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https://www.readbyqxmd.com/read/28723514/optimal-treatment-sequence-for-metastatic-castration-resistant-prostate-cancer
#1
REVIEW
David Lorente, Karim Fizazi, Christopher Sweeney, Johann S de Bono
CONTEXT: Unprecedented development of therapeutics for prostate cancer in recent years has left clinicians with the challenge of adequately sequencing therapeutic agents to optimise patient benefit. No clear guidelines exist on optimal treatment sequences. OBJECTIVE: To summarise the evidence on first-line activity, cross-resistance, and potential combinations of agents approved for metastatic castration-resistant prostate cancer (mCRPC). EVIDENCE ACQUISITION: A nonsystematic literature search of articles on agent sequencing in mCRPC in PubMed and relevant cancer conferences up to June 2016 was performed...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723416/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-2-neuroendocrine-tumours-hepatocellular-carcinoma-and-gastro-intestinal-stromal-tumours
#2
REVIEW
Cindy Neuzillet, Louis de Mestier, Benoît Rousseau, Olivier Mir, Mohamed Hebbar, Hemant M Kocher, Philippe Ruszniewski, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28722479/oxindole-based-syk-and-jak3-dual-inhibitors-for-rheumatoid-arthritis-designing-synthesis-and-biological-evaluation
#3
Maninder Kaur, Manjinder Singh, Om Silakari
AIM: Autoimmune disorders have complex pathophysiology and focus is laid on the development of multitargeted agents. Two well-established kinases: SYK and JAK3, were considered to design dual inhibitors as potential therapeutics using various molecular-modeling approaches. Mehodology: Pharmacophore models for SYK and JAK3 were generated using oxindole-based inhibitors. Furthermore, an in-house database was designed that was screened against the best selected models. The obtained hits were employed for docking analysis and subjected to MM-GBSA analysis and molecular dynamic simulation...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28722301/recent-research-advances-in-selective-matrix-metalloproteinase-13-inhibitors-as-anti-osteoarthritis-agents
#4
REVIEW
Xin-Wen Xie, Ren-Zhong Wan, Zhao-Peng Liu
Matrix metalloproteinase-13 (MMP-13) plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). The subtle differences between the S1' loop of MMP-13 and that of other MMPs offer a structural base for the design of selective MMP-13 inhibitors to mitigate the unperceived risk associated with inhibiting other MMP isoforms. In this review, we summarize zinc-binding and non-zinc-binding selective MMP-13 inhibitors. The zinc-binding MMP-13 inhibitors contain a small set of zinc-binding groups (ZBGs), including hydroxamic acid, pyrimidinetrione, reversed hydroxamic acid and hydantoin, carboxylic acid, 1,2,4,-triazole, and 1,2,4,-triazolone...
July 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28722154/application-of-headspace-solid-phase-microextraction-followed-by-gas-chromatography-coupled-with-mass-spectrometry-spme-gc-ms-to-determine-esters-of-carboxylic-acids-and-other-volatile-compounds-in-d-maculatus-and-d-ater-lipids
#5
Magdalena Cerkowniak, Mieczysława I Boguś, Emilia Włóka, Piotr Stepnowski, Marek Gołębiowski
A constant problem in veterinary medicine, human healthcare, agriculture, forestry or horticulture is the large number of pests, and the lack of effective methods to combat them which cause no harm to the rest of the environment. It is recommended and desired to reduce the use of chemicals and increase the use of agents based on the knowledge acquired in the field of biology, chemistry, and agrochemicals. To learn the defense mechanisms of insects we should consider not only the site of their physiological ability to protect against external factors (cuticle), but also check the possibility of chemical protection, formed by all compounds on the surface and in the body of insects...
July 19, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28721824/potential-anti-inflammatory-effects-of-hesperidin-from-the-genus-citrus
#6
Silvia Tejada, Samuel Pinya, Miquel Martorell, Xavier Capó, Josep A Tur, Antoni Pons, Antoni Sureda
The benefits of the Mediterranean diet for protecting against many diseases are usually attributed to high consumption of certain foods, characterized by the presence of bioactive substances such as polyphenols. Citrus fruits, which are cultivated and consumed worldwide, are typical products of the Mediterranean diet. Inflammation plays an important role in the pathogenesis of numerous diseases such as arthritis, allergies and neurodegenerative disorders, among others. Dietary polyphenols constitute a large family of bioactive substances with potential beneficial effects against a broad group of diseases...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721684/pharmacokinetics-microscale-distribution-and-dosimetry-of-alpha-emitter-labeled-anti-pd-l1-antibodies-in-an-immune-competent-transgenic-breast-cancer-model
#7
Jessie R Nedrow, Anders Josefsson, Sunju Park, Tom Bäck, Robert F Hobbs, Cory Brayton, Frank Bruchertseifer, Alfred Morgenstern, George Sgouros
BACKGROUND: Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted delivery of high LET radiation to the tumor microenvironment via an immune checkpoint inhibitor. METHODS: The impact of protein concentration on the distribution of (111)In-DTPA-anti-PD-L1-BC, an (111)In-antibody conjugate targeted to PD-L1, was evaluated in an immunocompetent mouse model of breast cancer...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28721618/biological-nanopesticides-a-greener-approach-towards-the-mosquito-vector-control
#8
Prabhakar Mishra, Brij Kishore Tyagi, Natarajan Chandrasekaran, Amitava Mukherjee
Mosquitoes, being a vector for some potentially dreadful diseases, pose a considerable threat to people all around the world. The control over the growth and propagation of mosquitoes comprises conventional pesticides, insect growth regulators and other microbial control agents. However, the usage of these common chemicals and conventional pesticides eventually has a negative impact on human health as well as the environment, which therefore becomes a major concern. The lacuna allows nanotechnology to come into action and exploit nanopesticides...
July 18, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28721609/susceptibility-of-diaphorina-citri-hemiptera-liviidae-and-its-parasitoid-tamarixia-radiata-hymenoptera-eulophidae-to-entomopathogenic-fungi-under-laboratory-conditions
#9
K H Ibarra-Cortés, A W Guzmán-Franco, H González-Hernández, L D Ortega-Arenas, J A Villanueva-Jiménez, A Robles-Bermúdez
Diaphorina citri (Kuwayama) is a global pest of citrus that transmits the bacteria associated with the disease, Huanglongbing. Entomopathogenic fungi and the parasitoid Tamarixia radiata (Waterston) are important biological control agents of this pest and likely to interact in D. citri populations. As a basis for interaction studies, we determined the susceptibility of nymphs and adults of D. citri and adults of the parasitoid T. radiata to six fungal isolates from the species Beauveria bassiana s.l. (Bals...
July 18, 2017: Neotropical Entomology
https://www.readbyqxmd.com/read/28721506/interaction-between-a-bacterivorous-ciliate-aspidisca-cicada-and-a-rotifer-lecane-inermis-doozers-and-fraggles-in-aquatic-flocs
#10
Aleksandra Walczyńska, Mateusz Sobczyk, Edyta Fiałkowska, Agnieszka Pajdak-Stós, Janusz Fyda, Krzysztof Wiąckowski
Activated sludge is a semi-natural habitat composed of macroaggregates made by flocculating bacteria and inhabited by numerous protozoans and metazoans, creating a complicated interactome. The activated sludge resembles the biological formation of naturally occurring floc habitats, such as "marine snow." So far, these two types of habitat have been analyzed separately, despite their similarities. We examined the effect of a bacterivorous ciliate, Aspidisca cicada, on the quality of the macroaggregate ecosystem by estimating (i) the floc characteristics, (ii) the proliferation of other bacterivores (rotifers), and (iii) the chemical processes...
July 19, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28721301/synthesis-and-characterization-of-n-mannich-based-prodrugs-of-ciprofloxacin-and-norfloxacin-in-vitro-anthelmintic-and-cytotoxic-evaluation
#11
Mona Piplani, Harish Rajak, Prabodh Chander Sharma
Prodrugs, the inert derivatives of existing drugs have successfully contributed to the modification of their physicochemical properties. The improved antimicrobial potential due to enhanced lipophilicity of some of the synthesized prodrugs of antibacterial agents by various schemes has already been reported. In the current study, synthesis, characterization, and biological evaluation of some more lipid based prodrugs/compounds of ciprofloxacin and norfloxacin has been carried out. The synthesized prodrugs/compounds have been screened for anthelmintic activity using Indian earthworms and cytotoxic activity against human lung cancer cell lines A-549 employing sulforhodamine B (SRB) assay method...
July 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28721016/a-review-of-the-literature-analyzing-benefits-and-concerns-of-infliximab-biosimilar-ct-p13-for-the-treatment-of-rheumatologic-diseases-focus-on-interchangeability
#12
REVIEW
Andrea Becciolini, Maria Gabriella Raimondo, Chiara Crotti, Elena Agape, Martina Biggioggero, Ennio Giulio Favalli
The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28721009/patient-profiles-and-clinical-utility-of-mepolizumab-in-severe-eosinophilic-asthma
#13
REVIEW
Pranabashis Haldar
Mepolizumab (Nucala(®)) is an effective and specific anti-eosinophil molecular therapy that has recently been approved as add-on therapy for the management of severe eosinophilic asthma by the US Food and Drug Administration (FDA), European Medicines Agency (EMA; European Union) and more recently National Institute for Health and Care Excellence (NICE; UK). It is one of several molecular therapies in development for this indication and is illustrative of the strategic trajectory for pharmaceutical drug development taken over the past decade in several disease areas...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28720849/melatonin-promotes-osteoblast-differentiation-by-regulating-osterix-protein-stability-and-expression
#14
Younho Han, Young-Mi Kim, Hyung Sik Kim, Kwang Youl Lee
Although the biological role of melatonin in osteogenic differentiation has been suggested, the mechanism of osteoblast differentiation remains unclear. Thus, the present study investigated the underlying molecular mechanisms based on osteoblast-specific transcription factors. We found that melatonin enhanced BMP-4-induced osteogenic differentiation and increased the expression of osteogenic markers, especially Osterix, which is an essential transcription factor for the differentiation of preosteoblasts into mature osteoblasts in the late stage of osteoblast differentiation...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720733/dengue-virus-hijacks-a-noncanonical-oxidoreductase-function-of-a-cellular-oligosaccharyltransferase-complex
#15
David L Lin, Natalia A Cherepanova, Leonia Bozzacco, Margaret R MacDonald, Reid Gilmore, Andrew W Tai
Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28720727/impact-of-paracoccin-gene-silencing-on-paracoccidioides-brasiliensis-virulence
#16
Fabrício F Fernandes, Aline F Oliveira, Taise N Landgraf, Cristina Cunha, Agostinho Carvalho, Patrícia E Vendruscolo, Relber A Gonçales, Fausto Almeida, Thiago A da Silva, Fernando Rodrigues, Maria Cristina Roque-Barreira
Among the endemic deep mycoses in Latin America, paracoccidioidomycosis (PCM), caused by thermodimorphic fungi of the Paracoccidioides genus, is a major cause of morbidity. Disease development and its manifestations are associated with both host and fungal factors. Concerning the latter, several recent studies have employed the methodology of gene modulation in P. brasiliensis using antisense RNA (AsRNA) and Agrobacterium tumefaciens-mediated transformation (ATMT) to identify proteins that influence fungus virulence...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28720504/synthesis-of-novel-hybrids-of-pyrazole-and-coumarin-as-dual-inhibitors-of-cox-2-and-5-lox
#17
Fa-Qian Shen, Zhong-Chang Wang, Song-Yu Wu, Shen-Zhen Ren, Ruo-Jun Man, Bao-Zhong Wang, Hai-Liang Zhu
In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin who was reported to exhibit 5-LOX inhibition to select potent compounds using adequate biological trials sequentially including selective inhibition of COX-2 and 5-LOX, anti-proliferation in vitro, cells apoptosis and cell cycle. Among them, the most potent compound 11g (IC50=0...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28720332/synthesis-and-biological-evaluation-of-fluoro-substituted-3-4-dihydroquinazoline-derivatives-for-cytotoxic-and-analgesic-effects
#18
Jin Han Kim, Hui Rak Jeong, Da Woon Jung, Hong Bin Yoon, Sun Young Kim, Hyoung Ja Kim, Kyung-Tae Lee, Vinicius M Gadotti, Junting Huang, Fang-Xiong Zhang, Gerald W Zamponi, Jae Yeol Lee
As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Cav3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound 8h (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Cav3.2 currents (>90% inhibition) at 10μM concentration and exhibited cytotoxic effect (IC50=5.9μM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28720320/hydrogen-sulfide-improves-diabetic-wound-healing-in-ob-ob-mice-via-attenuating-inflammation
#19
Huichen Zhao, Shengxia Lu, Jiachao Chai, Yuchao Zhang, Xiaoli Ma, Jicui Chen, Qingbo Guan, Meiyan Wan, Yuantao Liu
BACKGROUND: The proposed mechanisms of impaired wound healing in diabetes involve sustained inflammation, excess oxidative stress and compromised agiogenesis. Hydrogen sulfide (H2S) has been reported to have multiple biological activities. We aim to investigate the role of H2S in impaired wound healing in ob/ob mice and explore the possible mechanisms involved. PROCEDURES: Full-thickness skin dorsal wounds were created on ob/ob mice and C57BL/6 mice. Cystathionine-γ-lyase (CSE) expression and H2S production were determined in granulation tissues of the wounds...
June 30, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28720278/-development-of-a-liquid-fermentation-system-and-encystment-for-a-nitrogen-fixing-bacterium-strain-having-biofertilizer-potential
#20
Mauricio Camelo-Rusinque, Andrés Moreno-Galván, Felipe Romero-Perdomo, Ruth Bonilla-Buitrago
The indiscriminate use of chemical fertilizers has contributed to the deterioration of the biological, physical and chemical properties of the soil, resulting in the loss of its productive capacity. For this reason, the use of biofertilizers has emerged as a technological alternative. The objective of this research was to develop a suitable liquid fermentation system and encystment for the multiplication of Azotobacter chroococcum AC1 strain, a bacterium employed in a biofertilizer formulation produced at present by CARPOICA, Colombia...
July 15, 2017: Revista Argentina de Microbiología
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