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Pancreatic Neoplasms: HELP
Articles by Kshitij S. Arora
Based on 6 articles published since 2010
(Why 6 articles?)
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Between 2010 and 2020, Kshitij Arora wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer. 2019

Ligorio, Matteo / Sil, Srinjoy / Malagon-Lopez, Jose / Nieman, Linda T / Misale, Sandra / Di Pilato, Mauro / Ebright, Richard Y / Karabacak, Murat N / Kulkarni, Anupriya S / Liu, Ann / Vincent Jordan, Nicole / Franses, Joseph W / Philipp, Julia / Kreuzer, Johannes / Desai, Niyati / Arora, Kshitij S / Rajurkar, Mihir / Horwitz, Elad / Neyaz, Azfar / Tai, Eric / Magnus, Neelima K C / Vo, Kevin D / Yashaswini, Chittampalli N / Marangoni, Francesco / Boukhali, Myriam / Fatherree, Jackson P / Damon, Leah J / Xega, Kristina / Desai, Rushil / Choz, Melissa / Bersani, Francesca / Langenbucher, Adam / Thapar, Vishal / Morris, Robert / Wellner, Ulrich F / Schilling, Oliver / Lawrence, Michael S / Liss, Andrew S / Rivera, Miguel N / Deshpande, Vikram / Benes, Cyril H / Maheswaran, Shyamala / Haber, Daniel A / Fernandez-Del-Castillo, Carlos / Ferrone, Cristina R / Haas, Wilhelm / Aryee, Martin J / Ting, David T. ·Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. · Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. · Clinic of Surgery, UKSH Campus Lübeck, Germany. · Institute of Pathology, University Medical Center Freiburg, Germany. · Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: aryee.martin@mgh.harvard.edu. · Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: dting1@mgh.harvard.edu. ·Cell · Pubmed #31155233.

ABSTRACT: Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland "units." Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.

2 Article Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms. 2018

Franses, Joseph W / Basar, Omer / Kadayifci, Abdurrahman / Yuksel, Osman / Choz, Melissa / Kulkarni, Anupriya S / Tai, Eric / Vo, Kevin D / Arora, Kshitij S / Desai, Niyati / Licausi, Joseph A / Toner, Mehmet / Maheswaran, Shyamala / Haber, Daniel A / Ryan, David P / Brugge, William R / Ting, David T. ·Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA. · Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA. · Center for Engineering in Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Howard Hughes Medical Institute, Chevy Chase, Maryland, USA. · Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA brugge.william@mgh.harvard.edu dting1@mgh.harvard.edu. · Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA brugge.william@mgh.harvard.edu dting1@mgh.harvard.edu. ·Oncologist · Pubmed #28860411.

ABSTRACT: BACKGROUND: Recent work has demonstrated early shedding of circulating epithelial cells (CECs) from premalignant intraductal papillary mucinous neoplasms (IPMNs). However, the potential use of CECs as a "liquid biopsy" for patients with IPMNs has been limited by antigen dependence of CEC isolation devices and the lack of robust detection biomarkers across CEC phenotypes. MATERIALS AND METHODS: We utilized a negative depletion microfluidic platform to purify CECs from contaminating leukocytes and coupled this platform with immunofluorescence, RNA in situ hybridization, and RNA sequencing (RNA-seq) detection and enumeration. RESULTS: Using established protein (EpCAM, cytokeratins) and novel noncoding RNA (HSATII, cytokeratins) biomarkers, we detected CECs in 88% of patients bearing IPMN lesions. RNA-seq analysis for MUC genes confirm the likely origin of these CECs from pancreatic lesions. CONCLUSION: Our findings increase the sensitivity of detection of these cells and therefore could have clinical implications for cancer risk stratification. IMPLICATIONS FOR PRACTICE: This work describes a high-sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at high risk of malignant transformation. Further research efforts are underway to define the transcriptional programs that might allow discrimination between circulating cells released from tumors that will become malignant and cells released from tumors that will not. After further refinement, this combination of technologies could be deployed for monitoring and early detection of patients at high risk for developing new or recurrent pancreatic malignancies.

3 Article STK38L kinase ablation promotes loss of cell viability in a subset of KRAS-dependent pancreatic cancer cell lines. 2017

Grant, Trevor J / Mehta, Anita K / Gupta, Anamika / Sharif, Ahmad A D / Arora, Kshitij S / Deshpande, Vikram / Ting, David T / Bardeesy, Nabeel / Ganem, Neil J / Hergovich, Alexander / Singh, Anurag. ·Department of Pharmacology and Experimental Therapeutics, Center for Cancer Research, Boston University Graduate School of Medicine, Boston, MA, USA. · University College London, Cancer Institute, London, United Kingdom. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, USA. ·Oncotarget · Pubmed #29108249.

ABSTRACT: Pancreatic ductal adenocarcinomas (PDACs) are highly aggressive malignancies, associated with poor clinical prognosis and limited therapeutic options. Oncogenic

4 Article SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b. 2016

Kugel, Sita / Sebastián, Carlos / Fitamant, Julien / Ross, Kenneth N / Saha, Supriya K / Jain, Esha / Gladden, Adrianne / Arora, Kshitij S / Kato, Yasutaka / Rivera, Miguel N / Ramaswamy, Sridhar / Sadreyev, Ruslan I / Goren, Alon / Deshpande, Vikram / Bardeesy, Nabeel / Mostoslavsky, Raul. ·The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA. · The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA. · Broad Technology Labs (BTL), The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. · The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA. · Department of Molecular Biology, The Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. · The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: rmostoslavsky@mgh.harvard.edu. ·Cell · Pubmed #27180906.

ABSTRACT: Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD(+)-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This epigenetic program defines a distinct subset with a poor prognosis, representing 30%-40% of human PDAC, characterized by reduced SIRT6 expression and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor and uncover the Lin28b pathway as a potential therapeutic target in a molecularly defined PDAC subset. PAPERCLIP.

5 Article Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma. 2016

Moy, Andrea P / Arora, Kshitij / Deshpande, Vikram. ·Pathology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. ·Histopathology · Pubmed #26841202.

ABSTRACT: AIMS: Bile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well-differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma. METHODS AND RESULTS: We studied 26 bile duct adenomas, three bile duct hamartomas, and 158 pancreatic ductal adenocarcinomas. Branched-chain in-situ hybridization (bISH) for albumin was performed; bISH is based on the branched DNA technology, wherein signal amplification is achieved via a series of sequential steps. Additionally, BRAFV600E immunohistochemistry (IHC) was performed on a subset of cases. Twenty-three of 25 (92%) bile duct adenomas were positive for albumin; 18 (72%) showed diffuse staining, and five showed focal staining (20%), including two challenging examples. Two bile duct hamartomas also stained positively. All pancreatic adenocarcinomas were negative for albumin. Seven of 16 (44%) bile duct adenomas and five of 106 (5%) pancreatic ductal adenocarcinomas were positive for BRAFV600E by IHC. The sensitivity and specificity of expression of albumin, as detected by bISH, for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 92% and 100%, respectively; the sensitivity and specificity of BRAFV600E IHC for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 43.8% and 95.3%, respectively. CONCLUSIONS: Diagnostically challenging examples of bile duct adenoma may be distinguished from metastatic pancreatic adenocarcinoma by the use of albumin bISH.

6 Article Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. 2014

Ting, David T / Wittner, Ben S / Ligorio, Matteo / Vincent Jordan, Nicole / Shah, Ajay M / Miyamoto, David T / Aceto, Nicola / Bersani, Francesca / Brannigan, Brian W / Xega, Kristina / Ciciliano, Jordan C / Zhu, Huili / MacKenzie, Olivia C / Trautwein, Julie / Arora, Kshitij S / Shahid, Mohammad / Ellis, Haley L / Qu, Na / Bardeesy, Nabeel / Rivera, Miguel N / Deshpande, Vikram / Ferrone, Cristina R / Kapur, Ravi / Ramaswamy, Sridhar / Shioda, Toshi / Toner, Mehmet / Maheswaran, Shyamala / Haber, Daniel A. ·Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Harvard Medical School, Boston, MA 02114, USA; Department of Health Sciences, University of Genoa, 16126 Genoa, Italy. · Center for Engineering in Medicine, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Harvard Medical School, Boston, MA 02114, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Radiation Oncology, Harvard Medical School, Boston, MA 02114, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Harvard Medical School, Boston, MA 02114, USA; Department of Pathology, Harvard Medical School, Boston, MA 02114, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Pathology, Harvard Medical School, Boston, MA 02114, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Harvard Medical School, Boston, MA 02114, USA. · Center for Engineering in Medicine, Harvard Medical School, Boston, MA 02114, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Surgery, Harvard Medical School, Boston, MA 02114, USA. Electronic address: maheswaran@helix.mgh.harvard.edu. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: haber@helix.mgh.harvard.edu. ·Cell Rep · Pubmed #25242334.

ABSTRACT: Circulating tumor cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To define their composition, we compared genome-wide expression profiles of CTCs with matched primary tumors in a mouse model of pancreatic cancer, isolating individual CTCs using epitope-independent microfluidic capture, followed by single-cell RNA sequencing. CTCs clustered separately from primary tumors and tumor-derived cell lines, showing low-proliferative signatures, enrichment for the stem-cell-associated gene Aldh1a2, biphenotypic expression of epithelial and mesenchymal markers, and expression of Igfbp5, a gene transcript enriched at the epithelial-stromal interface. Mouse as well as human pancreatic CTCs exhibit a very high expression of stromal-derived extracellular matrix (ECM) proteins, including SPARC, whose knockdown in cancer cells suppresses cell migration and invasiveness. The aberrant expression by CTCs of stromal ECM genes points to their contribution of microenvironmental signals for the spread of cancer to distant organs.