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https://www.readbyqxmd.com/read/27889647/activation-of-wnt-%C3%AE-catenin-signaling-enhances-pancreatic-cancer-development-and-the-malignant-potential-via-up-regulation-of-cyr61
#1
Makoto Sano, David R Driscoll, Wilfredo E DeJesus-Monge, Brian Quattrochi, Victoria A Appleman, Jianhong Ou, Lihua Julie Zhu, Nao Yoshida, Shintaro Yamazaki, Tadatoshi Takayama, Masahiko Sugitani, Norimichi Nemoto, David S Klimstra, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly develops following activating mutations in the KRAS oncogene. Activation of WNT signaling is also commonly observed in PDAC. To ascertain the impact of postnatal activation of WNT-stimulated signaling pathways in PDAC development, we combined the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL-Kras(G12D), Ptf1a-cre model. Delivery of RCAS viruses encoding β-catenin(S37A) and WNT1 stimulated the progression of premalignant pancreatic intraepithelial neoplasias (PanIN) and PDAC development...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27829276/biliary-carcinomas-pathology-and-the-role-of-dna-mismatch-repair-deficiency
#2
Vitor Werneck Krauss Silva, Gokce Askan, Tanisha D Daniel, Maeve Lowery, David S Klimstra, Ghassan K Abou-Alfa, Jinru Shia
The pathology of biliary carcinomas is diverse with different gross and histological features in tumors arising in the different segments of the biliary system. Various epidemiological risk factors, varied genetic makeup, and tissue microenvironment are contributory factors. As biliary tumors have been shown to be a part of the Lynch syndrome tumor spectrum, it is plausible to speculate that DNA mismatch repair (MMR) deficiency plays a role in biliary tumors. Literature data suggest that DNA MMR deficiency indeed occurs in these tumors, albeit infrequently with the reported frequencies (weighted for sample size) of high level microsatellite instability (MSI) being 5% each for gallbladder carcinoma and carcinoma of extra-hepatic bile ducts, and 10% each for intrahepatic cholangiocarcinoma and ampullary carcinoma...
October 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/27799312/a-role-for-human-skin-mast-cells-in-dengue-virus-infection-and-systemic-spread
#3
Andrea Troupin, Devon Shirley, Berlin Londono-Renteria, Alan M Watson, Cody McHale, Alex Hall, Adam Hartstone-Rose, William B Klimstra, Gregorio Gomez, Tonya M Colpitts
Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENV infection and systemic spread. Here, we show that mast cells are a target of DENV in human skin and that DENV infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENV localizes within secretory granules in infected skin mast cells...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27759713/treatment-response-and-outcomes-of-grade-3-pancreatic-neuroendocrine-neoplasms-based-on-morphology-well-differentiated-versus-poorly-differentiated
#4
Nitya Raj, Emily Valentino, Marinela Capanu, Laura H Tang, Olca Basturk, Brian R Untch, Peter J Allen, David S Klimstra, Diane Reidy-Lagunes
OBJECTIVES: Emerging data suggest that not all grade 3 (G3) pancreatic neuroendocrine neoplasms (panNENs) behave the same; tumor differentiation may predict outcome. METHODS: Patients with G3 panNENs treated at our institution between 1999 and 2014 were identified. Demographics, response to therapy, and overall survival were determined. RESULTS: Forty-five patients were identified, 16 with G3 well differentiated pancreatic neuroendocrine tumors (WD-panNETs) and 29 with poorly differentiated neuroendocrine carcinomas (PDNEC)...
October 18, 2016: Pancreas
https://www.readbyqxmd.com/read/27758884/mtorc2-signaling-drives-the-development-and-progression-of-pancreatic-cancer
#5
David R Driscoll, Saadia A Karim, Makoto Sano, David M Gay, Wright Jacob, Jun Yu, Yusuke Mizukami, Aarthi Gopinathan, Duncan I Jodrell, T R Jeffry Evans, Nabeel Bardeesy, Michael N Hall, Brian J Quattrochi, David S Klimstra, Simon T Barry, Owen J Sansom, Brian C Lewis, Jennifer P Morton
mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27685844/circulating-plasma-levels-of-microrna-21-and-microrna-221-are-potential-diagnostic-markers-for-primary-intrahepatic-cholangiocarcinoma
#6
Camilo Correa-Gallego, Danilo Maddalo, Alexandre Doussot, Nancy Kemeny, T Peter Kingham, Peter J Allen, Michael I D'Angelica, Ronald P DeMatteo, Doron Betel, David Klimstra, William R Jarnagin, Andrea Ventura
BACKGROUND: MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility. METHODS: Using deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers...
2016: PloS One
https://www.readbyqxmd.com/read/27664376/p53-and-p16-ink4a-p19-arf-loss-promotes-different-pancreatic-tumor-types-from-pymt-expressing-progenitor-cells
#7
Stephanie Azzopardi, Sharon Pang, David S Klimstra, Yi-Chieh Nancy Du
In human studies and mouse models, the contributions of p53 and p16(Ink4a)/p19(Arf) loss are well established in pancreatic ductal adenocarcinoma (PDAC). Although loss of functional p53 pathway and loss of Ink4a/Arf in human pancreatic acinar cell carcinoma (PACC) and pancreatic neuroendocrine tumor (PanNET) are identified, their direct roles in tumorigenesis of PACC and PanNET remain to be determined. Using transgenic mouse models expressing the viral oncogene polyoma middle T antigen (PyMT), we demonstrate that p53 loss in pancreatic Pdx1+ progenitor cells results in aggressive PACC, whereas Ink4a/Arf loss results in PanNETs...
October 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27632170/aedes-aegypti-d7-saliva-protein-inhibits-dengue-virus-infection
#8
Michael J Conway, Berlin Londono-Renteria, Andrea Troupin, Alan M Watson, William B Klimstra, Erol Fikrig, Tonya M Colpitts
Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection...
September 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27591765/distinct-pathways-of-pathogenesis-of-intraductal-oncocytic-papillary-neoplasms-and-intraductal-papillary-mucinous-neoplasms-of-the-pancreas
#9
Olca Basturk, Sun M Chung, Ralph H Hruban, N Volkan Adsay, Gokce Askan, Christine Iacobuzio-Donahue, Serdar Balci, Sui Y Zee, Bahar Memis, Jinru Shia, David S Klimstra
Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is classified as a variant of intraductal papillary mucinous neoplasm (IPMN) in the WHO guidelines. However, the neoplastic cells of IOPNs are unique, with distinctive architecture/oncocytic cytoplasm. Although molecular/immunohistochemical features of other IPMN variants have been extensively studied, those of IOPNs have not been well characterized. Expression profile of antibodies associated with genetic alterations previously described for ductal adenocarcinomas (DAs) and IPMNs (SMAD4/β-catenin/p53/mesothelin/claudin-4) as well as antibodies to mucins and differentiation markers [MUC1/MUC2/MUC5AC/MUC6/CDX2/hepatocyte paraffin-1 (HepPar-1)] was investigated in 24 IOPNs and 22 IPMNs to assess the similarities/differences between these tumors...
November 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27573170/cyst-fluid-analysis-in-pancreatic-intraductal-papillary-mucinous-neoplasms
#10
Peter J Allen, Christine A Iacobuzio-Donahue, David S Klimstra
Pancreatic intraductal papillary mucinous neoplasms (IPMN) are surgically treatable cancer precursors, if high-risk features can be identified. Analysis of proteins and genes in cyst fluid helps diagnostically, but prior biomarkers had limited ability to detect high-risk cases. Cyst fluid telomerase activity may be a useful biomarker for high-risk IPMNs. Clin Cancer Res; 22(20); 4966-7. ©2016 AACRSee related article by Hata et al., p. 5141.
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27508975/undifferentiated-carcinoma-with-osteoclastic-giant-cells-of-the-pancreas-clinicopathologic-analysis-of-38-cases-highlights-a-more-protracted-clinical-course-than-currently-appreciated
#11
Takashi Muraki, Michelle D Reid, Olca Basturk, Kee-Taek Jang, Gabriela Bedolla, Pelin Bagci, Pardeep Mittal, Bahar Memis, Nora Katabi, Sudeshna Bandyopadhyay, Juan M Sarmiento, Alyssa Krasinskas, David S Klimstra, Volkan Adsay
Undifferentiated carcinomas with osteoclastic giant cells of the pancreas (OGC) are rare tumors. The current impression in the literature is that they are highly aggressive tumors similar in prognosis to ductal adenocarcinomas. In this study, the clinicopathologic characteristics of 38 resected OGCs were investigated and contrasted with 725 resected pancreatic ductal adenocarcinomas without osteoclastic cells (PDCs). The frequency among systematically reviewed pancreatic cancers was 1.4%. OGCs showed a slight female predominance (62...
September 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27463517/the-17d-204-vaccine-strain-induced-protection-against-virulent-yellow-fever-virus-is-mediated-by-humoral-immunity-and-cd4-but-not-cd8-t-cells
#12
Alan M Watson, L K Metthew Lam, William B Klimstra, Kate D Ryman
A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens...
July 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27443512/patterns-and-prognostic-relevance-of-pd-1-and-pd-l1-expression-in-colorectal-carcinoma
#13
Lik Hang Lee, Marcela S Cavalcanti, Neil H Segal, Jaclyn F Hechtman, Martin R Weiser, J Joshua Smith, Julio Garcia-Aguilar, Eran Sadot, Peter Ntiamoah, Arnold J Markowitz, Moshe Shike, Zsofia K Stadler, Efsevia Vakiani, David S Klimstra, Jinru Shia
Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation...
November 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27425386/expression-of-markers-of-hepatocellular-differentiation-in-pancreatic-acinar-cell-neoplasms-%C3%A2-a-potential-diagnostic-pitfall
#14
Gokce Askan, Vikram Deshpande, David S Klimstra, Volkan Adsay, Carlie Sigel, Jinru Shia, Olca Basturk
OBJECTIVES: Pancreatic acinar cell carcinoma (ACC) is a rare tumor that frequently metastasizes to the liver and may present a diagnostic challenge due to its morphologic similarity to hepatocellular carcinoma. We investigated α-fetoprotein (AFP), hepatocyte paraffin antigen 1 (HepPar 1), glypican 3, arginase 1, and albumin messenger RNA (mRNA) in situ hybridization (ISH) in pancreatic neoplasms with ACC differentiation to assess their diagnostic value. METHODS: AFP, HepPar 1, glypican 3, and arginase 1 immunohistochemical staining was performed on 28 ACCs using a tissue microarray...
August 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27421291/neuromechanical-interactions-between-the-limbs-during-human-locomotion-an-evolutionary-perspective-with-translation-to-rehabilitation
#15
E Paul Zehr, Trevor S Barss, Katie Dragert, Alain Frigon, Erin V Vasudevan, Carlos Haridas, Sandra Hundza, Chelsea Kaupp, Taryn Klarner, Marc Klimstra, Tomoyoshi Komiyama, Pamela M Loadman, Rinaldo A Mezzarane, Tsuyoshi Nakajima, Gregory E P Pearcey, Yao Sun
During bipedal locomotor activities, humans use elements of quadrupedal neuronal limb control. Evolutionary constraints can help inform the historical ancestry for preservation of these core control elements support transfer of the huge body of quadrupedal non-human animal literature to human rehabilitation. In particular, this has translational applications for neurological rehabilitation after neurotrauma where interlimb coordination is lost or compromised. The present state of the field supports including arm activity in addition to leg activity as a component of gait retraining after neurotrauma...
July 15, 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/27320062/acinar-neoplasms-of-the-pancreas-a-summary-of-25-years-of-research
#16
David S Klimstra, Volkan Adsay
Our understanding about the family of acinar neoplasms of the pancreas has grown substantially over the past 25 years. The prototype is acinar cell carcinoma, an uncommon variant of pancreatic carcinoma that demonstrates production of pancreatic exocrine enzymes, verifiable using immunohistochemistry, and exhibits characteristic histologic features. Related neoplasms include mixed acinar carcinomas such as mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma. In the pediatric age group, pancreatoblastoma is also closely related...
September 2016: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/27318152/host-translation-shutoff-mediated-by-non-structural-protein-2-is-a-critical-factor-in-the-antiviral-state-resistance-of-venezuelan-equine-encephalitis-virus
#17
Nishank Bhalla, Chengqun Sun, L K Metthew Lam, Christina L Gardner, Kate D Ryman, William B Klimstra
Most previous studies of interferon-alpha/beta (IFN-α/β) response antagonism by alphaviruses have focused upon interruption of IFN-α/β induction and/or receptor signaling cascades. Infection of mice with Venezuelan equine encephalitis alphavirus (VEEV) or Sindbis virus (SINV) induces serum IFN-α/β, that elicits a systemic antiviral state in uninfected cells successfully controlling SINV but not VEEV replication. Furthermore, VEEV replication is more resistant than that of SINV to a pre-existing antiviral state in vitro...
September 2016: Virology
https://www.readbyqxmd.com/read/27282352/mammary-analog-secretory-carcinoma-of-the-thyroid-gland-a-primary-thyroid-adenocarcinoma-harboring-etv6-ntrk3-fusion
#18
Snjezana Dogan, Lu Wang, Ryan N Ptashkin, Robert R Dawson, Jatin P Shah, Eric J Sherman, R Michael Tuttle, James A Fagin, David S Klimstra, Nora Katabi, Ronald A Ghossein
ETV6-NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype...
September 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27282351/the-oncocytic-subtype-is-genetically-distinct-from-other-pancreatic-intraductal-papillary-mucinous-neoplasm-subtypes
#19
Olca Basturk, Marcus Tan, Umesh Bhanot, Peter Allen, Volkan Adsay, Sasinya N Scott, Ronak Shah, Michael F Berger, Gokce Askan, Esra Dikoglu, Vaidehi Jobanputra, Kazimierz O Wrzeszczynski, Carlie Sigel, Christine Iacobuzio-Donahue, David S Klimstra
In 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the 'oncocytic subtype' of intraductal papillary mucinous neoplasm. Although several key molecular alterations of other intraductal papillary mucinous neoplasm subtypes have been discovered, including common mutations in KRAS, GNAS, and RNF3, those of oncocytic subtype have not been well characterized. We analyzed 11 pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms...
September 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27259015/a-practical-approach-to-the-classification-of-who-grade-3-g3-well-differentiated-neuroendocrine-tumor-wd-net-and-poorly-differentiated-neuroendocrine-carcinoma-pd-nec-of-the-pancreas
#20
Laura H Tang, Olca Basturk, Jillian J Sue, David S Klimstra
High-grade neuroendocrine neoplasms (World Health Organization [WHO] G3) of the pancreas include both well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC). According to the WHO classification scheme, the diagnosis of this group of tumors is based on both the histopathology of the tumor and the assessment of proliferation fraction. However, the former can be challenging due to the lack of well-defined histologic criteria, and the latter alone (ie, >20 mitoses/10 high-power fields or Ki67>20%) may not sufficiently distinguish WD-NETs from PD-NECs...
September 2016: American Journal of Surgical Pathology
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