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Targeted therapy

H D Guo, Y J Chu, W P Yuan
No abstract text is available yet for this article.
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Karen E Bowker, Alan R Noel, Sharon Tomaselli, Marie Attwood, Alasdair P MacGowan
Background: The pharmacodynamics of inhaled antimicrobials are poorly studied. Amikacin is being developed for inhalational therapy as BAY 41-6551. Objectives: We employed an in vitro pharmacokinetic model to study the pharmacokinetics/pharmacodynamics of amikacin. Methods: A dose-ranging design was used to establish fAUC/MIC and fCmax/MIC targets for static, -1 log drop and -2 log drop effects for strains of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa...
March 19, 2018: Journal of Antimicrobial Chemotherapy
Heitor S P de Souza, Claudio Fiocchi
Despite unquestionable progress in the management of inflammatory bowel disease (IBD) and the much improved clinical results achievable today in Crohn's disease (CD) and ulcerative colitis (UC) patients, the overall therapeutic outcome remains far from optimal. The main reason of this partial success is that all current medications only block individual components of a highly complex disease process that results from the integration of multiple and incompletely identified pathogenic components. Thus, if further progress is to be achieved in IBD therapeutics and we want to move from the current success rate to nearly 100%, bold new ideas must be entertained and new approaches put into practice...
March 19, 2018: Inflammatory Bowel Diseases
Xu-Tao Lin, Xiao-Bin Zheng, De-Jun Fan, Qiu-Qiong Yao, Jian-Cong Hu, Lei Lian, Xiao-Jian Wu, Ping Lan, Xiao-Sheng He
Background: Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including Crohn's disease (CD). Genetic analyses have found that microRNA (miRNA) levels are altered in the intestinal tissues of CD patients. Methods: The Sequencing Alternative Poly-Adenylation Sites (SAPAS) method was used to compare the 3' end of the total mRNA sequence of 3 surgical specimens of CD patients (including inflamed tissues and corresponding noninflamed tissues in each case)...
March 19, 2018: Inflammatory Bowel Diseases
Mark Sherman, Lydia Contreras
Recent advances in computational and experimental methods have led to novel avenues for therapeutic development. Utilization of nucleic acids as therapeutic agents and/or targets has been recently gaining attention due to their potential as high-affinity, selective molecular building blocks for various therapies. Notably, development of computational algorithms for predicting accessible RNA binding sites, identifying therapeutic target sequences, modeling delivery into tissues, and designing binding aptamers have enhanced therapeutic potential for this new drug category...
March 18, 2018: Current Opinion in Biotechnology
Jingjing Song, Da Ma, Xiangqi Liu, Yichen Chen, Juan Fang, Vivian Wai Yan Lui, Sijia Zhao, Juan Xia, Bin Cheng, Zhi Wang
Thrombomodulin (TM, also known as CD141), which functions as an anticoagulant, is widely expressed on cell surface of a variety of cell types, including human blood cells as well as certain immune cells. To determine whether TM could be a potential marker for OSCC diagnosis as well as a molecular target for OSCC therapy, we examined the expression of TM in an oral cancer tissue microarray with 153 oral cancer tissues. Further, we also analyzed the expression of TM on DCs of 36 OSCC patients and 36 healthy donors...
March 18, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Shetal A Patel, Andy J Minn
The success of immune checkpoint blockade in patients with a wide variety of malignancies has changed the treatment paradigm in oncology. However, combination therapies with immune checkpoint blockade will be needed to overcome resistance and broaden the clinical utility of immunotherapy. Here we discuss a framework for rationally designing combination therapy strategies based on enhancing major discriminatory functions of the immune system that are corrupted by cancer-namely, antigenicity, adjuvanticity, and homeostatic feedback inhibition...
March 20, 2018: Immunity
Jie Gao, Jun Li, Wen-Chao Geng, Fang-Yuan Chen, Xingchen Duan, Zhe Zheng, Dan Ding, Dong-Sheng Guo
Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although displaying the efficacy in construction of activatable photosensitizers (PSs), direct covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host-guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state)...
March 21, 2018: Journal of the American Chemical Society
Jeffrey M Pernica, Andrew P Steenhoff, Margaret Mokomane, Banno Moorad, Kwana Lechiile, Marek Smieja, Loeto Mazhani, Ji Cheng, Matthew S Kelly, Mark Loeb, Ketil Stordal, David M Goldfarb
[This corrects the article DOI: 10.1371/journal.pone.0185177.].
2018: PloS One
Simon Heeke, Véronique Hofman, Elodie Long-Mira, Virginie Lespinet, Salomé Lalvée, Olivier Bordone, Camille Ribeyre, Virginie Tanga, Jonathan Benzaquen, Sylvie Leroy, Charlotte Cohen, Jérôme Mouroux, Charles Hugo Marquette, Marius Ilié, Paul Hofman
Background : With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of NGS for routine clinical practice is still hampered by sophisticated workflows, complex bioinformatics analysis and medical interpretation. Therefore, the performance of the novel QIAGEN GeneReader NGS system was compared to an in-house ISO-15189 certified Ion PGM NGS platform...
March 21, 2018: Cancers
Benjamin B Kasten, Patsy G Oliver, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. There is a clinical need for effective, targeted therapy strategies that destroy both differentiated TNBC cells and TNBC cancer initiating cells (CICs), as the latter are implicated in the metastasis and recurrence of TNBC. Chondroitin sulfate proteoglycan 4 (CSPG4) is overexpressed on differentiated tumor cells and CICs obtained from TNBC patient specimens, suggesting that CSPG4 may be a clinically relevant target for the imaging and therapy of TNBC...
March 21, 2018: International Journal of Molecular Sciences
Robert Campbell, Geoffrey Chong, Eliza A Hawkes
Bruton's tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in proliferation of solid malignancies is expanding the indication of BTKi into non-hematological malignancies...
March 21, 2018: Journal of Clinical Medicine
Pradeep Phadnis, Purnima Dey Sarkar, Mithun Singh Rajput
BACKGROUND: Initial evidences have shown that diabetes mellitus occurs concomitantly with obsessive-compulsive disorder (OCD) symptomatology. Serotonergic psychiatric therapy posits that serotonin is a central character in the management of OCD. Hence, it is worth investigating novel chemical entities affecting the serotonergic system for targeting OCD. An isoflavonoid phytoestrogen, genistein, has been recognized as of great pharmacological value especially for protecting neurodegeneration, depression (serotonin regulation), and diabetes...
March 21, 2018: Journal of Basic and Clinical Physiology and Pharmacology
Riccardo Moia, Fary Diop, Chiara Favini, Ahad Ahmed Kodipad, Gianluca Gaidano
Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Deregulation of apoptosis is a major pathogenetic feature, and represents a therapeutic target. TP53 disrupted patients are categorized as high risk patients and are treated with novel target therapies. Among these new drugs, venetoclax, an orally bioavailable BCL2 inhibitor, has shown high efficacy also in relapsed/refractory CLL with TP53 disruption. Venetoclax has also been tested in combination with other drugs without compromising venetoclax dose and with a good safety profile...
March 21, 2018: Expert Review of Hematology
Yuanqin Yin, Jingjing Cai, Fandong Meng, Chengguang Sui, Youhong Jiang
OBJECTIVE: The study aimed to investigate the molecular mechanism of miR-144 and CEP55 as well as the influence of their interaction on the cell proliferation, migration, invasion, cell cycle and cell apoptosis in breast cancer. METHODS: In this study, The Cancer Genome Atlas (TCGA, ) database was used for microarray analysis. The expressions of miR-144 and CEP55 in 40 adjacent tissues and 36 tumor tissues were examined by western blot, qRT-PCR and immunohistochemistry...
March 21, 2018: Cancer Biology & Therapy
Marzieh Salehi Fadardi, Larry Allen Abel
SIGNIFICANCE: This study compares saccades and visual task performance in patients with infantile nystagmus syndrome (INS) with that in normally sighted individuals under mental load. The results highlighted that to more completely evaluate INS therapies recognition time should also be measured with mental load, resembling real-world conditions. PURPOSE: Patients with INS may complain of "being slow to see." Stress is reported to worsen nystagmus and to prolong visual recognition time...
March 21, 2018: Optometry and Vision Science: Official Publication of the American Academy of Optometry
Lihong Wang, Chih-Hsin Tang, Tingting Lu, Yi Sun, Guohong Xu, Chien-Chung Huang, Shun-Fa Yang, Chen-Ming Su
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. To date, the specific mechanisms that drive RA disease remain unknown and provide the impetus for genetic investigations into the development of RA. Researchers hope to identify gene polymorphisms that could serve as treatment targets in patients with RA. We have previously suggested that the gene encoding the pro-inflammatory adipokine resistin (RETN) may correlate with RA development. In this report, we sought to determine whether selected RETN single nucleotide polymorphisms (SNPs) are associated with RA susceptibility and clinicopathological characteristics...
March 2018: Medicine (Baltimore)
Mohamed Ahmed Abdel-Mohsen, Ahlam Abd-Allah El-Braky, Abeer Abd El-Rahim Ghazal, Mohammed Mohammed Shamseya
The aims of this study were to investigate the interplay between autophagy and apoptosis and to investigate the association between both of autophagy and apoptosis and vitamin D and its receptor in hepatitis C virus (HCV) viral infection and its implication in the progression into hepatocellular carcinoma (HCC).A cross-sectional study where serum levels of microtubule-associated protein 1A/1B-light chain 3 (LC3); marker of autophagy, caspase-3; marker of apoptosis, vitamin D3 and vitamin D receptor (VDR) were measured in healthy subjects as well as HCV and HCV-HCC patients using enzyme-linked immunosorbent assay technique...
March 2018: Medicine (Baltimore)
Ioana Agache, Liliana Rogozea
PURPOSE OF REVIEW: The precision medicine concept is both appealing and challenging. We review here the recent findings in the endotype-driven approach for major allergic diseases. RECENT FINDINGS: Stratified medicine for different allergic diseases can identify patients who are more likely to benefit or experience an adverse reaction in response to a given therapy and anticipate their long-term outcome and vital risk. In addition, this approach potentially facilitates drug development and prevention strategies...
March 20, 2018: Current Opinion in Allergy and Clinical Immunology
Anthony S Wierzbicki, Timothy M Reynolds, Adie Viljoen
PURPOSE OF REVIEW: A number of novel trials have assessed the efficacy of new lipid-lowering therapies in cardiovascular disease (CVD). RECENT FINDINGS: Proprotein convertase subtilisin kexin-9 inhibitors reduce low-density lipoprotein cholesterol (LDL-C) by 50-55%. A CVD outcome trial in patients with acute coronary syndromes with evolocumab achieved a LDL-C of 0.8 mmol/l (31 mg/dl) and a 20% relative risk reduction in CVD events in 2.2 years. Cholesterol ester transfer protein inhibitors raise high-density lipoprotein cholesterol and can lower LDL-C...
March 19, 2018: Current Opinion in Cardiology
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