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Biological therapies

Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Edouard Louis
Biologic treatments have revolutionized the way we treat inflammatory bowel disease patients (IBD). Anti-tumor necrosis factor (anti-TNF) antibodies are superior to conventional therapies to achieve sustained remission without steroids and mucosal healing. The objective of IBD treatment has evolved from symptom alleviation to a combination of absence of symptoms and intestinal healing. Nevertheless, biologics are expensive and are associated with an increased risk of infections and possibly skin cancers. Therefore, the duration of these treatments may be questioned, and stopping them may be contemplated by some patients and clinicians, while it is sometimes even imposed by some jurisdictions across the world...
March 14, 2018: Inflammatory Bowel Diseases
A Hillary Steinhart
No abstract text is available yet for this article.
March 14, 2018: Inflammatory Bowel Diseases
P D Tar, N A Thacker, M Babur, Y Watson, S Cheung, R A Little, R G Gieling, K J Williams, J P B O'Connor
Motivation: Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both normal development and also in response to treatment. The large variations observed in control group tumors can obscure detection of significant therapeutic effects due to the ambiguity in attributing causes of change. This can hinder development of effective therapies due to limitations in experimental design, rather than due to therapeutic failure...
March 14, 2018: Bioinformatics
Jiang He, Yuzu Zhao, Erhu Zhao, Xianxing Wang, Zhen Dong, Yibiao Chen, Liqun Yang, Hongjuan Cui
Background: The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods: An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5...
March 14, 2018: Neuro-oncology
Silvia Salerno, Aída Nelly García-Argáez, Elisabetta Barresi, Sabrina Taliani, Francesca Simorini, Concettina La Motta, Giorgio Amendola, Stefano Tomassi, Sandro Cosconati, Ettore Novellino, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via
Inhibition of angiogenesis via blocking vascular endothelial growth factor receptor (VEGFR) signaling pathway emerged as an established approach in anticancer therapy. So far, many monoclonal antibodies and ATP-competitive small molecule inhibitors have been clinically validated and approved. In this study, structure-activity relationships (SAR) within the 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidine class of kinase inhibitors were further refined by the synthesis and biological evaluation of new compounds 1-21 featuring different substitution patterns on the pendant phenyl moiety, combined with H, OCH3 , or Cl at 8-position...
March 7, 2018: European Journal of Medicinal Chemistry
Sweet Ping Ng, Joseph M Herman
Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies commonly utilize conventional radiotherapy treatment fractionation and technique (typically 3-D conformal radiotherapy or intensity modulated radiotherapy). Although no clear benefit in overall survival was demonstrated in those studies, those who received radiotherapy did have a clear benefit in terms of local control...
March 16, 2018: Cancers
Guido Kobbe, Thomas Schroeder, Rainer Haas, Ulrich Germing
Allogeneic blood stem cell transplantation (aBSCT) still is the only curative therapy for patients with myelodysplastic syndromes. While it carries the hope for cure for some patients, it may result in severe toxicity and death from complications or recurrent disease in others. Recent developments have improved patient and donor selection as well as technical aspects of the transplant procedure and post-transplant care, including early detection and treatment of relapse. Areas covered: This review will discuss current stratification tools to identify suitable patients, donors and transplant techniques...
March 16, 2018: Expert Review of Hematology
Lesley Uttley, Iñigo Bermejo, Shijie Ren, Marrissa Martyn-St James, Ruth Wong, David L Scott, Adam Young, Matt Stevenson
As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Pfizer) of tofacitinib (TOF; Xeljanz® ) to submit evidence of the drug's clinical and cost-effectiveness in the treatment of rheumatoid arthritis (RA) after the failure of conventional disease-modifying antirheumatic drugs (cDMARDs). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
March 15, 2018: PharmacoEconomics
Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Haseeb Khaliq, Zhong Juming, Peng Ke-Mei
Boron is an essential mineral that plays an important role in several biological processes. Boron is required for growth of plants, animals, and humans. There are increasing evidences of this nutrient showing a variety of pleiotropic effects, ranging from anti-inflammatory and antioxidant effects to the modulation of different body systems. In the past few years, the trials showed disease-related polymorphisms of boron in different species, which has drawn attention of scientists to the significance of boron to health...
March 15, 2018: Biological Trace Element Research
Maliha Khan, Rabbia Siddiqi, Kiran Naqvi
Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2-5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression...
March 15, 2018: Annals of Hematology
Fariba Tayyari, G A Nagana Gowda, Olufunmilayo F Olopade, Richard Berg, Howard H Yang, Maxwell P Lee, Wilfred F Ngwa, Suresh K Mittal, Daniel Raftery, Sulma I Mohammed
Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology...
February 20, 2018: Oncotarget
Long Chen, Yifeng Jiang, Zhen Du
Although previous studies have demonstrated that dental pulp stem cells (DPSCs) from mature and immature teeth exhibit potential for multi-directional differentiation, the molecular and biological difference between the DPSCs from mature and immature permanent teeth has not been fully investigated. In the present study, 500 differentially expressed genes from dental pulp cells (DPCs) in mature and immature permanent teeth were obtained from the Gene Expression Omnibus online database. Based on bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery, these genes were divided into a number of subgroups associated with immunity, inflammation and cell signaling...
April 2018: Experimental and Therapeutic Medicine
Emmanuelle A D Schindler, Ryan M Wallace, Jordan A Sloshower, Deepak C D'Souza
Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class...
2018: Frontiers in Pharmacology
Barry H Smith, Lawrence S Gazda, Thomas J Fahey, Angelica Nazarian, Melissa A Laramore, Prithy Martis, Zoe P Andrada, Joanne Thomas, Tapan Parikh, Sudipta Sureshbabu, Nathaniel Berman, Allyson J Ocean, Richard D Hall, David J Wolf
Objective: The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Fleur M Ferguson, Nathanael S Gray
Receptor tyrosine kinase signalling pathways have been successfully targeted to inhibit proliferation and angiogenesis for cancer therapy. However, kinase deregulation has been firmly demonstrated to play an essential role in virtually all major disease areas. Kinase inhibitor drug discovery programmes have recently broadened their focus to include an expanded range of kinase targets and therapeutic areas. In this Review, we provide an overview of the novel targets, biological processes and disease areas that kinase-targeting small molecules are being developed against, highlight the associated challenges and assess the strategies and technologies that are enabling efficient generation of highly optimized kinase inhibitors...
March 16, 2018: Nature Reviews. Drug Discovery
(no author information available yet)
▼Dupilumab (Dupixent - Sanofi-Aventis Groupe), a monoclonal antibody for the treatment of moderate-to-severe atopic dermatitis in adults who require systemic therapy, was licensed by the European Medicines Agency in September 2017. It is the first biological drug approved specifically for this condition. Here, we review the evidence for its efficacy and safety and consider its place in therapy.
March 2018: Drug and Therapeutics Bulletin
Konstantinos H Katsanos, Konstantinos Papamichael, Joseph D Feuerstein, Dimitrios K Christodoulou, Adam S Cheifetz
The pharmacological management of inflammatory bowel disease (IBD) over the last two decades has transitioned from reliance on aminosalycilates, corticosteroids and immunomodulators to earlier treatment with anti-tumor necrosis factor (anti-TNF) therapy. Nevertheless, 20-30% of patients discontinue anti-TNF therapy for primary non-response and another 30-40% for losing response within one year of treatment. These undesirable therapeutic outcomes can be attributed to pharmacokinetic (anti-drug antibodies and/or low drug concentrations) or pharmacodynamic issues characterized by a non-TNF driven inflammation...
March 12, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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