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Innovative Drugs

Turki Turki, Jason T L Wang
Predicting the response, or sensitivity, of a clinical drug to a specific cancer type is an important research problem. By predicting the clinical drug response correctly, clinicians are able to understand patient-to-patient differences in drug sensitivity outcomes, which in turn results in lesser time spent and lower cost associated with identifying effective drug candidates. Although technological advances in high-throughput drug screening in cells led to the generation of a substantial amount of relevant data, the analysis of such data would be a challenging task...
January 3, 2019: Computers in Biology and Medicine
Arrvind Raghunath, Kunal Desai, Manmeet S Ahluwalia
In the past, the standard of care for treatment of BM was whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. There has been a greater role for medical therapies in the last two decades due to the discovery of driver mutations and corresponding targeted therapies. These innovations have dramatically altered the approach to treating these patients. Some of the important mutations include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in small cell lung cancer, human epidermal growth factor receptor (HER2) mutation in breast cancer, and BRAF mutation in melanoma...
February 15, 2019: Current Treatment Options in Oncology
Bernhard Hladik, Florence Buscke, Robert Frost, Uwe Rothhaar
The pharmacopeia method for the measurement of the chemical durability for parenteral packaging is the hydrolytic resistance test for which the vial is filled to 90% of it's brimfull volume as described USP <660> (1). However, an increasing amount of innovative drugs are filled significantly below the nominal volume of the vial. As a consequence the determined hydrolytic resistance is not representative of the concentrations of leached "glass" elements for low filling volumes. This is attributable to two main factors: (1) an increasing ratio of the wetted surface to volume, and (2) an increased leaching tendency typically observed with borosilicate glass of the wall near bottom area, especially when standard manufacturing technology is applied...
February 15, 2019: PDA Journal of Pharmaceutical Science and Technology
Diana Caridha, Mark Hickman, Lisa Xie, Franklyn Ngundam, Erin Milner, Amanda Schenk, Kirk Butler, Dylan Nugent, Patricia Lee, Norma Roncal, Susan Leed, Eve Hosford, Jangwoo Lee, Richard J Sciotti, Gregory Reichard, Chad Black, Mara Kreishman-Deitrick, Qigui Li, Brian Vesely
BACKGROUND: Rodent malaria models are extensively used to predict treatment outcomes in human infections. There is a constant need to improve and refine these models by innovating ways to apply new scientific findings and cutting edge technologies. In addition, and in accordance with the three R's of animal use in research, in vivo studies should be constantly refined to avoid unnecessary pain and distress to the experimental animals by using preemptive euthanasia as soon as the main scientific study objective has been accomplished...
February 15, 2019: Malaria Journal
Kevin Dzobo
The human epigenome plays a key role in determining cellular identity and eventually function. Drug discovery undertakings have focused mainly on the role of genomics in carcinogenesis, with the focus turning to the epigenome recently. Drugs targeting DNA and histone modifications are under development with some such as 5-azacytidine, decitabine, vorinostat, and panobinostat already approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This expert review offers a critical analysis of the epigenomics-guided drug discovery and development and the opportunities and challenges for the next decade...
February 2019: Omics: a Journal of Integrative Biology
Wei Gao, Hiroki Ota, Daisuke Kiriya, Kuniharu Takei, Ali Javey
Wearable sensors play a crucial role in realizing personalized medicine, as they can continuously collect data from the human body to capture meaningful health status changes in time for preventive intervention. However, motion artifacts and mechanical mismatches between conventional rigid electronic materials and soft skin often lead to substantial sensor errors during epidermal measurement. Because of its unique properties such as high flexibility and conformability, flexible electronics enables a natural interaction between electronics and the human body...
February 15, 2019: Accounts of Chemical Research
Patrice Trouiller
The main problems of the system governing the development and dissemination of innovative medicines are known. Despite relatively low manufacturing costs, patented drugs are unduly expensive, and neglected diseases attract little pharmaceutical research. Both problems are compounded by patients who, discouraged by high prices, lack of access to competent medical services and low quality medicines, do not complete their treatment.
July 20, 2018: Journal International de Bioéthique et D'éthique des Sciences
Maurice-Pierre Planel
Several innovative drugs including the first gene therapy drugs are expected shortly. In light of the debates on the new products for the treatment of hepatitis C and cancer, this wave of innovation raises questions about the ability of our health insurance systems to bear the expense and pay the price claimed by the laboratories. This situation has led to a reflection on the criteria for setting the price of drugs. Public authorities have developed new regulatory mechanisms and have opened a debate to explore new rules that would take into account - in the construction of contracts and prices - real world evidence...
July 20, 2018: Journal International de Bioéthique et D'éthique des Sciences
Angel Mauricio Castro-Gamero, Julia Alejandra Pezuk, María Sol Brassesco, Luiz Gonzaga Tone
Glioblastoma (GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division...
November 2018: Cancer Biology & Medicine
Mirjam Simoons, Henricus G Ruhé, Eric N van Roon, Robert A Schoevers, Richard Bruggeman, Daniëlle C Cath, Diny Muis, Johan Arends, Bennard Doornbos, Hans Mulder
BACKGROUND: At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment. Improvement of monitoring practices provides an opportunity to ensure that somatic complications and adverse drug effects are detected and dealt with in a timely manner...
February 14, 2019: BMC Health Services Research
Christopher A John
This review article discusses how social approaches to tuberculosis elimination might contribute to realizing the targets stipulated in the World Health Organization's (WHO) End TB Strategy (2016⁻2035), with an emphasis on opportunities for progress in Asia and the Pacific. Many factors known to advance tuberculosis transmission and progression are pervasive in Asia and the Pacific, such as worsening drug resistance, unregulated private sector development, and high population density. This review article argues that historically successful social solutions must be revisited and improved upon if current worldwide tuberculosis rates are to be sustainably reduced in the long term...
February 5, 2019: Tropical Medicine and Infectious Disease
Fabio Barra, Giovanni Grandi, Matteo Tantari, Carolina Scala, Fabio Facchinetti, Simone Ferrero
Endometriosis is a chronic benign estrogen dependent disease characterized by the presence of endometriotic glands and stroma outside the uterine cavity. Although combined hormonal contraceptives and progestins, currently available first-line treatments for endometriosis, are efficacious and well tolerated for treating disease-related pain, some women experience partial or no improvement of pain or its recurrence is frequent after discontinuation of the therapies. For these reasons, new drugs are under investigation for the treatment of endometriosis...
February 14, 2019: Expert Opinion on Biological Therapy
Minh Pham, Feng Cheng, Kandethody Ramachandran
INTRODUCTION: It is important to monitor the safety profile of drugs, and mining for strong associations between drugs and adverse events is an effective and inexpensive method of post-marketing safety surveillance. OBJECTIVE: The objective of our work was to compare the accuracy of both common and innovative methods of data mining for pharmacovigilance purposes. METHODS: We used the reference standard provided by the Observational Medical Outcomes Partnership, which contains 398 drug-adverse event pairs (165 positive controls, 233 negative controls)...
February 14, 2019: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Andrés Pizzorno, Olivier Terrier, Claire Nicolas de Lamballerie, Thomas Julien, Blandine Padey, Aurélien Traversier, Magali Roche, Marie-Eve Hamelin, Chantal Rhéaume, Séverine Croze, Vanessa Escuret, Julien Poissy, Bruno Lina, Catherine Legras-Lachuer, Julien Textoris, Guy Boivin, Manuel Rosa-Calatrava
Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials...
2019: Frontiers in Immunology
Jamie Berry, Isabella Jacomb, Jo Lunn, Antoinette Sedwell, Anthony Shakeshaft, Peter J Kelly, Pooria Sarrami, Megan James, Skye Russell, Talia Nardo, Daniel Barker, Jennifer Holmes
BACKGROUND: Executive functioning impairment is common in substance use disorder and is a major risk factor for poor treatment outcomes, including treatment drop-out and relapse. Cognitive remediation interventions seek to improve executive functioning and offer a promising approach to increase the efficacy of alcohol and other drug (AOD) treatments and improve long-term therapeutic outcomes. This protocol describes a study funded by the NSW Agency for Clinical Innovation that assesses the effectiveness of delivering a six-week group-based intervention of cognitive remediation in an ecologically valid sample of people attending residential AOD treatment services...
February 13, 2019: BMC Psychiatry
Heidi Noels, Christian Weber, Rory R Koenen
With the incidence and impact of atherosclerotic cardiovascular disease and its clinical manifestations still rising, therapeutic options that target the causal mechanisms of this disorder are highly desired. Since the CANTOS trial has demonstrated that lowering inflammation can be beneficial, focusing on mechanisms underlying inflammation, for example, leukocyte recruitment, is feasible. Being key orchestrators of leukocyte trafficking, chemokines have not lost their attractiveness as therapeutic targets, despite the difficult road to drug approval thus far...
February 14, 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Satoshi Ōmura, Andy Crump
Lactacystin exemplifies the role that serendipity plays in drug discovery and why "finding things without actually looking for them" retains such a pivotal role in the search for the useful properties of chemicals. The first proteasome inhibitor discovered, lactacystin stimulated new possibilities in cancer control. New and innovative uses are regularly being found for lactacystin, including as a model to study dementia, while new formulations and delivery systems may facilitate its use clinically as an anticancer agent...
February 12, 2019: Journal of Antibiotics
M Gogia, C Lawlor, N Shengelia, K Stvilia, H F Raymond
BACKGROUND: The HIV epidemic in Georgia is increasing. Data shows that compared to previous years, Georgia has increasingly more HIV-infected individuals than previous assessments. Select client groups remain hard to reach by harm reduction programs. The need for innovative strategies to involve these individuals is imperative. METHODS: The following study examines demographics and risk factors of participants, previously known and not known to harm reduction services, for HIV and other infectious disease in towns across Georgia in 2015 and compares risk among different groups, while also assessing the rationale for implementing Peer-Driven Interventions in Georgian Harm Reduction activities...
February 12, 2019: Harm Reduction Journal
Tian Tian, Xiaoyi Li, Jinhua Zhang
The mammalian or mechanistic target of rapamycin (mTOR) pathway plays a crucial role in regulation of cell survival, metabolism, growth and protein synthesis in response to upstream signals in both normal physiological and pathological conditions, especially in cancer. Aberrant mTOR signaling resulting from genetic alterations from different levels of the signal cascade is commonly observed in various types of cancers. Upon hyperactivation, mTOR signaling promotes cell proliferation and metabolism that contribute to tumor initiation and progression...
February 11, 2019: International Journal of Molecular Sciences
Daniela Chirio, Elena Peira, Chiara Dianzani, Elisabetta Muntoni, Casimiro Luca Gigliotti, Benedetta Ferrara, Simona Sapino, Giulia Chindamo, Marina Gallarate
Background : Solid lipid nanoparticles (SLNs) are attractive drug delivery systems for lipophilic molecules like curcumin (CURC) with low chemical stability. Methods : A simple, innovative, and cold-operating method, named "cold dilution of microemulsion" is developed by the authors to produce SLNs. An oil-in-water microemulsion (µE), whose disperse phase consisted of a solution of trilaurin in a partially water-miscible solvent, was prepared after mutually saturating solvent and water. Trilaurin SLNs precipitated following solvent removal upon water dilution of the µE...
February 8, 2019: Nanomaterials
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