Genetics of Endometrial Cancers

Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A β-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas

Angiomyolipoma of the tunica dartos of the scrotum in infancy

AbstractA 12-month-old boy presented with left scrotal swelling. The mass was irregular, soft, fleshy, and nontender. It adhered to the scrotal skin and gradually enlarged. Operative findings revealed a mass fixed to the scrotal fundus and diagnosed as angiomyolipoma. This is apparently the first report of scrotal angiomyolipoma in infancy

Hospital pharmacist intervention improves the quality indicator of warfarin control : A retrospective cohort study

Background/Aims Our previous study showed that time in therapeutic range (TTR) control of warfarin therapy was negatively affected in non-valvular atrial fibrillation (NVAF) patients with heart failure. This study assesses the effect of intervention byhospital pharmacists on TTR control in Japanese NVAF patients with heart failure. Method This retrospective cohort study included NVAF patients with heart failure admitted and discharged from the cardiovascular internal medicine ward between March 2011 and July 2013. Participants were classified into two groups according to the instructions by hospital pharmacists and physicians (Intervention group) and by physicians only (Usual care group). The primary outcome was TTR. Secondary outcomes were major bleeding and minor bleeding. Results In total, 57 participants (35males, 22 females ; mean age : 69.7 years) were classified into the Intervention (n = 25) and Usual care (n = 32) groups. TTR within-therapeutic range was significantly higher and within sub-therapeutic range was significantly lower in the Intervention than the Usual care group. Major bleeding and minor bleeding were not significantly different between the two groups. Conclusion The intervention of hospital pharmacists with anticoagulation therapy can lead to proper use of warfarin, which can be useful when physicians prescribe warfarin

Disease history and risk of comorbidity in women's life course : a comprehensive analysis of the Japan Nurses’ Health Study baseline survey

Objective: To classify diseases based on age at peak incidence to identify risk factors for later disease in women’s life course. Design: A cross-sectional baseline survey of participants in the Japan Nurses’ Health Study. Setting: A nationwide prospective cohort study on the health of Japanese nurses. The baseline survey was conducted between 2001 and 2007 (n=49 927). Main outcome measures: Age at peak incidence for 20 diseases from a survey of Japanese women was estimated using the Kaplan-Meier method with the Kernel smoothing technique. The incidence rate and peak incidence for diseases whose peak incidence occurred before the age of 45 years or before the perimenopausal period were selected as early-onset diseases. The OR and 95% CI were estimated to examine the risk of comorbidity between early-onset and other diseases. Results: Four early-onset diseases (endometriosis, anaemia, migraine headache and uterine myoma) were significantly correlated with one another. Late-onset diseases significantly associated (OR>2) with early-onset diseases included comorbid endometriosis with ovarian cancer (3.65 (2.16 to 6.19)), endometrial cancer (2.40 (1.14 to 5.04)) and cerebral infarction (2.10 (1.15 to 3.85)); comorbid anaemia with gastric cancer (3.69 (2.68 to 5.08)); comorbid migraine with transient ischaemic attack (3.06 (2.29 to 4.09)), osteoporosis (2.11 (1.71 to 2.62)), cerebral infarction (2.04 (1.26 to 3.30)) and angina pectoris (2.00 (1.49 to 2.67)); and comorbid uterine myoma with colorectal cancer (2.31 (1.48 to 3.61)). Conclusions: While there were significant associations between four early-onset diseases, women with a history of one or more of the early-onset diseases had a higher risk of other diseases later in their life course. Understanding the history of early-onset diseases in women may help reduce the subsequent risk of chronic diseases in later life

Dependence of alkyl-substituent length for bulk heterojunction solar cells utilizing 1,4,8,11,15,18,22,25-octaalkylphthalocyanine

Tetsuro Hori, Yasuo Miyake, Tetsuya Masuda, Takeshi Hayashi, Kaoru Fukumura, Hiroyuki Yoshida, Akihiko Fujii, Masanori Ozaki, and Yo Shimizu "Dependence of alkyl-substituent length for bulk heterojunction solar cells utilizing 1,4,8,11,15,18,22,25-octaalkylphthalocyanine," Journal of Photonics for Energy 2(1), 021004 (2 March 2012). DOI: https://doi.org/10.1117/1.JPE.2.02100

A Role of Suppressor of Cytokine Signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated Interleukin 2 Production

Suppressor of cytokine signaling (SOCS)3 has been characterized as a negative feedback regulator in cytokine-mediated Janus kinase signal transducer and activator of transcription signaling. However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T cells are costimulated with CD28. Decreased protein expression in SOCS3+/− mice enhanced CD28-mediated IL-2 production, clearly indicating the correlation between expression level of SOCS3 and IL-2 production ability. The SOCS3 protein interacted with phosphorylated CD28 through its SH2 domain but not the kinase inhibitory region. In addition, a point mutation in the SOCS3 SH2 domain attenuated the inhibition of CD28 function in IL-2 promoter activation. Committed T helper (Th)2 cells exclusively expressed SOCS3 and production of Th2 cytokines, such as IL-4 and IL-5, was much less dependent on CD28 costimulation compared with interferon γ and IL-2 production in Th1 cells. Consistent with this notion, the expression level of SOCS3 in early T cell activation influenced the ability of IL-2 production induced by CD28 costimulation. Therefore, the SOCS3 may play an alternative role in prohibiting excessive progression of CD28-mediated IL-2 production