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Pancreatic Neoplasms: HELP
Articles by Mehmet Toner
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Mehmet Toner wrote the following 3 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 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.

3 Article RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. 2012

Yu, Min / Ting, David T / Stott, Shannon L / Wittner, Ben S / Ozsolak, Fatih / Paul, Suchismita / Ciciliano, Jordan C / Smas, Malgorzata E / Winokur, Daniel / Gilman, Anna J / Ulman, Matthew J / Xega, Kristina / Contino, Gianmarco / Alagesan, Brinda / Brannigan, Brian W / Milos, Patrice M / Ryan, David P / Sequist, Lecia V / Bardeesy, Nabeel / Ramaswamy, Sridhar / Toner, Mehmet / Maheswaran, Shyamala / Haber, Daniel A. ·Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA. ·Nature · Pubmed #22763454.

ABSTRACT: Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. Although these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as a candidate gene enriched in CTCs. Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 (also known as TAK1) kinase. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes, and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer.