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Pancreatic Neoplasms: HELP
Articles by Sally E. Hodges
Based on 10 articles published since 2009
(Why 10 articles?)
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Between 2009 and 2019, S. Hodges wrote the following 10 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. 2016

Gingras, Marie-Claude / Covington, Kyle R / Chang, David K / Donehower, Lawrence A / Gill, Anthony J / Ittmann, Michael M / Creighton, Chad J / Johns, Amber L / Shinbrot, Eve / Dewal, Ninad / Fisher, William E / Anonymous1060856 / Pilarsky, Christian / Grützmann, Robert / Overman, Michael J / Jamieson, Nigel B / Van Buren, George / Drummond, Jennifer / Walker, Kimberly / Hampton, Oliver A / Xi, Liu / Muzny, Donna M / Doddapaneni, Harsha / Lee, Sandra L / Bellair, Michelle / Hu, Jianhong / Han, Yi / Dinh, Huyen H / Dahdouli, Mike / Samra, Jaswinder S / Bailey, Peter / Waddell, Nicola / Pearson, John V / Harliwong, Ivon / Wang, Huamin / Aust, Daniela / Oien, Karin A / Hruban, Ralph H / Hodges, Sally E / McElhany, Amy / Saengboonmee, Charupong / Duthie, Fraser R / Grimmond, Sean M / Biankin, Andrew V / Wheeler, David A / Gibbs, Richard A. ·Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: mgingras@bcm.edu. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, NSW 2170, Australia. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. · The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. · Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA; Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, TX 77030, USA. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. · The Kinghorn Cancer Centre and the Cancer Research Program Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia. · Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; The Elkins Pancreas Center at Baylor College of Medicine, Houston, TX 77030, USA. · Department of Surgery, TU Dresden, 01307 Dresden, Germany. · Department of Surgery, Universitätsklinikum Erlangen, 91054 Erlangen, Germany. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; Academic Unit of Surgery, Institute of Cancer Sciences, Glasgow Royal Infirmary, Level 2, New Lister Building, University of Glasgow, Glasgow G31 2ER, UK. · Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia; Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia; QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia. · Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. · Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Pathology, TU Dresden, 01307 Dresden, Germany. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Department of Pathology, Southern General Hospital, Greater Glasgow and Clyde NHS, Glasgow G51 4TF, UK. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. · Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; The Elkins Pancreas Center at Baylor College of Medicine, Houston, TX 77030, USA. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. · Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia. · Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: wheeler@bcm.edu. ·Cell Rep · Pubmed #26804919.

ABSTRACT: The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis.

2 Article Antiproliferative effects and mechanisms of liver X receptor ligands in pancreatic ductal adenocarcinoma cells. 2014

Candelaria, Nicholes R / Addanki, Sridevi / Zheng, Jine / Nguyen-Vu, Trang / Karaboga, Husna / Dey, Prasenjit / Gabbi, Chiara / Vedin, Lise-Lotte / Liu, Ka / Wu, Wanfu / Jonsson, Philip K / Lin, Jean Z / Su, Fei / Bollu, Lakshmi Reddy / Hodges, Sally E / McElhany, Amy L / Issazadeh, Mehdi A / Fisher, William E / Ittmann, Michael M / Steffensen, Knut R / Gustafsson, Jan-Åke / Lin, Chin-Yo. ·Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas, United States of America. · Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. · Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas, United States of America; Center for Diabetes Research, Houston Methodist Research Institute, Houston, Texas, United States of America. · Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America; The Elkins Pancreas Center at Baylor College of Medicine, Houston, Texas, United States of America. · Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America. · Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, Texas, United States of America; Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Huddinge, Sweden. ·PLoS One · Pubmed #25184494.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect early and is often resistant to standard chemotherapeutic options, contributing to extremely poor disease outcomes. Members of the nuclear receptor superfamily carry out essential biological functions such as hormone signaling and are successfully targeted in the treatment of endocrine-related malignancies. Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol homeostasis, lipid metabolism, and inflammation, and LXR agonists have been developed to regulate LXR function in these processes. Intriguingly, these compounds also exhibit antiproliferative activity in diverse types of cancer cells. In this study, LXR agonist treatments disrupted proliferation, cell-cycle progression, and colony-formation of PDAC cells. At the molecular level, treatments downregulated expression of proteins involved in cell cycle progression and growth factor signaling. Microarray experiments further revealed changes in expression profiles of multiple gene networks involved in biological processes and pathways essential for cell growth and proliferation following LXR activation. These results establish the antiproliferative effects of LXR agonists and potential mechanisms of action in PDAC cells and provide evidence for their potential application in the prevention and treatment of PDAC.

3 Article A tumorigenic factor interactome connected through tumor suppressor microRNA-198 in human pancreatic cancer. 2013

Marin-Muller, Christian / Li, Dali / Bharadwaj, Uddalak / Li, Min / Chen, Changyi / Hodges, Sally E / Fisher, William E / Mo, Qianxing / Hung, Mien-Chie / Yao, Qizhi. ·Authors' Affiliations: Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Department of Molecular Virology and Microbiology, Duncan Cancer Center, Baylor College of Medicine; and Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. ·Clin Cancer Res · Pubmed #23989979.

ABSTRACT: PURPOSE: The majority of pancreatic cancers overexpress mesothelin (MSLN), which contributes to enhanced proliferation, invasion, and migration. However, the MSLN regulatory network is still unclear. Here, we investigated the regulation of a panel of tumorigenic factors and explored the potential of MSLN-regulated miR-198 treatment in vivo. EXPERIMENTAL DESIGN: The expression and functional regulation of the tumorigenic factors MSLN, NF-κB, and the homeobox transcription factors (TF) POU2F2 (OCT-2), Pre-B-cell leukemia homeobox factor 1 (PBX-1), valosin-containing protein (VCP), and miR-198 were studied in pancreatic cancer cell lines, patient tumor samples, and xenograft pancreatic cancer mouse models. RESULTS: We found that miR-198 is downregulated in pancreatic cancer and is involved in an intricate reciprocal regulatory loop with MSLN, which represses miR-198 through NF-κB-mediated OCT-2 induction. Furthermore, miR-198 repression leads to overexpression of PBX-1 and VCP. The dysregulated PBX-1/VCP axis leads to increased tumorigenicity. Reconstitution of miR-198 in pancreatic cancer cells results in reduced tumor growth, metastasis, and increased survival through direct targeting MSLN, PBX-1, and VCP. Most interestingly, reduced levels of miR-198 in human tissue samples are associated with upregulation of these tumorigenic factors (MSLN, OCT-2, PBX-1, VCP) and predict poor survival. Reduced miR-198 expression links this tumor network signature and prognosticates poor patient outcome. High miR-198 disrupts the network and predicts better prognosis and increased survival. CONCLUSIONS: miR-198 acts as a central tumor suppressor and modulates the molecular makeup of a critical interactome in pancreatic cancer, indicating a potential prognostic marker signature and the therapeutic potential of attacking this tumorigenic network through a central vantage point.

4 Article A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer growth. 2013

Zhang, Yuqing / Yang, Jingxuan / Cui, Xiaobo / Chen, Yong / Zhu, Vivian F / Hagan, John P / Wang, Huamin / Yu, Xianjun / Hodges, Sally E / Fang, Jing / Chiao, Paul J / Logsdon, Craig D / Fisher, William E / Brunicardi, F Charles / Chen, Changyi / Yao, Qizhi / Fernandez-Zapico, Martin E / Li, Min. ·Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA. ·EMBO Mol Med · Pubmed #23857777.

ABSTRACT: Changes in the intracellular levels of the essential micronutrient zinc have been implicated in multiple diseases including pancreatic cancer; however, the molecular mechanism is poorly understood. Here, we report a novel mechanism where increased zinc mediated by the zinc importer ZIP4 transcriptionally induces miR-373 in pancreatic cancer to promote tumour growth. Reporter, expression and chromatin immunoprecipitation assays demonstrate that ZIP4 activates the zinc-dependent transcription factor CREB and requires this transcription factor to increase miR-373 expression through the regulation of its promoter. miR-373 induction is necessary for efficient ZIP4-dependent enhancement of cell proliferation, invasion, and tumour growth. Further analysis of miR-373 in vivo oncogenic function reveals that it is mediated through its negative regulation of TP53INP1, LATS2 and CD44. These results define a novel ZIP4-CREB-miR-373 signalling axis promoting pancreatic cancer growth, providing mechanistic insights explaining in part how a zinc transporter functions in cancer cells and may have broader implications as inappropriate regulation of intracellular zinc levels plays an important role in many other diseases.

5 Article Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer. 2013

Yang, J / Zhang, Y / Cui, X / Yao, W / Yu, X / Cen, P / Hodges, S E / Fisher, W E / Brunicardi, F C / Chen, C / Yao, Q / Li, M. ·Vivian L. Smith Department of Neurosurgery, University of Texas Medical School at Houston, 6431 Fannin Street, MSE R266, Houston, TX 77030, USA. ·Curr Mol Med · Pubmed #23331012.

ABSTRACT: Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

6 Article Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. 2012

Biankin, Andrew V / Waddell, Nicola / Kassahn, Karin S / Gingras, Marie-Claude / Muthuswamy, Lakshmi B / Johns, Amber L / Miller, David K / Wilson, Peter J / Patch, Ann-Marie / Wu, Jianmin / Chang, David K / Cowley, Mark J / Gardiner, Brooke B / Song, Sarah / Harliwong, Ivon / Idrisoglu, Senel / Nourse, Craig / Nourbakhsh, Ehsan / Manning, Suzanne / Wani, Shivangi / Gongora, Milena / Pajic, Marina / Scarlett, Christopher J / Gill, Anthony J / Pinho, Andreia V / Rooman, Ilse / Anderson, Matthew / Holmes, Oliver / Leonard, Conrad / Taylor, Darrin / Wood, Scott / Xu, Qinying / Nones, Katia / Fink, J Lynn / Christ, Angelika / Bruxner, Tim / Cloonan, Nicole / Kolle, Gabriel / Newell, Felicity / Pinese, Mark / Mead, R Scott / Humphris, Jeremy L / Kaplan, Warren / Jones, Marc D / Colvin, Emily K / Nagrial, Adnan M / Humphrey, Emily S / Chou, Angela / Chin, Venessa T / Chantrill, Lorraine A / Mawson, Amanda / Samra, Jaswinder S / Kench, James G / Lovell, Jessica A / Daly, Roger J / Merrett, Neil D / Toon, Christopher / Epari, Krishna / Nguyen, Nam Q / Barbour, Andrew / Zeps, Nikolajs / Anonymous1421514 / Kakkar, Nipun / Zhao, Fengmei / Wu, Yuan Qing / Wang, Min / Muzny, Donna M / Fisher, William E / Brunicardi, F Charles / Hodges, Sally E / Reid, Jeffrey G / Drummond, Jennifer / Chang, Kyle / Han, Yi / Lewis, Lora R / Dinh, Huyen / Buhay, Christian J / Beck, Timothy / Timms, Lee / Sam, Michelle / Begley, Kimberly / Brown, Andrew / Pai, Deepa / Panchal, Ami / Buchner, Nicholas / De Borja, Richard / Denroche, Robert E / Yung, Christina K / Serra, Stefano / Onetto, Nicole / Mukhopadhyay, Debabrata / Tsao, Ming-Sound / Shaw, Patricia A / Petersen, Gloria M / Gallinger, Steven / Hruban, Ralph H / Maitra, Anirban / Iacobuzio-Donahue, Christine A / Schulick, Richard D / Wolfgang, Christopher L / Morgan, Richard A / Lawlor, Rita T / Capelli, Paola / Corbo, Vincenzo / Scardoni, Maria / Tortora, Giampaolo / Tempero, Margaret A / Mann, Karen M / Jenkins, Nancy A / Perez-Mancera, Pedro A / Adams, David J / Largaespada, David A / Wessels, Lodewyk F A / Rust, Alistair G / Stein, Lincoln D / Tuveson, David A / Copeland, Neal G / Musgrove, Elizabeth A / Scarpa, Aldo / Eshleman, James R / Hudson, Thomas J / Sutherland, Robert L / Wheeler, David A / Pearson, John V / McPherson, John D / Gibbs, Richard A / Grimmond, Sean M. ·The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia. ·Nature · Pubmed #23103869.

ABSTRACT: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

7 Article Genomic sequencing of key genes in mouse pancreatic cancer cells. 2012

Wang, Y / Zhang, Y / Yang, J / Ni, X / Liu, S / Li, Z / Hodges, S E / Fisher, W E / Brunicardi, F C / Gibbs, R A / Gingras, M-C / Li, M. ·Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China. ·Curr Mol Med · Pubmed #22208613.

ABSTRACT: Pancreatic cancer is a multiple genetic disorder with many mutations identified during the progression. Two mouse pancreatic cancer cell lines were established which showed different phenotype in vivo: a non-metastatic cell line, Panc02, and a highly metastatic cell line, Panc02-H7, a derivative of Panc02. In order to investigate whether the genetic mutations of key genes in pancreatic cancer such as KRAS, TP53 (p53), CDKN2A (p16), SMAD4, ZIP4, and PDX-1 contribute to the phenotypic difference of these two mouse pancreatic cancer cells, we sequenced the exonic regions of these key genes in both cell lines and in the normal syngeneic mouse pancreas and compared them with the reference mouse genome sequence. The exons of KRAS, SMAD4, CDKN2A (p16), TP53 (p53), ZIP4, and PDX-1 genes were amplified and the genotype of these genes was determined by Sanger sequencing. The sequences were analyzed with Sequencher software. A mutation in SMAD4 was identified in both cell lines. This homozygote G to T mutation in the first position of codon 174 (GAA) generated a stop codon resulting in the translation of a truncated protein. Further functional analysis indicates that different TGF-β/SMAD signaling pathways were involved in those two mouse cell lines, which may explain the phonotypic difference between the two cells. A single nucleotide polymorphism (SNP) in KRAS gene (TAT to TAC at codon 32) was also identified in the normal pancreas DNA of the syngenic mouse and in both derived tumoral Panc02 and Panc02-H7 cells. No mutation or SNP was found in CDKN2A (p16), TP53 (p53), ZIP4, and PDX-1 genes in these two cell lines. The absence of mutations in genes such as KRAS, TP53, and CDKN2A, which are considered as key genes in the development of human pancreatic cancer suggests that SMAD4 might play a central and decisive role in mouse pancreatic cancer. These results also suggest that other mechanisms are involved in the substantial phenotypic difference between these two mouse pancreatic cancer cell lines. Further studies are warranted to elucidate the molecular pathways that lead to the aggressive metastatic potential of Panc02-H7.

8 Article Engineered T cells for pancreatic cancer treatment. 2011

Katari, Usha L / Keirnan, Jacqueline M / Worth, Anna C / Hodges, Sally E / Leen, Ann M / Fisher, William E / Vera, Juan F. ·Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA. ·HPB (Oxford) · Pubmed #21843265.

ABSTRACT: OBJECTIVE: Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells. METHODS: Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr(51)) release. RESULTS: Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach. CONCLUSIONS: Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer.

9 Article Intra-abdominal fat predicts survival in pancreatic cancer. 2010

Balentine, Courtney J / Enriquez, Jose / Fisher, William / Hodges, Sally / Bansal, Vivek / Sansgiry, Shubhada / Petersen, Nancy J / Berger, David H. ·Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. cb131098@bcm.tmc.edu ·J Gastrointest Surg · Pubmed #20725799.

ABSTRACT: BACKGROUND: Body mass index (BMI) has proven unreliable in predicting survival following pancreaticoduodenectomy for cancer. While measures of intra-abdominal fat correlate with medical and postoperative complications of obesity, the impact of intra-abdominal fat on pancreatic cancer survival is uncertain. We hypothesized that the quantity of intra-abdominal fat would predict survival following resection of pancreatic cancer. METHODS: Preoperative CT imaging was used to measure intra-abdominal fat. Cox regression analyses were used to identify independent predictors of survival. RESULTS: Sixty-one patients from 2000-2009 underwent pancreaticoduodenectomy for exocrine pancreatic adenocarcinoma. After adjusting for age and perineural invasion status, preoperative BMI did not predict overall survival (p < 0.827). Unlike BMI, quartile of intra-abdominal fat predicted survival. Relative to patients with the least intra-abdominal fat (lowest quartile), those with more intra-abdominal fat demonstrated worse overall survival, but in a non-linear fashion. Individuals in the second quartile showed a fourfold increase in likelihood of death (HR 4.018, 95% CI 1.099-14.687, p < 0.035) relative to the lowest quartile. Patients in the third (HR 2.124, 95% CI 0.278-16.222, p < 0.468) and fourth quartile (HR 1.354, 95% CI 0.296-6.190, p < 0.696) also showed greater risk of death. CONCLUSIONS: Measuring intra-abdominal fat identifies a subset of patients with worse prognosis in pancreatic cancer.

10 Article Developing a tissue resource to characterize the genome of pancreatic cancer. 2009

Voidonikolas, Georgios / Gingras, Marie-Claude / Hodges, Sally / McGuire, Amy L / Chen, Changyi / Gibbs, Richard A / Brunicardi, F Charles / Fisher, William E. ·Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden, Suite 1500, Houston, TX 77030, USA. ·World J Surg · Pubmed #19137368.

ABSTRACT: With recent advances in DNA sequencing technology, medicine is entering an era in which a personalized genomic approach to diagnosis and treatment of disease is feasible. However, discovering the role of altered DNA sequences in various disease states will be a challenging task. The genomic approach offers great promise for diseases, such as pancreatic cancer, in which the effect of current diagnostic and treatment modalities is disappointing. To facilitate the characterization of the genome of pancreatic cancer, high-quality and well-annotated tissue repositories are needed. This article summarizes the basic principles that guide the creation of such a repository, including sample processing and preservation techniques, sample size and composition, and collection of clinical data elements.