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Pancreatic Neoplasms: HELP
Articles by Juan Pablo Arnoletti
Based on 13 articles published since 2009
(Why 13 articles?)

Between 2009 and 2019, J. P. Arnoletti wrote the following 13 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Guideline Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. 2012

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen W / Ben-Josef, Edgar / Benson, Al B / Casper, Ephraim S / Cohen, Steven J / Czito, Brian / Ellenhorn, Joshua D I / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Ma, Wen Wee / Malafa, Mokenge P / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Sasson, Aaron R / Tally, Anitra / Thayer, Sarah P / Whiting, Samuel / Wolff, Robert A / Wolpin, Brian M / Freedman-Cass, Deborah A / Shead, Dorothy A / Anonymous1061005. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

2 Guideline Pancreatic adenocarcinoma. 2010

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen / Ben-Josef, Edgar / Benson, Al B / Berlin, Jordan D / Cameron, John L / Casper, Ephraim S / Cohen, Steven J / Duff, Michelle / Ellenhorn, Joshua D I / Hawkins, William G / Hoffman, John P / Kuvshinoff, Boris W / Malafa, Mokenge P / Muscarella, Peter / Nakakura, Eric K / Sasson, Aaron R / Thayer, Sarah P / Tyler, Douglas S / Warren, Robert S / Whiting, Samuel / Willett, Christopher / Wolff, Robert A / Anonymous3820673. · ·J Natl Compr Canc Netw · Pubmed #20876541.

ABSTRACT: -- No abstract --

3 Review Beyond cytology: why and when does the oncologist require core tissue? 2014

de la Fuente, Sebastian G / Arnoletti, J Pablo. ·Florida Hospital Orlando, University of Central Florida, Orlando, FL, USA. ·Gastrointest Endosc Clin N Am · Pubmed #24215757.

ABSTRACT: There are 2 main reasons why oncologists may require additional tissue and a histologic section in addition to cytopathology from FNA specimens: improved diagnostic accuracy and molecular characterization of tumors. Rather than mutually exclusive diagnostic procedures, EUS-FNA and EUS-CNB must be viewed as supplementary techniques and both approaches should be incorporated as essential tools in the current endoscopic armamentarium.

4 Review Primary pancreatic Ewing's sarcoma with portal vein tumor thrombosis. 2013

Reilly, Chris / Zenoni, Scott / Hasan, Muhammad K / Varadarajulu, Shyam / Tran, Tien-Anh / de la Fuente, Sebastian G / Arnoletti, Juan P. ·University of Central Florida College of Medicine, Oviedo, FL 32765, USA. creilly@knights.ucf.edu ·J Gastrointest Surg · Pubmed #23192427.

ABSTRACT: BACKGROUND: Extraosseous Ewing's sarcoma (EES) is a mesenchyme-derived small blue cell tumor, which is distinguished by its rarity, aggressiveness, dismal prognosis, and distinct pathogenesis. Occurring almost exclusively among children and young adults, EES can arise from a variety of organs and portends a rapid clinical deterioration and high likelihood of recurrence. DISCUSSION: We present the first reported case of a primary pancreatic Ewing's sarcoma in a patient with concomitant portal vein thrombosis. The atypical presentation of this extraordinarily rare tumor underscores the imperative to maintain EES in the differential diagnosis of suspicious, indistinct pancreatic lesions in young patients. In addition, we review the available literature describing additional cases of primary pancreatic Ewing's sarcoma.

5 Clinical Trial A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer. 2011

Arnoletti, J P / Frolov, A / Eloubeidi, M / Keene, K / Posey, J / Wood, T / Greeno, Edward / Jhala, N / Varadarajulu, S / Russo, S / Christein, J / Oster, R / Buchsbaum, D J / Vickers, S M. ·Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. ·Cancer Chemother Pharmacol · Pubmed #20589377.

ABSTRACT: PURPOSE: (1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial-mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment. METHODS: Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0-300 mg/m(2)/week) given concurrently with cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens. RESULTS: Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1-2 adverse events was 96%, and incidence of 3-4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients. CONCLUSIONS: Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m(2)/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer.

6 Article Portal Venous Blood Circulation Supports Immunosuppressive Environment and Pancreatic Cancer Circulating Tumor Cell Activation. 2017

Arnoletti, Juan Pablo / Zhu, Xiang / Almodovar, Alvin J O / Veldhuis, Paula P / Sause, Ryan / Griffith, Elizabeth / Corpus, George / Chang, Jeffrey C C / Fanaian, Naʼim / Litherland, Sally A. ·From the *Florida Hospital Cancer Institute, †Institute for Surgical Advancement/Center for Specialized Surgery, ‡Center for Interventional Endoscopy, and §Diagnostic Pathology, Florida Hospital, Orlando, FL. ·Pancreas · Pubmed #27400259.

ABSTRACT: OBJECTIVES: Aggressive spread and liver metastases are predominant features of pancreatic ductal adenocarcinoma (PDAC). This study investigates activation of PDAC circulating tumor cells (CTC) and immunosuppression in the portal venous system. METHODS: Portal venous and peripheral blood were collected during pancreaticoduodenectomy from patients with PDAC (n = 21) or other non-PDAC pancreatic conditions (n = 20). Circulating tumor cells were isolated by fluorescence-activated cell sorting and characterized for messenger RNA (mRNA) expression and acetylated chromatin encoding K-RAS exon 12 mutation (K-RASmut). Myeloid-derived suppressor cells (MDSC) were identified using flow cytometry. RESULTS: Pancreatic ductal adenocarcinoma K-RASmut mRNA expression in portal venous blood CTC was significantly elevated compared with preoperative and postoperative peripheral blood (P = 0.0123 and P = 0.0246, respectively). There was no significant variation in total CTC numbers between portal and peripheral blood.Portal venous M-MDSC were elevated compared with peripheral blood in PDAC patients (P = 0.0065). M-MDSC increases correlated with K-RASmut mRNA-expressing CTC present in PDAC portal blood (P < 0.0001). CONCLUSIONS: Association of MDSC with active CTC in portal venous blood may support immunosuppression within the portal venous circulation to promote PDAC CTC survival.

7 Article The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. 2016

Garcia, P L / Miller, A L / Kreitzburg, K M / Council, L N / Gamblin, T L / Christein, J D / Heslin, M J / Arnoletti, J P / Richardson, J H / Chen, D / Hanna, C A / Cramer, S L / Yang, E S / Qi, J / Bradner, J E / Yoon, K J. ·Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA. · Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA. · Division of General Surgery, Gastrointestinal Surgery or Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. · Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, USA. · Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA. ·Oncogene · Pubmed #25961927.

ABSTRACT: The primary aim of this study was to evaluate the antitumor efficacy of the bromodomain inhibitor JQ1 in pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (tumorgraft) models. A secondary aim of the study was to evaluate whether JQ1 decreases expression of the oncogene c-Myc in PDAC tumors, as has been reported for other tumor types. We used five PDAC tumorgraft models that retain specific characteristics of tumors of origin to evaluate the antitumor efficacy of JQ1. Tumor-bearing mice were treated with JQ1 (50 mg/kg daily for 21 or 28 days). Expression analyses were performed with tumors harvested from host mice after treatment with JQ1 or vehicle control. An nCounter PanCancer Pathways Panel (NanoString Technologies) of 230 cancer-related genes was used to identify gene products affected by JQ1. Quantitative RT-PCR, immunohistochemistry and immunoblots were carried out to confirm that changes in RNA expression reflected changes in protein expression. JQ1 inhibited the growth of all five tumorgraft models (P<0.05), each of which harbors a KRAS mutation; but induced no consistent change in expression of c-Myc protein. Expression profiling identified CDC25B, a regulator of cell cycle progression, as one of the three RNA species (TIMP3, LMO2 and CDC25B) downregulated by JQ1 (P<0.05). Inhibition of tumor progression was more closely related to decreased expression of nuclear CDC25B than to changes in c-Myc expression. JQ1 and other agents that inhibit the function of proteins with bromodomains merit further investigation for treating PDAC tumors. Work is ongoing in our laboratory to identify effective drug combinations that include JQ1.

8 Article Development and histopathological characterization of tumorgraft models of pancreatic ductal adenocarcinoma. 2013

Garcia, Patrick L / Council, Leona N / Christein, John D / Arnoletti, J Pablo / Heslin, Marty J / Gamblin, Tracy L / Richardson, Joseph H / Bjornsti, Mary-Ann / Yoon, Karina J. ·Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America. ·PLoS One · Pubmed #24194913.

ABSTRACT: Pancreatic cancer is the one of the deadliest of all malignancies. The five year survival rate for patients with this disease is 3-5%. Thus, there is a compelling need for novel therapeutic strategies to improve the clinical outcome for patients with pancreatic cancer.  Several groups have demonstrated for other types of solid tumors that early passage human tumor xenograft models can be used to define some genetic and molecular characteristics of specific human tumors. Published studies also suggest that murine tumorgraft models (early passage xenografts derived from direct implantation of primary tumor specimens) may be useful in identifying compounds with efficacy against specific tumor types.  Because pancreatic cancer is a fatal disease and few well-characterized model systems are available for translational research, we developed and characterized a panel of pancreatic tumorgraft models for biological evaluation and therapeutic drug testing.  Of the 41 primary tumor specimens implanted subcutaneously into mice, 35 produced viable tumorgraft models.  We document the fidelity of histological and morphological characteristics and of KRAS mutation status among primary (F0), F1, and F2 tumors for the twenty models that have progressed to the F3 generation.  Importantly, our procedures produced a take rate of 85%, higher than any reported in the literature. Primary tumor specimens that failed to produce tumorgrafts were those that either contained <10% tumor cells or that were obtained from significantly smaller primary tumors. In view of the fidelity of characteristics of primary tumor specimens through at least the F2 generation in mice, we propose that these tumorgraft models represent a useful tool for identifying critical characteristics of pancreatic tumors and for evaluating potential therapies. 

9 Article Targeting ErbB3-mediated stromal-epithelial interactions in pancreatic ductal adenocarcinoma. 2011

Liles, J S / Arnoletti, J P / Kossenkov, A V / Mikhaylina, A / Frost, A R / Kulesza, P / Heslin, M J / Frolov, A. ·Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA. ·Br J Cancer · Pubmed #21792199.

ABSTRACT: BACKGROUND: We sought to investigate the role of ErbB3-mediated signalling on the interaction between pancreatic cancer-associated fibroblasts (CAF) and carcinoma cells in an effort to disrupt tumourigenic pancreatic ductal adenocarcinoma (PDAC) stromal-epithelial cross-communication. METHODS: Primary CAF cultures were established from human PDAC surgical specimens. AsPC-1 pancreatic cancer cell murine subcutaneous xenografts were developed in the presence and absence of CAF and were subsequently treated with epidermal growth factor receptor (EGFR) inhibitors (erlotinib) and ErbB3 inhibitors (MM-121, monoclonal ErbB3 antibody). RESULTS: Cancer-associated fibroblasts were found to secrete neuregulin-1 (NRG-1), which promoted proliferation via phosphorylation of ErbB3 and AKT in AsPC-1 PDAC cells. This signalling cascade was effectively inhibited both in vitro and in vivo by specific ErbB3 blockade with MM-121, with greater degree of tumourigenesis inhibition when combined with erlotinib. The CAF-AsPC-1 pancreatic cancer xenografts reached significantly greater tumour volume than those xenografts lacking CAF and were resistant to the anti-tumour effects of EGFR inhibition with erlotinib. CONCLUSION: Cancer-associated fibroblasts-derived NRG-1 promote PDAC tumourigenesis via ErbB3-AKT signalling and overcomes single-agent EGFR inhibition. Disruption of this stromally mediated tumourigenic mechanism is best obtained through combined EGFR-ErbB3 inhibition with both erlotinib and MM-121. We have identified the NRG-1/ErbB3 axis as an attractive molecular target for the interruption of tumourigenic stromal-epithelial interactions within the PDAC microenvironment.

10 Article Mucinous cystic neoplasm of the pancreas. 2011

Bang, Ji Young / Varadarajulu, Shyam / Arnoletti, Juan Pablo. ·Department of Internal Medicine, University of Alabama at Birmingham, USA. ·Clin Gastroenterol Hepatol · Pubmed #21596157.

ABSTRACT: -- No abstract --

11 Article Serum biomarker panels for the detection of pancreatic cancer. 2011

Brand, Randall E / Nolen, Brian M / Zeh, Herbert J / Allen, Peter J / Eloubeidi, Mohamad A / Goldberg, Michael / Elton, Eric / Arnoletti, Juan P / Christein, John D / Vickers, Selwyn M / Langmead, Christopher J / Landsittel, Douglas P / Whitcomb, David C / Grizzle, William E / Lokshin, Anna E. ·Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. ·Clin Cancer Res · Pubmed #21325298.

ABSTRACT: PURPOSE: Serum-biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations. EXPERIMENTAL DESIGN: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers. RESULTS: Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19-9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19-9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19-9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19-9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19-9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer. CONCLUSIONS: The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations.

12 Article ErbB3 expression promotes tumorigenesis in pancreatic adenocarcinoma. 2010

Liles, J Spencer / Arnoletti, Juan Pablo / Tzeng, Ching-Wei D / Howard, J Harrison / Kossenkov, Andrew V / Kulesza, Peter / Heslin, Martin J / Frolov, Andrey. ·Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. ·Cancer Biol Ther · Pubmed #20647770.

ABSTRACT: Historically, ErbB3 has been overlooked within the ErbB receptor family due to its perceived lack of tyrosine kinase activity. We have previously demonstrated that in pancreatic cancer ErbB3 is the preferred dimerization partner of EGFR, ErbB3 protein expression level directly correlates with the anti-proliferative effect of erlotinib (an EGFR-specific tyrosine kinase inhibitor), and transient knockdown of ErbB3 expression results in acquired resistance to EGFR-targeted therapy. In this study, we develop a stable isogenic model of ErbB3 expression in an attempt to decipher ErbB3's true contribution to pancreatic cancer tumorigenesis and to examine how this receptor affects cellular sensitivity to EGFR-targeted therapy. Analysis of the EGFR-ErbB3 heterodimer demonstrates that ligand-induced PI3K-AKT signaling is limited to ErbB3-expressing cells and that this signaling cascade can be partially abrogated by inhibiting EGFR function with erlotinib. Using our model of exogenous ErbB3 expression we showed a direct relationship between ErbB3 protein levels and increased pancreatic cancer cell proliferation in vitro. In vivo, ErbB3(+)PANC-1 xenografts had a significantly larger tumor volume than PANC-1 control xenografts (ErbB3-PANC-1) and displayed increased sensitivity to EGFR-targeted therapy. In pancreatic cancer, ErbB3 appears to be critically involved in EGFR signaling as evidenced by its profound effect on cellular proliferation and its ability to influence response to EGFR-targeted therapy.

13 Article Epidermal growth factor receptor (EGFR) intron 1 polymorphism and clinical outcome in pancreatic adenocarcinoma. 2010

Frolov, Andrey / Liles, J Spencer / Kossenkov, Andrew V / Tzeng, Ching-Wei D / Jhala, Nirag / Kulesza, Peter / Varadarajulu, Shyam / Eloubeidi, Mohamad / Heslin, Martin J / Arnoletti, J Pablo. ·Department of Surgery, University of Alabama at Birmingham, USA. frolov@uab.edu ·Am J Surg · Pubmed #20409526.

ABSTRACT: BACKGROUND: Epidermal growth factor receptor (EGFR) intron 1 has a polymorphic region of CA repeats that is believed to be associated with increased EGFR expression, tumor aggressiveness, and worse survival in cancer patients. METHODS: A large population of pancreatic adenocarcinoma patients was investigated to evaluate this polymorphism as a potential prognostic marker of clinical outcome. Deoxyribonucleic acid obtained from 50 resected pancreatic adenocarcinomas and from 85 diagnostic endoscopic ultrasound-guided fine-needle aspiration procedures corresponding to patients with unresectable tumors was included. The correlation between CA repeat length and EGFR messenger ribonucleic acid levels was also examined. RESULTS: Analysis of the 135 patients revealed no correlation between EGFR intron 1 CA repeat length and tumor stage. There was no difference in overall patient survival when stratified by allele length. A correlation between EGFR intron 1 length and EGFR transcript and protein levels could not be established. CONCLUSIONS: The length of the EGFR intron 1 CA repeats does not correlate with levels of EGFR expression and cannot be used as marker of clinical prognosis in pancreatic cancer patients.