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https://www.readbyqxmd.com/read/28330284/in-vitro-evaluation-of-anti-proliferative-anti-inflammatory-and-pro-apoptotic-activities-of-the-methanolic-extracts-of-andrographis-nallamalayana-ellis-on-a375-and-b16f10-melanoma-cell-lines
#1
Guroji Purushotham, Yerukala Padma, Yusuf Nabiha, R R Venkata Raju
Natural plant products have been widely used in controlling cancer with fewer or no side effects and the use of plant extracts as complementary to synthetic medicine is gaining increased popularity. Members of Andrographis plants possess important medicinal properties. In the present study, anti-cancerous properties of Andrographis nallamalayana (AN) were tested on A375 and B16F10 skin melanoma cancer cell lines. The leaf extracts of AN significantly reduced the cell viability and cell survival of skin cancer cell lines, achieved by MTT assay and clonogenic assays, respectively...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330111/effect-of-stat3-inhibitor-in-chronic-myeloid-leukemia-associated-signaling-pathway-a-mathematical-modeling-simulation-and-systems-biology-study
#2
Himansu Kumar, Swapnil Tichkule, Utkarsh Raj, Saurabh Gupta, Swati Srivastava, Pritish Kumar Varadwaj
Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to abnormal growth of basophil cells. Several proangiogenic molecules have been reported to be associated in CML progression, including the hepatocyte growth factor (HGF). However, detail mechanism about the cellular distribution and function of HGF in CML is yet to be revealed. The proliferation of hematopoietic cells are regulated by some of the growth factors like interleukin 3 (IL-3), IL-6, erythropoietin, thrombopoietin, etc...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330089/discovery-of-potential-alk-inhibitors-by-virtual-screening-approach
#3
Anish Kumar, V Shanthi, K Ramanathan
Crizotinib is an anticancer drug used for the treatment of non-small cell lung cancer. Evidences available suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene. It is therefore necessary to develop potent anti-cancer drugs for the treatment of crizotinib resistance non-small cell lung cancer types. In the present study, a novel class of lead molecule was identified using virtual screening, molecular docking and molecular dynamic approach...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329758/lactb-is-a-tumour-suppressor-that-modulates-lipid-metabolism-and-cell-state
#4
Zuzana Keckesova, Joana Liu Donaher, Jasmine De Cock, Elizaveta Freinkman, Susanne Lingrell, Daniel A Bachovchin, Brian Bierie, Verena Tischler, Aurelia Noske, Marian C Okondo, Ferenc Reinhardt, Prathapan Thiru, Todd R Golub, Jean E Vance, Robert A Weinberg
Post-mitotic, differentiated cells exhibit a variety of characteristics that contrast with those of actively growing neoplastic cells, such as the expression of cell-cycle inhibitors and differentiation factors. We hypothesized that the gene expression profiles of these differentiated cells could reveal the identities of genes that may function as tumour suppressors. Here we show, using in vitro and in vivo studies in mice and humans, that the mitochondrial protein LACTB potently inhibits the proliferation of breast cancer cells...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28329629/basal-cell-carcinoma-nevus-syndrome-population-of-patients-negative-for-chromosome-9-mutations
#5
Brittany Urso, Katelyn Updyke, James A Solomon
Patients with Basal Cell Carcinoma Nevus syndrome are assumed to have a chromosome 9 mutation, such as a PTCH1 [9q22] mutation, despite the majority of patients with BCCNS being diagnosed through the presence of major and minor diagnostic criterion. The main treatment for BCCNS, Hedgehog inhibitors (HhI), targets these mutations. The results of an internet based survey of self-identified adults with BCCNS which was launched through SurveyMonkey with access provided by the Basal Cell Carcinoma Nevus Syndrome Life Support Network (www...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329508/tumor-necrosis-factor-antagonist-induced-psoriasis-in-a-3-year-old-boy-with-kawasaki-disease
#6
Lauren Geller, Roselyn Kellen
Tumor necrosis factor (TNF) antagonists have beenknown to trigger new-onset psoriasis in adult andpediatric patients. Here we report a case of TNFantagonist-induced psoriasis in a 3-year-old boytreated with infliximab for Kawasaki disease. Ourpatient is a 3-year-old boy with Kawasaki diseaseunresponsive to intravenous immunoglobulinwho was then treated with one dose of infliximab.A few days later he developed psoriatic plaqueson the face and extremities. The psoriatic plaqueswere treated with topical calcineurin inhibitors andtopical corticosteroids, with marked improvement...
February 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329446/in-vitro-intrinsic-permeability-a-transporter-independent-measure-of-caco-2-cell-permeability-in-drug-design-and-development
#7
Linda Fredlund, Susanne Winiwarter, Constanze Hilgendorf
In-vitro permeability data have a central place in absorption risk assessments in drug discovery and development. For compounds where active efflux impacts permeability in vitro, the inherent passive membrane permeability ("intrinsic permeability"), gives a concentration-independent measure of the compound's permeability. This work describes the validation of an in-vitro intrinsic permeability assay and application of the data in a predictive in-silico model. Apparent intrinsic permeability (Papp) across Caco-2 cell monolayers is determined in presence of an optimized cocktail of chemical inhibitors towards the three major efflux transporters ABCB1, ABCC2, and ABCG2...
March 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28329421/naproxen-inhibits-uvb-induced-basal-cell-and-squamous-cell-carcinoma-development-in-ptch1-skh-1-hairless-mice
#8
Sandeep C Chaudhary, Mohammad Waseem, Mehtab Rana, Hui Xu, Levy Kopelovich, Craig A Elmets, Mohammad Athar
Naproxen possesses anti-proliferative and pro-apoptotic effects besides its known anti-inflammatory functions. Here, we demonstrate the anti-cancer effects of naproxen against UVB-induced BCCs and SCCs in a highly susceptible murine model of UVB carcinogenesis. Naproxen significantly inhibited UVB-induced BCCs and SCCs in this model. Tumor number and volume were significantly decreased (p<0.005 and p<0.05, respectively). Inhibition in UVB-induced SCCs and BCCs was 77% and 86%, respectively, which was associated with reduced PCNA and cyclin D1 and increased apoptosis...
March 22, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28329187/bumped-kinase-inhibitors-for-therapy-of-cryptosporidiosis
#9
Matthew A Hulverson, Sumiti Vinayak, Ryan Choi, Deborah A Schaefer, Alejandro Castellanos-Gonzalez, Rama S R Vidadala, Carrie F Brooks, Gillian T Herbert, Dana P Betzer, Grant R Whitman, Hayley N Sparks, Samuel L M Arnold, Kasey L Rivas, Lynn K Barrett, A Clinton White, Maly Dustin J, Michael W Riggs, Boris Striepen, Wesley C Van Voorhis, Kayode K Ojo
Bumped kinase inhibitors (BKIs) of Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) are leading candidates for treatment of cryptosporidiosis diarrhea. Potential cardiotoxicity related to anti-human ether-à-go-go potassium channel (hERG) activity of the first generation anti-Cryptosporidium BKIs triggered further testing for efficacy. A luminescence assay adapted for high-throughput screening was used to measure inhibitory activities of BKIs on in vitro C. parvum. Furthermore, neonatal and interferon-γ knockout mouse models of C...
March 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329009/the-expression-and-localization-of-rnase-and-rnase-inhibitor-in-blood-cells-and-vascular-endothelial-cells-in-homeostasis-of-the-vascular-system
#10
Ayaka Ohashi, Aya Murata, Yuichiro Cho, Shizuko Ichinose, Yuriko Sakamaki, Miwako Nishio, Osamu Hoshi, Silvia Fischer, Klaus T Preissner, Takatoshi Koyama
RNA may be released from vascular cells including endothelial cells in the event of injury and in vascular disease. Extracellular RNAs have been recognized as novel procoagulant and permeability-increasing factors. Extracellular RNA may function as inflammatory host alarm signals that serve to amplify the defense mechanism, but it may provide important links to thrombus formation. Extracellular RNA is degraded by RNase. We propose that RNase and its inhibitor RNase inhibitor (RI) act as modulators of homeostasis in the vasculature to control the functions of extracellular RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28328837/atypical-presentation-of-paroxysmal-nocturnal-hemoglobinuria-treated-by-eculizumab-a-case-report
#11
Anne Quinquenel, Quentin Maestraggi, Carinne Lecoq-Lafon, Peffault de Latour Régis, Alain Delmer, Amélie Servettaz
RATIONALE: Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant acquired hematopoietic stem cell disease, which can be revealed by hemolytic anemia, thromboembolism, or bonemarrow failure. Thrombosis can occur at any site, but coronary thrombosis is extremely rare. Controlled trials have demonstrated that eculizimab, an inhibitor of the terminal complement cascade, was able to reduce both hemolysis and thrombosis, but its efficacy in cases of PNH with coronary thrombosis is unknown...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28328682/early-tranexamic-acid-administration-ameliorates-the-endotheliopathy-of-trauma-and-shock-in-an-in-vitro-model
#12
Lawrence N Diebel, Jonathan V Martin, David M Liberati
BACKGROUND: Systemic vascular endothelial injury is a consequence of trauma-hemorrhagic shock (T/HS) which results in disturbances of coagulation, inflammation and endothelial barrier integrity. The effect of T/HS on the endothelium (Endotheliopathy of Trauma)[EoT] is of intense research interest and may lead to EoT directed therapies. Administration of tranexamic acid (TXA) in trauma patients is associated with a survival benefit and fewer complications if given early after injury. Mechanisms for this protective effect include the anti-fibrinolytic and anti-inflammatory effects of TXA...
March 21, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28328322/novel-lc-ms-ms-and-high-throughput-mass-spectrometric-assays-for-monoacylglycerol-acyltransferase-inhibitors
#13
Jenson Qi, John A Masucci, Wensheng Lang, Margery A Connelly, Gary W Caldwell, Ioanna Petrounia, Jennifer Kirkpatrick, Alexander N Barnakov, Geoffrey Struble, Robyn Miller, Keli Dzordzorine, Gee-Hong Kuo, Michael Gaul, Alessandro Pocai, Seunghun Lee
Monoacylglycerol acyltransferase enzymes (MGAT1, MGAT2, and MGAT3) convert monoacylglycerol to diacylglycerol (DAG). MGAT1 and MGAT2 are both implicated in obesity-related metabolic diseases. Conventional MGAT enzyme assays use radioactive substrates, wherein the product of the MGAT-catalyzed reaction is usually resolved by time-consuming thin layer chromatography (TLC) analysis. Furthermore, microsomal membrane preparations typically contain endogenous diacylglycerol acyltransferase (DGAT) from the host cells, and these DGAT activities can further acylate DAG to form triglyceride (TG)...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28328316/a-high-throughput-screening-assay-using-a-photoconvertable-protein-for-identifying-inhibitors-of-transcription-translation-or-proteasomal-degradation
#14
David K Heidary, Ashley Fox, Chris I Richards, Edith C Glazer
Dysregulated transcription, translation, and protein degradation are common features of cancer cells, regardless of specific genetic profiles. Several clinical anticancer agents take advantage of this characteristic vulnerability and interfere with the processes of transcription and translation or inhibit protein degradation. However, traditional assays that follow the process of protein production and removal require multistep processing and are not easily amenable to high-throughput screening. The use of recombinant fluorescent proteins provides a convenient solution to this problem, and moreover, photoconvertable fluorescent proteins allow for ratiometric detection of both new protein production and removal of existing proteins...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28328298/the-synthetic-progestin-gestodene-affects-functional-biomarkers-in-neonatal-rat-osteoblasts-through-an-estrogen-receptor-related-mechanism-of-action
#15
Juana Enríquez, Gustavo García, Bertha Herrero, Fernando Larrea
BACKGROUND: Clinical studies have shown that gestodene (GDN), a potent third-generation synthetic progestin, affects bone resorption. However, its mode of action in bone cells is not fully understood. The aim of this study was to establish whether GDN affects bone directly or through its bioconversion to other metabolites with different biological activities. METHODS: In this study, we investigated the effects of GDN and its A-ring reduced metabolites on proliferation, differentiation, and mineralization of calvarial osteoblasts isolated from neonatal rat and their capacity to displace [(3)H]-E2 at ER binding sites...
March 22, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28328292/il-6-is-involved-in-malignancy-and-doxorubicin-sensitivity-of-renal-carcinoma-cells
#16
Yanqiang Chen, Jianzhen Liu, Pei Lv, Jiangyan Gao, Mingzheng Wang, Yongjun Wang
Various survival factors such as the pleiotropic cytokine interleukin-6 (IL-6), a major mediator of inflammation and activator of signal transducer and activator of transcription 3 (STAT3), serve to block apoptosis in cancer cells. Our present study revealed that the expression of IL-6, while not other IL-2, IL-4, IL-8, or IL-10, was significantly elevated in resistance of renal carcinoma cells (RCC) when compared with human renal proximal tubule epithelial cell line HK-2. The inhibition of IL-6 by siRNA can suppress the proliferation, migration and invasion of RCC cells and increase the doxorubicin (Dox) sensitivity...
March 22, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28328152/microrna-206-regulates-vascular-smooth-muscle-cell-phenotypic-switch-and-vascular-neointimal-formation
#17
Huiyan Sun, Songzhi Cai, Mei Zhang, Juan Zhao, Shuping Wei, Yuyu Luo, Xiangyan Meng, Xin Zhou, Yuming Li, Wencheng Zhang
MiR-206 has been found to play a critical role in skeletal muscle proliferation, differentiation and regeneration. However, little is known about the function of miR-206 in vascular smooth muscle cells (VSMCs) biology. In this study, we will investigate its roles in phenotypic switching of VSMCs and neointimal lesion formation. First, we identified the expression of miR-206 in VSMCs treated with various concentrations of TGFβ1 and in rat carotid arteries after angioplasty by using qPCR. TGFβ1 inhibited the expression of miR-206 and TGFβ1 inhibitor induced miR-206 expression...
March 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28328109/a-cohort-study-of-gorlin-syndrome-with-emphasis-on-standardised-phenotyping-and-quality-of-life-assessment
#18
Aamira J Huq, Michael Bogwitz, Alexandra Gorelik, Ingrid M Winship, Susan M White, Alison H Trainer
BACKGROUND: Gorlin syndrome (Nevoid Basal Cell Carcinoma Syndrome) is a rare genetic predisposition to basal cell carcinomas (BCCs), keratocysts of the jaw and calcification of the falx cerebri amongst other clinical features. With the advent of sonic hedgehog inhibitors for the treatment of BCCs, it is timely to establish a cohort of individuals with Gorlin syndrome and collect standardised phenotypic information on these individuals. Moreover, the health-related quality of life (QoL) in individuals with Gorlin syndrome is not well studied...
March 22, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28328081/btk-inhibition-is-a-potent-approach-to-block-ige-mediated-histamine-release-in-human-basophils
#19
Dubravka Smiljkovic, Katharina Blatt, Gabriele Stefanzl, Yulia Dorofeeva, Cathrin Skrabs, Margarete Focke-Tejkl, Wolfgang R Sperr, Ulrich Jaeger, Rudolf Valenta, Peter Valent
BACKGROUND: Recent data suggest that Bruton's tyrosine kinase (BTK) is an emerging therapeutic target in IgE receptor (IgER) cross-linked basophils. METHODS: We examined the effects of four BTK inhibitors (ibrutinib, dasatinib, AVL-292, CNX-774) on IgE-dependent activation and histamine release in blood basophils obtained from allergic patients (n=11) and non-allergic donors (n=5). In addition, we examined the effects of these drugs on the growth of the human basophil cell line KU812 and the human mast cell line HMC-1...
March 22, 2017: Allergy
https://www.readbyqxmd.com/read/28327934/pazopanib-or-placebo-in-completely-resected-stage-i-nsclc-patients-results-of-the-phase-ii-ifct-0703-trial
#20
B Besse, J Mazières, L Ribassin-Majed, F Barlesi, J Bennouna, R Gervais, L Moreau, H Berard, D Debieuvre, O Molinier, D Moro-Sibilot, P J Souquet, S Jacquot, L Petit, H Lena, J P Pignon, B Lacas, F Morin, B Milleron, G Zalcman, J C Soria
Background: Adjuvant treatment in resected stage I non-small cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population. Patients and methods: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/d (P800) for 6 months with a two-step Fleming design...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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