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Pancreatic cancer

Přemysl Frič, Jan Škrha, Aleksi Šedo, Tomaš Zima, Petr Bušek, Klára Kmochová, Martin Laclav, Bohuš Bunganič, Svatopluk Solař, Petr Hrabal, František Bělina, Pavel Záruba, Pavel Škrha, Miroslav Zavoral
High-resolution imaging methods (HRIMs) and biomarkers present the second step of pancreatic cancer (PC) diagnostics in at-risk individuals. These include patients with positive risk factors, early symptoms, nonresponders to the initial antidiabetic therapy, patients older than 50 years of age with new-onset unstable diabetes requiring insulin as well as patients with long-term insulin-non-dependent diabetes and recent (up to 6 months) failure of antidiabetic therapy. The procedures should be started without delay and the co-operation between the primary and tertiary medical centers is highly desirable...
December 2016: European Journal of Gastroenterology & Hepatology
Michael Chalick, Oded Jacobi, Edward Pichinuk, Christian Garbar, Armand Bensussan, Alan Meeker, Ravit Ziv, Tania Zehavi, Nechama I Smorodinsky, John Hilkens, Franz-Georg Hanisch, Daniel B Rubinstein, Daniel H Wreschner
Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C- sequences flanking it differ entirely from those of MUC1-TM...
2016: PloS One
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
A Kautzky-Willer, S Thurner, P Klimek
AIM: There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population. METHODS: Medical claims data of 1 847 051 patients with hospital stays during 2006-2007 were used to estimate age- and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins...
October 21, 2016: Journal of Internal Medicine
Yong Lin, Xin Ge, Yiyang Wen, Zhu-Mei Shi, Qiu-Dan Chen, Min Wang, Ling-Zhi Liu, Bing-Hua Jiang, Yuan Lu
Pancreatic adenocarcinoma is one of the most leading causes of cancer-related deaths worldwide. Although recent advances provide various treatment options, pancreatic adenocarcinoma has poor prognosis due to its late diagnosis and ineffective therapeutic multimodality. Gemcitabine is the effective first-line drug in pancreatic adenocarcinoma treatment. However, gemcitabine chemoresistance of pancreatic adenocarcinoma cells has been a major obstacle for limiting its treatment effect. Our study found that p70S6K1 plays an important role in gemcitabine chemoresistence...
September 27, 2016: Oncotarget
Stepana Boukalova, Jan Stursa, Lukas Werner, Zuzana Ezrova, Jiri Cerny, Ayenachew Bezawork-Geleta, Alena Pecinova, Lanfeng Dong, Zdenek Drahota, Jiri Neuzil
Pancreatic cancer is one of the hardest-to-treat types of neoplastic diseases. Metformin, a widely prescribed drug against type 2 diabetes mellitus, is being trialed as an agent against pancreatic cancer, although its efficacy is low. With the idea of delivering metformin to its molecular target, the mitochondrial complex I (CI), we tagged the agent with the mitochondrial vector, triphenylphosphonium group. Mitochondrially targeted metformin (MitoMet) was found to kill a panel of pancreatic cancer cells 3-4 orders of magnitude more efficiently than found for the parental compound...
October 7, 2016: Molecular Cancer Therapeutics
Khaldoun Almhanna, Gopi K Prithviraj, Petter Veiby, Thea Kalebic
Antibody-directed cancer chemotherapy in the form of antibody-drug conjugates (ADCs) may improve the therapeutic index with the potential to enhance efficacy and decrease systemic toxicity. ADCs consist of three key components including an antibody that specifically binds to the target, a toxic agent and a linker which releases the toxic agent inside tumor cells. A novel ADC, MLN0264 (TAK-264) was recently investigated in patients with gastrointestinal (GI) malignancies. TAK-264 is an anti- guanylyl cyclase C (GCC) antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE) (linker and toxin licensed from Seattle Genetics)...
October 17, 2016: Pharmacology & Therapeutics
Divya Arora, Nisha Sharma, Venugopal Singamaneni, Vishal Sharma, Manoj Kushwaha, Vidushi Abrol, Santosh Guru, Sonia Sharma, Ajai Prakash Gupta, Shashi Bhushan, Sundeep Jaglan, Prasoon Gupta
BACKGROUND: The genus Xylaria has been reported as a rich source of biologically active secondary metabolites. In the present study, an endophytic fungus Xylaria psidii has been isolated from the leaf sample of Aegle marmelos (L.) Corr., characterized on the basis of its morphological features and sequence data for the ITS region (KU291350) of the nuclear ribosomal DNA. Biological screening of ethyl acetate extract of Xylaria psidii displayed a potential therapeutic effect on pancreatic cancer cells...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Si Yeol Song, Kyu-Pyo Kim, Seong-Yun Jeong, Jin Park, Jaesook Park, Joohee Jung, Hye Kyung Chung, Sa-Won Lee, Min Hyo Seo, Jung-Shin Lee, Kyung Hae Jung, Eun Kyung Choi
We assessed the efficacy of the polymeric nanoparticle containing docetaxel (PNP-DTX) in preclinical mouse models and determined the maximum tolerated dose (MTD) through clinical study. Subcutaneous and orthotopic mouse models were dedicated. Tumor growth delay in orthotopic model and quantification of in vivo imaging in orthotopic model were evaluated. Phase I clinical study was a single-center, prospective, open-label trial in advanced solid tumors. PNP-DTX was injected intravenously and the starting dose was 20 mg/m2 escalated to 35 mg/m2, 45 mg/m2, 60 mg/m2 and 75 mg/m2...
October 14, 2016: Oncotarget
Qiang Zhang, Yaqing Zhang, Joshua D Parsels, Ines Lohse, Theodore S Lawrence, Marina Pasca di Magliano, Yi Sun, Meredith A Morgan
Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown. To determine potential cooperation between Kras mutation and Fbxw7 inactivation in pancreatic tumorigenesis, we generated P48-Cre;LSL-Kras(G12D);Fbxw7(fl/fl) (KFC(fl/fl)) compound mice. We found that KFC(fl/fl) mice displayed accelerated tumorigenesis: all mice succumbed to pancreatic ductal adenocarcinoma (PDA) by 40 days of age, with PDA onset occurring by 2 weeks of age...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
Dariusz Wodziak, Aiwen Dong, Michael F Basin, Anson W Lowe
A recently published study identified Anterior Gradient 2 (AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model...
2016: PloS One
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Lingxiang Wu, Xiujie Chen, Denan Zhang, Wubing Zhang, Lei Liu, Hongzhe Ma, Jingbo Yang, Hongbo Xie, Bo Liu, Qing Jin
Analysis of gene sets has been widely applied in various high-throughput biological studies. One weakness in the traditional methods is that they neglect the heterogeneity of genes expressions in samples which may lead to the omission of some specific and important gene sets. It is also difficult for them to reflect the severities of disease and provide expression profiles of gene sets for individuals. We developed an application software called IGSA that leverages a powerful analytical capacity in gene sets enrichment and samples clustering...
2016: PloS One
Adam Durczynski, Anna Kumor, Piotr Grzelak, Marcin Strzelczyk, Piotr Hogendorf, Grazyna Poznanska, Aleksander Skulimowski, Dariusz Szymanski, Janusz Strzelczyk
No abstract text is available yet for this article.
October 18, 2016: Pancreas
David Altree-Tacha, Jillian Tyrrell, Thomas Haas
CONTEXT: -CDH17, which is expressed in the intestinal epithelium, is a novel oncogene involved in tumor invasion and metastasis. A panel consisting of cytokeratin (CK) 7, CD20, and CDX2 antibodies is typically used to diagnose gastrointestinal adenocarcinomas. However, studies have shown that CDH17 is a highly specific marker for gastrointestinal adenocarcinoma and may be important in clinical diagnosis. OBJECTIVE: -To evaluate the sensitivity and specificity of CDH17, CK20, and CDX2 antibodies in neoplastic tissues, with emphasis on colon, stomach, and esophageal gastrointestinal lineage...
October 20, 2016: Archives of Pathology & Laboratory Medicine
O Strobel, S Brangs, U Hinz, T Pausch, F J Hüttner, M K Diener, L Schneider, T Hackert, M W Büchler
BACKGROUND: Chyle leak is a well known but poorly characterized complication after pancreatic surgery. Available data on incidence, risk factors and clinical significance of chyle leak are highly heterogeneous. METHODS: For this cohort study all patients who underwent pancreatic surgery between January 2008 and December 2012 were identified from a prospective database. Chyle leak was defined as any drainage output with triglyceride content of 110 mg/dl or more...
October 20, 2016: British Journal of Surgery
Yang Li, Hebin Wang, Kai Wang, Qinglian Hu, Qi Yao, Youqing Shen, Guocan Yu, Guping Tang
A new type of tumor-targeted nanovehicle peptide-conjugated PSPG (PSPGP) is successfully synthesized for co-delivery of paclitaxel (PTX) and TR3 small interfering RNA (siRNA). In vitro and in vivo investigations demonstrate that the redox-responsive PSPGP exhibit enhanced endosomal escape and intracellular degradation, which facilitate PTX and TR3 siRNA release, effectively improving the antitumor efficacy.
October 20, 2016: Small
Takeshi Harada, Hideki Yamamoto, Shosei Kishida, Michiko Kishida, Chihiro Awada, Toshifumi Takao, Akira Kikuchi
Wnt5b, a member of the same family of proteins as Wnt5a of which overexpression is associated with cancer aggressiveness, is suggested to be involved in cancer progression, however details remain unclarified. We analyzed biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b are essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a...
October 20, 2016: Cancer Science
Angelyn V Nguyen, Kendra D Nyberg, Michael B Scott, Alia M Welsh, Andrew H Nguyen, Nanping Wu, Sophia V Hohlbauch, Nicholas A Geisse, Ewan A Gibb, A Gordon Robertson, Timothy R Donahue, Amy C Rowat
Metastasis is a fundamentally physical process in which cells are required to deform through narrow gaps as they invade surrounding tissues and transit to distant sites. In many cancers, more invasive cells are more deformable than less invasive cells, but the extent to which mechanical phenotype, or mechanotype, can predict disease aggressiveness in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here we investigate the invasive potential and mechanical properties of immortalized PDAC cell lines derived from primary tumors and a secondary metastatic site, as well as noncancerous pancreatic ductal cells...
October 20, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Preeti Rawat, Lokesh M Saroj, Anil Kumar, Tryambak D Singh, S K Tewari, Mahesh Pal
BACKGROUND: The plant Launaea procumbens belongs to the family Asteraceae and traditionally used in the treatment rheumatism, kidney, liver dysfunctions and eye diseases. In the present study Phytochemical analysis and fractions of methanolic extract of L. procumbens leaves were tested in vitro for their cytotoxicity. OBJECTIVES: Phytochemical analysis and cytotoxic activity of methanolic extract and fractions of Launaea procumbens against four cancer cell lines K562, HeLa, MIA-Pa-Ca-2 and MCF-2 by SRB assay...
July 2016: Pharmacognosy Magazine
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