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https://www.readbyqxmd.com/read/29351570/joint-adolescent-adult-early-phase-clinical-trials-to-improve-access-to-new-drugs-for-adolescents-with-cancer-proposals-from-the-multi-stakeholder-platform-accelerate
#1
N Gaspar, L V Marshall, D Binner, R Herold, R Rousseau, P Blanc, R Capdeville, J Carleer, C Copland, Y Kerloeguen, K Norga, L Pacaud, M-A Sevaux, C Spadoni, J Sterba, F Ligas, T Taube, M Uttenreuther-Fischer, S Chioato, M A O'Connell, B Geoerger, J-Y Blay, J C Soria, S Kaye, B Wulff, L Brugières, G Vassal, A D J Pearson
The impressive progress recently observed in adult cancers through the introduction of new drugs has not yet been translated to adolescents between 12 and 17 years of age. Currently adolescents are grouped with children, so their access to new, effective drugs already available for adults is delayed because paediatric drug development starts late relative to adult programmes. Moreover, specific early phase trials designed exclusively for adolescents in rare diseases recruit poorly, even if conducted internationally...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29351242/-vessels-in-the-storm-searching-for-prognostic-and-predictive-angiogenic-factors-in-colorectal-cancer
#2
REVIEW
Adriano Angelucci, Simona Delle Monache, Alessio Cortellini, Monica Di Padova, Ficorella Corrado
High expectations are placed upon anti-angiogenic compounds for metastatic colorectal cancer (mCRC), the first malignancy for which such type of treatment has been approved. Indeed, clinical trials have confirmed that targeting the formation of new vessels can improve in many cases clinical outcomes of mCRC patients. However, current anti-angiogenic drugs are far from obtaining the desirable or expected curative results. Many are the factors probably involved in such disappointing results, but particular attention is currently focused on the validation of biomarkers able to improve the direction of treatment protocols...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350758/obesity-and-pediatric-drug-development
#3
Janelle D Vaughns, Laurie S Conklin, Ying Long, Panli Zheng, Fahim Faruque, Dionna J Green, John N van den Anker, Gilbert J Burckart
There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies...
January 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29350549/abiraterone-acetate-and-its-use-in-the-treatment-of-metastatic-prostate-cancer-a-review
#4
Orazio Caffo, Antonello Veccia, Stefania Kinspergher, Francesca Maines
Abiraterone acetate, which targets enzymatic complexes playing a central role in steroidogenesis, demonstrated to increase survival significantly in both chemo-naive and docetaxel pretreated, becoming one of the drugs of choice for metastatic castration-resistant prostate cancer. More recently, this agent in combination to androgen deprivation therapy demonstrated to be efficacious also in metastatic castration-sensitive prostate cancer. The present review is aimed to outline the clinical development of abiraterone acetate, the pivotal trials which led to its approval for the clinical practice, new evidence about its efficacy in metastatic castration-sensitive prostate cancer, its place in the therapeutic landscape of prostate cancer and future directions of development...
January 19, 2018: Future Oncology
https://www.readbyqxmd.com/read/29350495/the-current-landscape-of-3d-in-vitro-tumor-models-what-cancer-hallmarks-are-accessible-for-drug-discovery
#5
REVIEW
Darren Rodenhizer, Teresa Dean, Elisa D'Arcangelo, Alison P McGuigan
Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted...
January 19, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29350320/ethical-implications-in-vaccine-pharmacotherapy-for-treatment-and-prevention-of-drug-of-abuse-dependence
#6
Anna Carfora, Paola Cassandro, Alessandro Feola, Francesco La Sala, Raffaella Petrella, Renata Borriello
Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway...
January 19, 2018: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/29349597/drug-repurposing-screening-identifies-bortezomib-and-panobinostat-as-drugs-targeting-cancer-associated-fibroblasts-cafs-by-synergistic-induction-of-apoptosis
#7
Hak-Min Lee, Eunmyong Lee, So-Young Yeo, Sang Shin, Hyun-Kyu Park, Do-Hyun Nam, Seok-Hyung Kim
Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval...
January 18, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29348854/acid-ceramidase-and-its-inhibitors-a-de-novo-drug-target-and-a-new-class-of-drugs-for-killing-glioblastoma-cancer-stem-cells-with-high-efficiency
#8
Ninh B Doan, Hisham Alhajala, Mona M Al-Gizawiy, Wade M Mueller, Scott D Rand, Jennifer M Connelly, Elizabeth J Cochran, Christopher R Chitambar, Paul Clark, John Kuo, Kathleen M Schmainda, Shama P Mirza
Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348161/cns-metastases-needn-t-rule-out-trial-inclusion
#9
(no author information available yet)
New guidelines from an expert working group describe when to include or exclude patients with brain metastases from clinical trials. In the past, these patients have often been inappropriately excluded from trials, resulting in a dearth of information on the efficacy of cancer drugs in the central nervous system.
January 18, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29344777/giant-cell-arteritis-practical-pearls-and-updates
#10
REVIEW
Swati Pradeep, Jonathan H Smith
PURPOSE OF REVIEW: The purpose of this review is to summarize recent updates and distill practical points from the literature which can be applied to the care of patients with suspected and confirmed giant cell arteritis (GCA). RECENT FINDINGS: Contemporary thinking implicates a fundamental failure of T regulatory cell function in GCA pathophysiology, representing opportunity for novel therapeutic avenues. Tocilizumab has become the first Food and Drug Administration-approved treatment for GCA following demonstration of efficacy and safety in a phase 3 clinical trial...
January 17, 2018: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/29344438/new-therapeutic-approaches-in-obesity-and-metabolic-syndrome-associated-with-polycystic-ovary-syndrome
#11
REVIEW
Fatima Saleem, Syed W Rizvi
Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting reproductive and metabolic indices. PCOS is commonly associated with a high prevalence of insulin resistance and obesity; this association carries an increased risk of developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. Guidelines recommend lifestyle modification, metformin, hormonal contraceptives (HCs), and bariatric surgery as the main treatment options in obese patients with PCOS. Studies are being conducted to test the efficacy of existing treatment options as well as to discover new therapies...
November 13, 2017: Curēus
https://www.readbyqxmd.com/read/29344329/major-adverse-cardiovascular-event-reduction-with-glp-1-and-sglt2-agents-evidence-and-clinical-potential
#12
REVIEW
Michael E Røder
Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29344327/secukinumab-a-review-of-the-anti-il-17a-biologic-for-the-treatment-of-psoriasis
#13
REVIEW
Jillian Frieder, Dario Kivelevitch, Alan Menter
Psoriasis is a systemic inflammatory disease associated with numerous comorbidities and a profound impact on patients' quality of life. While its complex immune pathogenesis is still not fully delineated, current evidence supports a fundamental role of the T-helper-17 (TH-17) pathway and its related interleukin-17 (IL-17) cytokine. Thus, new antipsoriatic therapies have been developed to block this key cytokine and its downstream effects. Secukinumab is a fully humanized, monoclonal anti-IL-17A antibody, and the first in its class to be approved by the US Food and Drug Administration for the treatment of moderate to severe plaque psoriasis...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29343694/sertraline-paroxetine-and-chlorpromazine-are-rapidly-acting-anthelmintic-drugs-capable-of-clinical-repurposing
#14
Janis C Weeks, William M Roberts, Caitlyn Leasure, Brian M Suzuki, Kristin J Robinson, Heather Currey, Phurpa Wangchuk, Ramon M Eichenberger, Aleen D Saxton, Thomas D Bird, Brian C Kraemer, Alex Loukas, John M Hawdon, Conor R Caffrey, Nicole F Liachko
Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343688/wee1-inhibitor-mk1775-sensitizes-kras-mutated-nsclc-cells-to-sorafenib
#15
Elisa Caiola, Roberta Frapolli, Michele Tomanelli, Rossana Valerio, Alice Iezzi, Marina C Garassino, Massimo Broggini, Mirko Marabese
Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where a specific driving and druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently mutated genes in NSCLC and patients harboring these mutations do not benefit from specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was proposed as a potentially active drug in KRAS-mutated NSCLC patients, but clinical trials results were not conclusive...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343266/identification-of-pain-categories-associated-with-change-in-pain-in-patients-receiving-placebo-data-from-two-phase-3-randomized-clinical-trials-in-symptomatic-knee-osteoarthritis
#16
Asger Reinstrup Bihlet, Inger Byrjalsen, Anne-Christine Bay-Jensen, Jeppe Ragnar Andersen, Claus Christiansen, Bente Juel Riis, Ivo Valter, Morten A Karsdal, Marc C Hochberg
BACKGROUND: Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinical characteristics and pain categories particularly associated with this phenomenon is needed. The purpose of this post-hoc analysis was to investigate clinical characteristics and pain categories and their association with radiographic progression and placebo pain reduction (PPR) in OA patients as measured the Western Ontario and McMasters Arthritis (WOMAC)...
January 17, 2018: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29342497/non-antipsychotic-catecholaminergic-drugs-for-antipsychotic-induced-tardive-dyskinesia
#17
REVIEW
Hany G El-Sayeh, John Rathbone, Karla Soares-Weiser, Hanna Bergman
BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. OBJECTIVES: 1...
January 18, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29341164/patient-derived-organoid-models-help-define-personalized-management-of-gastrointestinal-cancer
#18
REVIEW
M R Aberle, R A Burkhart, H Tiriac, S W M Olde Damink, C H C Dejong, D A Tuveson, R M van Dam
BACKGROUND: The prognosis of patients with different gastrointestinal cancers varies widely. Despite advances in treatment strategies, such as extensive resections and the addition of new drugs to chemotherapy regimens, conventional treatment strategies have failed to improve survival for many tumours. Although promising, the clinical application of molecularly guided personalized treatment has proven to be challenging. This narrative review focuses on the personalization of cancer therapy using patient-derived three-dimensional 'organoid' models...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29340741/-platelet-inhibition-in-patients-with-coronary-cerebral-and-peripheral-macroangiopathy-what-when-and-how-long
#19
REVIEW
M Halbach, S Baldus
BACKGROUND: Inhibition of platelet aggregation can reduce the rate of vascular events in patients with coronary artery disease, carotid artery stenosis and symptomatic peripheral arterial disease. The choice of platelet inhibitors in monotherapy and combination therapy as well as the duration of dual platelet inhibition depend on the clinical situation and individual patient characteristics. GOAL: The present review summarizes the latest data from clinical trials and recommendations regarding platelet inhibition in coronary, cerebral and peripheral arterial disease...
January 16, 2018: Der Internist
https://www.readbyqxmd.com/read/29339063/evolution-of-intravitreal-therapy-for-retinal-diseases-from-cmv-to-cnv-the-lxxiv-edward-jackson-memorial-lecture
#20
Daniel F Martin
PURPOSE: To present the evolution of intravitreal therapy for retinal diseases and its impact on clinical practice. DESIGN: Retrospective literature review and personal perspective. METHODS: Retrospective literature review and personal perspective. RESULTS: Pharmacotherapeutic advances in retinal disease have been remarkable over the last 25 years. Almost all of the new drugs developed have required intravitreal administration to be highly effective, leading to an exponential increase in the annual number of intravitreal injections given...
January 12, 2018: American Journal of Ophthalmology
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