tissues. We have already reported that Gimeracil had radiosensitizing effects by partially inhibiting homologous recombination (HR) in the repair of DNA double strand breaks. We investigated the mechanisms of Gimeracil radiosensitization. Comet assay and radiation-induced focus formation of various kinds of proteins involved in HR was carried out. siRNA for DPYD were transfected to HeLa cells to investigate the target protein for radiosensitization with Gimeracil. SCneo assay was carried out to examine whether DPYD depletion by siRNA inhibited HR repair of DNA double strand breaks. Tail moments in neutral comet assay increased in Gimeracil-treated cells. Gimeracil restrained the formation of foci of Rad51 and replication protein A (RPA), whereas it increased the number of foci of Nbs1, Mre11, Rad50, and FancD2. When HeLa cells were transfected with the DPYD siRNA before irradiation, the cells became more radiosensitive. The degree of radiosensitization by transfection of DPYD siRNA was similar to that of Gimeracil. Gimeracil did not sensitize DPYD-depleted cells. Depletion of DPYD by siRNA significantly reduced the frequency of neopositive clones in SCneo assay. Gimeracil partially inhibits the early step in HR. It was found that DPYD is the target protein for radiosensitization by Gimeracil. The inhibitors of DPYD, such as Gimeracil, could enhance the efficacy of radiotherapy through partial suppression of HR-mediated DNA repair. (Cancer Sci 2011; 102: 1712‐1716)
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Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo.
Oncology reports, 2010Co-Authors: Masakazu Fukushima, Kazuki Sakamoto, Minoru Sakata, Fumio Nakagawa, Hitoshi Saito, Y. U. SakataAbstract: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 dose-dependent manner. Furthermore, we observed decreased expression of γ-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.
Wang Dong - One of the best experts on this subject based on the ideXlab platform.
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Clinical effects of Nedaplatin,Tegafur Gimeracil Oteracil Potassium capsule combined with three-dimensional conformal radiotherapy in elderly patients with locally advanced non-small cell lung cancer
Journal of Hainan Medical University, 2012Co-Authors: Wang DongAbstract:Objective: To investigate the clinical effects and safety of Nedaplati,Tegafur Gimeracil Oteracil Potassium capsule combined with three-dimensional conformal radiotherapy in elderly patients with locally advanced non-small cell lung cancer.Methods: A total of 50 elderly patients with locally advanced non-small cell lung cancer that were treated in our hospital from January 2010 to January 2011 were selected and randomly divided into control group(only three-dimensional conformal radiotherapy group)and observation group(Nedaplatin,Tegafur Gimeracil Oteracil Potassium Capsule combined with three-dimensional conformal radiotherapy group)with 25 cases in each group,then the total effective rate,clinical benefit rate,progression-free survival,one-year survival rate and adverse reactions of two groups were compared.Results:The total effective rate and clinical benefit rate of observation group were 88.00% and 96.00%,and they were significant higher than 56.00% and 84.00% of observation group,progression-free survival time of the observation group was(17.5±1.8)months,significant longer than(11.9±1.3)months of the control group,one-year survival rate was 72.00%,and it was higher than 48.00% of control group(P0.05).Hematological toxicity of the observation group was higher than that of control group(P0.05).However,the rates of radioactive esophagitis and radiation pneumonitis of two groups was not significantly different(P0.05).Conclusion:The clinical effects and safety of Nedaplatin,Tegafur Gimeracil Oteracil Potassium Capsule combined with three-dimensional conformal radiotherapy in the treatment of elderly patients with locally advanced non-small cell lung cancer is better,and the adverse reactions is tolerable.