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1.
Article in Chinese | WPRIM | ID: wpr-880148

ABSTRACT

OBJECTIVE@#To analyze one case of multiple myeloma (MM) initially presenting cold agglutinin syndrome (CAS), so as to improve clinical understanding and screening of this disease.@*METHODS@#The clinical data, laboratory examination, bone marrow result, diagnosis and treatment of the patient were analyzed and summarized to provide ideas and clinical experience for the early diagnosis and treatment of CAS secondary to MM.@*RESULTS@#The clinical manifestations of asthenia, hemolysis, jaundice and scattered livedo reticularis were caused by CAS secondary to MM, which was different from the general Raynaud's phenomenon. IgMκ type MM was definitely diagnosed according to the morphological features of bone marrow cells and immunofixation electrophoresis. After 3 courses of chemotherapy with BAD regimen and enhanced thermal support, anemia was corrected, M protein was decreased and the cold agglutinin phenomenon was significantly reduced. The evaluation of efficacy reached very good partial response.@*CONCLUSION@#There are very few MM patients with CAS as the initial presentation, so it is easy to misdiagnose. Early diagnosis and individual therapy are particularly important, which requires clinicians to observe and gain experience further.


Subject(s)
Anemia, Hemolytic, Autoimmune/diagnosis , Cryoglobulins , Early Diagnosis , Humans , Multiple Myeloma/diagnosis
2.
Article in Chinese | WPRIM | ID: wpr-880111

ABSTRACT

OBJECTIVE@#To explore the clinical features, prognosis and survival of patients with IgD multiple myeloma (MM).@*METHODS@#The clinical data of 20 patients with IgD MM was analyzed retrospectively. The prognostic factors and survival analysis was carried out. We summarized their clinical characteristics. The survival analysis was carried out by Kaplan-Meier method, and the prognostic factor were analyzed by using log-rank test for single factor analysis of observation index. Variables of P<0.15 in single factor analysis were enrolled in multifactor cox regression analysis.@*RESULTS@#IgD MM patients accounted for 4.3% of all MM patients in the same period, among which 80% were male, the median age of patients was 57.5(35-77) years old, 90% of the patients belongs to λ light chain type. At the time of diagnosis, 18 patients (90%) were in DS-Ⅲ stages, while 10 patients were in ISS-Ⅲ stage. The first clinical manifestations were fatigue, bone pain, kidney function impairment, anemia (Hb<100 g/L) in 14 cases (70%), 12 cases (60%) with osteolytic bone destruction≥3, combined with renal impairment in 8 cases (40%), and elevated blood calcium in 11 cases (51.4%). In only 5 patients the ratio of albumin to globntin was inverted, hypoalbuminemia accounted for 40%, and globulin increase accounted for only 15%. FISH results showed that the positive rate of 1q21 amplification (50%) was the highest, and it was easy to occur at the same time as other cytogenetic abnormalities. Extramedullary infiltration occurred in 4 cases (20%). The analysis of prognostic factors showed that only the increase of lactate dehydrogenase (LDH) level was an independent poor prognostic factor for IgD MM patients. Extramedullary infiltration and various cytogenetic abnormalities were found in 2 IgD MM patients with primary drug resistance, suggesting that extramedullary infiltration and various cytogenetic abnormalities may be prognostic factors, but the difference was not statistically significant, Which maybe related to the small sample size. All 20 patients were treated with bortezomib-containing regimen, of which 19 patients were evaluated, 17 patients (89.4%) showed effective, including CR+VGPR (52.6%), PR (31.5%), MR (5.3%), 2 patients primary drug resistance. The median PFS and OS was 9.5 and 10.5 months, respectively.@*CONCLUSION@#IgD MM is a rare and invasive disease. Increased LDH is an independent prognostic factor. Bortizomib-containing regimen can improve the prognosis of IgD MM patients.


Subject(s)
Aged , Disease-Free Survival , Female , Humans , Immunoglobulin D , Male , Middle Aged , Multiple Myeloma , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
3.
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 , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Humans , Multiple Myeloma/drug therapy , Prognosis , Retrospective Studies , Treatment Outcome
4.
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)
Bortezomib , Disease-Free Survival , Humans , Multiple Myeloma , Prognosis , Proportional Hazards Models , Retrospective Studies
5.
Journal of Experimental Hematology ; (6): 1667-1670, 2021.
Article in Chinese | WPRIM | ID: wpr-922314

ABSTRACT

Autoimmune cytopenia is a general term for all hemocytopenia diseases caused by humoral or cellular immunity abnormalities, and its common immune mechanism determines the importance of immunosuppressive therapy. Sirolimus, as an immunosuppressant against of mTOR, induces immune tolerance by adjusting Treg cells, which has application prospect in the treatment of refractory autoimmune cytopenia. This article reviews the mechanism, application, and possible adverse reactions of sirolimus in the treatment of idiopathic autoimmune cytopenia.


Subject(s)
Humans , Immunosuppressive Agents , Sirolimus , T-Lymphocytes, Regulatory , Thrombocytopenia
6.
Journal of Experimental Hematology ; (6): 1540-1547, 2019.
Article in Chinese | WPRIM | ID: wpr-775688

ABSTRACT

OBJECTIVE@#To investigate the expression, mechanism and methylation level of miR-28-5p in multiple myeloma (MM), so as to provide the expirement basis for searching new targeted therapy.@*METHODS@#RT-PCR was used to detect the expression levels of miR-28-5p and potential target CCND1 in CD138 cells of the patients with MM and bone marrow mononuclear cells of patients with iron defficiency anemia(IDA) as control, Methylation-specific PCR(MSP) was used to detect methylation levels of CpG island in LPP/miR-28-5p promoter region and the correlation with other clinical indicators was analyzed. The 5-aza-2'-deoxycytidine (5-Aza-dC,DAC) was used to treat MM cell line U266; after drug treatment,MSP was used to analyze the methylation status of the CpG islands in LPP/miR-28-5p promoter; the qPCR was used to detect the expression levels of miR-28-5p,and the regulatory mechanism of miR-28-5p expression was explored furtherly.@*RESULTS@#The methylation level of CpG island in LPP/miR-28-5p promoter region of MM patients was significantly higher than that of IDA patients. The relative expression level of miR-28-5p in MM patients was significantly lower than that of IDA patients. The relative expression level of miR-28-5p in newly diagnosed MM patients was higher than that in relapsed/progressive patients. The miR-28-5p target CCND1 was expressed at high levels in MM patients with LPP / miR-28-5p methylation, the expression level of miR-28-5p in MM patients correlated with β-MG concentration. 5-aza-dc could significantly inhibit the growth of U266 cell line, arrest the cell cycle in G phase, inhibit the biosynthesis of cellular RNA and protein and promote cell apoptosis. At the same time, up-regulation of miR-28-5p expression was found.@*CONCLUSION@#The expression of miR-28-5p in MM patients is regulated by methylation of CpG islands in the promoter region of the genome.miR-28-5p may act as a tumor suppressor gene, and its low expression may be involved in the occurrence and development of MM, suggesting that miR-28-5p may become a new target for the treatment of MM.


Subject(s)
Cell Line, Tumor , CpG Islands , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs , Genetics , Multiple Myeloma , Genetics
7.
Journal of Experimental Hematology ; (6): 1556-1560, 2019.
Article in Chinese | WPRIM | ID: wpr-775686

ABSTRACT

OBJECTIVE@#To investigate the effect of eukaryotic translation initiation factor 4E(eIF4E) on the autophagy of CD138 plasma cells in multiple myeloma(MM).@*METHODS@#Multiple myeloma CD138 plasma cells were treated with eIF4E inhibitor 4EGI, the changes of autophagy-related factors LC3-II and Beclin1 were detected by fluorescent quantitative PCR and Western blot, the changes of cell proliferation inhibition were detected by MTT assay, and cell apoptosis was detected by flow cytometry.@*RESULTS@#Quantitative fluorescence PCR showed that after treatment of myeloma cells with 4EGI, the expression levels of LC3-II and Beclin1 mRNA gradually increased with the enhancomer of 4EGI concentration and the prolongation of action time, and the differences were statistically significant (48 h: LC3-Ⅱ,r=0.942, Beclin1,r=0.952; 80 μg/ml: LC3-Ⅱ,r=0.966, Beclin1,r=0.998); Western blot showed that with the enhancement of 4EGI concentration, the expression of LC3-II and Beclin1 protein gradually increased(LC3-Ⅱ,r=0.923, Beclin1,r=0.977); CCK-8 showed that the inhibition rate of cells gradually increased (r=0.996); the apoptotic rate of 4EGI-treated groups (23.23±4.47, 7.59±1.67, 2.03±0.19) was significantly different from that of control group (0.03±0.04) (P<0.05).@*CONCLUSION@#The inhibition of eIF4E can activate the autophagy of CD138 plasma cells in multiple myeloma and induce the death of myeloma cells.


Subject(s)
Autophagy , Beclin-1 , Cell Line, Tumor , Eukaryotic Initiation Factor-4E , Humans , Multiple Myeloma
8.
Chinese Medical Journal ; (24): 1591-1598, 2019.
Article in English | WPRIM | ID: wpr-771223

ABSTRACT

BACKGROUND@#Natural anti-sense transcripts (NATs), which are transcribed from the complementary DNA strand of annotated genes, exert regulatory function of gene expression. Increasing studies recognized anti-sense transcription widespread throughout human cytomegalovirus (HCMV) genome, whereas the anti-sense transcription of RNA1.2 gene locus has never been investigated. In this study, the transcription of the RNA1.2 anti-sense strand was investigated in clinically isolated HCMV strain.@*METHODS@#Strand-specific high-through RNA-sequencing (RNA-seq) was performed to find possible anti-sense transcripts (ASTs). For analyzing and visualization of RNA-seq data sets, Integrative Genomics Viewer software was applied. To confirm these possibilities, Northern blotting and rapid amplification of cDNA ends (RACE) were used.@*RESULTS@#Transcription of the opposite strand of RNA1.2 gene locus was detected by RNA-sequencing using RNAs extracted from human embryonic lung fibroblasts infected with HCMV clinical isolate HAN. At least three HCMV NATs, named RNA1.2 AST 1, RNA1.2 AST2, and RNA1.2 AST3, were characterized by Northern blotting and RACE analyses. These RNA1.2 ASTs orientated from the complementary strand of RNA1.2 locus during the late phase of HCMV infection. The 5'- and 3'-termini of these transcripts were located within the opposite sequence of the predicted RNA1.2 gene.@*CONCLUSION@#A cluster of novel NATs was transcribed from the opposite sequence of the HCMV RNA1.2 gene region.

9.
Chinese Medical Journal ; (24): 1591-1598, 2019.
Article in English | WPRIM | ID: wpr-802558

ABSTRACT

Background@#Natural anti-sense transcripts (NATs), which are transcribed from the complementary DNA strand of annotated genes, exert regulatory function of gene expression. Increasing studies recognized anti-sense transcription widespread throughout human cytomegalovirus (HCMV) genome, whereas the anti-sense transcription of RNA1.2 gene locus has never been investigated. In this study, the transcription of the RNA1.2 anti-sense strand was investigated in clinically isolated HCMV strain.@*Methods@#Strand-specific high-through RNA-sequencing (RNA-seq) was performed to find possible anti-sense transcripts (ASTs). For analyzing and visualization of RNA-seq data sets, Integrative Genomics Viewer software was applied. To confirm these possibilities, Northern blotting and rapid amplification of cDNA ends (RACE) were used.@*Results@#Transcription of the opposite strand of RNA1.2 gene locus was detected by RNA-sequencing using RNAs extracted from human embryonic lung fibroblasts infected with HCMV clinical isolate HAN. At least three HCMV NATs, named RNA1.2 AST 1, RNA1.2 AST2, and RNA1.2 AST3, were characterized by Northern blotting and RACE analyses. These RNA1.2 ASTs orientated from the complementary strand of RNA1.2 locus during the late phase of HCMV infection. The 5′- and 3′-termini of these transcripts were located within the opposite sequence of the predicted RNA1.2 gene.@*Conclusion@#A cluster of novel NATs was transcribed from the opposite sequence of the HCMV RNA1.2 gene region.

10.
Article in English | WPRIM | ID: wpr-690616

ABSTRACT

<p><b>OBJECTIVE</b>To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni (C. jejuni) isolated from Shenzhen.</p><p><b>METHODS</b>Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively.</p><p><b>RESULTS</b>In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat (36.5%) was higher than that in cattle meat (1.1%). However, the prevalence in poultry cloacal swabs (27.0%) was lower than that in cattle stool (57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST 21 (11.9%), ST-22 (10.3%), and ST-403 (7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin (89.7%), followed by tetracycline (74.6%), and nalidixic acid (69.0%).</p><p><b>CONCLUSION</b>This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.</p>

11.
Journal of Experimental Hematology ; (6): 1022-1026, 2018.
Article in Chinese | WPRIM | ID: wpr-689535

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the proliferation- inhibitory and apoptosis inducing effect of ganglioside GM3 on human multiple myeloma cell line U266 cells and its possible mechanisms.</p><p><b>METHODS</b>MTT assay and flow cytometry were used to observe the effects of GM3 ganglioside on proliferation and apoptosis of human myeloma cell line U266. Effects of different concentration of ganglioside GM3 on the mRNA expression level of BCL-2 and BAX were detected by Real-time PCR.</p><p><b>RESULTS</b>MTT assay and Flow Cytometry showed that ganglioside GM3 could induce the apoptosis and inhibit the proliferation of multiple myeloma U266 cell line, and both the effects were enhanced with the increase of GM3 ganglioside concentration. Compared with the control group, the relative expression of BAX mRNA with the increase of GM3 concentration in experimental group was enhanced gradually(r=0.968), while the relative mRNA expression of anti-apoptotic gene BCL-2 was decreased gradually(r=-0.727).</p><p><b>CONCLUSION</b>GM3 ganglioside can induce apoptosis and inhibit the proliferation of U266 cell line in a concentration dependent manner. The mechanism may be related with up- regulation of BAX expression and down-regulation of BCL-2.</p>


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Gangliosides , Humans , Multiple Myeloma
12.
Article in Chinese | WPRIM | ID: wpr-271913

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression of insulin-like growth factor binding protein 7 (IGFBP7 ) gene in multiple myeloma cell line U266, and study the effect of 5-aza-2'-deoxycytidine (5-aza-dc) on proliferation of U266 cells.</p><p><b>METHODS</b>multiple myeloma cell line U266 was cultured in vitro. The bone marrow mononuclear cells from healthy persons(N-BMMNC) were collected and used as normal controls. The IGFBP7 mRNA expression of U266 cells and N-BMMNC were detected by real-time fluorescence quantitative PCR, the DNA methylation status of the IGFBP7 CpG island was measured by using methylation-specific PCR(MSP). The different concentrations of 5-aza-dc (5 µmol/L, 10 µmol/L, 20 µmol/L) were used to treat U266 cells for 48 hours, the RT-PCR and Western blot were used to detect the effect of IGFBP7 mRNA and protein expressions, the cell growth curve and Annexin V/PI were analyzed by flow cytometry.</p><p><b>RESULTS</b>As compared with normal BMMNC, the lower expression of IGFBP7 gene was found in U266 cells, the obvious hypermethylation of the CpG island in the IGFBP7 promoter was observed. After treatment of U266 treating with different concentrations of 5-aza-dc, the IGFBP7 mRNA expression was up-regulated dose-dependently(P<0.05), the U266 cells grew slowly and apoptosis rates were enhanced dose-dependently.</p><p><b>CONCLUSION</b>As the hypermethylalion of CpG island in IGFBP7 promoter is a frequent event in lower expression of IGFBP7 gene in U226 cells, the 5-aza-dc can up-regulate the expression of IGFBP7 , and can inhibit cell proliferation through induction of cell apoptosis and arrest of cell cycle.</p>

13.
Article in Chinese | WPRIM | ID: wpr-315001

ABSTRACT

HIV/AIDS patients in high prevalence areas with different routes of infection (sexually transmitted 878 cases, 527 cases of intravenous drug user, paid blood donor 652 cases) were choosen for traditional Chinese medicine (TCM) syndrome investigation for one-year clinical follow-up. This paper primarily concluded the nature, location and pathogenesis of AIDS diseases. Deficiency of Yang and Yin, combining deficiency of Qi are the basic deficiency syndromes, while stagnation of dampness, toxic fire are the excess syndromes; the disease location of HIV infector is spleen, main syndrome is deficiency of spleen Qi; the disease location of AIDS patient is kidney, main syndrome is deficiency of spleen and kidney Yang. The pathogenic development tendency is from deficiency of Qi to combining stagnation of dampness and toxic fire, finally to deficiency of Qi and Yin, deficiency of Yang.


Subject(s)
Adolescent , Adult , Aged , Female , Follow-Up Studies , HIV Infections , Diagnosis , Humans , Male , Medicine, Chinese Traditional , Methods , Middle Aged , Young Adult
14.
Journal of Experimental Hematology ; (6): 1496-1500, 2013.
Article in Chinese | WPRIM | ID: wpr-264988

ABSTRACT

The objective of this study was to investigate the effect of the new generation of tyrosine kinase inhibitor flumatinib mesylate on C-MYC, HIF-1α and VEGF in multiple myeloma (MM) cell line U266. Different concentrations (1, 5, 10 µmol/L) of flumatinib mesylate were used to act on U266 cell line for 8, 16 and 24 h, and the expression of C-MYC, and HIF-1α genes was detected by real-time fluorescence-quantitative PCR, the expression of C-MYC, HIF-1α and VEGF was measured by Western blot. The results showed that the gene expression of C-MYC and HIF-1 genes decreased gradually with the increasing of flumatinib mesylate concentration (P < 0.05). At the same concentration of flumatinib mesylate, the expression of C-MYC and HIF-1α gene decreased gradually with prolonging of treatment time with the flumatinib mesylate (P < 0.05). When the flumatinib mesylate acted the U266 cell line for 16 h, the expression of C-MYC, HIF-1α and VEGF decreased gradually with the increasing of flumatinib mesylate concentration (P < 0.05). It is concluded that the flumatinib mesylate can reduce the expression of C-MYC, HIF-1 α and VEGF in U266 cell line in a time- and dose-dependent manners, so flumatinib mesylate may become a new drug for MM therapy.


Subject(s)
Aminopyridines , Pharmacology , Benzamides , Pharmacology , Cell Line, Tumor , Gene Expression Regulation, Leukemic , Genes, myc , Humans , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Vascular Endothelial Growth Factor A , Metabolism
15.
Article in Chinese | WPRIM | ID: wpr-325202

ABSTRACT

This study was purposed to explore the relationship between the mRNA expression of telomere protection protein TIN2 and POT1 and the pathogenesis of myelodysplastic syndrome (MDS). The expression of TIN2 and POT1 genes at the mRNA levels were detected by real-time fluorescence quantitative PCR in 51 patients with MDS and 10 normal controls. The results showed that the mRNA expressions of TIN2 in RA/RARS/RCMD/MDS-U, RAEB-1 and RAEB-2 groups according to the World Health Organization criteria were significantly higher than that in the controls (P < 0.05); the mRNA expressions of POT1 in RA/RARS/RCMD/MDS-U, RAEB-1 and RAEB-2 groups were significantly lower than that in the controls (P < 0.05). The mRNA expressions of TIN2 in high-risk group, inter risk-2 group and inter risk-1 group according to the international prognostic scoring system criteria were significantly higher than that in controls (P < 0.05). There was no significant difference between low risk group and the control group. The mRNA expressions of POT1 in high risk group, inter-risk-2 group and inter-risk-1 group were significantly lower than the controls (P < 0.05). There was no significant difference between low risk group and the control group. The mRNA expression of TIN2 in normal chromosome group was significantly lower than that in abnormal chromosome group (P < 0.05). There was no significant difference between normal chromosome group and the control group. The mRNA expression of POT1 in normal chromosome group was significantly higher than that in abnormal chromosome group (P < 0.05). There was no significant difference between normal chromosome group and the control group. It is concluded that the abnormal mRNA expression of TIN2 and POT1 may be involved in the regulation of telomere dynamics of MDS patients, the regulatory mechanism may be related to the telomere length and the pathogenesis of MDS.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow , Metabolism , Pathology , Case-Control Studies , Cell Adhesion Molecules , Genetics , Metabolism , Female , Humans , Male , Middle Aged , Myelodysplastic Syndromes , Genetics , Metabolism , Pathology , RNA, Messenger , Genetics , Telomere , Metabolism , Telomere-Binding Proteins , Genetics , Metabolism , Young Adult
16.
Journal of Experimental Hematology ; (6): 1122-1126, 2012.
Article in Chinese | WPRIM | ID: wpr-278423

ABSTRACT

This study was purposed to explore the effect of a new generation of histone deacetylase inhibitor LBH589 alone or combined with bortezomib (Bor) on multiple myeloma cells (MM1R) in vitro. The effect of LBH589 (10, 20, 50 nmol/L) alone or combined with Bor (10, 20 nmol/L) on MM1R proliferation was detected by MTT method; the effect of LBH589 on cell cycle and apoptosis of MM1R cells were determined by flow cytometry; the histone H4 acetylation level of MM1R cells treated with LBH589 (10, 20, 50 nmol/L) for 24 h was analyzed by Western blot. The results showed that the LBH589 alone or combined with Bor all could inhibit the proliferation of MM1R cells in a concentration- and time-dependent manner. After MM1R cells were treated with drugs for 48 h, the cells in G(0)/G(1) phase increased, the cells in G(2)/M and S phase decreased, suggesting the arrest of cells in G(0)/G(1) phase, at the same time, the apoptosis rate of MM1R cells treated with drugs increased in a concentration-dependent manner, while the effect of LBH589 combined with Bor was more obvious than that of LBH589 alone (P < 0.001). Western blot analysis showed that the histone H4 acetylation level was enhanced in concentration-dependent manner after MM1R cells were treated with different concentrations of LBH589 for 24 h. It is concluded that the LBH589 can inhibit the proliferation of MM1R cells, block the cell cycle, induce cell apoptosis, moreover LBH589 combined with Bor has synergistic effect on MM1R cells.


Subject(s)
Acetylation , Apoptosis , Boronic Acids , Pharmacology , Bortezomib , Cell Cycle , Cell Line, Tumor , Histone Deacetylase Inhibitors , Pharmacology , Humans , Hydroxamic Acids , Pharmacology , Indoles , Pharmacology , Multiple Myeloma , Pathology , Pyrazines , Pharmacology
17.
Journal of Experimental Hematology ; (6): 1127-1130, 2012.
Article in Chinese | WPRIM | ID: wpr-278422

ABSTRACT

The objective of this study was to investigate expression of interferon regulatory factors (ICSBP/IRF8) and the potential role of DNA methylation in silencing ICSBP/IRF8 gene in multiple myeloma (MM) cell line U266 and bone marrow mononuclear cells from 10 MM patients (MM-BMMNC). The bone marrow mononuclear cells from 10 healthy persons (N-BMMNC) were collected and used as normal controls. Expression of ICSBP/IRF8 gene was detected by real-time fluorescence quantitative PCR (using 2(-ΔΔCT) to calculate); DNA methylation level of the ICSBP/IRF8 gene was measured using methylation-specific PCR (using the ratio of interest gene ICSBP/IRF8 and internal reference β-actin expression as results). The results showed that as compared with N-BMMNC the lower expression of ICSBP/IRF8 gene was found in U266 cells and MM-BMMNC, the hypermethylation of the CpG island in the ICSBP/IRF8 promoter was observed, there were significant differences between N-BMMNC and MM-BMMNC or U266 cells (P < 0.05). It is concluded that the expression of ICSBP/IRF8 gene can be silenced in the MM-BMMNC and U226 cells. As the hypermethylation of CpG island in ICSBP/IRF8 promoter is a frequent event in MM cells, the ICSBP/IRF8 gene silencing caused by DNA methylation may take part in the pathogenesis and development of MM.


Subject(s)
Bone Marrow Cells , Metabolism , Case-Control Studies , Cell Line, Tumor , DNA Methylation , Gene Silencing , Humans , Interferon Regulatory Factors , Genetics , Metabolism , Multiple Myeloma , Genetics , Metabolism
18.
Chinese Journal of Hematology ; (12): 926-931, 2012.
Article in Chinese | WPRIM | ID: wpr-278298

ABSTRACT

<p><b>OBJECTIVE</b>To explore the impact of a new generation of histone deacetylase inhibitor LBH589 alone or in combination with proteasome inhibitor bortezomib on multiple myeloma (MM) cells proliferation and its mechanism.</p><p><b>METHODS</b>MM cell line U266 and dexamethasone resistant cell line MM1R cells were treated with different concentrations of LBH589 alone or in combination with bortezomib, the inhibition of cells proliferation was detected by MTT, the cell cycle and apoptosis by flow cytometry. The expression level of histone H4 acetylation and PARP, Bcl-X protein was analyzed by western blot, expression level of caspase-3, APAF-1 and TOSO gene by real-time fluorescence quantitative PCR.</p><p><b>RESULTS</b>U266 and MM1R cell proliferation were inhibited by different concentrations of LBH589 (0, 10, 20, 50 nmol/L) alone or 50 nmol/L of LBH589 in combination with bortezomib (10, 20 nmol/L) in a dose- and time-dependent manner. Inhibition effect was significantly higher in all combinative groups than in single agent groups (all P < 0.05). The percentage of G(0)/G(1) phase in MM1R cells were 36.60%, 46.50%, 51.40%, 57.10%, 75.48%, 79.73%, respectively, and the apoptosis rate were 5.27%, 31.41%, 39.78%, 44.07%, 73.60%, 83.27%, respectively. The effects appeared to occur in a dose-dependent manner, and being significantly higher in all combinative groups than in single agent groups (all P < 0.05). The expression of the caspase-3 and APAF-1 gene up-regulated gradually, while TOSO gene expression in MM1R cells down-regulated gradually in a dose- and time-dependent manner (all P < 0.05).</p><p><b>CONCLUSIONS</b>LBH589 can inhibit the growth of MM cells, block the cell cycle and induce cell apoptosis, which has anti-resistant effect on multidrug resistant cell. At the same time LBH589 in combination with bortezomib on myeloma cell has a synergistic effect, its mechanism and reversal of drug resistance mechanism involves in multiple changes in gene expression.</p>


Subject(s)
Acetylation , Antineoplastic Agents , Pharmacology , Apoptosis , Boronic Acids , Pharmacology , Bortezomib , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Drug Synergism , Histone Deacetylase Inhibitors , Pharmacology , Humans , Hydroxamic Acids , Pharmacology , Indoles , Pharmacology , Multiple Myeloma , Pathology , Pyrazines , Pharmacology
19.
Article in Chinese | WPRIM | ID: wpr-244914

ABSTRACT

This study was aimed to explore the influence of brucine on the early differentiation of osteoblasts and the metabolic pathway of osteoclast in multiple myeloma (MM) and to compare the effects of brucine and bortezomib on MM. The half inhibitory concentration (IC(50)) of brucine and bortezomib on MM cell line U266 was determined by MTT method; the mRNA levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG) and osteoprotegerin ligand (RANKL) were detected by RT-PCR after the supernatant of cultured U266 cells was added into the culture system for inducing the differentiation of osteoblast line MC3T3-E1 and culturing. The results showed that the IC(50)of bortezomib and brucine on U266 cells for 48 hours were 22.4 nmol/L and 0.16 mg/ml respectively. As compared with osteoblasts treated by supernatant of cultured MM cells alone, the mRNA levels of ALP, OC and OPG in osteoblasts treated by brucine combined with supernatant of cultured MM cells were enhanced (p < 0.05), while the RANKL mRNA level was lowered (p < 0.05), moreover the enhanced and lowered degree also was large (p < 0.05). It is concluded that the influence of brucine on metabolism of osteoblasts and osteoclasts in MM may be realized through the regulation of osteoclasts by osteoblasts. The therapeutic efficacy of brucine on MM is superior to bortezomib.


Subject(s)
Animals , Cell Line , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Mice , Multiple Myeloma , Metabolism , Osteoblasts , Cell Biology , Metabolism , Osteoclasts , Cell Biology , Metabolism , Strychnine , Pharmacology
20.
Article in Chinese | WPRIM | ID: wpr-243352

ABSTRACT

This study was aimed to investigate the correlation of heat shock protein 90 (HSP90) expression with migration ability of human multiple myeloma cells. The HSP90 mRNA expression and migration change of human multiple myeloma cell line (U266) were detected by RT-PCR and Transwell chamber respectively after treatment of U266 cells with final concentration 50, 100, 150, 200 nmol/L of bortezomib (proteosome inhibitor) for 4 hours. The results indicated that along with the increasing of bortezomib concentration, the expression level of HSP90alpha mRNA in U266 cells was enhanced, while no obvious increase of HSP90beta mRNA expression was observed in spite of statistical difference as a whole (p<0.05), but with the increasing of drug concentration in cells, their migration ability gradually decreased (p<0.05). It is concluded that the correlation of HSP90 expression with migration ability of human multiple myeloma cells exists.


Subject(s)
Cell Line, Tumor , Cell Movement , HSP90 Heat-Shock Proteins , Genetics , Humans , Multiple Myeloma , Genetics , Pathology , RNA, Messenger , Genetics
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