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Biological therapies

M J Santos, M Conde, A F Mourão, F O Ramos, M Cabral, I Brito, M P Ramos, R C Marques, S M Gomes, M Guedes, M J Gonçalves, P Estanqueiro, C Zilhão, M Rodrigues, C Henriques, M Salgado, H Canhão, J E Fonseca, J M Gomes
OBJECTIVE: To provide evidence-based guidance for the rational and safe prescription of biological therapies in children and adolescents with juvenile idiopathic arthritis (JIAs) considering the latest available evidence and the new licensed biologics. METHODS: Rheumatologists and Pediatricians with expertise in Pediatric Rheumatology updated the recommendations endorsed by the Portuguese Society of Rheumatology and the Portuguese Society of Pediatrics based on published evidence and expert opinion...
July 2016: Acta Reumatológica Portuguesa
Rory J McCrimmon
Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Andreas Zietzer, Eva Elina Buschmann, Doreen Janke, Lulu Li, Michèle Brix, Heike Meyborg, Philipp Stawowy, Constantin Jungk, Ivo Buschmann, Philipp Hillmeister
AIM: Physical activity is a potent way to impede vascular aging. However, patients who suffer from peripheral artery disease (PAD) are often unable to exercise adequately. For those patients, we have developed individual shear rate therapy (ISRT), which is an adaptation of external counterpulsation and enhances endovascular fluid shear stress to increase collateral growth (arteriogenesis). To evaluate the effects of physical exercise and ISRT on the telomere biology of peripheral blood mononuclear cells (PBMCs), we conducted two clinical trials...
October 22, 2016: Acta Physiologica
Pat Whitworth, Peter Beitsch, Angela Mislowsky, James V Pellicane, Charles Nash, Mary Murray, Laura A Lee, Carrie L Dul, Michael Rotkis, Paul Baron, Lisette Stork-Sloots, Femke A de Snoo, Jennifer Beatty
PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity...
October 21, 2016: Annals of Surgical Oncology
Aditya K Gupta, Jessie Carviel, William Abramovits
Alopecia areata (AA) is non-scarring hair loss resulting from an autoimmune disorder. Severity varies from patchy hair loss that often spontaneously resolves to severe and chronic cases that can progress to total loss of scalp and body hair. Many treatments are available; however, the efficacy of these treatments has not been confirmed, especially in severe cases, and relapse rates are high. First-line treatment often includes corticosteroids such as intralesional or topical steroids for mild cases and systemic steroids or topical immunotherapy with diphenylcyclopropenone or squaric acid dibutylester in severe cases...
October 22, 2016: American Journal of Clinical Dermatology
Danielle L Brunjes, Adam Castano, Autumn Clemons, Jonah Rubin, Mathew S Maurer
Wild type transthyretin cardiac amyloidosis (ATTRwt), formerly called senile cardiac amyloidosis (SCA), is almost exclusively a disorder of older adults. As the population ages, the diagnosis of ATTRwt will increase making it the most common form of cardiac amyloidosis. An important precondition to reduce under-diagnosis and misdiagnosis is to maintain a high index of suspicion for cardiac amyloidosis. Several clues can be gleaned from the clinical history, physical exam, electrocardiogram and non-invasive imaging techniques...
October 18, 2016: Journal of Cardiac Failure
Simon Tarp, Daniel E Furst, Anna Dossing, Mikkel Østergaard, Tove Lorenzen, Michael S Hansen, Jasvinder A Singh, Ernest H Choy, Maarten Boers, Maria E Suarez-Almazor, Lars E Kristensen, Henning Bliddal, Robin Christensen
OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events...
September 14, 2016: Seminars in Arthritis and Rheumatism
Shuai Wang, Li-Jie Zhao, Yi-Chao Zheng, Dan-Dan Shen, Er-Fei Miao, Xue-Peng Qiao, Li-Juan Zhao, Ying Liu, Ruilei Huang, Bin Yu, Hong-Min Liu
A new series of [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1 inhibitors were designed, synthesized, and further evaluated for their cytotoxicity against MGC-803, EC109, A549 and PC-9 cells as well as the ability of inhibiting LSD1. Some of these compounds showed potent inhibition toward LSD1 and selectively inhibited growth of A549 and PC-9 cells. Compound 6l potently inhibited growth of PC-9 cells (IC50 = 0.59 μM), about 4-fold more potent than 5-FU. Further SARs studies led to the identification of compounds 6l-m, which had good growth inhibition against all the tested cancer cell lines and were much more potent than 5-FU and GSK2879552...
October 14, 2016: European Journal of Medicinal Chemistry
Sarah Fernandes Teixeira, Ricardo Alexandre de Azevedo, Arthur Carvalho Silva, Rodolpho Campos Braga, Salomão Dória Jorge, José Alexandre Marzagão Barbuto, Carolina Horta Andrade, Adilson Kleber Ferreira
Even with all improvements in both diagnostic and therapeutic techniques, lung cancer remains as the most lethal and prevalent cancer in the world. Therefore, new therapeutic drugs and new strategies of drug combination are necessary to provide treatments that are more efficient. Currently, standard therapy regimen for lung cancer includes platinum drugs, such as cisplatin, oxaliplatin, and carboplatin. Besides of the better toxicity profile of oxaliplatin when compared with cisplatin, peripheral neuropathy remains as a limitation of oxaliplatin dose...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
J J Paredes, Nelly Andarawis-Puri
Tendon injuries, known as tendinopathies, are common musculoskeletal injuries that affect a wide range of the population. Canonical tendon healing is characterized by fibrosis, scar formation, and the loss of tissue mechanical and structural properties. Understanding the regenerative tendon environment is an area of increasing interest in the field of musculoskeletal research. Previous studies have focused on utilizing individual elements from the fields of biomechanics, developmental biology, cell and growth factor therapy, and tissue engineering in an attempt to develop regenerative tendon therapeutics...
October 21, 2016: Annals of the New York Academy of Sciences
Gaia Palmini, Roberto Zonefrati, Carmelo Mavilia, Alessandra Aldinucci, Ettore Luzi, Francesca Marini, Alessandro Franchi, Rodolfo Capanna, Annalisa Tanini, Maria Luisa Brandi
The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients...
October 14, 2016: Journal of Visualized Experiments: JoVE
Stacey Bagby, Wells A Messersmith, Todd M Pitts, Anna Capasso, Marileila Varella-Garcia, Peter J Klauck, Jihye Kim, Aik-Choon Tan, S Gail Eckhardt, John J Tentler, John Arcaroli
Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology...
September 30, 2016: Journal of Visualized Experiments: JoVE
S Sengupta, G Mao, Z S Gokaslan, P Sampath
Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment...
October 21, 2016: Cancer Gene Therapy
Daniel M Czyż, Neeta Jain-Gupta, Howard A Shuman, Sean Crosson
Brucella abortus is an intracellular bacterial pathogen and an etiological agent of the zoonotic disease known as brucellosis. Brucellosis can be challenging to treat with conventional antibiotic therapies and, in some cases, may develop into a debilitating and life-threatening chronic illness. We used multiple independent assays of in vitro metabolism and intracellular replication to screen a library of 480 known bioactive compounds for novel B. abortus anti-infectives. Eighteen non-cytotoxic compounds specifically inhibited B...
October 21, 2016: Scientific Reports
Peter J Meikle, Scott A Summers
Obesity, insulin resistance, type 2 diabetes mellitus and cardiovascular disease form a metabolic disease continuum that has seen a dramatic increase in prevalence in developed and developing countries over the past two decades. Dyslipidaemia resulting from hypercaloric diets is a major contributor to the pathogenesis of metabolic disease, and lipid-lowering therapies are the main therapeutic option for this group of disorders. However, the fact that dysfunctional lipid metabolism extends far beyond cholesterol and triglycerides is becoming increasingly clear...
October 21, 2016: Nature Reviews. Endocrinology
Marco Giardiello, Neill J Liptrott, Tom O McDonald, Darren Moss, Marco Siccardi, Phil Martin, Darren Smith, Rohan Gurjar, Steve P Rannard, Andrew Owen
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral...
October 21, 2016: Nature Communications
Y-M Chiu, C-H Tang, S-T Hung, Y-W Yang, C-H Fang, H-Y Lin
OBJECTIVES: Few studies on tumour necrosis factor (TNF) inhibitor-associated tuberculosis (TB) and hepatic events have been performed in regions where these risks are elevated. This study aimed to provide a direct comparison between adalimumab and etanercept in a high-risk population and to address the implications for physicians working with patients in such an environment. METHOD: Data collected from the National Health Insurance Research Database (NHIRD) in Taiwan between 2007 and 2011 were analysed retrospectively for incidences of eight adverse events associated with TNF-α inhibitors...
October 21, 2016: Scandinavian Journal of Rheumatology
Liron Frishman-Levy, Shai Izraeli
Central nervous system acute lymphoblastic leukaemia (CNS-ALL) is a major clinical problem. CNS-directed 'prophylactic' chemo- or radio - therapy is associated with significant early and long-term toxicity. Moreover, greater than a third of the relapses occur in the CNS. To design specific, more effective and less toxic therapy and for personalized precise adjustment of prophylactic therapy there is a need for better understanding of the biology of this disease. Specifically, the precise neurotropic mechanisms of ALL are currently unclear, as is the pathogenesis of CNS relapse...
October 21, 2016: British Journal of Haematology
Davod Pashoutan Sarvar, Karim Shamsasenjan, Parvin Akbarzadehlaleh
Mesenchymal stromal/stem cells (MSCs) are involved in tissue homeostasis through direct cell-to-cell interaction, as well as secretion of soluble factors. Exosomes are the sort of soluble biological mediators that obtained from MSCs cultured media in vitro. MSC-derived exosomes (MSC-DEs) which produced under physiological or pathological conditions are central mediators of intercellular communications by conveying proteins, lipids, mRNAs, siRNA, ribosomal RNAs and miRNAs to the neighbor or distant cells. MSC-DEs have been tested in various disease models, and the results have revealed that their functions are similar to those of MSCs...
September 2016: Advanced Pharmaceutical Bulletin
Francesca Salamanna, Veronica Borsari, Silvia Brogini, Gianluca Giavaresi, Annapaola Parrilli, Simona Cepollaro, Matteo Cadossi, Lucia Martini, Antonio Mazzotti, Milena Fini
One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively...
October 19, 2016: Oncotarget
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