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https://www.readbyqxmd.com/read/28108739/targeting-oncogenic-vulnerabilities-in-triple-negative-breast-cancer-biological-bases-and-ongoing-clinical-studies
#1
Alberto Ocana, Atanasio Pandiella
Triple negative breast cancer (TNBC) is still an incurable disease despite the great scientific effort performed during the last years. The huge heterogeneity of this disease has motivated the evaluation of a great number of therapies against different molecular alterations. In this article, we review the biological bases of this entity and how the known molecular evidence supports the current preclinical and clinical development of new therapies. Special attention will be given to ongoing clinical studies and potential options for future drug combinations...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28108531/plasmodium-sporozoite-biology
#2
Friedrich Frischknecht, Kai Matuschewski
Plasmodium sporozoite transmission is a critical population bottleneck in parasite life-cycle progression and, hence, a target for prophylactic drugs and vaccines. The recent progress of a candidate antisporozoite subunit vaccine formulation to licensure highlights the importance of sporozoite transmission intervention in the malaria control portfolio. Sporozoites colonize mosquito salivary glands, migrate through the skin, penetrate blood vessels, breach the liver sinusoid, and invade hepatocytes. Understanding the molecular and cellular mechanisms that mediate the remarkable sporozoite journey in the invertebrate vector and the vertebrate host can inform evidence-based next-generation drug development programs and immune intervention strategies...
January 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28108360/archaeal-lipids-in-oral-delivery-of-therapeutic-peptides
#3
Ann-Christin Jacobsen, Sara M Jensen, Gert Fricker, Martin Brandl, Alexander Treusch
Archaea contain membrane lipids that differ from those found in the other domains of life (Eukarya and Bacteria). These lipids consist of isoprenoid chains attached via ether bonds to the glycerol carbons at the sn-2,3 positions. Two types of ether lipids are known, polar diether lipids and bipolar tetraether lipids. The inherent chemical stability and unique membrane-spanning characteristics of tetraether lipids render them interesting for oral drug delivery purposes. Archaeal lipids form liposomes spontaneously (archaeosomes) and may be incorporated in conventional liposomes (mixed vesicles)...
January 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28108325/mononuclear-phagocytes-as-a-target-not-a-barrier-for-drug-delivery
#4
Seok-Beom Yong, Yoonsung Song, Hyung Jin Kim, Qurrat Ul Ain, Yong-Hee Kim
Mononuclear phagocytes have been generally recognized as a barrier to drug delivery. Recently, a new understanding of mononuclear phagocytes (MPS) ontogeny has surfaced and their functions in disease have been unveiled, demonstrating the need for re-evaluation of perspectives on mononuclear phagocytes in drug delivery. In this review, we described mononuclear phagocyte biology and focus on their accumulation mechanisms in disease sites with explanations of monocyte heterogeneity. In the 'MPS as a barrier' section, we summarized recent studies on mechanisms to avoid phagocytosis based on two different biological principles: protein adsorption and self-recognition...
January 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28108249/synthesis-and-biological-evaluation-of-thiazole-derivatives-as-novel-usp7-inhibitors
#5
Chao Chen, Jiemei Song, Jinzheng Wang, Chang Xu, Caiping Chen, Wei Gu, Hongbin Sun, Xiaoan Wen
Herpesvirus-associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with and stabilizes Mdm2, and represents one of the first examples that deubiquitinases oncogenic proteins. USP7 has been regarded as a potential drug target for cancer therapy. Inhibitors of USP7 have been recently shown to suppress tumor cell growth in vitro and in vivo. Based on leading USP7 inhibitors P5091 and P22077, we designed and synthesized a series of thiazole derivatives. The results of in vitro assays showed that the thiazole compounds exhibited low micromolar inhibition activity against both USP7 enzyme and cancer cell lines...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108072/treatment-of-metastatic-breast-cancer-in-eu-analysis-of-market-research-data-from-4q2013-till-3q2014
#6
Mario Cepparulo, Nina Schmidt
OBJECTIVE: Despite the scientific evidence undoubtedly influencing current guidelines on the management of metastatic Breast cancer (mBC), marketing research data suggests this may not be reflected in EU prescribing behavior. Specifically we would like to understand the use of combination chemotherapy vs monotherapy in mBC patients. METHODOLOGY: This study is based on IMS Oncology Analyzer™, a web-based physician panel survey set-up by IMS Health, a global company which specializes in health care information including market research data...
January 17, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28107981/recent-progress-challenges-and-trends-in-trace-determination-of-drug-analysis-using-molecularly-imprinted-solid-phase-microextraction-technology
#7
REVIEW
Saeedeh Ansari, Majid Karimi
The quantification of drugs in biological samples is a significant task for determination of the physiological efficiency in evaluated drugs in the drug discovery. To analysis of the chemical compounds at the trace and ultratrace levels, adequate analytical procedures should be applied. Therefore, sample preparation method undoubtedly is the most important stage in the trace determination process. In spite of the great growth of analytical instrumentation during the recent years, sample preparation is still nowadays considered the impasse of the all analytical procedure, especially in drugs analysis...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107776/activity-based-probes-for-the-multicatalytic-proteasome
#8
REVIEW
David S Hewings, John A Flygare, Ingrid E Wertz, Matthew Bogyo
Proteasomes are multisubunit protease complexes responsible for degrading most intracellular proteins. In addition to removing damaged proteins, they regulate many important cellular processes through the controlled degradation of transcription factors, cell cycle regulators and enzymes. Eukaryotic proteasomes have three catalytic subunits, β1, β2 and β5, that each have different substrate specificities. Additionally, although we know that diverse cell types express proteasome variants with distinct activity and specificity profiles, the functions of these different pools of proteasomes are not fully understood...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107700/comparative-pharmacokinetics-of-eight-major-bioactive-components-in-normal-and-bacterial-diarrhea-mini-pigs-after-oral-administration-of-gegen-qinlian-decoction
#9
Xiao Ling, Yuqiang Xiang, Qingfa Tang, Feilong Chen, Xiaomei Tan
Healthy animals are most widely used in current pharmacokinetic(PK) studies. However, neglecting the effects of specific diseases on drug absorption results in the PK parameters of those experiments not accurately reflecting in vivo drug concentration changes during treatment. In this study, an E. coli infective diarrheal minipig model was applied to explore the pharmacokinetics of Gegen Qinlian decoction (GQD). A simple and rapid ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine the concentrations of the eight GQD components in minipig plasma after intragastric administration of GQD...
January 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28107651/one-ring-to-fight-them-all-the-sulfazecin-story
#10
Daniel Braga, Gerald Lackner
In this issue of Cell Chemical Biology, Li et al. (2017) report on the biosynthesis of the monobactam sulfazecin by Pseudomonas acidophila and hypothesize a novel mechanism of β-lactam ring formation. As monobactam antibiotics are unaffected by some emerging resistance mechanisms (particularly metallo-β-lactamases), this discovery opens prospects to engineer β-lactam antibiotics against multi-drug resistant pathogens.
January 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#11
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28107391/recreational-drug-use-among-chinese-msm-and-transgender-individuals-results-from-a-national-online-cross-sectional-study
#12
Peizhen Zhao, Songyuan Tang, Cheng Wang, Ye Zhang, John Best, Thitikarn May Tangthanasup, Shujie Huang, Bin Yang, Chongyi Wei, Joseph D Tucker, Weiming Tang
BACKGROUND: Recreational drug use has increased considerably among Chinese men who have sex with men (MSM). The phenomenon has the potentially to increase HIV transmission among Chinese MSM. The aims of this study were: 1) to investigate the prevalence of recreational drug use among Chinese MSM, and 2) to explore the correlation between gay smartphone based sex-seeking applications (gay apps), HIV/STIs testing, group sex, commercial sex, sexual roles and poppers use among Chinese MSM...
2017: PloS One
https://www.readbyqxmd.com/read/28107379/experimental-and-in-silico-investigation-of-anti-microbial-activity-of-1-chloro-2-isocyanatoethane-derivatives-of-thiomorpholine-piperazine-and-morpholine
#13
Charles O Nwuche, Oguejiofo T Ujam, Akachukwu Ibezim, Ifeoma B Ujam
The Antibiogram properties of 1-chloro-2-isocyanatoethane derivatives of thiomorpholine (CTC), piperazine (CPC) and morpholine (CMC) were evaluated by the approved agar well diffusion, the minimum inhibitory concentration (MIC) and in silico techniques. A total of fourteen microbial cultures consisting of ten bacteria and four yeast strains were used in the biological study while affinity of the compounds for DNA gyrase, a validated antibacterial drug target, was investigated by docking method. Results indicate that both thiomorpholine and piperazine had zero activity against the Gram negative organisms tested...
2017: PloS One
https://www.readbyqxmd.com/read/28106896/the-2016-bowman-lecture-conjunctival-curses-scarring-conjunctivitis-30-years-on
#14
J K Dart
This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described...
January 20, 2017: Eye
https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#15
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106668/primidone-inhibits-trpm3-and-attenuates-thermal-nociception-in-vivo
#16
Ute Krügel, Isabelle Straub, Holger Beckmann, Michael Schaefer
The melastatin-related transient receptor potential channel TRPM3 is a nonselective cation channel expressed in nociceptive neurons and activated by heat. Since TRPM3-deficient mice show inflammatory thermal hyperalgesia, pharmacological inhibition of TRPM3 may exert antinociceptive properties. Fluorometric Ca influx assays and a compound library containing approved or clinically tested drugs were used to identify TRPM3 inhibitors. Biophysical properties of channel inhibition were assessed using electrophysiological methods...
January 12, 2017: Pain
https://www.readbyqxmd.com/read/28106223/next-generation-of-network-medicine-interdisciplinary-signaling-approaches
#17
REVIEW
Tamas Korcsmaros, Maria Victoria Schneider, Giulio Superti-Furga
In the last decade, network approaches have transformed our understanding of biological systems. Network analyses and visualizations have allowed us to identify essential molecules and modules in biological systems, and improved our understanding of how changes in cellular processes can lead to complex diseases, such as cancer, infectious and neurodegenerative diseases. "Network medicine" involves unbiased large-scale network-based analyses of diverse data describing interactions between genes, diseases, phenotypes, drug targets, drug transport, drug side-effects, disease trajectories and more...
January 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28105946/a-physarum-inspired-prize-collecting-steiner-tree-approach-to-identify-subnetworks-for-drug-repositioning
#18
Yahui Sun, Pathima Nusrath Hameed, Karin Verspoor, Saman Halgamuge
BACKGROUND: Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning...
December 5, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/28105862/structural-data-and-immunomodulatory-properties-of-a-water-soluble-heteroglycan-extracted-from-the-mycelium-of-an-italian-isolate-of-ganoderma-lucidum
#19
Raffaele Carrieri, Rosanna Manco, Daniela Sapio, Marco Iannaccone, Andrea Fulgione, Marina Papaianni, Bruna de Falco, Laura Grauso, Paola Tarantino, Flora Ianniello, Virginia Lanzotti, Ernesto Lahoz, Rosanna Capparelli
Mushrooms produce a wide range of bioactive polysaccharides, different from each other in chemical structure and biological effects. In the last years, the idea to develop functional foods or drugs containing fungal polysaccharides is attracting great attention. Fruiting bodies of Basidiomycetes Ganoderma lucidum are commonly used in Oriental medicine to treat several disorders. G. lucidum polysaccharides - mainly β-glucans and heteroglycans - have numerous biological properties such as antitumour and immunomodulatory activities...
January 20, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28105728/invention-of-stimulus-responsive-peptide-bond-cleaving-residue-spr-and-its-application-to-chemical-biology-tools
#20
Akira Shigenaga, Jun Yamamoto, Taiki Kohiki, Tsubasa Inokuma, Akira Otaka
Elucidation of biological functions of peptides and proteins is essential for understanding peptide/protein-related biological events and developing drugs. Caged peptides and proteins that release a parent active peptide/protein by photo-irradiation have successfully been employed to elucidate the functions. Whereas the usual caged peptide/protein enables conversion of an inactive form to an active form (OFF-to-ON conversion) by photo-induced deprotection, photo-triggered main chain cleavage is reported to be applicable to ON-to-OFF conversion...
January 19, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
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