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Clinical pathways and cancer

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https://www.readbyqxmd.com/read/29346775/brd4-promotes-dna-repair-and-mediates-the-formation-of-tmprss2-erg-gene-rearrangements-in-prostate-cancer
#1
Xiangyi Li, GuemHee Baek, Susmita G Ramanand, Adam Sharp, Yunpeng Gao, Wei Yuan, Jon Welti, Daniel N Rodrigues, David Dolling, Ines Figueiredo, Semini Sumanasuriya, Mateus Crespo, Adam Aslam, Rui Li, Yi Yin, Bipasha Mukherjee, Mohammed Kanchwala, Ashley M Hughes, Wendy S Halsey, Cheng-Ming Chiang, Chao Xing, Ganesh V Raj, Sandeep Burma, Johann de Bono, Ram S Mani
BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346386/histological-subtypes-of-mouse-mammary-tumors-reveal-conserved-relationships-to-human-cancers
#2
Daniel P Hollern, Matthew R Swiatnicki, Eran R Andrechek
Human breast cancer has been characterized by extensive transcriptional heterogeneity, with dominant patterns reflected in the intrinsic subtypes. Mouse models of breast cancer also have heterogeneous transcriptomes and we noted that specific histological subtypes were associated with particular subsets. We hypothesized that unique sets of genes define each tumor histological type across mouse models of breast cancer. Using mouse models that contained both gene expression data and expert pathologist classification of tumor histology on a sample by sample basis, we predicted and validated gene expression signatures for Papillary, EMT, Microacinar and other histological subtypes...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29345572/breaking-the-dna-damage-response-via-serine-threonine-kinase-inhibitors-to-improve-cancer-treatment
#3
Wioletta Rozpedek, Dariusz Pytel, Alicja Nowak-Zdunczyk, Dawid Lewko, Radoslaw Wojtczak, John Alan Diehl, Ireneusz Majsterek
Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345357/the-prognostic-value-of-pi3k-mutational-status-in-breast-cancer-a-meta-analysis
#4
N Sobhani, G Roviello, S P Corona, M Scaltriti, A Ianza, M Bortul, F Zanconati, D Generali
Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20-40% of BC. We performed a meta-analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor and predictor of response to anti-cancer treatments...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345289/no-erythropoietin-induced-growth-is-observed-in-non-small-cell-lung-cancer-cells
#5
Armin Frille, Katharina Leithner, Andrea Olschewski, Horst Olschewski, Christoph Wohlkönig, Andelko Hrzenjak
Lung cancer patients have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (Epo) has consistently been shown to reduce the need for blood transfusions and to increase hemoglobin levels in lung cancer patients with chemotherapy-induced anemia. However, clinical and preclinical studies have prompted concerns that Epo and the presence of its receptor, EpoR, in tumor cells may be responsible for adverse effects and, eventually, death. The question has been raised whether Epo promotes tumor growth and inhibits the death of cancer cells...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344898/methods-for-high-throughput-drug-combination-screening-and-synergy-scoring
#6
Liye He, Evgeny Kulesskiy, Jani Saarela, Laura Turunen, Krister Wennerberg, Tero Aittokallio, Jing Tang
Gene products or pathways that are aberrantly activated in cancer but not in normal tissue hold great promises for being effective and safe anticancer therapeutic targets. Many targeted drugs have entered clinical trials but so far showed limited efficacy mostly due to variability in treatment responses and often rapidly emerging resistance. Toward more effective treatment options, we will need multi-targeted drugs or drug combinations, which selectively inhibit the viability and growth of cancer cells and block distinct escape mechanisms for the cells to become resistant...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344654/tunicamycin-inhibits-colon-carcinoma-growth-and-aggressiveness-via-modulation-of-the-erk-jnk-mediated-akt-mtor-signaling-pathway
#7
Shuping You, Weihong Li, Yun Guan
Epidemiology and evidence have demonstrated that colon carcinoma is one of the most common gastrointestinal tumors in the clinic. Reports have suggested that Tunicamycin significantly inhibits aggressiveness of colon carcinoma cells by promotion of apoptosis. In the present study, the inhibitory effect of tunicamycin on colon cancer cells and the potential underlying molecular mechanism was investigated. Western blotting, immunohistochemistry, apoptotic assays and immunofluorescence were used to analyze the therapeutic effects of tunicamycin on apoptosis, growth, aggressiveness and cell cycle of colon tumor cells, by downregulation of fibronectin, vimentin and E‑cadherin expression levels...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344282/clinical-significance-of-glycoprotein-non-metastatic-b-and-its-association-with-egfr-her2-in-gastrointestinal-cancer
#8
Jesse Yu Tajima, Manabu Futamura, Siqin Gaowa, Ryutaro Mori, Toshiyuki Tanahashi, Yoshihiro Tanaka, Nobuhisa Matsuhashi, Takao Takahashi, Kazuya Yamaguchi, Tatsuhiko Miyazaki, Kazuhiro Yoshida
Glycoprotein non-metastatic B (GPNMB), a type I transmembrane glycoprotein, is overexpressed in melanoma and breast cancer and promotes cancer-cell invasion and motility. We previously reported cross-talk between GPNMB and human epidermal growth factor receptor 2 (HER2) in breast cancer, suggesting that GPNMB might play an important role in resistance to anti-HER2 therapy in breast cancer. Here, we clarified the association between GPNMB and HER-family proteins in gastrointestinal cancer by examining their relationships using gastric and colorectal cancer cell lines...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344262/hedyotis-diffusa-willd-extract-suppresses-colorectal-cancer-growth-through-multiple-cellular-pathways
#9
Jianyu Feng, Yiyi Jin, Jun Peng, Lihui Wei, Qiaoyan Cai, Zhaokun Yan, Zijun Lai, Jiumao Lin
The development of colorectal cancer (CRC) is strongly associated with the imbalance of various intracellular signal transduction cascades, including protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal transducer and activator of transcription 3 (STAT3), as well as crosstalk between these signaling networks. At present, anti-tumor agents are often single-targeted and therefore are not always therapeutically effective. Moreover, long-term use of these anti-tumor agents often generates drug resistance and potential side effects...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344237/chloroform-extract-of-hedyotis-diffusa-willd-inhibits-viability-of-human-colorectal-cancer-cells-via-suppression-of-akt-and-erk-signaling-pathways
#10
Zhaokun Yan, Jianyu Feng, Jun Peng, Zijun Lai, Ling Zhang, Yiyi Jin, Hong Yang, Wujin Chen, Jiumao Lin
Hedyotis diffusa Willd (HDW) is a widely used traditional Chinese medicine in clinical therapy to treat various types of cancer, including colorectal cancer (CRC), but its effective polar fractions and functional mechanisms remain unclear. The aim of the present study was to determine the most effective extract of HDW and to investigate its effects on the regulation of CRC cell proliferation and apoptosis, as well as to investigate the underlying molecular mechanisms. The results demonstrated that the chloroform extract of HDW (CEHDW) exhibited the most anticancer ability...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344233/lidamycin-decreases-cd133-expression-in-hepatocellular-carcinoma-via-the-notch-signaling-pathway
#11
Yi Chen, Wenwei Sun, Ran He, Feiyan Zhang, Hongyu Wang, Panhong Li, Rong-Guang Shao, Xiaoyu Xu
Cluster of differentiation (CD)133 is considered a molecular marker of cancer stem cells in hepatocellular carcinoma. In the present study, the effect of lidamycin (LDM) on CD133 expression in hepatocellular carcinoma (Huh7 cells) was evaluated and the potential molecular mechanism was investigated. Flow cytometry analysis, as well as sorting, sphere formation and western-blot assays, were performed in vitro to explore the effects of LDM on CD133 expression. A subcutaneous tumor model in nude mice was used to observe the effects of LDM on tumor volume and CD133 protein in vivo...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344189/phosphorylated-akt-expression-in-tumor-adjacent-normal-tissue-is-associated-with-poor-prognosis-in-patients-with-hepatocellular-carcinoma
#12
Yao-Li Chen, Po-Ming Chen, Ying-Zi Ming, Ping-Yi Lin, Chih-Ping Chu, Pei-Yi Chu
The AKT pathway serves important roles in tumor cell growth. Its overexpression is associated with poor prognosis in a number of types of cancer; however, the role of AKT in the role of the pathogenesis of hepatocellular carcinoma (HCC) remains unclear. The present study was undertaken to explore the clinical relevance of phosphorylated AKT (p-AKT) in HCC. The level of p-AKT in tumor (TU) and paired adjacent normal liver (AN) tissue from 202 HCC patients was evaluated with immunohistochemistry. The results demonstrated that p-AKT was more highly expressed in TU than in AN tissue...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344186/downregulation-of-klotho-%C3%AE-is-associated-with-invasive-ductal-carcinoma-progression
#13
Ping Li, Meng Zhao, Xiaoli Qi, Xuegong Zhu, Jie Dai
Klotho β (KLB) is a single-pass transmembrane protein measuring 1,043 amino acids in length that shares 41.2% homology with klotho α (KLA). KLB is a co-receptor and key regulator of the fibroblast growth factor receptor 4 (FGFR4) pathway. KLB interacts with FGFR4 to induce apoptosis and inhibit the proliferation of hepatoma cells, and KLA has been demonstrated to be a tumor suppressor in human breast cancer; however, little is known regarding the role of KLB in breast cancer. In the present study, through an immunohistochemical analysis of invasive ductal carcinoma tissue arrays, low KLB expression was identified in invasive ductal carcinoma samples compared with paired adjacent non-tumorous breast tissues (82 cases)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344166/identification-and-functional-analysis-of-risk-related-micrornas-for-the-prognosis-of-patients-with-bladder-urothelial-carcinoma
#14
Ji Gao, Hongyan Li, Lei Liu, Lide Song, Yanting Lv, Yuping Han
The aim of the present study was to investigate risk-related microRNAs (miRs) for bladder urothelial carcinoma (BUC) prognosis. Clinical and microRNA expression data downloaded from the Cancer Genome Atlas were utilized for survival analysis. Risk factor estimation was performed using Cox's proportional regression analysis. A microRNA-regulated target gene network was constructed and presented using Cytoscape. In addition, the Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, followed by protein-protein interaction (PPI) network analysis...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344157/expression-and-clinical-significance-of-programmed-death-1-on-lymphocytes-and-programmed-death-ligand-1-on-monocytes-in-the-peripheral-blood-of-patients-with-cervical-cancer
#15
Ying Zhang, Weipei Zhu, Xueguang Zhang, Qiuxia Qu, Liyuan Zhang
The programmed death-1 (PD-1) signaling pathway serves a critical role in immune regulation and tolerance by suppressing the activation and proliferation of T cells. The aim of the present study was to investigate the effect of PD-1 and programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40 patients with CIN and 66 newly diagnosed cervical cancer patients were recruited. The expression level of PD-1 expression on peripheral cluster of differentiation (CD)4+ and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344121/a-five-gene-based-risk-score-with-high-prognostic-value-in-colorectal-cancer
#16
Yida Pan, Hongyang Zhang, Mingming Zhang, Jie Zhu, Jianghong Yu, Bangting Wang, Jigang Qiu, Jun Zhang
Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343814/intrinsic-apoptotic-pathway-activation-increases-response-to-anti-estrogens-in-luminal-breast-cancers
#17
Michelle M Williams, Linus Lee, Thomas Werfel, Meghan M Morrison Joly, Donna J Hicks, Bushra Rahman, David Elion, Courtney McKernan, Violeta Sanchez, Monica V Estrada, Suleiman Massarweh, Richard Elledge, Craig Duvall, Rebecca S Cook
Estrogen receptor-α positive (ERα+) breast cancer accounts for approximately 70-80% of the nearly 25,0000 new cases of breast cancer diagnosed in the US each year. Endocrine-targeted therapies (those that block ERα activity) serve as the first line of treatment in most cases. Despite the proven benefit of endocrine therapies, however, ERα+ breast tumors can develop resistance to endocrine therapy, causing disease progression or relapse, particularly in the metastatic setting. Anti-apoptotic Bcl-2 family proteins enhance breast tumor cell survival, often promoting resistance to targeted therapies, including endocrine therapies...
January 17, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29343775/impact-of-concurrent-genomic-alterations-detected-by-comprehensive-genomic-sequencing-on-clinical-outcomes-in-east-asian-patients-with-egfr-mutated-lung-adenocarcinoma
#18
Seijiro Sato, Masayuki Nagahashi, Terumoto Koike, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Takada, Ryota Nakanishi, Eiji Oki, Tatsuro Okamoto, Kouhei Akazawa, Stephen Lyle, Yiwei Ling, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai, Masanori Tsuchida
Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343273/inpp4b-promotes-cell-survival-via-sgk3-activation-in-npm1-mutated-leukemia
#19
Hongjun Jin, Liyuan Yang, Lu Wang, Zailin Yang, Qian Zhan, Yao Tao, Qin Zou, Yuting Tang, Jingrong Xian, Shuaishuai Zhang, Yipei Jing, Ling Zhang
BACKGROUND: Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been recognized as a distinct leukemia entity in the 2016 World Health Organization (WHO) classification. The genetic events underlying oncogenesis in NPM1-mutated AML that is characterized by a normal karyotype remain unclear. Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently found a clinically relevant role in AML...
January 17, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29343144/cell-surface-proteomics-for-the-identification-of-novel-therapeutic-targets-in-cancer
#20
Laura Kuhlmann, Emma Cummins, Ismael Samudio, Thomas Kislinger
Cancer is the second most common cause of death worldwide and its heterogeneity complicates therapy. Standard cytotoxic regiments disrupt rapidly dividing cells, regardless of their neoplastic status. The introduction of less toxic targeted therapies has partially contributed to the observed decrease in cancer-related mortality. Cell-surface proteins represent attractive targets for therapy, due to their easily-accessible localization and their involvement in essential signaling pathways, often dysregulated in cancer...
January 18, 2018: Expert Review of Proteomics
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