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https://www.readbyqxmd.com/read/29784741/management-of-multiple-myeloma
#1
Shaji K Kumar
The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as "preferred," "other," and "useful in certain circumstances." For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29780690/an-update-on-the-treatment-of-pediatric-autoimmune-encephalitis
#2
Cory Stingl, Kathleen Cardinale, Heather Van Mater
Purpose of review: Autoimmune encephalitis (AE) is an increasingly recognized etiology for neuropsychiatric deficits that are highly responsive to immunotherapy. As a result, rheumatologists are often called upon to help with the diagnosis and treatment of these conditions. The purpose of this review is to provide an update on the pharmacologic treatment of AE. Recent findings: To date, there are no prospective randomized placebo-controlled trials to guide treatment recommendations for AE...
March 2018: Current Treatment Options in Rheumatology
https://www.readbyqxmd.com/read/29779352/-effect-of-1q21-amplification-on-bortezomib-therapeutic-response-and-prognosis-of-newly-diagnosed-multiple-myeloma-patients
#3
X L Liu, P Y Yang, X Y Yu, J C Chen, X L Liu, J Bai, Y M Liu, H He, J N Sun, H Q Fan, C Zhang, Y Zhang, K J Su, C S Liu, Y H Tan, S J Gao, W Li, F Y Jin
Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29774521/patient-reported-outcomes-of-multiple-myeloma-patients-treated-with-panobinostat-after-%C3%A2-2-lines-of-therapy-based-on-the-international-phase-3-randomized-double-blind-placebo-controlled-panorama-1-trial
#4
Paul G Richardson, Robert L Schlossman, Anuja N Roy, Ashok Panneerselvam, Suddhasatta Acharyya, Monika Sopala, Sagar Lonial
The phase 3 PANORAMA-1 trial led to regulatory approvals of panobinostat (PAN) in combination with bortezomib (BTZ) and dexamethasone (DEX) for the treatment of multiple myeloma after ≥2 prior regimens, including BTZ and an immunomodulatory drug. Patient-reported outcomes (PROs) were assessed in PANORAMA-1, with data available for 73 patients in the PAN + BTZ + DEX arm and 74 patients in the placebo (PBO) + BTZ + DEX arm. Per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), global health status/quality of life (QoL) scores initially declined with PAN + BTZ + DEX during the first 24 weeks before approaching baseline scores and remaining steady during the next 24 weeks, with no difference between arms at Week 48...
May 17, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29773987/celastrol-attenuates-the-invasion-and-migration-and-augments-the-anticancer-effects-of-bortezomib-in-a-xenograft-mouse-model-of-multiple-myeloma
#5
Muthu K Shanmugam, Kwang S Ahn, Jong H Lee, Radhamani Kannaiyan, Nurulhuda Mustafa, Kanjoormana A Manu, Kodappully S Siveen, Gautam Sethi, Wee J Chng, Alan P Kumar
Several lines of evidence have demonstrated that deregulated activation of NF-κB plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-κB upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated. In addition, we studied whether CSL can potentiate the apoptotic effect of bortezomib, a proteasome inhibitor in MM cells and in a xenograft mouse model...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773864/igg-single-chain-trail-fusion-proteins-for-tumour-therapy
#6
Martin Siegemund, Felix Schneider, Meike Hutt, Oliver Seifert, Ines Müller, Dagmar Kulms, Klaus Pfizenmaier, Roland E Kontermann
Single-chain formats of TNF-related apoptosis inducing ligand (scTRAIL) can serve as effector components of tumour-associated antigen-targeted as well as non-targeted fusion proteins, being characterized by high tumour cell-specific induction of apoptosis through death receptor activation. We studied the suitability of immunoglobulin G as a scaffold for oligovalent and bispecific TRAIL fusion proteins. Thus, we developed novel targeted hexa- and dodecavalent IgG-scTRAIL molecules by fusing scTRAIL to the C-terminus of either light (LC-scTRAIL) or heavy immunoglobulin chain (HC-scTRAIL), or to both ends (LC/HC-scTRAIL) of the anti-EGFR IgG antibody hu225...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773504/discovery-of-novel-20s-proteasome-inhibitors-by-rational-topology-based-scaffold-hopping-of-bortezomib
#7
Yulong Xu, Xicheng Yang, Yiyi Chen, Hao Chen, Huijiao Sun, Wei Li, Qiong Xie, Linqian Yu, Liming Shao
A series of structurally novel proteasome inhibitors 1-12 have been developed based rational topology-based scaffold hopping of bortezomib. Among these novel proteasome inhibitors, compound 10 represents an important advance due to the comparable proteasome-inhibitory activity (IC50  = 9.7 nM) to bortezomib (IC50  = 8.3 nM), the remarkably higher BEI and SEI values and the effectiveness in metabolic stability. Therefore, compound 10 provides an excellent lead suitable for further optimization.
May 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29766327/characterization-of-carfilzomib-resistant-non-small-cell-lung-cancer-cell-lines
#8
Neale T Hanke, Elliot Imler, Marilyn T Marron, Bruce E Seligmann, Linda L Garland, Amanda F Baker
PURPOSE: We previously showed that carfilzomib (CFZ) has potent anti-proliferative and cytotoxic activity in a broad range of lung cancer cell lines. Here we investigate possible mechanisms of CFZ acquired resistance in lung cancer cell lines. METHODS: CFZ-resistant non-small cell lung cancer (NSCLC) cell lines were developed by exposing A549 and H520 cells to stepwise increasing concentrations of CFZ. Resistance to CFZ and cross-resistance to bortezomib and other chemotherapy drugs was measured using the MTT assay...
May 15, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29765356/soluble-and-cell-cell-mediated-drivers-of-proteasome-inhibitor-resistance-in-multiple-myeloma
#9
REVIEW
Mariah L Farrell, Michaela R Reagan
It is becoming clear that myeloma cell-induced disruption of the highly organized bone marrow components (both cellular and extracellular) results in destruction of the marrow and support for multiple myeloma (MM) cell proliferation, survival, migration, and drug resistance. Since the first phase I clinical trial on bortezomib was published 15 years ago, proteasome inhibitors (PIs) have become increasingly common for treatment of MM and are currently an essential part of any anti-myeloma combination therapy...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29761122/bortezomib-treatment-for-severe-refractory-anti-nmda-receptor-encephalitis
#10
Yong-Won Shin, Soon-Tae Lee, Tae-Joon Kim, Jin-Sun Jun, Kon Chu
Objective: To evaluate the therapeutic potential of bortezomib, a proteasome inhibitor that target plasma cells, in order to revive stalled recovery in patients with anti- N -methyl-d-aspartate (NMDA) receptor encephalitis who remain bedridden even after aggressive immunotherapy. Methods: We consecutively enrolled patients with anti-NMDA receptor encephalitis who remained bedridden after first-line immunotherapy (steroids and intravenous immunoglobulin), second-line immunotherapy (rituximab), and tocilizumab treatment, and treated them with subcutaneous bortezomib...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29757607/dual-ph-responsive-shell-cleavable-polycarbonate-micellar-nanoparticles-for-in-vivo-anticancer-drug-delivery
#11
Shaoqiong Liu, Robert Ono, Chuan Yang, Shujun Gao, Jordan Tan, James L Hedrick, Yi Yan Yang
To exploit tumor and intracellular microenvironments, pH-responsive diblock copolymers of PEG and catechol-functionalized polycarbonate with acid-labile acetal bond as the linker are synthesized to prepare micellar nanoparticles that shed the shell at acidic tumor tissues and inside cancer cells, hence accelerating drug release at the target. The pH-dependent cleavage of the shell is demonstrated at pH 5.0 and 6.5 using GPC and 1H NMR. Bortezomib (BTZ, an anticancer drug containing a phenylboronic acid group) is conjugated to the polymers through formation of pH-responsive boronate ester bond between boronic acid and cetachol in the polymers...
May 14, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29756564/clinical-and-pharmacologic-features-of-monoclonal-antibodies-and-checkpoint-blockade-therapy-in-multiple-myeloma
#12
Mattia D'Agostino, Giulia Gazzera, Giusy Cetani, Sara Bringhen, Mario Boccadoro, Francesca Gay
BACKGROUND: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. METHODS: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756171/real-world-data-on-len-dex-combination-at-second-line-therapy-of-multiple-myeloma-treatment-at-biochemical-relapse-is-a-significant-prognostic-factor-for-progression-free-survival
#13
Eirini Katroditou, Marie-Christine Kyrtsonis, Sosana Delimpasi, Despoina Kyriakou, Argiris Symeonidis, Emmanouil Spanoudakis, Georgios Vasilopoulos, Achilles Anagnostopoulos, Anna Kioumi, Panagiotis Zikos, Anthi Aktypi, Evangelos Briasoulis, Aikaterini Megalakaki, Panayiotis Repousis, Ioannis Adamopoulos, Dimitrios Gogos, Maria Kotsopoulou, Vassiliki Pappa, Eleni Papadaki, Despoina Fotiou, Eftychia Nikolaou, Evlambia Giannopoulou, Eleftheria Hatzimichael, Nikolaos Giannakoulas, Vassiliki Douka, Kyriaki Kokoviadou, Despoina Timotheatou, Evangelos Terpos
We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation...
May 13, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29755672/inhibition-of-mtor-complex-2-restrains-tumor-angiogenesis-in-multiple-myeloma
#14
Aurelia Lamanuzzi, Ilaria Saltarella, Vanessa Desantis, Maria Antonia Frassanito, Patrizia Leone, Vito Racanelli, Beatrice Nico, Domenico Ribatti, Paolo Ditonno, Marcella Prete, Antonio Giovanni Solimando, Francesco Dammacco, Angelo Vacca, Roberto Ria
The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization, and drug resistance through AKT hyper-phosphorylation on Ser473...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755666/impact-of-lenalidomide-maintenance-on-the-immune-environment-of-multiple-myeloma-patients-with-low-tumor-burden-after-autologous-stem-cell-transplantation
#15
Karel Fostier, Jo Caers, Nathalie Meuleman, Katrijn Broos, Jurgen Corthals, Kris Thielemans, Rik Schots, Brenda De Keersmaecker
Lenalidomide is a potent anti-myeloma drug with immunomodulatory properties. It is increasingly used in a low-dose maintenance setting to prolong remission duration after standard treatment. Data on the in vivo effects of lenalidomide are scarce and sometimes different from the well-described in vitro effects. We therefore evaluated the numerical, phenotypical and functional impact of lenalidomide maintenance on several immune cell types in a cohort of seventeen homogeneously treated myeloma patients achieving a low residual myeloma burden after a bortezomib based-induction followed by autologous stem cell transplantation...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755650/preclinical-comparison-of-proteasome-and-ubiquitin-e1-enzyme-inhibitors-in-cutaneous-squamous-cell-carcinoma-the-identification-of-mechanisms-of-differential-sensitivity
#16
Angela McHugh, Kenneth Fernandes, Andrew P South, Jemima E Mellerio, Julio C Salas-Alanís, Charlotte M Proby, Irene M Leigh, Mark K Saville
Proteasome inhibitors have distinct properties and the biochemical consequences of suppressing ubiquitin E1 enzymes and the proteasome differ. We compared the effects of the proteasome inhibitors bortezomib, ixazomib and carfilzomib and the ubiquitin E1 enzyme inhibitor MLN7243/TAK-243 on cell viability and cell death in normal keratinocytes and cutaneous squamous cell carcinoma (cSCC) cell lines. The effects of both a pulse of treatment and more extended incubation were investigated. This is relevant to directly-delivered therapy (topical treatment/intratumoral injection) where the time of exposure can be controlled and a short exposure may better reflect systemically-delivered inhibitor pharmacokinetics...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29753692/treatment-with-bortezomib-based-therapy-followed-by-autologous-stem-cell-transplantation-improves-outcomes-in-light-chain-amyloidosis-a-retrospective-study
#17
Tania Jain, Heidi E Kosiorek, Shu T Kung, Vishal S Shah, Amylou C Dueck, Veronica Gonzalez-Calle, Susan Luft, Craig B Reeder, Roberta Adams, Pierre Noel, Jeremy T Larsen, Joseph Mikhael, Leif Bergsagel, A Keith Stewart, Rafael Fonseca
BACKGROUND: The hematologic response is critical in patients with light chain amyloidosis because a good response is known to improve organ response and overall survival. We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis. PATIENTS AND METHODS: Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT)...
May 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29753690/successful-use-of-bortezomib-lenalidomide-combination-as-treatment-for-a-patient-with-plasmablastic-lymphoma
#18
William D Marrero, Alexis Cruz-Chacón, Christian Castillo, Fernando Cabanillas
No abstract text is available yet for this article.
May 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29747599/predicting-multi-level-drug-response-with-gene-expression-profile-in-multiple-myeloma-using-hierarchical-ordinal-regression
#19
Xinyan Zhang, Bingzong Li, Huiying Han, Sha Song, Hongxia Xu, Yating Hong, Nengjun Yi, Wenzhuo Zhuang
BACKGROUND: Multiple myeloma (MM), like other cancers, is caused by the accumulation of genetic abnormalities. Heterogeneity exists in the patients' response to treatments, for example, bortezomib. This urges efforts to identify biomarkers from numerous molecular features and build predictive models for identifying patients that can benefit from a certain treatment scheme. However, previous studies treated the multi-level ordinal drug response as a binary response where only responsive and non-responsive groups are considered...
May 10, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29746371/bortezomib-associated-optic-atrophy-in-two-patients-with-multiple-myeloma
#20
Joseph G Chacko, Raed Behbehani, Kelsey N Hundley, Yazan Al-Fanek
No abstract text is available yet for this article.
May 8, 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
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