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Cancer genetics

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https://www.readbyqxmd.com/read/28822237/beyond-genomics-targeting-the-epigenome-in-diffuse-large-b-cell-lymphoma
#1
REVIEW
Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced...
August 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28822109/consumer-attitudes-towards-the-establishment-of-a-national-australian-familial-cancer-research-database-by-the-inherited-cancer-connect-iccon-partnership
#2
Laura Forrest, Gillian Mitchell, Letitia Thrupp, Lara Petelin, Kate Richardson, Lyon Mascarenhas, Mary-Anne Young
Clinical genetics units hold large amounts of information which could be utilised to benefit patients and their families. In Australia, a national research database, the Inherited Cancer Connect (ICCon) database, is being established that comprises clinical genetic data held for all carriers of mutations in cancer predisposition genes. Consumer input was sought to establish the acceptability of the inclusion of clinical genetic data into a research database. A qualitative approach using a modified nominal group technique was used to collect data through consumer forums conducted in three Australian states...
August 18, 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#3
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28821810/extracting-intercellular-signaling-network-of-cancer-tissues-using-ligand-receptor-expression-patterns-from-whole-tumor-and-single-cell-transcriptomes
#4
Joseph X Zhou, Roberto Taramelli, Edoardo Pedrini, Theo Knijnenburg, Sui Huang
Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of the cell community which forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on intercellular communication between cancer cells themselves and between cancer-stromal cells by secreted signaling molecules (ligands) and their cognate receptors. We analyzed public cancer transcriptome database for changes in cell-cell interactions as the characteristic of malignancy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821750/rap1-and-cdc13-have-complementary-roles-in-preventing-exonucleolytic-degradation-of-telomere-5-ends
#5
Rikard Runnberg, Saishyam Narayanan, Marita Cohn
Telomere DNA ends with a single-stranded 3' overhang. Long 3' overhangs may cause aberrant DNA damage responses and accelerate telomere attrition, which is associated with cancer and aging, respectively. Genetic studies have indicated several important players in preventing 5' end hyper-resection, yet detailed knowledge about the molecular mechanism in which they act is still lacking. Here, we use an in vitro DNA 5' end protection assay, to study how N. castellii Cdc13 and Rap1 protect against 5' exonucleolytic degradation by λ-exonuclease...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821592/global-analysis-of-gene-expression-in-response-to-whole-chromosome-aneuploidy-in-hexaploid-wheat
#6
Ai Zhang, Ning Li, Lei Gong, Xiaowan Gou, Bin Wang, Xin Deng, Changping Li, Qianli Dong, Huakun Zhang, Bao Liu
Aneuploidy, a condition of unbalanced chromosome content, represents a large-effect mutation that bears significant relevancy to human health and microbe adaptation. As such, extensive studies of aneuploidy have been conducted in unicellular model organisms and cancer cells. Aneuploidy also frequently is associated with plant polyploidization, but its impact on gene expression and relevance to polyploid genome evolution/functional innovation remain largely unknown. Here, we used a panel of diverse types of whole-chromosome aneuploidy of hexaploid wheat, all under the common genetic background of cv...
August 18, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28821558/defective-cyclin-b1-induction-in-trastuzumab-emtansine-t-dm1-acquired-resistance-in-her2-positive-breast-cancer
#7
MohammadA Sabbaghi, Gabriel Gil-Gómez, Cristina Guardia, Sonia Servitja, Oriol Arpi, Sara García-Alonso, Silvia Menéndez, Montserrat Arumi-Uria, Laia Serrano, Marta Salido, Aura Muntasell, Maria Martinez-Garcia, Sandra Zazo, Cristina Chamizo, Paula González-Alonso, Juan Madoz-Gúrpide, Pilar Eroles, Joaquin Arribas, Ignasi Tusquets, Ana Lluch, Atanasio Pandiella, Federico Rojo, Ana Rovira, Joan Albanell
Purpose: Trastuzumab-emtansine (T-DM1) is a standard treatment in advanced HER2 positive breast cancer. However, resistance inevitably occurs. We aimed to identify mechanisms of acquired T-DM1 resistance. <p>Experimental Design: HER2-positive breast cancer cells (HCC1954, HCC1419, SKBR3 and BT474) were treated in a pulse-fashion with T-DM1 to induce a resistant phenotype. Cellular and molecular effects of T-DM1 in parental versus resistant cells were compared. CDK1 kinase activity and cyclin B1 expression were assayed under various conditions...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821557/selected-alkylating-agents-can-overcome-drug-tolerance-of-g0-like-tumor-cells-and-eradicate-brca1-deficient-mammary-tumors-in-mice
#8
Marina Pajic, Sohvi Blatter, Charlotte Guyader, Maaike Gonggrijp, Ariena Kersbergen, Aslı Küçükosmanoğlu, Wendy Sol, Rinske Drost, Jos Jonkers, Piet Borst, Sven Rottenberg
We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.<br /><br />Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Due to the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore no BRCA1-dependent acquired resistance occurs. To characterize the cell cycle stage from which Brca1(-/-);p53(-/-) mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell cycle indicator (FUCCI) construct into the tumor cells...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28820644/national-estimates-of-genetic-testing-in-women-with-a-history-of-breast-or-ovarian-cancer
#9
Christopher P Childers, Kimberly K Childers, Melinda Maggard-Gibbons, James Macinko
Purpose In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria. Methods We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey...
August 18, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28819856/fiber-optic-array-scanning-technology-fast-for-detection-and-molecular-characterization-of-circulating-tumor-cells
#10
Zheng Ao, Xiaohe Liu
Circulating tumor cell (CTC) as an important component in "liquid biopsy" holds crucial clinical relevance in cancer prognosis, treatment efficiency evaluation, prediction and potentially early detection. Here, we present a Fiber-optic Array Scanning Technology (FAST) that enables antigen-agnostic, size-agnostic detection of CTC. By immunofluorescence staining detection of a combination of a panel of markers, FAST technology can be applied to detect rare CTC in non-small cell lung cancer (NSCLC) setting with high sensitivity and specificity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28819846/filter-adapted-fluorescent-in-situ-hybridization-fa-fish-for-filtration-enriched-circulating-tumor-cells
#11
Marianne Oulhen, Emma Pailler, Vincent Faugeroux, Françoise Farace
Circulating tumor cells (CTCs) may represent an easily accessible source of tumor material to assess genetic aberrations such as gene-rearrangements or gene-amplifications and screen cancer patients eligible for targeted therapies. As the number of CTCs is a critical parameter to identify such biomarkers, we developed fluorescent in situ hybridization (FISH) for CTCs enriched on filters (filter-adapted-FISH, FA-FISH). Here, we describe the FA-FISH protocol, the combination of immunofluorescent staining (DAPI/CD45) and FA-FISH techniques, as well as the semi-automated microscopy method that we developed to improve the feasibility and reliability of FISH analyses in filtration-enriched CTC...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28819444/association-of-hla-drb1-hla-dqb1-polymorphisms-with-hpv-16-e6-variants-among-young-cervical-cancer-patients-in-china
#12
Yan Hu, Jin-Ze Wu, Hua Zhu, Sheng-Hui Zhang, Yan-Ying Zhu, Yi-Yao Wu, Ci-Xia Shuai
Potential correlation of human papillomavirus (HPV) 16 E6 variants and human leukocyte antigen (HLA) class II polymorphisms has been suggested in patients with cervical cancer, so far little information is available about the possible interaction between E6 variants and HLA class II variability during the obviously accelerated progression to cervical cancer in young women. In this study, we aimed to explore the association between the HPV16 E6 variants and HLA-DRB1, DQB1 alleles in a Chinese young cervical cancer population...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819441/vsv-based-virotherapy-in-ovarian-cancer-the-past-the-present-and-%C3%A2-future
#13
REVIEW
Beata Urszula Orzechowska, Marcin Jędryka, Katarzyna Zwolińska, Rafał Matkowski
The standard approach to treating patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery remains taxane and platinum-based chemotherapy. Despite treatment with this strategy, the vast majority of patients relapse and develop drug-resistant metastatic disease that may be driven by cancer stem cells (CSCs) or cancer initiating cells (CICs). Oncolytic viruses circumvent typical drug-resistance mechanisms, therefore they may provide a safe and effective alternative treatment for chemotherapy-resistant CSCs/CICs...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819408/opposite-effects-of-set7-9-on-apoptosis-of-human-acute-myeloid-leukemia-cells-and-lung-cancer-cells
#14
Ye Gu, Yuan Wang, Xinling Wang, Lili Gao, Weiping Yu, Wei-Feng Dong
SET7/9 is a protein lysine methyltransferases (PLMTs or PKMTs) which methylates both histone H3K4 and non-histone proteins including transcriptional factors, tumor suppressors, and membrane-associated receptors. Methylation of these proteins alters protein activity and leads to changes in cellular behavior and a series of biological processes. This study aims to investigate the role of SET7/9 in human acute myeloid leukemia (AML) and non-small-cell lung cancer (NSCLC). We examined the expression of SET7/9 in AML cells and NSCLC cells and detected the methylation status of the SET7/9 promoter region...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819158/discovering-condition-specific-gene-co-expression-patterns-using-gaussian-mixture-models-a-cancer-case-study
#15
Stephen P Ficklin, Leland J Dunwoodie, William L Poehlman, Christopher Watson, Kimberly E Roche, F Alex Feltus
A gene co-expression network (GCN) describes associations between genes and points to genetic coordination of biochemical pathways. However, genetic correlations in a GCN are only detectable if they are present in the sampled conditions. With the increasing quantity of gene expression samples available in public repositories, there is greater potential for discovery of genetic correlations from a variety of biologically interesting conditions. However, even if gene correlations are present, their discovery can be masked by noise...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818953/new-horizons-for-precision-medicine-in-biliary-tract-cancers
#16
REVIEW
Juan W Valle, Angela Lamarca, Lipika Goyal, Jorge Barriuso, Andrew X Zhu
Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e...
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#17
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28818333/li-fraumeni-syndrome-disease-model-a-platform-to-develop-precision-cancer-therapy-targeting-oncogenic-p53
#18
REVIEW
Ruoji Zhou, An Xu, Julian Gingold, Louise C Strong, Ruiying Zhao, Dung-Fang Lee
Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder. Germline mutations in TP53, the gene encoding p53, are responsible for most cases of LFS. TP53 is also the most commonly mutated gene in human cancers. Because inhibition of mutant p53 is considered to be a promising therapeutic strategy to treat these diseases, LFS provides a perfect genetic model to study p53 mutation-associated malignancies as well as to screen potential compounds targeting oncogenic p53. In this review we briefly summarize the biology of LFS and current understanding of the oncogenic functions of mutant p53 in cancer development...
August 14, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28818315/screening-for-familial-cancer-risk-focus-on-breast-cancer
#19
REVIEW
Christine Rousset-Jablonski, Anne Gompel
A breast or an ovarian cancer occurring at a young age and/or in a family where other cases preexist suggests that those patients should be candidates for screening for mutations. Despite decades of medical research, less than 30% of cases with a suggestive personal and/or family history of hereditary breast cancer have an identified causative gene mutation. The vast majority of these cases are due to a mutation in one of the highly penetrant breast cancer genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11) and various guidelines direct the management of these patients...
August 7, 2017: Maturitas
https://www.readbyqxmd.com/read/28817827/role-of-next-generation-sequencing-as-a-diagnostic-tool-for-the-evaluation-of-bone-and-soft-tissue-tumors
#20
Kinga Szurian, Karl Kashofer, Bernadette Liegl-Atzwanger
Bone and soft-tissue tumors are in general rare. Diagnosing these tumors is challenging based on the significant number of different tumor entities, the rareness of these tumors, and the considerable morphological heterogeneity which can be found within a single tumor entity. Considering that more than half of the described soft-tissue tumors and approximately 25% of the bone tumors harbor recurrent genetic alterations, the use of auxiliary molecular examinations should be strongly considered. Molecular analyses are important to confirm the diagnosis, to guide treatment, to provide information about prognosis, and to allow patient recruitment for basket trials based on the molecular signature of a tumor...
August 18, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
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