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https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#1
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28077296/extracellular-vesicle-communication-pathways-as-regulatory-targets-of-oncogenic-transformation
#2
REVIEW
Dongsic Choi, Tae Hoon Lee, Cristiana Spinelli, Shilpa Chennakrishnaiah, Esterina D'Asti, Janusz Rak
Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids...
January 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28060367/applications-of-molecular-testing-in-surgical-pathology-of-the-head-and-neck
#3
Jennifer L Hunt
Molecular testing in routine surgical pathology is becoming an important component of the workup of many different types of tumors. In fact, in some organ systems, guidelines now suggest that the standard of care is to obtain specific molecular panels for tumor classification and/or therapeutic planning. In the head and neck, clinically applicable molecular tests are not as abundant as in other organ systems. Most current head and neck biomarkers are utilized for diagnosis rather than as companion diagnostic tests to predict therapeutic response...
January 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28057616/rucaparib-approved-for-ovarian-cancer
#4
(no author information available yet)
The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test. The agency also gave a nod to the FoundationFocus CDxBRCA test to detect BRCA alterations.
January 5, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28044295/negative-enrichment-of-circulating-tumor-cells-in-blood-using-a-microfluidic-chip
#5
Hamizah A Cognart, Chia-Pin Chang
The enumeration and analysis of circulating tumor cells (CTCs) is an increasing interest for monitoring disease progression or response to treatment, specifically as a companion diagnostic for new anticancer drugs, and for research into the mechanisms of disease progression and metastases. Ideally, CTCs would be enriched from very small samples, with minimal handling, high recovery, and no requirement for the expression of specific surface markers. Here, we describe negative enrichment as the preferred approach for cancer cell isolation using a microfluidic platform...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28032602/detection-of-alk-rearrangements-in-lung-cancer-patients-using-a-homebrew-pcr-assay
#6
Hui Yu, JianHua Chang, Fang Liu, Qifeng Wang, YongMing Lu, ZhuanXu Zhang, Jiabing Shen, Qing Zhai, Xia Meng, Jialei Wang, Xun Ye
Lung cancer patients with anaplastic lymphoma kinase (ALK) rearrangements are candidates for targeted therapeutics. However, patients must be tested with a companion diagnostic assay to realize their ALK rearrangement status. We analyzed the publicly available E-GEOD-31210 microarray dataset and identified a non-coding RNA, sweyjawbu, which is strongly associated with ALK rearrangements. We validated these results using quantitative real-time PCR in an independent cohort consisting of 4 cell lines and 83 clinical samples...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/28000172/implementation-of-a-precision-pathology-program-focused-on-oncology-based-prognostic-and-predictive-outcomes
#7
Michael J Donovan, Carlos Cordon-Cardo
Personalized or precision medicine as a diagnostic and therapeutic paradigm was introduced some 10-15 years ago, with the advent of biomarker discovery as a mechanism for identifying prognostic and predictive attributes associated with treatment indication and outcome. While the concept is not new, the successful development and implementation of novel 'companion diagnostics', especially in oncology, continues to represent a significant challenge and is currently at the forefront of smart trial design and therapeutic choice...
December 20, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27993967/an-fda-perspective-on-the-regulatory-implications-of-complex-signatures-to-predict-response-to-targeted-therapies
#8
Julia A Beaver, Abraham Tzou, Gideon M Blumenthal, Amy E McKee, Geoffrey Kim, Richard Pazdur, Reena Philip
As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation...
December 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27993328/diagnostic-quality-assurance-pilot-a-model-to-demonstrate-comparative-laboratory-test-performance-with-an-oncology-companion-diagnostic-assay
#9
EDITORIAL
Barbara Zehnbauer, Catherine Lofton-Day, John Pfeifer, Elizabeth Shaughnessy, Lindee Goh
This Editorial highlights a model demonstrating laboratory test performance with a companion diagnostic assay.
January 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27978765/a-systematic-review-and-checklist-presenting-the-main-challenges-for-health-economic-modeling-in-personalized-medicine-towards-implementing-patient-level-models
#10
Koen Degeling, Hendrik Koffijberg, Maarten J IJzerman
The ongoing development of genomic medicine and the use of molecular and imaging markers in personalized medicine (PM) has arguably challenged the field of health economic modeling (HEM). This study aims to provide detailed insights into the current status of HEM in PM, in order to identify if and how modeling methods are used to address the challenges described in literature. Areas covered: A review was performed on studies that simulate health economic outcomes for personalized clinical pathways. Decision tree modeling and Markov modeling were the most observed methods...
December 27, 2016: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/27971045/overcoming-hta-hurdles-through-early-collaboration-between-pharmaceutical-companies-and-companion-diagnostic-companies
#11
J Gambari, P Senatore, B Oshinowo, P Armeni, S Duttagupta, M Chalmers
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27955717/environmental-scan-on-pharmaceuticals-requiring-companion-diagnostics
#12
Tara Cowling, Michel Boucher
OBJECTIVES: Companion diagnostic tests (CDx) are used to measure an individual's protein or gene expression (biomarkers) to inform choice of therapy. The increasing number of drugs requiring CDx poses challenges for regulatory and reimbursement policies. To better understand this issue, an environmental scan was conducted by the Canadian Agency for Drugs and Technologies in Health (CADTH). METHODS: The environmental scan was based on a focused literature search and feedback solicited from targeted stakeholders...
January 2016: International Journal of Technology Assessment in Health Care
https://www.readbyqxmd.com/read/27928132/improved-fret-biosensor-for-the-measurement-of-bcr-abl-activity-in-chronic-myeloid-leukemia-cells
#13
Mika Horiguchi, Mari Fujioka, Takeshi Kondo, Yoichiro Fujioka, Xinxin Li, Kosui Horiuchi, Aya O Satoh, Prabha Nepal, Shinya Nishide, Asuka Nanbo, Takanori Teshima, Yusuke Ohba
Although the co-development of companion diagnostics with molecular targeted drugs is desirable, truly efficient diagnostics are limited to diseases in which chromosomal translocations or overt mutations are clearly correlated with drug efficacy. Moreover, even for such diseases, few methods are available to predict whether drug administration is effective for each individual patient whose disease is expected to respond to the drug(s). We have previously developed a biosensor based on the principle of Förster resonance energy transfer (FRET) to measure the activity of the tyrosine kinase BCR-ABL and its response to drug treatment in patient-derived chronic myeloid leukemia cells...
December 8, 2016: Cell Structure and Function
https://www.readbyqxmd.com/read/27896765/blood-bio-sampling-procedures-for-multiplex-biomarkers-studies
#14
Paul C Guest, Hassan Rahmoune
A major challenge in single or panel of biomarker discovery and validation is the inherent biological complexity underlying disease heterogeneity and inconsistent responses to treatment. Moreover, the lack of standardization in the sampling, processing, and storage of biological fluids such as plasma and serum disrupts the discovery and validation of blood-based biomarker tests in preclinical and clinical settings. This chapter presents a reproducible sample collection and handling procedure that aims to enhance analyte stability and ensure compatibility with the corresponding multiplex biomarker profiling platforms...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27890448/vaccines-against-pseudorabies-virus-prv
#15
C M Freuling, T F Müller, T C Mettenleiter
Aujeszkýs disease (AD, pseudorabies) is a notifiable herpesvirus infection of pigs causing substantial economic losses to swine producers. AD in pigs is controlled by the use of vaccination with inactivated and attenuated live vaccines. Starting with classically attenuated live vaccines derived from low virulent field isolates, AD vaccination has pioneered novel strategies in animal disease control by the first use of genetically engineered live virus vaccines lacking virulence-determining genes, and the concept of DIVA, i...
November 18, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#16
Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27888307/monitoring-doxorubicin-cellular-uptake-and-trafficking-using-in-vitro-raman-microspectroscopy-short-and-long-time-exposure-effects-on-lung-cancer-cell-lines
#17
Zeineb Farhane, Franck Bonnier, Hugh J Byrne
Raman microspectroscopy is a non-invasive, in vitro analytical tool which is being increasingly explored for its potential in clinical applications and monitoring the uptake, mechanism of action and cellular interaction at a molecular level of chemotherapeutic drugs, ultimately as a potential label-free preclinical screening and companion diagnostic tool. In this study, doxorubicin (DOX), a "gold standard" chemotherapeutic drug, is employed as a model in the in vitro lung cancer cell line A549 in order to demonstrate the potential of Raman microspectroscopy to screen and identify spectroscopic markers of its trafficking and mechanism of action...
November 25, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27886248/ultrasensitive-rapid-and-inexpensive-detection-of-dna-using-paper-based-lateral-flow-assay
#18
Miriam Jauset-Rubio, Markéta Svobodová, Teresa Mairal, Calum McNeil, Neil Keegan, Ayman Saeed, Mohammad Nooredeen Abbas, Mohammad S El-Shahawi, Abdulaziz S Bashammakh, Abdulrahman O Alyoubi, Ciara K O Sullivan
Sensitive, specific, rapid, inexpensive and easy-to-use nucleic acid tests for use at the point-of-need are critical for the emerging field of personalised medicine for which companion diagnostics are essential, as well as for application in low resource settings. Here we report on the development of a point-of-care nucleic acid lateral flow test for the direct detection of isothermally amplified DNA. The recombinase polymerase amplification method is modified slightly to use tailed primers, resulting in an amplicon with a duplex flanked by two single stranded DNA tails...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27849442/to-genotype-or-phenotype-for-personalized-medicine-cyp450-drug-metabolizing-enzyme-genotype-phenotype-concordance-and-discordance-in-the-ecuadorian-population
#19
Fernando De Andrés, Santiago Terán, Francisco Hernández, Enrique Terán, Adrián LLerena
Genetic variations within the cytochrome P450 (CYP450) superfamily of drug metabolizing enzymes confer substantial person-to-person and between-population differences in pharmacokinetics, and by extension, highly variable clinical effects of medicines. In this context, "personalized medicine," "precision medicine," and "stratified medicine" are related concepts attributed to what is essentially targeted therapeutics and companion diagnostics, aimed at improving safety and effectiveness of health interventions...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27843626/tumour-and-cellular-distribution-of-activated-forms-of-pr-in-breast-cancers-a-novel-immunohistochemical-analysis-of-a-large-clinical-cohort
#20
Jacques Bonneterre, Jacques Bosq, Philippe Jamme, Alexander Valent, Erard M Gilles, Alexander A Zukiwski, Suzanne A W Fuqua, Carol A Lange, Joyce O'Shaughnessy
BACKGROUND: The progesterone receptor (PR) is expressed by ∼70% of early breast tumours and is implicated in the progression of breast cancer. In cancerous tissues PR may be activated in the absence of a ligand, or when ligand concentrations are very low, resulting in aberrantly activated PR (APR). The presence of APR may indicate that patients with breast cancer are more likely to respond to antiprogestins. The aims of this study were to describe and classify the histological subnuclear morphology of active and inactive PR in archival breast cancer samples...
2016: ESMO Open
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