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https://www.readbyqxmd.com/read/28329763/the-allosteric-inhibitor-abl001-enables-dual-targeting-of-bcr-abl1
#1
Andrew A Wylie, Joseph Schoepfer, Wolfgang Jahnke, Sandra W Cowan-Jacob, Alice Loo, Pascal Furet, Andreas L Marzinzik, Xavier Pelle, Jerry Donovan, Wenjing Zhu, Silvia Buonamici, A Quamrul Hassan, Franco Lombardo, Varsha Iyer, Michael Palmer, Giuliano Berellini, Stephanie Dodd, Sanjeev Thohan, Hans Bitter, Susan Branford, David M Ross, Timothy P Hughes, Lilli Petruzzelli, K Gary Vanasse, Markus Warmuth, Francesco Hofmann, Nicholas J Keen, William R Sellers
Chronic myeloid leukaemia (CML) is driven by the activity of the BCR-ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Studies in patients with chronic-phase CML have shown that around 50% of patients who achieve and maintain undetectable BCR-ABL1 transcript levels for at least 2 years remain disease-free after the withdrawal of treatment...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#2
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328796/increased-incidence-of-cancer-observed-in-hiv-hcv-coinfected-patients-versus-hiv-monoinfected-1993-2014
#3
Héctor Meijide, Sonia Pértega, Iria Rodríguez-Osorio, Ángeles Castro-Iglesias, Josefa Baliñas, Guillermo Rodríguez-Martínez, Álvaro Mena, Eva Poveda
BACKGROUND: Cancer is a growing problem in persons living with HIV infection (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort were evaluated and compared to identify any differences between these two populations. METHODS: A retrospective cohort study was conducted including all cancers in PLWH between 1993 and 2014. Cancers were classified in two groups, AIDS-defining cancer (ADC) and non AIDS-defining cancer (NADC)...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28327996/genome-sequencing-of-the-sweetpotato-whitefly-bemsia-tabaci-med-q
#4
Wen Xie, Chunhai Chen, Zezhong Yang, Litao Guo, Xin Yang, Dan Wang, Ming Chen, Jinqun Huang, Yanan Wen, Yang Zeng, Yating Liu, Jixing Xia, Lixia Tian, Hongying Cui, Qingjun Wu, Shaoli Wang, Baoyun Xu, Xianchun Li, Xinqiu Tan, Murad Ghanim, Baoli Qiu, Huipeng Pan, Dong Chu, Helene Delatte, M N Maruthi, Feng Ge, Xueping Zhou, Xiaowei Wang, Fanghao Wan, Yuzhou Du, Chen Luo, Fengming Yan, Evan L Preisser, Xiaoguo Jiao, Brad S Coates, Jinyang Zhao, Qiang Gao, Jinquan Xia, Ye Yin, Yong Liu, Judith K Brown, Xuguo Joe Zhou, Youjun Zhang
Background: The sweetpotato whitefly Bemisia tabaci is a highly destructive agricultural and ornamental crop pest. It damages host plants through both phloem feeding and vectoring plant pathogens. Introductions of B. tabaci are difficult to quarantine and eradicate because of its high reproductive rates, broad host plant range, and insecticide resistance. Findings: A total of 791 Gb of raw DNA sequence from whole genome shotgun sequencing, and 13 BAC pooling libraries were generated by Illumina sequencing using different combinations of mate-pair and pair-end libraries...
March 15, 2017: GigaScience
https://www.readbyqxmd.com/read/28327498/activity-of-sulfa-drugs-and-their-combinations-against-stationary-phase-b-burgdorferi-in-vitro
#5
Jie Feng, Shuo Zhang, Wanliang Shi, Ying Zhang
Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B...
March 22, 2017: Antibiotics
https://www.readbyqxmd.com/read/28327271/novel-anti-staphylococcal-and-anti-biofilm-properties-of-two-anti-malarial-compounds-mmv665953-1-3-chloro-4-fluorophenyl-3-3-4-dichlorophenyl-urea-and-mmv665807-5-chloro-2-hydroxy-n-3-trifluoromethyl-phenyl-benzamide
#6
Marta Zapotoczna, Nabila Boksmati, Sinead Donohue, Baizurina Bahtiar, Ahmad Boland, Hamzah Al Somali, Alysia Cox, Hilary Humphreys, James P O'Gara, Marian Brennan, Eoghan O'Neill
PURPOSE: The treatment of device-related infections is challenging and current anti-microbial compounds have poor anti-biofilm activity. We aimed to identify and characterize novel compounds effective in the eradication of Staphylococcus aureus biofilms. METHODOLOGY: Two novel compounds, MMV665953 {1-(3-chloro-4-fluorophenyl)-3-(3,4-dichlorophenyl)urea} and MMV665807{5-chloro-2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide}, effective in killing S. aureus biofilms, were identified by screening of the open access 'malaria box' chemical library...
March 23, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28326664/the-corpus-predominant-gastritis-index-can-be-an-early-and-reversible-marker-to-identify-the-gastric-cancer-risk-of-helicobacter-pylori-infected-nonulcer-dyspepsia
#7
Hsiu-Chi Cheng, Yu-Ching Tsai, Hsiao-Bai Yang, Yi-Chun Yeh, Wei-Lun Chang, Hsin-Yu Kuo, Cheng-Chan Lu, Bor-Shyang Sheu
BACKGROUND: Corpus-predominant gastritis index (CGI) is an early histological marker to identify Helicobacter pylori-infected gastric cancer relatives at risk of cancer. This study validated whether CGI is more prevalent in H. pylori-infected nonulcer dyspepsia (NUD) subjects than in duodenal ulcer (DU) controls and whether it is reversible after H. pylori eradication or is correlated with noninvasive biomarkers. MATERIALS AND METHODS: In this longitudinal cohort study, 573 H...
March 22, 2017: Helicobacter
https://www.readbyqxmd.com/read/28326446/blastocystis-how-do-specific-diets-and-human-gut-microbiota-affect-its-development-and-pathogenicity
#8
REVIEW
M Lepczyńska, J Białkowska, E Dzika, K Piskorz-Ogórek, J Korycińska
Blastocystis is an enteric parasite that inhabits the gastrointestinal tract of humans and many animals. This emerging parasite has a worldwide distribution. It is often identified as the most common eukaryotic organism reported in human fecal samples. This parasite is recognized and diagnosed more often than ever before. Furthermore, some strains develop resistance against currently recommended drugs, such as metronidazole; therefore, the use of natural remedies or special diets has many positive aspects that may address this problem...
March 22, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28325625/-serological-detection-of-brucella-suis-influenza-virus-and-aujeszky-s-disease-virus-in-backyard-and-small-swine-holders-in-argentina
#9
Marina Dibarbora, Javier A Cappuccio, María N Aznar, Fernando A Bessone, Hernán Piscitelli, Ariel J Pereda, Daniel R Pérez
Farmers raising less than 100 sows represent more than 99% of swine producers in Argentina, although little is known about their sanitary status and productive characteristics in the country. Sanitary and productive information was obtained. Furthermore, samples for serological studies were taken to detect antibodies against Brucella suis (Bs), Aujeszky's disease virus (AV) and influenza virus (IV) in 68 backyard and small producers with less than 100 sows located in the north, central and south regions of Argentina...
March 18, 2017: Revista Argentina de Microbiología
https://www.readbyqxmd.com/read/28325289/specific-and-stable-suppression-of-hiv-provirus-expression-in%C3%A2-vitro-by-chimeric-zinc-finger-dna-methyltransferase-1
#10
Junxiao Deng, Xiying Qu, Panpan Lu, Xinyi Yang, Yuqi Zhu, Haiyan Ji, Yanan Wang, Zhengtao Jiang, Xian Li, Yangcheng Zhong, He Yang, Hanyu Pan, Won-Bin Young, Huanzhang Zhu
HIV-1 inserts its proviral DNA into the infected host cells, by which HIV proviral DNA can then be duplicated along with each cell division. Thus, provirus cannot be eradicated completely by current antiretroviral therapy. We have developed an innovative strategy to silence the HIV provirus by targeted DNA methylation on the HIV promoter region. We genetically engineered a chimeric DNA methyltransferase 1 composed of designed zinc-finger proteins to become ZF2 DNMT1. After transient transfection of the molecular clone encoding this chimeric protein into HIV-1 infected or latently infected cells, efficient suppression of HIV-1 expression by the methylation of CpG islands in 5'-LTR was observed and quantified...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325246/challenges-and-prospects-for-providing-radiation-oncology-services-in-africa
#11
REVIEW
Onyinye Balogun, Danielle Rodin, Wilfred Ngwa, Surbhi Grover, John Longo
There are considerable challenges to meeting the demands of the impending cancer crisis in Africa. These include a rising incidence of cancer and cancer-related deaths, equipment and maintenance costs, and deficits in human resources and training. Addressing these issues would be crucial to tackling the increasing burden of cancer on the continent. Innovations in technology and collaborative efforts within the global oncology community have created promising solutions for establishing quality cancer care in Africa and eradicating the massive disparities that currently exist...
April 2017: Seminars in Radiation Oncology
https://www.readbyqxmd.com/read/28325194/multimodality-treatment-of-gastric-lymphoma
#12
REVIEW
Naruhiko Ikoma, Brian D Badgwell, Paul F Mansfield
Gastric lymphoma is rare, accounting for 3% of gastric neoplasms and 10% of lymphomas. Treatment should be stratified based on histologic type, stage, Helicobacter pylori infection, and t(11;18) translocation status. Surgery is no longer a mainstay for treatment and should be reserved for rare situations such as perforation, fistula formation, and severe bleeding. Multimodal treatment, including H pylori eradication, radiation therapy, chemotherapy, and immunotherapy, should be provided as appropriate and can result in excellent outcomes...
April 2017: Surgical Clinics of North America
https://www.readbyqxmd.com/read/28323552/helicobacter-pylori-eradication-in-the-swedish-population
#13
Eva Doorakkers, Jesper Lagergren, Vijaya Krishna Gajulapuri, Steven Callens, Lars Engstrand, Nele Brusselaers
OBJECTIVES: Helicobacter pylori is associated with peptic ulcers and gastric cancer and its eradication aims to prevent these conditions. The recommended eradication regimen is triple therapy, consisting of a proton-pump inhibitor in combination with clarithromycin and amoxicillin or metronidazole for 7 days. Yet, other antibiotic regimens are sometimes prescribed. We aimed to assess the use of eradication therapy for H. pylori in the Swedish population during the last decade. MATERIALS AND METHODS: This population-based study used data from the Swedish Prescribed Drug Register...
March 21, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28323141/mechanistic-and-pharmacologic-insights-on-immune-checkpoint-inhibitors
#14
REVIEW
Randy F Sweis, Jason J Luke
The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to augment the anti-tumor immune response. Unprecedented responses across a broad array of cancer types elevated this class of therapies to the forefront of cancer treatment. The most successful drugs to date target the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28323111/nanoparticles-for-tumor-immunotherapy
#15
REVIEW
Xinlong Zang, Xiuli Zhao, Haiyang Hu, Mingxi Qiao, Yihui Deng, Dawei Chen
Although most researches and therapies have been focused on the tumor itself, it is becoming clear that immune cells can not only suppress tumor development but support and maintain their malignant type. Promising recent developments in immunology will provide opportunities for tumor-specific immunotherapy, which can orchestrate the patients immune system to target, fight and eradicate cancer cells without destroying healthy cells. However, antitumor immunity driven by self-immune system alone may be therapeutically insufficient...
March 18, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28323033/application-of-mathematical-models-to-metronomic-chemotherapy-what-can-be-inferred-from-minimal-parameterized-models
#16
Urszula Ledzewicz, Heinz Sch Attler
Metronomic chemotherapy refers to the frequent administration of chemotherapy at rela-tively low, minimally toxic doses without prolonged treatment interruptions. Different from conventional or maximum-tolerated-dose chemotherapy which aims at an eradication of all malignant cells, in a metronomic dosing the goal often lies in the long-term management of the disease when eradication proves elusive. Mathematical modeling and subsequent analysis (theoretical as well as numerical) have become an increasingly more valuable tool (in silico) both for determining conditions under which specific treatment strategies should be preferred and for numerically optimizing treatment regimens...
March 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322295/alterations-in-gastric-microbiota-after-h-pylori-eradication-and-in-different-histological-stages-of-gastric-carcinogenesis
#17
Tung Hiu Li, Youwen Qin, Pak Chung Sham, K S Lau, Kent-Man Chu, Wai K Leung
The role of bacteria other than Helicobacter pylori (HP) in the stomach remains elusive. We characterized the gastric microbiota in individuals with different histological stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP negative controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominant H...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322292/a-structure-and-chemical-genomics-based-approach-for-repositioning-of-drugs-against-vcp-p97-atpase
#18
Aldo Segura-Cabrera, Reshmi Tripathi, Xiaoyi Zhang, Lin Gui, Tsui-Fen Chou, Kakajan Komurov
Valosin-containing protein (VCP/p97) ATPase (a.k.a. Cdc48) is a key member of the ER-associated protein degradation (ERAD) pathway. ERAD and VCP/p97 have been implicated in a multitude of human diseases, such as neurodegenerative diseases and cancer. Inhibition of VCP/p97 induces proteotoxic ER stress and cell death in cancer cells, making it an attractive target for cancer treatment. However, no drugs exist against this protein in the market. Repositioning of drugs towards new indications is an attractive alternative to the de novo drug development due to the potential for significantly shorter time to clinical translation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322258/optimum-soil-frost-depth-to-alleviate-climate-change-effects-in-cold-region-agriculture
#19
Yosuke Yanai, Yukiyoshi Iwata, Tomoyoshi Hirota
On-farm soil frost control has been used for the management of volunteer potatoes (Solanum tuberosum L.), a serious weed problem caused by climate change, in northern Japan. Deep soil frost penetration is necessary for the effective eradication of unharvested small potato tubers; however, this process can delay soil thaw and increase soil wetting in spring, thereby delaying agricultural activity initiation and increasing nitrous oxide emissions from soil. Conversely, shallow soil frost development helps over-wintering of unharvested potato tubers and nitrate leaching from surface soil owing to the periodic infiltration of snowmelt water...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321982/susceptibility-of-insecticide-resistant-bed-bugs-cimex-lectularius-to-infection-by-fungal-biopesticide
#20
Alexis M Barbarin, Giovani S Bellicanta, Jason A Osborne, Coby Schal, Nina E Jenkins
BACKGROUND: Bed bugs are a public health concern, and their incidence is increasing worldwide. Bed bug infestations are notoriously difficult to eradicate, further exacerbated by widespread resistance to pyrethroid and neonicotinoid insecticides. This study evaluated the efficacy of the newly developed fungal biopesticide, Aprehend™, containing Beauveria bassiana, against insecticide-resistant bed bugs. RESULTS: Overall mortality for the Harold Harlan (insecticide-susceptible) strain was high (98-100%) following exposure to Aprehend™ or Suspend SC (deltamethrin)...
March 20, 2017: Pest Management Science
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