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https://www.readbyqxmd.com/read/29785121/association-between-angiogenesis-and-cytotoxic-signatures-in-the-tumor-microenvironment-of-gastric-cancer
#1
Yi Feng, Ying Dai, Zhihua Gong, Jia-Nan Cheng, Longhui Zhang, Chengdu Sun, Xianghua Zeng, Qingzhu Jia, Bo Zhu
Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29775211/proanthocyanidins-will-they-effectively-restrain-conspicuous-bacterial-strains-devolving-on-urinary-tract-infection
#2
REVIEW
Venkataseshan Jagannathan, Pragasam Viswanathan
Struvite or infection stones are one of the major clinical burdens among urinary tract infection, which occur due to the interaction between microbes and urine mineral components. Numerous urinary tract infection (UTI) causing microbes regulate through biofilm formation for survival from host defense, it is often found difficult in its eradication with simple anti-microbial agents and also the chance of recurrence and resistance development is significantly high. Cranberry consumption and maintenance of urinary tract health have been supported by clinical, epidemiological, and mechanistic studies...
May 18, 2018: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29755650/preclinical-comparison-of-proteasome-and-ubiquitin-e1-enzyme-inhibitors-in-cutaneous-squamous-cell-carcinoma-the-identification-of-mechanisms-of-differential-sensitivity
#3
Angela McHugh, Kenneth Fernandes, Andrew P South, Jemima E Mellerio, Julio C Salas-Alanís, Charlotte M Proby, Irene M Leigh, Mark K Saville
Proteasome inhibitors have distinct properties and the biochemical consequences of suppressing ubiquitin E1 enzymes and the proteasome differ. We compared the effects of the proteasome inhibitors bortezomib, ixazomib and carfilzomib and the ubiquitin E1 enzyme inhibitor MLN7243/TAK-243 on cell viability and cell death in normal keratinocytes and cutaneous squamous cell carcinoma (cSCC) cell lines. The effects of both a pulse of treatment and more extended incubation were investigated. This is relevant to directly-delivered therapy (topical treatment/intratumoral injection) where the time of exposure can be controlled and a short exposure may better reflect systemically-delivered inhibitor pharmacokinetics...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29745335/experimental-drugs-for-neuropathic-pain
#4
Kinga Salat, Beata Gryzlo, Katarzyna Kulig
Background Neuropathic pain (NP) is an important public health problem and despite recent progress in the understanding, diagnosis, pathophysiological mechanisms and the treatment of NP, many patients remain refractory to pharmacotherapy. OBJECTIVE: Currently used drugs have limited efficacy and dose-limiting adverse effects, and thus there is a substantial need for further development of novel medications for its treatment. Alternatively, drugs approved for the use in diseases other than NP can be applied as experimental for NP conditions...
May 10, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29743981/induction-of-nlrp3-inflammasome-activation-by-heme-in-human-endothelial-cells
#5
Judit Erdei, Andrea Tóth, Enikő Balogh, Benard Bogonko Nyakundi, Emese Bányai, Bernhard Ryffel, György Paragh, Mario D Cordero, Viktória Jeney
Hemolytic or hemorrhagic episodes are often associated with inflammation even when infectious agents are absent suggesting that red blood cells (RBCs) release damage-associated molecular patterns (DAMPs). DAMPs activate immune and nonimmune cells through pattern recognition receptors. Heme, released from RBCs, is a DAMP and induces IL-1 β production through the activation of the nucleotide-binding domain and leucine-rich repeat-containing family and pyrin domain containing 3 (NLRP3) in macrophages; however, other cellular targets of heme-mediated inflammasome activation were not investigated...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29743559/antigen-specific-primed-cytotoxic-t-cells-eliminate-tumour-cells-in-vivo-and-prevent-tumour-development-regardless-of-the-presence-of-anti-apoptotic-mutations-conferring-drug-resistance
#6
Paula Jaime-Sánchez, Elena Catalán, Iratxe Uranga-Murillo, Nacho Aguiló, Llipsy Santiago, Pilar M Lanuza, Diego de Miguel, Maykel A Arias, Julián Pardo
Cytotoxic CD8+ T (Tc) cells are the main executors of transformed and cancer cells during cancer immunotherapy. The latest clinical results evidence a high efficacy of novel immunotherapy agents that modulate Tc cell activity against bad prognosis cancers. However, it has not been determined yet whether the efficacy of these treatments can be affected by selection of tumoural cells with mutations in the cell death machinery, known to promote drug resistance and cancer recurrence. Here, using a model of prophylactic tumour vaccination based on the LCMV-gp33 antigen and the mouse EL4 T lymphoma, we analysed the molecular mechanism employed by Tc cells to eliminate cancer cells in vivo and the impact of mutations in the apoptotic machinery on tumour development...
May 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29738780/3-nitroacridine-derivatives-arrest-cell-cycle-at-g0-g1-phase-and-induce-apoptosis-in-human-breast-cancer-cells-may-act-as-dna-target-anticancer-agents
#7
Qian Zhou, Chaoqun You, Cong Zheng, Yawen Gu, Hongchao Gu, Rui Zhang, Hongshuai Wu, Baiwang Sun
DNA is considered to be one of the most promising targets for anticancer agents. Acridine analogues have anticancer activity based on DNA binding and topoisomerases inhibition. However, due to the side effects, resistance and low bioavailability, a few have entered into clinical usage and the mechanisms of action are not fully understood. Novel acridine derivatives are needed for effective cancer therapy. A series of novel 3-nitroacridine-based derivatives were synthesized, their DNA binding and anticancer activities were evaluated...
May 5, 2018: Life Sciences
https://www.readbyqxmd.com/read/29734689/the-interaction-of-the-metallo-glycopeptide-anti-tumour-drug-bleomycin-with-dna
#8
REVIEW
Vincent Murray, Jon K Chen, Long H Chung
The cancer chemotherapeutic drug, bleomycin, is clinically used to treat several neoplasms including testicular and ovarian cancers. Bleomycin is a metallo-glycopeptide antibiotic that requires a transition metal ion, usually Fe(II), for activity. In this review, the properties of bleomycin are examined, especially the interaction of bleomycin with DNA. A Fe(II)-bleomycin complex is capable of DNA cleavage and this process is thought to be the major determinant for the cytotoxicity of bleomycin. The DNA sequence specificity of bleomycin cleavage is found to at 5′-GT* and 5′-GC* dinucleotides (where * indicates the cleaved nucleotide)...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29731739/single-gene-congenic-strain-reveals-the-effect-of-zbtb16-on-dexamethasone-induced-insulin-resistance
#9
Michaela Krupková, František Liška, Ludmila Kazdová, Lucie Šedová, Adéla Kábelová, Drahomíra Křenová, Vladimír Křen, Ondřej Šeda
Background: Glucocorticoids (GCs) are potent therapeutic agents frequently used for treatment of number of conditions, including hematologic, inflammatory, and allergic diseases. Both their therapeutic and adverse effects display significant interindividual variation, partially attributable to genetic factors. We have previously isolated a seven-gene region of rat chromosome 8 sensitizing to dexamethasone (DEX)-induced dyslipidemia and insulin resistance (IR) of skeletal muscle. Using two newly derived congenic strains, we aimed to investigate the effect of one of the prime candidates for this pharmacogenetic interaction, the Zbtb16 gene...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29725025/single-vector-platform-vaccine-protects-against-lethal-respiratory-challenge-with-tier-1-select-agents-of-anthrax-plague-and-tularemia
#10
Qingmei Jia, Richard Bowen, Barbara Jane Dillon, Saša Masleša-Galić, Brennan T Chang, Austin C Kaidi, Marcus A Horwitz
Bacillus anthracis, Yersinia pestis, and Francisella tularensis are the causative agents of Tier 1 Select Agents anthrax, plague, and tularemia, respectively. Currently, there are no licensed vaccines against plague and tularemia and the licensed anthrax vaccine is suboptimal. Here we report F. tularensis LVS ΔcapB (Live Vaccine Strain with a deletion in capB)- and attenuated multi-deletional Listeria monocytogenes (Lm)-vectored vaccines against all three aforementioned pathogens. We show that LVS ΔcapB- and Lm-vectored vaccines express recombinant B...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29723246/early-changes-in-rps6-phosphorylation-and-bh3-profiling-predict-response-to-chemotherapy-in-aml-cells
#11
Martin Grundy, Thomas Jones, Liban Elmi, Michael Hall, Adam Graham, Nigel Russell, Monica Pallis
Blasts from different patients with acute myeloid leukemia (AML) vary in the agent(s) to which they are most responsive. With a myriad of novel agents to evaluate, there is a lack of predictive biomarkers to precisely assign targeted therapies to individual patients. Primary AML cells often survive poorly in vitro, thus confounding conventional cytotoxicity assays. The purpose of this work was to assess the potential of two same-day functional predictive assays in AML cell lines to predict long-term response to chemotherapy...
2018: PloS One
https://www.readbyqxmd.com/read/29718569/grp78-targeted-in-silico-virtual-screening-of-novel-anticancer-agents
#12
Ambily Nath Indu Viswanath, Ji Woong Lim, Seon Hee Seo, Jae Yeol Lee, Sang Min Lim, Ae Nim Pae
Overexpression of GRP78 in a variety of cancers such as glioblastoma, leukaemia, lung, prostate, breast, gastric, and colon makes it a prime target for anticancer drug development. Present study reports GRP78-based design of novel anticancer agents using in silico methods. As a first step towards the work, the interactions between GRP78 and 15 known ligands were modeled by docking simulation. The docked complex, GRP78-13, superior to other compounds with respect to its experimental activity and energy descriptors, was deduced into a structure-based pharmacophore...
May 2, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29695749/oncolytic-viruses-as-engineering-platforms-for-combination-immunotherapy
#13
REVIEW
Kwame Twumasi-Boateng, Jessica L Pettigrew, Y Y Eunice Kwok, John C Bell, Brad H Nelson
To effectively build on the recent successes of immune checkpoint blockade, adoptive T cell therapy and cancer vaccines, it is critical to rationally design combination strategies that will increase and extend efficacy to a larger proportion of patients. For example, the combination of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and anti-programmed cell death protein 1 (PD1) immune checkpoint inhibitors essentially doubles the response rate in certain patients with metastatic melanoma. However, given the heterogeneity of cancer, it seems likely that even more complex combinations of immunomodulatory agents may be required to obtain consistent, durable therapeutic responses against a broad spectrum of cancers...
April 25, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29695159/polymeric-sorbent-with-controlled-surface-polarity-an-alternate-for-solid-phase-extraction-of-nerve-agents-and-their-markers-from-organic-matrix
#14
Kanchan Sinha Roy, Ajay Kumar Purohit, Buddhadeb Chandra, D Raghavender Goud, Deepak Kumar Pardasani, Devendra K Dubey
Extraction and identification of lethal nerve agents and their markers in complex organic background have prime im-portance from the forensic & verification view point of the Chemical Weapons Convention (CWC). Liquid-liquid extraction with acetonitrile and commercially available solid phase silica cartridges are extensively used for this purpose. Silica car-tridges exhibit limited applicability for relatively polar analytes and acetonitrile extraction shows limited efficacy towards relatively nonpolar analytes...
April 26, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29693601/rapid-high-affinity-binding-by-a-fluorescein-templated-copolymer-combining-covalent-hydrophobic-and-acid%C3%A2-base-noncovalent-crosslinks
#15
Casey J Grenier, Anthony Timberman, Rongfang Yang, John Csoros, Alex Papantones, Leila F Deravi, W Rudolf Seitz
A new type of biomimetic templated copolymer has been prepared by reverse addition fragmentation chain transfer polymerization (RAFT) in dioxane. The initial formulation includes the template fluorescein, N -isopropylacrylamide (NIPAM, 84 mol %), methacrylic acid (MAA, 5-mol %), 4-vinylpyridine (4-VP, 9 mmol %), and N , N ′-methylenebis(acrylamide) (MBA, 2 mol %). PolyNIPAM is a thermosensitive polymer that comes out of aqueous solution above its lower critical solution temperature forming hydrophobic ‘crosslinks’...
April 25, 2018: Sensors
https://www.readbyqxmd.com/read/29679934/nanopriming-with-zero-valent-iron-nzvi-enhances-germination-and-growth-in-aromatic-rice-cultivar-oryza-sativa-cv-gobindabhog-l
#16
Titir Guha, K V G Ravikumar, Amitava Mukherjee, Anita Mukherjee, Rita Kundu
Engineered nanoparticles are utilized in agriculture for various purposes. They can be used as fertilizer, carrier for macro/micro nutrients or priming agents. Various nanoparticles are reported to have toxicity at very high doses, but at optimum concentration, they can be beneficial for plant growth and development. In the present study, low concentrations of nZVI nanoparticles were evaluated for their growth enhancement potential as seed priming agent in an aromatic rice cultivar, Oryza sativa cv. Gobindabhog...
April 12, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29676972/effect-of-resin-luting-systems-and-alumina-particle-air-abrasion-on-bond-strength-to-zirconia
#17
R Grasel, M J Santos, Hm Chagas Rêgo, M P Rippe, L F Valandro
This study aimed to evaluate the effect of different primer/resin luting agent combinations and alumina air abrasion on the adhesion to zirconia. Eighty blocks (4×4×3 mm) of Lava Frame Zirconia (3M ESPE) were produced and randomly assigned into eight groups (n=10) according to two zirconia surface treatments (untreated or air abrasion with 50-μm alumina particles) and four luting systems (SU: Scotchbond Universal/RelyX Unicem 2; ZP: Z-Prime Plus/Duo-link Universal; MB: Monobond Plus/Variolink II; and AP: Alloy Primer/ED Primer II/Panavia F 2...
May 2018: Operative Dentistry
https://www.readbyqxmd.com/read/29676630/international-approach-to-environmental-and-lung-health-a-perspective-from-the-fogarty-international-center
#18
Roger I Glass, Joshua P Rosenthal
The global burden of lung disease is substantial, accounting for an estimated 7.5 million deaths per year, approximately 14% of annual deaths worldwide. The prime illnesses include, in descending order, chronic obstructive pulmonary disease, lung cancer, tuberculosis, acute respiratory infections, asthma, and interstitial lung fibrosis. Key risk factors include smoking, both indoor and outdoor air pollution, and occupational exposures. Although the distribution of both the diseases and the risk factors varies greatly by age, geography, and setting, the greatest burden falls on populations living in low- and middle-income countries...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29675515/ceramic-surface-treatment-with-a-single-component-primer-resin-adhesion-to-glass-ceramics
#19
Mayara Prado, Catina Prochnow, Ana Maria Estivalete Marchionatti, Paolo Baldissara, Luiz Felipe Valandro, Vinicius Felipe Wandscher
PURPOSE: To evaluate the microshear bond strength (μSBS) of composite cement bonded to two machined glass ceramics and its durability, comparing conventional surface conditioning (hydrofluoric acid + silane) to a one-step primer (Monobond Etch & Prime). MATERIALS AND METHODS: Machined slices of lithium disilicate ceramic (LDC) (IPS e.max CAD) and feldspathic ceramic (FC) (VITA Mark II) glass ceramics were divided into two groups (n = 10) according to two factors: 1...
April 19, 2018: Journal of Adhesive Dentistry
https://www.readbyqxmd.com/read/29675465/elimination-of-established-tumors-with-nanodisc-based-combination-chemoimmunotherapy
#20
Rui Kuai, Wenmin Yuan, Sejin Son, Jutaek Nam, Yao Xu, Yuchen Fan, Anna Schwendeman, James J Moon
Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein-mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models...
April 2018: Science Advances
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