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https://www.readbyqxmd.com/read/27912731/predicting-the-recurrence-of-noncoding-regulatory-mutations-in-cancer
#1
Woojin Yang, Hyoeun Bang, Kiwon Jang, Min Kyung Sung, Jung Kyoon Choi
BACKGROUND: One of the greatest challenges in cancer genomics is to distinguish driver mutations from passenger mutations. Whereas recurrence is a hallmark of driver mutations, it is difficult to observe recurring noncoding mutations owing to a limited amount of whole-genome sequenced samples. Hence, it is required to develop a method to predict potentially recurrent mutations. RESULTS: In this work, we developed a random forest classifier that predicts regulatory mutations that may recur based on the features of the mutations repeatedly appearing in a given cohort...
December 3, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27911867/decreased-5-hydroxymethylcytosine-levels-correlate-with-cancer-progression-and-poor-survival-a-systematic-review-and-meta-analysis
#2
Zhaoli Chen, Xuejiao Shi, Lanwei Guo, Yuan Li, Mei Luo, Jie He
Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and then to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), resulting in genomic DNA demethylation. Decreased 5-hmC levels have been reported in a variety of cancers, and loss of 5-hmC might be considered an epigenetic hallmark of cancer. However, the prognostic value of decreased 5-hmC in cancers remain controversial. Here, a systematic review was performed by conducting an electronic search of PubMed, EMBASE, Web of Science and the Cochrane Library...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911865/mitochondrial-pyruvate-carrier-function-is-negatively-linked-to-warburg-phenotype-in-vitro-and-malignant-features-in-esophageal-squamous-cell-carcinomas
#3
Yaqing Li, Xiaoran Li, Quancheng Kan, Mingzhi Zhang, Xiaoli Li, Ruiping Xu, Junsheng Wang, Dandan Yu, Mariusz Adam Goscinski, Jian-Guo Wen, Jahn M Nesland, Zhenhe Suo
Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911230/bromodomain-inhibitors-and-cancer-therapy-from-structures-to-applications
#4
Montserrat Pérez-Salvia, Manel Esteller
Aberrations in the epigenetic landscape are a hallmark of cancer. Alterations in enzymes that are "writers", "erasers", or "readers" of histone modification marks are common. Bromodomains are "readers" that bind acetylated lysines in histone tails. Their most important function is the regulation of gene transcription by the recruitment of different molecular partners. Moreover, proteins containing bromodomains are also epigenetic regulators, although little is known about the specific function of these domains...
December 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27904736/the-biology-behind-b-cell-lymphoma-2-as-a-target-in-chronic-lymphocytic-leukemia
#5
REVIEW
Valentín Ortíz-Maldonado, Pablo Mozas, Julio Delgado
B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main 'hallmarks of cancer', BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#6
Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff, Albrecht Schwab
Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all "hallmarks of cancer" such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903678/adnp-is-a-therapeutically-inducible-repressor-of-wnt-signaling-in-colorectal-cancer
#7
Cristina Blaj, Agnes Bringmann, Eva Marina Schmidt, Manuela Urbischek, Sebastian Lamprecht, Thomas Fröhlich, Georg J Arnold, Stefan Krebs, Helmut Blum, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
PURPOSE: Constitutively active WNT signaling is hallmark of colorectal cancers and driver of malignant tumor progression. Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Here we identify the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer. EXPERIMENTAL DESIGN: We used transcriptomic, proteomic, and in situ analyses to identify ADNP expression in colorectal cancer, and cell biology approaches to determine its function...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27900245/image-analysis-assisted-study-of-mitotic-figures-in-oral-epithelial-dysplasia-and-squamous-cell-carcinoma-using-differential-stains
#8
Ankita Tandon, Narendra Nath Singh, V R Brave, Gadiputi Sreedhar
BACKGROUND: Mitosis is a process of cell division resulting in two genetically equivalent daughter cells. Excessive proliferation of cells due to mitosis is the hallmark in pre cancer and cancer. AIMS: This study was conducted to count the number of mitotic figures in normal oral mucosa, oral epithelial dysplasia and squamous cell carcinoma in both Hematoxylin and Eosin (H&E) and Crystal Violet stained sections. Also the overall number of mitotic figures with both stains were compared along with the evaluation of staining efficacy of both the stains...
November 2016: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/27899894/moderate-load-eccentric-exercise-a-distinct-novel-training-modality
#9
REVIEW
Hans Hoppeler
Over the last 20 years a number of studies have been published using progressive eccentric exercise protocols on motorized ergometers or similar devices that allow for controlled application of eccentric loads. Exercise protocols ramp eccentric loads over an initial 3 weeks period in order to prevent muscle damage and delayed onset muscle soreness. Final training loads reach 400-500 W in rehabilitative settings and over 1200 W in elite athletes. Training is typically carried out three times per week for durations of 20-30 min...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27899621/cooperative-genomic-alteration-network-reveals-molecular-classification-across-12-major-cancer-types
#10
Hongyi Zhang, Yulan Deng, Yong Zhang, Yanyan Ping, Hongying Zhao, Lin Pang, Xinxin Zhang, Li Wang, Chaohan Xu, Yun Xiao, Xia Li
The accumulation of somatic genomic alterations that enables cells to gradually acquire growth advantage contributes to tumor development. This has the important implication of the widespread existence of cooperative genomic alterations in the accumulation process. Here, we proposed a computational method HCOC that simultaneously consider genetic context and downstream functional effects on cancer hallmarks to uncover somatic cooperative events in human cancers. Applying our method to 12 TCGA cancer types, we totally identified 1199 cooperative events with high heterogeneity across human cancers, and then constructed a pan-cancer cooperative alteration network...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27898232/unfolded-protein-response-promotes-doxorubicin-induced-nonsmall-cell-lung-cancer-cells-apoptosis-via-the-mtor-pathway-inhibition
#11
Xiaofang Zhao, Yan Yang, Fuli Yao, Bin Xiao, Ying Cheng, Chunhong Feng, Chunyan Duan, Chunyan Zhang, Youping Liu, Hong Li, Bo Xiao, Rongyang Dai
Drug resistance is extremely common in nonsmall-cell lung cancer (NSCLC) and is one of the major problems in NSCLC chemotherapy. However, the detailed mechanisms remain largely unknown. Unfolded protein response (UPR) is involved in the tumorigenesis of NSCLC. Here, the authors demonstrated that the UPR promotes poly (ADP-ribose) polymerase activation (PARP) cleavage in NSCLC cells on doxorubicin treatment, which is a hallmark of apoptosis and caspase activation. In NSCLC cells, doxorubicin treatment triggers the UPR activation, which subsequently promotes doxorubicin-mediated apoptosis...
November 29, 2016: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27895790/corosolic-acid-inhibits-the-proliferation-of-osteosarcoma-cells-by-inducing-apoptosis
#12
Yong Jia, Hua Yuan, Shouqin Shan, Gang Xu, Jie Yu, Chenguang Zhao, Xiang Mou
Corosolic acid (CRA), a pentacyclic triterpene isolated from medicinal herbs, has been reported to exhibit anticancer properties in several cancers. However, the anticancer activity of CRA in osteosarcoma cells is still unclear. In the present study, the inhibitory effect of CRA in osteosarcoma MG-63 cells was investigated, and the results revealed that CRA significantly inhibited the viability of MG-63 cells in a dose- and time-dependent manner. A typical apoptotic hallmark such as DNA ladder was detected by agarose gel electrophoresis following treatment with CRA...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895163/g-protein-coupled-receptor-kinase-2-grk2-as-a-potential-modulator-of-the-hallmarks-of-cancer
#13
Laura Nogues, Clara Reglero, Veronica Rivas, Maria Neves, Petronila Penela, Federico Mayor
Malignant features such as sustained proliferation, refractoriness to growth suppressors, resistance to cell death or aberrant motility and metastasis can be triggered by a variety of mutations and signaling adaptations. Signaling nodes can act as cancer-associated factors by cooperating with oncogene-governed pathways or participating in compensatory transduction networks to strengthen tumor properties. G-protein-coupled receptor kinase 2 (GRK2) is arising as one of such nodes. Via its complex network of connections with other cellular proteins, GRK2 contributes to the modulation of basic cellular functions such as cell proliferation, survival or motility, and is involved in metabolic homeostasis, inflammation or angiogenic processes...
November 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27894085/tracing-anti-cancer-and-cancer-promoting-actions-of-all-trans-retinoic-acid-in-breast-cancer-to-a-rar%C3%AE-epigenetic-mechanism-of-mammary-epithelial-cell-fate
#14
Stefano Rossetti, MingQiang Ren, Nicolo Visconti, Francesca Corlazzoli, Vincenzo Gagliostro, Giulia Somenzi, Jin Yao, Yijun Sun, Nicoletta Sacchi
A hallmark of cancer cells is the ability to evade the growth inhibitory/pro-apoptotic action of physiological all-trans retinoic acid (RA) signal, the bioactive derivative of Vitamin A. However, as we and others reported, RA can also promote cancer cell growth and invasion. Here we show that anticancer and cancer-promoting RA actions in breast cancer have roots in a mechanism of mammary epithelial cell morphogenesis that involves both transcriptional (epigenetic) and non-transcriptional RARα (RARA) functions...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893964/aneuploidy-in-cancer-and-aging
#15
Ryan M Naylor, Jan M van Deursen
Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs cellular fitness and prevents neoplastic transformation. Here, we suggest a new perspective to reconcile this apparent paradox and share an unexpected link between aneuploidy and aging that was discovered through attempts to investigate the CIN-cancer relationship...
November 23, 2016: Annual Review of Genetics
https://www.readbyqxmd.com/read/27892457/amplification-of-usp13-drives-ovarian-cancer-metabolism
#16
Cecil Han, Lifeng Yang, Hyun Ho Choi, Joelle Baddour, Abhinav Achreja, Yunhua Liu, Yujing Li, Jiada Li, Guohui Wan, Cheng Huang, Guang Ji, Xinna Zhang, Deepak Nagrath, Xiongbin Lu
Dysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27891063/cell-division-cycle-7-kinase-inhibitor-pha-767491-hydrochloride-suppresses-glioblastoma-growth-and-invasiveness
#17
Zubeyde Erbayraktar, Begum Alural, Resat Serhat Erbayraktar, Erdogan Pekcan Erkan
BACKGROUND: Genomic instability is a hallmark of cancer cells, and this cellular phenomenon can emerge as a result of replicative stress. It is possible to take advantage of replicative stress, and enhance it in a targeted way to fight cancer cells. One of such strategies involves targeting the cell division cycle 7-related protein kinase (CDC7), a protein with key roles in regulation of initiation of DNA replication. CDC7 overexpression is present in different cancers, and small molecule inhibitors of the CDC7 have well-documented anti-tumor effects...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27889665/a-three-dimensional-spheroidal-cancer-model-based-on-peg-fibrinogen-hydrogel-microspheres
#18
Shantanu Pradhan, Jacob M Clary, Dror Seliktar, Elizabeth A Lipke
Three-dimensional (3D) in vitro cancer models offer an attractive approach towards the investigation of tumorigenic phenomena and other cancer studies by providing dimensional context and higher degree of physiological relevance than that offered by conventional two-dimensional (2D) models. The multicellular tumor spheroid model, formed by cell aggregation, is considered to be the "gold standard" for 3D cancer models, due to its ease and simplicity of use. Although better than 2D models, tumor spheroids are unable to replicate key features of the native tumor microenvironment, particularly due to a lack of surrounding extracellular matrix components and heterogeneity in shape, size and aggregate forming tendencies...
November 1, 2016: Biomaterials
https://www.readbyqxmd.com/read/27889645/suppression-of-tumor-growth-and-muscle-wasting-in-a-transgenic-mouse-model-of-pancreatic-cancer-by-the-novel-histone-deacetylase-inhibitor-ar-42
#19
Sally E Henderson, Li-Yun Ding, Xiaokui Mo, Tanios Bekaii-Saab, Samuel K Kulp, Ching-Shih Chen, Po-Hsien Huang
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. This study was aimed at evaluating the efficacy of AR-42 (formerly OSU-HDAC42), a novel histone deacetylase (HDAC) inhibitor currently in clinical trials, in suppressing tumor growth and/or cancer-induced muscle wasting in murine models of PDAC. EXPERIMENTAL DESIGN: The in vitro antiproliferative activity of AR-42 was evaluated in six human pancreatic cancer cell lines (AsPC-1, COLO-357, PANC-1, MiaPaCa-2, BxPC-3, SW1990)...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27887848/simvastatin-inhibits-tumor-angiogenesis-in-her2-overexpressing-human-colorectal-cancer
#20
Gang Li, Junhua Zheng, Bin Xu, Jie Ling, Wei Qiu, Yongbing Wang
Overexpression of the HER2 oncogene contributes to tumor angiogenesis, which is an essential hallmark of cancer. Simvastatin has been reported to exhibit antitumor activities in several cancers; however, its roles and molecular mechanismsin the regulation of colorectal angiogenesis remain to be clarified. Here, we show that colon cancer cells express high levels of VEGF, total HER2 and phosphorylated HER2, and simvastatin apparently decreased their expression in HER2-overexpressing colon cancer cells. Simvastatin pretreatment reduced endothelial tube formation in vitro and microvessel density in vivo...
November 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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