keyword
MENU ▼
Read by QxMD icon Read
search

Double Hit

keyword
https://www.readbyqxmd.com/read/29453370/a-multitarget-approach-to-drug-discovery-inhibiting-mycobacterium-tuberculosis-pyrg-and-pank
#1
Laurent R Chiarelli, Giorgia Mori, Beatrice Silvia Orena, Marta Esposito, Thomas Lane, Ana Luisa de Jesus Lopes Ribeiro, Giulia Degiacomi, Júlia Zemanová, Sára Szádocka, Stanislav Huszár, Zuzana Palčeková, Marcello Manfredi, Fabio Gosetti, Joël Lelièvre, Lluis Ballell, Elena Kazakova, Vadim Makarov, Emilio Marengo, Katarina Mikusova, Stewart T Cole, Giovanna Riccardi, Sean Ekins, Maria Rosalia Pasca
Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new antitubercular drugs as well as novel targets are crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and 7904688, which target the CTP synthetase PyrG, were identified and characterized. In this work, microbiological, biochemical, and in silico methodologies were used to demonstrate that both prodrugs possess a second target, the pantothenate kinase PanK...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29452344/overexpression-of-blm-promotes-dna-damage-and-increased-sensitivity-to-platinum-salts-in-triple-negative-breast-and-serous-ovarian-cancers
#2
N J Birkbak, Y Li, S Pathania, A Greene-Colozzi, M Dreze, C Bowman-Colin, Z Sztupinszki, M Krzystanek, M Diossy, N Tung, P D Ryan, J E Garber, D P Silver, J D Iglehart, Z C Wang, D Szuts, Z Szallasi, A L Richardson
Background: Platinum based therapy is an effective treatment for a subset of triple negative breast cancer and ovarian cancer patients. In order to increase response rate and decrease unnecessary use, robust biomarkers that predict response to therapy are needed. Patients and methods: We performed an integrated genomic approach combining differential analysis of gene expression and DNA copy number in sensitive compared to resistant triple negative breast cancers in two independent neoadjuvant cisplatin treated cohorts...
February 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29449860/adaptive-genetic-divergence-despite-significant-isolation-by-distance-in-populations-of-taiwan-cow-tail-fir-keteleeria-davidiana-var-formosana
#3
Kai-Ming Shih, Chung-Te Chang, Jeng-Der Chung, Yu-Chung Chiang, Shih-Ying Hwang
Double digest restriction site-associated DNA sequencing (ddRADseq) is a tool for delivering genome-wide single nucleotide polymorphism (SNP) markers for non-model organisms useful in resolving fine-scale population structure and detecting signatures of selection. This study performs population genetic analysis, based on ddRADseq data, of a coniferous species, Keteleeria davidiana var. formosana , disjunctly distributed in northern and southern Taiwan, for investigation of population adaptive divergence in response to environmental heterogeneity...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29440177/ponatinib-shows-potent-antitumor-activity-in-small-cell-carcinoma-of-the-ovary-hypercalcemic-type-sccoht-through-multi-kinase-inhibition
#4
Jessica D Lang, William P D Hendricks, Krystal A Orlando, Hongwei Yin, Jeffrey Kiefer, Pilar Ramos, Ritin Sharma, Patrick Pirrotte, Elizabeth A Raupach, Chris Sereduk, Nanyun Tang, Winnie S Liang, Megan Washington, Salvatore J Facista, Victoria L Zismann, Emily M Cousins, Michael B Major, Yemin Wang, Anthony N Karnezis, Aleksandar Sekulic, Ralf Hass, Barbara C Vanderhyden, Praveen Nair, Bernard E Weissman, David G Huntsman, Jeffrey M Trent
PURPOSE: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive ovarian cancer in young women that is universally driven by loss of the SWI/SNF ATPase subunits SMARCA4 and SMARCA2. A great need exists for effective targeted therapies for SCCOHT. EXPERIMENTAL DESIGN: To identify underlying therapeutic vulnerabilities in SCCOHT, we conducted high-throughput siRNA and drug screens. Complementary proteomics approaches profiled kinases inhibited by ponatinib...
February 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29433109/pathogenesis-of-aortic-wall-complications-in-marfan-syndrome
#5
Nimrat Grewal, Adriana C Gittenberger-de Groot
BACKGROUND: Patients with Marfan (MFS) syndrome and patients with a bicuspid aortic valve (BAV) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common as well as distinct pathways of clinical relevance, we compared the histopathological substrates of aortic pathology. PATIENT AND METHODS: Ascending aortic wall specimen were divided in five groups: BAV (n=36) and TAV (n=23) without and with dilation and non-dilated MFS (n=8)...
February 2, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29426286/monitoring-of-argatroban-and-lepirudin-anticoagulation-in-critically-ill-patients-by-conventional-laboratory-parameters-and-rotational-thromboelastometry-a-prospectively-controlled-randomized-double-blind-clinical-trial
#6
Martin Beiderlinden, Patrick Werner, Astrid Bahlmann, Johann Kemper, Tobias Brezina, Maximilian Schäfer, Klaus Görlinger, Holger Seidel, Peter Kienbaum, Tanja A Treschan
BACKGROUND: Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients...
February 9, 2018: BMC Anesthesiology
https://www.readbyqxmd.com/read/29420582/ethyl-pyruvate-ameliorates-hepatic-injury-following-blunt-chest-trauma-and-hemorrhagic-shock-by-reducing-local-inflammation-nf-kappab-activation-and-hmgb1-release
#7
Nils Wagner, Scott Dieteren, Niklas Franz, Kernt Köhler, Katharina Mörs, Luka Nicin, Julia Schmidt, Mario Perl, Ingo Marzi, Borna Relja
BACKGROUND: The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored...
2018: PloS One
https://www.readbyqxmd.com/read/29419530/challenges-and-opportunities-for-high-grade-b-cell-lymphoma-with-myc-and-bcl2-and-or-bcl6-rearrangement-double-hit-lymphoma
#8
Dongfeng Zeng, Aakash Desai, Fangfang Yan, Tiejun Gong, Haige Ye, Makhdum Ahmed, Krystle Nomie, Jorge Romaguera, Richard Champlin, Shaoying Li, Michael Wang
The most common subtype of non-Hodgkin lymphoma, diffuse large B-cell lymphoma, is cured in approximately two thirds of patients after initial therapy. The remaining one-third of patients who suffer relapse or become refractory have very poor survival outcomes despite salvage chemotherapy with or without stem cell transplantation. A considerable proportion of relapsed or refractory large B cells belong to the WHO subtype known as high-grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6, also known as double-hit lymphoma (DHL)...
February 6, 2018: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29416618/preclinical-efficacy-and-biological-effects-of-the-oral-proteasome-inhibitor-ixazomib-in-diffuse-large-b-cell-lymphoma
#9
Wei Liu, Juan Chen, Archito T Tamayo, Changgeng Ruan, Li Li, Shouhao Zhou, Chan Shen, Ken H Young, Jason Westin, Richard E Davis, Shimin Hu, Leonard J Medeiros, Richard J Ford, Lan V Pham
Despite advances in deciphering the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL), patients with relapsed/refractory disease, particularly those with adverse genetic features (e.g., mutated p53 or double hit lymphoma (DHL)) have very poor prognoses, and effective therapies are lacking. In this study we examined the preclinical efficacy and associated biological effects of the first oral proteasome inhibitor, ixazomib, in DLBCL in vitro and in vivo models. We demonstrated that ixazomib exhibited anti-tumor activities in 28 representative DLBCL cell lines, 10 primary DLBCL samples, and a DHL xenotransplant mouse model, at clinically achievable drug concentrations...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29399573/de-novo-cd5-positive-primary-gastric-diffuse-large-b-cell-lymphoma-coexpressing-myc-and-bcl6-towards-a-proper-subset-of-double-hit-triple-hit-and-maybe-quadruple-hit-b-cell-lymphomas
#10
EDITORIAL
https://www.readbyqxmd.com/read/29386360/therapeutic-synergy-between-tigecycline-and-venetoclax-in-a-preclinical-model-of-myc-bcl2-double-hit-b-cell-lymphoma
#11
Micol Ravà, Aleco D'Andrea, Paola Nicoli, Ilaria Gritti, Giulio Donati, Mirko Doni, Marco Giorgio, Daniela Olivero, Bruno Amati
High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provides a therapeutic window in a mouse model of MYC-driven lymphoma. We now addressed the utility of this antibiotic for treatment of DHL. BCL2 activation in mouse Eμ-myc lymphomas antagonized tigecycline-induced cell death, which was specifically restored by combined treatment with the BCL2 inhibitor venetoclax...
January 31, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29383130/gsk-3%C3%AE-inhibitor-9-ing-41-reduces-cell-viability-and-halts-proliferation-of-b-cell-lymphoma-cell-lines-as-a-single-agent-and-in-combination-with-novel-agents
#12
Reem Karmali, Vineela Chukkapalli, Leo I Gordon, Jeffrey A Borgia, Andrey Ugolkov, Andrew P Mazar, Francis J Giles
The complexities of GSK-3β function and interactions with PI3K/AKT/mTOR signaling, cell cycling, and apoptotic pathways are poorly understood in the context of lymphomagenesis and cancer therapeutics. In this study, we explored the anti-tumor effects of the GSK-3β inhibitor, 9-ING-41, in lymphoma cell lines as a single agent and in combination with novel agents comprising BCL-2 inhibitor (Venetoclax), CDK-9 inhibitor (BAY-1143572) and p110δ-PI3K inhibitor (Idelalisib). Treatment of Daudi, SUDHL-4, Karpas 422, KPUM-UH1, and TMD8 lymphoma cell lines with 1 μM 9-ING-41 reduced cell viability by 40-70% (p<0...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29383095/polo-like-kinase-1-plk-1-and-c-myc-inhibition-with-the-dual-kinase-bromodomain-inhibitor-volasertib-in-aggressive-lymphomas
#13
Carlos Murga-Zamalloa, Avery Polk, Walter Hanel, Pinki Chowdhury, Noah Brown, Alexandra C Hristov, Nathanael G Bailey, Tianjiao Wang, Tycel Phillips, Sumana Devata, Pradeep Poonnen, Juan Gomez-Gelvez, Kedar V Inamdar, Ryan A Wilcox
Survival following anthracycline-based chemotherapy remains poor among patients with most T-cell lymphoproliferative disorders. This may be attributed, at least in part, to cell-autonomous mechanisms of chemotherapy resistance observed in these lymphomas, including the loss of important tumor suppressors and the activation of signaling cascades that culminate in the expression and activation of transcription factors promoting cell growth and survival. Therefore, the identification of novel therapeutic targets is needed...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29368541/double-hit-lymphoma-do-we-need-a-double-hit-of-intensive-therapy
#14
Diego Villa, Laurie H Sehn
No abstract text is available yet for this article.
January 25, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29364511/-18-f-ge180-positron-emission-tomographic-imaging-indicates-a-potential-double-hit-insult-in-the-intrahippocampal-kainate-mouse-model-of-temporal-lobe-epilepsy
#15
Mirjam Brackhan, Pablo Bascuñana, Tobias L Ross, Frank M Bengel, Jens P Bankstahl, Marion Bankstahl
OBJECTIVE: Accumulating evidence suggests that brain inflammation, elicited by epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear imaging of brain inflammation in animal models of epileptogenesis represents a diagnostic in vivo approach with potential for direct translation into the clinic. Here, we investigated up-regulation of the translocator protein (TSPO) indicative of microglial activation by serial [18 F]GE180 positron emission tomographic (PET) imaging in a mouse model of temporal lobe epilepsy...
January 24, 2018: Epilepsia
https://www.readbyqxmd.com/read/29353886/the-bet-bromodomain-inhibitor-cpi203-overcomes-resistance-to-abt-199-venetoclax-by-downregulation-of-bfl-1-a1-in-in-vitro-and-in-vivo-models-of-myc-bcl2-double-hit-lymphoma
#16
A Esteve-Arenys, J G Valero, A Chamorro-Jorganes, D Gonzalez, V Rodriguez, I Dlouhy, I Salaverria, E Campo, D Colomer, A Martinez, G Rymkiewicz, P Pérez-Galán, A Lopez-Guillermo, G Roué
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, mostly known as double-hit lymphoma (DHL), is a rare entity characterized by morphologic and molecular features between Burkitt lymphoma and the clinically manageable diffuse large B-cell lymphoma (DLBCL). DHL patients usually undergo a rapidly progressing clinical course associated with resistance to standard chemo-immunotherapy. As a consequence, the prognosis of this entity is particularly poor with a median overall survival inferior to 1 year...
January 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#17
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29339272/an-old-friend-is-trouble-for-double-expressor-and-double-hit-lymphoma
#18
Michael Scordo
No abstract text is available yet for this article.
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29332092/early-life-stress-activates-glial-cells-in-the-hippocampus-but-attenuates-cytokine-secretion-in-response-to-an-immune-challenge-in-rat-pups
#19
Luis Miguel Saavedra, Bertha Fenton Navarro, Luz Torner
OBJECTIVE: Early life stress (ELS) increases the vulnerability to developing psychopathological disorders in adulthood that are accompanied by brain inflammatory processes. However, it is not known how a combined double hit (stress and immune) at an early age affects the response of the neuroimmune system. Here we investigated the effect of periodic maternal separation (MS) followed by administration of lipopolysaccharide (LPS) on glial cells in the CA3 region and hilus of the hippocampus and on cytokine release on postnatal day (PN) 15...
January 13, 2018: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29326077/mechanism-of-nanoparticle-induced-hypersensitivity-in-pigs-complement-or-not-complement
#20
János Szebeni
A recent study on nanoparticle-induced hypersensitivity reactions in pigs showed robust pulmonary intravascular macrophage clearance of Polybead® carboxylate microspheres in mediating the adverse cardiopulmonary distress, irrespective of the ability of these particles to activate the Complement (C) system in vitro. Focusing on this observation, this article highlights the controversies in projecting in vitro C assay data to in vivo conditions and applying data on polystyrene particles to therapeutic nanopharmaceuticals...
January 8, 2018: Drug Discovery Today
keyword
keyword
46198
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"