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Aim: Little information is available on the incidence per population of adverse drug reactions (ADR) to Kampo medicines. We estimated the incidence of ADRs for each Kampo medicine and examined the crude drug components of Kampo medicines that may cause ADRs. Methods: We extracted information on ADRs caused by Kampo medicines from the Japanese Adverse Drug Event Report database (JADER) between fiscal years 2008 and 2014. The number of people who took Kampo medicines was estimated based on the production value of the Kampo formulation, the drug price, and the duration of administration. Results: The incidences of interstitial pneumonia and liver disorder were highest for formulations that contained Scutellaria root. However, 33% of interstitial pneumonia and 39% of liver disorder cases were reported for formulations that did not contain Scutellaria root. The majority of pseudoaldosteronism cases were caused by formulations that contained Glycyrrhiza. Mesenteric phlebosclerosis occurred most commonly in response to formulations that contained Gardenia fruit. The incidences of these ADRs varied among formulations containing these crude drugs. Odds ratio analysis indicated that additional crude drugs may have also been responsible for these ADRs. In addition, some crude drugs may prevent these ADRs. Conclusion: Estimation of the incidence of ADRs caused by Kampo medicines could be a prelude to a new risk management plan, and may focus attention on formulations and crude drug components associated with previously unindicated risks. [ABSTRACT FROM AUTHOR]

Background: The Japan Society for Oriental Medicine makes a compilation of structured abstracts of randomized controlled trials (RCTs) of Kampo medicines available on its Evidence Reports of Kampo Treatment (EKAT) website. Methods: Using EKAT, we conducted a systematic review and meta-analysis on the efficacy of using daikenchuto (https://mpdb.nibiohn.go.jp/stork) for bowel dysfunction after surgery for gastrointestinal cancer. The primary outcomes were the time to first postoperative flatus and the time to first postoperative bowel movement (BM). Results: We found nine relevant RCTs. The mean differences between the daikenchuto group and control group (daikenchuto was not administered) were − 0.43 (95% CI: − 0.77 to − 0.09) days for the time to first postoperative flatus, − 0.29 (95% CI: − 0.59 to 0.01) days for the time to first postoperative BM, and − 0.95 (95% CI: − 1.70 to − 0.21) days for the length of postoperative hospital stay, and the risk ratio of the incidence of intestinal obstruction was 0.60 (95% CI: 0.35–1.03). The time to first postoperative flatus and the length of postoperative hospital stay were significantly shorter in the daikenchuto group than those in the control group (P = 0.01). However, only double-blind studies were evaluated; the results turned to be non-significant. Conclusion: As a result of meta-analysis by all retrieved according to the registered protocol, daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers. However, limiting to articles with description of COI and blindness, significance disappeared. [ABSTRACT FROM AUTHOR]

Objective: To provide an evidence-based recommendation for the management of olfactory dysfunction in accordance with the consensus reached by the Subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction in the Japanese Rhinologic Society.Methods: Seven clinical questions (CQs) regarding the management of olfactory dysfunction were formulated by the subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction. We searched the literature published between April 1990 and September 2014 using PubMed, the Cochrane Library, and Ichushi Web databases. The main search terms were "smell disorder," "olfactory dysfunction," "olfactory loss," "olfactory disturbance," "olfactory impairments," "olfaction disorder," "smell disorder," "anosmia," "cacosmia," and "dysosmia." Based on the results of the literature review and the expert opinion of the Subcommittee, 4 levels of recommendation, from A-strongly recommended to D-not recommended, were adopted for the management of olfactory dysfunction.Results: Both oral and locally administered corticosteroids have been strongly recommended for patients with olfactory dysfunction due to chronic rhinosinusitis. Nasal steroid spray and antihistamine drugs have been moderately recommended for patients with allergic rhinitis. Although no drugs have been deemed to be truly effective for post-viral olfactory dysfunction by randomized-controlled trials (RCTs) or placebo-controlled trials, olfactory training using odorants has been reported to be effective for improving olfactory function. There is considerable evidence that olfactory testing is useful for differential diagnosis, prediction of disease progression, and early detection of cognitive decline in neurodegenerative diseases.Conclusion: The Clinical Practice Guideline has developed recommendations for the management of various aspects of olfactory dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the social problems experienced by cancer patients in non-Western countries. The aims of this study were (1) to explore the characteristics and frequencies of social problems in cancer outpatients, as well as their associations with the need for help, and (2) to take the initial steps to develop an instrument for the assessment of cancer-related social problems in Japan.Methods: A cross-sectional group of 109 patients completed the Social Problem Checklist and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Participants rated the levels of the problem severity and the need for help on each item. Factor structure, internal consistency, and construct validity were also assessed.Results: In total, 72.5% of the participants encountered ≥1 problem, and 33% experienced ≥1 serious problem. The amount of help needed tended to be lower than problem severity, especially for family and social life issues. The most common reason for not needing help, as reported by approximately 40% of patients who experienced problems, was the preference for self-management. A 3-factor model was extracted that included financial matters, medical information, and family and social life. Excellent internal consistencies for each factor and convergent correlations between the relevant subscales of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Social Problem Checklist were confirmed.Conclusions: A substantial proportion of participants had cancer-related social problems, but they had ambivalent help-related needs. Interventions that enhance the patient's abilities for self-care could be essential to help cancer outpatients manage social problems in Japan. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is obstinate and resistant to gemcitabine, a standard chemotherapeutic agent for the disease. We previously showed a therapeutic effect of glycogen synthase kinase-3β (GSK3β) inhibition against gastrointestinal cancer and glioblastoma. Here, we investigated the effect of GSK3β inhibition on pancreatic cancer cell sensitivity to gemcitabine and the underlying molecular mechanism. Methods: Expression, phosphorylation, and activity of GSK3β in pancreatic cancer cells (PANC-1) were examined by Western immunoblotting and in vitro kinase assay. The combined effect of gemcitabine and a GSK3β inhibitor (AR-A014418) against PANC-1 cells was examined by isobologram and PANC-1 xenografts in mice. Changes in gene expression in PANC-1 cells following GSK3β inhibition were studied by cDNA microarray and reverse transcription (RT)-PCR. Results: PANC-1 cells showed increased GSK3β expression, phosphorylation at tyrosine 216 (active form), and activity compared with non-neoplastic HEK293 cells. Administration of AR-A014418 at pharmacological doses attenuated proliferation of PANC-1 cells and xenografts, and significantly sensitized them to gemcitabine. Isobologram analysis determined that the combined effect was synergistic. DNA microarray analysis detected GSK3β inhibition-associated changes in gene expression in gemcitabine-treated PANC-1 cells. Among these changes, RT-PCR and Western blotting showed that expression of tumor protein 53-induced nuclear protein 1, a gene regulating cell death and DNA repair, was increased by gemcitabine treatment and substantially decreased by GSK3β inhibition. Conclusions: The results indicate that GSK3β inhibition sensitizes pancreatic cancer cells to gemcitabine with altered expression of genes involved in DNA repair. This study provides insight into the molecular mechanism of gemcitabine resistance and thus a new strategy for pancreatic cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that TP53INP1 expression is dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and this decrease occurs early during pancreatic cancer development. TP53INP1 reexpression in the pancreatic cancer-derived cell line MiaPaCa2 strongly reduced its capacity to form s.c., i.p., and intrapancreatic tumors in nude mice. This anti-tumoral capacity is, at least in part, due to the induction of caspase 3-mediated apoptosis. In addition, TP53INP1-/- mouse embryonic fibroblasts (MEFs) transformed with a retrovirus expressing E1A/rasv12 oncoproteins developed bigger tumors than TP53INP1+/+ transformed MEFs or TP53INP1-/- transformed MEFs with restored TP53INP1 expression. Finally. TP53INP1 expression is repressed by the oncogenic micro RNA miR-155, which is overexpressed in PDAC cells. TP53INP1 is a previously unknown miR-155 target presenting anti-tumoral activity. [ABSTRACT FROM AUTHOR]