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https://www.readbyqxmd.com/read/27913204/the-selective-bcl-2-inhibitor-venetoclax-a-bh3-mimetic-does-not-dysregulate-intracellular-ca-2-signaling
#1
Tamara Vervloessem, Hristina Ivanova, Tomas Luyten, Jan B Parys, Geert Bultynck
Anti-apoptotic B cell-lymphoma-2 (Bcl-2) proteins are emerging as therapeutic targets in a variety of cancers for precision medicines, like the BH3-mimetic drug venetoclax (ABT-199), which antagonizes the hydrophobic cleft of Bcl-2. However, the impact of venetoclax on intracellular Ca(2+) homeostasis and dynamics in cell systems has not been characterized in detail. Here, we show that venetoclax did not affect Ca(2+)-transport systems from the endoplasmic reticulum (ER) in permeabilized cell systems. Venetoclax (1μM) did neither trigger Ca(2+) release by itself nor affect agonist-induced Ca(2+) release in a variety of intact cell models...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27888878/the-spectrum-of-double-hit-lymphomas
#2
REVIEW
Jeremy S Abramson
Double-hit lymphomas (DHLs) characterize a unique subset of B-cell non-Hodgkin lymphomas. DHL typically presents in older adults with high-risk clinical features. This entity carries a significantly inferior prognosis compared with typical cases of diffuse large B-cell lymphoma; however, emerging literature can identify discrete clinical features within DHL that are associated with a favorable prognosis. Emerging literature is also demonstrating that intensive upfront treatment strategies may improve outcome...
December 2016: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27888664/ebv-associated-but-hhv8-unrelated-double-hit-effusion-based-lymphoma
#3
Bo-Jung Chen, David Yen-Ting Chen, Chun-Chi Kuo, Shih-Sung Chuang
Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion...
November 26, 2016: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/27858214/synthesis-and-biological-evaluation-of-n-3-oxo-3-4-dihydro-2h-benzo-b-1-4-oxazin-7-yl-benzenesulfonamide-derivatives-as-new-bet-bromodomain-inhibitors-for-anti-hematologic-malignancies-activities
#4
Li Liu, Yongxia Zhu, Zhihao Liu, Tinghong Ye, Weiqiong Zuo, Cuiting Peng, Kunjie Xiao, Ningyu Wang, Luoting Yu
The bromodomain and extra-terminal proteins (BETs), in particular BRD4, has been reported to play important roles in cancer, inflammation, obesity, cardiovascular disease, and neurological disorders. In this paper, a series of benzomorpholinone derivatives were synthesized and biologically evaluated as BETs inhibitors. Detailed structure-activity relationship studies led to the discovery of several new potent compounds, of which 15h and 15i displayed [Formula: see text] values of 2.8 and 4.5 [Formula: see text] against BRD4 (D1), respectively, and showed good anti-proliferation activities against four hematologic malignancies cell lines at low-micromolar concentrations, including MV4-11, OCI-LY10, Pfeifer, and Su-DHL-6 cells...
November 17, 2016: Molecular Diversity
https://www.readbyqxmd.com/read/27846451/sar-study-of-5-alkynyl-substituted-quinazolin-4-3h-ones-as-phosphoinositide-3-kinase-delta-pi3k%C3%AE-inhibitors
#5
Manman Wei, Xi Zhang, Xiang Wang, Zilan Song, Jian Ding, Ling-Hua Meng, Ao Zhang
PI3Kδ is a key component in the aberrant signaling transduction in B cell malignancy, therefore specific targeting PI3Kδ has become an attractive molecularly targeted therapy for chronic lymphocytic leukemia (CLL). Herein, we describe the discovery and optimization of a series of 5-alkynyl substituted PI3Kδ inhibitors based on the first FDA-approved inhibitor idelalisib. Compound 8d bearing the 1-morpholinohex-5-yn-1-one moiety as the C5-substituent was identified to have high potency against PI3Kδ (3.82 nM) and SU-DHL-6 cells (7...
November 9, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27825800/dhl-hiszn-a-novel-antioxidant-enhances-adipogenic-differentiation-and-antioxidative-response-in-adipose-derived-stem-cells
#6
Chien-Chih Chen, Li-Wen Hsu, Toshiaki Nakano, Kuang-Tzu Huang, Kuang-Den Chen, Chia-Yun Lai, Shigeru Goto, Chao-Long Chen
Adipose-derived stem cells (ASCs) are multipotent progenitor cells that have the capacity to differentiate into specific mesenchymal cell lineages including adipocytes in response to environmental cues. Dysfunctional adipose tissue, rather than an excess of adipose tissue, has been proposed as a key factor in the pathogenesis of obesity-related diseases. The insulin-sensitizing effects of antidiabetic drugs are mediated by activation of peroxisome proliferator-activated receptor gamma (PPARγ). Here, we investigated the effects of sodium zinc histidine dithiooctanamide (DHL-HisZn), a strong antioxidant, on PPARγ activation, adipocyte differentiation and insulin sensitivity...
November 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27806821/double-hit-lymphoma-arare-subset-of-diffuse-large-b-cell-lymphoma-with-poor-outcome
#7
Sajid Zaman, Jawad A Gillani, Rashid Rasheed
Double-hit lymphoma (DHL) has been identified as a subset of diffuse large B-cell lymphoma with poor clinical outcomes. It is because of genetic translocation of C-myc and Bcl2 gene that make it more aggressive and un-responsive to conventional and salvage treatments. DHLis an extremely rare entity of non-Hodgkin's lymphoma (NHL) having no established incidence data so far. In literature very limited data is available to guide therapeutic decisions and despite aggressive chemotherapy followed by autologus hematopoietic cell transplantation, outcomes still remain poor...
October 2016: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/27806737/effect-of-guaianolides-in-the-meiosis-reinitiation-of-amphibian-oocytes
#8
J Zapata-Martínez, G Sánchez-Toranzo, F Chaín, C A N Catalán, M I Bühler
Sesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs...
November 3, 2016: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/27803769/hepatitis-c-and-double-hit-b-cell-lymphoma-successfully-treated-by-antiviral-therapy
#9
Giovanni Galati, Lorenzo Rampa, Umberto Vespasiani-Gentilucci, Mirella Marino, Francesco Pisani, Carlo Cota, Alessandro Guidi, Antonio Picardi
B cells lymphoma is one of the most challenging extra-hepatic manifestations of hepatitis C virus (HCV). Recently, a new kind of B-cell lymphoma, named double-hit B (DHL), was characterized with an aggressive clinical course whereas a potential association with HCV was not investigated. The new antiviral direct agents (DAAs) against HCV are effective and curative in the majority of HCV infections. We report the first case, to our knowledge, of DHL and HCV-infection successfully treated by new DAAs. According to our experience, a DHL must be suspected in case of HCV-related lymphoma, and an early diagnosis could direct towards a different hematological management because a worse prognosis might be expected...
October 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27799353/posaconazole-loaded-leukocytes-as-a-novel-treatment-strategy-targeting-invasive-pulmonary-aspergillosis
#10
Shane R Baistrocchi, Mark J Lee, Melanie Lehoux, Benjamin Ralph, Brendan D Snarr, Robert Robitaille, Donald C Sheppard
BACKGROUND:  Impaired delivery of antifungals to hyphae within necrotic lesions is thought to contribute to therapeutic failure in invasive pulmonary aspergillosis (IPA). We hypothesized that transfusion of leukocytes loaded ex-vivo with the lipophilic antifungal posaconazole could improve delivery of antifungals to the sites of established infection and improve outcome in experimental IPA. METHODS:  The HL-60 leukemia cell line was differentiated to a neutrophil-like phenotype (dHL-60 cells) then exposed to a range of posaconazole concentrations...
October 31, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27742770/inhibition-of-demethylase-kdm6b-sensitizes-diffuse-large-b-cell-lymphoma-to-chemotherapeutic-drugs
#11
Rohit Mathur, Lalit Sehgal, Ondrej Havranek, Stefan Köhrer, Tamer Khashab, Neeraj Jain, Jan A Burger, Sattva S Neelapu, R Eric Davis, Felipe Samaniego
Histone methylation and demethylation regulates B-cell development, and their deregulation correlates with tumor chemoresistance in diffuse large B-cell lymphoma, limiting curative rates. Since histone methylation status correlates with disease aggressiveness and relapse, we investigated the therapeutic potential of inhibiting histone 3 Lys27 demethylase KDM6B, in-vitro, using the small molecule inhibitor GSK-J4. KDM6B is overexpressed in the DLBCL germinal center B-cell subtype, and higher KDM6B levels are associated with worse survival in DLBCL patients treated with R-CHOP...
October 14, 2016: Haematologica
https://www.readbyqxmd.com/read/27728396/dengue-haemorrhagic-fever-with-acute-respiratory-distress-syndrome
#12
Harshad L Patel, Dhl Patel, A A Nikam
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27671304/dehydroleucodine-induces-a-tp73-dependent-transcriptional-regulation-of-multiple-cell-death-target-genes-in-human-glioblastoma-cells
#13
Edward A Ratovitski
Dehydroleucodine (DhL), a natural sesquiterpene lactone from Artemisia douglassiana Besser (Argentine) and Gynoxys verrucosa (Ecuador) was shown to induce a cell death in cancer cells through senescence, apoptosis, and DNA damage. Here, we found that the DhL exposure upregulated the total and phosphorylated (p-Y99) levels of TP73 in human glioblastoma U87-MG cells. We further found that TP73 silencing led to a partial rescue of U87-MG cells from the cell death induced by DhL. Upon the DhL exposure numerous gene targets were upregulated and downregulated through a TP73-dependent transcriptional mechanism...
September 23, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27639717/selection-and-characterization-of-single-domain-antibodies-against-human-cd20
#14
Jinny L Liu, Dan Zabetakis, Ellen R Goldman, George P Anderson
CD20 is a membrane protein with four integral membrane regions and a large extracellular loop between residues 142 and 187, which serves as a target binding region for rituximab (RTX) and most other anti-CD20 monoclonal antibodies. It is highly expressed in B-lymphoma cells and B lymphocytes and often serves as a target for immunotherapy. In this study, we developed single domain antibodies (sdAbs) for the sensitive detection of CD20. To achieve this, an immune sdAb library was prepared from llamas immunized with a fusion between the large loop from CD20 and Hoc, a highly antigenic protein from the T4 bacteriophage, (CD20-Hoc)...
October 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27615202/barium-sulfate-micro-and-nanoparticles-as-bioinert-reference-material-in-particle-toxicology
#15
Kateryna Loza, Isabell Föhring, Jürgen Bünger, Götz A Westphal, Manfred Köller, Matthias Epple, Christina Sengstock
The inhalation of particles and their exposure to the bronchi and alveoli constitute a major public health risk. Chemical as well as particle-related properties are important factors for the biological response but are difficult to separate from each other. Barium sulfate is a completely inert chemical compound, therefore it is ideally suited to separate these two factors. The biological response of rat alveolar macrophages (NR8383) was analyzed after exposure to barium sulfate particles with three different diameters (40 nm, 270 nm, and 1...
September 27, 2016: Nanotoxicology
https://www.readbyqxmd.com/read/27566572/subclones-in-b-lymphoma-cell-lines-isogenic-models-for-the-study-of-gene-regulation
#16
Hilmar Quentmeier, Claudia Pommerenke, Ole Ammerpohl, Robert Geffers, Vivien Hauer, Roderick Af MacLeod, Stefan Nagel, Julia Romani, Emanuela Rosati, Anders Rosén, Cord C Uphoff, Margarete Zaborski, Hans G Drexler
Genetic heterogeneity though common in tumors has been rarely documented in cell lines. To examine how often B-lymphoma cell lines are comprised of subclones, we performed immunoglobulin (IG) heavy chain hypermutation analysis. Revealing that subclones are not rare in B-cell lymphoma cell lines, 6/49 IG hypermutated cell lines (12%) consisted of subclones with individual IG mutations. Subclones were also identified in 2/284 leukemia/lymphoma cell lines exhibiting bimodal CD marker expression. We successfully isolated 10 subclones from four cell lines (HG3, SU-DHL-5, TMD-8, U-2932)...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27496158/attenuation-and-quantitation-of-virulence-gene-expression-in-quorum-quenched-dickeya-chrysanthemi
#17
Saeed Hosseinzadeh, Masoud Shams-Bakhsh, Majid Sadeghizadeh
N-Acyl-homoserine lactones (AHLs)-dependent quorum sensing (QS) system(s) is recruited by the soft rot bacterium Dickeya chrysanthemi for coordinating its social activities such as secretion of plant cell wall-degrading enzymes, while the main signal molecule and quantity dependence of virulence to QS in this bacterium have not been clarified. To do this end, the involvement of AHLs in African violet leaves and potato tuber maceration; swarming motility; pectate lyase and polygalacturonase enzymes production and in planta expression of virulence genes including pelE, pehX and pemA by electroporating two quorum-quenching vectors...
August 5, 2016: Archives of Microbiology
https://www.readbyqxmd.com/read/27494885/bromodomain-inhibitor-otx015-mk-8628-combined-with-targeted-agents-shows-strong-in-vivo-antitumor-activity-in-lymphoma
#18
Eugenio Gaudio, Chiara Tarantelli, Maurilio Ponzoni, Elodie Odore, Keyvan Rezai, Elena Bernasconi, Luciano Cascione, Andrea Rinaldi, Anastasios Stathis, Eugenia Riveiro, Esteban Cvitkovic, Emanuele Zucca, Francesco Bertoni
The bromodomain inhibitor OTX015 (MK-8628) has shown anti-lymphoma activity as a single agent in both the preclinical and clinical settings, as well as in vitro synergism with several anticancer agents. Here, we report in vivo data for OTX015 in combination with the histone deacetylase inhibitor vorinostat, the Bruton's tyrosine kinase inhibitor ibrutinib, the anti-CD20 monoclonal antibody rituximab, and the mTOR inhibitor everolimus in a diffuse large B cell lymphoma model. The antitumor effect of OTX015-containing combinations in SU-DHL-2 xenografts in mice was much stronger than the activity of the corresponding single agents with almost complete tumor eradication for all four combinations...
August 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27469075/sole-rearrangement-but-not-amplification-of-myc-is-associated-with-a-poor-prognosis-in-patients-with-diffuse-large-b-cell-lymphoma-and-b-cell-lymphoma-unclassifiable
#19
Daniel J Landsburg, Marissa K Falkiewicz, Adam M Petrich, Benjamin A Chu, Amir Behdad, Shaoying Li, L Jeffrey Medeiros, Ryan D Cassaday, Nishitha M Reddy, Martin A Bast, Julie M Vose, Kimberly R Kruczek, Scott E Smith, Priyank Patel, Francisco Hernandez-Ilizaliturri, Reem Karmali, Saurabh Rajguru, David T Yang, Joseph J Maly, Kristie A Blum, Weiqiang Zhao, Charles Vanslambrouck, Chadi Nabhan
Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy...
November 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27203548/prognostic-impact-of-history-of-follicular-lymphoma-induction-regimen-and-stem-cell-transplant-in-patients-with-myc-bcl2-double-hit-lymphoma
#20
Shaoying Li, Annapurna Saksena, Parth Desai, Jie Xu, Zhuang Zuo, Pei Lin, Guilin Tang, C Cameron Yin, Adam Seegmiller, Jeffrey L Jorgensen, Roberto N Miranda, Nishitha M Reddy, Carlos Bueso-Ramos, L Jeffrey Medeiros
MYC/BCL2 double hit lymphoma (DHL) has been the subject of many studies; however, no study has systemically compared the clinicopathologic features and prognostic factors between patients with de novo disease versus those with a history of follicular lymphoma (FL). In addition, the prognostic importance of several other issues remains controversial in these patients. In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma...
June 21, 2016: Oncotarget
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