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https://www.readbyqxmd.com/read/29053970/mtorc1-activator-slc38a9-is-required-to-efflux-essential-amino-acids-from-lysosomes-and-use-protein-as-a-nutrient
#1
Gregory A Wyant, Monther Abu-Remaileh, Rachel L Wolfson, Walter W Chen, Elizaveta Freinkman, Laura V Danai, Matthew G Vander Heiden, David M Sabatini
The mTORC1 kinase is a master growth regulator that senses many environmental cues, including amino acids. Activation of mTORC1 by arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. Here, we validate that SLC38A9 is an arginine sensor for the mTORC1 pathway, and we uncover an unexpectedly central role for SLC38A9 in amino acid homeostasis. SLC38A9 mediates the transport, in an arginine-regulated fashion, of many essential amino acids out of lysosomes, including leucine, which mTORC1 senses through the cytosolic Sestrin proteins...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053565/a-synthetic-analogue-of-neopeltolide-8-9-dehydroneopeltolide-is-a-potent-anti-austerity-agent-against-starved-tumor-cells
#2
Haruhiko Fuwa, Mizuho Sato
Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium...
October 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29053398/the-involvement-of-lncrnas-in-the-development-and-progression-of-pancreatic-cancer
#3
Li Duguang, He Jin, Qian Xiaowei, Xu Peng, Wang Xiaodong, Li Zhennan, Qian Jianjun, Yao Jie
Pancreatic cancer is one of the most malignant tumors that are difficult to diagnose at its early stage and there is no effective therapy. Recent studies uncovered that many non-protein-coding RNAs including the class of long noncoding RNAs (lncRNAs) are differentially expressed in various types of tumors and they are potent regulators of tumor progression and metastasis. LncRNA can mediate tumor initiation, proliferation, migration and metastasis through modulating epigenetic modification, alternative splicing, transcription, and protein translation...
October 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29053185/expression-of-the-dna-repair-gene-mlh1-correlates-with-survival-in-patients-who-have-resected-pancreatic-cancer-and-have-received-adjuvant-chemoradiation-nrg-oncology-rtog-study-9704
#4
Yaacov R Lawrence, Jennifer Moughan, Anthony M Magliocco, Alexander C Klimowicz, William F Regine, Rex B Mowat, Thomas A DiPetrillo, William Small, Jeffry P Simko, Talia Golan, Kathryn A Winter, Chandan Guha, Christopher H Crane, Adam P Dicker
BACKGROUND: The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. METHODS: Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials...
October 20, 2017: Cancer
https://www.readbyqxmd.com/read/29052535/large-cell-neuroendocrine-carcinoma-of-the-kidney-with-cardiac-metastasis-a-case-report
#5
Moeka Shimbori, Kimito Osaka, Takashi Kawahara, Ryo Kasahara, Sayuki Kawabata, Kazuhide Makiyama, Keiichi Kondo, Noboru Nakaigawa, Shoji Yamanaka, Masahiro Yao
BACKGROUND: Primary large cell neuroendocrine carcinoma of the kidney is a rare and generally very aggressive disease. We present a case of a patient with primary large cell neuroendocrine carcinoma of the kidney with cardiac metastasis. CASE PRESENTATION: A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart...
October 20, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29052509/a-yin-yang-1-mir-30a-regulatory-circuit-modulates-autophagy-in-pancreatic-cancer-cells
#6
Chuang Yang, Jing-Jing Zhang, Yun-Peng Peng, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Wen-Tao Gao, Kui-Rong Jiang, Yi Miao
BACKGROUND: Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. METHODS: The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting...
October 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29051402/t-tube-biliary-drainage-during-reconstruction-after-pancreaticoduodenectomy-a-single-center-experience
#7
Pasquale Cianci, Gloria Giaracuni, Nicola Tartaglia, Alberto Fersini, Antonio Ambrosi, Vincenzo Neri
AIM: The purpose of this study is to communicate our experience about the results and effectiveness in the use of the Ttube biliary drainage during pancreaticoduodenectomy. MATERIAL OF STUDY: In accordance whit Whipple we perform the gastric antrum resection during pancreaticoduodenectomy. We have treated 42 patients with pancreaticoduodenectomy, 25 males and 17 females with a mean age of 62 years (range: 53-79 years), and in each of them we have placed a biliary T-tube...
2017: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/29051395/role-of-computer-tomography-and-endoscopic-ultrasonography-in-assessing-portal-and-superior-mesenteric-vessels-invasion-in-cephalo-pancreatic-adenocarcinoma
#8
Raluca Bodea, Andrada Seicean, Tudor Vasile, Tudor Calinici, Irina Ciuca, Nadim Al Hajjar, Cornel Iancu, Constantin Iordache
AIM: The aim of this study is to evaluate the information given by contrast-enhanced computer tomography (CECT) and ultrasound endoscopy (EUS) regarding vascular involvement of cephalo-pancreatic cancer, data compared with intraoperative findings. MATERIAL AND METHODS: We choose to analyze the most often interested vessels by tumor development, such as superior mesenteric artery (SMA), superior mesenteric vein (SMV) and portal vein (PV). The patients included in the study (n=425) had a cephalo-pancreatic tumor diagnosed in our Institute and a positive histology for pancreatic adenocarcinoma...
2017: Annali Italiani di Chirurgia
https://www.readbyqxmd.com/read/29051346/data-driven-prioritization-and-review-of-targets-for-molecular-based-theranostic-approaches-in-pancreatic-cancer
#9
Marjory Koller, Elmire Hartmans, Derk Jan A de Groot, Xiao Juan Zhao, Gooitzen Michell van Dam, Wouter Nagengast, Rudolf S N Fehrmann
Molecular targeted therapeutical and imaging strategies directed at aberrant signaling-pathways in pancreatic tumor cells may improve the poor outcome of pancreatic ductal adenocarcinoma (PDA). Therefore, relevant molecular targets need to be identified. Methods: We collected publicly available expression profiles of patient derived normal pancreatic tissue (n = 77) and PDA samples (n = 103). Functional Genomic mRNA (FGmRNA) profiling was applied to predict target upregulation on the protein level. We prioritized these targets based on current status of (pre)-clinical therapeutical and imaging evaluation in PDA...
October 19, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29051322/a-multicenter-phase-i-study-evaluating-dual-pi3k-and-braf-inhibition-with-px-866-and-vemurafenib-in-patients-with-advanced-braf-v600-mutant-solid-tumors
#10
Clinton Yam, Xiaowei Xu, Michael A Davies, Phyllis A Gimotty, Jennifer Jd Morrissette, Michael T Tetzlaff, Khalida Wani, Shujing Liu, Wanleng Deng, Meghan Buckley, Jianhua Zhao, Ravi K Amaravadi, Naomi Haas, Ragini R Kudchadkar, Anna Pavlick, Jeffrey A Sosman, Hussein Tawbi, Luke Walker, Lynn M Schuchter, Giorgos C Karakousis, Tara C Gangadhar
PURPOSE: The objectives of the study were to evaluate the safety of daily oral PX-866 in combination with twice daily vemurafenib and to identify potential predictive biomarkers for this novel combination. EXPERIMENTAL DESIGN: We conducted a phase I, open-label, dose escalation study in patients with advanced BRAF V600 mutant solid tumors. PX-866 was administered on a continuous schedule in combination with vemurafenib. Patients underwent a baseline and on-treatment biopsy after 1-week of PX-866 monotherapy for biomarker assessment...
October 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29051320/combinatorial-treatment-with-mtor-inhibitors-and-streptozotocin-leads-to-synergistic-in-vitro-and-in-vivo-antitumor-effects-in-insulinoma-cells
#11
Julien Bollard, Céline Patte, Patrick Massoma, Isabelle Goddard, Nicolas Gadot, Noura Benslama, Valérie Hervieu, Carole Ferraro-Peyret, Martine Cordier-Bussat, Jean-Yves Scoazec, Colette Roche, Thomas Walter, Cécile Vercherat
Streptozotocin (STZ)-based chemotherapy is the first-line chemotherapy recommended for advanced pancreatic neuroendocrine tumors (pNETs), while targeted therapies, including mTOR inhibitors, are available in second-line treatment. Unfortunately objective response rates to both treatments are limited. Since mTOR pathway activation, commonly observed in pNETs, has been reported as one of the major mechanisms accounting for chemoresistance, we investigated the potential benefit of mTOR inhibition combined with STZ treatment in a subset of pNETs, namely insulinomas...
October 19, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29050294/the-density-of-mast-cells-c-kit-and-tryptase-correlates-with-each-other-and-with-angiogenesis-in-pancreatic-cancer-patients
#12
Michele Ammendola, Cosmo Damiano Gadaleta, Adam Enver Frampton, Tullio Piardi, Riccardo Memeo, Valeria Zuccalà, Maria Luposella, Rosa Patruno, Nicola Zizzo, Pietro Gadaleta, Patrick Pessaux, Rosario Sacco, Giuseppe Sammarco, Girolamo Ranieri
Literature data suggest that inflammatory cells such as mast cells (MCs) are involved in angiogenesis. MCs can stimulate angiogenesis by releasing of well identified pro-angiogenic cytokines stored in their cytoplasm. In particular, MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor. Nevertheless, few data are available concerning the role of MCs positive to tryptase in primary pancreatic cancer angiogenesis. This study analyzed the correlation between mast cells positive to c-Kit receptor (c-Kit(+) MCs), the density of MCs expressing tryptase (MCD-T) and microvascular density (MVD) in primary tumor tissue from patients affected by pancreatic ductal adenocarcinoma (PDAC)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050177/-application-of-three-dimensional-visualization-in-pancreatic-tumor-a-pilot-study
#13
S Z Wang, X B Wang, M Li, R X Shen, H Rong, J S Li
Objective: To study the value of three-dimensional(3D) visualization in the diagnosis and surgical treatment for pancreatic tumor. Methods: From June to September 2016, 26 patients with pancreatic tumors in Jinling Hospital, Medical School of Nanjing University were involved. The study included 26 patients(8 females and 18 males) with mean age of (57±12)years (ranging from 23 to 77 years). And there were 20 malignant tumors and 6 benign tumors. All of them were examined with abdominal thin slice CT scanning and the CT images were imported into 3D visualization system for 3D visualization...
October 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29050176/-analysis-of-diagnosis-therapy-and-prognosis-factors-of-103-patients-with-pancreatic-neuroendocrine-tumors
#14
Q Luo, Y N Liu, H Y Ma, S Li, J Y Huang, G Li, G Jin
Objective: To discuss the clinical pathology characteristics, strategies of diagnosis and therapy, and related prognosis factors of pancreatic neuroendocrine tumors(pNET). Methods: Clinical data of 103 pNET cases in Department of Pancreatic Surgery, Changhai Hospital of Second Military Medical University were collected from January 2006 to December 2015. There were 44 males and 59 females, aged from 21 to 77 years with mean age of 48 years.Of the 103 patients, there were functional type in 21 cases and no functional type in 82 cases...
October 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29049340/pressurized-intra-peritoneal-aerosol-chemotherapy-in-patients-suffering-from-peritoneal-carcinomatosis-of-pancreatic-adenocarcinoma
#15
Tanja Khosrawipour, Veria Khosrawipour, Urs Giger-Pabst
BACKGROUND: Patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma were treated with Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC), initial clinical findings are presented. METHODS: Single institution, tertiary referral center certified for therapy of peritoneal disease. Prospective data collection of PIPAC therapy with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2 of body surface delivered at intervals of six weeks. The outcome criteria were microscopic pathological response, survival and adverse events (v4...
2017: PloS One
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#16
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048622/enhancement-of-cytotoxic-effects-of-gemcitabine-by-dclk1-inhibition-through-suppression-of-chk1-phosphorylation-in-human-pancreatic-cancer-cells
#17
Daichi Kawamura, Yoshihiro Takemoto, Arata Nishimoto, Koji Ueno, Tohru Hosoyama, Bungo Shirasawa, Toshiki Tanaka, Naruji Kugimiya, Eijiro Harada, Kimikazu Hamano
Although gemcitabine (GEM) is frequently used in the treatment of pancreatic cancer, the effects are limited. To increase the inhibitory effect of GEM, the identification of a molecular target is needed. Recent studies have revealed that doublecortin-like kinase 1 (Dclk1) positively regulates tumor growth, invasion, metastasis, factors related to epithelial-mesenchymal transition (EMT), pluripotency, angiogenesis, and anti-apoptosis in pancreatic cancer cells. Therefore, Dclk1 is a potential therapeutic target for pancreatic cancer...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048549/curcumin-sensitizes-pancreatic-cancer-cells-to-gemcitabine-by-attenuating-prc2-subunit-ezh2-and-the-lncrna-pvt1-expression
#18
Kazuhiro Yoshida, Shusuke Toden, Preethi Ravindranathan, Haiyong Han, Ajay Goel
Development of resistance to chemotherapeutic drugs is a major challenge in the care of patients with pancreatic ductal adenocarcinoma (PDAC). Acquired resistance to chemotherapeutic agents in PDAC has been linked to a subset of cancer cells termed 'cancer stem cells' (CSCs). Therefore, an improved understanding of the molecular events underlying the development of pancreatic CSCs is required to identify new therapeutic targets to overcome chemoresistance. Accumulating evidence indicates that curcumin, a phenolic compound extracted from turmeric, can overcome de novo chemoresistance and re-sensitize tumors to various chemotherapeutic agents...
October 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29047068/intraductal-papillary-mucinous-neoplasm-of-the-pancreas-in-young-patients-tumor-biology-clinical-features-and-survival-outcomes
#19
Vicente Morales-Oyarvide, Mari Mino-Kenudson, Cristina R Ferrone, Andrew L Warshaw, Keith D Lillemoe, Dushyant V Sahani, Ilaria Pergolini, Marc A Attiyeh, Mohammad Al Efishat, Neda Rezaee, Ralph H Hruban, Jin He, Matthew J Weiss, Peter J Allen, Christopher L Wolfgang, Carlos Fernández-Del Castillo
AIM: The aim of this paper is to describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in young patients. METHODS: We evaluated 1693 patients from the Pancreatic Surgery Consortium who underwent resection for IPMN and classified them as younger or older than 50 years of age at the time of surgery. We assessed the relationship of age with clinical, radiological, pathological, and prognostic features. RESULTS: We identified 90 (5%) young patients...
October 18, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/29045811/top2a-induces-malignant-character-of-pancreatic-cancer-through-activating-%C3%AE-catenin-signaling-pathway
#20
Yao-Fei Pei, Xi-Min Yin, Xi-Qiang Liu
It has been reported that Topoisomerase II alpha (TOP2A) could induce tumor development and progression in many cancer types. Herein, through analysis of different independent cohorts, we found TOP2A was up-regulated in pancreatic cancer as compared with non-tumor tissues. Moreover, the up-regulation of TOP2A was significantly correlated with tumor metastasis and shorter survival in patients with pancreatic cancer. Knockdown of TOP2A in pancreatic cancer cell lines inhibited cell proliferation and migration...
October 15, 2017: Biochimica et Biophysica Acta
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