Progression and Metastasis of Lung Cancer - A Study of Predominant Cellular Interactions in Tumor Microenvironment.

The heterotypic view of cancer envisions solid tumors as ecosystems consisting of abnormal epithelial tumor cells and a plethora of cell types collectively referred to as stromal cells. In these ecosystems, innate immune cells are highly represented and most abundant among these are macrophages. Macrophages commonly designated as Tumor associated macrophages (TAMs) in the tumor microenvironment, originate from circulating pool of monocytes and play a critical role in orchestrating and promoting tumor growth. The acquisition of tumorigenic properties by TAMs relies upon a complex interplay between them and tumor cells. In this study, we demonstrated through co-culture experiments that such properties of TAMs are shaped up by the tumor-derived secretory signals which favor their tumor promoting phenotypes. Co-culture of model human monocytes (THP-1) with model human lung carcinoma cells (A549) enabled THP-1 cells to secrete tumor-promoting cytokines and therefore enhanced proliferation, migration and invasiveness of A549 cells. We demonstrated that A549 cells consistently secrete EDA-containing Fibronectin that mediates the pro-inflammatory response from THP-1 monocytes in a paracrine manner.Digital copy of Thesis.University of Kashmir

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Posterolateral thoracotomy complicating paraplegia

Paraplegia complicating thoracotomy has been reported in literature in mid forties. However in sufficient data are available about the incidence of such a catastrophic complication. In the present study five cases of paraplegia following thoracotomy are presented. Pneumonectomy, lobectomy for bronchogenic carcinoma decortication for tubercular empyemas and thoracotomy for ductus ligation constituted one, one, two and one patient respectively. Two patients died in post operative period, two died in follow up and one patient is still on follow for the last twelve years.Department of Cardiovascular and Thoracic Surgery SKIMS, Soura, Srinaga