RESUMO
This study aimed to investigate the mechanism underlying the inhibitory effect of tumor suppressor gene miR-186 and zinc finger protein 545 (ZNF545) on the proliferation of multiple myeloma (MM) cells. CD138 magnetic beads were used to isolate different types of myeloma cell lines (KM3, U266, RPMI-8226, and H929), which were then infected by lentivirus carrying the miR-186 gene. Using uninfected myeloma cells as the control, MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide] assay was performed to calculate the rate of cell proliferation at different time points. In addition, the correlation between the expression of Jagged 1 and miR-186 was analyzed by real-time Polymerase Chain Reaction (PCR). Furthermore, the effect of 5-Aza-2-deoxycytidine and acetylase inhibitor Trichomycin A (TSA) on the expression of ZNF545 and proliferation/apoptosis of MM cells was investigated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blotting (WB), MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] cell proliferation assay, and Annexin V-FITC/PI staining. Compared with the control group, the proliferation of miR-186-overexpressing U266 and RPMI-8226 cells was significantly decreased. In cell cloning experiments, miR-186 decreased the number of U266 and RPMI-8226 clones while reducing the protein expression of Jagged 1. The expression level of ZNF545 in myeloma patients was also reduced to some extent. ZNF545 protein also promoted the apoptosis of myeloma cells. By inhibiting the proliferation of myeloma cells, miR-186 gene and ZNF protein may be used as tumor suppressors in the treatment of myeloma.
Assuntos
Proliferação de Células , MicroRNAs/metabolismo , Mieloma Múltiplo/patologia , Proteínas Nucleares/metabolismo , Apoptose , Linhagem Celular Tumoral , HumanosRESUMO
BACKGROUND: Pain assessment and monitoring is a prerequisite for its adequate treatment in patients with cancer. We performed a feasibility study on the use of short message service (SMS) and interactive voice response (IVR) to improve pain management in patients with cancer, including terminally ill patients. METHODS: During 4 weeks, palliative patients received a daily IVR asking to provide their pain score on a numeric rating scale (NRS) with their mobile phone. If pain was moderate or high, the nurse contacted the patient the same day and, if required, adapted the treatment. RESULTS: Thirteen of the 17 invited patients agreed to participate (79%), four died during the study period. IVR/SMS provides a reliable assessment of the pain intensity, and if required, treatment can be rapidly adapted. All patients were satisfied with the intervention. There were no difficulties for the, mainly older, patients in handling this communication way on pain intensity. The mean pain score decreased from 4.78 to 3.33 (P = 0.07). The pain scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) decreased significantly from 56 to 35 (P = 0.047). DISCUSSION: Monitoring and managing pain with IVR/SMS in patients with cancer at home appeared acceptable and feasible, even in terminally ill patients. The reluctance for actively contacting the professional in case of increased pain intensity is circumvented in this setting. Further research, preferably in a controlled study, is needed to establish the use of this intervention in a larger patient population.
Assuntos
Neoplasias/complicações , Pacientes Ambulatoriais , Manejo da Dor/métodos , Medição da Dor/métodos , Dor/etiologia , Interface para o Reconhecimento da Fala , Adulto , Idoso , Telefone Celular , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Dor/diagnóstico , Cuidados Paliativos , Satisfação do Paciente , Qualidade de Vida , Envio de Mensagens de TextoRESUMO
OBJECTIVE: To observe the activity of histone deacetylase and the mRNA expression level of HDAC1 and HDAC2 in human bone marrow mononuclear cells, which induced by hydroquinone and exposed to hydroquinone plus Trichostatin as a histone deacetylase inhibitor for 10 hours respectively. METHODS: Collect the bone marrow mononuclear cells suspension,divided into control group,HQ group (3 h, 6 h, 12 h, 24 h) , HQ+TSA 10 h group and HQ 10 h group. Extract the nuclear proteins and RNA, test the activity of histone deacetylase with the colorimetric HDAC assay kit and detect the mRNA expression level of HDAC1 and HDAC2 by real-time Polymerase Chain Reaction (PCR). RESULTS: The HDAC activity of HQ3 h group, HQ6 h group and HQ12 h group were 1.31 times, 1.53 times and 1.148 times than that of control group respectively. And the difference was statistically significant (P<0.05). Except the HQ24 h group (P>0.05) , the HDAC1 mRNA expression of HQ3 h group, HQ6 h group and HQ12 h group were 1.173 times, 1.901 times and 2.348 times than that of control group respectively. And the difference was statistically significant (P<0.05). The HDAC2 mRNA expression of HQ6 h group and HQ12 h group were 1.426 times and 1.766 times than that of the control group respectively. And the difference was statistically significant (P<0.05). No significant difference was observed between HQ3 h group, HQ24 h group and control group (P>0.05). The cells were treated by hydroquinone plus TSA for 10 hours. The HDAC activity of HQ+TSA 10h group was reduced by 25.6% than that of HQ 10 h group (P<0.05) and rised 13.0% compared to the control group (P<0.05). And the difference was statistically significant between groups (P<0.05) .The cells were treated by hydroquinone plus TSA for 10 hours. The HDAC1 mRNA expression of the HQ+TSA 10h group is reduced by 26.9% than that of HQ10h group. The HDAC2 mRNA expression is reduced by 19.3% compared to the HQ 10h group.And the difference was statistically significant between groups (P<0.05). The HDAC1 and HDAC2 mRNA expression is obviously higher than the control group, the difference was statistically significant (P<0.05). CONCLUSION: Treatment of hydroquinone, the histone deacetylase activity and the mRNA expression of HDAC1 and HDAC2 were increased in a certain time range. The histone deacetylase inhibitor (TSA) can reduce the histone deacetylase activity and the mRNA expression level of HDAC1 and HDAC2 in the bone marrow mononuclear cell induce by hydroquinone.It can be confirmed that hematopoietic damage induced by the benzene metabolites is related to the histone acetylation modification level.
Assuntos
Células da Medula Óssea , Medula Óssea , Histona Desacetilase 1 , Histona Desacetilase 2 , Inibidores de Histona Desacetilases , Histona Desacetilases , Humanos , Hidroquinonas , Ácidos Hidroxâmicos , RNA MensageiroRESUMO
OBJECTIVE: The aim of this study was to examine the association of sarcopenia and low muscle attenuation with survival and other clinical outcomes in patients with ovarian cancer. MATERIALS AND METHODS: Systematic search was done in PubMed, EMBASE and Scopus databases for observational studies that documented the link between sarcopenia and outcomes of interest in patients with ovarian cancer, with long-term survival as a primary outcome. Other outcomes included risk of recurrence, progression-free survival and complications. Pooled effect sizes were reported as hazards ratio (HR), relative risk ratio (RR) or weighted mean difference (WMD). Random effects model was used for the analysis. RESULTS: Twenty-two studies were selected, of which all, except one, were retrospective in design. Low skeletal muscle index (SMI, indicating muscle mass) (HR 1.30, 95% CI: 1.07, 1.58) and low muscle quality (HR 1.24, 95% CI: 1.03, 1.49) were associated with poor long-term survival, but not with the risk of recurrence and progression-free survival. Both low skeletal muscle index (SMI) (RR 1.49, 95% CI: 1.13, 1.98) and low muscle quality (RR 1.99, 95% CI: 1.04, 3.79) were associated with increased risk of complications. CONCLUSIONS: Both low skeletal muscle mass and low muscle quality showed significant association with poor long-term survival and an increased risk of complications. However, they do not have a significant association with the risk of recurrence and progression-free survival. There is a need for more prospective studies to confirm these associations.