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1.
Sâo Paulo med. j ; 140(2): 222-228, Jan.-Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1366039

ABSTRACT

Abstract BACKGROUND: In this era of target therapies, novel data on the correlation between response endpoints and survival outcomes in multiple myeloma have arisen. OBJECTIVE: To determine the impact of quality of response on clinical outcomes, using first-line treatment, and identify risk factors influencing progression-free survival (PFS) and overall survival (OS) among myeloma patients. DESIGN AND SETTING: Retrospective analysis on myeloma patients who were treated at the Clinic of Hematology and Clinical Immunology, University Clinical Centre, Niš, Serbia, over a four-year period. METHODS: A total of 108 newly diagnosed patients who received first-line therapy consisting of conventional chemotherapy or novel agent-based regimens were included in this analysis. RESULTS: The quality of response to first-line therapy for the whole cohort was classified as follows: complete response (CR) in 19%; very good partial response (VGPR) in 23%; partial response (PR) in 38%; and less than PR for the remaining patients. After a median follow-up of 25.4 months, the three-year PFS and OS for the entire study population were 47% and 70%, respectively. Achievement of CR was the main factor associated with significantly prolonged PFS and OS, in comparison with patients who reached VGPR and PR. Likewise, addition of the new drugs bortezomib and thalidomide to standard chemotherapy led to considerably extended PFS and OS, compared with conventional therapy alone. CONCLUSIONS: This analysis demonstrated that the quality of response after application of first-line treatment using novel agent-based regimens among multiple myeloma patients was a prognostic factor for PFS and OS, which are the most clinically relevant outcomes.


Subject(s)
Multiple Myeloma/drug therapy , Remission Induction , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Treatment Outcome , Serbia , Bortezomib/therapeutic use
2.
Article in Chinese | WPRIM | ID: wpr-928740

ABSTRACT

OBJECTIVE@#To investigate the prognostic value of hemopoietic scoring system composed of hemoglobin (HB), platelet count (PLT) and mean corpuscular volume (MCV) in MM patients and its correlation with curative effect.@*METHODS@#The clinical data of 172 newly diagnosed MM patients treated by bortezomib as the first-line regimen in our hospital from May 2014 to December 2019 were collected, three variables (HB≤100 g/L, PLT≤150×109/L, MCV≥96 fl) were introduced, each variable was distributed 1 score, the patients were divided into four groups (0, 1, 2 and 3 points in group 1, 2, 3 and 4, respectively), and the clinical characteristics and prognosis of the patients in the four groups were analyzed. The initial efficacy evaluation after 3-4 courses of treatment was carried out, and the curative effect of the patients in the different hematopoiesis score groups were compared.@*RESULTS@#The median OS time of the patients in group 1, 2, 3 and 4 was 27.0, 22.5, 20.7 and 18.1 months, while the median PFS time were 23.0, 19.0, 18.0 and 14.0 months, respectively. The OS and PFS of the patients in low score group were significantly better than those in high score group (P=0.045, P=0.048). There was no significant difference in the curative effect of the patients treated by bortezomib after 3-4 courses (P>0.05).@*CONCLUSION@#Hematopoiesis score can preliminarily predict the overall survival of newly diagnosed MM patients, but there is no significant difference between different scoring groups in the initial curative effect.


Subject(s)
Humans , Bortezomib/therapeutic use , Erythrocyte Indices , Hemoglobins/therapeutic use , Multiple Myeloma/diagnosis , Prognosis , Retrospective Studies
3.
Article in Chinese | WPRIM | ID: wpr-928689

ABSTRACT

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.


Subject(s)
Humans , Apoptosis , Bortezomib/pharmacology , Cell Line, Tumor , Cell Proliferation , Interleukin-1 Receptor-Associated Kinases , Multiple Myeloma , Pentacyclic Triterpenes , Signal Transduction
4.
Article in Chinese | WPRIM | ID: wpr-928688

ABSTRACT

OBJECTIVE@#To compare the efficacy and safety of different chemotherapy regimens in elderly multiple myeloma (MM) patients with different Frailty scores.@*METHODS@#The clinical data of elderly patients with MM were retrospectively analyzed, including age, treatment regimen, efficacy, adverse reactions, and the Frailty score included in the activity of daily living score, the instrumental activity of daily living scale and the Charlson comorbidity index. The patients were divided into fit group, mediate fit group and frail group according to the scoring standard. The treatment efficiency and adverse reaction rates of elderly MM with different physical conditions treated by different chemotherapy regimens were analyzed.@*RESULTS@#Among the 70 patients, the effective rates of the patients in fit group, the mediate fit group, and the frail group were 79.5%, 81%, and 40%, and the effective rates of the fit patients in double and triple groups were 54.5% and 89.3%, 70% and 90.9% for mediate fit patients, 42.9% and 33.3% for frail patients, the triple regimen in fit patients showed obvious advantages, and the difference showed statistically significant (P<0.05), while the efficacy for mediate patients and frail patients showed no significant difference. During the induction of bortezomib, the incidence of adverse reactions for the patients in the triple group (78.6%) was higher than 67.9% in the double group, and the difference showed no statistically significant (P>0.05).There was no significant difference in the 1-year overall survival rate of the patients and with molecular genetic abnormalities among each groups.@*CONCLUSION@#The therapeutic effect is related to the patient's physical condition. For patients with healthy physique, the triple regimen should be used first. For patients with weak physical constitution, the chemotherapy regimen with low drug toxicity should be selected for safety.


Subject(s)
Aged , Humans , Bortezomib , Frailty , Multiple Myeloma/drug therapy , Retrospective Studies
5.
Chinese Journal of Hematology ; (12): 414-419, 2022.
Article in Chinese | WPRIM | ID: wpr-929629

ABSTRACT

Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.


Subject(s)
Animals , Humans , Mice , Bortezomib/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Mice, Inbred NOD , Mice, SCID , Multiple Myeloma/drug therapy
6.
Journal of Experimental Hematology ; (6): 1216-1223, 2021.
Article in Chinese | WPRIM | ID: wpr-888541

ABSTRACT

OBJECTIVE@#To evaluate the predictive value of pre-treatment serum uric acid (sUA) level for the prognosis of newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#The NDMM patients admitted to our center from January 2014 to December 2018 were analyzed retrospectively, and 94 patients among them who were initially treated with bortezomib-based chemotherapy for at least 4 cycles were included in this study. Clinical characteristics, laboratory data and follow-up information were collected, and the predictive value of sUA on the overall survival (OS) of NDMM was evaluated by using receiver operating characteristic (ROC) curve based on the patient's pre-treatment sUA level and the survival status at the end of follow-up, and the correlation of the sUA level with patient's clinical, laboratory characteristics and overall survival (OS) was further analyzed. The univariate and multivariate Cox proportional-hazards model were used to identify the potential factors affecting OS.@*RESULTS@#ROC analysis showed that the area under the curve for predicting OS in NDMM patients with sUA level was 0.702 (P<0.001), and the optimal cut-off value was 455.4 μmol/L. Compared to patients with low sUA (<455.4 μmol/L), patients with higher sUA (≥455.4 μmol/L) were more likely to have international staging system (ISS) stage III disease, beta2-microglobulin (β@*CONCLUSION@#Pre-treatment sUA level is a potential biomarker for the prognosis evaluation in NDMM patients, which deserves a further exploration and verification.


Subject(s)
Humans , Middle Aged , Bortezomib , Multiple Myeloma , Prognosis , Retrospective Studies , Uric Acid
7.
Journal of Experimental Hematology ; (6): 1187-1194, 2021.
Article in Chinese | WPRIM | ID: wpr-888537

ABSTRACT

OBJECTIVE@#To investigate the effects of chidamide combined with anti-myeloma drugs on the proliferation and apoptosis of myeloma cells.@*METHODS@#The proliferation inhibition of the cells was detected by CCK-8 method, and flow cytometry was used to detected the apoptosis of the cells.@*RESULTS@#Chidamide could inhibit the proliferation of myeloma cells and promote the apoptosis of primary myeloma plasma cells in a time- and dose-dependent manner (P<0.05). In NCI-H929 cell line, chidamide combined with low-dose bortezomib and lenalidomide showed synergistic effect, while combined with dexamethasone and pomalidomide showed additive effect. In MM.1s cell line, chidamide combined with bortezomib, dexamethasone, lenalidomide and pomalidomide all showed synergistic effects.@*CONCLUSION@#Chidamide inhibits proliferation of myeloma cells in a time- and dose-dependent manner and promotes apoptosis of primary myeloma plasma cells. Furthermore, it can enhance the inhibitory effect of anti-myeloma drugs.


Subject(s)
Humans , Aminopyridines , Apoptosis , Benzamides , Bortezomib/pharmacology , Cell Line, Tumor , Cell Proliferation , Multiple Myeloma , Pharmaceutical Preparations
8.
Article in Chinese | WPRIM | ID: wpr-880154

ABSTRACT

OBJECTIVE@#To investigate the significance of CD27 and CD56 in the prognosis of multiple myeloma (MM) patients, and to establish a simple and convenient prognostic risk score.@*METHODS@#One hundred and eleven newly diagnosed MM patients treated by bortezomib in Shengjing hospital from January 1, 2013 to January 1, 2019 were selected, and the relationship between clinical characteristics and survival time of patients was analyzed.@*RESULTS@#The overall survival (OS) of patients in CD27@*CONCLUSION@#Among patients with MM treated by bortezomib, CD27


Subject(s)
Humans , Bortezomib , CD56 Antigen , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Prognosis , Retrospective Studies
9.
Article in Chinese | WPRIM | ID: wpr-880150

ABSTRACT

OBJECTIVE@#To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines.@*METHODS@#Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8.@*RESULTS@#ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC@*CONCLUSION@#ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.


Subject(s)
Humans , Apoptosis , Autophagy , Bortezomib/pharmacology , Cell Line, Tumor , Cell Proliferation , Hydroxychloroquine/analogs & derivatives , Multiple Myeloma
10.
Article in Chinese | WPRIM | ID: wpr-880105

ABSTRACT

OBJECTIVE@#To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib.@*METHODS@#MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H@*RESULTS@#MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G@*CONCLUSION@#PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.


Subject(s)
Humans , Apoptosis , Bortezomib/pharmacology , Cell Line, Tumor , Cell Proliferation , Multiple Myeloma
11.
Article in Chinese | WPRIM | ID: wpr-880046

ABSTRACT

OBJECTIVE@#To analyze the risk factors, distribution of pathogenic strains and tolerance of pulmonary infection in patients with multiple myeloma(MM) during bortezomib chemotherapy.@*METHODS@#The clinical data of 85 patients with multiple myeloma treated by bortezomib in our hospital from January 2015 to January 2019 was analyzed. The patients were divided into infection group and control group according to whether they were infected. The tolerance, pathogen distribution, and related risk factors were retrospectively analyzed.@*RESULTS@#Pulmonary infection rate was 55.29% in 85 MM patients. The proportions of the patients with anemia, neutropenia, and ECOG score ≥2 points in the infection group were significantly higher than those in the control group (P<0.05). In this study, 30 strains of pathogenic bacteria were detected, with gram-negative bacteria accounting for 60%, gram-positive bacteria for 33.33%, fungi for 3.3% and tuberculosis bacteria for 3.3%. Pseudomonas aeruginosa, klebsiella pneumoniae, streptococcus pneumoniae, staphylococcus aureus accounted showed the highest proportion. Most of MM patients with pulmonary infection showed a heterprognosis after two weeks antibiotic treatment, while 3 patients died. About 30 percent of early deaths were due to pulmonary infections.@*CONCLUSION@#Anemia, neutropenia, ECOG score ≥2 points are the major clinical characteristics of the multiple myeloma patients with pulmonary infections. Pulmonary infection is an important cause of early death in patients with multiple myeloma. Pathogenic bacteria are mainly composed of gram-negative bacteria. Beta-lacta/ beta-lactamase inhibitor combinations or Carbapenems are effective empiric treatment for controlling the progression of pulmonary infection.


Subject(s)
Humans , Bortezomib , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Multiple Myeloma/drug therapy , Retrospective Studies
12.
Article in Chinese | WPRIM | ID: wpr-880045

ABSTRACT

OBJECTIVE@#To explore the risk factors, prognosis and curative effect of elderly patients with MM renal damage.@*METHODS@#118 patients with primary elderly MM treated in our hospital from January 2011 to December 2018, were enrolled analyzed retrospectively. The clinical characteristics and prognosis of renal function impairment group (RI group) and normal renal function group (non-RI group) were compared. The difference of renal efficacy and survival benefit between the patients treated with bortezomib, thalidomide (combination group) and chemotherapy regimen containing only one of them (single drug group) in RI group was compared.@*RESULTS@#Univariate analysis showed that DS stage, pulmonary infection, uric acid, β @*CONCLUSION@#The prognosis of elderly MM patients with impaired renal function is poor. The prognosis of these patients can be improved by selecting chemotherapy regimen containing bortezomib and thalidomide at the same time, and monitoring, controlling all kinds of risk factors actively.


Subject(s)
Aged , Humans , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Multiple Myeloma/drug therapy , Prognosis , Retrospective Studies , Treatment Outcome
13.
Article in Chinese | WPRIM | ID: wpr-880044

ABSTRACT

OBJECTIVE@#To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM).@*METHODS@#Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression.@*RESULTS@#Anemia, renal dysfunction, hypoproteinemia and high level of β @*CONCLUSION@#The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.


Subject(s)
Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
14.
Article in Chinese | WPRIM | ID: wpr-880043

ABSTRACT

OBJECTIVE@#To investigate the efficacy, survival and adverse effects of non-transplanted multiple myeloma (MM) patients treated with bortezomib maintenance.@*METHODS@#A total of 25 newly diagnosed/relapsed non-transplanted MM patients treated in West District of Beijing Chaoyang Hospital from June 2004 to November 2015 were analyzed retrospectively. All patients received PD regimen (bortezomib and dexamethasone), including bortezomib at a dose of 1.3 mg/m@*RESULTS@#Till November 1, 2017, 5 patients achieved stringent complete response (sCR), 8 patients achieved complete response (CR), 7 patients achieved very good partial response (VGPR), 4 patients achieved partial reponse (PR), while 1 patient achieved stable disease (SD). After maintenance therapy, 21 patients maintained the efficacy above PR, of which 1 patient was improved from CR to sCR; 4 patients adjusted chemotherapy after disease progressed. Median maintenance therapy was 9 cycles (range from 6 to 31), and the median maintenance time was 27 months (range from 18 to 97). Median follow-up time was 73 months (range from 25 to 171). Median progress-free survival (PFS) time was 30 months (range from 9 to 105) and overall survival (OS) time was 57 months (range from 27 to 160). Till November 1, 2019, 3-year survival rate was 84% (21/25), and 5-year survival rate was 72% (13/18). The most common adverse events were transient leukopenia, thrombocytopenia and peripheral neuropathy, which the patients could tolerate after the prevention and treatment.@*CONCLUSION@#Bortezomib-based maintenance therapy for non-transplanted MM patients can be an option in consideration of its safety and efficacy.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Multiple Myeloma/drug therapy , Retrospective Studies , Treatment Outcome
15.
Article in Chinese | WPRIM | ID: wpr-880041

ABSTRACT

OBJECTIVE@#To investigate the effect of clinical baseline data on prognosis in patients with multiple myeloma (MM) complicated by extramedullary disease (EMD).@*METHODS@#The clinical data of 46 MM patients with EMD were retrospectively analyzed. The clinical data and survival prognosis of MM patients in primary EMD group and recurrent EMD group were analyzed. The classified baseline data were expressed by the number of cases (percentage), the χ@*RESULTS@#β @*CONCLUSION@#The remission depth of primary EMD group≥VGPR is lower than that of recurrent EMD group,and the OS time of patients in primary EMD group is shorter than that in recurrent EMD group. Bortezomib-based chemotherapy could not improve the prognosis of patients with primary EMD and recurrent EMD, and the prognosis of patients with primary EMD is even worse.


Subject(s)
Humans , Bortezomib , Disease-Free Survival , Multiple Myeloma , Prognosis , Proportional Hazards Models , Retrospective Studies
16.
Acta sci. vet. (Impr.) ; 49: Pub. 1826, 2021. ilus, tab
Article in English | LILACS, VETINDEX | ID: biblio-1363758

ABSTRACT

Bortezomib, an inhibitor of 26S proteasome, is an anti-cancer therapeutic agent used in different cancer types. It leads to the arrest of the cancerous cell cycle by inhibiting angiogenesis and inducing apoptosis. Liver is the vital organ for detoxification and excretion of toxic products. The treatment with chemotherapy is a challenge, drugs are used to destroy cancer cells, but healthy cells can be affected during cancer treatment as well. The main objective of this study was to analyze the histopathological and biochemical effects of bortezomib on liver. Twenty-four female C57BL/6 mice were distributed into 4 groups, bortezomib injected treatment groups (Btz1, Btz2) and saline injected control groups (C1, C2). Bortezomib and saline were treated twice per week for 6 weeks and sacrificed at the end of one day (Btz1, C1) and 4 weeks (Btz2, C2) after the last injection. Liver samples were examined for histopathological analysis and the serum samples processed for biochemical analysis. Tissue samples were fixed, routinely processed, sectioned, and stained with Hematoxylin and Eosin (H&E). Periodic Acid-Schiff (PAS), Sudan Black staining and Masson's trichrome histochemical staining methods were performed to characterize the lesions. Histopathological analysis of the Btz1 and Btz2 groups revealed acute hepatic morphological changes such as hepatocellular swelling (cloudy swelling), necro-inflammatory reaction, and increased mononuclear polyploidy. Based on the negative staining with PAS and Sudan Black staining, hepatocellular swelling was diagnosed as hydropic degeneration. Necro-inflammatory reaction observed in the form of acute hepatitis was composed of mainly mononuclear cell infiltration accompanied by multifocal necrotic foci. Kupffer cell proliferation was observed in parallel with degenerative and necrotic changes. An Increase in hepatocellular mononuclear polyploidy visualized as hepatocytes with a single enlarged nucleus was detected in all liver sections of Btz1 and Btz2 groups. Individual cases of cholestasis (n = 1) and mild hepatic fibrosis (n = 1) were also reported. Significant elevated levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were detected in bortezomib treated groups. Few clinical cases reported liver injury related to bortezomib used for cancer treatment. However, the liver was not considered as a target for bortezomib treatment. Our data suggesting that bortezomib caused liver damage and induces elevations in serum levels. The reported hepatic lesions including hepatocellular swelling, acute hepatitis and mononuclear polyploidy were mainly mild and moderate in severity. The increase of polyploidy in liver tissue of mice treated with bortezomib in this study was explained as a reaction of the liver facing the drug-induced hepatic damage. The mechanism leading to the hepatotoxicity of bortezomib treatment is not known but the production of a toxic metabolite through its metabolism in the liver can be suggested. Moreover, no recovery was also observed in histopathological and biochemical analyses suggesting that the bortezomib effect is non-reversible four weeks after the drug was withdrawn. Patients should be informed about the possibility of acute drug-induced hepatitis and hepatotoxicity of this chemotherapeutic agent after the treatment.(AU)


Subject(s)
Animals , Female , Mice , Biochemical Phenomena/drug effects , Proteasome Inhibitors/therapeutic use , Bortezomib , Liver/drug effects , Mice
17.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(2): 118-124, Apr.-June 2020. tab, ilus
Article in English | LILACS | ID: biblio-1134012

ABSTRACT

ABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Bone Marrow Transplantation , Bortezomib , Multiple Myeloma , Antineoplastic Agents , Thalidomide , Dexamethasone , Cyclophosphamide/therapeutic use
19.
Journal of Experimental Hematology ; (6): 1972-1976, 2020.
Article in Chinese | WPRIM | ID: wpr-880001

ABSTRACT

OBJECTIVE@#To explore and analyze the risk factors of herpes zoster in patients with multiple myeloma (MM) during the chemotherapy with bortezomib.@*METHODS@#Clinical data of 85 MM patients treated with bontizomib from January 2015 to January 2019 were selected and divided into case group and control group accroding to the occurred of herpes zoster. The clinical characteristic, treatment outcome and related factor of herpes zoster were retrospective analyzed.@*RESULTS@#Twenty of the 85 patients with MM treated with bortezomib developed herpes zoster occurred (23.5%). Single-factor analysis showed that age≥65 years, lymphocytopenia occurred before treatment, neutropenia occurred before treatment, ECOG score≥2, application of cyclophosphamide, absence of preventive antiviral therapy were associated with the genesis of herpes zoster (P<0.05). Multivariate logistic regression analysis showed that lymphocytopenia occurred before treatment, the application of cyclophosphamide and the absence of preventive antiviral therapy were the independent risk factors for herpes zoster (P<0.05).@*CONCLUSION@#The incidence of herpes zoster is high in the multiple myeloma patients treated with bortezomib. Lymphocytopenia occurred before treatment, the application of cyclophosphamide, and the absence of prophylactic antiviral therapy are the important risk factors for herpes zoster, for which the clinicians should attach great importance.


Subject(s)
Humans , Boronic Acids , Bortezomib , Herpes Zoster/epidemiology , Multiple Myeloma/drug therapy , Patients , Pyrazines , Retrospective Studies , Risk Factors
20.
Journal of Experimental Hematology ; (6): 1197-1204, 2020.
Article in Chinese | WPRIM | ID: wpr-827140

ABSTRACT

OBJECTIVE@#To investigate the effects of decitabine combined with bortezomib on the proliferation of mantle cell lymphoma cell lines (Jeko-1 and Grante519) in vitro and explore the underlying mechanisms.@*METHODS@#Jeko-1 and Grante519 cells were treated with different concentrations of decitabine and/or bortezomib alone and their combination.The cell proliferation was determined by CCK-8 assay. the cell apoptosis were detected by flow cytometry, the mRNA and protein expression levels of genes related with the cell cycle and apoptosis were analyzed by RT-PCR and Western blot respactively.@*RESULTS@#Low dose DAC could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner. After DAC treatment, caspase 3, BAX and PCDH8 expression levels increased, while BCL-2 and CCND1 expression levels decreased in Jeko-1 and Grante519 cells, but there was no significant difference in NF-κB expression. High dose BTZ could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner; single drug BTZ could increase the expression level of Caspase 3 and BAX, and decrease the expression level of NF-κB, BCL-2 and CCDN1 in Jeko-1 and Grante519 cells, but there was significant difference in PCDH8 expression level. Compared with single-drug treatment group, DAC combined with BTZ significantly increased the inhibitory rate and apoptotic rate of Jeko-1 and Grante519 cells; PCDH8, Caspase 3 and BAX expression levels significantly increased, and the expression levels of NF-κB, BCL-2 and CCND1 significantly decreased in Jeko-1 and Grante519 cells.@*CONCLUSION@#The combination of DAC and BTZ has obviously synergistic effects on the growth inhibition of Jeko-1 and Grante519 cells which maybe relates with enhancing inbibitory effect on NF-κB signal pathway, down-regulating BAX expression, up-regulating BAX expression as well as increasing cospase 3 expression. This study provides a novel therapeutic approach for mantle cell lymphoma.


Subject(s)
Adult , Humans , Apoptosis , Bortezomib , Cadherins , Cell Line, Tumor , Cell Proliferation , Decitabine , Lymphoma, Mantle-Cell
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