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Stratified medicine in cancer

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https://www.readbyqxmd.com/read/28075351/circulating-nucleosomes-and-nucleosome-modifications-as-biomarkers-in-cancer
#1
REVIEW
Peter McAnena, James A L Brown, Michael J Kerin
Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment...
January 8, 2017: Cancers
https://www.readbyqxmd.com/read/28034454/comprehensive-genomic-sequencing-and-the-molecular-profiles-of-clinically-advanced-breast-cancer
#2
Jeffrey S Ross, Laurie M Gay
Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events...
December 26, 2016: Pathology
https://www.readbyqxmd.com/read/27998972/looking-beyond-drivers-and-passengers-in-cancer-genome-sequencing-data
#3
REVIEW
S De, S Ganesan
Cancer arises as a result of acquired changes in the DNA sequence of the genome of somatic cells. A subset of the genetic changes, dubbed driver mutations, propels tumor growth, and the remaining changes are passengers, apparently inconsequential for neoplastic transformation. Massive genome sequencing of thousands of tumors from all major cancer types has enabled cataloging of the so-called driver and passenger mutations, and facilitated molecular classification of cancer, guiding precision medicine approach for the patients...
December 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27975130/does-alcohol-consumption-modify-the-risk-of-endometrial-cancer-a-dose-response-meta-analysis-of-prospective-studies
#4
Quan Zhou, Peng Guo, Hui Li, Xiao-Dan Chen
BACKGROUND: Epidemiological studies have provided controversial evidence of an association between alcohol intake and endometrial cancer (EC) risk. The World Cancer Research Fund/American Institute for Cancer Research classifies alcohol as having a "limited-no conclusion" grade of evidence in the Endometrial Cancer 2013 Report (the latest version). OBJECTIVE: The purpose of this meta-analysis is to systematically analyze the effect of alcohol intake on EC risk. METHODS: We conducted a dose-response meta-analysis of prospective cohort studies identified from the PubMed, Embase, Cochrane Library and China Biological Medicine databases...
December 14, 2016: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/27943255/self-reported-physical-activity-levels-of-older-cancer-survivors-results-from-the-2014-national-health-interview-survey
#5
Yelena Tarasenko, Chen Chen, Nancy Schoenberg
OBJECTIVES: To examine adherence to the American College of Sports Medicine and American Cancer Society guidelines on leisure-time aerobic and muscle-strengthening physical activity (PA) of older cancer survivors. DESIGN: Cross-sectional study based on the 2014 National Health Interview Survey. SETTING: United States. PARTICIPANTS: Young-old (65-74) (n = 627), old-old (≥75) (n = 656), and middle-aged (45-64) (n = 786) cancer survivors and adults without cancer (n = 18,369), stratified according to the same age groups...
December 9, 2016: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/27936622/dna-adducts-from-anticancer-drugs-as-candidate-predictive-markers-for-precision-medicine
#6
Alessia Stornetta, Maike Zimmermann, George D Cimino, Paul T Henderson, Shana J Sturla
Biomarker-driven drug selection plays a central role in cancer drug discovery and development, and in diagnostic strategies to improve the use of traditional chemotherapeutic drugs. DNA-modifying anticancer drugs are still used as first line medication, but drawbacks such as resistance and side effects remain an issue. Monitoring the formation and level of DNA modifications induced by anticancer drugs is a potential strategy for stratifying patients and predicting drug efficacy. In this perspective, preclinical and clinical data concerning the relationship between drug-induced DNA adducts and biological response for platinum drugs and combination therapies, nitrogen mustards and half-mustards, hypoxia-activated drugs, reductase-activated drugs, and minor groove binding agents are presented and discussed...
January 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27933213/molecular-pathology-of-cancer-how-to-communicate-with-disease
#7
REVIEW
Peter Birner, Gerald Prager, Berthold Streubel
: Recent technical advances have brought insights into the biology of cancer in human, establishing it as a disease driven by genetic mutations. Beside inherited family tumour syndromes caused by germline mutations, somatic genetic alterations occur early in tumourigenesis, which accumulate during the progression of the disease and its treatment. Based on these observations, medical oncology has started to enter an era of stratified medicine, where treatment selection is becoming tailored to drugable molecular pathways...
2016: ESMO Open
https://www.readbyqxmd.com/read/27925421/reducing-the-incidence-of-hospital-associated-venous-thromboembolism-within-a-network-of-academic-hospitals-findings-from-five-university-of-california-medical-centers
#8
REVIEW
Ian H Jenkins, Richard H White, Alpesh N Amin, Nasim Afsarmanesh, Andrew D Auerbach, Raman Khanna, Gregory A Maynard
BACKGROUND: Almost 700 patients suffered from hospital-associated venous thromboembolism (HA-VTE) across 5 University of California hospitals in calendar year 2011. OBJECTIVE: Optimize venous thromboembolism (VTE) prophylaxis (VTEP) in adult medical/surgical inpatients and reduce HA-VTE by at least 20% within 3 years. DESIGN: Prospective, unblinded, open-intervention study with historical controls. SETTING: Five independent but cooperating academic hospitals...
December 2016: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
https://www.readbyqxmd.com/read/27924449/translation-and-adaptation-of-skin-cancer-genomic-risk-education-materials-for-implementation-in-primary-care
#9
Vivian M Rodríguez, Erika Robers, Kate Zielaskowski, C Javier González, Keith Hunley, Kimberly A Kaphingst, Dolores D Guest, Andrew Sussman, Kirsten A Meyer White, Matthew R Schwartz, Jennie Greb, Yvonne Talamantes, Jessica Bigney, Marianne Berwick, Jennifer L Hay
Genomic medicine has revolutionized disease risk identification and subsequent risk reduction interventions. Skin cancer risk genomic feedback is a promising vehicle to raise awareness and protective behaviors in the general population, including Hispanics who are largely unaware of their risks. Yet, personalized genomics currently has limited reach. This study is the initial phase of a randomized controlled trial investigating the personal utility and reach of genomic testing and feedback for melanoma. Semi-structured cognitive interviews (N = 28), stratified across education level, were conducted to assess the comprehension and acceptability of translated skin cancer genomic risk education materials with Spanish-speaking Hispanic primary care patients...
December 6, 2016: Journal of Community Genetics
https://www.readbyqxmd.com/read/27902695/text-mining-genotype-phenotype-relationships-from-biomedical-literature-for-database-curation-and-precision-medicine
#10
Ayush Singhal, Michael Simmons, Zhiyong Lu
The practice of precision medicine will ultimately require databases of genes and mutations for healthcare providers to reference in order to understand the clinical implications of each patient's genetic makeup. Although the highest quality databases require manual curation, text mining tools can facilitate the curation process, increasing accuracy, coverage, and productivity. However, to date there are no available text mining tools that offer high-accuracy performance for extracting such triplets from biomedical literature...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27862181/identification-of-biomarker-by-treatment-interactions-in-randomized-clinical-trials-with-survival-outcomes-and-high-dimensional-spaces
#11
Nils Ternès, Federico Rotolo, Georg Heinze, Stefan Michiels
Stratified medicine seeks to identify biomarkers or parsimonious gene signatures distinguishing patients that will benefit most from a targeted treatment. We evaluated 12 approaches in high-dimensional Cox models in randomized clinical trials: penalization of the biomarker main effects and biomarker-by-treatment interactions (full-lasso, three kinds of adaptive lasso, ridge+lasso and group-lasso); dimensionality reduction of the main effect matrix via linear combinations (PCA+lasso (where PCA is principal components analysis) or PLS+lasso (where PLS is partial least squares)); penalization of modified covariates or of the arm-specific biomarker effects (two-I model); gradient boosting; and univariate approach with control of multiple testing...
November 15, 2016: Biometrical Journal. Biometrische Zeitschrift
https://www.readbyqxmd.com/read/27846280/development-and-application-of-a-microfluidics-based-panel-in-the-basal-luminal-transcriptional-characterization-of-archival-bladder-cancers
#12
Doris Kim, YounJeong Choi, James Ireland, Oded Foreman, Rachel N Tam, Rajesh Patel, Erica B Schleifman, Maipelo Motlhabi, Dorothy French, Cheryl V Wong, Eric Peters, Luciana Molinero, Rajiv Raja, Lukas C Amler, Garret M Hampton, Mark R Lackner, Omar Kabbarah
In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes...
2016: PloS One
https://www.readbyqxmd.com/read/27837553/biobanking-an-important-resource-for-precision-medicine-in-glioblastoma
#13
Si Yan Melanie Tan, Edwin Sandanaraj, Carol Tang, Beng Ti Christopher Ang
The Cancer Genome Atlas effort has generated significant interest in a new paradigm shift in tumor tissue analysis, patient diagnosis and subsequent treatment decision. Findings have highlighted the limitation of sole reliance on histology, which can be confounded by inter-observer variability. Such studies demonstrate that histologically similar grade IV brain tumors can be divided into four molecular subtypes based on gene expression, with each subtype demonstrating unique genomic aberrations and clinical outcome...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27819294/big-genomics-and-clinical-data-analytics-strategies-for-precision-cancer-prognosis
#14
Ghim Siong Ow, Vladimir A Kuznetsov
The field of personalized and precise medicine in the era of big data analytics is growing rapidly. Previously, we proposed our model of patient classification termed Prognostic Signature Vector Matching (PSVM) and identified a 37 variable signature comprising 36 let-7b associated prognostic significant mRNAs and the age risk factor that stratified large high-grade serous ovarian cancer patient cohorts into three survival-significant risk groups. Here, we investigated the predictive performance of PSVM via optimization of the prognostic variable weights, which represent the relative importance of one prognostic variable over the others...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27814611/targeted-drugs-and-diagnostic-assays-companions-in-the-race-to-combat-ethnic-disparity
#15
Nikita Wright, Padmashree Rida, Uma Krishnamurti, Xiaoxian Li, Ritu Aneja
African Americans (AAs) are more likely than European Americans to develop aggressive breast cancer subtypes, and have higher recurrence and mortality rates; this results in a stark breast-cancer related ethnic disparity in clinical outcomes. In this era of personalized oncology, companion diagnostics (CDx) are transforming the cancer treatment narrative slowly but steadily, by enabling the use of safety and/or efficacy biomarkers to stratify patient populations, and thus ensuring more effective deployment of targeted therapeutics...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27793177/approaches-to-modernize-the-combination-drug-development-paradigm
#16
REVIEW
Daphne Day, Lillian L Siu
Recent advances in genomic sequencing and omics-based capabilities are uncovering tremendous therapeutic opportunities and rapidly transforming the field of cancer medicine. Molecularly targeted agents aim to exploit key tumor-specific vulnerabilities such as oncogenic or non-oncogenic addiction and synthetic lethality. Additionally, immunotherapies targeting the host immune system are proving to be another promising and complementary approach. Owing to substantial tumor genomic and immunologic complexities, combination strategies are likely to be required to adequately disrupt intricate molecular interactions and provide meaningful long-term benefit to patients...
October 28, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27775837/chemotherapy-decisions-and-patient-experience-with-the-recurrence-score-assay-for-early-stage-breast-cancer
#17
Christopher R Friese, Yun Li, Irina Bondarenko, Timothy P Hofer, Kevin C Ward, Ann S Hamilton, Dennis Deapen, Allison W Kurian, Steven J Katz
BACKGROUND: The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor-positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making. METHODS: This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%)...
January 1, 2017: Cancer
https://www.readbyqxmd.com/read/27775669/towards-stratified-medicine-in-plasma-cell-myeloma
#18
REVIEW
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27735926/experiences-from-a-pilot-program-bringing-brca1-2-genetic-screening-to-theus-ashkenazi-jewish-population
#19
Chana Wiesman, Esther Rose, Allison Grant, Adam Zimilover, Susan Klugman, Nicole Schreiber-Agus
PURPOSE: The notion of offering population-based screening to the Ashkenazi Jewish (AJ) population for the BRCA1/2 founder mutations continues to gain support. A program called the BRCAcommunity initiative was designed to identify the benefits and barriers associated with implementing this screening in a clinical setting. METHODS: Interested AJ individuals were stratified into high-risk (HR) and low-risk (LR) groups based on self-reported cancer histories. Those at HR were offered traditional genetic counseling/testing; those at LR were offered group genetic counseling and subsidized AJ BRCA founder mutation testing...
October 13, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27604327/new-initiatives-in-critical-care-distinguishing-hype-from-hope
#20
John L Moran, Patricia J Solomon
Recent viewpoints on critical care have expressed frustration at the slow development of new therapeutic agents and the failure of investigator-initiated trials. Several new directions have been proposed: personalised medicine and the embracing of "omic" technologies, resolving the heterogeneity of treatment effects, and adaptive trial designs. We examine these approaches in the context of analysis of randomised controlled trials (RCTs). The curse of treatment effect heterogeneity is found not only in critical care but also in cancer oncology...
September 2016: Critical Care and Resuscitation: Journal of the Australasian Academy of Critical Care Medicine
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