Neoadjuvant Gastric Score: How Response to Neoadjuvant Chemotherapy Affects Overall Survival and Adjuvant Benefit.

Introduction: The Neoadjuvant Rectal score (NAR) was developed as a short-term surrogate for 5-year overall survival (OS) prediction in locally advanced rectal cancer on the basis of response to neoadjuvant therapy. We aim to assess whether this score can be repurposed for locally advanced gastric adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection.

Methods: Patients with gastric adenocarcinoma treated with neoadjuvant systemic therapy followed by surgical resection were extracted from the National Cancer Database.

Loss of CDKN2A Cooperates with WWTR1(TAZ)-CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma.

Purpose: Epithelioid hemangioendothelioma (EHE) is a vascular sarcoma caused by the WWTR1(TAZ)-CAMTA1 (TC) gene fusion. This fusion gene has been observed in almost all reported EHE cases and functions as a constitutively activated TAZ. Sequencing of human tumors has, however, identified additional secondary mutations in approximately 50% of EHE, most commonly the loss of tumor suppressor CDKN2A.

Unraveling the Biology of Epithelioid Hemangioendothelioma, a TAZ-CAMTA1 Fusion Driven Sarcoma.

The activities of YAP and TAZ, the end effectors of the Hippo pathway, are consistently altered in cancer, and this dysregulation drives aggressive tumor phenotypes. While the actions of these two proteins aid in tumorigenesis in the majority of cancers, the dysregulation of these proteins is rarely sufficient for initial tumor development. Herein, we present a unique TAZ-driven cancer, epithelioid hemangioendothelioma (EHE), which harbors a gene fusion in at least 90% of cases.

The TAZ-CAMTA1 Fusion Protein Promotes Tumorigenesis via Connective Tissue Growth Factor and Ras-MAPK Signaling in Epithelioid Hemangioendothelioma.

Purpose: A consistent genetic alteration in vascular cancer epithelioid hemangioendothelioma (EHE) is the t(1;3)(p36;q25) chromosomal translocation, which generates a WWTR1(TAZ)-CAMTA1 (TC) fusion gene. TC is a transcriptional coactivator that drives EHE. Here, we aimed to identify the TC transcriptional targets and signaling mechanisms that underlie EHE tumorigenesis.

Aurintricarboxylic acid is a canonical disruptor of the TAZ-TEAD transcriptional complex.

Disrupting the formation of the oncogenic YAP/TAZ-TEAD transcriptional complex holds substantial therapeutic potential. However, the three protein interaction interfaces of this complex cannot be easily disrupted using small molecules. Here, we report that the pharmacologically active small molecule aurintricarboxylic acid (ATA) acts as a disruptor of the TAZ-TEAD complex.

(TAZ)- gene fusion is sufficient to dysregulate YAP/TAZ signaling and drive epithelioid hemangioendothelioma tumorigenesis.

Epithelioid hemangioendothelioma (EHE) is a genetically homogenous vascular sarcoma that is a paradigm for TAZ dysregulation in cancer. EHE harbors a (TAZ)- gene fusion in >90% of cases, 45% of which have no other genetic alterations. In this study, we used a first of its kind approach to target the gene fusion to the locus, to develop a conditional EHE mouse model whereby is controlled by the endogenous transcriptional regulators upon Cre activation.

Impact of Surgery Program Characteristics on Fate of Non-designated Preliminary Surgery Interns.

Objective: Non-designated preliminary (NDP) general surgery residents face the daunting challenge of obtaining a categorical residency position while undertaking the rigors of a general surgery residency. This additional application cycle represents a stressful time for these trainees and limited data exists to help guide applicants and program directors regarding the factors predictive of application success. While previous studies have focused solely on applicant related factors, no study to date has evaluated the effect of the residency program structure, institutional resources, or administrative support on these outcomes.

CD4+CD25 FoxP3+ regulatory T cells in long-term cardiac xenotransplantation.

Background: CD4+CD25 FoxP3+ T (Treg) cells are a small subset of CD4+ T cells that have been shown to exhibit immunoregulatory function. Although the absolute number of Treg cells in peripheral blood lymphocytes (PBL) is very small, they play an important role in suppressing immune reactivity. Several studies have demonstrated that the number of Treg cells, rather than their intrinsic suppressive capacity, may contribute to determining the long-term fate of transplanted grafts.

Ex-vivo expanded baboon CD4+ CD25 Hi Treg cells suppress baboon anti-pig T and B cell immune response.

Background: CD4(+) CD25(+) FoxP3(+) regulatory T (Treg) cells play an important role in regulating immune responses. A very small number of Treg cells are present in peripheral blood and lymphoid organs, but due to their ability to suppress the immune response, they have a high potential for immunotherapy in clinics. Successful ex-vivo expansion of naturally occurring CD4(+) CD25(+) T cells has been achieved after TCR stimulation in the presence of T cell growth factors.

Rapid and dynamic alterations of gene expression profiles of adult porcine bone marrow-derived stem cell in response to hypoxia.

This study sought to identify the gene expression patterns of porcine bone marrow-derived MSC in response to hypoxia and to investigate novel specific hypoxic targets that may have a role in determining MSC proliferation/survival and differentiation. MSC from 15 animals were incubated in 1% oxygen and 8% carbon dioxide for 6, 12, and 24 h. RNA samples were isolated and assayed with Affymetrix porcine arrays and quantitative reverse-transcription PCR.