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pancreatic adenocarcinoma chemotherapy

Manjusha Thakar, Yue Hu, Michael Morreale, Lane Lerner, Wan Ying Lin, Rupashree Sen, Yi Cai, Enusha Karunasena, Maya Thakar, Soren Saggi, Harold Keer, Nita Ahuja
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations...
2018: PloS One
Yoshihiko Fukukura, Yuichi Kumagae, Ryutaro Higashi, Hiroto Hakamada, Koji Takumi, Kosei Maemura, Michiyo Higashi, Kiyohisa Kamimura, Masanori Nakajo, Takashi Yoshiura
OBJECTIVES: To assess whether extracellular volume (ECV) fraction with equilibrium contrast-enhanced multidetector computed tomography (MDCT) predicts outcomes for unresectable pancreatic adenocarcinoma patients treated with chemotherapy METHODS: Sixty-seven patients (42 men, 25 women; mean age, 67.5 years; range, 45-83 years) with histologically confirmed surgically unresectable pancreatic adenocarcinoma underwent contrast-enhanced MDCT before systemic chemotherapy. Tumour contrast enhancement (CE) and ECV fraction were calculated using region-of-interest measurement within the pancreatic adenocarcinoma and aorta on unenhanced and equilibrium phase-enhanced CT...
June 19, 2018: European Radiology
Feng Shao, Mei Huang, Futao Meng, Qiang Huang
Gemcitabine resistance is currently the main problem of chemotherapy for advanced pancreatic cancer patients. The resistance is thought to be caused by altered drug metabolism or reduced apoptosis of cancer cells. However, the underlying mechanism of Gemcitabine resistance in pancreatic cancer remains unclear. In this study, we established Gemcitabine resistant PANC-1 (PANC-1-GR) cell lines and compared the circular RNAs (circRNAs) profiles between PANC-1 cells and PANC-1-GR cells by RNA sequencing. Differentially expressed circRNAs were demonstrated using scatter plot and cluster heatmap analysis...
2018: Frontiers in Pharmacology
Hirokazu Shoji, Nami Miura, Hideki Ueno, Kazufumi Honda
The standard therapeutic strategy recommended for locally advanced pancreatic cancer (LAPC) is typically chemotherapy or chemoradiotherapy (CRT). Although the clinical benefit of chemotherapy alone versus CRT for LAPC has been compared in a number of clinical trials, the optimal therapy for LAPC remains unclear. Moreover, the clinical benefit derived from treatment in each clinical trial is a matter of controversy, and the superiority of one treatment over another has yet to be definitively demonstrated. The poor outcomes seen among patients with LAPC owe largely to the emergence of metastatic disease; therefore, accurately evaluating occult distant metastasis before choosing a therapeutic strategy could be expected to help stratify patients with LAPC into the most appropriate treatment regimen, namely local control or systemic therapy...
June 16, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Dalong Sun, Jing Chen, Longzi Liu, Guangxi Zhao, Pingping Dong, Bingrui Wu, Jun Wang, Ling Dong
A robust and accurate gene expression signature is essential to assist oncologists to determine which subset of patients at similar Tumor-Lymph Node-Metastasis (TNM) stage has high recurrence risk and could benefit from adjuvant therapies. Here we applied a two-step supervised machine-learning method and established a 12-gene expression signature to precisely predict colon adenocarcinoma (COAD) prognosis by using COAD RNA-seq transcriptome data from The Cancer Genome Atlas (TCGA). The predictive performance of the 12-gene signature was validated with two independent gene expression microarray datasets: GSE39582 includes 566 COAD cases for the development of six molecular subtypes with distinct clinical, molecular and survival characteristics; GSE17538 is a dataset containing 232 colon cancer patients for the generation of a metastasis gene expression profile to predict recurrence and death in COAD patients...
2018: PeerJ
Shohei Kawashiro, Shigeru Yamada, Masahiko Okamoto, Tatsuya Ohno, Takashi Nakano, Makoto Shinoto, Yoshiyuki Shioyama, Kenji Nemoto, Yuka Isozaki, Hiroshi Tsuji, Tadashi Kamada
PURPOSE: The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS: Patients with LAPC treated with C-ion RT from April 2012 to December 2014 at 3 institutions were retrospectively analyzed. Patients with pathologically-confirmed invasive ductal adenocarcinoma of the pancreas were eligible. The prescribed dose was 52.8 Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
Somala Mohammed, Jose E Mendez-Reyes, Amy McElhany, Daniel Gonzales-Luna, George Van Buren, Daniel S Bland, Nicole Villafane-Ferriol, Jeanne A Pierzynski, Charles A West, Eric J Silberfein, William E Fisher
BACKGROUND: Addition of en bloc segmental venous reconstruction (VR) to pancreaticoduodenectomy (PD) for venous involvement of pancreatic tumors increases the complexity of the operation and may increase complications. The long-term mesenteric venous patency rate and oncologic outcome has not been well defined. METHODS: Our prospective database was reviewed to assess 90-day postoperative outcomes for patients who underwent PD or PD + VR (September 2004-June 2016)...
August 2018: Journal of Surgical Research
Adrian M J Pokorny, Venessa T Chin, Adnan M Nagrial, Desmond Yip, Lorraine A Chantrill
Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a lethal disease with a poor 5-year survival. Systemic treatments can be used to control symptoms and prolong life. Cytotoxic chemotherapies are commonly administered, with combination treatments, such as fluorouracil, folinic acid, irinotecan and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine showing the largest clinical benefits. Newer genomic classifications of PDAC may provide a rationale for targeted therapies or immunotherapies, although at present these remain largely experimental...
June 2018: Internal Medicine Journal
Andrés Muñoz Martín, Manuel Hidalgo, Rafael Alvarez, Virginia Arrazubi, Joaquina Martínez-Galán, Mercedes Salgado, Teresa Macarulla, Alfredo Carrato
The current management of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is based on systemic chemotherapy. The results of the MPACT and PRODIGE clinical trials have demonstrated that the combination of nab-paclitaxel and gemcitabine (GEM) as well as FOLFIRINOX regimen result in improvement in overall survival when compared to GEM alone. Treatment guidelines now recommend either one of these two regimens as first line treatment for fit patients with mPDAC. Because no head-to-head comparison between the two regimens exists, the selection of one versus the other is based on clinical criteria...
2018: Journal of Cancer
Yann Wallez, Charles R Dunlop, Timothy Isaac Johnson, Siang-Boon Koh, Chiara Fornari, James Wt Yates, Sandra Bernaldo de Quirós Fernández, Alan Lau, Frances M Richards, Duncan I Jodrell
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers and overall survival rates have barely improved over the past five decades. The antimetabolite gemcitabine remains part of the standard-of-care, but shows very limited anti-tumor efficacy. Ataxia telangiectasia and Rad3-related protein (ATR), the apical kinase of the intra-S-phase DNA damage response (DDR), plays a central role in safeguarding cells from replication stress (RS) and can therefore limit the efficacy of antimetabolite drug therapies...
June 11, 2018: Molecular Cancer Therapeutics
Sang Hyun Shin, Song Cheol Kim, Ki-Byung Song, Dae Wook Hwang, Jae Hoon Lee, Kwang-Min Park, Young-Joo Lee
BACKGROUND: To identify chronologic changes in clinical and survival features of pancreatic ductal adenocarcinoma based on diagnosis and treatment strategy development since 2000. METHODS: Among 2,029 patients enrolled in this study, 746 and 1,283 were treated between 2000 and 2009 (group 1) and between 2010 and 2016 (group 2), respectively. We used patient clinicopathologic, biologic, and molecular factors to assess the prognostic factors. RESULTS: Group 2 had a better survival outcome than group 1 (median survival time: 24...
June 5, 2018: Surgery
Ryosuke Yamaga, Koji Tezuka, Shuichiro Sugawara, Toshihiro Watanabe, Ichiro Hirai, Tamio Suzuki, Wataru Kimura
BACKGROUND: Metastatic recurrence after resection of pancreatic cancer is considered to be an incurable disease, and discoid lupus erythematosus (DLE)-like lesions are known as a side effect of fluorouracil agents. We report a very rare case of metastatic recurrence of pancreatic cancer in a Japanese man with DLE-like lesions in which long-term complete response was achieved through S-1 monotherapy. CASE PRESENTATION: A 65-year-old man who had undergone distal pancreatectomy with splenectomy for pancreatic body cancer and had received adjuvant gemcitabine developed postoperative para-aortic lymph node recurrence 17 months after surgery...
June 7, 2018: Surgical Case Reports
Kai-Wen Huang, Po-Chih Yang, Uei Pua, Man-Deuk Kim, Sheng-Ping Li, Yu-Dong Qiu, Tian-Qiang Song, Po-Chin Liang
BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). METHODS: From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE...
June 7, 2018: Journal of Surgical Oncology
Caitlin A Hester, Mathew M Augustine, Michael A Choti, John C Mansour, Rebecca M Minter, Patricio M Polanco, Matthew R Porembka, Sam C Wang, Adam C Yopp
BACKGROUND: A paucity of data exists regarding the natural history and outcome measures of adenosquamous carcinoma of the pancreas (ASCP), a histology distinct from pancreatic adenocarcinoma (PDAC). The aim of this study is to characterize the clinicopathological features of ASCP in a large cohort of patients comparing outcome measures of surgically resected patients to PDAC. METHODS: We identified patients diagnosed with ASCP or PDAC from the National Cancer Database from 2004 to 2012...
June 7, 2018: Journal of Surgical Oncology
Naru Kondo, Yoshiaki Murakami, Kenichiro Uemura, Naoya Nakagawa, Kenjiro Okada, Shinya Takahashi, Taijiro Sueda
BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the prognostic impact of postoperative complications after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) stratified by resectability status. METHODS: Medical records of 226 patients with pancreatic head carcinoma who underwent PD, including 115 with resectable (R) and 111 with borderline resectable/unresectable (BR/UR) PDAC, were reviewed retrospectively. Major complications were defined as grade III or IV based on the Clavien-Dindo classification system...
June 7, 2018: Journal of Surgical Oncology
Etienne D Foucher, Clément Ghigo, Salem Chouaib, Jérôme Galon, Juan Iovanna, Daniel Olive
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with very few available treatments. For many decades, gemcitabine was the only treatment for patients with PDAC. A recent attempt to improve patient survival by combining this chemotherapy with FOLFIRINOX and nab-paclitaxel failed and instead resulted in increased toxicity. Novel therapies are urgently required to improve PDAC patient survival. New treatments in other cancers such as melanoma, non-small-cell lung cancer, and renal cancer have emerged, based on immunotherapy targeting the immune checkpoints cytotoxic T-lymphocyte-associated antigen 4 or programmed death 1 ligand...
2018: Frontiers in Immunology
Jung Hoon Kim, Sang-Cheol Lee, Sung Yong Oh, Seo-Young Song, Namsu Lee, Eun Mi Nam, Soonil Lee, In Gyu Hwang, Hyo Rak Lee, Kyu Taek Lee, Sang-Byung Bae, Han Jo Kim, Joung Soon Jang, Do Hyoung Lim, Hyun Woo Lee, Seok Yun Kang, Jung Hun Kang
BACKGROUND: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. METHODS: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals...
June 4, 2018: Cancer communications
Maria Antonietta Bali, Serena Pullini, Thierry Metens, Julie Absil, Shih-Li Chao, Raphael Marechal, Celso Matos, Bibi Mooneera Peerboccus, Jean-Luc Van Laethem
PURPOSE: To prospectively assess chemotherapy-induced changes in pancreatic ductal adenocarcinoma (PDA) with diffusion-weighted (DW)-MR quantitative metrics, including apparent diffusion coefficient (ADC) and histogram-derived parameters, compared with RECIST 1.1. METHODS: 24 patients underwent DW-MR at baseline, week-2 and week-8 after chemotherapy initiation. Tumour diameter was assessed on T2-weighted images. Regions-of-interest (ROI) were drawn on ADC map for ROI-ADC...
July 2018: European Journal of Radiology
S Drápela, R Fedr, P Khirsariya, K Paruch, M Svoboda, K Souček
BACKGROUND: Nucleoside analogues represent a relevant class of antimetabolites used for therapy of various types of cancer. However, their effectivity is limited by drug resistance. The nucleoside transport capability of tumour cells is considered to be a determinant of the clinical outcome of treatment regimens using antimetabolites. Due to hydrophilic properties of antimetabolites, their transport across the plasma membrane is mediated by two families of transmembrane proteins, the SLC28 family of cation-linked concentrative nucleoside transporters (hCNTs) and SLC29 family of energy-independent equilibrative nucleoside transporters (hENTs)...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
E Vicente, Y Quijano, B Ielpo, H Duran
BACKGROUND: Pancreatectomy for locally advanced adenocarcinoma affecting the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) is still under discussion [1]. However, in selected cases, in light of the advancement of recent neoadjuvant treatments, it must be taken into account [2,3]. This video demonstrates some of the technical aspects of SMA and SMV resection as well as some tips of vascular reconstruction. METHODS: A 48-year-old man with a large adenocarcinoma of the uncinated process affecting the SMA and SMV underwent 3 cycles of gemcitabine and nab-paclitaxel neoadjuvancy...
September 2017: Surgical Oncology
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