Oncology Commons^™

Translational Study Of Liver Cancer And Hypertrophy: Translich, Mauro Enrique Tun Abraham

Electronic Thesis and Dissertation Repository

Abstract

Background: Associating liver partition with portal vein ligation for staged-hepatectomy (ALPPS) is a technique for inducing accelerated hypertrophy in patients with insufficient future liver remnant (FLR). It remains unknown whether this hypertrophy may lead to rapid cancer cell dissemination and/or alteration of immune cell/function reconstitution in the FLR. We aimed to determine if the rapid hypertrophy during ALPPS procedure results in more circulating tumour cell (CTCs) dissemination and whether the FLR remains immunologically competent in patients with CRLM.

Methods: In our prospective, observational, 2-arm study, we assessed the utility of CTCs as an evaluation tool for disease dissemination. Moreover, …

Impact Of Hur Inhibition By The Small Molecule Ms-444 On Colorectal Cancer Cell Tumorigenesis., Fernando F. Blanco, Ranjan Preet, Andrea Aguado, Vikalp Vishwakarma, Laura E. Stevens, Alok Vyas, Subhash Padhye, Liang Xu, Scott J. Weir, Shrikant Anant, Nicole Meisner-Kober, Jonathan R. Brody, Dan A. Dixon

Department of Surgery Faculty Papers

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality. Observed during CRC tumorigenesis is loss of post-transcriptional regulation of tumor-promoting genes such as COX-2, TNFα and VEGF. Overexpression of the RNA-binding protein HuR (ELAVL1) occurs during colon tumorigenesis and is abnormally present within the cytoplasm, where it post-transcriptionally regulates genes through its interaction with 3'UTR AU-rich elements (AREs). Here, we examine the therapeutic potential of targeting HuR using MS-444, a small molecule HuR inhibitor. Treatment of CRC cells with MS-444 resulted in growth inhibition and increased apoptotic gene expression, while similar treatment doses …

Four-Dimensional (4d) Subharmonic Aided Pressure Estimation For Monitoring Neoadjuvant Chemotherapy Response Of Breast Cancer, Kibo Nam, Maria Stanczak, Anush Sridharan, Adam C. Berger, Tiffany Avery, John R. Eisenbrey, Flemming Forsberg

Department of Radiology Posters

Introduction

Neoadjuvant chemotherapy is a well-established treatment option for patients with non-metastatic breast cancer. The patient response is correlated with survival. However, the optimal method for monitoring neoadjuvant therapy response has not been established. One factor that may affect the response of neoadjuvant therapy is the interstitial fluid pressure (IFP). Increased IFP prevents an effective delivery of therapeutic agents and reduces the efficacy of the therapy. Recently, subharmonic-aided pressure estimation (SHAPE) using contrast-enhanced ultrasound (CEUS) has been developed and its potential was demonstrated in animals as a non-invasive technique for IFP measurements. The SHAPE method estimates IFP based on the …

Asymptomatic Left Ventricular Myxoma In A 12-Year-Old Male., Meghan Chlebowski, James O'Brien, Casey Hertzenberg, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Cardiac myxoma is the most common cardiac tumor in patients of all ages; the majority are encountered as single left atrial tumors. Left ventricular myxomas are exceedingly rare, having been recorded in a small number of case reports involving children worldwide. We report a case of a left ventricular myxoma with left ventricular outflow tract obstruction in a previously healthy, asymptomatic adolescent black male. Transthoracic echocardiograms revealed a single, large (2.5 × 5-cm), lobulated, mobile mass within the left ventricular cavity that oscillated into the outflow tract, thereby causing moderate obstruction during systole. Advanced images delineated the location and tissue …

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Maharaj Singh

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy Tjoe, Philippe Gascard, Jianxin Zhao, Gary Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Judy Tjoe, MD

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

Mutational Profiles Reveal An Aberrant Tgf-Β-Cea Regulated Pathway In Colon Adenomas., Jian Chen, Gottumukkala S Raju, Wilma Jogunoori, Shoujun Gu, Lopa Mishra, + 27 More

Surgery Faculty Publications

Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway …

Vitamin D Deficiency Promotes Liver Tumor Growth In Transforming Growth Factor-Β/Smad3-Deficient Mice Through Wnt And Toll-Like Receptor 7 Pathway Modulation., Jian Chen, Lior H Katz, Nina M Muñoz, Shoujun Gu, Ji-Hyun Shin, Lopa Mishra, +13 Additional Authors

Surgery Faculty Publications

Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence …