シュジュツ フノウ シンコウ イガン ニ タイスル カガク リョウホウ

Although the incidence of gastric cancer is declining in Japan, it is still the second common cancer. After ２０００ year, several new anticancer drugs for gastric cancer have been developed, and overall response rate and survival have been ７‐５１％ and ６‐１２ months respectively. However, these are still unsatisfactory results and the majority of the metastatic gastric cancer is incurable. We proposed a triplet regimen consisting of docetaxel, cisplatin and S‐１（DCS）, and performed phase I and II study. The results showed that response rate was８７．１％ and overall survival was ２２ months. Now, phase III study is under way. In addition, recently efficacy of herceptin, an antibody agent against HER２, was proved for HER２ positive gastric cancer. This is the first molecular targeting drug that was approved for gastric cancer. In future, combination of herceptin and cytotoxic anticancer drugs such as DCS regimen will be tested

Response Predictors of DCS Therapy in Gastric Cancer

Objectives: The aim of this study was to identify biomarkers for predicting the efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric cancer using microarrays of biopsy specimens before chemotherapy. Methods: Nineteen samples were taken from 19 patients with unresectable metastatic gastric cancer who received DCS as a first-line therapy. Laser capture microdissection was performed, and total cellular RNA was extracted from each microdissected sample. Whole-gene expression was analyzed by microarray, and the difference in mRNA expression observed with the microarrays was confirmed by quantitative real-time PCR. Immunohistochemical staining was performed using clinical tissue sections obtained by endoscopic biopsy. Results: Eleven patients were identified as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine genes showed significant differences in relative expression ratios between tumor and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for distinguishing gene expression between 11 early responders and 8 nonresponders. Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for validation were well correlated with those 4 genes in microarrays. Conclusion: The genes identified may serve as efficient biomarkers for personalized cancer-targeted therapy

Opposing effects of estradiol and progesterone on the oxidative stress-induced production of chemokine and proinflammatory cytokines in murine peritoneal macrophages

In inflammatory and oxidative liver injury, virus proteins and reactive oxygen species are involved in the regulation of proinflammatory cytokine production by macrophages. This study investigated the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stress-stimulated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, macrophage inflammatory protein (MIP)-2, and macrophage chemotactic protein (MCP)-1 by peritoneal macrophages isolated from male and female mice. E2 inhibited the cytokine production of TNF-α, IL-1β, MIP-2, and MCP-1 by the unstimulated macrophages from males and females, which was then further stimulated by progesterone. The exposure to hydrogen peroxide in the macrophages from both sexes induced the production of cytokine. The hydrogen peroxide-stimulated cytokine production was suppressed by E2 and enhanced by progesterone. The sex hormone effects on the unstimulated and stimulated macrophages were blocked by their receptor antagonists and showed no significant difference between male and female subjects. These findings suggest that E2 may play a favorable role in the course of persistent liver injury, by inhibiting proinflammatory cytokine production, which, in addition, progesterone may counteract the favorable E2 effects through their receptors

Molecular Characteristics of Extended-Spectrum Beta-Lactamases and qnr Determinants in Enterobacter Species from Japan

The incidence of extended-spectrum β-lactamases (ESBLs) has been increasing worldwide, but screening criteria for detection of ESBLs are not standardized for AmpC-producing Enterobacteriaceae such as Enterobacter species. In this study, we investigated the prevalence of ESBLs and/or AmpC β-lactamases in Japanese clinical isolates of Enterobacter spp. and the association of plasmid-mediated quinolone resistance (PMQR) determinants with ESBL producers. A total of 364 clinical isolates of Enterobacter spp. collected throughout Japan between November 2009 and January 2010 were studied. ESBL-producing strains were assessed by the CLSI confirmatory test and the boronic acid disk test. PCR and sequencing were performed to detect CTX-M, TEM, and SHV type ESBLs and PMQR determinants. For ESBL-producing Enterobacter spp., pulsed-field gel electrophoresis (PFGE) was performed using XbaI restriction enzyme. Of the 364 isolates, 22 (6.0%) were ESBL producers. Seven isolates of Enterobacter cloacae produced CTX-M-3, followed by two isolates producing SHV-12. Two isolates of Enterobacter aerogenes produced CTX-M-2. Of the 22 ESBL producers, 21 had the AmpC enzyme, and six met the criteria for ESBL production in the boronic acid test. We found a significant association of qnrS with CTX-M-3-producing E. cloacae. The 11 ESBL-producing Enterobacter spp. possessing blaCTX-M, blaSHV, or blaTEM were divided into six unique PFGE types. This is the first report about the prevalence of qnr determinants among ESBL-producing Enterobacter spp. from Japan. Our results suggest that ESBL-producing Enterobacter spp. with qnr determinants are spreading in Japan

Association between mental health and bone mass among community-dwelling adults: Nagasaki Islands Study on bone health

Osteoporosis and its related fractures are important public health issues. This study examined the association between the Kessler Psychological Distress Scale (K6) and low bone mass in middle-aged community-dwelling men and women. A crosssectional study was nested in a prospective observational study of 1,101 participants (median age: 57 [49-62] years in men and 58 [50-62] years in women) residing in a rural city in western Japan. Participants were recruited during medical check-ups in 2016 and 2017 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. Of the participants, 56 men (14.9%) and 144 women (19.9%) had a bone mass of less than 70% of the mean of young adults. Univariate analysis revealed that there was a trend toward lower body mass index (BMI) and higher prevalence of low bone mass with an increase in K6 scores in men but not in women. Logistic regression analysis, adjusting for possible confounders(age, BMI, smoking, drinking habits, exercise habits, diabetes, hyperlipidemia, and hypertension), showed significant associations between the K6 scores and low bone mass (odds ratio (OR) = 2.66 for the men with 5 to 12 points of K6, OR = 7.51 for men with ≥ 13 of K6, not for women). We showed an association between psychological distress and low bone mass independent of cofounders among community-dwelling middle-aged men but not women. This suggests that healthy mental health in middle-aged men may be a possible target for the prevention of consequent osteoporosis or fragile bone fractures

Ba813 harboring Bacillus cereus, genetically closely related to Bacillus anthracis, causing nosocomial bloodstream infection: Bacterial virulence factors and clinical outcome.

Bacillus cereus commonly causes catheter-related bloodstream infections (BSIs) in hospital settings, and occasionally occurs fatal central nervous system (CNS) complications. B. cereus harboring Ba813, a specific chromosomal marker of Bacillus anthracis, has been found in patients with severe infection and nosocomial BSI. However, the bacteriological profile and clinical feature of Ba813 (+) B. cereus are unclear. Fifty-three patients with B. cereus BSI were examined. Isolates were evaluated for Ba813, B. anthracis-related and food poisoning-related virulence, multilocus sequencing typing, and biofilm formation. Patients' clinical records were reviewed retrospectively. The 53 isolates were comprised of 29 different sequence types in two distinct clades. Seventeen of the 53 (32%) B. cereus isolates including five sequence types possessed Ba813 and were classified into Clade-1/Cereus-III lineage which is most closely related to Anthracis lineage. No B. cereus possessed B. anthracis-related virulence genes. Ba813 (+) strains showed a lower prevalence of enterotoxin genes than Clade-2 strains (n = 4), but no difference from Clade-1. Ba813 (+) strains showed significantly lower biofilm formation than Clade-1/non-Cereus-III (n = 22) and Clade-2 strains, respectively. Compared to Clade-1/non-Cereus-III and Clade-2 B. cereus, Ba813 (+) strains were isolated more frequently from elderly patients, patients with indwelling central venous catheter rather than peripheral venous catheter, and patients who remained in the hospital for longer before BSI onset. No significant differences in disease severity or mortality were observed. Though two of the ten Ba813 (-) strains in Clade-1/Cereus III were isolated from the patients with CNS complication, no significant difference was observed in the bacterial profile and clinical characteristics among Clade-1/Cereus III strains. In conclusion, our report suggested that Ba813-harboring B. cereus strains, genetically closely related to B. anthracis, were abundant among B. cereus strains in the hospital setting, and might cause catheter-related nosocomial BSI. However, it did not affect the clinical outcomes

Severe epidemic myalgia with an elevated level of serum interleukin-6 caused by human parechovirus type 3: a case report and brief review of the literature

Abstract Background Human parechovirus type 3 (HPeV-3) is known to cause cold-like symptoms, diarrhea, or severe infections such as sepsis in infants and children. In adults, HPeV-3 infection is rarely diagnosed because the symptoms are generally mild and self-limiting; however, this infection has been linked to epidemic myalgia, regardless of the presence of underlying diseases, immunosuppression, or sex. Case presentation We describe an adult case of severe systemic myalgia and orchiodynia after infection with HPeV-3, which was transmitted from the child of the patient. Interleukin-6 (IL-6) level was found to be elevated in the patient’s serum. Conclusion Severe myalgia associated with HPeV-3 infection is potentially caused by an elevated serum level of IL-6