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Pancreatic adenocarcinoma

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https://www.readbyqxmd.com/read/29331808/simultaneous-inhibition-of-hedgehog-signaling-and-tumor-proliferation-remodels-stroma-and-enhances-pancreatic-cancer-therapy
#1
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
January 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331423/thymidylate-synthase-prompts-metastatic-progression-through-the-dtmp-associated-emt-process-in-pancreatic-ductal-adenocarcinoma
#2
Muxing Kang, Wen Zheng, Qing Chen, Wenjie Qin, Pengping Li, Shifei Huang, Yizhao Zhou, Lantian Wang, Haolei Cai, Wenjie Lu, Biao Jiang, Qingqu Guo, Jian Chen, Dylan Wan, Jianyu Rao, Yulian Wu
As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has been shown to be an effective therapy for human cancers. However, the genuine effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We systemically assessed the prognostic value and whether TS associated with malignant progression in PDA. Protein and mRNA expression level of TS were evaluated in en bloc PDA samples, the prognostic effect of TS expressed in cytoplasm or cytonuclear was determined separately in the first time...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330807/evaluation-of-macrophage-polarization-in-pancreatic-cancer-microenvironment-under-hypoxia
#3
Kuldeep S Attri, Kamiya Mehla, Pankaj K Singh
Hypoxic microenvironment found in pancreatic ductal adenocarcinoma and other solid tumors is central to physiological and metabolic alterations of immune cells that significantly impact tumor growth dynamics. Hypoxic adaptations in the immune cells are primarily mediated by the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which regulates cellular metabolism by modulating glycolysis and other interconnected metabolic pathways. HIF-1α plays distinct roles in M1 and M2 macrophage polarization, which, in turn, regulates tumor cell immune escape and growth...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330793/hypoxia-induced-metabolomic-alterations-in-pancreatic-cancer-cells
#4
Venugopal Gunda, Sushil Kumar, Aneesha Dasgupta, Pankaj K Singh
Hypoxic conditions in the pancreatic tumor microenvironment lead to the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which acts as the master regulator of cancer cell metabolism. HIF-1α-mediated metabolic reprogramming results in large-scale metabolite perturbations. Characterization of the metabolic intermediates and the corresponding metabolic pathways altered by HIF-1α would facilitate the identification of therapeutic targets for hypoxic microenvironments prevalent in pancreatic ductal adenocarcinoma and other solid tumors...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330203/personalized-rna-medicine-for-pancreatic-cancer
#5
Maud-Emmanuelle Gilles, Liangliang Hao, Ling Huang, Rajesha Rupaimoole, Pedro P Lopez-Casas, Emilia Pulver, Jong Cheol Jeong, Senthil K Muthuswamy, Manuel Hidalgo, Sangeeta N Bhatia, Frank J Slack
PURPOSE: Since drug responses vary between patients, it is crucial to develop pre-clinical or co-clinical strategies that forecast patient response. In this study, we tested whether RNA-based therapeutics were suitable for personalized medicine by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models.  Experimental Design: We performed microRNA (miRNA) profiling of PDX samples to determine the status of miRNA deregulation in individual pancreatic ductal adenocarcinoma (PDAC) patients...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29329518/the-use-of-eculizumab-in-gemcitabine-induced-thrombotic-microangiopathy
#6
Vinod Krishnappa, Mohit Gupta, Haikoo Shah, Abhijit Das, Natthavat Tanphaichitr, Robert Novak, Rupesh Raina
BACKGROUND: Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure...
January 12, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29329480/direct-endoscopy-and-diagnosis-of-adenocarcinoma-following-metal-stent-based-drainage-of-a-pancreatic-cyst
#7
Sebastian Zeissig, Renate Schmelz, Stefan Brückner, Daniela E Aust, Gustavo B Baretton, Jochen Hampe
No abstract text is available yet for this article.
January 12, 2018: Endoscopy
https://www.readbyqxmd.com/read/29329208/advances-in-molecular-profiling-and-categorisation-of-pancreatic-adenocarcinoma-and-the-implications-for-therapy
#8
REVIEW
Rille Pihlak, Jamie M J Weaver, Juan W Valle, Mairéad G McNamara
Pancreatic ductal adenocarcinoma (PDAC) continues to be a disease with poor outcomes and short-lived treatment responses. New information is emerging from genome sequencing identifying potential subgroups based on somatic and germline mutations. A variety of different mutations and mutational signatures have been identified; the driver mutation in around 93% of PDAC is KRAS, with other recorded alterations being SMAD4 and CDKN2A. Mutations in the deoxyribonucleic acid (DNA) damage repair pathway have also been investigated in PDAC and multiple clinical trials are ongoing with DNA-damaging agents...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29329159/overexpression-of-the-long-noncoding-rna-homeboxa-transcript-at-the-distal-tip-predicts-poor-prognosis-in-a-kras-independent-manner-in-periampullary-region-tumors
#9
Ozkan Balcin, Secil Ak Aksoy, Berrin Tunca, Ekrem Kaya, Unal Egeli, Gulcin Tezcan, Nesrin Ugras, Gulsah Cecener, Ozgen Isik, Halit Ziya Dundar, Omer Yerci
OBJECTIVES: Periampullary region tumors (PRTs) are the fifth highest cause of cancer-related deaths worldwide. Although recent studies have highlighted the prognostic value of the long noncoding RNA HomeboxA transcript at the distal tip (HOTTIP) in patients with pancreatic ductal adenocarcinoma, the relationship between HOTTIP and clinical outcome of all PRTs remains obscure. The aim of this study was to clarify the prognostic significance of HOTTIP in patients with all PRTs related to KRAS mutational status...
January 12, 2018: Pancreas
https://www.readbyqxmd.com/read/29329157/smad4-loss-correlates-with-higher-rates-of-local-and-distant-failure-in-pancreatic-adenocarcinoma-patients-receiving-adjuvant-chemoradiation
#10
Joseph M Herman, Salma K Jabbour, Steven H Lin, Matthew P Deek, Charles C Hsu, Elliot K Fishman, Sinae Kim, John L Cameron, Marina Chekmareva, Daniel A Laheru, Amol K Narang, Timothy M Pawlik, Ralph H Hruban, Christopher L Wolfgang, Christine A Iacobuzio-Donahue
OBJECTIVES: The tumor suppressor gene SMAD4 (DPC4) is genetically inactivated in approximately half of pancreatic ductal adenocarcinomas (PDAs). We examined whether Smad4 tumor status was associated with outcomes after adjuvant chemoradiation (CRT) for resected PDAs. METHODS: Patients treated with adjuvant CRT were identified (N = 145). Smad4 status was determined by immunolabeling and graded as intact or lost. Kaplan-Meier method and multivariable competing risk analyses were performed...
January 12, 2018: Pancreas
https://www.readbyqxmd.com/read/29328656/design-and-synthesis-of-novel-reactive-oxygen-species-inducers-for-the-treatment-of-pancreatic-ductal-adenocarcinoma
#11
Yuting Kuang, Mario Sechi, Salvatore Nurra, Mats Ljungman, Nouri Neamati
Altering redox homeostasis provides distinctive therapeutic opportunities for the treatment of pancreatic cancer. Quinazolinediones (QDs) are novel redox modulators that we previously showed to induce potent growth inhibition in pancreatic ductal adenocarcinoma (PDAC) cell lines. Our lead optimization campaign yielded QD325 as the most potent redox modulator candidate inducing substantial reactive oxygen species (ROS) in PDAC cells. Nascent RNA sequencing following treatments with the QD compounds revealed induction of stress responses in nucleus, endoplasmic reticulum, and mitochondria of pancreatic cancer cells...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29327180/chemotherapy-with-or-without-definitive-radiation-therapy-in-inoperable-pancreatic-cancer
#12
Jim Zhong, Jeffrey Switchenko, Madhusmita Behera, David Kooby, Shishir K Maithel, Mark W McDonald, Jolinta Y Lin, Richard J Cassidy, Bassel El-Rayes, Jerome Landry, Pretesh R Patel
BACKGROUND: The LAP07 randomized trial calls into question the role of radiation therapy (RT) in the modern treatment of locally advanced pancreatic cancer (LAPC). However, advances in chemotherapy and RT limit application of the LAP07 results to current clinical practice. Here we utilize the National Cancer Database (NCDB) to evaluate the effects of RT in patients receiving chemotherapy for LAPC. METHODS: Using the NCDB, patients with American Joint Committee on Cancer (AJCC) clinical stage T2-4, N0-1, M0 adenocarcinoma of the pancreas from 2004 to 2014 were analyzed...
January 11, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29326012/stereotactic-body-radiotherapy-sbrt-for-patients-with-locally-advanced-pancreatic-cancer-a-single-center-experience
#13
Raphaël Jumeau, Guila Delouya, David Roberge, David Donath, Dominic Béliveau-Nadeau, Marie-Pierre Campeau
INTRODUCTION: Despite advances in treatment, notably in systemic therapy, the prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We review outcomes of SBRT for PADC at our institution. METHODS: We reviewed patients treated with SBRT for either unresectable PADC or locally recurrent PADC after surgery. Treatment was delivered using a robotic radiosurgery system with respiratory tracking...
December 21, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29325740/indocyanine-green-loaded-hyaluronan-derived-nanoparticles-for-fluorescence-enhanced-surgical-imaging-of-pancreatic-cancer
#14
Bowen Qi, Ayrianne J Crawford, Nicholas E Wojtynek, Megan B Holmes, Joshua J Souchek, Graca Almeida-Porada, Quan P Ly, Samuel M Cohen, Michael A Hollingsworth, Aaron M Mohs
Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas...
January 8, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29325707/successful-creation-of-pancreatic-cancer-organoids-by-means-of-eus-guided-fine-needle-biopsy-for-personalized-cancer-treatment
#15
Herve Tiriac, Juan Carlos Bucobo, Demetrios Tzimas, Suman Grewel, Joseph F Lacomb, Leahana M Rowehl, Satish Nagula, Maoxin Wu, Joseph Kim, Aaron Sasson, Shivakumar Vignesh, Laura Martello, Maria Munoz-Sagastibelza, Jonathan Somma, David A Tuveson, Ellen Li, Jonathan M Buscaglia
BACKGROUND AND AIMS: Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately the vast majority of patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) in patients with PDA...
January 8, 2018: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29325463/compared-with-elastin-stains-h-caldesmon-and-desmin-offer-superior-detection-of-vessel-invasion-in-gastric-pancreatic-and-colorectal-adenocarcinomas
#16
Özgür Ekinci, Betül Öğüt, Bülent Çelik, Ayşe Dursun
BACKGROUND: The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens. MATERIALS AND METHODS: We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used...
January 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29324695/investigation-into-improving-the-aqueous-solubility-of-the-thieno-2-3-b-pyridine-anti-proliferative-agents
#17
Ayesha Zafar, Lisa I Pilkington, Natalie A Haverkate, Michelle van Rensburg, Euphemia Leung, Sisira Kumara, William A Denny, David Barker, Ali Alsuraifi, Clare Hoskins, Jóhannes Reynisson
It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategies were pursued. First, a morpholine moiety was tethered to the molecular scaffold by substituting the sulphur atom with nitrogen, resulting in a 1H-pyrrolo[2,3-b]pyridine core structure. The water solubility was increased by three orders of magnitude, from 1.2 µg/mL (1-thieno[2,3-b]pyridine) to 1...
January 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29322792/krasg12d-loh-promotes-malignant-biological-behavior-and-energy-metabolism-of-pancreatic-ductal-adenocarcinoma-cells-through-the-mtor-signaling-pathway
#18
X Shen, L G Chang, M Y Hu, D Yan, L N Zhou, Y Ma, S K Ling, Y Q Fu, S Y Zhang, B Kong, P L Huang
Oncogenic Kras with loss of heterozygosity (LOH) is frequently detected in various tumours. However, the exact function and mechanism by which KrasG12D-LOH operates remain unclear. Therefore, the current study investigated the effect of KrasG12D-LOH on the malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) cells. Our investigation revealed that KrasG12D-LOH is associated with increased proliferation, invasion and reduced apoptosis in PDAC cells. The results also exhibited enhanced glycolytic phenotype of KrasG12D-LOH PDAC cells...
2018: Neoplasma
https://www.readbyqxmd.com/read/29322643/disparities-in-cancer-outcomes-across-age-sex-and-race-ethnicity-among-patients-with-pancreatic-cancer
#19
Ryan Nipp, Angela C Tramontano, Chung Yin Kong, Pari Pandharipande, Emily C Dowling, Deborah Schrag, Chin Hur
Age, sex, and racial/ethnic disparities exist, but are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to determine whether survival and treatment disparities persist after adjusting for demographic and clinical characteristics. Our study included PDAC patients diagnosed between 1992 and 2011. We used Cox regression to compare survival across age, sex, and race/ethnicity within early-stage and late-stage cancer subgroups, adjusting for marital status, urban location, socioeconomics, SEER region, comorbidities, stage, lymph node status, tumor location, tumor grade, diagnosis year, and treatment received...
January 11, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29321164/kras-oncoprotein-expression-is-regulated-by-a-self-governing-eif5a-peak1-feed-forward-regulatory-loop
#20
Ken Fujimura, Huawei Wang, Felicia Watson, Richard L Klemke
There remains intense interest in tractable approaches to target or silence the KRAS oncoprotein as a rational therapeutic strategy to attack pancreatic adenocarcinoma (PDAC) and other cancers which overexpress it. Here we provide evidence that accumulation of the KRAS oncoprotein is controlled by a self-regulating feed-forward regulatory loop that utilizes a unique hypusinated isoform of the translation elongation factor eIF5A and the tyrosine kinase PEAK1. Oncogenic activation of KRAS increased eIF5A-PEAK1 translational signaling, which in turn facilitated increased KRAS protein synthesis...
January 10, 2018: Cancer Research
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