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https://www.readbyqxmd.com/read/29156849/interest-of-integrins-targeting-in-glioblastoma-according-to-tumor-heterogeneity-and-cancer-stem-cell-paradigm-an-update
#1
REVIEW
Laure Malric, Sylvie Monferran, Julia Gilhodes, Sabrina Boyrie, Perrine Dahan, Nicolas Skuli, Julie Sesen, Thomas Filleron, Aline Kowalski-Chauvel, Elizabeth Cohen-Jonathan Moyal, Christine Toulas, Anthony Lemarié
Glioblastomas are malignant brain tumors with dismal prognosis despite standard treatment with surgery and radio/chemotherapy. These tumors are defined by an important cellular heterogeneity and notably contain a particular subpopulation of Glioblastoma-initiating cells, which recapitulate the heterogeneity of the original Glioblastoma. In order to classify these heterogeneous tumors, genomic profiling has also been undertaken to classify these heterogeneous tumors into several subtypes. Current research focuses on developing therapies, which could take into account this cellular and genomic heterogeneity...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156842/associations-between-egfr-gene-polymorphisms-and-susceptibility-to-glioma-a-systematic-review-and-meta-analysis-from-gwas-and-case-control-studies
#2
Xiao Yu, Nian Rong Sun, Hai Tao Jang, Shi Wen Guo, Min Xue Lian
The results of genome-wide association studies (GWAS) and case-control studies performed to investigate the associations between epidermal growth factor receptor (EGFR) gene polymorphisms and glioma risk are controversial. The aim of this systematic review and meta-analysis is to determine whether EGFR gene polymorphisms are associated with glioma risk by searching 'PubMed', 'EMBASE', 'Web of Science', 'Cochrane Library' and 'China WeiPu Library' to retrieve studies that investigated associations between EGFR gene polymorphisms and glioma risk...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156836/the-role-of-rak-in-the-regulation-of-stability-and-function-of-brca1
#3
Jung-Lye Kim, Geun-Hyoung Ha, Loredana Campo, Mitchell F Denning, Tarun B Patel, Clodia Osipo, Shiaw-Yih Lin, Eun-Kyoung Breuer
BRCA1 is an important player in the DNA damage response signaling, and its deficiency results in genomic instability. A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting the existence of other regulatory mechanisms controlling BRCA1 protein expression. Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156829/mdm4-genetic-variants-predict-hpv16-positive-tumors-of-patients-with-squamous-cell-carcinoma-of-the-oropharynx
#4
Zhongming Lu, Hua Zhang, Ye Tao, Xiangping Li, Guojun Li
The increasing incidence of squamous cell carcinoma of the oropharynx (SCCOP) is majorly attributed to the human papillomavirus (HPV) infection. Both HPV and MDM4 play a critical role in inhibition of p53 activity, thus affecting HPV tumor status of SCCOP. Three polymorphisms in MDM4 were genotyped from blood genomic DNA samples and HPV16 status in tumor specimens was examined. Odds ratio (OR) and 95% confidence intervals (CIs) in univariate and multivariable logistic regression models were calculated for the associations between these polymorphisms and HPV16 status...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156814/screening-circular-rna-expression-patterns-following-focal-cerebral-ischemia-in-mice
#5
Cuiying Liu, Chencheng Zhang, Jian Yang, Xiaokun Geng, Huishan Du, Xunming Ji, Heng Zhao
Circular RNAs (circRNAs) have been demonstrated to act as microRNA (miRNA) sponges and they play important roles in regulating gene expression through a circRNA-miRNA-gene pathway. The specific roles of circRNAs in the pathogenesis of cerebral ischemia, however, are still unclear. Thus, the aim of this study is to determine circRNA expression profiles in the ischemic brain after stroke, which was induced by 45 min of transient middle cerebral artery occlusion (MCAO). The results from the circRNA microarrays revealed that 1027 circRNAs were significantly altered 48 hours after reperfusion in the ischemic brain compared with the sham group...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156805/circulating-tumor-dna-shows-variable-clonal-response-of-breast-cancer-during-neoadjuvant-chemotherapy
#6
Ji-Yeon Kim, Donghyun Park, Dae-Soon Son, Seok Jin Nam, Seok Won Kim, Hae Hyun Jung, Yeon Jeong Kim, Gahee Park, Woong-Yang Park, Jeong Eon Lee, Yeon Hee Park
Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer (BC). In this study, we aimed to identify genetic alterations during the process of tumor clonal evolution and examine if ctDNA level well indicated clinical response to neoadjuvant chemotherapy (NAC) and BC recurrence. We performed targeted ultra-deep sequencing of plasma DNAs, matched germline DNAs and tumor DNAs from locally advanced BC patients. Serial plasma DNAs were collected at diagnosis, after the 1(st) cycle of NAC and after curative surgery...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156801/genomic-characterization-of-human-papillomavirus-positive-and-negative-human-squamous-cell-cancer-cell-lines
#7
Nene N Kalu, Tuhina Mazumdar, Shaohua Peng, Li Shen, Vaishnavi Sambandam, Xiayu Rao, Yuanxin Xi, Lerong Li, Yuan Qi, Frederico O Gleber-Netto, Ameeta Patel, Jing Wang, Mitchell J Frederick, Jeffrey N Myers, Curtis R Pickering, Faye M Johnson
Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156798/arhi-is-a-novel-epigenetic-silenced-tumor-suppressor-in-sporadic-pheochromocytoma
#8
Dong Wang, Li Song, Liang Wang, Lianmei Zhao, Bai Xiang, Ying Li, Baoen Shan, Jing Liu
Pheochromocytoma (PCC) is related to germline mutations in 12 susceptibility genes. Although comparative genomic hybridization array has revealed some putative tumor suppressor genes on the short arm of chromosome 1 that are likely to be involved in PCC tumorigenesis, the molecules involved, except for those encoded by known susceptibility genes, have not been found in the generation of sporadic tumors. In the present work, we first identified that the unmethylated allele of Aplasia Ras homolog member I (ARHI) was deleted in most PCC tumors which retained a hypermethylated copy, while its mRNA level was significantly correlated with the unmethylated copy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156785/in-silico-and-in-vitro-identification-of-inhibitory-activities-of-sorafenib-on-histone-deacetylases-in-hepatocellular-carcinoma-cells
#9
Tsang-Pai Liu, Yi-Han Hong, Pei-Ming Yang
Although sorafenib has been approved for treating hepatocellular carcinoma (HCC), clinical results are not satisfactory. Polypharmacology (one drug with multiple molecular targets) is viewed as an attractive strategy for identifying novel mechanisms of a drug and then rationally designing more-effective next-generation therapeutic agents. In this study, a polypharmacological study of sorafenib was performed by mining the next-generation Connectivity Map (CMap) database, CLUE (https://clue.io/). We found that sorafenib may act as a histone deacetylase (HDAC) inhibitor based on similar gene expression profiles...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156779/selecting-lncrnas-in-gastric-cancer-cells-for-directed-therapy-with-bioactive-peptides-and-chemotherapy-drugs
#10
Wenyan Han, Rui Xiao, Chuanling Zhang, Qimuge Suyila, Xian Li, Xiulan Su
Selecting lncRNAs for directed therapy with bioactive peptides and chemotherapy drugs may be an effective approach to treating gastric cancer (GC). We show genome-scale identification and characterization of differentially expressed lncRNAs in GC cells treated with a novel anti-cancer bioactive peptide (ACBP) and the chemotherapy drug oxaliplatin (ASLB). A total of 17,897 lncRNAs were identified through pairwise comparison, including 2,074 novel lncRNAs. Of those, 1,386 lncRNAs were differentially expressed (over 1...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156765/network-directed-cis-mediator-analysis-of-normal-prostate-tissue-expression-profiles-reveals-downstream-regulatory-associations-of-prostate-cancer-susceptibility-loci
#11
Nicholas B Larson, Shannon K McDonnell, Zach Fogarty, Melissa C Larson, John Cheville, Shaun Riska, Saurabh Baheti, Alexandra M Weber, Asha A Nair, Liang Wang, Daniel O'Brien, Jaime Davila, Daniel J Schaid, Stephen N Thibodeau
Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis-acting associations due to study limitations. While trans-eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans-eQTL associations are mediated by cis-regulated genes, such as transcription factors...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156764/the-neil1-g83d-germline-dna-glycosylase-variant-induces-genomic-instability-and-cellular-transformation
#12
Heather A Galick, Carolyn G Marsden, Scott Kathe, Julie A Dragon, Lindsay Volk, Antonia A Nemec, Susan S Wallace, Aishwarya Prakash, Sylvie Doublié, Joann B Sweasy
Base excision repair (BER) is a key genome maintenance pathway. The NEIL1 DNA glycosylase recognizes oxidized bases, and likely removes damage in advance of the replication fork. The rs5745906 SNP of the NEIL1 gene is a rare human germline variant that encodes the NEIL1 G83D protein, which is devoid of DNA glycosylase activity. Here we show that expression of G83D NEIL1 in MCF10A immortalized but non-transformed mammary epithelial cells leads to replication fork stress. Upon treatment with hydrogen peroxide, we observe increased levels of stalled replication forks in cells expressing G83D NEIL1 versus cells expressing the wild-type (WT) protein...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156753/candidate-tumor-suppressor-znf154-suppresses-invasion-and-metastasis-in-npc-by-inhibiting-the-emt-via-wnt-%C3%AE-catenin-signalling
#13
Ying Hu, Min-Fang Qi, Qian-Lan Xu, Xiang-Yun Kong, Rui Cai, Qiu-Qiu Chen, Hua-Ying Tang, Wei Jiang
Background: Nasopharyngeal carcinoma (NPC) is especially prevalent in southeast Asia and southern China, but its molecular mechanisms remain poorly characterized. DNA methylation is associated with initiation and progression of tumors, including NPC. Through a genome-wide DNA methylation screening approach, we discovered ZNF154, but its methylation status and roles in NPC have not been investigated. Methods: The methylation status of ZNF154 in NPC was detected with Methylation specific-PCR (MSP) and Quantitative Sequenom MassARRAY...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156751/identification-of-potential-tissue-specific-cancer-biomarkers-and-development-of-cancer-versus-normal-genomic-classifiers
#14
Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar
Machine learning techniques for cancer prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. Recent "OMICS" studies which include a variety of cancer and normal tissue samples along with machine learning approaches have the potential to further accelerate such discovery. To demonstrate this potential, 2,175 gene expression samples from nine tissue types were obtained to identify gene sets whose expression is characteristic of each cancer class. Using random forests classification and ten-fold cross-validation, we developed nine single-tissue classifiers, two multi-tissue cancer-versus-normal classifiers, and one multi-tissue normal classifier...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156750/somatic-mutations-in-cdh1-and-ctnnb1-in-primary-carcinomas-at-13-anatomic-sites
#15
Evan L Busch, Jason L Hornick, Renato Umeton, Adem Albayrak, Neal I Lindeman, Laura E MacConaill, Elizabeth P Garcia, Matthew Ducar, Timothy R Rebbeck
Metastases are involved in most cancer deaths. Evidence has suggested that cancer cell detachment from primary tumors might occur largely via the mechanism of epithelial-mesenchymal transition (EMT) activated by epigenetic events, but data addressing other possible triggers of detachment, particularly genetic mutations, have been limited. Using the Profile study of cancer genomics at Dana-Farber Cancer Institute, we examined somatic mutations in the EMT genes CDH1 in 5,106 primary carcinomas and CTNNB1 in 7,578 primary carcinomas across 13 anatomic sites: urinary bladder, breast, colon/rectum, endometrium, esophagus, kidney, lung, ovary, pancreas, prostate, skin (non-melanoma), stomach, and thyroid...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156748/association-of-melatonin-membrane-receptor-1a-1b-gene-polymorphisms-with-the-occurrence-and-metastasis-of-hepatocellular-carcinoma
#16
Shih-Chi Su, Yung-Chuan Ho, Yu-Fan Liu, Russel J Reiter, Chia-Hsuan Chou, Chia-Ming Yeh, Hsiang-Lin Lee, Wen-Hung Chung, Ming-Ju Hsieh, Shun-Fa Yang
Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156685/whole-genome-and-transcriptome-analysis-reveal-maldi-tof-ms-and-sds-page-have-limited-performance-for-the-detection-of-the-key-outer-membrane-protein-in-carbapenem-resistant-klebsiella-pneumoniae-isolates
#17
Naina Adren Pinto, Roshan D'Souza, In Sik Hwang, Jongrak Choi, Yong Ha In, Hyung Soon Park, Choong-Min Ryu, Dongeun Yong, Kyungwon Lee
To detect the outer membrane protein (OMP), which plays a key role in carbapenem resistance, whole-genome and transcriptome analysis of the clinical carbapenem-resistant Klebsiella pneumoniae was carried out. The index strain lacked both OmpK35 and OmpK36, whereas the other strains lacked only OmpK35. After SDS-PAGE, the putative OMP bands were excised and identified as OmpA and OmpK36. MALDI-TOF MS showed peaks at ∼36 and ∼38 kDa that corresponded to OmpA and OmpK36, respectively. In all the strains except YMC2014/03/P345, the ∼38 kDa peaks were present...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156679/remote-intracranial-recurrence-of-idh-mutant-gliomas-is-associated-with-tp53-mutations-and-an-8q-gain
#18
Shunsuke Nakae, Takema Kato, Kazuhiro Murayama, Hikaru Sasaki, Masato Abe, Masanobu Kumon, Tadashi Kumai, Kei Yamashiro, Joji Inamasu, Mitsuhiro Hasegawa, Hiroki Kurahashi, Yuichi Hirose
Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156678/epigenetic-silencing-of-tumor-suppressor-candidate-3-confers-adverse-prognosis-in-early-colorectal-cancer
#19
Elke Burgermeister, Patrick Höde, Johannes Betge, Tobias Gutting, Andreas Merkel, Wen Wu, Marc Tänzer, Maximilian Mossner, Daniel Nowak, Julia Magdeburg, Felix Rückert, Carsten Sticht, Katja Breitkopf-Heinlein, Nadine Schulte, Nicolai Härtel, Sebastian Belle, Stefan Post, Timo Gaiser, Barbara Ingold Heppner, Hans-Michael Behrens, Christoph Röcken, Matthias P A Ebert
Colorectal cancer (CRC) is a biologically and clinically heterogeneous disease. Even though many recurrent genomic alterations have been identified that may characterize distinct subgroups, their biological impact and clinical significance as prognostic indicators remain to be defined. The tumor suppressor candidate-3 (TUSC3/N33) locates to a genomic region frequently deleted or silenced in cancers. TUSC3 is a subunit of the oligosaccharyltransferase (OST) complex at the endoplasmic reticulum (ER) which catalyzes bulk N-glycosylation of membrane and secretory proteins...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156626/surface-plasmon-resonance-sensing-of-biorecognition-interactions-within-the-tumor-suppressor-p53-network
#20
REVIEW
Ilaria Moscetti, Salvatore Cannistraro, Anna Rita Bizzarri
Surface Plasmon Resonance (SPR) is a powerful technique to study the kinetics of biomolecules undergoing biorecognition processes, particularly suited for protein-protein interactions of biomedical interest. The potentiality of SPR was exploited to sense the interactions occurring within the network of the tumor suppressor p53, which is crucial for maintaining genome integrity and whose function is inactivated, mainly by down regulation or by mutation, in the majority of human tumors. This study includes p53 down-regulators, p53 mutants and also the p53 family members, p63 and p73, which could vicariate p53 protective function...
November 20, 2017: Sensors
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