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https://www.readbyqxmd.com/read/28615231/single-nucleotide-polymorphism-leading-to-false-allelic-fraction-by-droplet-digital-pcr
#1
Eric S Christenson, William B Dalton, David Chu, Ian Waters, Karen Cravero, Daniel J Zabransky, Amy DeZern, Ben Ho Park
BACKGROUND: Molecular-based diagnostics have great utility for cancer detection. We have used droplet digital PCR (ddPCR) as a platform for identifying mutations in circulating plasma tumor DNA (ptDNA). We present the unexpected finding of a spurious mutant allele fraction that was discovered to be artifactual because of the presence of a single-nucleotide polymorphism (SNP) in a patient sample. DESIGN AND METHODS: Probe and primer combinations for the K700 and V701 loci of the SF3B1 spliceosome gene were designed for ddPCR to identify the percentage of mutant and wild-type alleles...
June 14, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28609695/what-do-we-need-to-make-circulating-tumour-dna-ctdna-a-routine-diagnostic-test-in-lung-cancer
#2
REVIEW
Reyes Bernabé, Nicholas Hickson, Andrew Wallace, Fiona Helen Blackhall
The gold standard test for detection of epidermal growth factor receptor (EGFR) mutation is to genotype somatic DNA extracted from a tissue biopsy or cytology specimen. Yet, in at least 20% of patients this is not possible for various reasons including insufficient availability of neoplastic tissue, lack of fitness of the available tissue for a biopsy or that a biopsy is not technically feasible. Consequently, there has been intense investigation of circulating tumour DNA (ctDNA), released into the plasma fraction of blood from cancer cells during apoptosis/necrosis, as a minimally invasive 'liquid biopsy' and surrogate for cancer tissue...
June 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28607584/a-combined-ulbp2-and-sema5a-expression-signature-as-a-prognostic-and-predictive-biomarker-for-colon-cancer
#3
Secil Demirkol, Ismail Gomceli, Murat Isbilen, Baris Emre Dayanc, Mesut Tez, Erdal Birol Bostanci, Nesrin Turhan, Musa Akoglu, Ezgi Ozyerli, Sevi Durdu, Ozlen Konu, Aviram Nissan, Mithat Gonen, Ali Osmay Gure
Background: Prognostic biomarkers for cancer have the power to change the course of disease if they add value beyond known prognostic factors, if they can help shape treatment protocols, and if they are reliable. The aim of this study was to identify such biomarkers for colon cancer and to understand the molecular mechanisms leading to prognostic stratifications based on these biomarkers. Methods and Findings: We used an in house R based script (SSAT) for the in silico discovery of stage-independent prognostic biomarkers using two cohorts, GSE17536 and GSE17537, that include 177 and 55 colon cancer patients, respectively...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28585618/-predictive-markers-of-immunotherapy-of-cancer-practical-issues-of-pd-l1-testing
#4
József Tímár, Andrea Ladányi
Pathologists have detected signs of antitumor immune reactions for a long time but only in case of a few cancer types became this part of the report. The advent of immunotherapy of cancers, however, radically alters this routine and promotes the development of clinically valid prognostic and predictive immunological makers. The most advanced immunological markers are the Immunoscore (density of T-cell subpopulations), and PD-L1 protein expression on tumor or immune cells. PD-L1 testing of cancers raises new issues since almost all novel therapies developed its own in vitro diagnostics...
June 6, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28581028/measuring-the-value-of-pharmacogenomics-evidence
#5
G P Patrinos, C Mitropoulou
In recent years, there is a growing need to measure the value of pharmacogenomics testing so that policymakers are well informed to decide about adopting and reimbursing pharmacogenomics testing, prioritizing pharmacogenomics research and development, and encouraging the application of companion diagnostics. Presently, there are limited economic evaluation studies of genome-guided treatment modalities that would allow decision-makers to comparatively assess the value and clinical utility of such interventions...
June 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28577957/egfr-t790m-mutation-testing-within-the-osimertinib-aura-phase-i-study
#6
Simon Dearden, Helen Brown, Suzanne Jenkins, Kenneth S Thress, Mireille Cantarini, Rebecca Cole, Malcolm Ranson, Pasi A Jänne
OBJECTIVES: Reliable epidermal growth factor receptor (EGFR) mutation testing techniques are required to identify eligible patients with EGFR mutation/T790M positive advanced non-small cell lung cancer (NSCLC), for treatment with osimertinib (AZD9291), an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI-sensitizing and T790M resistance mutations over wild-type EGFR. There is no current consensus regarding the best method to detect EGFR T790M mutations...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28526056/the-blood-schizonticidal-activity-of-tafenoquine-makes-an-essential-contribution-to-its-prophylactic-efficacy-in-nonimmune-subjects-at-the-intended-dose-200%C3%A2-mg
#7
REVIEW
Geoffrey Dow, Bryan Smith
Tafenoquine (TQ) is an 8-aminoquinoline anti-malarial being developed for malaria prophylaxis. It has been generally assumed that TQ, administered prophylactically, acts primarily on the developing exoerythrocytic stages of malaria parasites (causal prophylaxis), and that polymorphisms in metabolic enzymes thought to impact the activity of other 8-aminoquinolines also inhibit this property of TQ. Furthermore, it has been suggested that a diagnostic test for CYP2D6 metabolizer status might be required. In field studies in which metabolic status was not an exclusion criteria, TQ has been shown to exhibit similar prophylactic efficacy as blood schizonticidal drugs (mefloquine)...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28503213/epigenetic-modifications-of-the-immune-checkpoint-genes-ctla4-and-pdcd1-in-non-small-cell-lung-cancer-results-in-increased-expression
#8
Sebastian Marwitz, Swetlana Scheufele, Sven Perner, Martin Reck, Ole Ammerpohl, Torsten Goldmann
Targeting checkpoint inhibitors using monoclonal antibodies results in significantly better outcome of cancer patients compared to conventional chemotherapy. However, the current companion diagnostics to predict response is so far suboptimal, since they base on more or less reliable immunohistochemical approaches. In order to overcome these limitations, we analyzed epigenetic modifications of PDCD1 (PD1), CD274 (PD-L1), and CTLA4 in NSCLC tissues from 39 patients. Results were correlated with transcriptome data...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28501991/innovations-in-clinical-trial-design-in-the-era-of-molecular-profiling
#9
Julia D Wulfkuhle, Alexander Spira, Kirsten H Edmiston, Emanuel F Petricoin
Historically, cancer has been studied, and therapeutic agents have been evaluated based on organ site, clinical staging, and histology. The science of molecular profiling has expanded our knowledge of cancer at the cellular and molecular level such that numerous subtypes are being described based on biomarker expression and genetic mutations rather than traditional classifications of the disease. Drug development has experienced a concomitant revolution in response to this knowledge with many new targeted therapeutic agents becoming available, and this has necessitated an evolution in clinical trial design...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28501215/assessment-of-in-vitro-dopamine-neuroblastoma-cell-interactions-with-a-bioelectric-biosensor-perspective-for-a-novel-in-vitro-functional-assay-for-dopamine-agonist-antagonist-activity
#10
Theofylaktos Apostolou, Georgia Moschopoulou, Evdokia Kolotourou, Spyridon Kintzios
Current receptor-binding assays for dopamine do not measure the in vitro whole cellular response against dopamine or potential agonist/antagonist molecules. We herewith report the development of a novel functional assay concept for studying the in vitro interaction of the neurotransmitter dopamine with neural cells bearing dopamine receptors. The concept is based on the ultra-rapid measurement of changes in the electric properties of cultured N2a mouse neuroblastoma cells (corresponding to cumulative changes of the cell membrane potential)...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28487384/non-invasive-interrogation-of-dll3-expression-in-metastatic-small-cell-lung-cancer
#11
Sai Kiran Sharma, Jacob Pourat, Dalya Abdel-Atti, Sean D Carlin, Alessandra Piersigilli, Alexander J Bankovich, Eric E Gardner, Omar Hamdy, Kumiko Isse, Sheila Bheddah, Joseph Sandoval, Kristen M Cunanan, Eric B Johansen, Viola Allaj, Vikram Sisodiya, David Liu, Brian M Zeglis, Charles M Rudin, Scott J Dylla, J T Poirier, Jason S Lewis
The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T™; SC16LD6.5) is a first-in-class DLL3-targeted antibody-drug conjugate with encouraging initial safety and efficacy profiles in SCLC in the clinic. Here we demonstrate that tumor expression of DLL3, though orders of magnitude lower in surface protein expression than typical oncology targets of immunoPET, can serve as an imaging biomarker for SCLC...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28472036/accurate-detection-of-low-prevalence-akt1-e17k-mutation-in-tissue-or-plasma-from-advanced-cancer-patients
#12
Elza C de Bruin, Jessica L Whiteley, Claire Corcoran, Pauline M Kirk, Jayne C Fox, Javier Armisen, Justin P O Lindemann, Gaia Schiavon, Helen J Ambrose, Alexander Kohlmann
Personalized healthcare relies on accurate companion diagnostic assays that enable the most appropriate treatment decision for cancer patients. Extensive assay validation prior to use in a clinical setting is essential for providing a reliable test result. This poses a challenge for low prevalence mutations with limited availability of appropriate clinical samples harboring the mutation. To enable prospective screening for the low prevalence AKT1 E17K mutation, we have developed and validated a competitive allele-specific TaqMan® PCR (castPCR™) assay for mutation detection in formalin-fixed paraffin-embedded (FFPE) tumor tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28438082/radioimmunoconjugates-for-treating-cancer-recent-advances-and-current-opportunities
#13
Mickaël Bourgeois, Clément Bailly, Mathieu Frindel, François Guerard, Michel Chérel, Alain Faivre-Chauvet, Françoise Kraeber-Bodéré, Caroline Bodet-Milin
Radioimmunoconjugates have been used for 30 years to diagnose and treat cancer. For many years, the use of these therapeutic tools has been limited to haematological disorders, such as non-Hodgkin's lymphoma, given that they have only had a moderate effect on solid tumours. Areas covered: Recently, several strategies have revived the potential therapeutic application for radioimmunoconjugates. In this review, the authors review the advances in immunological engineering to develop new tools like monoclonal antibodies and their derivatives...
July 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28387329/introducing-the-esat-6-free-igra-a-companion-diagnostic-for-tb-vaccines-based-on-esat-6
#14
Morten Ruhwald, Lena de Thurah, Davis Kuchaka, Mostafa Rafaat Zaher, Ahmed M Salman, Abdel-Rahman Abdel-Ghaffar, Faten Aly Shoukry, Sascha Wilk Michelsen, Bolette Soborg, Thomas Blauenfeldt, Stellah Mpagama, Søren T Hoff, Else Marie Agger, Ida Rosenkrands, Claus Aagard, Gibson Kibiki, Nabila El-Sheikh, Peter Andersen
There is a need for an improved vaccine for tuberculosis. ESAT-6 is a cardinal vaccine antigen with unique properties and is included in several vaccine candidates in development. ESAT-6 is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection, rendering IGRA tests unspecific after vaccination. This challenge has prompted the development of a companion diagnostic for ESAT-6 based vaccines, an ESAT-6 free IGRA. We screened a panel of seven potential new diagnostic antigens not recognized in BCG vaccinated individuals...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28374784/targeting-c-met-in-gastrointestinal-tumours-rationale-opportunities-and-challenges
#15
REVIEW
Conor A Bradley, Manuel Salto-Tellez, Pierre Laurent-Puig, Alberto Bardelli, Christian Rolfo, Josep Tabernero, Hajrah A Khawaja, Mark Lawler, Patrick G Johnston, Sandra Van Schaeybroeck
Data from many preclinical studies, including those using cellular models of colorectal, gastric, gastro-oesophageal and gastro-oesophageal junction cancers, indicate that the hepatocyte growth factor (HGF)-hepatocyte growth factor receptor (c-MET) pathway is vital for the growth, survival and invasive potential of gastrointestinal cancers. Following the availability of data from these various studies, and data on c-MET expression as a biomarker that indicates a poor prognosis in patients with gastrointestinal cancer and increased c-MET expression, inhibitors targeting this pathway have entered the clinic in the past decade...
April 4, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28317395/clinical-metabolomics-a-pivotal-tool-for-companion-diagnostic-development-and-precision-medicine
#16
Vladimir Tolstikov, Viatcheslav R Akmaev, Rangaprasad Sarangarajan, Niven R Narain, Michael A Kiebish
No abstract text is available yet for this article.
March 29, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28299955/niraparib-for-the-treatment-of-ovarian-cancer
#17
REVIEW
Yada Kanjanapan, Stephanie Lheureux, Amit M Oza
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered: This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28293123/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-patient-selection-and-perspectives
#18
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28285688/plasma-epidermal-growth-factor-receptor-mutation-testing-with-a-chip-based-digital-pcr-system-in-patients-with-advanced-non-small-cell-lung-cancer
#19
Norimitsu Kasahara, Hirotsugu Kenmotsu, Masakuni Serizawa, Rina Umehara, Akira Ono, Yasushi Hisamatsu, Kazushige Wakuda, Shota Omori, Kazuhisa Nakashima, Tetsuhiko Taira, Tateaki Naito, Haruyasu Murakami, Yasuhiro Koh, Keita Mori, Masahiro Endo, Takashi Nakajima, Masanobu Yamada, Masatoshi Kusuhara, Toshiaki Takahashi
OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation testing is a companion diagnostic to determine eligibility for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-based EGFR testing by digital polymerase chain reaction (dPCR), which enables accurate quantification of target DNA, has shown promise as a minimally invasive diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation test developed using chip-based dPCR-based detection of 3 EGFR mutations (exon 19 deletions, L858R in exon 21, and T790M in exon 20)...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28284377/treatment-of-renal-fibrosis-turning-challenges-into-opportunities
#20
REVIEW
Barbara M Klinkhammer, Roel Goldschmeding, Jürgen Floege, Peter Boor
Current treatment modalities are not effective in halting the progression of most CKD. Renal fibrosis is a pathological process common to all CKD and thereby represents an excellent treatment target. A large number of molecular pathways involved in renal fibrosis were identified in preclinical studies, some of them being similar among different organs and some with available drugs in various phases of clinical testing. Yet only few clinical trials with antifibrotic drugs are being conducted in CKD patients...
March 2017: Advances in Chronic Kidney Disease
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