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Stratified medicine in cancer

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https://www.readbyqxmd.com/read/27902695/text-mining-genotype-phenotype-relationships-from-biomedical-literature-for-database-curation-and-precision-medicine
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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%)...
October 24, 2016: Cancer
https://www.readbyqxmd.com/read/27775669/towards-stratified-medicine-in-plasma-cell-myeloma
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27598680/challenges-in-molecular-testing-in-non-small-cell-lung-cancer-patients-with-advanced-disease
#12
REVIEW
Crispin T Hiley, John Le Quesne, George Santis, Rowena Sharpe, David Gonzalez de Castro, Gary Middleton, Charles Swanton
Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1...
September 3, 2016: Lancet
https://www.readbyqxmd.com/read/27569656/siah-and-egfr-two-ras-pathway-biomarkers-are-highly-prognostic-in-locally-advanced-and-metastatic-breast-cancer
#13
Lauren L Siewertsz van Reesema, Vasilena Zheleva, Janet S Winston, Rick J Jansen, Carolyn F O'Connor, Andrew J Isbell, Minglei Bian, Rui Qin, Patricia T Bassett, Virginia J Hinson, Kimberly A Dorsch, Brad W Kirby, Robert E Van Sciver, Angela M Tang-Tan, Elizabeth A Harden, David Z Chang, Cynthia A Allen, Roger R Perry, Richard A Hoefer, Amy H Tang
BACKGROUND: Metastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS "pathway" activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine...
September 2016: EBioMedicine
https://www.readbyqxmd.com/read/27563824/pediatric-hodgkin-lymphoma-biomarkers-drugs-and-clinical-trials-for-translational-science-and-medicine
#14
Poonam Nagpal, Mohamed R Akl, Nehad M Ayoub, Tatsunari Tomiyama, Tasheka Cousins, Betty Tai, Nicole Carroll, Themba Nyrenda, Pritish Bhattacharyya, Michael B Harris, Andre Goy, Andrew Pecora, K Stephen Suh
Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-κB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF-κB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging...
August 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27490113/modeling-the-prevention-of-colorectal-cancer-from-the-combined-impact-of-host-and-behavioral-risk-factors
#15
Matthew Frampton, Richard S Houlston
PURPOSE: This study investigated the utility of modeling modifiable lifestyle risk factors in addition to genetic variation in colorectal cancer (CRC) screening/prevention. METHODS: We derived a polygenic risk score for CRC susceptibility variants in combination with the established nongenetic risk factors of inflammatory bowel disease (IBD), adiposity, alcohol, red meat, fruit, vegetables, smoking, physical activity, and aspirin. We used the 37 known risk variants and 50 and 100% of all risk variants as calculated from a heritability estimate...
August 4, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/27487002/association-between-x-ray-repair-cross-complementing-group-1-arg399gln-polymorphism-and-cervical-cancer-risk-a-meta-analysis-in-the-chinese-population
#16
Fang Zhang, Bing Li, Hong-Yan Wu, Li-Xin Shang
BACKGROUND: Many studies have examined the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with cervical cancer susceptibility. However, the results of these studies are inconsistent. To further assess the effects of XRCC1 Arg399Gln polymorphism on the risk of cervical cancer in the Chinese population, a meta-analysis was performed. METHODS: Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through December 2015...
August 4, 2016: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/27460935/stratified-precision-or-personalised-medicine-cancer-services-in-the-real-world-of-a-london-hospital
#17
Sophie Day, R Charles Coombes, Louise McGrath-Lone, Claudia Schoenborn, Helen Ward
We conducted ethnographic research in collaboration with a large, research-intensive London breast cancer service in 2013-2014 so as to understand the practices and potential effects of stratified medicine. Stratified medicine is often seen as a synonym for both personalised and precision medicine but these three terms, we found, also related to distinct facets of treatment and care. Personalised medicine is the term adopted for the developing 2016 NHS England Strategy, in which breast cancer care is considered a prime example of improved biological precision and better patient outcomes...
July 27, 2016: Sociology of Health & Illness
https://www.readbyqxmd.com/read/27401887/cost-effectiveness-analysis-of-using-loss-of-heterozygosity-to-manage-premalignant-oral-dysplasia-in-british-columbia-canada
#18
Ian Cromwell, Dean A Regier, Stuart J Peacock, Catherine F Poh
BACKGROUND: Management of low-grade oral dysplasias (LGDs) is complicated, as only a small percentage of lesions will progress to invasive disease. The current standard of care requires patients to undergo regular monitoring of their lesions, with intervention occurring as a response to meaningful clinical changes. Recent improvements in molecular technologies and understanding of the biology of LGDs may allow clinicians to manage lesions based on their genome-guided risk. METHODS: We used a decision-analytic Markov model to estimate the cost-effectiveness of risk-stratified care using a genomic assay...
September 2016: Oncologist
https://www.readbyqxmd.com/read/27401439/bridging-the-etiologic-and-prognostic-outlooks-in-individualized-assessment-of-absolute-risk-of-an-illness-application-in-lung-cancer
#19
Igor Karp, Marie-Pierre Sylvestre, Michal Abrahamowicz, Karen Leffondré, Jack Siemiatycki
Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996-2001...
July 11, 2016: European Journal of Epidemiology
https://www.readbyqxmd.com/read/27392550/paper-based-survivorship-care-plans-may-be-less-helpful-for-cancer-patients-who-search-for-disease-related-information-on-the-internet-results-of-the-registrationsystem-oncological-gynecology-rogy-care-randomized-trial
#20
Kim Ah Nicolaije, Nicole Pm Ezendam, Johanna Ma Pijnenborg, Dorry Boll, Maria Caroline Vos, Roy Fpm Kruitwagen, Lonneke V van de Poll-Franse
BACKGROUND: The Institute of Medicine recommends Survivorship Care Plans (SCPs) for all cancer survivors. However, it is unclear whether certain patient groups may or may not benefit from SCPs. OBJECTIVE: The aim was to assess whether the effects of an automatically generated paper SCP on patients' satisfaction with information provision and care, illness perceptions, and health care utilization were moderated by disease-related Internet use. METHODS: Twelve hospitals were randomized to either SCP care or usual care in the pragmatic cluster randomized Registrationsystem Oncological GYnecology (ROGY) Care trial...
2016: Journal of Medical Internet Research
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