Overexpression of DNA Polymerase ζAffects Cisplatin Resistance in Ovarian Cancer: An Immunohistochemical Study

DNA polymerase ζ (Pol ζ) participates in translesional bypass replication. Pol ζ has been shown to be an important contributor to cis-diamminedichloroplatinum (II)(DDP; cisplatin) -induced genomic instability and the subsequent emergence of resistance in vitro. We immunohistochemically examined the expression of Pol ζ in ovarian cancer tissues to determine whether its expression affects the DDP resistance of human ovarian cancers and also to determine whether Pol ζ expression is a prognostic factor for ovarian cancers. We assessed 76 archival, formalin-fixed, paraffin-embedded tissue samples obtained from patients with epithelial ovarian cancers who underwent their first operation between 2003 and 2011. An ovarian cancer tissue array was also used in this study. Immunohistochemical staining of Pol ζ was performed using an anti-human Pol ζ monoclonal rabbit antibody. The strength of expression of Pol ζ was compared with the DDP resistance and clinical features of the study population. The Pol ζ over-expression in ovarian cancer tissue which compared with epithelial cells in normal ovaries was not affected by the histological types, FIGO stage, or patient age, but Pol ζ was significantly more overexpressed in the DDP-resistant group than in the DDP-sensitive group (P = 0.043). Pol ζ over-expression did not significantly affect the survival rate of the ovarian cancer patients; however, the Pol ζ positive group tended to have a poorer long-term prognosis. In conclusion, ovarian carcinoma patients with Pol ζ over-expression are likely to be resistant to DDP, especially in cases of recurrent disease. These results confirm the previous findings in vitro, wherein Pol ζ modulated the cytotoxicity and mutagenicity of DDP

Observational Studies on the Association Between Post-diagnostic Metformin Use and Survival in Ovarian Cancer: A Systematic Review and Meta-Analysis

Objectives: To summarize and quantify the relationship between post-diagnostic metformin use and ovarian cancer (OC) survival.Methods: We systematically conducted an updated meta-analysis based on observational studies published up to December 31, 2018, identified from PubMed and Web of Science. Two team members independently extracted data and assessed the quality of each study. Summary Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a random-effects model.Results: Five cohort studies including 3,582 OC patients were included. All studies were graded as low risk of bias according to the Newcastle-Ottawa quality assessment scale. Post-diagnostic metformin use was associated with improved overall survival (summarized HR = 0.42, 95% CI = 0.31–0.56; I2 = 0%, P = 0.842) and progression-free survival (summarized HR = 0.69, 95% CI = 0.45–1.07; I2 = 61.9%, P = 0.049) of OC patients. For OC patients with diabetes, post-diagnostic metformin use was associated with improved overall survival (summarized HR = 0.51, 95% CI = 0.28–0.95; I2 = 47.6%, P = 0.149) and progression-free survival (summarized HR = 0.38, 95% CI = 0.27–0.55; I2 = 0%, P = 0.594). No significant publication bias was detected in these analyses.Conclusions: Post-diagnostic metformin use is consistently associated with better survival of OC patients regardless of diabetes status. Studies with larger sample sizes and prospective designs are required to confirm these findings and obtain detailed information, including standardized references for comparison, intensity and dose of metformin use, and further adjustment for potential confounders

Development of a High-intensity Focused Ultrasound Exposure Device for Reducing Skin Burn Risk

High-intensity focused ultrasound（HIFU）can non-invasively irradiate inside the body. However, when used to treat fetuses, it can cause thermal burns of the mother’s abdominal wall at the skin interface. This study was carried out to determine whether a modified HIFU transducer enabling split-aperture irradiation can prevent thermal burns. Two HIFU transducers were compared: a conventional transducer using full-aperture irradiation and a modified transducer using split-aperture irradiation. The modified transducer was divided into six sectors for split-aperture irradiation and had a larger surface area and a smaller F number（focal length/aperture diameter）than the conventional transducer. HIFU was delivered to eight sites on the left and right leg of a three-month-old baby pig under general anesthesia, and the sites were assessed for thermal burning by two or more dermatologists. The same person performed all irradiations. Full-aperture irradiation with the conventional transducer caused deep dermal burns at all target sites, while split-aperture irradiation with the modified transducer caused only epidermal burns or superficial dermal burns. Split-aperture irradiation using a modified HIFU transducer with six sectors and a smaller F number reduces the severity of skin burns, and thus will improve the safety of HIFU therapy

A Pilot Study for the Detection of Protozoa Infections of the Gut at Autopsy

In order to investigate the incidence of latent infections by parasites within the human digestive tract, we examined fresh stool samples from the colon of 31 patients (37-90 years, median age 71; 26 men and 5 women) collected within 12 hours of death. These subjects had been admitted to a university hospital in Yokohama, Japan, and died between April 2007 and December 2008 from causes other than parasitosis. Stool samples were fixed and stained for microscopic analysis, and PCR analysis for Entamoeba histolytica was performed for the parasite-positive samples. Results showed that ten out of 31 subjects were infected by E. histolytica only, one subject was infected by Giardia intestinalis only, and four subjects were infected by both E. histolytica and G. intestinalis. These findings are in contrast to conventional theories concerning general parasite infection in Japan, and indicate continuous or latent infection within the human digestive tract. The presence of pathogens such as E. histolytica and G. intestinalis in elderly or immuno-compromised patients is a serious issue and warrants further attention as a public health issue, particularly in relation to its mode of transmission

Poly ADP-ribose Polymerase (PARP) Staining for Immunohistological Investigation of Primary Breast Cancer

Given that clinical trials of poly ADP-ribose polymerase (PARP) 1 inhibitors are underway, in the present study we investigated the prevalence of triple-negative breast cancer and PARP1 expression in patients with primary invasive breast cancer. Immunohistological studies plus PARP staining were performed on samples from 206 primary breast cancer patients undergoing surgery at Showa University Hospital between January 2010 and May 2011. Fifteen patients (7.3%) were found to have triple-negative breast cancer. Hormone receptor-positive patients were significantly more likely to be PARP1 negative. There were no PARP1-negative patients in the triple-negative group. However, there was no significant difference in the rate of PARP1 negativity between patients with triple-negative breast cancer and those with other breast cancer subtypes. There were no PARP1-negative patients in the triple-negative breast cancer group. Given that the effectiveness of PARP inhibitors has not been sufficiently established in clinical trials, a more in-depth analysis is required to determine the factors contributing to effective treatment. Future studies should include more subjects with triple-negative breast cancer and those with BRCA mutations

Mast Cell Infiltration is Associated with Myelofibrosis and Angiogenesis in Myelodysplastic Syndromes

Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by persistent peripheral cytopenia with morphological and functional abnormalities of hematopoietic cells. Mast cells infiltrate into or around tumor tissues and play a role in remodeling of the stromal microenvironment, contributing to tumor progression. Increased mast cell numbers are associated with fibrosis, angiogenesis and a poor prognosis in human carcinomas. The aim of this study was to determine whether mast cell infiltration contributes to myelofibrosis or angiogenesis in myelodysplastic syndromes. We evaluated the correlation between mast cell density and the extent of myelofibrosis and angiogenesis in myelodysplastic syndromes. Fifty bone marrow biopsies taken from patients with a diagnosis of myelodysplastic syndromes were examined. Grading of myelofibrosis was evaluated by silver impregnation staining. Mast cell density and microvessel density were evaluated by immunohistochemistry. Human mast cells have been divided into two phenotypes. We designated a tryptase-positive mast cell as MCT and a chymase-positive mast cell as MCTC. Microvessels were identified by CD34-positive endothelial cells. Microvessel density and the extent of myelofibrosis were significantly greater in patients with high MCT and MCTC density compared to those with low MC density. Based on this, we suggest that the presence of high mast cell numbers is associated with myelofibrosis and angiogenesis in myelodysplastic syndromes

Problems in the Pathological Diagnosis and Intraoperative Rapid Diagnosis of Mucinous Tumor of the Ovary

The pathological (histological and cytological) diagnosis of mucinous ovarian tumors presents the following problems: 1) conflicting definitions of borderline tumors, intraepithelial carcinoma and microinvasive carcinoma, 2) mural nodules within mucinous cystic tumors, 3) differential diagnosis in primary vs. metastatic mucinous tumors, and 4) difficulties in the intraoperative rapid diagnosis of mucinous ovarian tumors. Mucinous adenocarcinomas may include benign and/or borderline tumor components in other areas of the tumor. Therefore for pathological diagnosis, the sampling of these tumors must include up to one histological section per 1 to 2cm of tumor diameter as well as sampling of any suspicious lesions (multilocular and solid areas including mural nodules). The most important differential diagnosis for mucinous ovarian carcinoma is metastatic mucinous carcinoma. Histological findings from metastatic mucinous carcinoma from the appendix, large intestine, stomach, pancreas, and cervix are similar. In general, immunohistological staining, such as cytokeratin 7 (CK7) and CK20, is necessary to determine the origin of the cancer. False-negative diagnoses from frozen sections can occur due to limited sampling, as only a few frozen sections (1 or 2 in our hospital) can be taken from each tumor. Cytological specimens (scrape or imprint smears) which are sampled from any suspicious lesions or from almost all cut surfaces of the tumors can facilitate intraoperative rapid diagnosis of mucinous ovarian tumor

Estimation of Interest Levels From Behavior Features via Tensor Completion Including Adaptive Similar User Selection

A method for estimating interest levels from behavior features via tensor completion including adaptive similar user selection is presented in this paper. The proposed method focuses on a tensor that is suitable for data containing multiple contexts and constructs a third-order tensor in which three modes are "products", "users" and "user behaviors and interest levels" for these products. By complementing this tensor, unknown interest level estimation of a product for a target user becomes feasible. For further improving the estimation performance, the proposed method adaptively selects similar users for the target user by focusing on converged estimation errors between estimated interest levels and known interest levels in the tensor completion. Furthermore, the proposed method can adaptively estimate the unknown interest from the similar users. This is the main contribution of this paper. Therefore, the influence of users having different interests is reduced, and accurate interest level estimation can be realized. In order to verify the effectiveness of the proposed method, we show experimental results obtained by estimating interest levels of users holding books