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https://www.readbyqxmd.com/read/29166734/-a-retrospective-study-of-the-bird-regimen-in-the-treatment-of-relapsed-refractory-multiple-myeloma
#1
X L Liu, L Li, Q L Shi, L J Chen, X X Cao, J Li, A J Liao, D H Zou, J N Sun, S J Gao, W Li, J Hou, F Y Jin
Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29165070/bortezomib-in-kidney-transplant-current-use-and-perspectives
#2
Erika B Rangel, Lucio R Requião-Moura, Taina V de Sandes-Freitas, Gessika Marcelo-Gomes
BACKGROUND: Despite major advances in transplant medicine, antibody-mediated rejection (AMR) continues to have severe clinical implications and adversely affect graft survival. Therefore, the search for alternative drugs to treat AMR is widely pursued. The first-in-class proteasome inhibitor bortezomib (BZ) is a selective inhibitor of the 26S proteasome, which was initially approved for the treatment of malignant plasma cell disorders. METHODS: This review encompasses how our understanding of inhibiting proteasome pathway created the basis of BZ research and important milestones accomplished in AMR treatment in the transplant setting...
November 20, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29164606/safety-and-efficacy-of-pomalidomide-dexamethasone-and-pegylated-liposomal-doxorubicin-for-patients-with-relapsed-or-refractory-multiple-myeloma
#3
Alexa Cohen, Tanya M Spektor, Laura Stampleman, Alberto Bessudo, Peter J Rosen, Leonard M Klein, Thomas Woliver, Marshall Flam, Shahrooz Eshaghian, Youram Nassir, Tina Maluso, Regina A Swift, Robert Vescio, James R Berenson
Immunomodulatory drugs including thalidomide, lenalidomide (LEN) and pomalidomide (POM), are effective for treating multiple myeloma (MM). POM has shown enhanced efficacy with dexamethasone (DEX). Pegylated liposomal doxorubicin (PLD) with bortezomib is US Food and Drug Administration-approved for treating MM. PLD with LEN or thalidomide has shown efficacy for MM patients. LEN with DEX, PLD and bortezomib achieves high response rates. We evaluated the combination of POM with DEX 40 mg and PLD 5 mg/m(2) with the latter two drugs administered on days 1, 4, 8 and 11 on a 28-day cycle for the treatment of relapsed/refractory MM patients...
November 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29161153/protective-effects-of-agomelatine-on-testicular-damage-caused-by-bortezomib
#4
N Akaras, T Bal, H Atilay, J Selli, M B Halici
Bortezomib is a chemotherapeutic agent used to treat several cancers; however, it exhibits severe side effects in testicular tissue. We investigated the use of agomelatine to prevent testicular tissue damage caused by bortezomib. We used 36 male Sprague-Dawley rats divided randomly into six equal groups: group 1, no treatment control; group 2, agomelatine treatment only; group 3, bortezomib treatment only for 48 h; group 4, bortezomib + agomelatine treatment for 48 h; group 5, bortezomib treatment only for 72 h; and group 6, bortezomib + agomelatine treatment for 72 h...
November 21, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29159373/bortezomib-for-neuromyelitis-optica-spectrum-disorder-a-new-therapeutic-option-for-the-more-severe-forms
#5
Jennifer Taylor, Sarosh R Irani
No abstract text is available yet for this article.
November 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29159372/bortezomib-for-neuromyelitis-optica-spectrum-disorder-a-new-therapeutic-option-for-the-more-severe-forms
#6
Su-Hyun Kim
No abstract text is available yet for this article.
November 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29159366/bortezomib-for-neuromyelitis-optica-spectrum-disorder-a-new-therapeutic-option-for-the-more-severe-forms-reply
#7
Chao Zhang, Fu-Dong Shi
No abstract text is available yet for this article.
November 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29157092/single-agent-and-synergistic-combinatorial-efficacy-of-first-in-class-small-molecule-imipridone-onc201-in-hematological-malignancies
#8
Varun V Prabhu, Mala K Talekar, Amriti R Lulla, C Leah B Kline, Lanlan Zhou, Junior Hall, A Pieter J Van den Heuvel, David T Dicker, Jawad Babar, Stephan A Grupp, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Jeffrey J Pu, David F Claxton, Nadia Khan, Wolfgang Oster, Joshua E Allen, Wafik S El-Deiry
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29152775/new-insights-into-diagnosis-and-therapeutic-options-for-proliferative-hepatoblastoma
#9
Katarzyna B Hooks, Jérôme Audoux, Helena Fazli, Sarah Lesjean, Tony Ernault, Nathalie-Dugot Senant, Thierry Leste-Lasserre, Martin Hagedorn, Benoit Rousseau, Coralie Danet, Sophie Branchereau, Laurence Brugières, Sophie Taque, Catherine Guettier, Monique Fabre, Anne Rullier, Marie-Annick Buendia, Thérèse Commes, Christophe F Grosset, Anne-Aurélie Raymond
Surgery and cisplatin-based treatment of hepatoblastoma (HB) currently guarantee the survival of 70-80% of patients. However, some important challenges remain in diagnosing high risk tumors and identifying relevant targetable pathways offering new therapeutic avenues. Previously, two molecular subclasses of hepatoblastoma tumors have been described, namely C1 and C2; C2 being the subgroup with the poorest prognosis, a more advanced tumor stage and the worst overall survival rate. An associated 16-gene signature to discriminate the two tumoral subgroups was proposed but it has not been transferred into clinical routine...
November 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29151530/successful-autologous-hematopoietic-stem-cell-transplantation-followed-by-bortezomib-maintenance-in-a-patient-with-relapsed-cd138-low-multiple-solitary-plasmacytomas-harboring-a-17p-deletion
#10
Hiroaki Kitamura, Yasushi Kubota, Kyosuke Yamaguchi, Kazuharu Kamachi, Atsujiro Nishioka, Masako Yokoo, Takero Shindo, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Solitary plasmacytoma of bone (SBP) tends to progress to multiple myeloma (MM); however, progression to multiple solitary plasmacytomas (MSP) is rare. We report a case of CD138-low MSP with 17p deletion in a patient with relapsed SBP. 17p deletion is associated with a poor outcome in patients with MM, and the low expression of CD138 in myeloma cells is associated with drug resistance and a poor prognosis. The patient was successfully treated with bortezomib plus dexamethasone induction therapy and autologous hematopoietic stem cell transplantation followed by bortezomib maintenance therapy...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29150421/final-analysis-of-survival-outcomes-in-the-randomized-phase-3-first-trial
#11
Thierry Facon, Meletios A Dimopoulos, Angela Dispenzieri, John V Catalano, Andrew Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar J Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie D Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier De La Rubia, Darell White, Daniel Binder, Jin Lu, Kenneth C Anderson, Philippe Moreau, Michel Attal, Aurore Perrot, Bertrand Arnulf, Lugui Qiu, Murielle Roussel, Eileen Boyle, Salomon Manier, Mohamad Mohty, Herve Avet-Loiseau, Xavier Leleu, Annette Ervin-Haynes, Guang Chen, Vanessa Houck, Lotfi Benboubker, Cyrille Hulin
This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥ 60 months' follow-up)...
November 17, 2017: Blood
https://www.readbyqxmd.com/read/29127588/daratumumab-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#12
Hannah A Blair
Intravenous daratumumab (DARZALEX(®)) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29127199/the-full-length-interleukin-33-flil33-importin-5-interaction-does-not-regulate-flil33-s-nuclear-localization-but-controls-its-intracellular-degradation
#13
Andrew Clerman, Zahid Noor, Rita Fishelevich, Virginia Lockatell, Brian S Hampton, Nirav G Shah, Mariah V Salcedo, Nevins W Todd, Sergei P Atamas, Irina G Luzina
Human mature interleukin-33 (MIL33) is a member of the IL-1 family and a potent regulator of immunity through its pro-T helper cell 2 (Th2) activity. Its precursor form, full-length interleukin-33 (FLIL33), is an intranuclear protein in many cell types, including fibroblasts, and its intracellular levels can change in response to stimuli. However, the mechanisms controlling the nuclear localization of FLIL33 or its stability in cells are not understood. Here, we identified importin-5 (IPO5), a member of the importin family of nuclear transport proteins, as an intracellular binding partner of FLIL33...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29122646/drug-response-prediction-in-high-risk-multiple-myeloma
#14
A J Vangsted, S Helm-Petersen, J B Cowland, P B Jensen, P Gimsing, B Barlogie, S Knudsen
A Drug Response Prediction (DRP) score was developed based on gene expression profiling (GEP) from cell lines and tumor samples. Twenty percent of high-risk patients by GEP70 treated in Total Therapy 2 and 3A have a progression-free survival (PFS) of more than 10years. We used available GEP data from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged PFS, HR=2...
November 6, 2017: Gene
https://www.readbyqxmd.com/read/29121279/clinical-and-preclinical-perspectives-on-chemotherapy-induced-peripheral-neuropathy-cipn-a-narrative-review
#15
S J L Flatters, P M Dougherty, L A Colvin
This review provides an update on the current clinical and preclinical understanding of chemotherapy induced peripheral neuropathy (CIPN). The overview of the clinical syndrome includes a review of its assessment, diagnosis and treatment. CIPN is caused by several widely-used chemotherapeutics including paclitaxel, oxaliplatin, bortezomib. Severe CIPN may require dose reduction, or cessation, of chemotherapy, impacting on patient survival. While CIPN often resolves after chemotherapy, around 30% of patients will have persistent problems, impacting on function and quality of life...
October 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29120412/bortezomib-induced-mirnas-direct-epigenetic-silencing-of-locus-genes-and-trigger-apoptosis-in-leukemia
#16
Yu-Yi Chu, Chiung-Yuan Ko, Shao-Ming Wang, Pin-I Lin, Han-Ying Wang, Wen-Chi Lin, Dong-Yu Wu, Lu-Hao Wang, Ju-Ming Wang
MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death...
November 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29114004/dysproteinemias-and-glomerular-disease
#17
Nelson Leung, Maria E Drosou, Samih H Nasr
Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins...
November 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29113288/hdac6-inhibitor-wt161-downregulates-growth-factor-receptors-in-breast-cancer
#18
Teru Hideshima, Ralph Mazitschek, Jun Qi, Naoya Mimura, Jen-Chieh Tseng, Andrew L Kung, James E Bradner, Kenneth C Anderson
We have shown that WT-161, a histone deacetylase 6 (HDAC6) inhibitor, shows remarkable anti-tumor activity in multiple myeloma (MM) in preclinical models. However, its activity in other type of cancers has not yet been shown. In this study, we further evaluated the biologic sequelae of WT161 in breast cancer cell lines. WT161 triggers apoptotic cell death in MCF7, T47D, BT474, and MDA-MB231 cells, associated with decreased expression of EGFR, HER2, and ERα and downstream signaling. However, HDAC6 knockdown shows that cytotoxicity and destabilization of these receptors triggered by WT161 are not dependent on HDAC6 inhibition...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110190/pomalidomide-a-review-in-relapsed-and-refractory-multiple-myeloma
#19
Sheridan M Hoy
Pomalidomide (Imnovid(®); Pomalyst(®)), an analogue of thalidomide, is an immunomodulatory agent, with several mechanisms of action (both direct and indirect) thought to be involved in its anti-myeloma activity. Oral pomalidomide is available in several countries for use in combination with low-dose dexamethasone in adults with relapsed and refractory multiple myeloma. In multinational, phase II or III studies in patients with refractory, or relapsed and refractory multiple myeloma who had received ≥ 2 prior treatment regimens (including ≥ 2 cycles of both lenalidomide and bortezomib), pomalidomide plus low-dose dexamethasone was associated with prolonged progression-free survival (PFS) and overall survival and an improved overall response rate...
November 2017: Drugs
https://www.readbyqxmd.com/read/29109769/preclinical-activity-of-dcz3301-a-novel-aryl-guanidino-compound-in-the-therapy-of-multiple-myeloma
#20
Minjie Gao, Bo Li, Xi Sun, Yunfei Zhou, Yingcong Wang, Van S Tompkins, Zhijian Xu, Nekitsing Indima, Houcai Wang, Wenqin Xiao, Lu Gao, Gege Chen, Huiqun Wu, Xiaosong Wu, Yuanyuan Kong, Bingqian Xie, Yiwen Zhang, Gaomei Chang, Liangning Hu, Guang Yang, Bojie Dai, Yi Tao, Weiliang Zhu, Jumei Shi
We synthesized a novel aryl-guanidino compound, DCZ3301, and found that it has potent cytotoxicity against multiple human cancer cell lines. The anticancer activity was most potent against multiple myeloma (MM). DCZ3301 induced cytotoxicity in MM cell lines, as well as patient myeloma cells, in part by decreasing mitochondrial membrane potential to induce apoptosis. In contrast, DCZ3301 had no cytotoxic effect on normal cells. DCZ3301 also inhibited cell cycling and caused a G2/M accumulation that corresponded with downregulation of Cdc25C, CDK1, and Cyclin B1...
2017: Theranostics
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