Iatrogenic Ureteral Injury and Prophylactic Stent Use in Veterans Undergoing Colorectal Surgery.

Introduction: Iatrogenic ureteral injury (IUI) is an uncommon complication in colorectal surgery. Prophylactic ureteral stenting (PUS) gained acceptance to aid in intraoperative identification of the ureter. Despite its use, the benefit of pus to avoid IUI remains debatable.

IL-10 Signaling in the Tumor Microenvironment of Ovarian Cancer.

Unlike other malignancies, ovarian cancer (OC) creates a complex tumor microenvironment with distinctive peritoneal ascites consisting of a mixture of several immunosuppressive cells which impair the ability of the patient's immune system to fight the disease. The poor survival rates observed in advanced stage OC patients and the lack of effective conventional therapeutic options have been attributed in large part to the immature dendritic cells (DCs), IL-10 secreting regulatory T cells, tumor-associated macrophages, myeloid-derived suppressor cells, and cancer stem cells that secrete inhibitory cytokines. This review highlights the critical role played by the intraperitoneal presence of IL-10 in the generation of an immunosuppressive tumor microenvironment.

Outcomes of cholecystectomy in US veterans with cirrhosis: Predicting outcomes using nomogram.

Background: This study examines the outcomes of open and laparoscopic cholecystectomy (OC/LC) in veterans with cirrhosis and develops a nomogram to predict outcomes.

Methods: We analyzed the Veterans Affairs Surgical Quality Improvement Program to identify all patients with cirrhosis and ascites who underwent cholecystectomy from 2008 to 2015. Univariate and multivariate regression were used to identify predictors of morbidity and mortality.

Postoperative outcomes of ventral hernia repair in veterans.

Background: Ventral hernia repair is a common procedure with reported 15% to 37% morbidity and 0.3% to 1.4% mortality rates.

Recent trends in cholecystectomy in US veterans.

Introduction: We hypothesize that the recent trend in performing cholecystectomy in US Veterans shows wide adoption of the laparoscopic technique and improvement in the outcome following both laparoscopic (LC) and open cholecystectomy (OC). This study utilizes the Veterans Affairs Surgical Quality Improvement Program database to examine the status and outcome of cholecystectomy.

Methods: A retrospective review of veterans who underwent cholecystectomy between 2008 and 2015 was performed.

Engraftment of mesothelin chimeric antigen receptor using a hybrid Sleeping Beauty/minicircle vector into NK-92MI cells for treatment of pancreatic cancer.

Background: We have previously demonstrated in vitro cytotoxicity of mesothelin-chimeric antigen receptor autologous T cells against pancreatic cancer cells using lentiviral vectors, but these vectors pose safety concerns. Here, we incorporated Sleeping Beauty and minicircle design enhancements into interleukin-2-secreting natural NK-92MI cells to eliminate both bacterial and viral components and address inhibition by the tumor microenvironment.

Methods: Parental (conventional deoxyribonucleic acid)-mesothelin-chimeric antigen receptor and minicircle-mesothelin-chimeric antigen receptor vectors were electroporated into NK-92MI cells and engraftment was visualized by immunofluorescence analysis with protein-L staining.

Inhibition of Interleukin-10 in the tumor microenvironment can restore mesothelin chimeric antigen receptor T cell activity in pancreatic cancer in vitro.

Background: Pancreatic cancer cells are known to shield themselves from immunosurveillance by secreting immune inhibitory cytokines such as Interleukin-10. Using mesothelin, a differentiating antigen that is overexpressed in pancreatic cancer, we assessed the negative effect of the tumor microenvironment on chimeric antigen receptor T cell-based immunotherapy and its reversal via depletion of Interleukin-10.

Methods: T cells cultured in pancreatic cancer-cell-conditioned medium were transduced with lentiviruses encoding mesothelin-chimeric antigen receptor in the presence or absence of anti-Interleukin-10-blocking antibody.

Enhanced phosphorylation of p53 by microRNA-26a leading to growth inhibition of pancreatic cancer.

Purpose: MicroRNA (miR)-26a has been identified as a tumor suppressor in pancreatic cancer cells. Although wild-type p53 controls cell-cycle progression, its mutant form normally present in pancreatic cancer loses this capability. Phosphorylation is known to restore wild-type activity to mutant p53.

Raman spectroscopic modeling of early versus late T-lymphocyte activation via differential spectral detection of receptor expression.

The proven efficacy of renal transplantation has made it the definitive treatment for end-stage renal disease. Despite its wide acceptance, transplantation has been limited by organ shortages. In the face of this, preservation of allograft longevity is essential.

MAGE-A3 with cell-penetrating domain as an efficient therapeutic cancer vaccine.

Importance: In conjunction with chemotherapy, immunotherapy with dendritic cells (DCs) may eliminate minimal disease burden by generating cytotoxic T lymphocytes. Enhanced cytosolic bioavailability of tumor-specific antigens improves access to human leukocyte antigen (HLA) class I molecules for more efficient cytotoxic T lymphocyte generation. Various cell-penetrating domains (CPDs) are known to ferry covalently linked heterologous antigens to the intracellular compartment by traversing the plasma membrane.

Ritonavir-Mediated Induction of Apoptosis in Pancreatic Cancer Occurs via the RB/E2F-1 and AKT Pathways.

Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir.

Efficient lysis of epithelial ovarian cancer cells by MAGE-A3-induced cytotoxic T lymphocytes using rAAV-6 capsid mutant vector.

MAGE-A3 is highly expressed in epithelial ovarian cancer (EOC), making it a promising candidate for immunotherapy. We investigated whether dendritic cells (DCs) transduced with a rAAV-6 capsid mutant vector Y445F could elicit effective MAGE-A3-specific anti-tumor cytotoxic T lymphocyte (CTL) responses in vitro. MAGE-A3 was cloned and rAAV-6-MAGE-A3 purified, followed by proviral genome detection using real-time PCR.

EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma.

Purpose: Enhancer of zeste homologue 2 (EZH2), a component of the chromatin modification protein complex, is upregulated in pancreatic ductal adenocarcinoma (PDAC), whereas loss of p53 and its downstream target, p21(waf1/cip1), is also observed frequently. We sought to investigate the role of the p53-p21(waf1/cip1) pathway in relation to EZH2-mediated inhibition of PDAC.

Methods: The PANC-1 cell line was utilized in chromatin immunoprecipitation, gene profiling, Western blot, cell invasion, cell proliferation, and tumor xenograft assays.

EZH2 blockade by RNA interference inhibits growth of ovarian cancer by facilitating re-expression of p21(waf1/cip1) and by inhibiting mutant p53.

The enhancer of zeste homolog 2 (EZH2) methyltransferase is a transcriptional repressor. EZH2 is abnormally elevated in epithelial ovarian cancer (EOC). We demonstrated that EZH2 knockdown inhibited cell growth, activated apoptosis, and enhanced chemosensitivity.

Restoration of E-cadherin expression in pancreatic ductal adenocarcinoma treated with microRNA-101.

Purpose: To investigate the possibility of inhibiting the progression of pancreatic ductal adenocarcinoma (PDAC) by facilitating the expression of E-cadherin through the enforced expression of microRNA-101 (miR-101).

Methods: In situ hybridization was conducted with archival tissue using a double digoxigenin-labeled probe. Chromatin immunoprecipitation (ChIP) assay was conducted with EZ-Magna ChIPTM A.

MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf¹/cip¹).

Purpose: MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and proliferation in several solid epithelial cancers. Enhancer of zeste homolog 2 (EzH2) appears to be a functional target of miR-101. We explore the role of miR-101 and its interaction with EzH2 in epithelial ovarian carcinoma (EOC).

Laser capture microdissection of pancreatic ductal adeno-carcinoma cells to analyze EzH2 by Western Blot analysis.

Pure populations of tumor cells are essential for the identification of tumor-associated proteins for the development of targeted therapy. In recent years, laser capture microdissection (LCM) has been used successfully to obtain distinct populations of cells for subsequent molecular analysis. The polycomb group (PcG) protein, enhancer of zeste homolog 2 (EzH2), a methyl-transferase that plays a key role in -transcriptional gene repression, is frequently overexpressed in several malignant tumors.

Different patterns of cancer incidence among African American and Caucasian renal allograft recipients.

Background: Little data are available regarding cancer incidence in separately analyzed African American renal allograft recipients, with no study examining in detail the incidence and relative distribution of individual post-transplant malignancies versus those occurring in Caucasians.

Methods: We compared the incidence of nonskin cancer occurring in 495 African Americans transplanted at our center from 1984 to 2007 and followed through June 2009 with that occurring in 11,155 patients in the Canadian Organ Replacement Registry transplanted from 1981 to 1998 and followed through December 1999, of which 97% were Caucasian.

Results: Despite a shorter follow-up, the overall incidence of nonskin cancer, as well as that of prostate, renal cell, pancreatic, and esophageal cancer, was significantly higher in the African American group.

Does donor race still make a difference in deceased-donor African-American renal allograft recipients?

Background: Prior studies have demonstrated that African-American (AA) donor kidneys are independently associated with an increased risk for graft loss.

Methods: We examined outcomes in comparable groups of AA deceased-donor (DD) kidney transplant patients receiving an AA donor (n=35) versus a Caucasian donor (C group; n=150) organ.

Results: There were no differences between AA and C groups in patient survival, new-onset diabetes, or BK nephropathy.