Regulation of endothelial cell plasticity by TGF-β

Recent evidence has demonstrated that endothelial cells can have a remarkable plasticity. By a process called Endothelial-to-Mesenchymal Transition (EndMT) endothelial cells convert to a more mesenchymal cell type that can give rise to cells such as fibroblasts, but also bone cells. EndMT is essential during embryonic development and tissue regeneration. Interestingly, it also plays a role in pathological conditions like fibrosis of organs such as the heart and kidney. In addition, EndMT contributes to the generation of cancer associated fibroblasts that are known to influence the tumor-microenvironment favorable for the tumor cells. EndMT is a form of the more widely known and studied Epithelial-to-Mesenchymal Transition (EMT). Like EMT, EndMT can be induced by transforming growth factor (TGF)-β. Indeed many studies have pointed to the important role of TGF-β receptor/Smad signaling and downstream targets, such as Snail transcriptional repressor in EndMT. By selective targeting of TGF-β receptor signaling pathological EndMT may be inhibited for the therapeutic benefit of patients with cancer and fibrosis

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Review Article - Positron Emission Tomography imaging in Evaluation of Cancer Patients

Positron emission tomography (PET) is a diagnostic imaging technique that has progressed rapidly from being a research technique in laboratories to a routine clinical imaging modality. The most widely used radiotracer in PET is Fluorine18-fluorodeoxyglucose (F18-FDG), which is an analogue of glucose. The FDG uptake in cells is directly proportional to glucose metabolism of cells. Since glucose metabolism is increased many fold in malignant tumors PET has a high sensitivity and a high negative predictive value. PET with FDG is now the standard of care in initial staging, monitoring the response to the therapy, and management of lung cancer, colonic cancer, lymphoma, melanoma, esophageal cancer, head and neck cancer and breast cancer. Other indications of PET like bone tumor, ovarian cancer and cancer of unknown primary (CUP) has also been discussed in brief. The aim of this review article is to review the clinical applications of PET in various malignancies and only limited number of important studies will be discussed for this effort

Positron emission tomography imaging in evaluation of cancer patients

Positron emission tomography (PET) is a diagnostic imaging technique that has progressed rapidly from being a research technique in laboratories to a routine clinical imaging modality. The most widely used radiotracer in PET is Fluorine18-fluorodeoxyglucose (F18-FDG), which is an analogue of glucose. The FDG uptake in cells is directly proportional to glucose metabolism of cells. Since glucose metabolism is increased many fold in malignant tumors PET has a high sensitivity and a high negative predictive value. PET with FDG is now the standard of care in initial staging, monitoring the response to the therapy, and management of lung cancer, colonic cancer, lymphoma, melanoma, esophageal cancer, head and neck cancer and breast cancer. Other indications of PET like bone tumor, ovarian cancer and cancer of unknown primary (CUP) has also been discussed in brief. The aim of this review article is to review the clinical applications of PET in various malignancies and only limited number of important studies will be discussed for this effort

Fibroblasts in Kidney Fibrosis Emerge via Endothelial-to-Mesenchymal Transition

Fibroblasts are key mediators of fibrosis in the kidney and other organs, but their origin during fibrosis is still not completely clear. Activated fibroblasts likely arise from resident quiescent fibroblasts via epithelial-to-mesenchymal transition and from the bone marrow. Here, we demonstrate that endothelial cells also contribute to the emergence of fibroblasts during kidney fibrosis via the process of endothelial-to-mesenchymal transition (EndMT). We examined the contribution of EndMT to renal fibrosis in three mouse models of chronic kidney disease: (1) Unilateral ureteral obstructive nephropathy, (2) streptozotocin-induced diabetic nephropathy, and (3) a model of Alport renal disease. Approximately 30 to 50% of fibroblasts coexpressed the endothelial marker CD31 and markers of fibroblasts and myofibroblasts such as fibroblast specific protein-1 and α-smooth muscle actin. Endothelial lineage tracing using Tie2-Cre;R26R-stop-EYFP transgenic mice further confirmed the presence of EndMT-derived fibroblasts. Collectively, our results demonstrate that EndMT contributes to the accumulation of activated fibroblasts and myofibroblasts in kidney fibrosis and suggest that targeting EndMT might have therapeutic potential