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Pancreatic adenocarcinoma

Christopher J Halbrook, Marina Pasca di Magliano, Costas A Lyssiotis
In the event of an injury, normal tissues exit quiescent homeostasis and rapidly engage a complex stromal and immune program. These tissue repair responses are hijacked and become dysregulated in carcinogenesis to form a growth supportive tumor microenvironment. In pancreatic ductal adenocarcinoma (PDA), which remains one of the deadliest major cancers, the microenvironment is a key driver of tumor maintenance that impedes many avenues of therapy. In this review, we outline recent efforts made to uncover the microenvironmental crosstalk mechanisms which support pancreatic cancer cells, and detail the strategies which have been undertaken to help overcome these barriers...
March 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Kapo Saukkonen, Jaana Hagström, Harri Mustonen, Laura Lehtinen, Olli Carpen, Leif C Andersson, Hanna Seppänen, Caj Haglund
Expression of regenerating islet-derived protein 4 (REG4), a secretory protein involved in cell differentiation and proliferation, is upregulated in inflammatory bowel diseases and in many gastrointestinal malignancies. The prognostic significance of its expression in pancreatic ductal adenocarcinoma is unknown. Our aim was to investigate tumor tissue and serum REG4 expression in pancreatic ductal adenocarcinoma patients. We also evaluated as a control the diagnostic value of serum REG4 level in patients with chronic pancreatitis...
March 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Leticia Moreira, Basil Bakir, Priya Chatterji, Zahra Dantes, Maximilian Reichert, Anil K Rustgi
Pancreatic ductal adenocarcinoma is one of the most aggressive forms of cancer, and the third leading cause of cancer-related mortality in the United States. Although important advances have been made in the last decade, the mortality rate of pancreatic ductal adenocarcinoma has not changed appreciably. This review summarizes a rapidly emerging model of pancreatic cancer research, focusing on 3-dimensional organoids as a powerful tool for several applications, but above all, representing a step toward personalized medicine...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Carol Cremin, Sarah Howard, Lyly Le, Aly Karsan, David F Schaeffer, Daniel Renouf, Kasmintan A Schrader
Background: Approximately 5% to 10% of pancreatic ductal adenocarcinoma (PDAC) has a hereditary basis. In most of these defined hereditary cancer syndromes, PDAC is not the predominant cancer type. Traditional criteria for publicly funded genetic testing typically require the presence of a set combination of the predominant syndrome-associated cancer types in the family history.We report the identification of a CDKN2A pathogenic variant in a PDAC-prone family without the cutaneous features of multiple moles or melanoma that are characteristic of the Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome identified in a universal testing algorithm for inherited mutations in pancreatic cancer patients...
2018: Hereditary Cancer in Clinical Practice
Margareta Heby, Sebastian Lundgren, Björn Nodin, Jacob Elebro, Jakob Eberhard, Karin Jirström
BACKGROUND: Periampullary adenocarcinomas, including pancreatic cancer, are a heterogeneous group of tumors with poor prognosis, where classification into intestinal type (I-type) or pancreatobiliary type (PB-type) is a relevant prognostic factor. The clinical significance of deficient mismatch repair (dMMR) in periampullary adenocarcinoma is comparatively unexplored. Herein, we examined the associations of MMR immunophenotype with long-term survival in patients with resected periampullary adenocarcinoma, with particular reference to morphology and adjuvant treatment response...
March 14, 2018: Journal of Translational Medicine
Sun-Young Jun, Seung-Mo Hong, Young Kyung Bae, Hee Kyung Kim, Kyu Yun Jang, Dae Woon Eom
Heme oxygenase-1 (HO-1), a stress-response protein, is highly induced in various carcinomas. It is implicated in carcinogenesis and tumor progression. High HO-1 expression is associated with better prognosis of patients with colorectal and gastric cancers. Induction or inhibition of HO-1 can mediate chemo-sensitivity, therefore it might be a therapeutic target to develop anticancer agents. To define the clinicopathological and prognostic significance of HO-1 expression in small-intestinal adenocarcinomas (SIACs), immunohistochemical microarray analysis of HO-1 expression was performed for 191 surgically resected SIAC cases and results were compared with various clinicopathologic variables, including survival...
March 14, 2018: Pathology International
Carolina Torres, Paul J Grippo
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as one disease, accumulated evidences point to the clinical heterogeneity of this disease which translates into disparity in outcomes between patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last ten years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles...
March 14, 2018: Annals of Medicine
Jiyan Mohammad, Harsharan Dhillon, Shireen Chikara, Sujan Mamidi, Avinash Sreedasyam, Kishore Chittem, Megan Orr, John C Wilkinson, Katie M Reindl
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to a late diagnosis and poor response to available treatments. There is a need to identify complementary treatment strategies that will enhance the efficacy and reduce the toxicity of currently used therapeutic approaches. We investigated the ability of a known ROS inducer, piperlongumine (PL), to complement the modest anti-cancer effects of the approved chemotherapeutic agent gemcitabine (GEM) in PDAC cells in vitro and in vivo . PDAC cells treated with PL + GEM showed reduced cell viability, clonogenic survival, and growth on Matrigel compared to control and individually-treated cells...
February 13, 2018: Oncotarget
Andrew J Benjamin, Mary M Buschmann, Shuang Qin Zhang, Kristen Wroblewski, Hedy L Kindler, Kevin K Roggin, William Dale
OBJECTIVE: Sarcopenia is associated with poor outcomes in patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). However, few studies have assessed changes in sarcopenia during multimodality therapy or its effect on overall survival (OS). METHODS: Computed tomography (CT) total psoas area index (TPAI) and weighted average Hounsfield units (HU) were measured at each treatment interval in patients with resectable PDAC. Four cohorts were compared: 1...
March 10, 2018: Journal of Geriatric Oncology
Yasuhiro Kinugawa, Takeshi Uehara, Kazuyuki Matsuda, Yukihiro Kobayashi, Tomoyuki Nakajima, Hideaki Hamano, Shigeyuki Kawa, Kayoko Higuchi, Noriko Hosaka, Satoshi Shiozawa, Hiroki Ishigame, Toshitsugu Nakamura, Yasuhiro Maruyama, Koh Nakazawa, Masato Nakaguro, Kenji Sano, Hiroyoshi Ota
The relationship between methylation abnormality and autoimmune pancreatitis (AIP)-a representative IgG4-related disease-has not yet been elucidated. We identified SKI might have a significant methylation abnormality in AIP through methylation array analysis using the Illumina Infinium Human Methylation 450K BeadChip array, and investigated the relationship of SKI with AIP clinicopathological features. The methylation rate of SKI was assessed by quantitative SYBR green methylation-specific PCR, and the degree of SKI expression in tissue specimens was assessed by immunohistochemistry in 10 AIP cases, 14 cases of obstructive pancreatitis area in pancreatic ductal adenocarcinoma (PDA) without a history of AIP, and 9 normal pancreas (NP) cases...
March 6, 2018: Pathology, Research and Practice
X W Xu, R C Zhang, Y P Mou, Z Y Qian, C J Huang, Q C Zhu, W W Jin, Y C Zhou
Objective: To evaluate the safety and feasibility of laparoscopic radical antegrade modular pancreatosplenectomy(Lap-RAMPS) for left-sided pancreatic adenocarcinoma. Methods: Clinical data of total 12 patients underwent Lap-RAMPS for left-sided pancreatic adenocarcinoma at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital from March 2016 to August 2017 were reviewed retrospectively.There were 7 male patients and 5 female patients, with median age of 60.5 years old(47-68 years old)...
March 1, 2018: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
L P Fang, X Y Xu, Y Ji, P W Huang
Objective: To investigate the clinical outcomes and prognostic factors in patients with pancreatic cancer after surgical resection with curative intent and analyze factors affecting 2-year and 5-year survival of patients. Methods: A total of 469 patients with pancreatic adenocarcinoma undergoing curative resection were included in the study, and the clinical data of these patients were analyzed retrospectively. Univariate and multivariate analyses were performed to examine factors affecting prognosis of these patients...
February 27, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Zhimin Tao, Mandar Deepak Muzumdar, Alexandre Detappe, Xing Huang, Eric Xu, Yingjie Yu, Tarek H Mouhieddine, Haiqin Song, Tyler Jacks, P Peter Ghoroghchian
Human pancreatic ductal adenocarcinoma (PDAC) contains a distinctively dense stroma that limits the accessibility of anticancer drugs, contributing to its poor overall prognosis. Nanoparticles can enhance drug delivery and retention in pancreatic tumors and have been utilized clinically for their treatment. In preclinical investigations, various mouse models differentially recapitulate the microenvironmental features of human PDAC. Here, we demonstrate that through utilization of different organic co-solvents and by doping of a homopolymer of poly(ε-caprolactone), a diblock copolymer composition of poly(ethylene oxide)- block-poly(ε-caprolactone) may be utilized to generate biodegradable and nanoscale micelles with different physical properties...
March 13, 2018: Nano Letters
Stefano Menini, Carla Iacobini, Luisa de Latouliere, Isabella Manni, Vittoria Ionta, Claudia Blasetti Fantauzzi, Carlo Pesce, Paola Cappello, Francesco Novelli, Giulia Piaggio, Giuseppe Pugliese
Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, Western diet and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation endproducts (AGEs), which characterizes all the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumor-promoting role of RAGE, the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation...
March 13, 2018: Journal of Pathology
Bo Zhang, Honglan Wang, Ting Jiang, Kai Jin, Zimiao Luo, Wei Shi, Heng Mei, Huafang Wang, Yu Hu, Zhiqing Pang, Xinguo Jiang
As one of the most intractable tumors, pancreatic ductal adenocarcinoma (PDA) has a dense extracellular matrix (ECM) which could increase solid stress within tumors to compress tumor vessels, reduce tumor perfusion, and compromise nanomedicine delivery for PDA. Thus, alleviating solid stress represents a potential therapeutic target for PDA treatment. In this study, cyclopamine, a special inhibitor of the hedgehog signaling pathway which contributes a lot to ECM formation of PDA, was exploited to alleviate solid stress and improve nanomedicine delivery to PDA...
March 13, 2018: Journal of Drug Targeting
Zhipeng Zhang, Hongxi Chen, Yebin Lu, Tiecheng Feng, Weijia Sun
This study examined the effects of long non‑coding RNA (lncRNA) BC032020 on the development of human pancreatic ductal adenocarcinoma (PDAC), and the potential molecular mechanisms responsible for these effects. The expression of BC032020 was assessed in 20 pairs of PDAC tumor tissues and adjacent normal tissues. The overexpression of BC032020 was enforced in the AsPC‑1 and PANC‑1 cells, and the effects on cell proliferation, cell cycle distribution, cell migration and apoptosis were determined. We also analyzed the functions of zinc finger protein 451 (ZNF451), which shares a gene sequence with two exons of BC032020 and a non‑coding region with another two exons, in PDAC cells...
April 2018: International Journal of Oncology
Sjors Klompmaker, Jony van Hilst, Sarah L Gerritsen, Mustapha Adham, M Teresa Albiol Quer, Claudio Bassi, Frederik Berrevoet, Ugo Boggi, Olivier R Busch, Manuela Cesaretti, Raffaele Dalla Valle, Benjamin Darnis, Matteo De Pastena, Marco Del Chiaro, Robert Grützmann, Markus K Diener, Traian Dumitrascu, Helmut Friess, Arpad Ivanecz, Anastasios Karayiannakis, Giuseppe K Fusai, Knut J Labori, Carlo Lombardo, Santiago López-Ben, Jean-Yves Mabrut, Willem Niesen, Fernando Pardo, Julie Perinel, Irinel Popescu, Geert Roeyen, Alain Sauvanet, Raj Prasad, Christian Sturesson, Mickael Lesurtel, Jorg Kleeff, Roberto Salvia, Marc G Besselink
BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival...
March 12, 2018: Annals of Surgical Oncology
Silvia Zhou
No abstract text is available yet for this article.
February 2018: Hepatobiliary Surgery and Nutrition
Patricia Santofimia-Castaño, Bruno Rizzuti, Olga Abián, Adrián Velázquez-Campoy, Juan L Iovanna, José L Neira
BACKGROUND: NUPR1 is a multifunctional intrinsically disordered protein (IDP) involved, among other functions, in chromatin remodelling, and development of pancreatic ductal adenocarcinoma (PDAC). It interacts with several biomolecules through hydrophobic patches around residues Ala33 and Thr68. The drug trifluoperazine (TFP), which hampers PDAC development in xenografted mice, also binds to those regions. Because of the large size of the hot-spot interface of NUPR1, small molecules could not be adequate to modulate its functions...
March 9, 2018: Biochimica et Biophysica Acta
Hye-Yeong Kim, Xiaolei Wang, Rui Kang, Daolin Tang, Brian A Boone, Herbert J Zeh, Michael T Lotze, W Barry Edwards
Noninvasive detection of both early pancreatic neoplasia and metastases could enhance strategies to improve patient survival in this disease that is notorious for an extremely poor prognosis. There are almost no identifiable targets for non-invasive diagnosis by positron emission tomography (PET) for patients with pancreatic ductal adenocarcinoma (PDAC). Over-expression of the receptor for advanced glycation end products (RAGE) is found on the cell surface of both pre-neoplastic lesions and invasive PDAC. Here, a RAGE-specific single chain (scFv) was developed, specific for PET imaging in syngeneic mouse models of PDAC...
2018: PloS One
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