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Role of RHO GTPases and Bone Morphogenetic Proteins in Breast Cancer Metastasis Renu Sharma, Bithiah Grace Jaganathan Breast cancer is the most common cancer in women. The incidence of breast cancer increases with age and this is true in India like rest of the world. Around 70% of all patients living with advanced breast cancer have bone metastasis. Metastasis involves a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body. With an osteolytic metastasis, the cancer cells promote severe bone loss significantly increasing the risk of bone fractures. Matrix metalloproteinase (MMPs), Bone Morphogenetic proteins (BMPs), Ras homolog gene family member A (RHOA) and other factors like (Ras-related C3 botulinum toxin substrate) Rac1, Tissue inhibitor of metalloproteinase (TIMPS) are key factors for metastasis. MMPs are endopeptidase which has ability to degrade extracellular matrix protein and over-expression is associated with invasion and metastasis. In this study, four model breast cancer cell lines MDA-MB-231 (ER- PR- HER2-), T-47D (ER+ PR+ HER2-), MCF- 7 (ER+ PR+ HER2-) and Sk-Br-3 (ER- PR- HER2+) were used. We found that breast cancer cells express high RHOA in the periphery of the tumor suggesting their role in metastasis. All the three GTPases of RHO family, RHOA, RAC1 and CDC42 were expressed in both mRNA and transcript levels and significant levels of active form was seen in the breast cancer cell lines. The bone marrow derived factors increase the migration of metastatic cell line MDA-MB and RHOA activity regulates migration in a context dependent manner. RHOA and mitochondria were localized in the migratory front in metastatic breast cancer cells. High levels of MMPs were observed in all breast cancer cells and it was considerably high in TNBC samples. High levels of anti-apoptotic and stem cell self-renewal genes were expressed in TNBC samples. Both the secreted factors and the breast cancer cells themselves inhibit the differentiation of bone cells, osteoblasts. Metastatic MDA-MB cells showed higher resistance to cell death during adherence independent culture. We are studying the signaling pathways that are regulated by Rho GTPases and understanding the role of Rho GTPases in metastasis will help in identifying novel targets to inhibit breast cancer metastasis. [ABSTRACT FROM AUTHOR]

In this study, comparative analysis of skeletal muscle transcriptome was carried out for four biological replicates of Aseel, a fighter type breed and Punjab Brown, a meat type breed of India. The profusely expressed genes in both breeds were related to muscle contraction and motor activity. Differential expression analysis identified 961 up-regulated and 979 down-regulated genes in Aseel at a threshold of log2 fold change ≥ ±2.0 (padj<0.05). Significantly enriched KEGG pathways in Aseel included metabolic pathways and oxidative phosphorylation, with higher expression of genes associated with fatty acid beta-oxidation, formation of ATP by chemiosmotic coupling, response to oxidative stress, and muscle contraction. The highly connected hub genes identified through gene network analysis in the Aseel gamecocks were HNF4A, APOA2, APOB, APOC3, AMBP, and ACOT13, which are primarily associated with energy generating metabolic pathways. The up-regulated genes in Punjab Brown chicken were found to be related to muscle growth and differentiation. There was enrichment of pathways such as focal adhesion, insulin signaling pathway and ECM receptor interaction in these birds. The results presented in this study help to improve our understanding of the molecular mechanisms associated with fighting ability and muscle growth in Aseel and Punjab Brown chicken, respectively. [ABSTRACT FROM AUTHOR]

DOCK8 deficiency affects various cell subsets belonging to both the innate and adaptive immune systems. Clinical diagnosis is challenging, as many cases present with severe atopic dermatitis as the only initial manifestation. Though flow cytometry helps in the presumptive diagnosis of DOCK8‐deficient patients by evaluating their DOCK8 protein expression, it requires subsequent confirmation by molecular genetic analysis. Currently, haematopoietic stem cell transplantation (HSCT) is the only curative treatment option available for these patients. There is a paucity of data from India on the clinical diversity and molecular spectrum of DOCK8 deficiency. In the present study, we report the clinical, immunological and molecular findings of 17 DOCK8‐deficient patients from India diagnosed over the last 5 years. [ABSTRACT FROM AUTHOR]

The article presents abstracts of medical research concerning maternal medicine. They include "Outcome of women with cardiac disease undergoing first and second trimester elective abortions: A ten year experience from a tertiary care center in North India," "Smoking habits during pregnancy - What are women told and what do they remember?" and "Screening for anemia in the post partum period in low risk women - is it worthwhile?"

Background: Pancoast tumors represent a subset of bronchial carcinomas that occur in the apex of the lung and frequently invade the first two or three ribs, the nearby vertebral bodies and the lower part of the brachial plexus, the subclavian vessels and the stellate ganglion. These tumors present radiologically as homogeneous shadows of the extreme apex with local rib destruction and vertebral infiltration. However, infection as a cause for Pancoast tumor is rare. Tuberculosis continues to be a health problem despite efforts at eradication and control and a total of 9.2 million cases of tuberculosis are reported worldwide annually. Pulmonary tuberculosis exhibits variable radiological findings, mimicking all the other pathological conditions of the lung and present clinical difficulties for diagnosis. Bacterial pneumonias, fungal infections, and bronchogenic carcinoma are such common diseases which mimic Tuberculosis because of non-specific symptoms and similar radiological findings. Overreliance on clinical findings and imaging may lead to misdiagnosis. We present a case of Pancoast tumor which on investigations turned out to be tubercular. Case Details A 45 year old male smoker patient presented to the hospital with complaints of right sided chest pain radiating to right arm since one month. There was no history of parasthesia. General and local examination was unremarkable. No signs suggestive of Horner's syndrome were observed. Chest radiograph showed a mass lesion right upper zone. Contrast enhanced computed tomography showed mass in right upper lobe infiltrating into adjacent tracheal and mediastinal plane. CT guided Fine Needle Aspiration was done which showed Langerhans giant cells in a necrotic background. ZN staining for AFB was positive. A probable diagnosis of TB was made. Patient was advised CT guided biopsy/ Thoracoscopic biopsy for a more definitive diagnosis but he denied any further investigations and was lost to follow-up. Conclusions: This case report demonstrates that tuberculosis can mimic many other pathological conditions of lung and should be kept in mind as a differential diagnosis of thoracic lesions especially in an endemic country like India. However, malignant tumors always have to be confirmed by histologic examination since coexistence of tuberculosis and malignancy has been reported in literature. [ABSTRACT FROM AUTHOR]