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https://www.readbyqxmd.com/read/28106283/therapeutic-potential-of-curcumin-in-treatment-of-pancreatic-cancer-current-status-and-future-perspectives
#1
Mina Hosseini, Seyed Mahdi Hassanian, Elham Mohamamdazade, Soodabeh ShahidSales, Mina Maftouh, Hasan Fayazbakhsh, Majid Khazaei, Amir Avan
Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28105157/prognostic-impact-of-the-tumor-infiltrating-regulatory-t-cell-foxp3-activated-cytotoxic-t-lymphocyte-granzyme-b-ratio-on-resected-left-sided-pancreatic-cancer
#2
Ho Kyoung Hwang, Hyoung-Il Kim, Se Hoon Kim, Junjeong Choi, Chang Moo Kang, Kyung Sik Kim, Woo Jung Lee
Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B(+)) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)(+)] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104683/panin-neuroendocrine-cells-promote-tumorigenesis-via-neuronal-crosstalk
#3
Smrita Sinha, Ya-Yuan Fu, Adrien Grimont, Maren Ketcham, Kelly J Lafaro, Joseph A Saglimbeni, Gokce Askan, Jennifer M Bailey, Jerry P Melchor, Yi Zhong, Min Geol Joo, Olivera Grbovic-Huezo, In-Hong Yang, Olca Basturk, Lindsey Baker, Youngkyu Park, Robert C Kurtz, David A Tuveson, Steven D Leach, Pankaj Pasricha
Nerves are a notable feature of the tumor microenvironment in some epithelial tumors, but their role in the malignant progression of pancreatic ductal adenocarcinoma (PDAC) is uncertain. Here we identify dense innervation in the microenvironment of precancerous pancreatic lesions, known as pancreatic intraepithelial neoplasms (PanIN), and describe a unique subpopulation of neuroendocrine PanIN cells that express the neuropeptide substance P (SP) receptor Neurokinin 1-R (NK1-R). Using organoid culture, we demonstrated that sensory neurons promoted the proliferation of PanIN organoids via SP-NK1-R signaling and Stat3 activation...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28104621/high-prevalence-of-mutant-kras-in-circulating-exosome-derived-dna-from-early-stage-pancreatic-cancer-patients
#4
K Allenson, J Castillo, F A San Lucas, G Scelo, D U Kim, V Bernard, G Davis, T Kumar, M Katz, M J Overman, L Foretova, E Fabianova, I Holcatova, V Janout, F Meric-Bernstam, P Gascoyne, I Wistuba, G Varadhachary, P Brennan, S Hanash, D Li, A Maitra, H Alvarez
BACKGROUND: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR (ddPCR) was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13...
January 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28102958/sliding-window-prior-data-assisted-compressed-sensing-for-mri-tracking-of-lung-tumors
#5
Eugene Yip, Jihyun Yun, Keith Wachowicz, Zsolt Gabos, Satyapal Rathee, B G Fallone
PURPOSE: Hybrid magnetic resonance imaging and radiation therapy devices are capable of imaging in real-time to track intrafractional lung tumor motion during radiotherapy. Highly accelerated magnetic resonance (MR) imaging methods can potentially reduce system delay time and/or improves imaging spatial resolution, and provide flexibility in imaging parameters. Prior Data Assisted Compressed Sensing (PDACS) has previously been proposed as an acceleration method that combines the advantages of 2D compressed sensing and the KEYHOLE view-sharing technique...
January 2017: Medical Physics
https://www.readbyqxmd.com/read/28102193/tumour-derived-interleukin-35-promotes-pancreatic-ductal-adenocarcinoma-cell-extravasation-and-metastasis-by-inducing-icam1-expression
#6
Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren, Jihui Hao
Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28099921/stiehopus-japonieus-acidic-mucopolysaccharide-inhibits-the-proliferation-of-pancreatic-cancer-sw1990-cells-through-hippo-yap-pathway
#7
Xiaoyu Li, Yi Liu, Cuiping Zhang, Qinghui Niu, Hui Wang, Cong Che, Man Xie, Bin Zhou, Yonghong Xu, Qi Zhang, Jun Wu, Zibin Tian
Previous studies have indicated that stiehopus japonieus acidic mucopolysaccharide (SJAMP) could inhibit the proliferation of pancreatic cancer cell SW1990. However, the mechanism remains unclear. In our study, YAP expression was identified by immunohistochemistry and quantitative Real-time PCR from 45 pairs of human pancreatic ductal adenocarcinoma (PDAC) tissues and their adjacent non-tumor samples. We found that the YAP expression was associated with the histological differentiation degree, and negatively correlated with pancreatic cancer patients' survival...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099419/genomic-deletion-of-malic-enzyme-2-confers-collateral-lethality-in-pancreatic-cancer
#8
Prasenjit Dey, Joelle Baddour, Florian Muller, Chia Chin Wu, Huamin Wang, Wen-Ting Liao, Zangdao Lan, Alina Chen, Tony Gutschner, Yaan Kang, Jason Fleming, Nikunj Satani, Di Zhao, Abhinav Achreja, Lifeng Yang, Jiyoon Lee, Edward Chang, Giannicola Genovese, Andrea Viale, Haoqiang Ying, Giulio Draetta, Anirban Maitra, Y Alan Wang, Deepak Nagrath, Ronald A DePinho
The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28099362/laparoscopic-pancreaticoduodenectomy-in-a-92-older-chinese-patient-for-cancer-of-head-of-the-pancreas-a-case-report
#9
Jiayu Zhou, Chang Xin, Tao Xia, Yiping Mou, Xiaowu Xu, Renchao Zhang, Yucheng Zhou, Weiwei Jin, Chao Lu
INTRODUCTION: Laparoscopic pancreaticoduodenectomy (LPD) is one of the most complex gastrointestinal procedures performed in laparoscopic abdominal surgery. However, the concern for elderly undergoing LPD remains. To the best of our knowledge, there are no reports describing LPD for A-92-older patient. This study aimed to share the experience of a tertiary pancreatic center and confirm the safety, feasibility of LPD for the elderly. METHOD: The patient had complained of 6-months history of abdominal discomfort and progressive jaundice...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28099253/smoking-status-and-the-incidence-of-pancreatic-cancer-concomitant-with-intraductal-papillary-mucinous-neoplasm
#10
Takashi Nakagawa, Atsuhiro Masuda, Hirochika Toyama, Hideyuki Shiomi, Yoh Zen, Keitaro Sofue, Mamoru Takenaka, Takashi Kobayashi, Yosuke Yagi, Kodai Yamanaka, Masaru Yoshida, Yoshifumi Arisaka, Yoshihiro Okabe, Hiromu Kutsumi, Takumi Fukumoto, Yonson Ku, Takeshi Azuma
OBJECTIVES: The effect of smoking status on the incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) has not been clarified. This study investigated the association of smoking status with PDAC concomitant with IPMN. METHODS: The subjects were 124 consecutive patients undergoing resection of IPMNs (intraductal papillary mucinous adenoma (IPMA): N = 77, invasive IPMN: N = 31, and PDAC with IPMN: N = 16) between April 2008 and October 2015...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28099249/immunohistochemical-antibody-panel-for-the-differential-diagnosis-of-pancreatic-ductal-carcinoma-from-gastrointestinal-contamination-and-benign-pancreatic-duct-epithelium-in-endoscopic-ultrasound-guided-fine-needle-aspiration
#11
Ayako Furuhata, Sachiko Minamiguchi, Hiroyuki Shirahase, Yuzo Kodama, Souichi Adachi, Takaki Sakurai, Hironori Haga
OBJECTIVES: The diagnosis of pancreatic ductal adenocarcinoma (PDAC) by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can be challenging to distinguish tumor cells from benign epithelium (BE). The aim of the present study was to set a minimal antibody panel to differentiate PDAC from contaminated BE in EUS-FNA specimens. METHODS: Immunohistochemistry using claudin 4, EZH2, Ki-67, maspin, p53, and S100P was performed on tissue microarray sections containing 53 PDACs and 33 BE as well as cell blocks of EUS-FNA including 53 PDACs and 22 BE...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28097809/cancer-associated-fibroblasts-promote-m2-polarization-of-macrophages-in-pancreatic-ductal-adenocarcinoma
#12
Aibin Zhang, Yigang Qian, Zhou Ye, Haiyong Chen, Haiyang Xie, Lin Zhou, Yan Shen, Shusen Zheng
Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia with infiltration of distinct cellular components. Cancer-associated fibroblasts (CAFs) has been shown to be among the most prominent cells and played a significant role in shaping the tumor microenvironment by interacting with other type of cells. Here, we aimed to investigate the effect of CAFs in modulating phenotype of tumor-associated macrophages (TAM). Under treatment of CAFs conditioned medium (CM) or direct co-culture with CAFs, monocytes exhibited enhanced expression of CD206 and CD163 compared with control group (P < 0...
January 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28096419/stromal-cues-regulate-the-pancreatic-cancer-epigenome-and-metabolome
#13
Mara H Sherman, Ruth T Yu, Tiffany W Tseng, Cristovao M Sousa, Sihao Liu, Morgan L Truitt, Nanhai He, Ning Ding, Christopher Liddle, Annette R Atkins, Mathias Leblanc, Eric A Collisson, John M Asara, Alec C Kimmelman, Michael Downes, Ronald M Evans
A fibroinflammatory stromal reaction cooperates with oncogenic signaling to influence pancreatic ductal adenocarcinoma (PDAC) initiation, progression, and therapeutic outcome, yet the mechanistic underpinning of this crosstalk remains poorly understood. Here we show that stromal cues elicit an adaptive response in the cancer cell including the rapid mobilization of a transcriptional network implicated in accelerated growth, along with anabolic changes of an altered metabolome. The close overlap of stroma-induced changes in vitro with those previously shown to be regulated by oncogenic Kras in vivo suggests that oncogenic Kras signaling-a hallmark and key driver of PDAC-is contingent on stromal inputs...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093284/pancreatic-cancer-stroma-and-its-current-and-emerging-targeted-therapies
#14
Janaiah Kota, Julie Hancock, Jason Kwon, Murray Korc
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal human malignancies with a 5-year survival rate of 8%. Dense, fibrotic stroma associated with pancreatic tumors is a major obstacle for drug delivery to the tumor bed and plays a crucial role in pancreatic cancer progression. Targeting stroma is considered as a potential therapeutic strategy to improve anti-cancer drug efficacy and patient survival. Although numerous stromal depletion therapies have reached the clinic, they add little to overall survival and are often associated with toxicity...
January 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28093281/kindlin-2-in-pancreatic-stellate-cells-promotes-the-progression-of-pancreatic-cancer
#15
Naoki Yoshida, Atsushi Masamune, Shin Hamada, Kazuhiro Kikuta, Tetsuya Takikawa, Fuyuhiko Motoi, Michiaki Unno, Tooru Shimosegawa
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined...
January 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28092686/epigenomic-reprogramming-during-pancreatic-cancer-progression-links-anabolic-glucose-metabolism-to-distant-metastasis
#16
Oliver G McDonald, Xin Li, Tyler Saunders, Rakel Tryggvadottir, Samantha J Mentch, Marc O Warmoes, Anna E Word, Alessandro Carrer, Tal H Salz, Sonoko Natsume, Kimberly M Stauffer, Alvin Makohon-Moore, Yi Zhong, Hao Wu, Kathryn E Wellen, Jason W Locasale, Christine A Iacobuzio-Donahue, Andrew P Feinberg
During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28092668/upregulation-of-ret-induces-perineurial-invasion-of-pancreatic-adenocarcinoma
#17
M Amit, S Na'ara, L Leider-Trejo, Y Binenbaum, N Kulish, E Fridman, A Shabtai-Orbach, R J Wong, Z Gil
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092495/nonhypervascular-pancreatic-neuroendocrine-tumors-differential-diagnosis-from-pancreatic-ductal-adenocarcinomas-at-mr-imaging-retrospective-cross-sectional-study
#18
Sun Kyung Jeon, Jeong Min Lee, Ijin Joo, Eun Sun Lee, Hyun Jeong Park, Jin-Young Jang, Ji Kon Ryu, Kyung Bun Lee, Joon Koo Han
Purpose To determine useful magnetic resonance (MR) imaging features to differentiate nonhypervascular pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs). Materials and Methods The institutional review board approved this retrospective study and waived the informed consent requirement. Seventy-four patients with surgically confirmed PNETs and 82 patients with PDACs who underwent gadobutrol-enhanced MR imaging were included. Two radiologists independently evaluated the morphologic characteristics and temporal enhancement patterns of each tumor...
January 13, 2017: Radiology
https://www.readbyqxmd.com/read/28089341/neoadjuvant-external-beam-radiation-is-associated-with-no-benefit-in-overall-survival-for-early-stage-pancreatic-cancer
#19
Waseem Lutfi, Mark S Talamonti, Olga Kantor, Chi-Hsiung Wang, Susan J Stocker, David J Bentrem, Kevin K Roggin, David J Winchester, Robert Marsh, Richard A Prinz, Marshall S Baker
OBJECTIVE: Neoadjuvant protocols for early stage pancreatic adenocarcinoma (PDAC) frequently involve external beam radiation used in combination with systemic chemotherapy. The benefit of radiation in these protocols has not been determined. METHODS: We examined patients with stage I and II PDAC within the National Cancer Data Base between 2006 and 2012. Propensity score matching was used to compare patients receiving neoadjuvant chemotherapy including radiation (NCRT) to those receiving neoadjuvant chemotherapy without radiation (NCT) prior to pancreaticoduodenectomy...
November 30, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/28089234/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#20
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
December 24, 2016: EBioMedicine
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