Immunotoxic Effects of a New Antineoplastic Agent S-1 in Mice : Comparison With S-1, Uft and 5-Fu

Kouchi, Yasuhide; Maeda, Yasuhiro; Morinaga, Hidenobu; Ohuchida, Akinobu

doi:10.2131/jts.21.supplementiii_691

Cited by 4 publications

(6 citation statements)

References 3 publications

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“…Several authors have reported this immunosuppression on adult animals [65,66] and humans [67,68] . Other authors have observed that treatment with 5-FU produced a decrease of thymus and spleen weights [69,70] , as well as a reduction of the number of leukocytes in mice [69,71] . This negative effect on immunological cells is due to apoptotic effect of 5-FU, mediated by the activation of the CD95/CD95L system [72,73] and caspase 3 [74] .…”

Section: Discussionmentioning

confidence: 86%

Intestinal Toxicity Induced by 5-Fluorouracil in Pigs: A New Preclinical Model

Manzano¹,

Bueno²,

Rueda³

et al. 2007

Chemotherapy

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Background: The goal of this study was to develop an animal model of intestinal injury induced by 5-fluorouracil (5-FU) in pigs. Methods: Six domestic pigs were used as control (healthy group) and another 6 malnourished pigs orally received 5-FU (treated group). After 4 weeks of treatment, pigs were sacrificed and jejunum, ileum and colon were isolated for histological, immunological and biochemical analyses. Results: 5-FU caused a decrease in the intestinal mass. Disaccharidase, and phosphate alkaline activities, and glutathione redox cycle were disrupted by 5-FU. Histopathological alterations in the crypts and villous were greater in the small intestine than in the colon. 5-FU decreased the number of peripheral and intestinal leukocytes, promoting an increase in T-cytotoxic cells and a decrease in T-helper and B cells. Conclusion: This pig model of intestinal dysfunction closely mimics the common side effects of cancer chemotherapy in humans, and provides a useful tool for evaluating novel antimucotoxic agents.

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Section: Discussionmentioning

confidence: 86%

Intestinal Toxicity Induced by 5-Fluorouracil in Pigs: A New Preclinical Model

Manzano¹,

Bueno²,

Rueda³

et al. 2007

Chemotherapy

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“…Effects of chitosan on the reduction of immunofunction of spleen induced by 5-FU It has been reported that 5-FU causes immunosuppression and immunotoxicity [15][16][17][18][19] as well as a reduction in the weights of the spleen and thymus. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…[5][6][7][8][20][21][22][23] However, there are a number of reports that gastrointestinal toxicity, myelotoxicity and immunotoxicity are induced by the administration of 5-FU through its phosphorylation in the small intestine, bone marrow and spleen. 9,10,[16][17][18][19] Recently, the clinical application of the combination of 5-FU and a modulator, such as leucovorin, methotrexate or cisplatin, has resulted in relatively high response rates in patients with colorectal cancer, lung cancer and breast cancer. [24][25][26][27][28][29][30] However, in these treatments, severe gastrointestinal toxicity with diarrhea and mucositis and hematalogic toxicity with leukopenia appeared to be dose-limiting factors.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that the effects of chitosan might be due to selective inhibition of 5-FU uptake into small intestine and spleen tissues. It has been reported that 5-FU causes immunosuppression and immunotoxicity [15][16][17][18][19] together with a reduction of the spleen and thymus weights. We reported that chitosan enhances the natural killer (NK) activity of mouse lymphocytes in vitro.…”

Section: Discussionmentioning

confidence: 99%

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Prevention by Chitosan of Myelotoxicity, Gastrointestinal Toxicity and Immunocompetent Organic Toxicity Induced by 5‐Fluorouracil without Loss of Antitumor Activity in Mice

Kimura

Okuda

1999

Japanese Journal of Cancer Research

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“…For decades, 5-FU has been used for treatment of colon, stomach, pancreas, and breast cancers [3]. But 5-FU has many side-effects as other chemotherapeutic agents, such as myelotoxicity [4], immunotoxicity [5], and gastrointestinal toxicity [6]. Therefore, searching strategies to maintain chemotherapeutic efficacy and decrease the side-effects are important clinical issues.…”

Section: -Fluorouracil (5-fu)mentioning

confidence: 99%

Effects of Fungal-derived High Molecular Weight Chitosan on 5-Fluorouracil-induced Adverse Reactions

Uen

Wang

Hsu

et al. 2008

Journal of Bioactive and Compatible Polymers

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The effects of fungal-derived high molecular weight chitosan (HMWC) on the prevention of 5-fluorouracil (5-FU)-induced side-effects were studied in a sarcoma-bearing mice model. 5-FU (12.5 mg/kg) was gargled into Downloaded from the mice with or without HMWC (25, 75, and 150 mg/kg) every 12 h for consecutive 8 or 16 days in different experiments. The HMWC (25-150 mg/kg) exerted no toxicity and did not interfere with the anti-tumor activity of 5-FU on sarcoma-bearing mice. HMWC in a higher dose (150 mg/kg) partially protected 5-FU-induced cytotoxicity on peripheral leukocytes, lymphocytes, and bone marrow CD-19 positive cells. HMWC reversed the 5-FU suppression of intestine sucrase activity and attenuated the 5-FU-induced diarrhea. Bone marrow cells micronucleus and DNA comet assays demonstrated that HMWC significantly reversed 5-FU-induced genome toxicity to marrow cells. These results suggested that fungal-derived HMWC attenuated the 5-FU-induced bone marrow and gastrointestinal toxicity, and has the potential for clinical applications in the future.

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Immunotoxic Effects of a New Antineoplastic Agent S-1 in Mice : Comparison With S-1, Uft and 5-Fu

Cited by 4 publications

References 3 publications

Intestinal Toxicity Induced by 5-Fluorouracil in Pigs: A New Preclinical Model

Intestinal Toxicity Induced by 5-Fluorouracil in Pigs: A New Preclinical Model

Prevention by Chitosan of Myelotoxicity, Gastrointestinal Toxicity and Immunocompetent Organic Toxicity Induced by 5‐Fluorouracil without Loss of Antitumor Activity in Mice

Effects of Fungal-derived High Molecular Weight Chitosan on 5-Fluorouracil-induced Adverse Reactions

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