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International Journal of Cancer. Journal International du Cancer

Cristina Corbetta, Natalia Di Ianni, Maria Grazia Bruzzone, Monica Patanè, Bianca Pollo, Gabriele Cantini, Manuela Cominelli, Ileana Zucca, Federica Pisati, Pietro Luigi Poliani, Gaetano Finocchiaro, Serena Pellegatta
In glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate-aspartate transporter expressed by astrocytes with a role in glutamate uptake, is highly expressed on the plasma membrane of glioblastoma (GBM) cells, and its expression significantly correlates with shortened patient survival. Here, it was demonstrated that inhibition of GLAST expression limited the progression and invasion of GBM xenografts. Magnetic resonance spectroscopy was used to measure glutamate in GLAST-expressing gliomas showing that these tumors exhibit increased glutamate concentration compared to GLAST-depleted glioma...
November 12, 2018: International Journal of Cancer. Journal International du Cancer
Gang Wang, Qian Wang, Qichao Huang, Yibing Chen, Xiacheng Sun, Linjie He, Lei Zhan, Xu Guo, Chun Yin, Yujiang Fang, Xianli He, Jinliang Xing
It is now widely accepted that mitochondrial biogenesis is inhibited in most cancer cells. Interestingly, one of the possible exceptions is col orectal cancer (CRC), in which the content of mitochondria has been found to be higher than in normal colon mucosa. However, to date, the causes and effects of this phenomenon are still unclear. In the present study, we systematically investigated the functional role of mitochondrial single-strand DNA binding protein (mtSSB), a key molecule in the regulation of mitochondrial DNA (mtDNA) replication, in the mitochondrial biogenesis and CRC cell growth...
November 10, 2018: International Journal of Cancer. Journal International du Cancer
Thomas P Potjer, Sander Bollen, Anneliese J E M Grimbergen, Remco van Doorn, Nelleke A Gruis, Christi J van Asperen, Frederik J Hes, Nienke van der Stoep
Germline mutations in the major melanoma susceptibility gene CDKN2A explain genetic predisposition in only 10-40% of melanoma-prone families. In this study we comprehensively characterized 488 melanoma cases from 451 non-CDKN2A/CDK4 families for mutations in 30 established and candidate melanoma susceptibility genes using a custom-designed targeted gene panel approach. We identified (likely) pathogenic variants in established melanoma susceptibility genes in 18 families (n=3 BAP1, n=15 MITF p.E318K; diagnostic yield 4...
November 10, 2018: International Journal of Cancer. Journal International du Cancer
Maria Laura Falchetti, Quintino Giorgio D'Alessandris, Simone Pacioni, Mariachiara Buccarelli, Liliana Morgante, Stefano Giannetti, Valentina Lulli, Maurizio Martini, Luigi Maria Larocca, Eliza Vakana, Louis Stancato, Lucia Ricci-Vitiani, Roberto Pallini
Bevacizumab, a VEGF-targeting monoclonal antibody, may trigger an infiltrative growth pattern in glioblastoma. We investigated this pattern using both a human specimen and rat models. In the human specimen, a substantial fraction of infiltrating tumor cells were located along perivascular spaces in close relationship with endothelial cells. Brain xenografts of U87MG cells treated with bevacizumab were smaller than controls (p=0.0055; Student-t test), however, bands of tumor cells spread through the brain farther than controls (p<0...
November 10, 2018: International Journal of Cancer. Journal International du Cancer
Rie Kinoshita, Hiroki Sato, Akira Yamauchi, Yuta Takahashi, Yusuke Inoue, I Wayan Sumardika, Youyi Chen, Nahoko Tomonobu, Kota Araki, Kazuhiko Shien, Shuta Tomida, Hidejiro Torigoe, Kei Namba, Eisuke Kurihara, Yusuke Ogoshi, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Endy Widya Putranto, I Made Winarsa Ruma, Hiromasa Yamamoto, Junichi Soh, Toshihiko Hibino, Masahiro Nishibori, Eisaku Kondo, Shinichi Toyooka, Masakiyo Sakaguchi
The metastatic dissemination of cancer cells to remote areas of the body is the most problematic aspect in cancer patients. Among cancers, melanomas are notoriously difficult to treat due to their significantly high metastatic potential even during early stages. Hence, the establishment of advanced therapeutic approaches to regulate metastasis is required to overcome the melanoma disease. An accumulating mass of evidence has indicated a critical role of extracellular S100A8/A9 in melanoma distant metastasis...
November 10, 2018: International Journal of Cancer. Journal International du Cancer
Xinhui Fu, Yan Huang, Xinjuan Fan, Yanhong Deng, Huanliang Liu, Hongzhi Zou, Peihuang Wu, Zhiting Chen, Jinglin Huang, Jingxuan Wang, Hanjie Lin, Shuhui Huang, Xiaoli Tan, Ping Lan, Lei Wang, Jian-Ping Wang
The incidence of colorectal cancer (CRC) is increasing in China. Here, we aimed to evaluate the latest demographic trends and KRAS/BRAF mutations status of Chinese CRC. 5546 CRC patients diagnosed from 2010 to 2017 were involved. KRAS exon 2 and BRAFV600E mutations were detected by Sanger sequencing and high-resolution melting analysis or allelic-specific probe method. Gene mutation profiles and clinicopathologic characteristics of 5495 patients were analyzed. The joinpoint regression model was used to predict the demographic data in 2018...
November 10, 2018: International Journal of Cancer. Journal International du Cancer
Tao Cheng, Zhiheng Zhang, Ziying Jian, Susanne Raulefs, Anna Melissa Schlitter, Katja Steiger, Nadja Maeritz, Yamin Zhao, Shanshan Shen, Xiaoping Zou, Güralp O Ceyhan, Helmut Friess, Jörg Kleeff, Christoph W Michalski, Bo Kong
Pancreatitis is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). Previous studies in mice have demonstrated that pancreatitis contributes to oncogenic Kras-driven carcinogenesis, probably initiated in acinar cells; however, oncogenic Kras alone or in combination with caerulein-induced pancreatitis is not sufficient in initiating PDAC from the ductal compartment. We thus introduced ductal obstruction - which induces a more severe form of pancreatitis - by pancreatic ductal ligation in mice harbouring oncogenic Kras...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Yuanyuan Sheng, Jinwang Wei, Yu Zhang, Xiaomei Gao, Zheng Wang, Jing Yang, Shican Yan, Ying Zhu, Ze Zhang, Da Xu, Chaoqun Wang, Yan Zheng, Qiongzhu Dong, Lunxiu Qin
Exploring the genetic aberrations favoring metastasis is important for understanding and developing novel strategies to combat cancer metastasis. It is still lack of effective treatment for the dismal prognosis of intrahepatic cholangiocarcinoma (ICC). Here, we aimed to study genetic alternations during lymph node metastasis of ICC and investigate potential mechanisms and clinical strategy focused on mutations. We performed whole-exome sequencing and transcriptome sequencing on samples from 30 ICC patients, including lymph node metastases from five of the patients...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Darrel A Cook, Mel Krajden, Adam R Brentnall, Lovedeep Gondara, Tracy Chan, Jennifer H Law, Laurie W Smith, Dirk J van Niekerk, Gina S Ogilvie, Andrew J Coldman, Rhian Warman, Caroline Reuter, Jack Cuzick, Attila T Lorincz
Human papillomavirus (HPV)-based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case-control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25-65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from 257 women with known HPV/cytology results and pathology outcomes...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Haiyang Zhang, Lei Zhu, Ming Bai, Ying Liu, Yang Zhan, Ting Deng, Haiou Yang, Wu Sun, Xinyi Wang, Kegan Zhu, Qian Fan, Jialu Li, Guoguang Ying, Yi Ba
Cancer-related cachexia is a metabolic syndrome characterized by a wasting disorder of adipose and skeletal muscle and is accompanied by body weight loss and systemic inflammation. The treatment options for cancer cachexia are limited, and the molecular mechanism remains poorly understood. Circular RNAs (circRNAs) are a novel family of endogenous noncoding RNAs that have been proposed to regulate gene expression in mammals. Exosomes are small vesicles derived from cells, and recent studies have shown that circRNAs are stable in exosomes...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Sandra D Isidean, Yishu Wang, Marie-Hélène Mayrand, Sam Ratnam, François Coutlée, Eduardo L Franco, Michal Abrahamowicz
Accurate assessment of risks for developing cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) following a given set of screening test results is instrumental to reaching valid conclusions and informing cervical cancer screening recommendations. Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we assessed prognostic values of enrollment screening test results to predict CIN2+ among women attending routine cervical screening using multivariable Cox proportional hazards (PH) regression and its flexible extension during each of two follow-up periods (protocol-defined and extended)...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Efrat L Amitay, Katarina Cuk, Tobias Niedermaier, Korbinian Weigl, Hermann Brenner
In recent years fecal immunochemical tests (FITs) have been offered as a primary screening test for colorectal cancer (CRC) in a growing number of countries. This study aims to identify factors associated with apparently false positive results of FITs. In this cross-sectional study within the German population-based screening colonoscopy program, participants were invited to provide a stool sample for FIT prior to colonoscopy. 4656 participants aged 50-79 years with no known history of CRC or inflammatory bowel disease (IBD) and no findings of neoplasms at screening colonoscopy were included in the current analyses...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Vincent Chin-Hung Chen, Hsiang-Lin Chan, Tsai-Ching Hsu, Mong-Liang Lu, Yi-Chen Lee, Yena Lee, Jing Yi Siow, Roger S McIntyre, Aileen J Zhou, Bor-Show Tzang, Charles Tzu-Chi Lee
It has been encouraged to use large existing data like insurance claims data to investigate the new indications of old drugs. New strategies of research are warranted to identify feasible drugs. We conducted a dual research model with a population-based case-control study using Taiwan's National Health Insurance Research Database and an in-vitro study to investigate the association between atypical antipsychotic and Hepatocellular carcinoma (HCC) risk. The study herein consists of two components. The first is a population-based case-control study using existing data from the Taiwan National Health Insurance Research Database...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Chen Yuan, Irene M Shui, Kathryn M Wilson, Meir J Stampfer, Lorelei A Mucci, Edward L Giovannucci
We previously found that higher total 25-hydroxyvitamin D [25(OH)D] levels were associated with lower risk of lethal prostate cancer. However, the relationships of bioavailable 25(OH)D and vitamin D binding protein (VDBP) with risk of advanced and lethal prostate cancer are unclear. In a prospective case-control study of 156 pairs of advanced prostate cancer cases and controls, we directly measured prediagnostic circulating 25(OH)D and VDBP and calculated bioavailable 25(OH)D using a validated formula. We examined the association of bioavailable 25(OH)D and VDBP levels with risk of advanced and lethal prostate cancer and whether total 25(OH)D levels interacted with VDBP levels to affect the risk...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Karama Asleh, Stina Lyck Carstensen, Charlotte L Tykjaer Jørgensen, Samantha Burugu, Dongxia Gao, Jennifer R Won, Maj-Britt Jensen, Eva Balslev, Anne-Vibeke Laenkholm, Dorte L Nielsen, Bent Ejlertsen, Torsten O Nielsen
In a formal prospective-retrospective analysis of the phase III SBG0102 clinical trial randomizing metastatic breast cancer patients to gemcitabine-docetaxel or to single agent docetaxel, patients with basal-like tumors by PAM50 gene expression had significantly better overall survival in the gemcitabine arm. By immunohistochemistry (IHC), triple negative status was not predictive, but more specific biomarkers have since become available defining basal-like by nestin positivity or loss of inositol-polyphosphate-4-phosphate (INPP4B)...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Nora Sahnane, Giorgia Ottini, Mario Turri-Zanoni, Daniela Furlan, Paolo Battaglia, Apostolos Karligkiotis, Chiara Albeni, Roberta Cerutti, Eleonora Mura, Anna Maria Chiaravalli, Paolo Castelnuovo, Fausto Sessa, Carla Facco
Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In this study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for ten genes involved in EGFR signalling. . HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Mitsukuni Suenaga, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Satoshi Okazaki, Martin D Berger, Yuji Miyamoto, Marta Schirripa, Shivani Soni, Afsaneh Barzi, Toshiharu Yamaguchi, Heinz-Josef Lenz
Early VEGF-A reduction (EVR) by targeting abundant VEGF-A is a potential predictive marker of bevacizumab (BEV). The CCL5/CCR5 axis modulates VEGF-A production via endothelial progenitor cells migration. We tested whether genetic polymorphisms in the CCL5/CCR5 pathway could predict efficacy of BEV in patients with metastatic colorectal cancer (mCRC) in a first-line setting. Genomic DNA was extracted from 215 samples from three independent cohorts: 61 patients receiving FOLFOX+BEV (evaluation cohort); 83 patients receiving FOLFOX (control cohort); 71 patients receiving FOLFOX/XELOX+BEV (exploratory cohort) for validation and serum biochemistry assay (n=48)...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Octavia Ramayanti, Sandra A W M Verkuijlen, Putri Novianti, Chantal Scheepbouwer, Branislav Misovic, Danijela Koppers-Lalic, Jan van de Weering, Lisa Beckers, Marlinda Adham, Debora Martorelli, Jaap M Middeldorp, D Michiel Pegtel
Cell-free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle-bound form, represent promising minimally-invasive cancer biomarkers. However, a highly abundant non-tumor background in human plasma and serum complicates the discovery and detection of tumor-selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus-encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC...
November 9, 2018: International Journal of Cancer. Journal International du Cancer
Pamela Minicozzi, Liesbet Van Eycken, Florence Molinie, Kaire Innos, Marcela Guevara, Rafael Marcos-Gragera, Clara Castro, Elisabetta Rapiti, Alexander Katalinic, Ana Torrella, Tina Žagar, Magdalena Bielska-Lasota, Paolo Giorgi Rossi, Nerea Larrañaga, Joana Bastos, Maria José Sánchez, Milena Sant
Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7,581 stage I/IIA cases diagnosed in 9 European countries in 2009-13, and 4 STs: surgery; breast-conserving surgery plus radiotherapy (BCS+RT); reconstruction after mastectomy; and prompt treatment (≤6 weeks after diagnosis)...
November 8, 2018: International Journal of Cancer. Journal International du Cancer
Mei-Chun Cai, Minjiang Chen, Pengfei Ma, Jie Wu, Haijiao Lu, Shengzhe Zhang, Jin Liu, Xiaojing Zhao, Guanglei Zhuang, Zhuang Yu, Yujie Fu
Somatic KEAP1-NRF2 pathway alterations are frequently detected in both lung adenocarcinomas and squamous cell carcinomas. However, the biological characteristics and molecular subtypes of KEAP1/NRF2-mutant lung cancer remain largely undefined. Here, we performed a stepwise, integrative analytic and experimental interrogation of primary tumors and cancer cell lines harboring KEAP1 or NFE2L2 (encoding NRF2) gene mutations. First, we discovered that KEAP1/NRF2-mutant lung cancer presented APOBEC-mediated mutational signatures, impaired tumor angiogenesis, elevated hypoxic stress and deficient immune-cell infiltrates...
November 8, 2018: International Journal of Cancer. Journal International du Cancer
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