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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
May 4, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28280626/current-companion-diagnostics-in-advanced-colorectal-cancer-getting-a-bigger-and-better-piece-of-the-pie
#15
REVIEW
Jonathan M Loree, Scott Kopetz, Kanwal P S Raghav
While the treatment of colorectal cancer continues to rely heavily on conventional cytotoxic therapy, an increasing number of targeted agents are under development. Many of these treatments require companion diagnostic tests in order to define an appropriate population that will derive benefit. In addition, a growing number of biomarkers provide prognostic information about a patient's malignancy. As we learn more about these biomarkers and their assays, selecting the appropriate companion diagnostic becomes increasingly important...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28247182/impact-of-availability-of-companion-diagnostics-on-the-clinical-development-of-anticancer-drugs
#16
Ariadna Tibau, Laura Díez-González, Beatriz Navarro, Eva M Galán-Moya, Arnoud J Templeton, Bostjan Seruga, Atanasio Pandiella, Eitan Amir, Alberto Ocana
BACKGROUND: Companion diagnostics permit the selection of patients likely to respond to targeted anticancer drugs; however, it is unclear if the drug development process differs between drugs developed with or without companion diagnostics. Identification of differences in study design could help future clinical development. PATIENTS AND METHODS: Anticancer drugs approved for use in solid tumors between 28 September 2000 and 4 January 2014 were identified using a search of the US FDA website...
June 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28237197/toward-a-broader-concept-of-value-identifying-and-defining-elements-for-an-expanded-cost-effectiveness-analysis
#17
Louis P Garrison, Sachin Kamal-Bahl, Adrian Towse
This commentary identifies and defines potentially useful expansions to traditional cost-effectiveness analysis as often used in health technology assessment. Since the seminal 1977 article by Weinstein and Stason, the recommended approach has been the use of the incremental cost-effectiveness ratio based on the metric of the cost per quality-adjusted life-year gained, allowing comparisons across different technologies. An expanded framework, incorporating a wider range of the elements of value, is proposed...
February 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28231414/mir-135a-3p-as-a-promising-biomarker-and-nucleic-acid-therapeutic-agent-for-ovarian-cancer
#18
Satoshi Fukagawa, Kohei Miyata, Fusanori Yotsumoto, Chihiro Kiyoshima, Sung Ouk Nam, Haruchika Anan, Takahiro Katsuda, Daisuke Miyahara, Masaharu Murata, Hiroshi Yagi, Kyoko Shirota, Shin'ichiro Yasunaga, Kiyoko Kato, Shingo Miyamoto
Ovarian cancer is the most lethal gynecologic malignancy. Recently, several molecularly targeted anticancer agents have been developed for ovarian cancer; however, its prognosis has remained extremely poor. The development of molecularly targeted therapy, as well as companion diagnostics, is required to improve outcomes for patients with ovarian cancer. In this study, to identify microRNAs involved in the progression of ovarian cancer we analyzed serum microRNAs in patients with ovarian cancer using microRNA array and qRT-PCR and examined the anticancer properties of microRNA expression in ovarian cancer cells...
February 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28230858/ngs-based-transcriptome-profiling-reveals-biomarkers-for-companion-diagnostics-of-the-tgf-%C3%AE-receptor-blocker-galunisertib-in-hcc
#19
Yuan Cao, Rahul Agarwal, Francesco Dituri, Luigi Lupo, Paolo Trerotoli, Serena Mancarella, Peter Winter, Gianluigi Giannelli
Transforming growth factor-beta (TGF-β) signaling has gained extensive interest in hepatocellular carcinoma (HCC). The small molecule kinase inhibitor galunisertib, targeting the TGF-β receptor I (TGF-βRI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, this study was aimed at identifying new companion diagnostics biomarkers for patient stratification. Next-generation sequencing-based massive analysis of cDNA ends was used to investigate the transcriptome of an invasive HCC cell line responses to TGF-β1 and galunisertib...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#20
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
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