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Drug therapies

Ines van Dooren, Kenn Foubert, Sebastiaan Bijttebier, Mart Theunis, Stefaniya Velichkova, Magda Claeys, Luc Pieters, Vassiliki Exarchou, Sandra Apers
Stone diseases present a major health problem in the Western society, since both urinary and biliary stones occur with a relatively high prevalence of 10-12 % and 10-20 %, respectively, and demonstrate a high recurrence rate. At the moment treatment is mainly based on interventional procedures, or prophylactic and dissolution therapy. However, many of the current drugs cause severe side effects, and therefore, there is an increasing interest in natural medicines. At the moment no registered herbal medicinal products are available for treatment of gallstones...
October 24, 2016: Planta Medica
Righab Hamdan, Pierre Nassar, Ali Zein, Mohamad Issa, Hassan Mansour, Mohamad Saab
Peripartum cardiomyopathy remains a challenging obstetric and cardiologic emergency. We report 5 interesting cases of peripartum cardiomyopathy with different clinical courses, with 3 patients requiring left ventricular assist device implantation. One patient underwent pump explantation and aortic balloon valvuloplasty postsurgery. Two patients improved with the medical treatment alone without the need of assistance. We will review main important related issues.
October 11, 2016: Journal of Critical Care
Guang-Hui Ma, Yan Ye, Dan Zhang, Xin Xu, Pei Si, Jian-Long Peng, Yong-Long Xiao, Rui-Yuan Cao, Yu-Ling Yin, Jing Chen, Lin-Xiang Zhao, Yu Zhou, Wu Zhong, Hong Liu, Xiao-Min Luo, Li-Li Chen, Xu Shen
Hand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3C(pro) in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3C(pro) inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3C(pro). The best inhibitor DC07090 exhibited the inhibition potency with an IC50 value of 21...
October 11, 2016: European Journal of Medicinal Chemistry
Lixia Yuan, Min Liu, Guiqin Liu, Dacheng Li, Zhengping Wang, Bingquan Wang, Jun Han, Min Zhang
Combination therapy with more than one therapeutic agent can improve therapeutic efficiency and decrease drug resistance. In this study, the interactions of human serum albumin (HSA) with individual or combined anticancer drugs, (-)-epigallocatechin-3-gallate (EGCG) and 5-fluorouracil (FU), were investigated by fluorescence and circular dichroism (CD) spectroscopy. The results demonstrated that the interaction of EGCG or FU with HSA is a process of static quenching and EGCG formed a more stable complex. The competitive experiments of site markers suggested that both anti-carcinogens mainly bound to site I (subdomain IIA)...
October 18, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
E Sawicki, J H M Schellens, J H Beijnen, B Nuijen
Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and with that suboptimal or even failing therapy. This review discusses pharmaceutical formulation aspects and absorption pharmacokinetics of currently licensed orally administered oncolytics. In nearly half of orally dosed oncolytics poor dissolution is likely to play a major role in low and unpredictable absorption...
September 20, 2016: Cancer Treatment Reviews
Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
October 19, 2016: Journal of Colloid and Interface Science
Sara Westrøm, Tina B Bønsdorff, Nasir Abbas, Øyvind S Bruland, Thora J Jonasdottir, Gunhild M Mælandsmo, Roy H Larsen
BACKGROUND: Osteosarcoma is a rare form of cancer but with a substantial need for new active drugs. There is a particular need for targeted therapies to combat metastatic disease. One possible approach is to use an antibody drug conjugate or an antibody radionuclide conjugate to target the osteosarcoma metastases and circulating tumor cells. Herein we have evaluated a radiolabeled monoclonal antibody targeting CD146 both in vitro and in vivo. METHODS AND RESULTS: A murine monoclonal anti-CD146 IgG1 isotype antibody, named OI-3, was developed along with recombinant chimeric versions with human IgG1 or human IgG3 Fc sequences...
2016: PloS One
Mohammad Islamuddin, Garima Chouhan, Muzamil Yaqub Want, Hani A Ozbak, Hassan A Hemeg, Farhat Afrin
BACKGROUND: The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation...
October 2016: PLoS Neglected Tropical Diseases
Alana T Brennan, Mary-Ann Davies, Jacob Bor, Gilles Wandeler, Kathryn Stinson, Robin Wood, Hans Prozesky, Frank Tanser, Geoffrey Fatti, Andrew Boulle, Izukanji Sikazwe, Kara Wool-Kaloustian, Constantin Yiannoutsos, Valériane Leroy, Nathalie de Rekeneire, Matthew P Fox
OBJECTIVE: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy(ART) in accordance with World Health Organization 2010 policy and single-drug substitutions (SDS)(substituting the nucleoside reverse transcriptase inhibitor(NRTI) in first-line ART) in sub-Saharan Africa. DESIGN: Prospective cohort analysis (IeDEA-Multiregional) including ART-naïve, HIV-infected patients ≥16 years initiating ART between January 2005-December 2012...
October 20, 2016: AIDS
Amalia Vartanian, Maria Baryshnikova, Olga Burova, Dariya Afanasyeva, Vsevolod Misyurin, Alexander Belyаvsky, Zoya Shprakh
The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug...
October 21, 2016: Melanoma Research
Emmanuel Fortier, Maryam Alavi, Julie Bruneau, Michelle Micallef, Jacinta Perram, Sanjeev Sockalingam, Adrian J Dunlop, Annie C Balcomb, Carolyn A Day, Carla Treloar, Nicky Bath, Paul S Haber, Gregory J Dore, Jason Grebely
OBJECTIVE: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. METHODS: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia)...
October 21, 2016: Journal of Addiction Medicine
Sanjay K Agarwal, Dipankar Bhowmik, Sandeep Mahajan, Soumita Bagchi
INTRODUCTION: Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipient (RTR). Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB. METHODS: In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded...
October 24, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Alejandro Parrales, Atul Ranjan, Swathi V Iyer, Subhash Padhye, Scott J Weir, Anuradha Roy, Tomoo Iwakuma
Stabilization of mutant p53 (mutp53) in tumours greatly contributes to malignant progression. However, little is known about the underlying mechanisms and therapeutic approaches to destabilize mutp53. Here, through high-throughput screening we identify statins, cholesterol-lowering drugs, as degradation inducers for conformational or misfolded p53 mutants with minimal effects on wild-type p53 (wtp53) and DNA contact mutants. Statins preferentially suppress mutp53-expressing cancer cell growth. Specific reduction of mevalonate-5-phosphate by statins or mevalonate kinase knockdown induces CHIP ubiquitin ligase-mediated nuclear export, ubiquitylation, and degradation of mutp53 by impairing interaction of mutp53 with DNAJA1, a Hsp40 family member...
October 24, 2016: Nature Cell Biology
Mary Jc Hendrix, Irawati Kandela, Andrew P Mazar, Elisabeth A Seftor, Richard Eb Seftor, Naira V Margaryan, Luigi Strizzi, George F Murphy, Georgina V Long, Richard A Scolyer
Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. It is the leading cause of skin cancer deaths with a median overall survival for advanced-stage metastatic disease of <6 months. Despite advances in the field with conventional and targeted therapies, the heterogeneity of melanoma poses the greatest ongoing challenge, ultimately leading to relapse and progression to a more drug-resistant tumor in most patients. Particularly noteworthy are recent findings, indicating that these therapies exert selective pressure on tumors resulting in the activation of pathways associated with cancer stem cells that are unresponsive to current therapy...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
Shuo Wang, Heinz Schattler
We consider cancer chemotherapy as an optimal control problem with the aim to minimize a combination of the tumor volume and side effects over an a priori specified therapy horizon when the tumor consists of a heterogeneous agglomeration of many subpopulations. The mathematical model, which accounts for different growth and apoptosis rates in the presence of cell densities, is a finite-dimensional approximation of a model originally formulated by Lorz et al. [18,19] and Greene et al. [10,11] with a continuum of possible traits...
December 1, 2016: Mathematical Biosciences and Engineering: MBE
Ami B Shah, Katarzyna A Rejniak, Jana L Gevertz
While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment...
December 1, 2016: Mathematical Biosciences and Engineering: MBE
Yana K Rennie, Patrick J McIntyre, Tito Akindele, Richard Bayliss, Andrew G Jamieson
Inhibition of protein kinases using ATP-competitive compounds is an important strategy in drug discovery. In contrast, the allosteric regulation of kinases through the disruption of protein-protein interactions has not been widely adopted, despite the potential for selective targeting. Aurora-A kinase regulates mitotic entry and mitotic spindle assembly, and is a promising target for anti-cancer therapy. The microtubule-associated protein TPX2 activates Aurora-A through binding to two sites. Aurora-A recognition is mediated by two motifs within the first 43 residues of TPX2, connected by a flexible linker...
October 24, 2016: ACS Chemical Biology
Jie Chen, Hong Liang, Lin Lin, Zhaopei Guo, Pingjie Sun, Meiwan Chen, Huayu Tian, MingXiao Deng, Xuesi Chen
Multifunctional nanoparticles with high gene transfection activity, low cytotoxicity, photoacoustic imaging ability, and photothermal therapeutic properties were prepared by conjugating low-molecular-weight polyethylenimine onto the surfaces of gold nanorods through the formation of stable S-Au bonded conjugates. Results revealed that the gene transfection efficiency of the prepared polyethylenimine-modified gold nanorods (GNRs-PEI1.8k) was higher and their cytotoxicity was less than those of the commercial reagent PEI25k...
October 24, 2016: ACS Applied Materials & Interfaces
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