MUC1 positive, Kras and Pten driven mouse gynecologic tumors replicate human tumors and vary in survival and nuclear grade based on anatomical location

Activating mutations of Kras oncogene and deletions of Pten tumor suppressor gene play important roles in cancers of the female genital tract. We developed here new preclinical models for gynecologic cancers, using conditional (Cre-loxP) mice with floxed genetic alterations in Kras and Pten. The triple transgenic mice, briefly called MUC1KrasPten, express human MUC1 antigen as self and carry a silent oncogenic KrasG12D and Pten deletion mutation. Injection of Cre-encoding adenovirus (AdCre) in the ovarian bursa, oviduct or uterus activates the floxed mutations and initiates ovarian, oviductal, and endometrial cancer, respectively. Anatomical site-specific Cre-loxP recombination throughout the genital tract of MUC1KrasPten mice leads to MUC1 positive genital tract tumors, and the development of these tumors is influenced by the anatomical environment. Endometrioid histology was consistently displayed in all tumors of the murine genital tract (ovaries, oviducts, and uterus). Tumors showed increased expression of MUC1 glycoprotein and triggered de novo antibodies in tumor bearing hosts, mimicking the immunobiology seen in patients. In contrast to the ovarian and endometrial tumors, oviductal tumors showed higher nuclear grade. Survival for oviduct tumors was significantly lower than for endometrial tumors (p = 0.0015), yet similar to survival for ovarian cancer. Oviducts seem to favor the development of high grade tumors, providing preclinical evidence in support of the postulated role of fallopian tubes as the originating site for high grade human ovarian tumors. © 2014 Tirodkar et al

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Women’s Reproductive Health in Slum Populations in India: Evidence From NFHS-3

The urban population in India is one of the largest in the world. Its unprecedented growth has resulted in a large section of the population living in abject poverty in overcrowded slums. There have been limited efforts to capture the health of people in urban slums. In the present study, we have used data collected during the National Family Health Survey-3 to provide a national representation of women’s reproductive health in the slum population in India. We examined a sample of 4,827 women in the age group of 15–49 years to assess the association of the variable slum with selected reproductive health services. We have also tried to identify the sociodemographic factors that influence the utilization of these services among women in the slum communities. All analyses were stratified by slum/non-slum residence, and multivariate logistic regression was used to analyze the strength of association between key reproductive health services and relevant sociodemographic factors. We found that less than half of the women from the slum areas were currently using any contraceptive methods, and discontinuation rate was higher among these women. Sterilization was the most common method of contraception (25%). Use of contraceptives depended on the age, level of education, parity, and the knowledge of contraceptive methods (p < 0.05). There were significant differences in the two populations based on the timing and frequency of antenatal visits. The probability of ANC visits depended significantly on the level of education and economic status (p < 0.05). We found that among slum women, the proportion of deliveries conducted by skilled attendants was low, and the percentage of home deliveries was high. The use of skilled delivery care was found to be significantly associated with age, level of education, economic status, parity, and prior antenatal visits (p < 0.05). We found that women from slum areas depended on the government facilities for reproductive health services. Our findings suggest that significant differences in reproductive health outcomes exist among women from slum and non-slum communities in India. Efforts to progress towards the health MDGs and other national or international health targets may not be achieved without a focus on the urban slum population