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Bortezomib

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https://www.readbyqxmd.com/read/28817601/bortezomib-initiates-endoplasmic-reticulum-stress-elicits-autophagy-and-death-in-echinococcus-granulosus-larval-stage
#1
María Celeste Nicolao, Julia A Loos, Christian Rodriguez Rodrigues, Viviana Beas, Andrea C Cumino
Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28817190/a-phase-1-and-2-study-of-filanesib-alone-and-in-combination-with-low-dose-dexamethasone-in-relapsed-refractory-multiple-myeloma
#2
Jatin J Shah, Jonathan L Kaufman, Jeffrey A Zonder, Adam D Cohen, William I Bensinger, Brandi W Hilder, Selena A Rush, Duncan H Walker, Brian J Tunquist, Kevin S Litwiler, Mieke Ptaszynski, Robert Z Orlowski, Sagar Lonial
BACKGROUND: Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity. METHODS: This open-label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28811872/current-and-emerging-treatment-options-for-mantle-cell-lymphoma
#3
REVIEW
Bita Fakhri, Brad Kahl
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy...
August 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28810334/-bortezomib-based-treatment-of-26-cases-multiple-myeloma-complicating-with-intestinal-obstruction
#4
Q L Zhang, Y Z Liu, Q D Lin, L N Liu, Z Y Mei, M L Nie, Y P Song, B J Fang
No abstract text is available yet for this article.
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28801984/low-dose-bortezomib-and-dexamethasone-as-primary-therapy-in-elderly-patients-with-waldenstr%C3%B3-m-macroglobulinemia
#5
Ya-Ping Zhang, Xi Yang, Zeng-Hua Lin, Xin-Feng Wang, Xin Cao, Xue-Fen You, Hong-Ming Huang, Wen-Yu Shi, Hong Liu
OBJECTIVE: This retrospective study was designed to determine the efficacy and safety of low-dose bortezomib and dexamethasone (lBD) in elderly Chinese patients with Waldenstrӧm macroglobulinemia (WM). METHODS: Ten WM patients aged over 60 years received first-line treatment with lBD. RESULTS: The median age was 70 years (range, 61-77 years). The overall response rate was 80%, including 1 patient who achieved a complete response, 1 patient with very good partial response, and 6 patients with a partial response...
August 12, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28801967/retreatment-and-prolonged-therapy-with-subcutaneous-bortezomib-in-patients-with-relapsed-multiple-myeloma-a-randomized-controlled-phase-iii-study
#6
Evangelos Terpos, Marco Gobbi, Anna Potamianou, Marjolein Lahaye, Catherine Couturier, Michele Cavo
OBJECTIVES: This randomized, international, multicenter, open-label phase III study investigated the effects of experimental retreatment with subcutaneous bortezomib plus dexamethasone (VD) followed by prolonged bortezomib therapy vs. standard VD retreatment in patients with relapsed/refractory multiple myeloma. METHODS: Patients were randomized (2:1) to receive either experimental (n = 53) or standard (n = 27) retreatment, stratified by the number of prior therapy lines...
August 12, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28801299/-effect-of-bortezomib-in-inducing-apoptosis-of-imatinib-resistant-k562-cells-and-the-mechanism
#7
Jia-Ye Hua, Xu-Hong Zhou, Shu-Ting Ouyang, Yong-Bin Wu
OBJECTIVE: To investigate the effect of bortezomib in inducing apoptosis in imatinib-resistant K562 (K562R) cells and its possible mechanism. METHODS: K562 cells were cultured in gradient concentrations of imatinib for several months to generate imatinib-resistant K562 cells. The viability of K562R cells treated with bortezomib was measured using CCK-8 cell proliferation assay, and the cell apoptosis was analyzed by flow cytometry with annexin V/PI dual staining...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28800777/bortezomib-treatment-induces-a-higher-mortality-rate-in-lupus-model-mice-with-a-higher-disease-activity
#8
Tomoko Ikeda, Hiroshi Fujii, Masato Nose, Yukiko Kamogawa, Tsuyoshi Shirai, Yuko Shirota, Tomonori Ishii, Hideo Harigae
BACKGROUND: Bortezomib (Bz) is a proteasome inhibitor that directly targets antibody-producing plasma cells. We recently reported the first randomized control trial that evaluated the effects of Bz in patients with systemic lupus erythematosus (SLE). In that study, we demonstrated that Bz treatment is associated with many adverse reactions in patients with refractory disease. In the present study, we examine the therapeutic and toxic effects of Bz on MRL/MpJ-lpr/lpr (MRL/lpr) mice with severe disease activity...
August 11, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28799231/efficacy-of-daratumumab-based-therapies-in-patients-with-relapsed-refractory-multiple-myeloma-treated-outside-of-clinical-trials
#9
Arjun Lakshman, Jithma P Abeykoon, Shaji K Kumar, S Vincent Rajkumar, David Dingli, Francis K Buadi, Wilson I Gonsalves, Nelson Leung, Angela Dispenzieri, Taxiarchis V Kourelis, Ronald S Go, Martha Q Lacy, Miriam A Hobbs, Yi Lin, Rahma Warsame, John Lust, Amie L Fonder, Yi L Hwa, Suzanne R Hayman, Stephen J Russell, Robert A Kyle, Morie A Gertz, Prashant Kapoor
Outside of clinical trials, experience with daratumumab-based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43-93) years. High-risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1-14) and time to first DCT from diagnosis was 4...
August 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28798402/nutlin-3-enhances-the-bortezomib-sensitivity-of-p53-defective-cancer-cells-by-inducing-paraptosis
#10
Dong Min Lee, In Young Kim, Min Ji Seo, Mi Ri Kwon, Kyeong Sook Choi
The proteasome inhibitor, bortezomib, is ineffective against many solid tumors. Nutlin-3 is a potent antagonist of human homolog of murine double minute 2/p53 interaction exhibiting promising therapeutic anti-cancer activity. In this study, we show that treatment of various p53-defective bortezomib-resistant solid tumor cells with bortezomib plus nutlin-3 induces paraptosis, which is a cell death mode accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Bortezomib alone did not markedly alter cellular morphology, and nutlin-3 alone induced only a transient mitochondrial dilation...
August 11, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28798071/bortezomib-as-a-new-therapeutic-approach-for-blastic-plasmacytoid-dendritic-cell-neoplasm
#11
Laure Philippe, Adam Ceroi, Elodie Bôle-Richard, Alizée Jenvrin, Sabeha Biichle, Sophie Perrin, Samuel Limat, Francis Bonnefoy, Eric Deconinck, Philippe Saas, Francine Garnache-Ottou, Fanny Angelot-Delettre
Blastic plasmacytoid dendritic cell neoplasm is an aggressive hematological malignancy with a poor prognosis. No consensus for optimal treatment modalities is available today. Targeting the NF-κB pathway is considered as a promising approach since blastic plasmacytoid dendritic cell neoplasm have been reported to exhibit a constitutive activation of the NF-κB pathway. Moreover, NF-κB inhibition in blastic plasmacytoid dendritic cell neoplasm cell lines using either an experimental specific inhibitor JSH23 or the clinical drug bortezomib interferes in vitro with leukemic cell proliferation and survival...
August 10, 2017: Haematologica
https://www.readbyqxmd.com/read/28795151/kidney-transplantation-in-patients-with-active-multiple-myeloma-case-reports
#12
Erik Lawrence Lum, Neil Kogut, Thu Pham, Gabriel M Danovitch, Suphamai Bunnapradist
Kidney disease is a common complication in patients with multiple myeloma. Traditionally, patients with active multiple myeloma and end-stage renal disease have been excluded from kidney transplantation due to the risk of malignancy progression. The introduction of bortezomib-based therapy for patients with multiple myeloma and renal impairment has significantly improved survival in this population. In this report, we present 2 cases of patients with active and controlled multiple myeloma who underwent successful kidney transplantation without progression of their underlying malignancy...
August 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28789585/co-delivery-of-docetaxel-and-bortezomib-based-on-a-targeting-nanoplatform-for-enhancing-cancer-chemotherapy-effects
#13
Junpeng Nie, Wei Cheng, Yunmei Peng, Gan Liu, Yuhan Chen, Xusheng Wang, Chaoyu Liang, Wei Tao, Yinping Wei, Xiaowei Zeng, Lin Mei
Using facile polydopamine (PDA)-based surface modification and a pH-sensitive catechol-boronate binding mechanism, a novel drug delivery system was designed for the treatment of breast cancer. The system was able to achieve the following goals: active targeting, pH responsiveness, in vivo blood circulation for a prolonged period of time, and dual drug loading. After coating with PDA, the docetaxel (DTX)-loaded star-shaped copolymer cholic acid-poly(lactide-co-glycolide) nanoparticles (CA-PLGA@PDA/NPs) were functionalized with amino-poly(ethylene glycol)-folic acid (NH2-PEG-FA) and bortezomib (BTZ) to form the targeting composition, DTX-loaded CA-PLGA@PDA-PEG-FA + BTZ/NPs...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28781837/carfilzomib-and-dexamethasone-for-extramedullary-myeloma-with-pleuropericardial-involvement
#14
Ignacio Español, Marta Romera, María Dolores Gutiérrez-Meca, Maria Del Carmen García, Aurelia Tejedor, Antonio Martínez, Jerónima Ibáñez, Felipe De Arriba, Alfredo Minguela, Teodoro Iturbe, Maria Dolores López
The dismal outcome of pleuropericardial extramedullary multiple myeloma (EMM) reflects both the selection of resistant disease and absence of useful drugs. Carfilzomib and dexamethasone should be explored in advanced EMM patients, even for bortezomib-resistant patients, as may provide much longer overall survival than previously reported treatments.
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28776319/improved-survival-in-medicare-patients-with-multiple-myeloma-findings-from-a-large-nationwide-and-population-based-cohort
#15
Ying Chen, David R Lairson, Wenyaw Chan, Xianglin L Du
The aim of this study was to examine whether novel agents proteasome inhibitor bortezomib and immunomodulatory drugs lenalidomide and thalidomide are effective in prolonging overall survival (OS) for patients with newly diagnosed multiple myeloma (MM) in the real-world practice setting. A nationwide and population-based retrospective cohort of elderly patients with advanced newly diagnosed MM from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare linked data. Survival was compared between cases in 2005-2009 and in 2000-2004, and between patients treated with anti-MM therapy and the untreated among cases in 2005-2009, using Cox proportional hazards models, Kaplan-Meier methods, and propensity score adjustment to further control for baseline confounding...
September 2017: Medical Oncology
https://www.readbyqxmd.com/read/28770558/long-non-coding-rna-malat1-is-an-inducible-stress-response-gene-associated-with-extramedullary-spread-and-poor-prognosis-of-multiple-myeloma
#16
Hiroshi Handa, Yuko Kuroda, Kei Kimura, Yuta Masuda, Hikaru Hattori, Lobna Alkebsi, Morio Matsumoto, Tetsuhiro Kasamatsu, Nobuhiko Kobayashi, Ken-Ichi Tahara, Makiko Takizawa, Hiromi Koiso, Takuma Ishizaki, Hiroaki Shimizu, Akihiko Yokohama, Norifumi Tsukamoto, Takayuki Saito, Hirokazu Murakami
Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo-resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non-coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28766538/-prognostic-value-of-1q21-amplification-in-multiple-myeloma
#17
T V Abramova, T N Obukhova, L P Mendeleeva, O S Pokrovskaya, E O Gribanova, V V Ryzhko, L A Grebenyuk, M V Nareyko, M V Solovyev, O M Votyakova, S M Kulikov, M A Rusinov, V G Savchenko
AIM: To determine the prevalence of amp1q21 and its relationship to the clinical manifestations of multiple myeloma (MM). SUBJECTS AND METHODS: In December 2009 to March 2016, a total 134 patients aged 30 to 81 years (median 57 years) underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53, and t(8q24)/cMYC...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28766537/-multiple-myeloma-maintenance-therapy-after-autologous-hematopoietic-stem-cell-transplantation-depending-on-minimal-residual-disease
#18
M V Solovyev, L P Mendeleeva, O S Pokrovskaya, M V Nareyko, M V Firsova, I V Galtseva, Yu O Davydova, N M Kapranov, L A Kuzmina, E G Gemdzhian, V G Savchenko
AIM: To determine the efficiency of maintenance therapy with bortezomib in patients with multiple myeloma (MM) who have achieved complete remission (CR) after autologous hematopoietic stem cell (auto-HSCT), depending on the presence of minimal residual disease (MRD). SUBJECTS AND METHODS: In January 2014 to February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years (median 54 years), who had achieved CR after auto-HSCT, were randomized to perform maintenance therapy with bortezomib during a year...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28763310/elderly-patients-with-multiple-myeloma-towards-a-frailty-approach
#19
Sonja Zweegman, Monika Engelhardt, Alessandra Larocca
PURPOSE OF REVIEW: To describe how to better identify frail multiple myeloma patients and to treat them appropriately. RECENT FINDINGS: Proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, and immunomodulatory agents (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, have significantly improved the outcome of multiple myeloma patients in the last decade. However, both in clinical trials and in daily clinical practice, elderly multiple myeloma patients have shown lesser benefit...
July 29, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28761239/sequential-autologous-hematopoietic-stem-cell-transplant-followed-by-renal-transplant-in-multiple-myeloma
#20
D Bhowmik, S Yadav, L Kumar, S Agarwal, S K Agarwal, S Gupta
A 30-year-old female was symptomatic with headache, fatigue, and weakness since October 2011 and was told to have anemia. In January 2012, she was admitted outside with pulmonary edema. Investigations revealed advanced azotemia, anemia, and hypercalcemia. Urine showed 2 + proteins and 30-35 red blood cells. There was no history of oral ulcers, rash, Raynaud's phenomenon, or hemoptysis. She was evaluated for causes of rapidly progressive "renal failure." Hemolytic work-up; antinuclear antibody, double-stranded DNA, and anti-neutrophil cytoplasmic antibody were negative...
July 2017: Indian Journal of Nephrology
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