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https://www.readbyqxmd.com/read/27936464/refractory-testicular-germ-cell-tumors-are-highly-sensitive-to-the-second-generation-dna-methylation-inhibitor-guadecitabine
#1
Costantine Albany, Mary P Hever-Jardine, Katherine M von Herrmann, Christina Y Yim, Janice Tam, Joshua M Warzecha, Leah Shin, Sarah E Bock, Brian S Curran, Aneeq S Chaudhry, Fred Kim, George E Sandusky, Pietro Taverna, Sarah J Freemantle, Brock C Christensen, Lawrence H Einhorn, Michael J Spinella
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936442/label-free-colorimetric-detection-of-cancer-related-gene-based-on-two-step-amplification-of-molecular-machine
#2
Huo Xu, Dong Wu, Chen-Qiao Li, Zheng Lu, Xiao-Yun Liao, Jie Huang, Zai-Sheng Wu
Highly sensitive detection of K-ras gene is of great significance in biomedical research and clinical diagnosis. Here, we developed a colorimetric biosensing system for the detection of proto-oncogene K-ras based on enhanced amplification effect of DNA molecular machine, where dual isothermal circular strand-displacement amplification (D-SDA) occurs on two arms in one-to-one correspondence. Specifically, we designed a primer-locked hairpin probe (HP) and a primer-contained linear polymerization template (PPT)...
December 2, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27936393/suppression-of-protein-tyrosine-phosphatase-ptpn22-gene-induces-apoptosis-in-t-cell-leukemia-cell-line-jurkat-through-the-akt-and-erk-pathways
#3
Elham Baghbani, Behzad Baradaran, Fatemeh Pak, Leila Mohammadnejad, Daryoush Shanehbandi, Behzad Mansoori, Vahid Khaze, Noushin Montazami, Ali Mohammadi, Parviz Kokhaei
The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay...
December 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27936238/trehalose-6-phosphate-mediated-toxicity-determines-essentiality-of-otsb2-in-mycobacterium-tuberculosis-in-vitro-and-in-mice
#4
Jan Korte, Marina Alber, Carolina M Trujillo, Karl Syson, Hendrik Koliwer-Brandl, René Deenen, Karl Köhrer, Michael A DeJesus, Travis Hartman, William R Jacobs, Stephen Bornemann, Thomas R Ioerger, Sabine Ehrt, Rainer Kalscheuer
Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27936237/the-immunomodulatory-small-molecule-imiquimod-induces-apoptosis-in-devil-facial-tumour-cell-lines
#5
Amanda L Patchett, Jocelyn M Darby, Cesar Tovar, A Bruce Lyons, Gregory M Woods
The survival of the Tasmanian devil (Sarcophilus harrisii) is threatened by devil facial tumour disease (DFTD). This transmissible cancer is usually fatal, and no successful treatments have been developed. In human studies, the small immunomodulatory molecule imiquimod is a successful immunotherapy, activating anti-tumour immunity via stimulation of toll-like receptor-7 (TLR7) signaling pathways. In addition, imiquimod is a potent inducer of apoptosis in human tumour cell lines via TLR7 independent mechanisms...
2016: PloS One
https://www.readbyqxmd.com/read/27935899/-algorithm-for-selection-of-individual-therapy-with-clopidogrel-in-vascular-surgical-practice
#6
A I Shevela, A A Slepukhina, E M Zelenskaya, T A Seredina, G I Lifshits
For treatment of patients with diseases of lower limb arteries and prevention of cardiovascular complications in high-risk patients (those with diabetes mellitus, arterial hypertension, dyslipidemia, obesity) permanent antiplatelet therapy is indicated. A problem is variable individual sensitivity to therapeutic agents. For antiplatelet therapy in patients with atherosclerosis of lower limb arteries there has been obtained an evidence-supported base concerning efficacy of long-term administration of clopidogrel preparations, unlike patients with acute coronary syndrome, for whom there has been accumulated an evidence-confirmed base of administering clopidogrel preparations, as well as ticagrelor and prasugrel in various clinical situations...
2016: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/27935897/-thrombosis-of-the-portal-upper-mesenteric-and-splenic-veins-in-a-patient-with-thrombophilia-a-clinical-case-report
#7
A E Shklyaev, I G Malakhova, A G Bessonov, I Yu Utkin
Currently there are several dozens of hereditarily associated thrombophilias and acquired states known to condition the development of a thrombus. Thrombosis of visceral veins appears to be a considerably less often encountered event than thrombosis in the system of visceral arteries. Presented herein in the article is a clinical case report concerning subacute thrombosis of the portal, upper mesenteric and splenic veins, having developed on the background of mutations of 7 genes of the system of haemostasis in a young adult patient...
2016: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#8
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935605/evolution-of-the-circuitry-for-conscious-color-vision-in-primates
#9
J Neitz, M Neitz
There are many ganglion cell types and subtypes in our retina that carry color information. These have appeared at different times over the history of the evolution of the vertebrate visual system. They project to several different places in the brain and serve a variety of purposes allowing wavelength information to contribute to diverse visual functions. These include circadian photoentrainment, regulation of sleep and mood, guidance of orienting movements, detection and segmentation of objects. Predecessors to some of the circuits serving these purposes presumably arose before mammals evolved and different functions are represented by distinct ganglion cell types...
December 9, 2016: Eye
https://www.readbyqxmd.com/read/27935058/bimodal-targeting-using-sulfonated-mannosylated-pei-for-combined-gene-delivery-and-photodynamic-therapy
#10
Upendra Chitgupi, Yi Li, Mingfu Chen, Shuai Shao, Marie Beitelshees, Myles Joshua Tan, Sriram Neelamegham, Blaine A Pfeifer, Charles Jones, Jonathan F Lovell
Photodynamic therapy (PDT) and gene delivery have both been used to target both cancer cells and tumor-associated macrophages (TAMs). Given the complex nature of tumor tissue, there could be merit in combining these strategies simultaneously. In this study, we developed a bimodal targeting approach to both cancer cells and macrophages, employing materials conducive to both gene delivery and PDT. Polymers libraries were created that consisted of cationic polyethyleneimine (PEI) conjugated to the photosensitizer pyropheophorbide-α, with sulfonation (to target selectin-expressing cells) and mannosylation (to target TAMs)...
December 9, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27934912/bix01294-an-inhibitor-of-histone-methyltransferase-induces-autophagy-dependent-differentiation-of-glioma-stem-like-cells
#11
Iwona Anna Ciechomska, Piotr Przanowski, Judyta Jackl, Bartosz Wojtas, Bozena Kaminska
Glioblastoma (GBM) contains rare glioma stem-like cells (GSCs) with capacities of self-renewal, multi-lineage differentiation, and resistance to conventional therapy. Drug-induced differentiation of GSCs is recognized as a promising approach of anti-glioma therapy. Accumulating evidence suggests that unique properties of stem cells depend on autophagy. Here we demonstrate that BIX01294, an inhibitor of a G9a histone methyltransferase (introducing H3K9me2 and H3K27me3 repressive marks) triggers autophagy in human glioma cells...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934883/preclinical-evaluation-of-radiation-and-systemic-rgd-targeted-adeno-associated-virus-phage-tnf-gene-therapy-in-a-mouse-model-of-spontaneously-metastatic-melanoma
#12
T J Quinn, N Healy, A Sara, E Maggi, C S Claros, R Kabarriti, L Scandiuzzi, L Liu, J Gorecka, A Adem, I Basu, Z Yuan, C Guha
The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model...
December 9, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27934882/stable-knockdown-of-creb-hif-1-and-hif-2-by-replication-competent-retroviruses-abrogates-the-responses-to-hypoxia-in-hepatocellular-carcinoma
#13
D Shneor, R Folberg, J Pe'er, A Honigman, S Frenkel
The fast proliferation of tumor cells develops faster than the vasculature, resulting, in most malignant tumors, in generation of hypoxic regions. Hypoxia renders solid tumors resistant to radiation and chemotherapeutics while providing opportunities for tumor-selective therapies targeting tumor hypoxia. Here we exploit two properties of tumors: propagation of tumor cells and ongoing generation of hypoxic regions to construct a system that preferentially leads to the death of tumor cells and thus hinders tumor growth...
December 9, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27934832/in-vitro-sensitivity-pattern-of-chloroquine-and-artemisinin-in-plasmodium-falciparum
#14
Supriya Sharma, Kamlesh Kaitholia, Neelima Mishra, Bina Srivastava, C R Pillai, Neena Valecha, Anupkumar R Anvikar
Artemisinin (ART) and its derivatives form the mainstay of antimalarial therapy. Emergence of resistance to them poses a potential threat to future malaria control and elimination on a global level. It is important to know the mechanism of action of drug and development of drug resistance. We put forwards probable correlation between the mode of action of chloroquine (CQ) and ART. Modified trophozoite maturation inhibition assay, WHO Mark III assay and molecular marker study for CQ resistance at K76T codon in Plasmodium falciparum CQ-resistant transporter gene were carried out on cultured P...
October 2016: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27934820/molecular-characterisation-of-antimicrobial-resistance-in-pseudomonas-aeruginosa-and-acinetobacter-baumannii-during-2014-and-2015-collected-across-india
#15
A K Pragasam, S Vijayakumar, Y D Bakthavatchalam, A Kapil, B K Das, P Ray, V Gautam, S Sistla, S C Parija, K Walia, V C Ohri, S Anandan, B Veeraraghavan
BACKGROUND: Surveillance of antimicrobial resistance (AMR) is of great importance. Pseudomonas aeruginosa and Acinetobacter baumannii are important pathogens and emergence of resistance in these have increased the morbidity and mortality rates. This surveillance study was initiated by the Government of India - Indian Council of Medical Research. The aim of this study is to determine the antimicrobial susceptibility profile and to characterise the enzyme mediated antimicrobial resistance such as extended spectrum beta-lactamases (ESBLs) and carbapenemases among multidrug-resistant (MDR) P...
October 2016: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27934479/doxorubicin-and-sirna-codelivery-via-chitosan-coated-ph-responsive-mixed-micellar-polyplexes-for-enhanced-cancer-therapy-in-multidrug-resistant-tumors
#16
Adeel Masood Butt, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Nor Azian Abdul Murad, Rahman Jamal, Prashant Kesharwani
This study investigated the potential of chitosan-coated mixed micellar nanocarriers (polyplexes) for codelivery of siRNA and doxorubicin (DOX). DOX-loaded mixed micelles (serving as cores) were prepared by thin film hydration method and coated with chitosan (CS, serving as outer shell), and complexed with multidrug resistance (MDR) inhibiting siRNA. Selective targeting was achieved by folic acid conjugation. The polyplexes showed pH-responsive enhanced DOX release in acidic tumor pH, resulting in higher intracellular accumulation, which was further augmented by downregulation of mdr-1 gene after treatment with siRNA-complexed polyplexes...
December 5, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27934199/graphene-oxide-inhibits-antibiotic-uptake-and-antibiotic-resistance-gene-propagation
#17
Wei Zou, Xiaokang Li, Ziyang Lai, Xingli Zhang, Xiangang Hu, Qixing Zhou
Antibiotics and antibiotic resistance genes (ARGs) in the natural environment have become substantial threats to the ecosystem and public health. Effective strategies to control antibiotics and ARG contaminations are emergent. A novel carbon nanomaterial, graphene oxide (GO), has attracted a substantial amount of attention in environmental fields. This study discovered the inhibition effects of GO on sulfamethoxazole (SMZ) uptake for bacteria and ARG transfer among microorganisms. GO promoted the penetration of SMZ from intracellular to extracellular environments by increasing the cell membrane permeability...
December 7, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27934080/remote-control-of-light-triggered-virotherapy
#18
S-Ja Tseng, Kuo-Yen Huang, Ivan M Kempson, Shih-Han Kao, Meng-Chia Liu, Shuenn-Chen Yang, Zi-Xian Liao, Pan-Chyr Yang
Clinical virotherapy has been successfully approved for use in cancer treatment by the U.S. Food and Drug Administration; however, a number of improvements are still sought to more broadly develop virotherapy. A particular challenge is to administer viral therapy systemically and overcome limitations in intratumoral injection, especially for complex tumors within sensitive organs. To achieve this, however, a technique is required that delivers the virus to the tumor before the body's natural self-defense eradicates the virus prematurely...
November 22, 2016: ACS Nano
https://www.readbyqxmd.com/read/27933523/integrative-functional-genomics-for-systems-genetics-in-geneweaver-org
#19
Jason A Bubier, Michael A Langston, Erich J Baker, Elissa J Chesler
The abundance of existing functional genomics studies permits an integrative approach to interpreting and resolving the results of diverse systems genetics studies. However, a major challenge lies in assembling and harmonizing heterogeneous data sets across species for facile comparison to the positional candidate genes and coexpression networks that come from systems genetic studies. GeneWeaver is an online database and suite of tools at www.geneweaver.org that allows for fast aggregation and analysis of gene set-centric data...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933432/lupus-pathobiology-based-on-genomics
#20
REVIEW
Mohammad Saeed
Systemic lupus erythematosus (SLE) is an autoimmune disorder with complex genetic underpinnings. This review attempts to assemble the myriad of genomic findings to build a clearer picture of the pathobiology of SLE to serve as a guide for therapeutics. Over 100 genes are now known for SLE, and several more penetrant ones have led to the emergence of more defined lupus phenotypes. Also discussed here are the targeted therapies that have come up on the horizon and the specific biologic mechanisms of more traditional therapies which have only recently been explored...
December 8, 2016: Immunogenetics
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