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https://www.readbyqxmd.com/read/27932417/molecular-pathways-the-necrosome-a-target-for-cancer-therapy
#1
Lena Seifert, George Miller
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27916347/new-treatment-strategy-with-nuclear-factor-%C3%AE%C2%BAb-inhibitor-for-pancreatic-cancer
#2
Takashi Horiuchi, Tadashi Uwagawa, Yoshihiro Shirai, Nobuhiro Saito, Ryota Iwase, Koichiro Haruki, Hiroaki Shiba, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Because of difficulties with early diagnosis, most patients with pancreatic cancer receive chemotherapy. The National Comprehensive Cancer Network guidelines (version 2.2015) suggest therapy with gemcitabine (GEM) plus nab-paclitaxel (nPTX) as a category 1 recommendation for metastatic pancreatic ductal adenocarcinoma. According to the results of many studies, the activation of chemotherapeutic agents-induced nuclear factor-κB (NF-κB) causes chemoresistance. Hence, we hypothesized that the addition of nafamostat mesilate (NM), a potent NF-κB inhibitor, to GEM/nPTX therapy could enhance the antitumor effect in the treatment of pancreatic ductal adenocarcinoma...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27896469/ct-evaluation-after-neoadjuvant-folfirinox-chemotherapy-for-borderline-and-locally-advanced-pancreatic-adenocarcinoma
#3
Mathilde Wagner, Celia Antunes, Daniel Pietrasz, Christophe Cassinotto, Magaly Zappa, Antonio Sa Cunha, Oliver Lucidarme, Jean-Baptiste Bachet
AIM: To assess anatomic changes on computed tomography (CT) after neoadjuvant FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) chemotherapy for secondary resected borderline resectable (BR) and locally advanced (LA) pancreatic adenocarcinoma and their accuracy to predict resectability and pathological response. METHODS: Thirty-six patients with secondary resected BR/LA pancreatic adenocarcinoma after neoadjuvant FOLFIRINOX chemotherapy (± chemoradiotherapy) were retrospectively included...
November 28, 2016: European Radiology
https://www.readbyqxmd.com/read/27895310/tgf%C3%AE-1-overexpression-is-associated-with-improved-survival-and-low-tumor-cell-proliferation-in-patients-with-early-stage-pancreatic-ductal-adenocarcinoma
#4
Evan S Glazer, Eric Welsh, Jose M Pimiento, Jamie K Teer, Mokenge P Malafa
The role of transforming growth factor beta-type-1 (TGFβ1) in pancreatic ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that TGFβ1 expression is associated with survival and proliferation markers in patients with early-stage PDAC. We acquired clinicopathologic, treatment, and mRNA expression data from The Cancer Genome Atlas data set for 106 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients were categorized as high expression when mRNA expression was ≥75th percentile for each gene...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893535/cytoplasmic-hur-status-predicts-disease-free-survival-in-resected-pancreatic-cancer-a-post-hoc-analysis-from-the-international-phase-iii-espac-3-clinical-trial
#5
Talar Tatarian, Wei Jiang, Benjamin E Leiby, Amanda Grigoli, Masaya Jimbo, Nooreen Dabbish, John P Neoptolemos, William Greenhalf, Eithne Costello, Paula Ghaneh, Christopher Halloran, Daniel Palmer, Markus Buchler, Charles J Yeo, Jordan M Winter, Jonathan R Brody
OBJECTIVES: We tested cytoplasmic HuR (cHuR) as a predictive marker for response to chemotherapy by examining tumor samples from the international European Study Group of Pancreatic Cancer-3 trial, in which patients with resected pancreatic ductal adenocarcinoma (PDA) received either gemcitabine (GEM) or 5-fluorouracil (5-FU) adjuvant monotherapy. BACKGROUND: Previous studies have implicated the mRNA-binding protein, HuR (ELAVL1), as a predictive marker for PDA treatment response in the adjuvant setting...
November 23, 2016: Annals of Surgery
https://www.readbyqxmd.com/read/27889393/triple-amirna-vegfrs-inhibition-in-pancreatic-cancer-improves-the-efficacy-of-chemotherapy-through-emt-regulation
#6
Jianfei Huang, Haijun Mei, Zhiyuan Tang, Jieying Li, Xiaojing Zhang, Yixiang Lu, Fang Huang, Qin Jin, Zhiwei Wang
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal outcome. Both novel prognostic markers and therapeutic targets are needed to improve the overall outcome of patients. Although single or double VEGFRs have been studied in PDAC, little is known about the role of triple combination of VEGFRs (VEGFR1, 2, and 3) in prognosis and therapy. We determined VEGFRs protein expression in 241 pancreatic tissues by tissue microarray immunohistochemistry (TMA-IHC), and correlated with patients' clinical characteristics and overall survival...
November 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27888145/critical-role-of-hnrnp-a1-in-activating-kras-transcription-in-pancreatic-cancer-cells-a-molecular-mechanism-involving-g4-dna
#7
REVIEW
Susanna Cogoi, Valentina Rapozzi, Sabina Cauci, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. Its crucial role in the tumourigenesis of pancreatic ductal adenocarcinoma (PDAC) has been widely demonstrated. As this deadly cancer does not sufficiently respond to conventional chemotherapies, it is important to increase our knowledge of pancreatic cancer biology, in particular how oncogenic KRAS is regulated. The promoter of KRAS contains a GA-element composed of runs of guanines that fold into a G4 structure. This unusual DNA conformation is recognized by several nuclear proteins, including MAZ and hnRNP A1...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27885876/predictors-and-survival-for-pathologic-tumor-response-grade-in-borderline-resectable-and-locally-advanced-pancreatic-cancer-treated-with-induction-chemotherapy-and-neoadjuvant-stereotactic-body-radiotherapy
#8
Eric A Mellon, William H Jin, Jessica M Frakes, Barbara A Centeno, Tobin J Strom, Gregory M Springett, Mokenge P Malafa, Ravi Shridhar, Pamela J Hodul, Sarah E Hoffe
BACKGROUND: Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival. MATERIALS AND METHODS: We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24...
November 25, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27875849/-short-and-long-term-results-in-operable-pancreatic-ductal-adenocarcinomas-from-a-cooperation-between-two-departments-gastroenterology-visceral-surgery-at-non-university-hospitals-benchmarked-to-results-of-expert-centers
#9
W Dippold, V Sivanathan, K Statt, M Roitman, K H Link
The only curative approach in pancreatic ductal adenocarcinoma (PDAC) is resection, which is possible only in 15 - 30 % of patients. Local tumor spread or distant metastases are contraindications for resection in the majority of patients. Surgical-oncological quality with short- and long-term results are varying tremendously, so that "expertise/quality" are associated to hospital- or surgeon's volume and/or center formation. The treatment results also depend, to a great extent, on the medical diagnostic quality...
November 22, 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27865278/adjuvant-and-neoadjuvant-therapy-for-resectable-pancreatic-and-periampullary-cancer
#10
REVIEW
Stephanie M Kim, Jennifer R Eads
Pancreatic adenocarcinoma is a relatively uncommon malignancy associated with a high rate of cancer-related mortality despite best efforts to perform curative surgery. Adjuvant therapy in patients after surgical resection is associated with improved overall survival. Adjuvant treatment approaches may include either chemotherapy alone or a combination of chemotherapy and radiation therapy. Neoadjuvant approaches, also including either chemotherapy alone or a combination of chemotherapy and radiation therapy, are under investigation...
December 2016: Surgical Clinics of North America
https://www.readbyqxmd.com/read/27863846/chemotherapy-and-radiation-components-of-neoadjuvant-treatment-of-pancreatic-head-adenocarcinoma-impact-on-perioperative-mortality-and-long-term-survival
#11
J Franko, H W Hsu, P Thirunavukarasu, D Frankova, C D Goldman
BACKGROUND: We compared outcomes of neoadjuvant therapy delivered as chemotherapy-only (Chemo) versus concurrent chemoradiation (ChemoRT) versus chemotherapy followed by radiation (Chemo-ChemoRT) among pancreatic head adenocarcinoma patients receiving pancreaticoduodenectomy. METHODS: National Cancer Data Base cases diagnosed 2006-2011 treated by neoadjuvant therapy and pancreaticoduodenectomy. RESULTS: 1163 pts received neoadjuvant treatment with Chemo (n = 309; 26...
November 11, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27845911/deciphering-the-link-between-pi3k-and-pak-an-opportunity-to-target-key-pathways-in-pancreatic-cancer
#12
REVIEW
Kiruthikah Thillai, Hoyin Lam, Debashis Sarker, Claire M Wells
The development of personalised therapies has ushered in a new and exciting era of cancer treatment for a variety of solid malignancies. Yet pancreatic ductal adenocarcinoma (PDAC) has failed to benefit from this paradigm shift, remaining notoriously refractory to targeted therapies. Chemotherapy is the cornerstone of management but can offer only modest survival benefits of a few months with 5-year survival rates rarely exceeding 3%. Despite these disappointing statistics, significant strides have been made towards understanding the complex biology of pancreatic cancer, with deep genomic sequencing identifying novel genetic aberrations and key signalling pathways...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27845899/bisdemethoxycurcumin-exerts-pro-apoptotic-effects-in-human-pancreatic-adenocarcinoma-cells-through-mitochondrial-dysfunction-and-a-grp78-dependent-pathway
#13
Haopeng Yang, Shengjun Fan, Yu An, Xin Wang, Yan Pan, Yilixiati Xiaokaiti, Jianhui Duan, Xin Li, Lu Tie, Min Ye, Xuejun Li
Pancreatic cancer is a highly aggressive malignancy, which is intrinsically resistant to current chemotherapies. Herein, we investigate whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, potentiates gemcitabine in human pancreatic cancer cells. The result suggests that BDMC sensitizes gemcitabine by inducing mitochondrial dysfunctions and apoptosis in PANC-1 and MiaPaCa-2 pancreatic cancer cells. Utilizing two-dimensional gel electrophoresis and mass spectrometry, we identify 13 essential proteins with significantly altered expressions in response to gemcitabine alone or combined with BDMC...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27845339/a-combination-of-muc5ac-and-ca19-9-improves-the-diagnosis-of-pancreatic-cancer-a-multicenter-study
#14
Sukhwinder Kaur, Lynette M Smith, Asish Patel, Melanie Menning, Duncan C Watley, Saad S Malik, Shiv Ram Krishn, Kavita Mallya, Abhijit Aithal, Aaron R Sasson, Sonny L Johansson, Maneesh Jain, Shailender Singh, Sushovan Guha, Chandrakanth Are, Massimo Raimondo, Michael A Hollingsworth, Randall E Brand, Surinder K Batra
OBJECTIVES: Pancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets. METHODS: The expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry...
November 15, 2016: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/27835602/inhibiting-tumor-necrosis-factor-alpha-diminishes-desmoplasia-and-inflammation-to-overcome-chemoresistance-in-pancreatic-ductal-adenocarcinoma
#15
Xianda Zhao, Wei Fan, Zhigao Xu, Honglei Chen, Yuyu He, Gui Yang, Gang Yang, Hanning Hu, Shihui Tang, Ping Wang, Zheng Zhang, Peipei Xu, Mingxia Yu
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. RESULTS AND METHODS: To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27811314/epigenetic-treatment-of-pancreatic-cancer-is-there-a-therapeutic-perspective-on-the-horizon
#16
REVIEW
Elisabeth Hessmann, Steven A Johnsen, Jens T Siveke, Volker Ellenrieder
Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most aggressive malignancies with a 5-year survival rate of <7%. Due to growing incidence, late diagnosis and insufficient treatment options, PDAC is predicted to soon become one of the leading causes of cancer-related death. Although intensified cytostatic combinations, particularly gemcitabine plus nab-paclitaxel and the folinic acid, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX) protocol, provide some improvement in efficacy and survival compared with gemcitabine alone, a breakthrough in the treatment of metastatic pancreatic cancer remains out of sight...
November 3, 2016: Gut
https://www.readbyqxmd.com/read/27803598/predictors-of-adjuvant-treatment-for-pancreatic-adenocarcinoma-at-the-population-level
#17
D J Kagedan, M E Dixon, R S Raju, Q Li, M Elmi, E Shin, N Liu, A El-Sedfy, L Paszat, A Kiss, C C Earle, N Mittmann, N G Coburn
BACKGROUND: In the present study, we aimed to describe, at the population level, patterns of adjuvant treatment use after curative-intent resection for pancreatic adenocarcinoma (pcc) and to identify independent predictors of adjuvant treatment use. METHODS: In this observational cohort study, patients undergoing pcc resection in the province of Ontario (population 13 million) during 2005-2010 were identified using the provincial cancer registry and were linked to administrative databases that include all treatments received and outcomes experienced in the province...
October 2016: Current Oncology
https://www.readbyqxmd.com/read/27802454/impact-of-sparc-expression-on-outcome-in-patients-with-advanced-pancreatic-cancer-not-receiving-nab-paclitaxel-a-pooled-analysis-from-prospective-clinical-and-translational-trials
#18
Steffen Ormanns, Michael Haas, Sibylle Baechmann, Annelore Altendorf-Hofmann, Anna Remold, Detlef Quietzsch, Michael R Clemens, Martin Bentz, Michael Geissler, Helmut Lambertz, Stephan Kruger, Thomas Kirchner, Volker Heinemann, Stefan Boeck
BACKGROUND: Conflicting results on the role of secreted protein acidic and rich in cysteins (SPARC) expression have been reported in resected pancreatic ductal adenocarcinoma (PDAC), and its prognostic and/or predictive role in advanced PDAC (aPDAC) has not been extensively investigated yet. This study was designed to evaluate SPARC expression as a biomarker in aPDAC patients (pts) not receiving nab-paclitaxel. METHODS: Using immunohistochemistry, we examined the stromal as well as the tumoral (i...
December 6, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27792935/tissue-transglutaminase-activates-cancer-associated-fibroblasts-and-contributes-to-gemcitabine-resistance-in-pancreatic-cancer
#19
Jiyoon Lee, Bakhtiyor Yakubov, Cristina Ivan, David R Jones, Andrea Caperell-Grant, Melissa Fishel, Horacio Cardenas, Daniela Matei
Resistance to chemotherapy is a hallmark of pancreatic ductal adenocarcinoma (PDA) and has been partly attributed to the dense desmoplastic stroma, which forms a protective niche for cancer cells. Tissue transglutaminase (TG2), a Ca(2+)-dependent enzyme, is secreted by PDA cells and cross-links proteins in the tumor microenvironment (TME) through acyl-transfer between glutamine and lysine residues, promoting PDA growth. The objective of the current study was to determine whether secreted TG2 by PDA cells alters the response of pancreatic tumors to gemcitabine...
November 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27785418/clinical-significance-of-serum-omentin-1-levels-in-patients-with-pancreatic-adenocarcinoma
#20
Senem Karabulut, Cigdem Usul Afsar, Mehmet Karabulut, Halil Alis, Mehmet Abdussamet Bozkurt, Fatma Aydogan, Murat Serilmez, Faruk Tas
BACKGROUND: Omentin is related with metabolic syndrome and obesity. Pancreatic adenocarcinoma (PA) is a lethal and obesity-linked malignancy. This study was conducted to investigate the serum levels of omentin in patients with PA and the relationship with tumor progression and known prognostic parameters. MATERIAL AND METHODS: Serum samples were obtained from thirty-three patients on first admission before any treatment. Age, sex and body mass index (BMI) matched 30 healthy controls were included in the analysis...
December 2016: BBA Clinical
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