Efficacy Of Bortezomib In Patients Research Articles

Efficacy of bortezomib in reduction of systemic lupus erythematosus disease activity index score: A meta-analysis

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by the production of auto-antibodies against nuclear and cytoplasmic antigens, which can affect multiple organs. To date, no meta-analysis has reported the efficacy of bortezomib in SLE. We performed a meta-analysis to investigate the efficacy of bortezomib in patients with SLE. Methods: We searched the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Chinese BioMedical databases for articles published before 18 August 2021 to identify all studies relevant to SLE. The following were our inclusion criteria: (1) written in all languages, (2) bortezomib administration in patients with SLE and, (3) a clear description of SLE Disease Activity Index (SLEDAI) scores. Following were the exclusion criteria: (1) duplicate publications (the most recent article was included for analysis)and, (2) animal experiments, case reports, meeting reports, and reviews. The pooled data were analysed using a fixed- or random-effects model, depending on heterogeneity (determined using the I2 index). Results: Three articles that described 29 patients were included in this study. The forest plot showed a positive association between bortezomib therapy and SLE based on analysis of SLEDAI scores, with an odds ratio of 11.30 (95% confidence interval 7.03–15.56, p < .00001). Conclusion: Bortezomib treatment can reduce the SLEDAI scores in patients with SLE, which suggests the usefulness of this therapeutic approach for SLE.

Gabarap Loss Mediates Immune Escape in High Risk Multiple Myeloma

Gabarap Loss Mediates Immune Escape in High Risk Multiple Myeloma

Safety and efficacy of bortezomib in patients with poems syndrome

Safety and efficacy of bortezomib in patients with poems syndrome

Safety and Efficacy of Bortezomib in Patients With Highly Relapsing Neuromyelitis Optica Spectrum Disorder

This study examines the safety and efficacy of bortezomib in patients with highly relapsing neuromyelitis optica spectrum disorder.

Decitabine enhances bortezomib treatment in RPMI 8226 multiple myeloma cells.

The present study investigated the interactions between decitabine (DAC) and bortezomib (BTZ) in RPMI8226 multiple myeloma (MM) cells. Cells were exposed to DAC alone and in combination with BTZ for 48h. A Cell Counting Kit‑8 assay was performed to assess the rate of proliferation inhibition in the cells. Cell apoptosis was investigated by Annexin V-fluorescein isothiocyanate and propidium iodide staining. Flow cytometry was used to detect the different cell cycle stages. Western blotting was performed to analyze the protein expression levels of poly(ADP‑ribose) polymerase1 (PARP‑1), caspase‑3, ‑9 and DNA (cytosine‑5‑)‑methyltransferase 1 (DNMT1). Reverse transcription‑quantitative polymerase chain reaction was used to assess DNMT1 gene expression. The combination of DAC and BTZ increased the proliferation inhibition, apoptotic rate and G0‑G1 arrest compared with use of a single therapeutic agent. In addition, the combination treatment enhanced PARP‑1 cleavage, caspase‑3 and caspase‑9 activation and downregulated the protein and mRNA expression levels of DNMT1. Therefore, the current study determined that the combination of BTZ and the epigenetic agent DAC may be a novel therapeutic strategy to improve the efficacy of BTZ in patients with MM.

Bortezomib mitigates adverse prognosis conferred by Bcl-2 overexpression in patients with relapsed/refractory multiple myeloma

Overexpression of the Bcl-2 family of genes results in increased transcription of anti-apoptotic proteins. In vitro data suggest that this may enhance acquired chemoresistance and correlate with extramedullary invasion. This has led to pursuing the Bcl-2 family of proteins as therapeutic targets in several malignant disorders, including multiple myeloma (MM). The impact of novel therapeutic agents such as bortezomib on these molecular markers is not known. We investigated the association between the expression of anti-apoptotic members of the Bcl-2 family and the efficacy of bortezomib in patients with relapsed/refractory MM. Gene expression data generated prospectively from large clinical trials were utilized. Hypothesis testing using a multisample test for equivalence was performed. The association between Bcl-2 expression levels and clinical reponse was negated in bortezomib-treated patients (p = 0.014), while not so in dexamethasone-treated patients (p = 0.92). Similar results were noted for variant 2 of the Mcl-1 gene (p = 0.003). Results for Bcl-xl did not meet the level of significance. Thus, the importance of the Bcl-2 family of proteins as prognostic markers in MM should be reassessed in the novel therapeutic agent era. Our data suggest that bortezomib may overcome the prognostic effect conferred by overexpression of some of the anti-apoptotic Bcl-2 family of genes in patients with relapsed/refractory MM.

Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits

Bortezomib (VELCADE) is a potent inhibitor of the 26S proteasome with broad antitumor activity. We performed a phase II study of bortezomib to evaluate its clinical effects in patients with metastatic breast cancer. Twelve patients with metastatic breast cancer were treated with bortezomib (VELCADE) at a dosage of 1.5 mg/m(2) administered biweekly for 2 weeks with 1 week of rest in a 21-day cycle. The primary objective was clinical response rate. Toxicity and pharmacodynamics data were also obtained. No objective responses were observed. One patient had stable disease, and 11 others experienced disease progression. The median survival time was 4.3 months (range, 0.9-37 months). The most common grade 3 or 4 toxicities included fatigue (58%; n = 7) and skin rash (33%; n = 4). The mean inhibition of specific chymotryptic activity was 53.1% (+/- 13.33%). A statistically significant reduction in the plasma interleukin-6 level was seen (P = 0.0354). Bortezomib was well tolerated but showed limited clinical activity against metastatic breast cancer when used as a single agent. The future development of this agent for the treatment of breast cancer should be guided by in vivo models that optimize activity in combination with other antitumor agents.

Bortezomib Therapy in Patients With Relapsed or Refractory Lymphoma: Potential Correlation of In Vitro Sensitivity and Tumor Necrosis Factor Alpha Response With Clinical Activity

To determine the efficacy of bortezomib in patients with lymphoid malignancy, correlating clinical response with effect on plasma cytokines and in vitro activity in primary cultures. Patients received bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11 of a 3-week cycle. Plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-6 were measured before each treatment, and bortezomib activity was examined in patient samples grown in primary culture. Fifty-one patients received a total of 193 cycles of treatment. Twenty-four patients had mantle cell lymphoma (MCL), 13 had follicular lymphoma (FL), six had lymphoplasmacytic lymphoma, six had Hodgkin's disease (HD), and one each had diffuse large B-cell lymphoma and adult T-cell leukemia/lymphoma. Patients were heavily pretreated with a median of four previous therapies. Significant grade 3 to 4 toxicities were thrombocytopenia (n = 22), fatigue (n = 10), and peripheral neuropathy (n = 3). Seven patients with MCL responded to treatment (one complete response, six partial responses [PRs]; overall response rate, 29%). Two patients with FL achieved a late PR 3 months after discontinuing therapy. Two patients with Waldenström's macroglobulinemia and one patient with HD achieved a PR. MCL primary cultures demonstrated greater sensitivity to bortezomib than FL (median 50% effective concentration for viability, 209 nmol/L v 1,311 nmol/L, respectively; P = .07), which correlated with clinical response. A median reduction in plasma TNF-alpha of 98% was observed in six patients with MCL who responded to bortezomib compared with a reduction of 38% in six nonresponders (P = .07). Bortezomib demonstrates encouraging efficacy in MCL in heavily pretreated individuals. Response was associated with a reduction in plasma TNF-alpha and in vitro sensitivity in a small number of patients.