Preventive Effects of Hange-shashin-to on Irinotecan Hydrochloride-Caused Diarrhea and Its Relevance to the Colonic Prostaglandin E2 and Water Absorption in the Rat

Kase, Yoshio; Hayakawa, Terumasa; Aburada, Masaki; Komatsu, Yasuhiro; Kamataki, Tetsuya

doi:10.1254/jjp.75.407

Cited by 62 publications

(54 citation statements)

References 25 publications

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“…Specifically, the number of goblet cells in the colon crypt column increased by 49% (hyperplasia) but the number of non-goblet cells (mainly columnar absorptive cells) was decreased by 39% following treatment with CPT-11. The reduction in the number of columnar absorptive cells in the colon may help account for the reported malabsorption of water and electrolytes in the large bowel of CPT-11-treated individuals (Kase et al, 1997a).…”

Section: Discussionmentioning

confidence: 99%

Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects

1999

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SummaryThe cancer chemotherapeutic efficacy of the topoisomerase I inhibitor, is often limited by the induction of severe delayed diarrhoea. In animal studies, CPT-11 use is associated with histopathological damage to the mucosa of the small and large intestines. Results from the present study demonstrate that 60 mg CPT-11 per kg body weight (i.v. q4d ϫ 6) halted the growth, but did not cause significant regression, of MCF7 human breast carcinoma xenografts in mice fed a diet containing 7% corn oil. However, when the diet of the MCF7-bearing mice was supplemented with 3% or 6% fish oil, the same CPT-11 treatment caused significant regression of the MCF7 xenograft. Histomorphometric analyses of intestinal mucosa of mice treated with CPT-11 and fed the diet containing 7% corn oil indicated that treatment with CPT-11 induced structural changes in the intestinal mucosa which persisted at least 5 days after the last dose of CPT-11. The intestinal mucosal architecture of mice that were treated with CPT-11 and fed the diets containing fish oil was largely unchanged from the architecture of the group of mice which did not receive CPT-11. These findings indicate that fish oil supplements may be a useful adjunct to CPT-11 treatment.

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Section: Discussionmentioning

confidence: 99%

Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects

1999

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“…Hangeshashinto is reported to have the capabilities for the protection of the gastric mucosa 7) , the antidiarrheal effect 8,9) , the anti-inflammatory effect [9][10][11] and the enhancement of large intestinal water absorption 12) . From these indications, we considered that hangeshashinto could be useful for periodontal disease.…”

Section: Introductionmentioning

confidence: 99%

Preventive Effects of a Kampo Medicine, Hangeshashinto on Inflammatory Responses in Lipopolysaccharide-Treated Human Gingival Fibroblasts

Nakazono

Ara

Fujinami

et al. 2010

J. Hard Tissue Biology.

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In the present study, we investigated the effects of a Kampo medicine hangeshashinto (TJ-14) on the production of prostaglandin E 2 (PGE 2 ), interleukin (IL)-6 and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. HGFs proliferation was dose-dependently decreased with hangeshashinto at days 3 and 7. However, treatment with LPS (10 ng/ml), hangeshashinto (up to 1 mg/ml) and their combinations for 24 h did not affect the viability of HGFs. Hangeshashinto dose-dependently suppressed LPS-induced PGE 2 production but did not alter basal PGE 2 level. Hangeshashinto weakly decreased LPS-induced IL-6 and IL-8 productions. Hangeshashinto decreased cyclooxygenase (COX)-1 and COX-2 activities to approximately 60% at 1 mg/ml. Hangeshashinto decreased cytoplasmic phospholipase A 2 (cPLA 2 ) expression and LPS-induced COX-2 expression but not affected annexin1 expression. Hangeshashinto weakly suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA 2 phosphorylation. These results suggest that hangeshashinto decreased PGE 2 production by (1) suppression of cPLA 2 and LPS-induced COX-2 expression, and to a lesser extent, (2) inhibition of COX-2 activity and (3) inhibition of cPLA 2 phosphorylation and its activation via inhibition of ERK phosphorylation. Moreover, it is also suggested that hangeshashinto may be useful to improve gingival inflammation in periodontal disease.

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“…In clinical practice, TJ-14 has been used for acute or chronic diarrhea, acute gastroenteritis, and for chronic hypoperfusion of the gastrointestinal system [24,25]. It is reported that TJ-14 is effective against diarrhea which is the side effect of chemotherapeutic agents for gastrointestinal cancers [26]. Since TJ-14 contains baicalin, an inhibitor of β-glucuronidase, a randomized trial for advanced small cell lung cancer demonstrated the effect of TJ-14 in significantly controlling grade ≧3 diarrhea caused by cisplatin/irinotecan treatment with a p value of 0.018 [27,28].…”

Section: Discussionmentioning

confidence: 99%

Double-Blind, Placebo-Controlled, Randomized Phase II Study of TJ-14 (Hangeshashinto) for Infusional Fluorinated-Pyrimidine-based Colorectal Cancer Chemotherapy-induced Oral Mucositis

Matsuda

Kono

Munemoto

et al. 2013

Ann. Cancer Res. Therap.

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received the administration of placebo or TJ-14 for 2 weeks at the start of the next course of chemotherapy. Patients were assessed three times per week for safety and for COM incidence and its severity using the WHO grading. Results Ninety eligible patients (TJ-14; 43, placebo; 47) per protocol set analysis were included in the analysis after the key-opening. Although the incidence of grade ≧2 oral mucositis was lower for patients treated with TJ-14 compared to those treated with placebo, there was no significant difference (48.8 vs. 57.4 %; p = 0.41). The median duration of grade ≧2 mucositis was 5.5 versus 10.5 days (p = 0.018). No difference in other treatment toxicity was observed between the two groups, and patients exhibited high compliance in dosing administration. Conclusion The present study results did not meet the primary endpoint. However, TJ-14 demonstrated a significant effect in the treatment of grade ≧2 mucositis in patients with colorectal cancer compared to the placebo.

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Preventive Effects of Hange-shashin-to on Irinotecan Hydrochloride-Caused Diarrhea and Its Relevance to the Colonic Prostaglandin E2 and Water Absorption in the Rat

Cited by 62 publications

References 25 publications

Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects

Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects

Preventive Effects of a Kampo Medicine, Hangeshashinto on Inflammatory Responses in Lipopolysaccharide-Treated Human Gingival Fibroblasts

Double-Blind, Placebo-Controlled, Randomized Phase II Study of TJ-14 (Hangeshashinto) for Infusional Fluorinated-Pyrimidine-based Colorectal Cancer Chemotherapy-induced Oral Mucositis

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