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https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#1
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28339582/hypoxia-in-the-glioblastoma-microenvironment-shaping-the-phenotype-of-cancer-stem-like-cells
#2
Nicole Colwell, Mioara Larion, Amber J Giles, Ashlee N Seldomridge, Saman Sizdahkhani, Mark R Gilbert, Deric M Park
Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity...
January 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28334924/throat-swabs-in-children-with-respiratory-tract-infection-associations-with-clinical-presentation-and-potential-targets-for-point-of-care-testing
#3
Hannah V Thornton, Alastair D Hay, Niamh M Redmond, Sophie L Turnbull, Hannah Christensen, Tim J Peters, John P Leeming, Andrew Lovering, Barry Vipond, Peter Muir, Peter S Blair
Background and objectives.: Diagnostic uncertainty over respiratory tract infections (RTIs) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. If symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. This study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs. Methods.: Cross-sectional study of children ≥3 months to <16 years presenting with acute cough and RTI, with subset follow-up...
February 18, 2017: Family Practice
https://www.readbyqxmd.com/read/28334886/glioblastoma-associated-microglia-and-macrophages-targets-for-therapies-to-improve-prognosis
#4
Candice C Poon, Susobhan Sarkar, V Wee Yong, John J P Kelly
Glioblastoma is the most common and most malignant primary adult human brain tumour. Diagnosis of glioblastoma carries a dismal prognosis. Treatment resistance and tumour recurrence are the result of both cancer cell proliferation and their interaction with the tumour microenvironment. A large proportion of the tumour microenvironment consists of an inflammatory infiltrate predominated by microglia and macrophages, which are thought to be subverted by glioblastoma cells for tumour growth. Thus, glioblastoma-associated microglia and macrophages are logical therapeutic targets...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334546/-parathyroid-cancer
#5
Ivana Ságová, Matej Stančík, Peter Kentoš, Dušan Pavai, Daniela Kantárová, Anton Vaňuga, Peter Vaňuga
Parathyroid cancer is a rare endocrine malignancy, representing less than 1 % of all cases of primary hyperparathyroidism. The exact etiology of the disease remains unknown. Known risk factors include neck irradiation, end stage renal failure, genetic factors, particularly the the HPRT2/CDCT73 gene mutation. The clinical picture is often indolent, yet progressive with a trend of local invasion and metastasis formation in advanced disease. The clinical picture includes symptoms of severe and resistant hypercalcemia, requiring intensive therapy often with the need of dialysis...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28334207/oviposition-preference-and-larval-performance-of-cnaphalocrocis-medinalis-lepidoptera-pyralidae-on-rice-genotypes
#6
Chung-Ta Liao, Chung-Li Chen
Cnaphalocrocis medinalis Guenée is a noxious rice pest during cultivated periods. Cnaphalocrocis medinalis moths lay eggs on leaf surfaces, and larvae longitudinally roll the leaves to hide inside the leaf buds and feed on the upper epidermis and mesophyll tissues. In this study, we evaluated the female oviposition preference and larval performance of C. medinalis on six insect-resistant and six insect-susceptible rice genotypes. Female moth choice and no-choice oviposition preferences were studied. The number of eggs laid on the leaf varies among selected rice genotypes; however, female adults prefer to lay more eggs on both some resistant and susceptible rice genotypes...
March 8, 2017: Journal of Economic Entomology
https://www.readbyqxmd.com/read/28333380/smooth-muscle-ion-channels-and-regulation-of-vascular-tone-in-resistance-arteries-and-arterioles
#7
Nathan R Tykocki, Erika M Boerman, William F Jackson
Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body's tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333200/antibiotic-prescribing-frequency-amongst-patients-in-primary-care-a-cohort-study-using-electronic-health-records
#8
Laura Shallcross, Nick Beckley, Greta Rait, Andrew Hayward, Irene Petersen
Background: Reducing inappropriate antibiotic prescribing in primary care is a public health priority. Objectives: We hypothesized that a subset of patients account for the majority of antibiotic prescriptions in primary care. We investigated the relationship between the total amount of antibiotics prescribed, individual-level antibiotic use and comorbidity. Methods: This was a cohort study using electronic health records from 1 948 390 adults registered with 385 primary care practices in the UK in 2011-13...
February 21, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333153/a-novel-inhibitor-idpp-interferes-with-entry-and-egress-of-hcv-by-targeting-glycoprotein-e1-in-a-genotype-specific-manner
#9
Myungeun Lee, Jaewon Yang, Eunji Jo, Ji-Young Lee, Hee-Young Kim, Ralf Bartenschlager, Eui-Cheol Shin, Yong-Soo Bae, Marc P Windisch
Despite recent advances in curing chronic hepatitis C (CHC), the high economic burden to therapy, viral drug resistance, difficult to treat hepatitis C virus (HCV) genotypes and patient groups are still of concern. To address this unmet medical needs, we devised strategies to identify novel viral interventions through target-free high-throughput screening of small molecules utilizing a phenotypic-based HCV infection assay. Thereby, a very potent (EC50 46 ± 26 pM) iminodipyridinopyrimidine (IDPP) drug candidate was selected, and confirmed in primary human hepatocytes (EC50 0...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332225/molecular-dynamics-validation-of-crizotinib-resistance-to-alk-mutations-l1196m-and-g1269a-and-identification-of-specific-inhibitors
#10
Nagasundaram Nagarajan, Carlton Ranjith Wilson Alphonse, Prakash Vincent Samuel Gnana, Rajesh Kannan Rajaretinam
Anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are mostly treated with ALK tyrosine kinase inhibitors (TKIs). Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations. However, patients treated with these drugs invariably relapsed because of the development of new drug resistance mutations. In this study we explored the crizotinib resistance in the presence of ALK mutations L1196M and G1269A through molecular dynamics simulation studies...
March 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28332095/identification-of-t-cell-target-antigens-in-glioblastoma-stem-like-cells-using-an-integrated-proteomics-based-approach-in-patient-specimens
#11
Carmen Rapp, Rolf Warta, Slava Stamova, Ali Nowrouzi, Christoph Geisenberger, Zoltan Gal, Saskia Roesch, Steffen Dettling, Simone Juenger, Mariana Bucur, Christine Jungk, Philip DaoTrong, Rezvan Ahmadi, Felix Sahm, David Reuss, Valentina Fermi, Esther Herpel, Volker Eckstein, Niels Grabe, Christoph Schramm, Markus A Weigand, Juergen Debus, Andreas von Deimling, Andreas Unterberg, Amir Abdollahi, Philipp Beckhove, Christel Herold-Mende
Glioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells-often referred to as glioblastoma stem-like cells (GSCs)-has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28331999/the-acidic-microenvironment-as-a-possible-niche-of-dormant-tumor-cells
#12
REVIEW
Silvia Peppicelli, Elena Andreucci, Jessica Ruzzolini, Anna Laurenzana, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso, Francesca Bianchini, Lido Calorini
Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called "minimal residual disease". Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as "cancer dormancy". Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies...
March 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28331349/antibiotic-resistance-among-helicobacter-pylori-clinical-isolates-in-lima-peru
#13
Kevin F Boehnke, Manuel Valdivieso, Alejandro Bussalleu, Rachael Sexton, Kathryn C Thompson, Soledad Osorio, Italo Novoa Reyes, John J Crowley, Laurence H Baker, Chuanwu Xi
OBJECTIVES: Gastric carcinoma is the most common cancer and cause of cancer mortality in Peru. Helicobacter pylori, a bacterium that colonizes the human stomach, is a Group 1 carcinogen due to its causal relationship to gastric carcinoma. While eradication of H. pylori can help prevent gastric cancer, characterizing regional antibiotic resistance patterns is necessary to determine targeted treatment for each region. Thus, we examined primary antibiotic resistance in clinical isolates of H...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28331319/humanized-cd7-nanobody-based-immunotoxins-exhibit-promising-anti-t-cell-acute-lymphoblastic-leukemia-potential
#14
Yuan Yu, Jialu Li, Xuejun Zhu, Xiaowen Tang, Yangyi Bao, Xiang Sun, Yuhui Huang, Fang Tian, Xiaomei Liu, Lin Yang
BACKGROUND: Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies]), are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28331226/the-histone-deacetylase-inhibitor-givinostat-itf2357-exhibits-potent-anti-tumor-activity-against-crlf2-rearranged-bcp-all
#15
A M Savino, J Sarno, L Trentin, M Vieri, G Fazio, M Bardini, C Bugarin, G Fossati, K Davis, G Gaipa, S Izraeli, L H Meyer, G P Nolan, A Biondi, G Te Kronnie, C Palmi, G Cazzaniga
Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert antineoplastic activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations...
March 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#16
Xu Zhang, Tapan Maity, Manoj K Kashyap, Mukesh Bansal, Abhilash Venugopalan, Sahib Singh, Shivangi Awasthi, Arivusudar Marimuthu, Harrys Kishore Charles Jacob, Natalya Belkina, Stephanie Pitts, Constance M Cultraro, Shaojian Gao, Fatos Kirkali, Romi Biswas, Raghothama Chaerkady, Andrea Califano, Akhilesh Pandey, Udayan Guha
Mutations in the Epidermal growth factor receptor (EGFR) kinase domain, such as the L858R missense mutation and deletions spanning the conserved sequence 747LREA750, are sensitive to tyrosine kinase inhibitors (TKIs). The gatekeeper site residue mutation, T790M accounts for around 60% of acquired resistance to EGFR TKIs. The first generation EGFR TKIs, erlotinib and gefitinib, and the second generation inhibitor, afatinib are FDA approved for initial treatment of EGFR mutated lung adenocarcinoma. The predominant biomarker of EGFR TKI responsiveness is the presence of EGFR TKI-sensitizing mutations...
March 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28330446/eudor-a-multi-centre-research-program-a-naturalistic-european-multi-centre-clinical-study-of-edor-test-in-adult-patients-with-primary-depression
#17
Marco Sarchiapone, Miriam Iosue, Vladimir Carli, Mario Amore, Enrique Baca-Garcia, Anil Batra, Doina Cosman, Philippe Courtet, Guido Di Sciascio, Ricardo Gusmao, Tadeusz Parnowski, Peter Pestality, Pilar Saiz, Johannes Thome, Anders Tingström, Marcin Wojnar, Patrizia Zeppegno, Lars-Håkan Thorell
BACKGROUND: Electrodermal reactivity has been successfully used as indicator of interest, curiosity as well as depressive states. The measured reactivity depends on the quantity of sweat secreted by those eccrine sweat glands that are located in the hypodermis of palmar and plantar regions. Electrodermal hyporeactive individuals are those who show an unusual rapid habituation to identical non-significant stimuli. Previous findings suggested that electrodermal hyporeactivity has a high sensitivity and a high specificity for suicide...
March 23, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28330203/evaluation-of-several-ionic-liquids-for-in-situ-hydrolysis-of-empty-fruit-bunches-by-locally-produced-cellulase
#18
Amal Ahmed Elgharbawy, Md Zahangir Alam, Nassereldeen Ahmad Kabbashi, Muhammad Moniruzzaman, Parveen Jamal
Lignocellulosic biomasses, exhibit resistance to enzymatic hydrolysis due to the presence of lignin and hemicellulose. Ionic liquids proved their applicability in lignin degradation, however, ionic liquid removal has to be performed to proceed to hydrolysis. Therefore, this study reports an in situ hydrolysis of empty fruit bunches (EFB) that combined an ionic liquid (IL) pretreatment and enzymatic hydrolysis. For enzyme production, palm kernel cake (PKC) was used as the primary media for microbial cellulase (PKC-Cel) from Trichoderma reesei (RUTC30)...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329746/genotyping-platelet-activation-and-cardiovascular-outcome-in-patients-after-percutaneous-coronary-intervention-two-pieces-of-the-puzzle-of-clopidogrel-resistance
#19
Gerasimos Siasos, Evangelos Oikonomou, Manolis Vavuranakis, Eleni Kokkou, Konstantinos Mourouzis, Sotiris Tsalamandris, Marina Zaromitidou, Stamatios Kioufis, Vasiliki Tsigkou, Spyridon Defteros, Christodoulos Stefanadis, Dimitris Tousoulis
OBJECTIVES: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. METHODS: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI...
March 22, 2017: Cardiology
https://www.readbyqxmd.com/read/28329368/intermittent-preventive-treatment-with-dihydroartemisinin-piperaquine-for-the-prevention-of-malaria-among-hiv-infected-pregnant-women
#20
Paul Natureeba, Abel Kakuru, Mary Muhindo, Eric Littmann, Teddy Ochieng, John Ategeka, Catherine A Koss, Albert Plenty, Edwin D Charlebois, Tamara D Clark, Bridget Nzarubara, Miriam Nakalembe, Deborah Cohan, Gabrielle Rizzuto, Atis Muehlenbachs, Theodore Ruel, Prasanna Jagannathan, Diane V Havlir, Moses R Kamya, Grant Dorsey
Background.: Daily trimethoprim-sulfamethoxazole (TMP-SMX) and insecticide treated nets (ITNs) remain the main interventions for prevention of malaria in HIV-infected pregnant women in Africa. However, antifolate and pyrethroid resistance threaten the effectiveness of these intervention and new ones are needed. Methods.: We conducted a double-blind randomized placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine (DP) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Uganda where indoor residual spraying of insecticide (IRS) had recently been implemented...
February 22, 2017: Journal of Infectious Diseases
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