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Pancreatic Neoplasms: HELP
Articles by Jose Gilberto Trevino
Based on 37 articles published since 2010
(Why 37 articles?)
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Between 2010 and 2020, Jose Trevino wrote the following 37 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Partnering to advance early detection and prevention efforts for pancreatic cancer: the Florida Pancreas Collaborative. 2016

Permuth, Jennifer B / Trevino, Jose / Merchant, Nipun / Malafa, Mokenge / Anonymous6220857. ·Department of Cancer Epidemiology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Gastrointestinal Oncology, Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, FL, USA. · Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, FL, USA. ·Future Oncol · Pubmed #26863203.

ABSTRACT: -- No abstract --

2 Review Molecular therapeutic strategies targeting pancreatic cancer induced cachexia. 2018

Yakovenko, Anastasiya / Cameron, Miles / Trevino, Jose Gilberto. ·University of Florida College of Medicine, Gainesville, Florida 32610, United States. · Department of Surgery, University of Florida Health Sciences Center, Gainesville, Florida 32610, United States. jose.trevino@surgery.ufl.edu. ·World J Gastrointest Surg · Pubmed #30622678.

ABSTRACT: Pancreatic cancer (PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies. This review focuses on three main pathophysiologic processes implicated in the development and progression of cachexia in PC, as well as their utility in the discovery of novel targeted therapies. Skeletal muscle wasting is the most prominent pathophysiologic anomaly in cachectic patients and driven by multiple regulatory pathways. Several known molecular pathways that mediate muscle wasting and cachexia include transforming growth factor-beta (TGF-β), myostatin and activin, IGF-1/PI3K/AKT, and JAK-STAT signaling. TGF-β antagonism in cachectic mice reduces skeletal muscle catabolism and weight loss, while improving overall survival. Myostatin/activin inhibition has a great therapeutic potential since it plays an essential role in skeletal muscle regulation. Overexpression of insulin-like growth factor binding protein-3 (IGFBP-3) leads to increased ubiquitination associated proteolysis, inhibition of myogenesis, and decreased muscle mass in PC induced cachexia. IGFBP-3 antagonism alleviates muscle cell wasting. Another component of cachexia is profound systemic inflammation driven by pro-cachectic cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon gamma (INF-γ). IL-6 antagonism has been shown to reduce inflammation, reduce skeletal muscle loss, and ameliorate cachexia. While TNF-α inhibitors are clinically available, blocking TNF-α signaling is not effective in the treatment of cancer cachexia. Blocking the synthesis or action of acute phase reactants and cytokines is a feasible therapeutic strategy, but no anti-cytokine therapies are currently approved for use in PC. Metabolic alterations such as increased energy expenditure and gluconeogenesis, insulin resistance, fat tissue browning, excessive oxidative stress, and proteolysis with amino acid mobilization support tumor growth and the development of cachexia. Current innovative nutritional strategies for cachexia management include ketogenic diet, utilization of natural compounds such as silibinin, and supplementation with ω3-polyunsaturated fatty acids. Elevated ketone bodies exhibit an anticancer and anticachectic effect. Silibinin has been shown to inhibit growth of PC cells, induce metabolic alterations, and reduce myofiber degradation. Consumption of ω3-polyunsaturated fatty acids has been shown to significantly decrease resting energy expenditure and regulate metabolic dysfunction.

3 Review Clinical Factors as a Component of the Personalized Treatment Approach to Advanced Pancreatic Cancer: a Systematic Literature Review. 2018

Skelton, William Paul / Parekh, Hiral / Starr, Jason S / Trevino, Jose / Cioffi, Jessica / Hughes, Steven / George, Thomas J. ·Division of Hematology and Oncology, Department of Medicine, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL, 32610, USA. William.Skelton@medicine.ufl.edu. · Division of Hematology and Oncology, Department of Medicine, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL, 32610, USA. · Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA. · Division of Hematology and Oncology, Department of Medicine, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL, 32610, USA. Thom.George@medicine.ufl.edu. ·J Gastrointest Cancer · Pubmed #29110227.

ABSTRACT: INTRODUCTION: Pancreatic cancer is often diagnosed at late stages, where disease is either locally advanced unresectable or metastatic. Despite advances, long-term survival is relatively non-existent. DISCUSSION: This review article discusses clinical factors commonly encountered in practice that should be incorporated into the decision-making process to optimize patient outcomes, including performance status, nutrition and cachexia, pain, psychological distress, medical comorbidities, advanced age, and treatment selection. CONCLUSION: Identification and optimization of these clinical factors could make a meaningful impact on the patient's quality of life.

4 Review Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge. 2015

Rizwani, Wasia / Allen, Amanda E / Trevino, Jose G. ·Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007, India. wasia.rizwani@gmail.com. · Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610, USA. amanda.allen@ufl.edu. · Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610, USA. Jose.Trevino@surgery.ufl.edu. ·Cancers (Basel) · Pubmed #26404380.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

5 Review Multidisciplinary neoadjuvant management for potentially curable pancreatic cancer. 2015

Desai, Neelam V / Sliesoraitis, Sarunas / Hughes, Steven J / Trevino, Jose G / Zlotecki, Robert A / Ivey, Alison M / George, Thomas J. ·Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida. · Department of Surgery, University of Florida, Gainesville, Florida. · Department of Radiation Oncology, University of Florida, Gainesville, Florida. · University of Florida Health Cancer Center, Gainesville, Florida. ·Cancer Med · Pubmed #25766842.

ABSTRACT: Pancreatic adenocarcinoma remains the fourth leading cause of cancer mortality in the U.S. Despite advances in surgical technique, radiotherapy technologies, and chemotherapeutics, the 5-year survival rate remains approximately 20% for the 15% of patients who are eligible for surgical resection. The majority of this group suffers metastatic recurrence. However, despite advances in therapies for patients with advanced pancreatic cancer, only surgery has consistently proven to improve long-term survival. Various combinations of chemotherapy, biologic-targeted therapy, and radiotherapy have been evaluated in different settings to improve outcomes. In this context, a neoadjuvant (preoperative) treatment strategy offers numerous potential benefits: (1) ensuring delivery of early, systemic therapy, (2) improving selection of patients for surgical therapy with truly localized disease, (3) potential downstaging of the neoplasm facilitating a negative margin resection in patients with locally advanced disease, and (4) providing a superior clinical trial mechanism capable of rapid assessment of the efficacy of novel therapeutics. This article reviews the recent trends in the management of pancreatic adenocarcinoma, with a particular emphasis on a multidisciplinary neoadjuvant approach to treatment.

6 Review c-Met signaling in the development of tumorigenesis and chemoresistance: potential applications in pancreatic cancer. 2014

Delitto, Daniel / Vertes-George, Eva / Hughes, Steven J / Behrns, Kevin E / Trevino, Jose G. ·Daniel Delitto, Steven J Hughes, Kevin E Behrns, Jose G Trevino, Department of Surgery, University of Florida-Gainesville, Gainesville, FL 32610, United States. ·World J Gastroenterol · Pubmed #25024602.

ABSTRACT: Pancreatic ductal adenocarcinoma is the 4(th) leading cause of cancer deaths in the United States. The majority of patients are candidates only for palliative chemotherapy, which has proven largely ineffective in halting tumor progression. One proposed mechanism of chemoresistance involves signaling via the mesenchymal-epithelial transition factor protein (MET), a previously established pathway critical to cell proliferation and migration. Here, we review the literature to characterize the role of MET in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of MET as a therapeutic target in pancreatic cancer. In this review, we characterize the role of c-Met in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of c-Met as a therapeutic target in pancreatic cancer.

7 Article Cytotoxic effects of gemcitabine-loaded solid lipid nanoparticles in pancreatic cancer cells. 2020

Affram, Kevin O / Smith, Taylor / Ofori, Edward / Krishnan, Sunil / Underwood, Patrick / Trevino, Jose G / Agyare, Edward. ·College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, United States of America. · College of Pharmacy, Chicago State University, Chicago, Illinois, United States of America. · The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. · Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America. ·J Drug Deliv Sci Technol · Pubmed #31903101.

ABSTRACT: This study investigated the cytotoxic effects of gemcitabine-loaded solid lipid nanoparticle (Gem-SLN) on the patient-derived primary pancreatic cancer cell lines (PPCL-46) and MiaPaCa-2. Different SLN formulations were prepared from glyceryl monostearate (GMS), polysorbate 80 (Tween® 80) and poloxamer 188 (Pol 188) as surfactants using a cold homogenization method. Gem-SLN was characterized for particle size and charge distribution, entrapment efficiency and loading capacity. Fourier Transform Infra-Red (FTIR) spectroscopy was used to verify Gem and SLN interaction while differential scanning calorimetry (DSC) was used to acquire thermodynamic information on Gem-SLN. Cytotoxicity studies was conducted on PPCL-46 cells and Mia-PaCa-2 cells. Among the different Gem-SLN formulations prepared, Gem-SLN

8 Article Racial and ethnic disparities in a state-wide registry of patients with pancreatic cancer and an exploratory investigation of cancer cachexia as a contributor to observed inequities. 2019

Permuth, Jennifer B / Clark Daly, Ashley / Jeong, Daniel / Choi, Jung W / Cameron, Miles E / Chen, Dung-Tsa / Teer, Jamie K / Barnett, Tracey E / Li, Jiannong / Powers, Benjamin D / Kumar, Nagalakshmi B / George, Thomas J / Ali, Karla N / Huynh, Tri / Vyas, Shraddha / Gwede, Clement K / Simmons, Vani N / Hodul, Pamela J / Carballido, Estrella M / Judge, Andrew R / Fleming, Jason B / Merchant, Nipun / Trevino, Jose G. ·Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida. · Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida. · Division of Behavioral Health, Idaho Department of Health and Welfare, Boise, Idaho. · Department of Diagnostic Radiology, Moffitt Cancer Center, Tampa, Florida. · Department of Cancer Imaging & Metabolism, Moffitt Cancer Center, Tampa, Florida. · Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, Florida. · Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida. · School of Public Health, University of North Texas Health Science Center, Fort Worth, Texas. · Department of Medicine, University of Florida Health Sciences Center, Gainesville, Florida. · Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida. · Department of Physical Therapy, University of Florida, Gainesville, Florida. · Department of Surgical Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida. ·Cancer Med · Pubmed #31074202.

ABSTRACT: Pancreatic cancer (PC) is characterized by racial/ethnic disparities and the debilitating muscle-wasting condition, cancer cachexia. Florida ranks second in the number of PC deaths and has a large and understudied minority population. We examined the primary hypothesis that PC incidence and mortality rates may be highest among Black Floridians and the secondary hypothesis that biological correlates of cancer cachexia may underlie disparities. PC incidence and mortality rates were estimated by race/ethnicity, gender, and county using publicly available state-wide cancer registry data that included approximately 2700 Black, 25 200 Non-Hispanic White (NHW), and 3300 Hispanic/Latino (H/L) Floridians diagnosed between 2004 and 2014. Blacks within Florida experienced a significantly (P < 0.05) higher incidence (12.5/100 000) and mortality (10.97/100 000) compared to NHW (incidence = 11.2/100 000; mortality = 10.3/100 000) and H/L (incidence = 9.6/100 000; mortality = 8.7/100 000), especially in rural counties. To investigate radiologic and blood-based correlates of cachexia, we leveraged data from a subset of patients evaluated at two geographically distinct Florida Cancer Centers. In Blacks compared to NHW matched on stage, markers of PC-induced cachexia were more frequent and included greater decreases in core musculature compared to corresponding healthy control patients (25.0% vs 10.1% lower), greater decreases in psoas musculature over time (10.5% vs 4.8% loss), lower baseline serum albumin levels (3.8 vs 4.0 gm/dL), and higher platelet counts (332.8 vs 268.7 k/UL). Together, these findings suggest for the first time that PC and cachexia may affect Blacks disproportionately. Given its nearly universal contribution to illness and PC-related deaths, the early diagnosis and treatment of cachexia may represent an avenue to improve health equity, quality of life, and survival.

9 Article Mas Receptor Activation Slows Tumor Growth and Attenuates Muscle Wasting in Cancer. 2019

Murphy, Kate T / Hossain, Mohammed I / Swiderski, Kristy / Chee, Annabel / Naim, Timur / Trieu, Jennifer / Haynes, Vanessa / Read, Suzannah J / Stapleton, David I / Judge, Sarah M / Trevino, Jose G / Judge, Andrew R / Lynch, Gordon S. ·Centre for Muscle Research, Department of Physiology, The University of Melbourne, Victoria, Australia. ktmurphy@unimelb.edu.au. · Centre for Muscle Research, Department of Physiology, The University of Melbourne, Victoria, Australia. · Department of Physical Therapy, University of Florida Health Science Center, Gainesville, Florida. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, Florida. ·Cancer Res · Pubmed #30420474.

ABSTRACT: Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. Cachexia robs patients of their strength and capacity to perform daily tasks and live independently. Effective treatments are needed urgently. Here, we investigated the therapeutic potential of activating the "alternative" axis of the renin-angiotensin system, involving ACE2, angiotensin-(1-7), and the mitochondrial assembly receptor (MasR), for treating cancer cachexia. Plasmid overexpression of the MasR or pharmacologic angiotensin-(1-7)/MasR activation did not affect healthy muscle fiber size

10 Article Local and Systemic Cytokine Profiling for Pancreatic Ductal Adenocarcinoma to Study Cancer Cachexia in an Era of Precision Medicine. 2018

Gerber, Michael H / Underwood, Patrick W / Judge, Sarah M / Delitto, Daniel / Delitto, Andrea E / Nosacka, Rachel L / DiVita, Bayli B / Thomas, Ryan M / Permuth, Jennifer B / Hughes, Steven J / Wallet, Shannon M / Judge, Andrew R / Trevino, Jose G. ·Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. michael.gerber@surgery.ufl.edu. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. patrick.underwood@surgery.ufl.edu. · Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA. smsenf@phhp.ufl.edu. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. daniel.delitto@surgery.ufl.edu. · Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA. ADelitto@dental.ufl.edu. · Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA. rnoscaka@ufl.edu. · Department of Neurosurgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. Bayli.DiVita@neurosurgery.ufl.edu. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. ryan.thomas@surgery.ufl.edu. · North Florida/South Georgia Veterans Health System, Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA. ryan.thomas@surgery.ufl.edu. · Departments of Cancer Epidemiology and Gastroinestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. jenny.permuth@moffitt.org. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. steven.hughes@surgery.ufl.edu. · Department of Foundational Sciences, School of Dental Medicine, East Carolina University, Greenville, NC 27834, USA. wallets18@ecu.edu. · Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA. arjudge@phhp.ufl.edu. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. Jose.Trevino@surgery.ufl.edu. ·Int J Mol Sci · Pubmed #30513792.

ABSTRACT: Cancer cachexia is a debilitating condition seen frequently in patients with pancreatic ductal adenocarcinoma (PDAC). The underlying mechanisms driving cancer cachexia are not fully understood but are related, at least in part, to the immune response to the tumor both locally and systemically. We hypothesize that there are unique differences in cytokine levels in the tumor microenvironment and systemic circulation between PDAC tumors and that these varying profiles affect the degree of cancer cachexia observed. Patient demographics, operative factors, oncologic factors, and perioperative data were collected for the two patients in the patient derived xenograft (PDX) model. Human pancreatic cancer PDX were created by implanting fresh surgical pancreatic cancer tissues directly into immunodeficient mice. At PDX end point, mouse tumor, spleen and muscle tissues were collected and weighed, muscle atrophy related gene expression measured, and tumor and splenic soluble proteins were analyzed. PDX models were created from surgically resected patients who presented with different degrees of cachexia. Tumor free body weight and triceps surae weight differed significantly between the PDX models and control (P < 0.05). Both PDX groups had increased atrophy related gene expression in muscle compared to control (FoxO1, Socs3, STAT3, Acvr2b, Atrogin-1, MuRF1; P < 0.05). Significant differences were noted in splenic soluble protein concentrations in 14 of 15 detected proteins in tumor bearing mice when compared to controls. Eight splenic soluble proteins were significantly different between PDX groups (P < 0.05). Tumor soluble proteins were significantly different between the two PDX groups in 15 of 24 detected proteins (P < 0.05). PDX models preserve the cachectic heterogeneity found in patients and are associated with unique cytokine profiles in both the spleen and tumor between different PDX. These data support the use of PDX as a strategy to study soluble cachexia protein markers and also further efforts to elucidate which cytokines are most related to cachexia in order to provide potential targets for immunotherapy.

11 Article Aberrant expression of PDZ-binding kinase/T-LAK cell-originated protein kinase modulates the invasive ability of human pancreatic cancer cells via the stabilization of oncoprotein c-MYC. 2018

Hinzman, Charles P / Aljehane, Leala / Brown-Clay, Joshua D / Kallakury, Bhaskar / Sonahara, Fuminori / Goel, Ajay / Trevino, Jose / Banerjee, Partha P. ·Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, USA. · Department of Pathology, MedStar-Georgetown Hospital, Georgetown University Medical Center, Washington, DC, USA. · Center for Gastrointestinal Research, Center for Translational Genomics and Oncology Baylor Scott and White Research Institute and Charles A. Sammons Cancer Center, Dallas, TX, USA. · Department of Surgery, University of Florida Medical Center, Gainesville, FL, USA. ·Carcinogenesis · Pubmed #30165468.

ABSTRACT: High frequency of mortality in patients with pancreatic ductal adenocarcinoma (PDAC) is vastly associated with the invasive and metastatic nature of these cancer cells. Little is known about the factors involved in this invasive/metastatic process. The current challenge in the treatment of these patients is the lack of viable options besides gemcitabine. The aim of this study was to evaluate the role of PDZ-binding kinase (PBK)/T-LAK cell-originated protein kinase (TOPK) in invasive PDAC cells and to determine whether PBK/TOPK expression drives invasiveness in PDAC. Using gain-of-function and loss-of-function studies in established and patient-derived xenograft-PDAC cell lines, and examining patient-derived archival tissue samples, we demonstrate for the first time that PBK/TOPK is upregulated in pancreatic cancer and expression levels are closely associated with the invasive property of pancreatic cancer cells. Modulation of PBK/TOPK causally regulates the invasive ability of PDAC cells. We also demonstrate that two key players in metastatic invasion, matrix metalloproteinases-2 (MMP-2) and MMP-9 gelatinase activity and gene promoter activities, are regulated by PBK/TOPK. Moreover, we demonstrate for the first time that PBK/TOPK provides stability of an oncoprotein, c-MYC, which transcriptionally regulates MMP-2 and MMP-9 in these invasive PDAC cells. Our in vitro and in situ data corroborate that PBK/TOPK is closely associated with the invasive nature of PDAC and reveal a novel mechanism by which the metastatic behavior of human pancreatic cancer cells is regulated. These findings provide a rationale for targeting PBK/TOPK for the therapeutic intervention of invasive/metastatic pancreatic cancer in human.

12 Article Pancreatic Cancer Related Health Disparities: A Commentary. 2018

Scarton, Lisa / Yoon, Saunjoo / Oh, Sungho / Agyare, Edward / Trevino, Jose / Han, Bo / Lee, Eunsook / Setiawan, Veronica Wendy / Permuth, Jennifer B / Schmittgen, Thomas D / Odedina, Folakemi G / Wilkie, Diana J. ·Department of Family, Community and Health System Science, 1225 Center Drive, P. O. Box 100187, Gainesville, FL 32610, USA. lscarton@ufl.edu. · Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL 32610, USA. yoon@UFL.EDU. · Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL 32610, USA. sungho.oh@ufl.edu. · Department of Pharmaceutics, College of Pharmacy & Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32301, USA. edward.agyare@famu.edu. · Department of Surgery, College of Medicine, University of Florida, Gainesville, FL 32610, USA. Jose.Trevino@surgery.ufl.edu. · Department Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. bohan@usc.edu. · Department of Pharmacology and Toxicology, College of Pharmacy & Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL 32301, USA. eunsook.lee@famu.edu. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. vsetiawa@med.usc.edu. · Departments of Cancer Epidemiology and Gastroinestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. Jenny.Permuth@moffitt.org. · Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. TSchmittgen@cop.ufl.edu. · Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. FOdedina@cop.ufl.edu. · Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL 32610, USA. diwilkie@ufl.edu. ·Cancers (Basel) · Pubmed #30021952.

ABSTRACT: We summarize the risk factors that may significantly contribute to racial disparities in pancreatic cancer, which is now the third leading cause of cancer deaths and projected to be second around 2030 in 12 years. For decades, the incidence rate of pancreatic cancer among Blacks has been 30% to 70% higher than other racial groups in the United States and the 5-year survival rate is approximately 5%. Diabetes and obesity have been identified as potentially predisposing factors to pancreatic cancer and both are more common among Blacks. Smoking continues to be one of the most important risk factors for pancreatic cancer and smoking rates are higher among Blacks compared to other racial groups. The overall risk of pancreatic cancer due to changes in DNA is thought to be the same for most racial groups; however, DNA methylation levels have been observed to be significantly different between Blacks and Whites. This finding may underlie the racial disparities in pancreatic cancer. Identification and prevention of these factors may be effective strategies to reduce the high incidence and mortality rates for pancreatic cancer among Blacks.

13 Article Intestinal microbiota enhances pancreatic carcinogenesis in preclinical models. 2018

Thomas, Ryan M / Gharaibeh, Raad Z / Gauthier, Josee / Beveridge, Mark / Pope, Jillian L / Guijarro, Maria V / Yu, Qin / He, Zhen / Ohland, Christina / Newsome, Rachel / Trevino, Jose / Hughes, Steven J / Reinhard, Mary / Winglee, Kathryn / Fodor, Anthony A / Zajac-Kaye, Maria / Jobin, Christian. ·Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA. · Department of Surgery, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA. · Department of Medicine, University of Florida College of Veterinary Medicine, Gainesville, FL, USA. · Department of Anatomy and Cell Biology, University of Florida College of Veterinary Medicine, Gainesville, FL, USA. · Laboratory of Comparative Pathology, University of Florida College of Veterinary Medicine, Gainesville, FL, USA. · Department of Bioinformatics and Genomics, The University of North Carolina at Charlotte College of Computing and Informatics, Charlotte, NC, USA. · Department of Infectious Disease and Immunology, University of Florida College of Medicine, Gainesville, FL 32610, USA. ·Carcinogenesis · Pubmed #29846515.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States yet data are scant regarding host factors influencing pancreatic carcinogenesis. Increasing evidence support the role of the host microbiota in carcinogenesis but its role in PDAC is not well established. Herein, we report that antibiotic-mediated microbial depletion of KrasG12D/PTENlox/+ mice showed a decreased proportion of poorly differentiated tumors compared to microbiota-intact KrasG12D/PTENlox/+ mice. Subsequent 16S rRNA PCR showed that ~50% of KrasG12D/PTENlox/+ mice with PDAC harbored intrapancreatic bacteria. To determine if a similar observation in humans correlates with presence of PDAC, benign and malignant human pancreatic surgical specimens demonstrated a microbiota by 16S bacterial sequencing and culture confirmation. However, the microbial composition did not differentiate PDAC from non-PDAC tissue. Furthermore, murine pancreas did not naturally acquire a pancreatic microbiota, as germ-free mice transferred to specific pathogen-free housing failed to acquire intrapancreatic bacteria over time, which was not augmented by a murine model of colitis. Finally, antibiotic-mediated microbial depletion of Nod-SCID mice, compared to microbiota-intact, showed increased time to PDAC xenograft formation, smaller tumors, and attenuated growth. Interestingly, both xenograft cohorts were devoid of intratumoral bacteria by 16S rRNA PCR, suggesting that intrapancreatic/intratumoral microbiota is not the sole driver of PDAC acceleration. Xenografts from microbiota-intact mice demonstrated innate immune suppression by immunohistochemistry and differential regulation of oncogenic pathways as determined by RNA sequencing. Our work supports a long-distance role of the intestinal microbiota on PDAC progression and opens new research avenues regarding pancreatic carcinogenesis.

14 Article Viscoelastic properties of human pancreatic tumors and in vitro constructs to mimic mechanical properties. 2018

Rubiano, Andres / Delitto, Daniel / Han, Song / Gerber, Michael / Galitz, Carly / Trevino, Jose / Thomas, Ryan M / Hughes, Steven J / Simmons, Chelsey S. ·Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, United States. · Department of Surgery, College of Medicine, University of Florida, United States. · Department of Mathematics, College of Liberal Arts and Sciences, University of Florida, United States. · Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, United States; J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, United States. Electronic address: css@ufl.edu. ·Acta Biomater · Pubmed #29191507.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease. Mesoscale indentation quantified viscoelastic metrics of resected malignant tumors, inflamed chronic pancreatitis regions, and histologically normal tissue. Both pancreatitis (2.15 ± 0.41 kPa, Mean ± SD) and tumors (5.46 ± 3.18 kPa) exhibit higher Steady-State Modulus (SSM) than normal tissue (1.06 ± 0.25 kPa; p < .005). The average viscosity of pancreatitis samples (63.2 ± 26.7 kPa·s) is significantly lower than that of both normal tissue (252 ± 134 kPa·s) and tumors (349 ± 222 kPa·s; p < .005). To mimic this remodeling behavior, PDAC and TAS cells were isolated from human PDAC tumors. Conditioned medium from PDAC cells was used to culture TAS-embedded collagen hydrogels. After 7 days, TAS-embedded gels in control medium reached SSM (1.45 ± 0.12 kPa) near normal pancreas, while gels maintained with conditioned medium achieved higher SSM (3.38 ± 0.146 kPa) consistent with tumors. Taken together, we have demonstrated an in vitro system that recapitulates in vivo stiffening of PDAC tumors. In addition, our quantification of viscoelastic properties suggests that elastography algorithms incorporating viscosity may be able to more accurately distinguish between pancreatic cancer and pancreatitis. STATEMENT OF SIGNIFICANCE: Understanding tumor-stroma crosstalk in pancreatic ductal adenocarcinoma (PDAC) is challenged by a lack of stroma-mimicking model systems. To design appropriate models, pancreatic tissue must be characterized with a method capable of evaluating in vitro models as well. Our indentation-based characterization tool quantified the distinct viscoelastic signatures of inflamed resections from pancreatitis, tumors from PDAC, and otherwise normal tissue to inform development of mechanically appropriate engineered tissues and scaffolds. We also made progress toward a 3D in vitro system that recapitulates mechanical properties of tumors. Our in vitro model of stromal cells in collagen and complementary characterization system can be used to investigate mechanisms of cancer-stroma crosstalk in PDAC and to propose and test innovative therapies.

15 Article Pancreatic Mucinous Cystic Neoplasm Communicating with Main Pancreatic Duct: An Unrecognized Presentation of Pancreatic Mucinous Neoplasm? 2017

Zhou, Weixun / Saam, Trustin / Zhou, Yihua / Trevino, Jose / Liu, Xiuli / Cao, Dengfeng / Lai, Jinping. ·Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China. · Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, U.S.A. · Department of Radiology, Saint Louis University School of Medicine, St. Louis, MO, U.S.A. · Department of Surgery, University of Florida College of Medicine, Gainesville, FL, U.S.A. · Department of Pathology, Immunology, and Laboratory Medicine, Washington University in Saint Louis, St. Louis, MO, U.S.A. · Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, U.S.A. jinpinglai@ufl.edu. ·Anticancer Res · Pubmed #29187489.

ABSTRACT: Mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) are two well recognized entities of precursor cystic lesions of pancreatic duct adenocarcinoma. The characteristic features of MCNs are the lined mucinous epithelium with underlying ovarian-type stroma, but without communication with the ducts, while that for IPMNs are the communication with the ducts but without the underlying ovarian-type stroma. Here we report a case of MCN communicating with the main pancreatic duct in a 68-year-old woman. The initial radiographic diagnosis was pancreatic IPMN with main pancreatic involvement and this was also confirmed during gross examination. Histologically, the pancreatic cystic neoplasm was lined with mucinous epithelium with underlying ovarian-type of stroma. Immunohistochemical stains confirmed that the stroma cells were positive for ER, PR, alpha-inhibin and focally positive for CD10. The final pathologic diagnosis was pancreatic mucinous cystic neoplasm communicating with the main pancreatic duct. To the best of our knowledge, this is the second pathology confirmed case of MCN communicating with the main pancreatic duct. A careful gross examination and bivalvation of the main duct communicating with the cystic neoplasm helps render the correct diagnosis. If more cases are reported in the future, the MCN communicating with duct could become a new entity of pancreatic mucinous neoplasm.

16 Article The pancreatic tumor microenvironment drives changes in miRNA expression that promote cytokine production and inhibit migration by the tumor associated stroma. 2017

Han, Song / Gonzalo, David H / Feely, Michael / Delitto, Daniel / Behrns, Kevin E / Beveridge, Mark / Zhang, DongYu / Thomas, Ryan / Trevino, Jose G / Schmittgen, Thomas D / Hughes, Steven J. ·Department of Surgery, University of Florida, Gainesville, FL 32610, USA. · Department of Pathology, College of Medicine, University of Florida, Gainesville, FL 32610, USA. · College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. ·Oncotarget · Pubmed #28903323.

ABSTRACT: The pancreatic adenocarcinoma (PDAC) microenvironment is largely comprised of fibrotic tumor associated stroma (TAS) that contributes to the lethal biology of PDAC. microRNA (miRNA) are small non-coding RNAs that regulate gene expression. We hypothesized that interactions between PDAC cells and TAS cells within the microenvironment modulate miRNA expression and thus, tumor biology. We observed that miR-205 and members of the miR-200 family (miR-200a, -200b, -200c, -141 and miR-429) were exclusively expressed in PDAC cells, consistent with an epithelial miRNA signature, while miR-145 and miR-199 family members (miR-199a and -199b) were solely expressed in TAS cells, consistent with a stromal miRNA signature. This finding was confirmed by qRT-PCR of RNA obtained by laser-capture microdissection of surgical specimens. Using an

17 Article Linc-ing Circulating Long Non-coding RNAs to the Diagnosis and Malignant Prediction of Intraductal Papillary Mucinous Neoplasms of the Pancreas. 2017

Permuth, Jennifer B / Chen, Dung-Tsa / Yoder, Sean J / Li, Jiannong / Smith, Andrew T / Choi, Jung W / Kim, Jongphil / Balagurunathan, Yoganand / Jiang, Kun / Coppola, Domenico / Centeno, Barbara A / Klapman, Jason / Hodul, Pam / Karreth, Florian A / Trevino, Jose G / Merchant, Nipun / Magliocco, Anthony / Malafa, Mokenge P / Gillies, Robert. ·Departments of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. jenny.permuth@moffitt.org. · Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. jenny.permuth@moffitt.org. · Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Molecular Genomics Core Facility, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, Florida, USA. · Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, USA. ·Sci Rep · Pubmed #28874676.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective biomarkers for early detection. We hypothesized that circulating long non-coding RNAs (lncRNAs) may act as diagnostic markers of incidentally-detected cystic PDAC precursors known as intraductal papillary mucinous neoplasms (IPMNs) and predictors of their pathology/histological classification. Using NanoString nCounter® technology, we measured the abundance of 28 candidate lncRNAs in pre-operative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Results showed that two lncRNAs (GAS5 and SRA) aided in differentiating IPMNs from controls. An 8-lncRNA signature (including ADARB2-AS1, ANRIL, GLIS3-AS1, LINC00472, MEG3, PANDA, PVT1, and UCA1) had greater accuracy than standard clinical and radiologic features in distinguishing 'aggressive/malignant' IPMNs that warrant surgical removal from 'indolent/benign' IPMNs that can be observed. When the 8-lncRNA signature was combined with plasma miRNA data and quantitative 'radiomic' imaging features, the accuracy of predicting IPMN pathological classification improved. Our findings provide novel information on the ability to detect lncRNAs in plasma from patients with IPMNs and suggest that an lncRNA-based blood test may have utility as a diagnostic adjunct for identifying IPMNs and their pathology, especially when incorporated with biomarkers such as miRNAs, quantitative imaging features, and clinical data.

18 Article Orthotopic Patient-Derived Pancreatic Cancer Xenografts Engraft Into the Pancreatic Parenchyma, Metastasize, and Induce Muscle Wasting to Recapitulate the Human Disease. 2017

Go, Kristina L / Delitto, Daniel / Judge, Sarah M / Gerber, Michael H / George, Thomas J / Behrns, Kevin E / Hughes, Steven J / Judge, Andrew R / Trevino, Jose G. ·From the *Department of Surgery, College of Medicine; †Department of Physical Therapy; and ‡Department of Medicine, College of Medicine, University of Florida Health Science Center, Gainesville, FL. ·Pancreas · Pubmed #28609371.

ABSTRACT: OBJECTIVE: Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model. The purpose of this study was to evaluate the degree to which an orthotopic PDX model of PC recapitulates these aspects of the human disease. METHODS: Human PDX-derived PC tumors were implanted directly into the pancreas of NOD.Cg-Prkdc Il2rg/SzJ mice. Tumor growth, metastasis, and muscle wasting were then evaluated. RESULTS: Orthotopically implanted PDX-derived tumors consistently incorporated into the murine pancreatic parenchyma, metastasized to both the liver and lungs and induced muscle wasting directly proportional to the size of the tumor, consistent of the cancer cachexia syndrome. CONCLUSIONS: Through the orthotopic implantation technique described, we demonstrate a highly reproducible model that recapitulates both local and systemic aspects of human PC.

19 Article Analysis of the Cost Effectiveness of Laparoscopic Pancreatoduodenectomy. 2017

Gerber, Michael H / Delitto, Daniel / Crippen, Cristina J / George, Thomas J / Behrns, Kevin E / Trevino, Jose G / Cioffi, Jessica L / Hughes, Steven J. ·Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd, Room 6165, PO Box 100109, Gainesville, FL, 32610, USA. · Department of Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, USA. · Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Rd, Room 6165, PO Box 100109, Gainesville, FL, 32610, USA. steven.hughes@surgery.ufl.edu. ·J Gastrointest Surg · Pubmed #28567575.

ABSTRACT: OBJECTIVE: We sought to determine if laparoscopic pancreatoduodenectomy (LPD) is a cost-effective alternative to open pancreatoduodenectomy (OPD). METHODS: Hospital cost data, discharge disposition, readmission rates, and readmission costs from periampullary cancer patient cohorts of LPD and OPD were compared. The surgical cohorts over a 40-month period were clinically similar, consisting of 52 and 50 patients in the LPD and OPD groups, respectively. RESULTS: The total operating room costs were higher in the LPD group as compared to the OPD group (median US$12,290 vs US$11,299; P = 0.05) due to increased costs for laparoscopic equipment and regional nerve blocks (P ≤ 0.0001). Although hospital length of stay was shorter in the LPD group (median 7 vs 8 days; P = 0.025), the average hospital cost was not significantly decreased compared to the OPD group (median $28,496 vs $28,623). Surgery-related readmission rates and associated costs did not differ between groups. Compared to OPD patients, significantly more LPD patients were discharged directly home rather than to other healthcare facilities (88% vs 72%; P = 0.047). CONCLUSION: For the index hospitalization, the cost of LPD is equivalent to OPD. Total episode-of-care costs may favor LPD via reduced post-hospital needs for skilled nursing and rehabilitation.

20 Article A pilot study of radiologic measures of abdominal adiposity: weighty contributors to early pancreatic carcinogenesis worth evaluating? 2017

Permuth, Jennifer B / Choi, Jung W / Chen, Dung-Tsa / Jiang, Kun / DeNicola, Gina / Li, Jian-Nong / Coppola, Domenico / Centeno, Barbara A / Magliocco, Anthony / Balagurunathan, Yoganand / Merchant, Nipun / Trevino, Jose G / Jeong, Daniel. ·Departments of Cancer Epidemiology. · Gastrointestinal Oncology. · Diagnostic Imaging and Interventional Radiology. · Biostatistics and Bioinformatics. · Anatomic Pathology. · Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa 33612, FL, USA. · Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami 33136, FL, USA. · Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville 32611, FL, USA. ·Cancer Biol Med · Pubmed #28443205.

ABSTRACT: OBJECTIVE: Intra-abdominal fat is a risk factor for pancreatic cancer (PC), but little is known about its contribution to PC precursors known as intraductal papillary mucinous neoplasms (IPMNs). Our goal was to evaluate quantitative radiologic measures of abdominal/visceral obesity as possible diagnostic markers of IPMN severity/pathology. METHODS: In a cohort of 34 surgically-resected, pathologically-confirmed IPMNs (17 benign; 17 malignant) with preoperative abdominal computed tomography (CT) images, we calculated body mass index (BMI) and four radiologic measures of obesity: total abdominal fat (TAF) area, visceral fat area (VFA), subcutaneous fat area (SFA), and visceral to subcutaneous fat ratio (V/S). Measures were compared between groups using Wilcoxon two-sample exact tests and other metrics. RESULTS: Mean BMI for individuals with malignant IPMNs (28.9 kg/m CONCLUSIONS: Preliminary findings suggest measures of visceral fat from routine medical images may help predict IPMN pathology, acting as potential noninvasive diagnostic adjuncts for management and targets for intervention that may be more biologically-relevant than BMI. Further investigation of gender-specific associations in larger, prospective IPMN cohorts is warranted to validate and expand upon these observations.

21 Article δ-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem-like cells and prevents pancreatic cancer metastasis. 2017

Husain, Kazim / Centeno, Barbara A / Coppola, Domenico / Trevino, Jose / Sebti, Said M / Malafa, Mokenge P. ·Departments of Gastrointestinal Oncology, Tampa, FL, USA. · Departments of Pathology, Tampa, FL, USA. · Department of Surgery, University of Florida, Gainesville, FL, USA. · Departments of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. ·Oncotarget · Pubmed #28404939.

ABSTRACT: The growth, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC) is characterized by the activation and growth of tumor-initiating cells in distant organs that have stem-like properties. Thus, inhibiting growth of these cells may prevent PDAC growth and metastases. We have demonstrated that δ-tocotrienol, a natural form of vitamin E (VEDT), is bioactive against cancer, delays progression, and prevents metastases in transgenic mouse models of PDAC. In this report, we provide the first evidence that VEDT selectively inhibits PDAC stem-like cells. VEDT inhibited the viability, survival, self-renewal, and expression of Oct4 and Sox2 transcription factors in 3 models of PDAC stem-like cells. In addition, VEDT inhibited the migration, invasion, and several biomarkers of epithelial-to-mesenchymal transition and angiogenesis in PDAC cells and tumors. These processes are critical for tumor metastases. Furthermore, in the L3.6pl orthotopic model of PDAC metastases, VEDT significantly inhibited growth and metastases of these cells. Finally, in an orthotopic xenograft model of human PDAC stem-like cells, we showed that VEDT significantly retarded the growth and metastases of gemcitabine-resistant PDAC human stem-like cells. Because VEDT has been shown to be safe and to reach bioactive levels in humans, this work supports investigating VEDT for chemoprevention of PDAC metastases.

22 Article A clinically applicable muscular index predicts long-term survival in resectable pancreatic cancer. 2017

Delitto, Daniel / Judge, Sarah M / George, Thomas J / Sarosi, George A / Thomas, Ryan M / Behrns, Kevin E / Hughes, Steven J / Judge, Andrew R / Trevino, Jose G. ·Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL. · Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL. · Department of Medicine, College of Medicine, University of Florida Health Science Center, Gainesville, FL. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL; North Florida/South Georgia Veterans Health System, Department of Surgery, University of Florida College of Medicine, Gainesville, FL. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL. Electronic address: jose.trevino@surgery.ufl.edu. ·Surgery · Pubmed #27932030.

ABSTRACT: BACKGROUND: The relationship between myopenia, nutritional status, and long-term oncologic outcomes remains poorly characterized in patients with clinically resectable pancreatic cancer. We sought to reliably quantify prognostic indicators of preoperative cachexia in a manner applicable to any clinical setting. METHODS: Preoperative computed tomographies were available electronically and suitable for analysis in 73 of 82 consecutive patients with pancreatic cancer undergoing pancreatoduodenectomy between November 2010 and February 2014. The psoas index was computed from the cross-sectional area of the psoas muscles normalized to vertebral body area at the third lumbar vertebra. Correlation and proportional hazards analyses were performed to identify relationships between muscularity, preoperative nutritional markers, clinicopathologic parameters, and long-term survival. RESULTS: The psoas index correlated strongly with preoperative hemoglobin and albumin levels (P = .001 and .014, respectively) identifying a pattern of preoperative frailty. High psoas index and the albumin and hemoglobin levels were associated with improved long-term survival (hazard ratio 0.014, P < .001; hazard ratio 0.43, P < .001; and hazard ratio = 0.80, P = .014); however, on multivariate analysis, the psoas index proved to be the only independent predictor of survival (hazard ratio 0.021; P = .003). Rapid decreases in the psoas index during neoadjuvant chemotherapy were associated with poor postoperative outcomes, as were decreases in the psoas index during the postoperative period. CONCLUSION: The data indicate that the psoas index, a calculation derived from a clinically mandated, preoperative computed tomography, is a statistically powerful and easily calculated predictor of survival in pancreatic cancer when compared to tumor grade and stage as well as previously validated nutritional parameters.

23 Article Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia. 2017

Delitto, Daniel / Judge, Sarah M / Delitto, Andrea E / Nosacka, Rachel L / Rocha, Fernanda G / DiVita, Bayli B / Gerber, Michael H / George, Thomas J / Behrns, Kevin E / Hughes, Steven J / Wallet, Shannon M / Judge, Andrew R / Trevino, Jose G. ·Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. · Department of Physical Therapy, University of Florida Health Science Center, Gainesville, FL 32610, USA. · Department of Oral Biology, College of Dentistry, University of Florida Health Science Center, Gainesville, FL 32610, USA. · Department of Medicine, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. ·Oncotarget · Pubmed #27901481.

ABSTRACT: Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

24 Article Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to Promote a Tumor-Tolerant Immune Microenvironment. 2017

Delitto, Daniel / Delitto, Andrea E / DiVita, Bayli B / Pham, Kien / Han, Song / Hartlage, Emily R / Newby, Brittney N / Gerber, Michael H / Behrns, Kevin E / Moldawer, Lyle L / Thomas, Ryan M / George, Thomas J / Brusko, Todd M / Mathews, Clayton E / Liu, Chen / Trevino, Jose G / Hughes, Steven J / Wallet, Shannon M. ·Department of Surgery, University of Florida, Gainesville, Florida. · Department of Oral Biology, University of Florida, Gainesville, Florida. · Department of Pathology, Immunology, Laboratory Medicine, University of Florida, Gainesville, Florida. · Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School and Rutgers Robert Wood Johnson Medical School, Newark, New Jersey. · Department of Medicine, University of Florida, Gainesville, Florida. · Department of Surgery, University of Florida, Gainesville, Florida. swallet@dental.ufl.edu steven.hughes@surgery.ufl.edu. · Department of Oral Biology, University of Florida, Gainesville, Florida. swallet@dental.ufl.edu steven.hughes@surgery.ufl.edu. ·Cancer Res · Pubmed #27864347.

ABSTRACT: Cancer cells exert mastery over the local tumor-associated stroma (TAS) to configure protective immunity within the tumor microenvironment. The immunomodulatory character of pancreatic lysates of patients with cancer differs from those with pancreatitis. In this study, we evaluated the cross-talk between pancreatic cancer and its TAS in primary human cell culture models. Upon exposure of TAS to pancreatic cancer cell-conditioned media, we documented robust secretion of IL6 and IL8. This TAS response was MyD88-dependent and sufficient to directly suppress both CD4

25 Article Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms. 2016

Permuth, Jennifer B / Choi, Jung / Balarunathan, Yoganand / Kim, Jongphil / Chen, Dung-Tsa / Chen, Lu / Orcutt, Sonia / Doepker, Matthew P / Gage, Kenneth / Zhang, Geoffrey / Latifi, Kujtim / Hoffe, Sarah / Jiang, Kun / Coppola, Domenico / Centeno, Barbara A / Magliocco, Anthony / Li, Qian / Trevino, Jose / Merchant, Nipun / Gillies, Robert / Malafa, Mokenge / Anonymous850880. ·Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Department of Clinical Surgery/Surgical Oncology, Palmetto Health/USC School of Medicine, Columbia, South Carolina, USA. · Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. · Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. · Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, Florida, USA. · Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, USA. ·Oncotarget · Pubmed #27589689.

ABSTRACT: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cancer precursors incidentally discovered by cross-sectional imaging. Consensus guidelines for IPMN management rely on standard radiologic features to predict pathology, but they lack accuracy. Using a retrospective cohort of 38 surgically-resected, pathologically-confirmed IPMNs (20 benign; 18 malignant) with preoperative computed tomography (CT) images and matched plasma-based 'miRNA genomic classifier (MGC)' data, we determined whether quantitative 'radiomic' CT features (+/- the MGC) can more accurately predict IPMN pathology than standard radiologic features 'high-risk' or 'worrisome' for malignancy. Logistic regression, principal component analyses, and cross-validation were used to examine associations. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were estimated. The MGC, 'high-risk,' and 'worrisome' radiologic features had area under the receiver operating characteristic curve (AUC) values of 0.83, 0.84, and 0.54, respectively. Fourteen radiomic features differentiated malignant from benign IPMNs (p<0.05) and collectively had an AUC=0.77. Combining radiomic features with the MGC revealed an AUC=0.92 and superior sensitivity (83%), specificity (89%), PPV (88%), and NPV (85%) than other models. Evaluation of uncertainty by 10-fold cross-validation retained an AUC>0.80 (0.87 (95% CI:0.84-0.89)). This proof-of-concept study suggests a noninvasive radiogenomic approach may more accurately predict IPMN pathology than 'worrisome' radiologic features considered in consensus guidelines.

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