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https://www.readbyqxmd.com/read/28922619/identification-of-angiogenesis-inhibitors-using-a-co-culture-cell-model-in-a-high-content-and-high-throughput-screening-platform
#1
Shuaizhang Li, Chia-Wen Hsu, Srilatha Sakamuru, Chaozhong Zou, Ruili Huang, Menghang Xia
Angiogenesis is an important hallmark of cancer, contributing to tumor formation and metastasis. In vitro angiogenesis models for analyzing tube formation serve as useful tools to study these processes. However, current in vitro co-culture models using primary cells have limitations in usefulness and consistency. Therefore, in the present study, an in vitro co-culture assay system was optimized in a 1536-well format for high-throughput screening using human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and aortic endothelial cells...
September 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28919113/hepatic-tmem30a-deficiency-causes-intrahepatic-cholestasis-by-impairing-expression-and-localization-of-bile-salt-transporters
#2
Leiming Liu, Lingling Zhang, Lin Zhang, Fan Yang, Xudong Zhu, Zhongjie Lu, Yeming Yang, Haiqi Lu, Lifeng Feng, Zhuo Wang, Hui Chen, Sheng Yan, Lin Wang, Zhenyu Ju, Hongchuan Jin, Xianjun Zhu
Mutations in ATP8B1 or ATP11C (members of P4-type ATPases) cause progressive familial intrahepatic cholestasis type 1 (PFIC1) in human or intrahepatic cholestasis in mice. Transmembrane protein 30A (TMEM30A), as a β-subunit, is essential for the function of P4-type ATPases including ATP8B1 and ATP11C, however, its role in the etiology of cholestasis remains poorly understood. To investigate the function of TMEM30A in bile salt homeostasis, we developed Tmem30a liver-specific knockout (LKO) mice. Tmem30a LKO mice suffered from hyperbilirubinaemia, hypercholanaemia, inflammatory infiltration, ductular proliferation and liver fibrosis...
September 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#3
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28917152/pegylated-thermosensitive-lipid-coated-hollow-gold-nanoshells-for-effective-combinational-chemo-photothermal-therapy-of-pancreatic-cancer
#4
Bijay Kumar Poudel, Biki Gupta, Thiruganesh Ramasamy, Raj Kumar Thapa, Shiva Pathak, Kyung Taek Oh, Jee-Heon Jeong, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Pancreatic cancer has extremely poor prognosis with an 85% mortality rate that results from aggressive and asymptomatic growth, high metastatic potential, and rapid development of resistance to already ineffective chemotherapy. In this study, plasmonic hollow gold nanoshells (GNS) coated with PEGylated thermosensitive lipids were prepared as an efficient platform to ratiometrically co-deliver two drugs, bortezomib and gemcitabine (GNS-L/GB), for combinational chemotherapy and photothermal therapy of pancreatic cancer...
September 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28911826/immunoproteasome-selective-and-non-selective-inhibitors-a-promising-approach-for-the-treatment-of-multiple-myeloma
#5
REVIEW
Roberta Ettari, Maria Zappalà, Silvana Grasso, Caterina Musolino, Vanessa Innao, Alessandro Allegra
The ubiquitin-proteasome system (UPS) is the major non-lysosomal proteolytic system for the degradation of abnormal or damaged proteins no longer required. The proteasome is involved in degradation of numerous proteins which regulate the cell cycle, indicating a role in controlling cell proliferation and maintaining cell survival. Defects in the UPS can lead to anarchic cell proliferation and to tumor development. For these reasons UPS inhibition has become a significant new strategy for drug development in cancer treatment...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28906482/real-life-experience-with-bortezomib-based-regimens-in-elderly-comorbid-patients-with-newly-diagnosed-multiple-myeloma-polish-retrospective-multicenter-analysis
#6
Iwona Hus, Adam Walter-Croneck, Anna Masternak, Artur Jurczyszyn, Lidia Usnarska-Zubkiewicz, Łukasz Bołkun, Agnieszka Druzd-Sitek, Marcin Rymko, Jadwiga Łętowska, Ewa Lech-Marańda, Marcin Pasiarski, Anna Dmoszyńska
INTRODUCTION    Bortezomib was the first proteasome inhibitor approved in multiple myeloma therapy, initially for resistant/relapsed disease. Currently, VMP (bortezomib, melphalan, prednisone) is one of standard regimens recommended in a first line therapy for patients with multiple myeloma ineligible for high-dose chemotherapy/ autotransplantation (HDT/autoSCT) basing on the results of phase 3 clinical trial by Miguel et al that demonstrated its superiority to MP protocol.  OBJECTIVES    Patients participating in clinical trials are highly selected populations, so observations from clinical practice might provide important information for medical practitioners...
September 14, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28905994/microrna-324-5p-regulates-stemness-pathogenesis-and-sensitivity-to-bortezomib-in-multiple-myeloma-cells-by-targeting-hedgehog-signaling
#7
Bo Tang, Aoshuang Xu, Jian Xu, Haifan Huang, Lei Chen, Yan Su, Lannan Zhang, Junying Li, Fengjuan Fan, Jun Deng, Liang Tang, Chunyan Sun, Yu Hu
Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR-324-5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR-324-5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of Hedgehog (Hh) signaling components was elevated, indicating a correlation between miR-324-5p and Hh signaling in MM...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28905189/bortezomib-and-low-dose-dexamethasone-with-or-without-continuous-low-dose-oral-cyclophosphamide-for-primary-refractory-or-relapsed-multiple-myeloma-a-randomized-phase-iii-study
#8
Martin Kropff, Martin Vogel, Guido Bisping, Rudolf Schlag, Rudolf Weide, Wolfgang Knauf, Heinrich Fiechtner, Georgi Kojouharoff, Stephan Kremers, Wolfgang E Berdel
This phase III, open-label, randomized, controlled study aimed to evaluate the benefit of adding continuous low-dose oral cyclophosphamide to bortezomib-dexamethasone in patients with primary relapsed/refractory multiple myeloma. Patients were randomized 1:1 to receive up to eight 3-week cycles of bortezomib (1.3 mg/m(2)) and dexamethasone (20 mg; VD; n = 48) or bortezomib-dexamethasone plus oral cyclophosphamide (50 mg; VCD; n = 48). Median time to progression (primary endpoint) was slightly longer in the VD versus VCD group (12...
September 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28904172/fda-approval-summary-daratumumab-for-treatment-of-multiple-myeloma-after-one-prior-therapy
#9
Vishal Bhatnagar, Nicole J Gormley, Lola Luo, Yuan Li Shen, Rajeshwari Sridhara, Sriram Subramaniam, Guoxiang Shen, Lian Ma, Stacy Shord, Kirsten B Goldberg, Ann T Farrell, Amy E McKee, Richard Pazdur
On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone...
September 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28903971/extracellular-s100a9-protein-in-bone-marrow-supports-multiple-myeloma-survival-by-stimulating-angiogenesis-and-cytokine-secretion
#10
Kim De Veirman, Nathan De Beule, Ken Maes, Eline Menu, Elke De Bruyne, Hendrik De Raeve, Karel Fostier, Jerome Moreaux, Alboukadel Kassambara, Dirk Hose, Roy Heusschen, Helena Eriksson, Karin Vanderkerken, Els Van Valckenborgh
Dysregulated expression of S100 protein family members is associated with cancer proliferation, invasion, angiogenesis, and inflammation. S100A9 induces myeloid-derived suppressor cell (MDSC) accumulation and activity. MDSCs, immunosuppressive cells that contribute to tumor immune escape, are the main producers of S100A9. In this study, we evaluated the role of extracellular S100A9 and the therapeutic relevance of S100A9 inhibition in multiple myeloma (MM), using the immunocompetent murine 5T33MM model. We demonstrated the presence of S100A9 and its receptor TLR4 in both monocytic and granulocytic MDSCs in human and mouse samples...
September 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28903574/whole-exome-sequencing-of-aberrant-plasma-cells-in-a-patient-with-multiple-myeloma-minimal-residual-disease
#11
M Zatopkova, J Filipová, T Jelínek, P Vojta, T Sevcikova, M Simicek, L Rihova, R Bezdekova, K Growkova, Z Kufová, J Smejkalová, M Hajdúch, L Pour, J Minárik, A Jungová, V Maisnar, F Kryukov, R Hájek
Multiple myeloma is a plasma cell dyscrasia. It is the second most common hematological malignancy which is characterized by proliferation of clonal plasma cells producing harmful monoclonal immunoglobulin. Despite treatment modalities greatly evolved during the last decade, small amount of aberrant residual cells reside in patients after therapy and can cause relapse of the disease. Characterization of the residual, resistant clones can help to reveal important therapeutic targets for application of effective and precious treatment...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28899456/clc5-decreases-the-sensitivity-of-multiple-myeloma-cells-to-bortezomib-via-promoting-pro-survival-autophagy
#12
Huimin Zhang, Yuhui Pang, Chuanbao Ma, Jianying Li, Huaquan Wang, Zonghong Shao
Resistance to bortezomib (BZ) is the major problem that largely limits its clinical application in multiple myeloma treatment. In current study, we investigated whether ClC5, a member of the chloride channel family, involved in this process. The results of MTT assay showed that BZ treatment decreased cell viability in three multiple myeloma cell lines (ARH77, U266 and SKO-007), with the IC50 value of 2.83 nM, 4.37 nM and 1.91 nM, respectively. Moreover, BZ increased the conversion of LC3B-I to LC3B-II and expressions of Beclin-1 and ATG5, concomitantly with decreased p62 expression...
September 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28892086/allogeneic-stem-cell-transplantation-and-subsequent-treatments-as-a-comprehensive-strategy-for-long-term-survival-of-multiple-myeloma-patients
#13
V Montefusco, A Mussetti, F Rezzonico, F Maura, M Pennisi, C de Philippis, M Capecchi, P Corradini
We evaluated 71 patients treated with allogeneic hematopoietic cell transplantation (allo-HCT) for multiple myeloma (MM). Forty-three patients (61%) received allo-HCT after the first line of therapy. Fifty-eight patients (82%) had chemosensitive disease at the time of allo-HCT. A HLA-matched related or unrelated donor was available for 68 patients (96%). Non-myeloablative or reduced-intensity conditioning regimen and peripheral blood hematopoietic cells as a graft source were used in most patients. The cumulative incidence of grade II-IV acute GVHD at day +100 and chronic GVHD at 5 years was 13% (95% CI 7-23%) and 35% (95% CI 24-46), respectively...
September 11, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28888912/chemotherapy-induces-secretion-of-exosomes-loaded-with-heparanase-that-degrades-extracellular-matrix-and-impacts-tumor-and-host-cell-behavior
#14
Shyam K Bandari, Anurag Purushothaman, Vishnu C Ramani, Garrett J Brinkley, Darshan S Chandrashekar, Sooryanarayana Varambally, James A Mobley, Yi Zhang, Elizabeth E Brown, Israel Vlodavsky, Ralph D Sanderson
The heparan sulfate-degrading enzyme heparanase promotes the progression of many cancers by driving tumor cell proliferation, metastasis and angiogenesis. Heparanase accomplishes this via multiple mechanisms including its recently described effect on enhancing biogenesis of tumor exosomes. Because we recently discovered that heparanase expression is upregulated in myeloma cells that survive chemotherapy, we were prompted to investigate the impact of anti-myeloma drugs on exosome biogenesis. When myeloma cells were exposed to the commonly utilized anti-myeloma drugs bortezomib, carfilzomib or melphalan, exosome secretion by the cells was dramatically enhanced...
September 6, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28888547/green-nanotechnology-for-synthesis-and-characterization-of-poly-3-hydroxybutyrate-co-3-hydroxyhexanoate-nanoparticles-for-sustained-bortezomib-release-using-supercritical-co2-assisted-particle-formation-combined-with-electrodeposition
#15
Ruken Esra Demirdöğen, Fatih Mehmet Emen, Kasim Ocakoglu, Paramasivam Murugan, Kumar Sudesh, Göktürk Avşar
Carbon dioxide assisted particle formation combined with electrospraying using supercritical CO2 (scCO2) as an aid (Carbon Dioxide Assisted Nebulization-Electrodeposition, CAN-ED) was used to produce Bortezomib loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) P(3HB-co-3HHx) nanoparticles for sustained release. The morphology and structure of the prepared nanoparticles were investigated by SEM, TEM and FT-IR spectroscopy. Average diameter of particles obtained was 155nm and the average core sizes of P(3HB-co-3HHx) nanoparticles were between 6-13nm...
September 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28887129/disulfiram-is-a-slow-binding-partial-noncompetitive-inhibitor-of-20s-proteasome-activity
#16
Brian B Hasinoff, Daywin Patel
The alcohol abuse drug disulfiram has also been shown to exhibit potent cell growth inhibitory and anticancer activity. While a number of cellular and animal studies have suggested that disulfiram exhibits its anticancer activity through interaction with the proteasome, direct evidence for inhibition of proteasome activity is lacking. In this study we show that disulfiram potently inhibits the chymotrypsin-like activity of purified human 20S proteasome at low micromolar pharmacological concentrations. The enzyme progress curves displayed characteristics of a slow-binding reaction, similar to that observed for the FDA-approved proteasomal-targeted anticancer drugs bortezomib and carfilzomib...
September 5, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28886955/successful-combined-targeting-of-b-and-plasma-cells-in-treatment-refractory-anti-nmdar-encephalitis
#17
Olafur Sveinsson, Mathias Granqvist, Yngve Forslin, Kaj Blennow, Henrik Zetterberg, Fredrik Piehl
We describe an extremely severe case of therapy refractory NMDA receptor encephalitis (NMDAe) in a 26-year-old woman. After rituximab, bilateral oophorectomy, repeated cycles of high dose methylprednisolone and plasma exchange, she received repeated cyclophosphamide, tocilizumab (interleukin-6 inhibitor) and finally bortezomib (plasma cell depleting drug) leading to remission after 204days in intensive care. Two years after disease onset her cognitive functions are still affected, but slowly improving and the cerebral atrophy has been partly reversed...
August 25, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28885063/treatment-free-interval-as-a-metric-of-patient-experience-and-a-health-outcome-of-value-for-advanced-multiple-myeloma-the-case-for-the-histone-deacetylase-inhibitor-panobinostat-a-next-generation-novel-agent
#18
Paul Richardson, Anuja Roy, Acharyya Suddhasatta, Ashok Panneerselvam, Estella Mendelson, Andreas Günther, Sagar Lonial, Hermann Einsele
BACKGROUND: Patients with relapsed or relapsed/refractory multiple myeloma (RRMM) face poor treatment options by the time third-line therapy is required, despite advances in overall survival in recent years. Treatment free interval (TFI) and opportunities to maintain quality of life (QoL) have been cited as additional measures of efficacy that can be utilized in personalized treatment decisions. METHODS: The clinical health outcomes data from PANORAMA-1, the pivotal phase-3 trial comparing panobinostat-bortezomib-dexamethasone (PAN-BTZ-DEX) with placebo (PBO)-BTZ-DEX in RRMM patients treated with 1 to 3 prior regimens, retrospectively assessed TFI as a health outcome measure and metric of patient treatment experience relevant to the RRMM population...
September 8, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28883741/treatment-and-prognostic-factors-for-survival-in-newly-diagnosed-multiple-myeloma-patients-with-bortezomib-and-dexamethasone-regimen-a-single-chinese-center-retrospective-study
#19
Runzhe Chen, Xiaoping Zhang, Chong Gao, Chengxin Luan, Yujie Wang, Baoan Chen
OBJECTIVE: The aim of this retrospective study was to evaluate the efficacy and prognostic factors of bortezomib and dexamethasone (BD) chemotherapy regimen in the treatment of newly diagnosed multiple myeloma (MM) patients in our hospital. METHODS: A total of 47 newly diagnosed MM patients treated in our hospital from May 2010 to September 2016 were included in this study. All the enrolled patients received at least two cycles of BD chemotherapy regimen. RESULTS: The overall response rate after treatment was 68...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28883286/proteasome-inhibitors-in-first-line-treatment-of-transplant-ineligible-multiple-myeloma-patients
#20
Junya Kuroda, Yuji Shimura
Since the turn of the century, many agents against multiple myeloma (MM) have been introduced into daily clinical practice. The development of further agents is ongoing and some of these will reach the point of use in clinical practice in the near future. As various treatment options become available, the selection of an appropriate treatment strategy for an individual patient becomes more important. Treatment selection and decision making are based on the following two apparently opposite factors: 1) generalized findings and evidence from clinical trials, and 2) disease risks and background of individuals, which are diverse among patients...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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