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Pancreatic Neoplasms: HELP
Articles by A. Maitra
Based on 9 articles published since 2010
(Why 9 articles?)
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Between 2010 and 2020, A. Maitra wrote the following 9 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review The emerging role of endoscopic ultrasound-guided core biopsy for the evaluation of solid pancreatic masses. 2015

Bhutani, M / Koduru, P / Lanke, G / Bruno, M / Maitra, A / Giovannini, M. ·Department of Gastroenterology, Hepatology and Nutrition, University of Texas, MD Anderson Cancer Center, Houston, TX, USA - manoop.bhutani@mdanderson.org. ·Minerva Gastroenterol Dietol · Pubmed #25675155.

ABSTRACT: Pancreatic ductal adenocarcinoma is a lethal cancer with a 5-year survival rate of less than 5%. Surgical resection is the only curative treatment but only 20% are eligible for resection at the time of diagnosis. Early detection of cancer is of paramount importance in the management. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the preferred modality for obtaining tissue diagnosis of pancreatic masses. However, the diagnostic accuracy of EUS-FNA may be limited by several factors like availability of onsite cytopathology, adequacy of tissue core for histology, location of the mass, presence of underlying chronic pancreatitis, and experience of the endoscopist. Modern oncology is focusing on personalizing treatment based on tissue analysis of genetic aberrations and molecular biomarkers which are now available. Core tissue also aids in the diagnosis of disease entities like lymphoma, metastatic tumors, neuroendocrine tumors and autoimmune pancreatitis whose diagnosis rely on preserved tissue architecture and immunohistochemistry. Making accurate diagnosis of solid pancreatic masses is critical to avoid unnecessary resections in patients with benign lesions like focal lesions of chronic pancreatitis and autoimmune pancreatitis which mimic cancer. To overcome the limitations of FNA and to obtain adequate core tissue, a Tru-Cut biopsy needle was developed which met with variable success due to stiffness, cumbersome operation and technical failure using it in the duodenum/pancreatic head. More recently fine needle biopsy needles, with reverse bevel technology have become available in different sizes (19, 22, 25-gauge). The aim of this article was to review the emerging role of core biopsy needles in acquiring tissue in solid pancreatic masses and discuss its potential role in personalized medicine.

2 Article Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients. 2018

Castillo, J / Bernard, V / San Lucas, F A / Allenson, K / Capello, M / Kim, D U / Gascoyne, P / Mulu, F C / Stephens, B M / Huang, J / Wang, H / Momin, A A / Jacamo, R O / Katz, M / Wolff, R / Javle, M / Varadhachary, G / Wistuba, I I / Hanash, S / Maitra, A / Alvarez, H. ·Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · The University of Texas MD Anderson Cancer UTHealth Graduate School of Biomedical Sciences, Houston, USA. · Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA. · ContinuumDx, Houston, USA. · McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA. ·Ann Oncol · Pubmed #29045505.

ABSTRACT: Background: Detection of circulating tumor DNA can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We carried out a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal 'surfaceome' in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling. Patients and methods: Surface exosomal proteins were profiled in 13 human PDAC and 2 non-neoplastic cell lines by liquid chromatography-mass spectrometry. A total of 173 prospectively collected blood samples from 103 PDAC patients underwent exosome isolation. Droplet digital PCR was used on 74 patients (136 total exosome samples) to determine baseline KRAS mutation call rates while patients were on therapy. PDAC-specific exosome capture was then carried out on additional 29 patients (37 samples) using an antibody cocktail directed against selected proteins, followed by droplet digital PCR analysis. Exosomal DNA in a PDAC patient resistant to therapy were profiled using a molecular barcoded, targeted sequencing panel to determine the utility of enriched nucleic acid material for comprehensive molecular analysis. Results: Proteomic analysis of the exosome 'surfaceome' revealed multiple PDAC-specific biomarker candidates: CLDN4, EPCAM, CD151, LGALS3BP, HIST2H2BE, and HIST2H2BF. KRAS mutations in total exosomes were detected in 44.1% of patients undergoing active therapy compared with 73.0% following exosome capture using the selected biomarkers. Enrichment of exosomal cargo was amenable to molecular profiling, elucidating a putative mechanism of resistance to PARP inhibitor therapy in a patient harboring a BRCA2 mutation. Conclusion: Exosomes provide unique opportunities in the context of liquid biopsies for enrichment of tumor-specific material in circulation. We present a comprehensive surfaceome characterization of PDAC exosomes which allows for capture and molecular profiling of tumor-derived DNA.

3 Article A predictive model of inflammatory markers and patient-reported symptoms for cachexia in newly diagnosed pancreatic cancer patients. 2017

Fogelman, David R / Morris, J / Xiao, L / Hassan, M / Vadhan, S / Overman, M / Javle, S / Shroff, R / Varadhachary, G / Wolff, R / Vence, L / Maitra, A / Cleeland, C / Wang, X S. ·Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA. dfogelman@mdanderson.org. · Department of Biostatistics, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd Unit 426, Houston, TX, 77030, USA. · Department of Sarcoma Research, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Immunology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Pathology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Department of Symptom Research, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. ·Support Care Cancer · Pubmed #28111717.

ABSTRACT: BACKGROUND: Cachexia is a frequent manifestation of pancreatic cancer, can limit a patient's ability to take chemotherapy, and is associated with shortened survival. We developed a model to predict the early onset of cachexia in advanced pancreatic cancer patients. METHODS: Patients with newly diagnosed, untreated metastatic or locally advanced pancreatic cancer were included. Serum cytokines were drawn prior to therapy. Patient symptoms were recorded using the M.D. Anderson Symptom Inventory (MDASI). Our primary endpoint was either 10% weight loss or death within 60 days of the start of therapy. RESULTS: Twenty-seven of 89 patients met the primary endpoint (either having lost 10% of body weight or having died within 60 days of the start of treatment). In a univariate analysis, smoking, history symptoms of pain and difficulty swallowing, high levels of MK, CXCL-16, IL-6, TNF-a, and low IL-1b all correlated with this endpoint. We used recursive partition to fit a regression tree model, selecting four of 26 variables (CXCL-16, IL-1b, pain, swallowing difficulty) as important in predicting cachexia. From these, a model of two cytokines (CXCL-16 > 5.135 ng/ml and IL-1b < 0.08 ng/ml) demonstrated a better sensitivity and specificity for this outcome (0.70 and 0.86, respectively) than any individual cytokine or tumor marker. CONCLUSIONS: Cachexia is frequent in pancreatic cancer; one in three patients met our endpoint of 10% weight loss or death within 60 days. Inflammatory cytokines are better than conventional tumor markers at predicting this outcome. Recursive partitioning analysis suggests that a model of CXCL-16 and IL-1B may offer a better ability than individual cytokines to predict this outcome.

4 Article High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. 2017

Allenson, K / Castillo, J / San Lucas, F A / Scelo, G / Kim, D U / Bernard, V / Davis, G / Kumar, T / Katz, M / Overman, M J / Foretova, L / Fabianova, E / Holcatova, I / Janout, V / Meric-Bernstam, F / Gascoyne, P / Wistuba, I / Varadhachary, G / Brennan, P / Hanash, S / Li, D / Maitra, A / Alvarez, H. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA. · Genetic Epidemiology Group International Agency for Research on Cancer, Lyon, France. · Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia. · Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. · Department of Preventive Medicine, Palacky University of Medicine, Olomouc, Czech Republic. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. · Department of Investigational Cancer Therapeutics and the Institute for Personalized Cancer Therapy, Houston, USA. · Section of Experimental Pathology, University of Texas M.D. Anderson Cancer Center, Houston, USA · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA. ·Ann Oncol · Pubmed #28104621.

ABSTRACT: Background: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival. Results: KRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls. Conclusions: Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

5 Article Chronic inflammation initiates multiple forms of K-Ras-independent mouse pancreatic cancer in the absence of TP53. 2017

Swidnicka-Siergiejko, A K / Gomez-Chou, S B / Cruz-Monserrate, Z / Deng, D / Liu, Y / Huang, H / Ji, B / Azizian, N / Daniluk, J / Lu, W / Wang, H / Maitra, A / Logsdon, C D. ·Department of Cancer Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. · Department of Gastroenterology and Internal Medicine, University of Bialystok, Bialystok, Poland. · Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Ohio State University Wexner Medical Center, Columbus, OH, USA. · Department of Gastroenterology, Shanghai Hospital, Second Military Medical University, Shanghai, China. · Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL, USA. · Department of GI Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. · Department of Translational Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA. ·Oncogene · Pubmed #27991926.

ABSTRACT: Chronic inflammation (CI) is a risk factor for pancreatic cancer (PC) including the most common type, ductal adenocarcinoma (PDAC), but its role and the mechanisms involved are unclear. To investigate the role of CI in PC, we generated genetic mouse models with pancreatic specific CI in the presence or absence of TP53. Mice were engineered to express either cyclooxygenase-2 (COX-2) or IκB kinase-2 (IKK2), and TP53

6 Article Minimally invasive genomic and transcriptomic profiling of visceral cancers by next-generation sequencing of circulating exosomes. 2016

San Lucas, F A / Allenson, K / Bernard, V / Castillo, J / Kim, D U / Ellis, K / Ehli, E A / Davies, G E / Petersen, J L / Li, D / Wolff, R / Katz, M / Varadhachary, G / Wistuba, I / Maitra, A / Alvarez, H. ·Department of Translational Molecular Pathology Department of Pathology. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston. · Department of Pathology The University of Texas Graduate School of Biomedical Sciences at Houston, Houston. · Department of Pathology. · Avera Institute for Human Genetics, Sioux Falls. · Department of Gastrointestinal (GI) Medical Oncology. · Department of Translational Molecular Pathology. · Department of Translational Molecular Pathology Department of Pathology Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA amaitra@mdanderson.org. ·Ann Oncol · Pubmed #26681674.

ABSTRACT: BACKGROUND: The ability to perform comprehensive profiling of cancers at high resolution is essential for precision medicine. Liquid biopsies using shed exosomes provide high-quality nucleic acids to obtain molecular characterization, which may be especially useful for visceral cancers that are not amenable to routine biopsies. PATIENTS AND METHODS: We isolated shed exosomes in biofluids from three patients with pancreaticobiliary cancers (two pancreatic, one ampullary). We performed comprehensive profiling of exoDNA and exoRNA by whole genome, exome and transcriptome sequencing using the Illumina HiSeq 2500 sequencer. We assessed the feasibility of calling copy number events, detecting mutational signatures and identifying potentially actionable mutations in exoDNA sequencing data, as well as expressed point mutations and gene fusions in exoRNA sequencing data. RESULTS: Whole-exome sequencing resulted in 95%-99% of the target regions covered at a mean depth of 133-490×. Genome-wide copy number profiles, and high estimates of tumor fractions (ranging from 56% to 82%), suggest robust representation of the tumor DNA within the shed exosomal compartment. Multiple actionable mutations, including alterations in NOTCH1 and BRCA2, were found in patient exoDNA samples. Further, RNA sequencing of shed exosomes identified the presence of expressed fusion genes, representing an avenue for elucidation of tumor neoantigens. CONCLUSIONS: We have demonstrated high-resolution profiling of the genomic and transcriptomic landscapes of visceral cancers. A wide range of cancer-derived biomarkers could be detected within the nucleic acid cargo of shed exosomes, including copy number profiles, point mutations, insertions, deletions, gene fusions and mutational signatures. Liquid biopsies using shed exosomes has the potential to be used as a clinical tool for cancer diagnosis, therapeutic stratification and treatment monitoring, precluding the need for direct tumor sampling.

7 Article p53 mutations cooperate with oncogenic Kras to promote adenocarcinoma from pancreatic ductal cells. 2016

Bailey, J M / Hendley, A M / Lafaro, K J / Pruski, M A / Jones, N C / Alsina, J / Younes, M / Maitra, A / McAllister, F / Iacobuzio-Donahue, C A / Leach, S D. ·Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, The University of Texas Health Science Center at Houston, Houston, TX, USA. · The David Rubenstein Pancreatic Cancer Research Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA. · Departments of Pathology and Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Departments of Clinical Cancer Prevention and GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Oncogene · Pubmed #26592447.

ABSTRACT: Pancreatic cancer is one of the most lethal malignancies, with virtually all patients eventually succumbing to their disease. Mutations in p53 have been documented in >50% of pancreatic cancers. Owing to the high incidence of p53 mutations in PanIN 3 lesions and pancreatic tumors, we interrogated the comparative ability of adult pancreatic acinar and ductal cells to respond to oncogenic Kras and mutant Tp53(R172H) using Hnf1b:CreER(T2) and Mist1:CreER(T2) mice. These studies involved co-activation of a membrane-tethered GFP lineage label, allowing for direct visualization and isolation of cells undergoing Kras and mutant p53 activation. Kras activation in Mist1(+) adult acinar cells resulted in brisk PanIN formation, whereas no evidence of pancreatic neoplasia was observed for up to 6 months following Kras activation in Hnf1beta(+) adult ductal cells. In contrast to the lack of response to oncogenic Kras alone, simultaneous activation of Kras and mutant p53 in adult ductal epithelium generated invasive PDAC in 75% of mice as early as 2.5 months after tamoxifen administration. These data demonstrate that pancreatic ductal cells, whereas exhibiting relative resistance to oncogenic Kras alone, can serve as an effective cell of origin for pancreatic ductal adenocarcinoma in the setting of gain-of-function mutations in p53.

8 Article Differential in vivo tumorigenicity of diverse KRAS mutations in vertebrate pancreas: A comprehensive survey. 2015

Park, J T / Johnson, N / Liu, S / Levesque, M / Wang, Y J / Ho, H / Huso, D / Maitra, A / Parsons, M J / Prescott, J D / Leach, S D. ·Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Graduate Program in Human Genetics, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Molecular & Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · 1] Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Graduate Program in Human Genetics, Johns Hopkins Medical Institutions, Baltimore, MD, USA [3] Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ·Oncogene · Pubmed #25065594.

ABSTRACT: Somatic activation of the KRAS proto-oncogene is evident in almost all pancreatic cancers, and appears to represent an initiating event. These mutations occur primarily at codon 12 and less frequently at codons 13 and 61. Although some studies have suggested that different KRAS mutations may have variable oncogenic properties, to date there has been no comprehensive functional comparison of multiple KRAS mutations in an in vivo vertebrate tumorigenesis system. We generated a Gal4/UAS-based zebrafish model of pancreatic tumorigenesis in which the pancreatic expression of UAS-regulated oncogenes is driven by a ptf1a:Gal4-VP16 driver line. This system allowed us to rapidly compare the ability of 12 different KRAS mutations (G12A, G12C, G12D, G12F, G12R, G12S, G12V, G13C, G13D, Q61L, Q61R and A146T) to drive pancreatic tumorigenesis in vivo. Among fish injected with one of five KRAS mutations reported in other tumor types but not in human pancreatic cancer, 2/79 (2.5%) developed pancreatic tumors, with both tumors arising in fish injected with A146T. In contrast, among fish injected with one of seven KRAS mutations known to occur in human pancreatic cancer, 22/106 (20.8%) developed pancreatic cancer. All eight tumorigenic KRAS mutations were associated with downstream MAPK/ERK pathway activation in preneoplastic pancreatic epithelium, whereas nontumorigenic mutations were not. These results suggest that the spectrum of KRAS mutations observed in human pancreatic cancer reflects selection based on variable tumorigenic capacities, including the ability to activate MAPK/ERK signaling.

9 Article Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer. 2012

Caldwell, M E / DeNicola, G M / Martins, C P / Jacobetz, M A / Maitra, A / Hruban, R H / Tuveson, D A. ·Li Ka Shing Centre, Cambridge Research Institute, Cancer Research UK, Cambridge, UK. ·Oncogene · Pubmed #21860420.

ABSTRACT: During tumor initiation, oncogene-induced senescence (OIS) is proposed to limit the progression of preneoplasms to invasive carcinoma unless circumvented by the acquisition of certain tumor suppressor mutations. Using a variety of biomarkers, OIS has been previously reported in a wide range of human and murine precursor lesions, including the pancreas, lung, colon and skin. Here, we have characterized a panel of potential OIS biomarkers in human and murine pancreatic intraepithelial neoplasia (PanIN), and found that only senescence-associated β-galactosidase (SAβgal) activity is specifically enriched in these precursors, compared with pancreatic ductal adenocarcinoma (PDA). Indeed, many of the other proposed OIS biomarkers are detected in actively proliferating PanIN epithelium and in cells within the microenvironment. Surprisingly, acinar to ductal metaplasia (ADM), a distinct preneoplasm that is potentially a precursor for PanIN, also exhibits SAβgal activity and contains a higher content of p21 and p53 than PanIN. Therefore, SAβgal activity is the only biomarker that accurately identifies a small and heterogeneous population of non-proliferating premalignant cells in the pancreas, and the concomitant expression of p53 and p21 in ADM supports the possibility that PanIN and ADM each exhibit discrete senescence blocks.