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https://www.readbyqxmd.com/read/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#1
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
February 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28550735/clarithromycin-inhibits-tnf-%C3%AE-induced-muc5ac-mucin-gene-expression-via-the-mkp-1-p38mapk-dependent-pathway
#2
Said Ahmad Shah, Hajime Ishinaga, Kazuhiko Takeuchi
Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550712/combined-immune-checkpoint-blockade-anti-pd-1-anti-ctla-4-evaluation-and-management-of-adverse-drug-reactions
#3
REVIEW
Jessica C Hassel, Lucie Heinzerling, Jens Aberle, Oliver Bähr, Thomas K Eigentler, Marc-Oliver Grimm, Victor Grünwald, Jan Leipe, Niels Reinmuth, Julia K Tietze, Jörg Trojan, Lisa Zimmer, Ralf Gutzmer
Combined immune checkpoint blockade (ICB) provides unprecedented efficacy gains in numerous cancer indications, with PD-1 inhibitor nivolumab plus CTLA-4 inhibitor ipilimumab in advanced melanoma as first-ever approved therapies for combined ICB. However, gains in efficacy must be balanced against a higher frequency and severity of adverse drug reactions (ADR). Because delays in diagnosis and management might result in symptom worsening and further complications, clinicians shall be well trained to identify ADR promptly and monitor patients adequately...
May 18, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28550680/elemene-increases-autophagic-apoptosis-and-drug-sensitivity-in-human-cisplatin-ddp-resistant-lung-cancer-cell-line-spc-a-1-ddp-by-inducing-beclin-1-expression
#4
Kun Zhou, Liping Wang, Ruirui Cheng, Xia Liu, Shengya Mao, Yan Yan
Drug resistance is the major obstacle for the successful therapy of lung adenocarcinoma. It was suggested that ß-elemene, a major isoform of elemene, could reverse the drug resistance in lung cancer cells. However, the underlying mechanisms remains poorly known. Here, we aimed to investigate whether elemene is involved in the cisplatin (DDP)-resistance of lung adenocarcinoma cells and further explore the underlying mechanism. The results showed that human lung adenocarcinoma cell line SPC-A-1 and its DDP-resistant strain SPC-A-1/DDP had a similar sensitivity to elemene treatment...
May 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28550457/treatment-of-juvenile-dermatomyositis-an-update
#5
REVIEW
Charalampia Papadopoulou, Lucy R Wedderburn
The idiopathic inflammatory myopathies of childhood consist of a heterogeneous group of autoimmune diseases characterised by proximal muscle weakness and pathognomonic skin rashes. The overall prognosis of juvenile myositis has improved significantly over recent years, but the long-term outcome differs substantially from patient to patient, suggestive of distinct clinical phenotypes with variable responses to treatment. High doses of corticosteroids remain the cornerstone of therapy along with other immunosuppressant therapies depending on disease severity and response...
May 26, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28550362/the-role-of-solifenacin-as-monotherapy-or-combination-with-tamsulosin-in-ureteral-stent-related-symptoms-a-systematic-review-and-meta-analysis
#6
Jue Wang, Xiaobei Zhang, Tiande Zhang, Jianjun Mu, Bing Bai, Yi Lei
PURPOSE: Ureteral stenting is associated with various morbidity and reduced quality of life. We systematically evaluated the efficacy and safety of solifenacin as monotherapy, or combined therapy with tamsulosin versus control or tamsulosin monotherapy in stent-related symptoms (SRSs). MATERIALS AND METHODS: Randomized controlled trials evaluating solifenacin or its combination with tamsulosin for the treatment of SRSs were identified via a comprehensive search of Pubmed, Embase, Ovid, The Cochrane Library and relevant sources up to February 2017...
May 26, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28550055/potential-drug-interactions-mediated-by-renal-organic-anion-transporter-oatp4c1
#7
Toshihiro Sato, Eikan Mishima, Nariyasu Mano, Takaaki Abe, Hiroaki Yamaguchi
OATP4C1 is an organic anion transporter expressed in the basolateral membrane of the renal proximal tubules. It plays a major role in the urinary excretion of both exogenous drugs and endogenous compounds. Our previous studies have indicated the importance of OATP4C1 in pathological and physiological conditions; however, the majority of its pharmacological characteristics remained unclear. Therefore, to provide essential information for clinical drug therapy decisions and drug development, we, in this study, attempted to clarify drug interactions mediated by OATP4C1...
May 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28549954/amlexanox-enhances-premature-termination-codon-read-through-in-col7a1-and-expression-of-full-length-type-vii-collagen-potential-therapy-for-recessive-dystrophic-epidermolysis-bullosa
#8
Velina S Atanasova, Qiujie Jiang, Marco Prisco, Christina Gruber, Josefina Piñón Hofbauer, Mei Chen, Cristina Has, Leena Bruckner-Tuderman, John A McGrath, Jouni Uitto, Andrew P South
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. 46% of RDEB patients harbor at least one premature termination codon (PTC) mutation in COL7A1 and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing "read-through" and incorporation of an amino acid at the PTC site...
May 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28549799/a-randomized-controlled-trial-of-the-impact-of-pharmacist-led-patient-centered-pharmaceutical-care-on-patients-medicine-therapy-related-quality-of-life
#9
Phantipa Sakthong, Todsaporn Sangthonganotai
BACKGROUND: Due to a lack of pharmaceutical care (PC)-specific measures for health-related quality of life, a novel generic questionnaire "Patient-Reported Outcomes Measure of Pharmaceutical Therapy for Quality of Life (PROMPT-QoL) was developed. Little was also known about an impact of pharmaceutical care on medicine therapy-related quality of life. OBJECTIVE: First, evaluate the impact of PC on medicine therapy-related QoL using the PROMPT-QoL in Thai patients...
May 11, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28549731/clinical-and-sonographic-biomarkers-of-structural-damage-progression-in-ra-patients-in-clinical-remission-a-prospective-study-with-12-months-follow-up
#10
Julio Ramírez, José Antonio Narváez, Virginia Ruiz-Esquide, Javier Hernández-Gañán, Andrea Cuervo, José Inciarte-Mundo, Maria Victoria Hernández, Miguel Sampayo-Cordero, José Luis Pablos, Raimon Sanmartí, Juan D Cañete
OBJECTIVE: To determine clinical and sonographic biomarkers predicting structural damage progression at 12 months of follow-up as measured by magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) patients in clinical remission. PATIENTS AND METHODS: We included patients with RA in clinical remission, defined as 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for >6 months. Ultrasound scans of both hands and knees and MRI of the dominant hand were performed at baseline and at 12 months...
May 1, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28549390/clinical-and-molecular-monitoring-of-plasmodium-falciparum-resistance-to-antimalarial-drug-artesunate-sulphadoxine-pyrimethamine-in-two-highly-malarious-district-of-madhya-pradesh-central-india-from-2012-2014
#11
Sweta Mishra, Praveen K Bharti, Man M Shukla, Nazia A Ali, Sher S Kashyotia, Avdhesh Kumar, Akshay C Dhariwal, Neeru Singh
The spread of P. falciparum resistant strain has led to a significant resurgence of malaria morbidity and mortality. The current cornerstone in malaria treatment in India is Artemisinin based Combination (Artesunate + Sulphadoxine-Pyrimethamine) Therapy (ACT) for treatment of uncomplicated P. falciparum malaria since 2010. In the present study we assessed the therapeutic efficacy of ACT and molecular monitoring of antimalarial resistance. Therapeutic efficacy was determined by in vivo method using 28 days follow-up...
May 26, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28549377/biocompatibility-of-liposome-nanocarriers-in-the-rat-inner-ear-after-intratympanic-administration
#12
Jing Zou, Hao Feng, Rohit Sood, Paavo K J Kinnunen, Ilmari Pyykko
Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28549369/safety-analysis-of-occupational-exposure-of-healthcare-workers-to-residual-contaminations-of-cytotoxic-drugs-using-fmeca-security-approach
#13
Laetitia Minh Mai Le, Delphine Reitter, Sophie He, Franck Té Bonle, Amélie Launois, Diane Martinez, Patrice Prognon, Eric Caudron
Handling cytotoxic drugs is associated with chemical contamination of workplace surfaces. The potential mutagenic, teratogenic and oncogenic properties of those drugs create a risk of occupational exposure for healthcare workers, from reception of starting materials to the preparation and administration of cytotoxic therapies. The Security Failure Mode Effects and Criticality Analysis (FMECA) was used as a proactive method to assess the risks involved in the chemotherapy compounding process. FMECA was carried out by a multidisciplinary team from 2011 to 2016...
May 22, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28549238/risk-factors-and-mechanisms-contributing-to-tki-induced-vascular-events-in-patients-with-cml
#14
REVIEW
Peter Valent, Emir Hadzijusufovic, Gregor Hoermann, Wolfgang Füreder, Gerit-Holger Schernthaner, Wolfgang R Sperr, Rudolf Kirchmair, Dominik Wolf
Vascular adverse events (VAE) are an emerging problem in patients with chronic myeloid leukemia (CML) receiving second-generation BCR-ABL1 tyrosine kinase inhibitors (TKI). Relevant VAE comprise peripheral, cerebral, and coronary artery changes in patients receiving nilotinib, venous and arterial occlusive events during ponatinib therapy, and pulmonary hypertension in patients receiving dasatinib. Although each TKI binds to a unique profile of molecular targets in leukemic cells and vascular cells, the exact etiology of drug-induced vasculopathies remains uncertain...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28548943/intra-tumour-molecular-heterogeneity-of-clear-cell-renal-cell-carcinoma-reveals-the-diversity-of-the-response-to-targeted-therapies-using-patient-derived-xenograft-models
#15
Baoan Hong, Yong Yang, Sheng Guo, Shayiremu Duoerkun, Xiaohu Deng, Dawei Chen, Shijun Yu, Wubin Qian, Qixiang Li, Qing Li, Kan Gong, Ning Zhang
Inter- and intra-tumour molecular heterogeneity is increasingly recognized in clear cell renal cell carcinoma (ccRCC). It may partially explain the diversity of responses to targeted therapies and the various clinical outcomes. In this study, a 56-year-old male ccRCC patient with multiple metastases received radical nephrectomy and resection of the metastatic tumour in chest wall. The surgical specimens were implanted into nude mice to establish patient-derived xenograft (PDX) models with KI2367 model derived from the primary tumour and KI2368 model from the metastastic tumour...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548931/succinate-an-initiator-in-tumorigenesis-and-progression
#16
REVIEW
Ting Zhao, Xianmin Mu, Qiang You
As an intermediate metabolite of the tricarboxylic acid cycle in mitochondria, succinate is widely investigated for its role in metabolism. In recent years, an increasing number of studies have concentrated on the unanticipated role of succinate outside metabolism, acting as, for instance, an inflammatory signal or a carcinogenic initiator. Actually, succinate dehydrogenase gene mutations and abnormal succinate accumulation have been observed in a battery of hereditary and sporadic malignancies. In this review, we discuss the unexpected role of succinate and possible mechanisms that may contribute to its accumulation...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548923/tubb3-overexpression-has-a-negligible-effect-on-the-sensitivity-to-taxol-in-cultured-cell-lines
#17
Mihoko A Tame, Anna G Manjón, Daria Belokhvostova, Jonne A Raaijmakers, René H Medema
Microtubules are cellular targets for a variety of anticancer therapies because of their critical function in mitosis. Taxol belongs to a class of microtubule targeting agents that suppresses microtubule dynamics and interferes with the functioning of the mitotic spindle, thereby effectively blocking cell cycle progression of rapidly proliferating tumor cells. Despite its antitumor activity, drug resistance remains a common obstacle in improving its overall clinical efficacy. Previous studies have shown that the expression of a specific β-tubulin isotype, βIII-tubulin/TUBB3, is dysregulated in drug-refractory tumors...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548889/therapy-of-advanced-non-small-cell-lung-cancer-with-an-sn-38-anti-trop-2-drug-conjugate-sacituzumab-govitecan
#18
Rebecca Suk Heist, Michael J Guarino, Gregory Masters, W Thomas Purcell, Alexander N Starodub, Leora Horn, Ronald J Scheff, Aditya Bardia, Wells A Messersmith, Jordan Berlin, Allyson J Ocean, Serengulam V Govindan, Pius Maliakal, Boyd Mudenda, William A Wegener, Robert M Sharkey, David M Goldenberg, D Ross Camidge
Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points...
May 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28548676/the-diagnosis-and-management-of-chronic-migraine-in-primary-care
#19
Werner J Becker
BACKGROUND: Chronic migraine is common, affecting approximately 1% of the general population, and causes significant disability. OBJECTIVE: To summarize optimal involvement of primary care physicians in chronic migraine care, and to provide algorithms to assist them in the diagnosis and management of patients with chronic migraine. METHODS: An analysis of diagnostic and treatment needs in chronic migraine, based on a synthesis of the medical literature and clinical experience...
May 26, 2017: Headache
https://www.readbyqxmd.com/read/28548675/inducible-bcl-2-gene-rna-interference-mediated-by-aptamer-integrated-hdv-ribozyme-switch
#20
Yuanyuan Zhang, Jine Wang, Hui Cheng, Na Sun, Min Liu, Zhengyan Wu, Renjun Pei
The regulation of RNA interference (RNAi) could be a powerful method for the study of temporal and dose dependent effects of gene expression. In this study, we designed the hepatitis delta virus (HDV) ribozyme with an embedded theophylline aptamer as the sensor domain and the pri-miRNA of endogenous gene Bcl-2 as the effector domain to engineer an RNAi-regulatory device in MCF-7 cells. The system allowed us to control gene expression by adding theophylline into the culture media in a dose dependent fashion...
May 26, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
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