James Abbruzzese

Overview:

My research interests include the clinical study and treatment of pancreatic cancer.

Positions:

D. C. I. Professor of Medical Oncology

Medicine, Medical Oncology
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Chief, Division of Medical Oncology

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1978

University of Chicago

Intern, Internal Medicine

Johns Hopkins University School of Medicine

Resident, Internal Medicine

Johns Hopkins University School of Medicine

Grants:

Topic Refinement, Task order 9 Topic Briefs

Administered By
Duke Clinical Research Institute
Awarded By
Patient Centered Outcomes Research Institute
Role
Co Investigator
Start Date
End Date

Publications:

Imaging & Biomarker Correlates on Outcomes in a Phase II Trial of Neoadjuvant Gemcitabine/Nab-Paclitaxel and Hypofractionated Image-Guided Radiotherapy (HIGRT) in Potentially Resectable Pancreas Cancer

Authors
Kent, CL; Marin, D; Niedzwiecki, D; Stephens, SJ; Duffy, E; Malicki, M; Abbruzzese, J; Uronis, H; Blobe, G; Blazer, DG; Czito, B; Willett, CG; Palta, M
MLA Citation
Kent, C. L., et al. “Imaging & Biomarker Correlates on Outcomes in a Phase II Trial of Neoadjuvant Gemcitabine/Nab-Paclitaxel and Hypofractionated Image-Guided Radiotherapy (HIGRT) in Potentially Resectable Pancreas Cancer.” International Journal of Radiation Oncology*Biology*Physics, vol. 105, no. 1, Elsevier BV, 2019, pp. E238–39. Crossref, doi:10.1016/j.ijrobp.2019.06.2014.
URI
https://scholars.duke.edu/individual/pub1415201
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
105
Published Date
Start Page
E238
End Page
E239
DOI
10.1016/j.ijrobp.2019.06.2014

Oncogenic KRAS Reduces Expression of FGF21 in Acinar Cells to Promote Pancreatic Tumorigenesis in Mice on a High-Fat Diet.

BACKGROUND & AIMS: Obesity is a risk factor for pancreatic cancer. In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal adenocarcinoma (PDAC) by unknown mechanisms. We investigated how oncogenic KRAS regulates the expression of fibroblast growth factor 21, FGF21, a metabolic regulator that prevents obesity, and the effects of recombinant human FGF21 (rhFGF21) on pancreatic tumorigenesis. METHODS: We performed immunohistochemical analyses of FGF21 levels in human pancreatic tissue arrays, comprising 59 PDAC specimens and 45 nontumor tissues. We also studied mice with tamoxifen-inducible expression of oncogenic KRAS in acinar cells (KrasG12D/+ mice) and fElasCreERT mice (controls). KrasG12D/+ mice were placed on an HFD or regular chow diet (control) and given injections of rhFGF21 or vehicle; pancreata were collected and analyzed by histology, immunoblots, quantitative polymerase chain reaction, and immunohistochemistry. We measured markers of inflammation in the pancreas, liver, and adipose tissue. Activity of RAS was measured based on the amount of bound guanosine triphosphate. RESULTS: Pancreatic tissues of mice expressed high levels of FGF21 compared with liver tissues. FGF21 and its receptor proteins were expressed by acinar cells. Acinar cells that expressed KrasG12D/+ had significantly lower expression of Fgf21 messenger RNA compared with acinar cells from control mice, partly due to down-regulation of PPARG expression-a transcription factor that activates Fgf21 transcription. Pancreata from KrasG12D/+ mice on a control diet and given injections of rhFGF21 had reduced pancreatic inflammation, infiltration by immune cells, and acinar-to-ductal metaplasia compared with mice given injections of vehicle. HFD-fed KrasG12D/+ mice given injections of vehicle accumulated abdominal fat, developed extensive inflammation, pancreatic cysts, and high-grade pancreatic intraepithelial neoplasias (PanINs); half the mice developed PDAC with liver metastases. HFD-fed KrasG12D/+ mice given injections of rhFGF21 had reduced accumulation of abdominal fat and pancreatic triglycerides, fewer pancreatic cysts, reduced systemic and pancreatic markers of inflammation, fewer PanINs, and longer survival-only approximately 12% of the mice developed PDACs, and none of the mice had metastases. Pancreata from HFD-fed KrasG12D/+ mice given injections of rhFGF21 had lower levels of active RAS than from mice given vehicle. CONCLUSIONS: Normal acinar cells from mice and humans express high levels of FGF21. In mice, acinar expression of oncogenic KRAS significantly reduces FGF21 expression. When these mice are placed on an HFD, they develop extensive inflammation, pancreatic cysts, PanINs, and PDACs, which are reduced by injection of FGF21. FGF21 also reduces the guanosine triphosphate binding capacity of RAS. FGF21 might be used in the prevention or treatment of pancreatic cancer.
Authors
Luo, Y; Yang, Y; Liu, M; Wang, D; Wang, F; Bi, Y; Ji, J; Li, S; Liu, Y; Chen, R; Huang, H; Wang, X; Swidnicka-Siergiejko, AK; Janowitz, T; Beyaz, S; Wang, G; Xu, S; Bialkowska, AB; Luo, CK; Pin, CL; Liang, G; Lu, X; Wu, M; Shroyer, KR; Wolff, RA; Plunkett, W; Ji, B; Li, Z; Li, E; Li, X; Yang, VW; Logsdon, CD; Abbruzzese, JL; Lu, W
MLA Citation
Luo, Yongde, et al. “Oncogenic KRAS Reduces Expression of FGF21 in Acinar Cells to Promote Pancreatic Tumorigenesis in Mice on a High-Fat Diet..” Gastroenterology, vol. 157, no. 5, Nov. 2019, pp. 1413-1428.e11. Pubmed, doi:10.1053/j.gastro.2019.07.030.
URI
https://scholars.duke.edu/individual/pub1401549
PMID
31352001
Source
pubmed
Published In
Gastroenterology
Volume
157
Published Date
Start Page
1413
End Page
1428.e11
DOI
10.1053/j.gastro.2019.07.030

Preface

Authors
Neoptolemos, JP; Urrutia, R; Abbruzzese, JL; Büchler, MW
MLA Citation
Neoptolemos, J. P., et al. Preface. 2018, pp. ix–x. Scopus, doi:10.1007/978-1-4939-7193-0.
URI
https://scholars.duke.edu/individual/pub1353179
Source
scopus
Published Date
Start Page
ix
End Page
x
DOI
10.1007/978-1-4939-7193-0

FGF21 Delays Pancreatic Cancer Formation and Prevents Liver Metastasis in Oncogenic Kras Expressing Mice Fed on High-Fat Diet

Authors
Lu, W; Yang, Y; Luo, Y; Liu, Y; Wang, X; Liu, M; Wolff, RA; Abbruzzese, JL; Logsdon, CD
MLA Citation
Lu, W., et al. “FGF21 Delays Pancreatic Cancer Formation and Prevents Liver Metastasis in Oncogenic Kras Expressing Mice Fed on High-Fat Diet.” Pancreas, vol. 44, no. 8, LIPPINCOTT WILLIAMS & WILKINS, Nov. 2015, pp. 1393–1393.
URI
https://scholars.duke.edu/individual/pub1104264
Source
wos
Published In
Pancreas
Volume
44
Published Date
Start Page
1393
End Page
1393

SOX9: a useful marker for pancreatic ductal lineage of pancreatic neoplasms.

Previous studies showed that SOX9 plays a critical role in pancreatic ductal development. The aim of this study was to evaluate SOX9 as a marker for pancreatic ductal lineage. SOX9 expression was evaluated by immunohistochemistry in 146 benign pancreas (BP), 136 pancreatic ductal adenocarcinomas, 47 pancreatic intraepithelial neoplasia (PanIN), 21 intraductal papillary mucinous neoplasms (IPMNs), 14 mucinous cystic neoplasms, 10 serous cystadenomas, 39 pancreatic neuroendocrine tumors, 9 acinar cell carcinomas, and 23 solid pseudopapillary neoplasms. Nuclear expression of SOX9 was detected in the centroacinar cells and ductal cells, but not in acinar or endocrine cells in 100% BP. Focal or diffuse SOX9 expression was detected in 100% PanINs, 100% IPMNs, 100% mucinous cystic neoplasms, 100% serous cystadenomas, 89.0% pancreatic ductal adenocarcinomas, 2.6% pancreatic neuroendocrine tumors, 11.1% acinar cell carcinomas, and 0% solid pseudopapillary neoplasms. SOX9 expression was lower in PanIN2 and PanIN3 than in PanIN1 lesions (P < .01). Compared with BP, IPMN had lower SOX9 expression (P < .05). No correlation between SOX9 expression and other clinicopathologic parameters was identified. Our study showed that SOX9 is expressed in centroacinar and ductal epithelial cells of BP and is a useful marker for pancreatic ductal lineage of pancreatic neoplasms.
Authors
Shroff, S; Rashid, A; Wang, H; Katz, MH; Abbruzzese, JL; Fleming, JB; Wang, H
MLA Citation
Shroff, Stuti, et al. “SOX9: a useful marker for pancreatic ductal lineage of pancreatic neoplasms..” Hum Pathol, vol. 45, no. 3, Mar. 2014, pp. 456–63. Pubmed, doi:10.1016/j.humpath.2013.10.008.
URI
https://scholars.duke.edu/individual/pub1043364
PMID
24418153
Source
pubmed
Published In
Hum Pathol
Volume
45
Published Date
Start Page
456
End Page
463
DOI
10.1016/j.humpath.2013.10.008

Research Areas:

Adolescent
Adult
Age Distribution
Albumins
Animals
Blood Transfusion
Cell Differentiation
Cell Growth Processes
Cell Lineage
Cell Movement
Cell Transformation, Neoplastic
Chemotherapy, Adjuvant
Chi-Square Distribution
Child
Cisplatin
Clinical Competence
Combined Modality Therapy
Cytokines
DNA Repair
Diabetes Complications
Diabetes Mellitus, Type 2
Diagnosis, Differential
Disease Models, Animal
Disease-Free Survival
Drug Delivery Systems
Drug Therapy, Combination
Dyspnea
Epithelial Cells
False Positive Reactions
Fibrosis
Genetic Variation
Genotype
HEK293 Cells
HT29 Cells
Health Status
Homozygote
Hypothyroidism
Immunohistochemistry
Inflammation
Intercellular Signaling Peptides and Proteins
Islets of Langerhans
Isotope Labeling
Liver
Liver Neoplasms
Liver Neoplasms, Experimental
Lymph Nodes
Membrane Proteins
Mesoderm
Models, Biological
Mutation
Neoadjuvant Therapy
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Recurrence, Local
Neoplasm Staging
Neoplasms
Nervous System
Odds Ratio
Organoplatinum Compounds
Oxidative Stress
Pain
Pancreas
Pancreatectomy
Pancreatic Ducts
Pancreatic Neoplasms
Pancreaticoduodenectomy
Patient Care Team
Phenotype
Physicians
Polymorphism, Genetic
Probability
Prognosis
Proteolysis
Pyrimidines
Quinazolines
Radiation Tolerance
Radiotherapy, Adjuvant
Reactive Oxygen Species
Reference Values
Reproducibility of Results
Risk
Sensitivity and Specificity
Sepsis
Sex Distribution
Signal Transduction
Thiazoles
Time Factors
Treatment Outcome
Tumor Cells, Cultured
Tumor Markers, Biological
Water
Xenograft Model Antitumor Assays