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https://www.readbyqxmd.com/read/28442922/inhibition-of-pcsk9-protects-against-radiation-induced-damage-of-prostate-cancer-cells
#1
Si-Shun Gan, Jian-Qing Ye, Lei Wang, Fa-Jun Qu, Chuan-Min Chu, Yi-Jun Tian, Wei Yang, Xin-Gang Cui
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein expressed primarily in the liver, formerly known to maintain plasma lipid homeostasis by regulating low-density lipoprotein receptor levels, and its exact role in the radioresistance of prostate cancer (PCa) remains unclear. We aim to investigate the function of PCSK9 in the radioresistance of PCa cells. METHODS: PCSK9 small interfering RNA (siRNA) was introduced into the PCa cells by transient transfection...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28439107/e-selectin-ligands-recognised-by-heca452-induce-drug-resistance-in-myeloma-which-is-overcome-by-the-e-selectin-antagonist-gmi-1271
#2
A Natoni, T A G Smith, N Keane, C McEllistrim, C Connolly, A Jha, M Andrulis, E Ellert, M S Raab, S V Glavey, L Kirkham-McCarthy, S K Kumar, S C Locatelli-Hoops, I Oliva, W E Fogler, J L Magnani, M E O'Dwyer
Multiple Myeloma (MM) is characterized by the clonal expansion and metastatic spread of malignant plasma cells to multiple sites in the bone marrow (BM). Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the generation of E-selectin ligands, in MM BM homing and resistance to therapy. Since E-selectin is constitutively expressed in the BM microvasculature, we wished to establish the contribution of E-selectin ligands to MM biology. We report that functional E-selectin ligands are restricted to a minor subpopulation of MM cell lines which, upon expansion, demonstrate specific and robust interaction with recombinant E-selectin in vitro...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28433749/novel-sulphur-containing-imatinib-metabolites-found-by-untargeted-lc-hrms-analysis
#3
Ivo Vrobel, David Friedecký, Edgar Faber, Lukáš Najdekr, Kateřina Mičová, Radana Karlíková, Tomáš Adam
Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups were analyzed in full-scan mode and the unknown ions occurring only in the patient group were then, as potential imatinib metabolites, subjected to multi-stage fragmentation in order to elucidate their structure...
April 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28428041/structure-of-a-myeloid-cell-leukemia-1-mcl-1-inhibitor-bound-to-drug-site-3-of-human-serum-albumin
#4
Bin Zhao, John Sensintaffar, Zhiguo Bian, Johannes Belmar, Taekyu Lee, Edward T Olejniczak, Stephen W Fesik
Amplification of the gene encoding Myeloid cell leukemia-1 (Mcl-1) is one of the most common genetic aberrations in human cancer and is associated with high tumor grade and poor survival. Recently, we reported on the discovery of high affinity Mcl-1 inhibitors that elicit mechanism-based cell activity. These inhibitors are lipophilic and contain an acidic functionality which is a common chemical profile for compounds that bind to albumin in plasma. Indeed, these Mcl-1 inhibitors exhibited reduced in vitro cell activity in the presence of serum...
March 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28423727/paclitaxel-synergizes-with-exposure-time-adjusted-cd22-targeting-immunotoxins-against-b-cell-malignancies
#5
Fabian Müller, Stephanie Stookey, Tyler Cunningham, Ira Pastan
CD22-targeted recombinant immunotoxins (rIT) are active in hairy cell leukemia or acute lymphoblastic leukemia (ALL), but not in mantle cell lymphoma (MCL) patients. The goal was to enhance rIT efficacy in vivo and to define a strong combination treatment. Activity of Moxetumomab pasudotox (Moxe) and LR combined with paclitaxel was tested against MCL cell lines in vitro and as bolus doses or continuous infusion in xenograft models. In the KOPN-8 ALL xenograft, Moxe or paclitaxel alone was active, but all mice died from leukemia; when combined, 60% of the mice achieved a sustained complete remission...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423578/endothelial-microparticles-delivering-microrna-155-into-t-lymphocytes-are-involved-in-the-initiation-of-acute-graft-versus-host-disease-following-allogeneic-hematopoietic-stem-cell-transplantation
#6
Ran Zhang, Xiaoxiao Wang, Mei Hong, Ting Luo, Miaomiao Zhao, Haorui Shen, Jun Fang, Xiaojie Li, Sibin Zang, Ping Chen, Dimin Nie, Peng Zheng, Qiuling Wu, Linghui Xia
Endothelial microparticles (EMPs) upregulation has been observed in acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found that EMPs derived from TNF-α-stimulated human umbilical vein endothelial cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice were remarkably elevated and significantly higher than the levels in plasma...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418845/preclinical-development-of-g1t38-a-novel-potent-and-selective-inhibitor-of-cyclin-dependent-kinases-4-6-for-use-as-an-oral-antineoplastic-in-patients-with-cdk4-6-sensitive-tumors
#7
John E Bisi, Jessica A Sorrentino, Jamie L Jordan, David D Darr, Patrick J Roberts, Francis X Tavares, Jay C Strum
Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415607/thymoquinone-exerts-potent-growth-suppressive-activity-on-leukemia-through-dna-hypermethylation-reversal-in-leukemia-cells
#8
Jiuxia Pang, Na Shen, Fei Yan, Na Zhao, Liping Dou, Lai-Chu Wu, Christopher L Seiler, Li Yu, Ke Yang, Veronika Bachanova, Eric Weaver, Natalia Y Tretyakova, Shujun Liu
Thymoquinone (TQ), a bioactive constituent of the volatile oil of Monarda fistulosa and Nigella sativa, possesses cancer-specific growth inhibitory effects, but the underlying molecular mechanisms remain largely elusive. We propose that TQ curbs cancer cell growth through dysfunction of DNA methyltransferase 1 (DNMT1). Molecular docking analysis revealed that TQ might interact with the catalytic pocket of DNMT1 and compete with co-factor SAM/SAH for DNMT1 inhibition. In vitro inhibitory assays showed that TQ decreases DNMT1 methylation activity in a dose-dependent manner with an apparent IC50 of 30 nM...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405536/an-unfortunate-polyneuropathy-organomegaly-endocrinopathy-monoclonal-gammopathy-and-skin-change-poems
#9
Faraz Afridi, Jorge Otoya, Samantha F Bunting, Gerard Chaaya
POEMS syndrome is an acronym for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes, which is a rare paraneoplastic disease of monoclonal plasma cells. A mandatory criterion to diagnose POEMS syndrome is the presence of a monoclonal plasma cell dyscrasia in which plasma cell leukemia is the most aggressive form. Early identification of the features of the POEMS syndrome is critical for patients to identify an underlying plasma cell dyscrasias and to reduce the morbidity and mortality of the disease by providing early therapy...
March 8, 2017: Curēus
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#10
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28403213/m-copa-suppresses-endolysosomal-kit-akt-oncogenic-signalling-through-inhibiting-the-secretory-pathway-in-neoplastic-mast-cells
#11
Yasushi Hara, Yuuki Obata, Keita Horikawa, Yasutaka Tasaki, Kyohei Suzuki, Takatsugu Murata, Isamu Shiina, Ryo Abe
Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28401104/therapy-related-acute-promyelocytic-leukemia-in-plasma-cell-myeloma-treated-with-melphalan-a-case-report-and-literature-review
#12
Hyunjung Gu, Young Jin Kim, Woo-In Lee, Juhee Lee, Hwi-Joong Yoon, Tae Sung Park
No abstract text is available yet for this article.
March 2017: Blood Research
https://www.readbyqxmd.com/read/28389380/etumortype-an-algorithm-of-discriminating-cancer-types-for-circulating-tumor-cells-or-cell-free-dnas-in-blood
#13
Jinfeng Zou, Edwin Wang
With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone...
April 4, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28385786/host-virus-and-pneumococcus-specific-immune-responses-in-high-count-monoclonal-b-cell-lymphocytosis-and-chronic-lymphocytic-leukemia-implications-for-disease-progression
#14
Ignacio Criado, Santiago Muñoz-Criado, Arancha Rodríguez-Caballero, Wendy G Nieto, Alfonso Romero, Paulino Fernández-Navarro, Miguel Alcoceba, Teresa Contreras, Marcos González, Alberto Orfao, Julia Almeida
Patients diagnosed with chronic lymphocytic leukemia display a high incidence of infections due to an associated immunodeficiency that includes hypogammaglobulinemia. A higher risk of infections has also been recently reported for high-count monoclonal B-cell lymphocytosis, while no information is available in low-count monoclonal B-cell lymphocytosis. Here, we evaluated the status of the humoral immune system in patients with chronic lymphocytic leukemia (n=58), as well as in low- (n=71) and high-count (n=29) monoclonal B-cell lymphocytosis vs...
April 6, 2017: Haematologica
https://www.readbyqxmd.com/read/28381565/tetherin-inhibits-cell-free-virus-dissemination-and-retards-murine-leukemia-virus-pathogenesis
#15
Rachel A Liberatore, Emily J Mastrocola, Chelsea Powell, Paul D Bieniasz
The relative contributions of cell-free virion circulation versus direct cell-to-cell transmission to retroviral dissemination and pathogenesis are unknown. Tetherin/Bst2 is an antiviral protein that blocks enveloped virion release into the extracellular milieu, but may not inhibit cell-to-cell virus transmission. We developed live-cell imaging assays which show that tetherin does not affect Moloney murine leukemia virus (MoMLV) spread, and only minimally affects vesicular stomatitis virus (VSV) spread, to adjacent cells in a monolayer...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28372919/hematologic-malignancies-are-associated-with-adverse-perioperative-outcomes-after-total-hip-arthroplasty
#16
Jared M Newman, Jaiben George, W Trevor North, Suparna M Navale, Alison K Klika, Wael K Barsoum, Carlos A Higuera
BACKGROUND: Advancements in treating hematologic malignancies have improved survival, and these patients may be part of the growing population undergoing total hip arthroplasty (THA). Therefore, the purpose of this study was to evaluate the perioperative outcomes of THA in patients with hematologic malignancies. METHODS: The Nationwide Inpatient Sample identified patients who underwent THA from 2000 to 2011 (n = 2,864,412). Patients diagnosed with any hematologic malignancy (n = 18,012) were further stratified into Hodgkin disease (n = 786), non-Hodgkin lymphoma (n = 5062), plasma cell dyscrasias (n = 2067), leukemia (n = 5644), myeloproliferative neoplasms (n = 3552), and myelodysplastic syndromes (n = 1082)...
March 11, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28361523/nationwide-statistical-analysis-of-lymphoid-malignancies-in-korea
#17
Hyewon Lee, Hyeon Jin Park, Eun-Hye Park, Hee Young Ju, Chang-Mo Oh, Hyun-Joo Kong, Kyu-Won Jun, Byung-Kiu Park, Eunyoung Lee, Hyeon-Seok Eom, Young-Joo Won
Purpose: Regional differences in the incidence of lymphoid malignancies have been reported worldwide, but there has been no large-scale epidemiologic analysis in Korea. The aim of this study was to provide a nationwide population-based statistical analysis of Korean patients with lymphoid malignancies. Materials and Methods: The Korea Central Cancer Registry analyzed the incidence and survival of patients with lymphoid malignancies from the Korean National Cancer Incidence Database...
March 30, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28345657/multicolor-bioimaging-with-biosynthetic-zinc-nanoparticles-and-their-application-in-tumor-detection
#18
Yanjun Kang, Yi-Zhou Wu, Xianyun Hu, Xueqin Xu, Jie Sun, Rong Geng, Tongxing Huang, Xiaohang Liu, Yichen Ma, Ying Chen, Quan Wan, Xiaobang Qi, Gen Zhang, Xiaohui Zhao, Xin Zeng
Because they generate excellent images, nanoparticles (NPs), especially biosynthesized NPs, provide a new solution for tumor imaging. In this research, we unveil a novel type of biosynthesized NPs featuring multicolor fluorescence. These NPs exhibit little cytotoxicity to cells. The explored NPs, designated Zn-ZFP-GST NPs (Zinc NPs in abbreviation), are generated from leukemia cells treated with a Zn(2+) solution, while zinc-finger protein and glutathione S-transferase (GST) were also identified in the Zinc NPs...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340113/gata1-is-a-sensitive-and-specific-nuclear-marker-for-erythroid-and-megakaryocytic-lineages
#19
Winston Y Lee, Olga K Weinberg, Geraldine S Pinkus
Objectives: GATA binding factor 1 (GATA1) is a transcription factor essential for erythromegakaryocytic differentiation. Given its function in lineage specification, we sought to evaluate the immunohistochemical profile of GATA1 in normal marrow and acute leukemia and assess the use of GATA1 as a specific erythromegakaryocytic immunohistochemical marker. Methods: Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders...
April 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28337541/tyrosine-kinase-inhibitor-therapy-induced-changes-in-humoral-immunity-in-patients-with-chronic-myeloid-leukemia
#20
Hanna L M Rajala, Mohamed El Missiry, Anniina Ruusila, Perttu Koskenvesa, Tim H Brümmendorf, Bjorn T Gjertsen, Jeroen Janssen, Kourosh Lotfi, Berit Markevärn, Ulla Olsson-Strömberg, Leif Stenke, Jesper Stentoft, Johan Richter, Henrik Hjorth-Hansen, Anna Kreutzman, Satu Mustjoki
PURPOSE: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. METHODS: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment...
March 23, 2017: Journal of Cancer Research and Clinical Oncology
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