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https://www.readbyqxmd.com/read/28335509/novel-diagnostic-and-predictive-biomarkers-in-pancreatic-adenocarcinoma
#1
REVIEW
John C Chang, Madappa Kundranda
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for a multitude of reasons including very late diagnosis. This in part is due to the lack of understanding of the biological behavior of PDAC and the ineffective screening for this disease. Significant efforts have been dedicated to finding the appropriate serum and imaging biomarkers to help early detection and predict response to treatment of PDAC. Carbohydrate antigen 19-9 (CA 19-9) has been the most validated serum marker and has the highest positive predictive value as a stand-alone marker...
March 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334208/morphologically-constrained-spectral-unmixing-by-dictionary-learning-for-multiplex-fluorescence-microscopy
#2
Murad Megjhani, Pedro Correa de Sampaio, Julienne Leigh Carstens, Raghu Kalluri, Badrinath Roysam
Motivation: Current spectral unmixing methods for multiplex fluorescence microscopy have a limited ability to cope with high spectral overlap as they only analyze spectral information over individual pixels. Here, we present adaptive Morphologically Constrained Spectral Unmixing (MCSU) algorithms that overcome this limitation by exploiting morphological differences between sub-cellular structures, and their local spatial context. Results: The proposed method was effective at improving spectral unmixing performance by exploiting: (i) a set of dictionary-based models for object morphologies learned from the image data; and (ii) models of spatial context learned from the image data using a total variation algorithm...
March 2, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28319439/loss-of-a-primary-cilium-in-pdac
#3
Tetsuo Kobayashi, Hiroshi Itoh
No abstract text is available yet for this article.
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28317579/the-influence-of-neural-invasion-on-survival-and-tumor-recurrence-in-pancreatic-ductal-adenocarcinoma-a-systematic-review-and-meta-analysis
#4
REVIEW
Stephan Schorn, Ihsan Ekin Demir, Bernhard Haller, Florian Scheufele, Carmen Mota Reyes, Elke Tieftrunk, Mine Sargut, Ruediger Goess, Helmut Friess, Güralp Onur Ceyhan
OBJECTIVES: To assess the impact of neural invasion/NI on overall survival/OS and tumor recurrence in pancreatic ductal adenocarcinoma/PDAC. SUMMARY BACKGROUND DATA: NI is a histopathological hallmark of PDAC. Although some studies suggested an important role for NI on OS, disease-free/DFS and progression-free survival/PFS in PDAC, there is still no consensus on the actual role of NI on survival and local recurrence in PDAC. METHODS: Pubmed, Cochrane library, Ovid and Google Scholar were screened for the terms "pancreatic ductal adenocarcinoma", "pancreatic cancer", "survival", "tumor recurrence" and "perineural invasion"...
March 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28316954/molecular-pathways-controlling-autophagy-in-pancreatic-cancer
#5
REVIEW
Maria New, Tim Van Acker, Jaclyn S Long, Jun-Ichi Sakamaki, Kevin M Ryan, Sharon A Tooze
Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancer types where the 5-year survival rate shows no improvement. Despite conflicting evidence, the majority of data points to an essential role for autophagy in PDAC growth and survival, in particular constitutively activated autophagy, can provide crucial fuel to PDAC tumor cells in their nutrient-deprived environment. Autophagy, which is required for cell homeostasis, can both suppress and promote tumorigenesis and tumor survival in a context-dependent manner...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28315433/increased-semaphorin-3c-expression-promotes-tumor-growth-and-metastasis-in-pancreatic-ductal-adenocarcinoma-by-activating-the-erk1-2-signaling-pathway
#6
Xuejun Xu, Zhiping Zhao, Sixiang Guo, Jian Li, Songsong Liu, Yu You, Bing Ni, Huaizhi Wang, Ping Bie
Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315323/increased-serotonin-signaling-contributes-to-the-warburg-effect-in-pancreatic-tumor-cells-under-metabolic-stress-and-promotes-growth-of-pancreatic-tumors-in-mice
#7
Shu-Heng Jiang, Jun Li, Fang-Yuan Dong, Jian-Yu Yang, De-Jun Liu, Xiao-Mei Yang, Ya-Hui Wang, Min-Wei Yang, Xue-Liang Fu, Xiao-Xin Zhang, Qing Li, Xiu-Feng Pang, Yan-Miao Huo, Jiao Li, Jun-Feng Zhang, Ho-Young Lee, Su-Jae Lee, Wen-Xin Qin, Jian-Ren Gu, Yong-Wei Sun, Zhi-Gang Zhang
BACKGROUND & AIMS: The desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. METHODS: We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+); Trp53(R172H/+); Pdx1-Cre; (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples...
March 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28314962/pd-l1-expression-in-pancreatic-ductal-adenocarcinoma-is-a-poor-prognostic-factor-in-patients-with-high-cd8-tumor-infiltrating-lymphocytes-highly-sensitive-detection-using-phosphor-integrated-dot-staining
#8
So Yamaki, Hiroaki Yanagimoto, Koji Tsuta, Hironori Ryota, Masanori Kon
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. For the development of more effective immunotherapies, it is first necessary to elucidate the immunological escape mechanisms. In this study, we applied our recently developed highly sensitive immunostaining method employing fluorescent phosphor-integrated dot (PID) nanoparticles to evaluate the prevalence of programmed death ligand 1 (PD-L1) in patients with PDAC. METHODS: This study included 42 patients with PDAC who underwent pancreatectomy...
March 18, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28304379/development-of-bioluminescent-chick-chorioallantoic-membrane-cam-models-for-primary-pancreatic-cancer-cells-a-platform-for-drug-testing
#9
Maria Rovithi, Amir Avan, Niccola Funel, Leticia G Leon, Valentina E Gomez, Thomas Wurdinger, Arjan W Griffioen, Henk M W Verheul, Elisa Giovannetti
The aim of the present study was to develop chick-embryo chorioallantoic membrane (CAM) bioluminescent tumor models employing low passage cell cultures obtained from primary pancreatic ductal adenocarcinoma (PDAC) cells. Primary PDAC cells transduced with lentivirus expressing Firefly-luciferase (Fluc) were established and inoculated onto the CAM membrane, with >80% engraftment. Fluc signal reliably correlated with tumor growth. Tumor features were evaluated by immunohistochemistry and genetic analyses, including analysis of mutations and mRNA expression of PDAC pivotal genes, as well as microRNA (miRNA) profiling...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301556/early-versus-delayed-initiation-of-adjuvant-treatment-for-pancreatic-cancer
#10
Hyoung Woo Kim, Jong-Chan Lee, Jongchan Lee, Jin Won Kim, Jaihwan Kim, Jin-Hyeok Hwang
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC. METHODS: We retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20-83 days])...
2017: PloS One
https://www.readbyqxmd.com/read/28301276/epigenetic-alterations-as-biomarkers-in-pancreatic-ductal-adenocarcinoma
#11
Pascal Syren, Roland Andersson, Monika Bauden, Daniel Ansari
Pancreatic ductal adenocarcinoma (PDAC) prognosis remains very poor and has only marginally improved during the last decades. Epigenetic alterations have been the focus of many recent studies and offer valuable options for PDAC detection, prognosis and treatment. DNA methylation, histone modifications and microRNA (miR) level changes can be used as biomarkers. These alterations occur early in carcinogenesis and may be specific for PDAC. Additionally, epigenetic alterations can be analyzed from cell-free DNA, free-circulating nucleosomes or shed tumor cells in blood...
March 16, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28301088/survival-benefit-of-intravenous-and-intraperitoneal-paclitaxel-with-s-1-in-pancreatic-ductal-adenocarcinoma-patients-with-peritoneal-metastasis-a-retrospective-study-in-a-single-institution
#12
Sohei Satoi, Hiroaki Yanagimoto, Tomohisa Yamamoto, Satoshi Hirooka, So Yamaki, Hisashi Kosaka, Kentaro Inoue, Yuki Hashimoto, Yoichi Matsui, Masanori Kon
PURPOSE: We evaluated the clinical efficacy of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) combined with S-1 in patients with chemotherapy-naïve pancreatic ductal adenocarcinoma (PDAC) with peritoneal metastasis. METHODS: Forty-nine patients were diagnosed with peritoneal metastasis during 2007-2014; 29 received gemcitabine or S-1 based chemo(radio)therapy from 2007-11 (control group), and the remaining 20 received i.v. (50 mg/m(2) ) and i.p...
March 16, 2017: Journal of Hepato-biliary-pancreatic Sciences
https://www.readbyqxmd.com/read/28293721/post-whipple-imaging-in-patients-with-pancreatic-ductal-adenocarcinoma-association-with-overall-survival-a-multivariate-analysis
#13
Azadeh Elmi, Janet Murphy, Sandeep Hedgire, Shaunagh McDermott, Seyed-Mahdi Abtahi, Elkan Halpern, Carlos Fernandez-Del Castillo, Mukesh Harisinghani
PURPOSE: To compare the survival outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) who had regular imaging surveillance with those who had clinical follow-up after Whipple. METHOD: We identified 229 patients, who underwent Whipple for resection of PDAC from 2005 to 2011, and had regular postoperative clinical follow-up at our hospital. Patients were retrospectively selected for two follow-up groups: imaging surveillance (IS) defined as routine imaging at scheduled intervals, vs...
March 14, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28293485/a-long-term-survivor-of-metastatic-pancreatic-adenocarcinoma-free-of-recurrence-12-years-after-treatment-of-oligometastatic-disease
#14
John M Stahl, Zenta Walther, Bryan W Chang, Howard S Hochster, Kimberly L Johung
Aggressive local therapy for patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC) has traditionally not been pursued due to high rates of distant progression. We describe a 62-year-old male initially presenting with resectable PDAC who underwent the Whipple procedure but developed multiple liver metastases within two months of starting adjuvant gemcitabine. Oxaliplatin was added to the regimen and complete resolution of the liver lesions resulted. He remained disease-free for five years until re-staging revealed a small lung nodule...
February 2, 2017: Curēus
https://www.readbyqxmd.com/read/28292938/combinatorial-screening-of-pancreatic-adenocarcinoma-reveals-sensitivity-to-drug-combinations-including-bromodomain-inhibitor-plus-neddylation-inhibitor
#15
Casey G Langdon, James T Platt, Robert E Means, Pinar Iyidogan, Ramanaiah Mamillapalli, Michael Klein, Matthew A Held, Jong Woo Lee, Ja Seok Koo, Christos Hatzis, Howard S Hochster, David F Stern
Pancreatic adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the United States. PDAC is difficult to manage effectively, with a five-year survival rate of only 5%. PDAC is largely driven by activating KRAS mutations, and as such, cannot be directly targeted with therapeutic agents that affect the activated protein. Instead, inhibition of downstream signaling and other targets will be necessary to effectively manage PDAC. Here, we describe a tiered single-agent and combination compound screen to identify targeted agents that impair growth of a panel of PDAC cell lines...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28291966/molecular-characteristics-of-pancreatic-ductal-adenocarcinomas-with-high-grade-pancreatic-intraepithelial-neoplasia-panin-are-different-from-those-without-high-grade-panin
#16
Tetsuyuki Miyazaki, Yoshihiro Ohishi, Yoshihiro Miyasaka, Yasunori Oda, Shinichi Aishima, Keigo Ozono, Atsushi Abe, Eishi Nagai, Masafumi Nakamura, Yoshinao Oda
AIMS: We reported that pancreatic ductal adenocarcinomas (PDACs) without high-grade pancreatic intraepithelial neoplasia (PanIN) in the vicinity had worse prognoses than PDACs with high-grade PanIN. However, the molecular characteristics of PDACs with and without high-grade PanIN have not been compared. The aim of this study is to clarify the molecular characteristics of PDACs with and without high-grade PanIN. METHOD AND RESULTS: We reviewed all of a consecutive series of 100 patients with PDACs and divided them into 2 groups: the PDACs with PanIN-2 or PanIN-3 in the background (the PanIN-high group, n = 60) and the PDACs without PanIN-2 or PanIN-3 in the background (the PanIN-low group, n = 40)...
March 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28289921/genome-wide-in-vivo-rnai-screen-identifies-itih5-as-a-metastasis-suppressor-in-pancreatic-cancer
#17
Ken Sasaki, Hiroshi Kurahara, Eric D Young, Shoji Natsugoe, Asami Ijichi, Tomoo Iwakuma, Danny R Welch
The overwhelming majority of pancreatic ductal adenocarcinoma (PDAC) is not diagnosed until the cancer has metastasized, leading to an abysmal average life expectancy (3-6 months post-diagnosis). Earlier detection and more effective treatments have been hampered by inadequate understanding of the underlying molecular mechanisms controlling metastasis. We hypothesized that metastasis suppressors are involved in controlling metastasis in pancreatic cancer. Using an unbiased genome-wide shRNA screen, an shRNA library was transduced into the non-metastatic PDAC line S2-028 followed by intrasplenic injection...
March 13, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28289900/fhit-down-regulation-is-an-early-event-in-pancreatic-carcinogenesis
#18
Matteo Fassan, Borislav Rusev, Vincenzo Corbo, Pierluigi Gasparini, Claudio Luchini, Caterina Vicentini, Andrea Mafficini, Salvatore Paiella, Roberto Salvia, Ivana Cataldo, Aldo Scarpa, Kay Huebner
Aberrant Fhit expression characterizes a large proportion of primary pancreatic ductal adenocarcinomas (PDACs), but fragmentary information is available on Fhit expression during the phenotypic changes of pancreatic ductal epithelium during multistep transformation. We assessed Fhit expression by immunohistochemistry in two different multistep pancreatic carcinogenic processes: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). We considered 105 surgically treated PDACs/IPMNs and selected 30 samples of non-neoplastic pancreatic parenchyma, 50 PanIN lesions, 30 IPMNs, 15 IPMNs with associated invasive carcinoma, and 60 adenocarcinomas...
March 13, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28284058/the-transient-receptor-potential-melastatin-7-channel-regulates-pancreatic-cancer-cell-invasion-through-the-hsp90%C3%AE-upa-mmp2-pathway
#19
Pierre Rybarczyk, Alison Vanlaeys, Bertrand Brassart, Isabelle Dhennin-Duthille, Denis Chatelain, Henri Sevestre, Halima Ouadid-Ahidouch, Mathieu Gautier
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a very poor prognosis. There is an urgent need to better understand the molecular mechanisms that regulate PDAC cell aggressiveness. The transient receptor potential melastatin 7 (TRPM7) is a nonselective cationic channel that mainly conducts Ca(2+) and Mg(2+). TRPM7 is overexpressed in numerous malignancies including PDAC. In the present study, we used the PANC-1 and MIA PaCa-2 cell lines to specifically assess the role of TRPM7 in cell invasion and matrix metalloproteinase secretion...
March 8, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28282928/oxidative-stress-a-new-target-for-pancreatic-cancer-prognosis-and-treatment
#20
REVIEW
Javier Martinez-Useros, Weiyao Li, Marticela Cabeza-Morales, Jesus Garcia-Foncillas
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumors, and its incidence is rising worldwide. Survival can be improved when tumors are detected at an early stage; however, this cancer is usually asymptomatic, and the disease only becomes apparent after metastasis. Several risk factors are associated to this disease. Chronic pancreatitis, diabetes, and some infectious disease are the most relevant risk factors. Incidence of PDAC has increased in the last decades. It is hypothesized it could be due to other acquired risk habits, like smoking, high alcohol intake, and obesity...
March 9, 2017: Journal of Clinical Medicine
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