Update on the optimal use of bortezomib in the treatment of multiple myeloma

Mohan, Meera; Matin, Aasiya; Davies, Faith E.

doi:10.2147/cmar.s105163

Cited by 52 publications

(55 citation statements)

References 52 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…to CCR5 [52]. Several proteasome inhibitor drugs tested in this study, including carfilzomib and bortezomib, have been approved by the FDA for the therapy of various cancers, such as breast cancer, multiple myeloma, and Hodgkin's lymphoma [53][54][55][56]. Consequently, these drugs could potentially be repurposed to further evaluate their efficacy and tolerance in a clinical setting as novel therapies for ZIKV and DENV infection.…”

Section: Discussionmentioning

confidence: 99%

An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication

Song¹,

Lee

Pan³

et al. 2020

Preprint

View full text Add to dashboard Cite

The Zika (ZIKV) and dengue (DENV) flaviviruses exhibit similar replicative processes but distinct clinical outcomes. A systematic understanding of virus-host protein-protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes to identify host proteins required for ZIKV infection uncovered proteasome proteins. Third, a high-throughput screening of 6,016 bioactive compounds for ZIKV inhibitors yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoints proteasome as critical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for further studies of flavivirus-host interactions, disease pathogenesis, and new drug targets.

show abstract

Section: Discussionmentioning

confidence: 99%

An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication

Song¹,

Lee

Pan³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In these patients, clinical laboratory abnormalities include neutropenia and elevated aminotransferase levels. One of the most common side effects of bortezomib is peripheral neuropathy that is predominantly sensory with burning paresthesia, hyperesthesia–hypoesthesia, neuropathic pain, and weakness …”

Section: Next‐generation Targeted Immunomodulatory Therapiesmentioning

confidence: 99%

“…One of the most common side effects of bortezomib is peripheral neuropathy that is predominantly sensory with burning paresthesia, hyperesthesia-hypoesthesia, neuropathic pain, and weakness. 115…”

Section: Bortezomibmentioning

confidence: 99%

Innate and adaptive immunity in human epilepsies

et al. 2017

View full text Add to dashboard Cite

SummaryInflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology. In general, activation of both innate and adaptive immunity plays a role in refractory forms of epilepsy. Epilepsies in which seizures develop after infiltration of cells of the adaptive immune system in the central nervous system (CNS) include a broad range of epileptic disorders with different (known or unknown) etiologies. Infiltration of lymphocytes is observed in autoimmune epilepsies, especially the classical paraneoplastic encephalitides with antibodies against intracellular tumor antigens. The presence of lymphocytes in the CNS also has been found in focal cerebral dysplasia type 2 and in cortical tubers. Various autoantibodies have been shown to be associated with temporal lobe epilepsy (TLE) and hippocampal sclerosis of unknown etiology, which may be due to the presence of viral DNA. During the last decade, an increasing number of antineuronal autoantibodies directed against membranous epitopes have been discovered and are associated with various neurologic syndromes, including limbic encephalitis. A major challenge in epilepsy is to define biomarkers, which would allow the recognition of patient populations who might benefit from immune‐modulatory therapies. Some peripheral inflammatory markers appear to be differentially expressed in patients with medically controlled and medically refractory and, as such, could be used for diagnostic, prognostic, or therapeutic purposes. Establishing an autoimmune basis in patients with drug‐resistant epilepsy allows for efficacious and targeted immunotherapy. Although current immunotherapies can give great benefit to the correctly identified patient, there are limitations to their efficacy and they may have considerable side effects. Thus the identification of new immunomodulatory compounds remains of utmost importance.

show abstract

“…Bortezomib is one of the important drugs that have made breakthrough progress in MM in the last decade. However, MM remains an incurable disease ( 1 – 3 ). In the condition of no transplantation, most of the patients died of disease progression within 2 years ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

The (Neutrophils + Monocyte)/Lymphocyte Ratio Is an Independent Prognostic Factor for Progression-Free Survival in Newly Diagnosed Multiple Myeloma Patients Treated With BCD Regimen

et al. 2020

View full text Add to dashboard Cite

Objective Bortezomib is one of the important drugs that have made breakthrough progress in multiple myeloma (MM) in the past 10 years. However, the heterogeneity of its efficacy makes it difficult to predict the risk of disease progression. The purpose of this study is to determine the prognostic significance of the (neutrophils + monocytes)/lymphocytes ratio (NMLR) in newly diagnosed MM patients who received BCD regimen therapy in terms of progression-free survival (PFS). Methods A total of 150 patients who fulfilled the International Myeloma Working Group (IMWG) criteria were enrolled in the study retrospectively. The prognostic value of NMLR was evaluated by 150 patients with MM who were treated with BCD (bortezomib + cyclophosphamide + dexamethasone) regimen therapy. NMLR was calculated by the ratio of (neutrophils + monocyte) to lymphocytes. According to receiver operating characteristic curves, the cutoff value was 1.90. The patients were divided into high NMLR group (H-NMLR, NMLR ≥1.90) and low NMLR group (L-NMLR, NMLR <1.90). The clinical characteristics, treatment responses and PFS of the two groups were analyzed. Results The median age of the patients was 61 years. Fifty-five (36.67%) patients showed lower NMLR at initial diagnosis. Although NMLR was unable to discriminate prognosis in ISS stage I/II patients, interestingly, the addition of NMLR to the ISS further defined prognosis particularly in stage III. Low-NMLR group who achieved early immune reconstruction significantly higher than that of the high-NMLR group ( P < 0.001). NMLR value was 1.98 ± 1.02 for the patients who achieved early immune reconstruction, which was 3.26 ± 2.52 for the patients without immune reconstruction ( P < 0.05). Compared with the H-NMLR group, the levels of β2-microglobulin, serum creatinine and calcium were lower, and the very good partial response or better (≥VGPR) ratio was higher in L-NMLR group. The L-NMLR group experienced a superior median PFS compared with the H-NMLR group (24.0 versus 15.5 months; P < 0.001). In addition, several other prognostic factors of PFS were estimated, including the high-risk cytogenetics, β2-microglobulin and the depth of treatment response 3 months after treatment with BCD regimen. Moreover, NMLR was an independent predictor of PFS including non-high risk cytogenetics (0.587; P = 0.031). Conclusion In patients with newly diagnosed MM undergoing BCD regimen, the NMLR <1.90 was an independent prognostic factor for PFS as well as early immune reconstruction and lower disease burden.

show abstract

Update on the optimal use of bortezomib in the treatment of multiple myeloma

Cited by 52 publications

References 52 publications

An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication

An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication

Innate and adaptive immunity in human epilepsies

The (Neutrophils + Monocyte)/Lymphocyte Ratio Is an Independent Prognostic Factor for Progression-Free Survival in Newly Diagnosed Multiple Myeloma Patients Treated With BCD Regimen

Contact Info

Product

Resources

About