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https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#1
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938691/concomitant-eml4-alk-rearrangement-and-egfr-mutation-in-non-small-cell-lung-cancer-patients-a-literature-review-of-100-cases
#2
REVIEW
Giuseppe Lo Russo, Martina Imbimbo, Giulia Corrao, Claudia Proto, Diego Signorelli, Milena Vitali, Monica Ganzinelli, Laura Botta, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino
The discovery of EGFR mutations and EML4-ALK gene rearrangements has radically changed the therapeutic scenario for patients with advanced non-small cell lung cancer. ALK and EGFR tyrosine-kinase inhibitors showed better activity and efficacy than standard chemotherapy in the first and second line treatment settings, leading to a clear advantage in overall survival of advanced non-small cell lung cancer patients harboring these genetic alterations. Historically the coexistence of EGFR mutations and EML4-ALK rearrangements in the same tumor has been described as virtually impossible...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938685/a-case-control-study-of-the-association-between-the-egfr-gene-and-glioma-risk-in-a-chinese-han-population
#3
Mengdan Yan, Jingjie Li, Na He, Xugang Shi, Shuli Du, Bin Li, Tianbo Jin
The Epidermal Growth Factor Receptor gene has been reported to be involved in the progression of gliomas which is one of the deadliest primary brain tumors in humans. To determine potential association between EGFR and glioma risk, we performed a case-control study with 394 glioma patients and 298 cancer-free controls in which captured a total of 8 tag single nucleotide polymorphisms of EGFR gene from Xi'an, China. SPSS 19.0 statistical packages, χ(2) test, genetic model analysis and SHEsis software platform were analyzed s the variants in EGFR gene associations with glioma risk...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938655/prognostic-value-of-decreased-long-non-coding-rna-tusc7-expression-in-some-solid-tumors-a-systematic-review-and-meta-analysis
#4
Na Li, Meilan Yang, Ke Shi, Wei Li
Accumulating evidences indicated that tumor suppressor candidate 7 (TUSC7) is a putatively tumor suppressor gene in various tumors. We carried out current systematic review and meta-analysis to explore the decreased expression of TUSC7 associate with prognostic and clinicopathological characteristic in cancer patients. A literature collection search in the online electronic databases PubMed, Embase, Web of Science, and CNKI was conducted to obtain eligible studies (up to February 20, 2017). A total of nine studies comprise 757 patients were identified and included in present meta-analysis based on the selection and inclusion criteria...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938650/genomic-variants-link-to-hepatitis-c-racial-disparities
#5
Matthew M Yeh, Sarag Boukhar, Benjamin Roberts, Nairanjana Dasgupta, Sayed S Daoud
Chronic liver diseases are one of the major public health issues in United States, and there are substantial racial disparities in liver cancer-related mortality. We previously identified racially distinct alterations in the expression of transcripts and proteins of hepatitis C (HCV)-induced hepatocellular carcinoma (HCC) between Caucasian (CA) and African American (AA) subgroups. Here, we performed a comparative genome-wide analysis of normal vs. HCV+ (cirrhotic state), and normal adjacent tissues (HCCN) vs...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938648/a-novel-lncrna-ll22nc03-n64e9-1-represses-klf2-transcription-through-binding-with-ezh2-in-colorectal-cancer
#6
Yifan Lian, Changsheng Yan, Jie Ding, Rui Xia, Zhonghua Ma, Bingqing Hui, Hao Ji, Jing Zhou, Keming Wang
Long noncoding RNAs (lncRNA) have been implicated in variety human cancer but their mechanisms of function are mainly undocumented. In the present study, we investigated lncRNAs alteration that contributed to colorectal cancer (CRC) by utilizing TCGA RNA sequencing data and other publicly available lncRNAs expression profiling data. Here, We screened out the CRC-associated lncRNA LL22NC03-N64E9.1, a key regulator of CRC development and progression. We also revealed that knockdown of LL22NC03-N64E9.1 inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, both in vitro and in vivo...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938640/association-of-two-obesity-related-gene-polymorphisms-lepg2548a-rs7799039-and-leprq223r-rs1137101-with-the-risk-of-breast-cancer
#7
Hui Luan, Hong Zhang, Ying Li, Ping Wang, Lifei Cao, Honglan Ma, Qing Cui, Gang Tian
Many studies have been performed to investigate the correlation of leptin (LEP) and leptin receptor (LEPR) polymorphisms with breast cancer (BC) risk, however the results are inconclusive. To obtain a more precise estimation, we conducted this meta-analysis. We searched PubMed, EMBASE, and Web of Science databases to identify qualified studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association. Eight eligible studies (2,124 cases and 5,476 controls) for LEP G2548A (rs7799039) polymorphism, and thirteen studies (5,282 cases and 6,140 controls) for LEPR Q223R (rs1137101) polymorphism were included in our study...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938639/spondin2-is-a-new-prognostic-biomarker-for-lung-adenocarcinoma
#8
Xiaopeng Yuan, Tingting Bian, Jian Liu, Honggang Ke, Jia Feng, Qing Zhang, Li Qian, Xiaoli Li, Yifei Liu, Jianguo Zhang
Spondin 2 (SPON2) is a member of the F-spondin superfamily of genes that encode an extracellular matrix protein. SPON2 has been identified by mRNA differential display screening of cancerous and noncancerous lung cell lines in vitro [1], however, its role in pulmonary adenocarcinoma (ADC) patients remains unclear. In our study, we evaluated whether SPON2 can be used as a biomarker for the diagnosis of pulmonary ADC and any association between SPON2 protein levels and clinicopathological characteristics. Firstly, the mRNA levels of SPON2 in pulmonary ADCs and normal adjacent tissue samples were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 60) assay and the expression of SPON2 protein were detected by tissue microarray immunohistochemistry analysis (TMA-IHC) (n = 280)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938638/prognostic-modeling-of-oral-cancer-by-gene-profiles-and-clinicopathological-co-variables
#9
Steven W Mes, Dennis Te Beest, Tito Poli, Silvia Rossi, Kathrin Scheckenbach, Wessel N van Wieringen, Arjen Brink, Nicoletta Bertani, Davide Lanfranco, Enrico M Silini, Paul J van Diest, Elisabeth Bloemena, C René Leemans, Mark A van de Wiel, Ruud H Brakenhoff
Accurate staging and outcome prediction is a major problem in clinical management of oral cancer patients, hampering high precision treatment and adjuvant therapy planning. Here, we have built and validated multivariable models that integrate gene signatures with clinical and pathological variables to improve staging and survival prediction of patients with oral squamous cell carcinoma (OSCC). Gene expression profiles from 249 human papillomavirus (HPV)-negative OSCCs were explored to identify a 22-gene lymph node metastasis signature (LNMsig) and a 40-gene overall survival signature (OSsig)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938637/the-loss-of-function-of-dna-methyltransferase-1-by-sirna-impairs-the-growth-of-non-small-cell-lung-cancer-with-alleviated-side-effects-via-reactivation-of-rassf1a-and-apc-in-vitro-and-vivo
#10
Qi Lai, Yin-Hui Xu, Qiang Chen, Liang Tang, An-Gui Li, Li-Fei Zhang, Chun-Fang Zhang, Jian-Fei Song, Zhen-Zong Du
Hypermethylation of tumor suppressor genes (TSGs) promoters by DNA methyltransferase (DNMT) can be observed in almost all cancers which represent a hallmark of carcinogenesis, including lung cancer. DNMT inhibitors (e.g.5-Aza-CR/CdR) reactivate TSGs to exert anti-cancer activity and have been applied into the clinical. However, it is cytotoxic even at low concentrations, which might be not directly related to DNA methylation. We here investigated an alternative strategy in the lung cancer therapy and aimed to estimate and compare its efficiency and side effects of knockdown of DNMT1 in vitro and in vivo...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938627/prostate-tumor-overexpressed-1-ptov1-promotes-docetaxel-resistance-and-survival-of-castration-resistant-prostate-cancer-cells
#11
Verónica Cánovas, Yolanda Puñal, Valentina Maggio, Enric Redondo, Mercedes Marín, Begoña Mellado, Mireia Olivan, Matilde Lleonart, Jacques Planas, Juan Morote, Rosanna Paciucci
Metastatic prostate cancer is presently incurable. The oncogenic protein PTOV1, first described in prostate cancer, was reported as overexpressed and significantly correlated with poor survival in numerous tumors. Here, we investigated the role of PTOV1 in prostate cancer survival to docetaxel and self-renewal ability. Transduction of PTOV1 in docetaxel-sensitive Du145 and PC3 cells significantly increased cell survival after docetaxel exposure and induced docetaxel-resistance genes expression (ABCB1, CCNG2 and TUBB2B)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938622/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#12
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938616/identification-of-potential-cancer-related-pseudogenes-in-lung-adenocarcinoma-based-on-cerna-hypothesis
#13
Yunzhen Wei, Zhiqiang Chang, Cheng Wu, Yinling Zhu, Kun Li, Yan Xu
Pseudogenes are initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. Far from being silent, pseudogenes are proved to regulate the expression of protein-coding genes through function as microRNA sponge in vivo. The aim of our study was to propose an integrative systems biology approach to identify disease pseudogenes base on competitive endogenous RNA (ceRNA) hypothesis. Here, we applied our method to lung adenocarcinoma (LUAD) RNASeq data from TCGA and identified 33 candidate pseudogenes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#14
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938601/mutation-profile-based-methods-for-understanding-selection-forces-in-cancer-somatic-mutations-a-comparative-analysis
#15
Zhan Zhou, Yangyun Zou, Gangbiao Liu, Jingqi Zhou, Jingcheng Wu, Shimin Zhao, Zhixi Su, Xun Gu
Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes (CN /CS ) and normal populations (pN /pS ). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938599/a-pathways-based-prediction-model-for-classifying-breast-cancer-subtypes
#16
Tong Wu, Yunfeng Wang, Ronghui Jiang, Xinliang Lu, Jiawei Tian
Breast cancer is highly heterogeneous and is classified into four subtypes characterized by specific biological traits, treatment responses, and clinical prognoses. We performed a systemic analysis of 698 breast cancer patient samples from The Cancer Genome Atlas project database. We identified 136 breast cancer genes differentially expressed among the four subtypes. Based on unsupervised clustering analysis, these 136 core genes efficiently categorized breast cancer patients into the appropriate subtypes. Functional enrichment based on Kyoto Encyclopedia of Genes and Genomes analysis identified six functional pathways regulated by these genes: JAK-STAT signaling, basal cell carcinoma, inflammatory mediator regulation of TRP channels, non-small cell lung cancer, glutamatergic synapse, and amyotrophic lateral sclerosis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938593/endoplasmic-reticulum-stress-mediated-membrane-expression-of-crt-erp57-induces-immunogenic-apoptosis-in-drug-resistant-endometrial-cancer-cells
#17
Qin Xu, Chuanben Chen, An Lin, Yunqing Xie
OBJECTIVE: To investigate the role of endoplasmic reticulum (ER) stress-mediated CRT/ERp57 complex expression underlying the mechanism of resistance to doxorubicin (DOX) in endometrial carcinoma (EC) in vivo and in vitro. METHODS: The expression of CRT, ERp57, p-PERK, eIF2α, p-eIF2α in EC patients and EC cells was detected by Western blots and by immunofluorescence assay. MTT assay was used to determine the LC50 of EC cells to DOX and cell viability. Apoptosis was assayed using flow cytometer...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938581/targeting-progastrin-enhances-radiosensitization-of-colorectal-cancer-cells
#18
Aline Kowalski-Chauvel, Valerie Gouaze-Andersson, Alix Vignolle-Vidoni, Caroline Delmas, Christine Toulas, Elizabeth Cohen-Jonathan-Moyal, Catherine Seva
A high percentage of advanced rectal cancers are resistant to radiation. Therefore, increasing the efficacy of radiotherapy by targeting factors involved in radioresistance seems to be an attractive strategy. Here we demonstrated that the pro-hormone progastrin (PG), known to be over-expressed in CRC, and recognized as a pro-oncogenic factor, is a radioresistance factor that can be targeted to sensitize resistant rectal cancers to radiations. First, we observed an increase in PG mRNA expression under irradiation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938580/diagnostic-significance-of-urinary-long-non-coding-pca3-rna-in-prostate-cancer
#19
Tao Wang, Xiangyun Qu, Jiajia Jiang, Peng Gao, Dingding Zhao, Xueqi Lian, Xiaohua Li
Prostate cancer antigen 3(PCA3) is a long non-coding RNA, which was found increased expression in CaP patients than healthy individual. In this study, the individual nucleic acid of PCA3 and PSA was recombinant expressed as a reference reagent, and a quantitative RT-PCR with TaqMan assay was developed to examine the copies of PCA3 and PSA gene in urine. The results showed that the area under the receiver operating characteristic curve (AUROC) was 0.717, 0.444 and 0.916 for the number of PCA3 copy, PSA copy and for the score of PCA3/PSA RNA, respectively...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938577/mitochondria-chaperone-grp75-moonlighting-as-a-cell-cycle-controller-to-derail-endocytosis-provides-an-opportunity-for-nanomicrosphere-intracellular-delivery
#20
Zhihui Gao, Xiuran Niu, Qing Zhang, Hang Chen, Aiai Gao, Shanshan Qi, Rong Xiang, Mattias Belting, Sihe Zhang
Understanding how cancer cells regulate endocytosis during the cell cycle could lead us to capitalize this event pharmacologically. Although certain endocytosis pathways are attenuated during mitosis, the endocytosis shift and regulation during the cell cycle have not been well clarified. The conventional concept of glucose-regulated proteins (GRPs) as protein folding chaperones was updated by discoveries that translocated GRPs assume moonlighting functions that modify the immune response, regulate viral release, and control intracellular trafficking...
August 29, 2017: Oncotarget
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