Histone Deacetylase Inhibitor Therapy in Epithelial Ovarian Cancer

Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in a variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21WAF1 gene in human ovarian carcinoma cells. In xenograft models, some of HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for ovarian cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on preclinical studies and clinical trials

Growth rates, relative growth and a potential aging method using vertebral centra in Silurus biwaensis(Siluriformes: Siluridae)

Relative growth and relationship between age and growth in Silurus biwaensis were examined on the basis of the body size data of the catfish collected from Lake Biwa and the reared catfish which were hatched from artificially inseminated eggs. Although it had been reported that the proportion of head length to body length increased with growth in S. biwaensis, such a relationship was not found for 218 catfish that were examined in this study. On the other hand, the proportion of head length to head width significantly decreased with SL in females. This result indicated that the narrow head shape peculiar to S. biwaensis becomes slightly squarer in bigger females. The three catfish reared from the hatching grew to 196-410mm SL for 2.7 years (73-152mm/yr). This growth rate was in contrast with that of a tagged adult male, which grew only 50mm from 460mm SL to 510mm SL in the lake for two years (25mm/yr). These results suggested that the growth of the adults might extremely slow down after the fast growth at the immature stage. This study also reported that the number of transparent zones in vertebral centra of S. biwaensis increased with growth. The vertebral centrum may possibly be utilized as an age indicator for this species and the other kinds of Silurid

Outcomes after stereotactic body radiotherapy for lung tumors, with emphasis on comparison of primary lung cancer and metastatic lung tumors

BACKGROUND: The goal of this study was to determine the prognostic factors associated with an improved overall outcome after stereotactic body radiotherapy (SBRT) for primary lung cancer and metastatic lung tumors. METHODS: A total of 229 lung tumors in 201 patients were included in the study. SBRT of 45 Gy in 3 fractions, 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions was typically used to treat 172 primary lungs cancer in 164 patients and 57 metastatic lung tumors in 37 patients between January 2001 and December 2011. Prognostic factors for local control (LC) and overall survival (OS) were analyzed using a Cox proportional hazards model. RESULTS: The median biologically effective dose was 105.6 Gy based on alpha/beta = 10 (BED10). The median follow-up period was 41.9 months. The 3-year LC and OS rates were 72.5% and 60.9%, and the 5-year LC and OS rates were 67.8% and 38.1%, respectively. Radiation pneumonitis of grades 2, 3 and 5 occurred in 22 petients, 6 patients and 1 patient, respectively. Multivariate analyses revealed that tumor origin (primary lung cancer or metastatic lung tumor, p < 0.001), tumor diameter (p = 0.005), BED10 (p = 0.029) and date of treatment (p = 0.011) were significant independent predictors for LC and that gender (p = 0.012), tumor origin (p = 0.001) and tumor diameter (p < 0.001) were significant independent predictors for OS. CONCLUSIONS: SBRT resulted in good LC and tolerable treatment-related toxicities. Tumor origin and tumor diameter are significant independent predictors for both overall survival and local control

Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis

Background: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH. Methods: Twelve newborn C57BL/6 J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured. Results: Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 μmol/L, P = 0.001). Conclusions: FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production

Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery

Small cell carcinoma of the uterine cervix is a rare form of cervical cancer characterized by extreme aggressiveness and poor prognosis because of its rapid growth, frequent distant metastases, and resistance to conventional treatment modalities. We report here a case of advanced-stage small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy, followed by radical surgery, resulting in locoregional disease control. A 39-year-old Japanese woman was diagnosed as having stage IIIb small cell carcinoma of the uterine cervix. She was treated by neoadjuvant chemotherapy with irinotecan/cisplatin, followed by extended radical hysterectomy with pelvic and paraaortic lymphadenectomy. The patient was further treated by adjuvant chemotherapy with irinotecan/cisplatin. Intrapelvic recurrence has not been detected throughout the postoperative course. However, the patient died with distant metastases of the disease, 27 months following the initial treatment. It has been suggested that neoadjuvant chemotherapy therapy followed by radical surgery is a treatment option for advanced-stage small cell carcinoma of the uterine cervix for the locoregional disease control. Further studies are necessary to obtain information regarding multimodal treatment including sequence, duration, frequency, and type of effective chemotherapy agents to be used in the treatment of small cell carcinoma of the uterine cervix

Seasonal change in the diet of Adélie Penguins: insight from stable-isotope analysis

第2回極域科学シンポジウム/第33回極域生物シンポジウム 11月17日（木） 統計数理研究所 3階リフレッシュフロ

Structure of marine ecosystem under fast sea-ice: insight from stable-isotope analysis

第3回極域科学シンポジウム/第34回極域生物シンポジウム 11月26日（月） 統計数理研究所 ３階セミナー