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Pancreatic Neoplasms: HELP
Articles by Sam R. Grimaldo
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Sam Grimaldo wrote the following 3 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article p110γ deficiency protects against pancreatic carcinogenesis yet predisposes to diet-induced hepatotoxicity. 2019

Torres, Carolina / Mancinelli, Georgina / Cordoba-Chacon, Jose / Viswakarma, Navin / Castellanos, Karla / Grimaldo, Sam / Kumar, Sandeep / Principe, Daniel / Dorman, Matthew J / McKinney, Ronald / Hirsch, Emilio / Dawson, David / Munshi, Hidayatullah G / Rana, Ajay / Grippo, Paul J. ·Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL 60612; ctp@ugr.es pgrippo@uic.edu. · Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL 60612. · Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL 60612. · Research, Jesse Brown VA Medical Center, Chicago, IL 60612. · Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL 60612. · Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095. · Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095. · Department of Medicine, Northwestern University, Chicago, IL 60611. ·Proc Natl Acad Sci U S A · Pubmed #31266893.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor survival and resistance to conventional therapies. PI3K signaling is implicated in both disease initiation and progression, and specific inhibitors of selected PI3K p110 isoforms for managing solid tumors are emerging. We demonstrate that increased activation of PI3K signals cooperates with oncogenic Kras to promote aggressive PDAC in vivo. The p110γ isoform is overexpressed in tumor tissue and promotes carcinogenesis via canonical AKT signaling. Its selective blockade sensitizes tumor cells to gemcitabine in vitro, and genetic ablation of p110γ protects against Kras-induced tumorigenesis. Diet/obesity was identified as a crucial means of p110 subunit up-regulation, and in the setting of a high-fat diet, p110γ ablation failed to protect against tumor development, showing increased activation of pAKT and hepatic damage. These observations suggest that a careful and judicious approach should be considered when targeting p110γ for therapy, particularly in obese patients.

2 Article TM4SF18 is aberrantly expressed in pancreatic cancer and regulates cell growth. 2019

Singhal, Megha / Khatibeghdami, Mahsa / Principe, Daniel R / Mancinelli, Georgina E / Schachtschneider, Kyle M / Schook, Lawrence B / Grippo, Paul J / Grimaldo, Sam R. ·Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois, Chicago, Illinois, United States of America. · University of Illinois College of Medicine, Chicago, Illinois, United States of America. · Department of Radiology, University of Illinois at Chicago, Chicago, Illinois, United States of America. · Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois, United States of America. · National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America. · Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America. ·PLoS One · Pubmed #30897168.

ABSTRACT: Current therapies for pancreatic ductal adenocarcinoma (PDAC) only modestly impact survival and can be highly toxic. A greater understanding of the molecules regulating this disease is critical for identifying new drug targets and developing more effective therapies. The L6 family of proteins are known to be positive regulators of tumor growth and metastasis among various cancers. However, little is known about the L6 family member TM4SF18. We investigated the expression and localization of the TM4SF18 protein in normal human pancreas and in PDAC tissue. Utilizing immunohistochemistry (IHC) and western blot analysis, our studies for the first time demonstrate that TM4SF18 is highly expressed in PDAC tumor epithelium. Furthermore, we identified TM4SF18 to be expressed in normal acinar tissue and weakly expressed in normal ducts. Although there is minimal expression in normal ducts, we observed increased TM4SF18 levels in preneoplastic ducts and tumor epithelium. To investigate a functional role of TM4SF18 in PDAC we developed stably-expressing inducible shRNA pancreatic cancer cell lines. Knockdown of the TM4SF18 protein led to a significant decrease in Capan-1 cell growth as measured by the MTT assay, demonstrating this molecule to be a novel regulator of PDAC. Uniquely there is no ortholog of the TM4SF18 gene in mouse or rat prompting us to seek other in vivo experimental models. Using IHC and western blot analysis, expression of TM4SF18 was confirmed in the porcine PDAC model, thus we establish an alternative model to investigate this gene. TM4SF18 represents a promising novel biomarker and therapeutic target for pancreatic cancer.

3 Article Interplay between interferon regulatory factor 1 and BRD4 in the regulation of PD-L1 in pancreatic stellate cells. 2018

Ebine, Kazumi / Kumar, Krishan / Pham, Thao N / Shields, Mario A / Collier, Katharine A / Shang, Meng / DeCant, Brian T / Urrutia, Raul / Hwang, Rosa F / Grimaldo, Sam / Principe, Daniel R / Grippo, Paul J / Bentrem, David J / Munshi, Hidayatullah G. ·Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · Jesse Brown VA Medical Center, Chicago, IL, USA. · Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. krishan.kumar@northwestern.edu. · The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA. krishan.kumar@northwestern.edu. · Cold Spring Harbor Laboratory, Cold Spring Harbor, Cold Spring, NY, USA. · Laboratory of Epigenetics and Chromatin Dynamics, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Epigenomics Translational Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Medicine, University of Illinois, Chicago, IL, USA. · Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA. · Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. h-munshi@northwestern.edu. · Jesse Brown VA Medical Center, Chicago, IL, USA. h-munshi@northwestern.edu. · The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA. h-munshi@northwestern.edu. ·Sci Rep · Pubmed #30185888.

ABSTRACT: The fibrotic reaction is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of fibrosis in vivo. While there is increasing interest in the regulation of PD-L1 expression in cancer and immune cells, the expression and regulation of PD-L1 in other stromal cells, such as PSCs, has not been fully evaluated. Here we show that PSCs in vitro express higher PD-L1 mRNA and protein levels compared to the levels present in PDAC cells. We show that inhibitors targeting bromodomain and extra-terminal (BET) proteins and BRD4 knockdown decrease interferon-γ (IFN-γ)-induced PD-L1 expression in PSCs. We also show that c-MYC, one of the well-established targets of BET inhibitors, does not mediate IFN-γ-regulated PD-L1 expression in PSCs. Instead we show that interferon regulatory factor 1 (IRF1) mediates IFN-γ-induced PD-L1 expression in PSCs. Finally, while we show that BET inhibitors do not regulate IFN-γ-induced IRF1 expression in PSCs, BET inhibitors decrease binding of IRF1 and BRD4 to the PD-L1 promoter. Together, these results demonstrate the interplay between IRF1 and BRD4 in the regulation of PD-L1 in PSCs.