Squamous Cell Cancers: A Unified Perspective on Biology and Genetics.

Squamous cell carcinomas (SCCs) represent the most frequent human solid tumors and are a major cause of cancer mortality. These highly heterogeneous tumors arise from closely interconnected epithelial cell populations with intrinsic self-renewal potential inversely related to the stratified differentiation program. SCCs can also originate from simple or pseudo-stratified epithelia through activation of quiescent cells and/or a switch in cell-fate determination. Here, we focus on specific determinants implicated in the development of SCCs by recent large-scale genomic, genetic, and epigenetic studies, and complementary functional analysis. The evidence indicates that SCCs from various body sites, while clinically treated as separate entities, have common determinants, pointing to a unified perspective of the disease and potential new avenues for prevention and treatment

Suppression of MHC class I antigen expression by N-myc through enhancer inactivation

Amplification of the N-myc oncogene in human neuroblastoma is associated with increased metastatic ability. We previously found that over-expression of N-myc in rat neuroblastoma tumor cells causes a dramatic reduction in the expression of MHC class I mRNA. We show here that two distinct elements in the promoter render the MHC class I genes susceptible to N-myc-mediated suppression, one of which was identified as the MHC class I gene enhancer. Our data indicate that elevated N-myc expression is associated with reduced binding of a transcription factor that activates this enhancer. As a result, the activity of the MHC class I gene enhancer is greatly diminished. Elevated expression of the N-myc oncogene in human neuroblastomas and murine pre-B lymphoid lines also correlated with reduced factor binding to the MHC class I gene enhancer. Thus, an important effect of N-myc may be to impair the function of certain cellular enhancers by altering the levels of their cognate binding proteins

Pulmonary perfusion after rt-PA therapy for acute pulmonary embolism: early improvement assessed with segmental perfusion scanning

Year Book of Nuclear Medicin

ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis

BACKGROUND: The plasticity of pancreatic acinar cells to undergo acinar to ductal metaplasia (ADM) has been demonstrated to contribute to the regeneration of the pancreas in response to injury. Sox9 is critical for ductal cell fate and important in the formation of ADM, most likely in concert with a complex hierarchy of, as yet, not fully elucidated transcription factors. RESULTS: By using a mouse model of acute pancreatitis and three dimensional organoid culture of primary pancreatic ductal cells, we herein characterize the Ets-transcription factor Etv5 as a pivotal regulator of ductal cell identity and ADM that acts upstream of Sox9 and is essential for Sox9 expression in ADM. Loss of Etv5 is associated with increased severity of acute pancreatitis and impaired ADM formation leading to delayed tissue regeneration and recovery in response to injury. CONCLUSIONS: Our data provide new insights in the regulation of ADM with implications in our understanding of pancreatic homeostasis, pancreatitis and epithelial plasticity