An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

Usefulness of molecular biology performed with formaldehyde-fixed paraffin embedded tissue for the diagnosis of combined pulmonary invasive mucormycosis and aspergillosis in an immunocompromised patient

Immunocompromised patients who develop invasive filamentous mycotic infections can be efficiently treated if rapid identification of the causative fungus is obtained. We report a case of fatal necrotic pneumonia caused by combined pulmonary invasive mucormycosis and aspergillosis in a 66 year-old renal transplant recipient. Aspergillus was first identified during the course of the disease by cytological examination and culture (A. fumigatus) of bronchoalveolar fluid. Hyphae of Mucorales (Rhizopus microsporus) were subsequently identified by culture of a tissue specimen taken from the left inferior pulmonary lobe, which was surgically resected two days before the patient died. Histological analysis of the lung parenchyma showed the association of two different filamentous mycoses for which the morphological features were evocative of aspergillosis and mucormycosis. However, the definitive identification of the associative infection was made by polymerase chain reaction (PCR) performed on deparaffinized tissue sections using specific primers for aspergillosis and mucormycosis. This case demonstrates that discrepancies between histological, cytological and mycological analyses can occur in cases of combined mycotic infection. In this regard, it shows that PCR on selected paraffin blocks is a very powerful method for making or confirming the association of different filamentous mycoses and that this method should be made available to pathology laboratories

ICAR: endoscopic skull‐base surgery

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Prevalence of Osteoporosis in General Population above 50 Yrs of Age

Osteoporosis is currently a public health problem of major concern in Indiawhich leads to increased susceptibility to fracture. The condition clinically manifest in the form of generalized body ache, hip fracture, distal radius fracture or vertebral fractures. The level of peak bone mass is achieved by early adulthood and thereafter there is a progressive loss of bone density, roughly estimated to be around 1 per cent per year. Bone mineral density (BMD) is strongly influenced by body weight, Vitamin D levels, hormone replacement therapy sedentary life style, chronic liver disease, endocrinal disorders, smoking, excessive alcohol and caffeine intake. Dual energy X-ray absorptiometry (DEXA) is the gold standard for diagnosing osteoporosis by measuring bone density, AIMS AND OBJECTIVE The study intends to know the prevalence, distribution of osteoporosis by measurement of bone mineral density using Dual energy X-ray absorptiometry (DEXA) at L1-L5 vertebrae METHOD:  This is a prospective study in which 250 patients above 50 year of age were selected who presented with generalized body ache, backache and patients who were willing to be part of study. All patients underwent DEXA scan for estimation of bone mineral density at L1-L5 vertebrae. RESULTS:In our study 176 patients were females and 74 male. 147(58.8%) patients were aged between 50-59 years, 79(31.6%) patients were aged between 60-69 years and 24(9.6%) were above 70 years. Mean age in study was 59.6 years with age ranging from 50yrs to 81.6 years. Mean height and weight was 158.87cms and 65.46kgs respectively. Mean BMD was found to be lower in patients aged >70. Mean T score and Z score was -1.3360 and -.5509 respectively. Over all Prevalence of osteoporosis was found to be 27.2%, and that of osteopenia was 41.6%. CONCLUSION : Both sexes are equally at risk of developing osteoporosis. Risk of developing osteoporosis increases with increasing age. BMD is less in females compared to males. One of the important determinants of bone health is BMI which is directly proportional to BMD.The findings from the study suggest the need for large community‑based studies so that high‑risk population can be picked up and early interventions and other life style changes can be instituted