Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to co-transfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity

Posttransplant Solid Organ Malignancies in Lung Transplant Recipients: A Single-center Experience and Review of the Literature

Purpose: Solid-organ tumor incidences are higher in solid organ transplant patients than in the general population. The aim of this study was to analyze solid-organ tumor frequency and characteristics in a population of lung transplant patients and provide a brief review of the literature. Methods: A retrospective analysis was conducted of all patients who underwent a lung transplant in the Lung Transplant Program at the University Hospital of Siena, Italy, from 2001 to 2014 (n = 119). Patients' demographics, pretransplant characteristics, immunosuppressive therapy, and infectious factors were recorded. Results: Nine patients with a median age of 59.0 years (range 50-63) of our cohort developed a solid-organ tumor (7.5%). Most of the patients experienced nonmelanoma skin cancer (44.4%); the others were diagnosed with lung cancer (22.2%), breast cancer (22.2%), and colon-rectal cancer (11.2%). The median time from transplantation to tumor diagnosis was 895.0 days (range 321-2046). No differences in pretransplant characteristics, immunosuppressive therapy, or infectious factors were found between patients who developed solid organ tumors and those who did not. Conclusions: The present study confirmed that de novo malignancies are a major issue in lung transplant patients; in particular, skin and lung cancers demonstrated a higher incidence rate. Oncologic treatment of these patients is complex, requiring close collaboration between the transplant team and oncologist. Strict screening programs are key factors for an early diagnosis and to allow for prompt treatment resulting in a better outcome