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1.
Zhonghua Xue Ye Xue Za Zhi ; 45(3): 215-224, 2024 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-38716592

RESUMO

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.


Assuntos
Dasatinibe , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China , Dasatinibe/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , /uso terapêutico
2.
Zhonghua Xue Ye Xue Za Zhi ; 44(9): 728-736, 2023 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-38049316

RESUMO

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Adulto , Humanos , Adolescente , Mesilato de Imatinib/efeitos adversos , Incidência , Antineoplásicos/efeitos adversos , Estudos Retrospectivos , Pirimidinas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Resultado do Tratamento , Benzamidas/efeitos adversos , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Aminopiridinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico
3.
Artigo em Chinês | MEDLINE | ID: mdl-34666438

RESUMO

Objective: To evaluate the shoulder function in patients after repair of head and neck defects with supraclavicular flap. Methods: A retrospective analysis was performed on 56 patients (54 males, 2 females, aged 35-74 years old) who received the repair of head and neck defects with supraclavicular flaps at Department of Otorhinolaryngology Head and Neck Surgery of Beijing Tongren Hospital, Capital Medical University in January 2013-December 2020. The areas and types of flaps, disruption or infections of the incision at the donor sites and other postoperative complications were recorded. Quick disabilities of the arm, shoulder and hand (Quick-DASH) was used for evaluating the shoulder functions in 43 patients conforming to the standard for evaluation of the clinical functions of shoulders and upper limbs, to compare the postoperative upper limb functions between patients treated with clavicular flaps and patients with acromion flaps. Meanwhile, 30 patients who received bilateral neck lymph node dissection over the same period of time were selected for a comparative evaluation of the donor sides (observation group) and the opposite sides (control group). Data were processed with SPSS 22.0. Results: The areas of obtained supraclavicular flaps were (4-10) cm × (10-18) cm. Three patients (5%) showed the defect widths of 8-10 cm at the donor sites, which couldn't be sutured directly, received the repair of their shoulder defects with partial flaps. Defects in other patients were sutured directly. After surgery, 3 patients (5%) suffered from disruption of the acromion incision, which healed after 2 weeks of local dressing. The follow-up time was 6-43 (27±14) months. All patients expressed no dissatisfaction with the appearance. Among 43 patients, 28 (65%) were clavicular type and 15 (35%) were acromion type. The acromion type showed average motor ability and Quick-DASH scores higher than the clavicular type [(average motor ability: (14.4±4.7) vs. (11.8±3.1), t=2.105, P=0.048; Quick-DASH: (16.9±11.6) vs. (12.2±7.1), t=2.284, P=0.033]. Among 30 patients who received bilateral neck lymph node dissection over the same period of time, the observation group showed higher average motor ability, local symptoms and Quick-DASH scores than the control group [average motor ability: (13.4±5.8) vs. (9.8±4.2), t=3.024, P=0.004; average local symptoms: (4.1±1.0) vs. (3.4±1.0), t=2.537, P=0.014; Quick-DASH: (15.6±14.7) vs. (5.2±11.1), t=3.106, P=0.003]. Conclusion: Shoulder dysfunction exists after treatment with supraclavicular flap, which is related to the flap type.


Assuntos
Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ombro/cirurgia , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Resultado do Tratamento
4.
Artigo em Chinês | MEDLINE | ID: mdl-34218558

RESUMO

Objective: To study the effect of preventive intervention on occupational exposure of nurses after tumor particle implantation in thoracic surgery. Methods: In March 2020, 99 nurses who were engaged in postoperative nursing of tumor particle implantation in thoracic surgery department of our hospital from February 2019 to February 2020 were selected as the research objects. According to different preventive interventions, they were divided into observation group (51 cases) and control group (48 cases) . The observation group received preventive intervention, while the control group received routine intervention. The differences of radiation dose, psychological state and abnormal rate of important organ function between the two groups were analyzed. Results: Compared with the control group, the radiation dose of the observation group was significantly less, and the scores of anxiety and depression were lower after the intervention, the difference were statistically significant (P<0.05) . There was no significant difference of the abnormal rate of important organ function between the two groups (P>0.05) . Conclusion: Preventive intervention can reduce the risk of occupational exposure and improve the psychological status of nurses after tumor particle implantation in thoracic surgery.


Assuntos
Neoplasias , Enfermeiras e Enfermeiros , Exposição Ocupacional , Cirurgia Torácica , Transtornos de Ansiedade , Humanos
5.
Eur Rev Med Pharmacol Sci ; 23(19): 8287-8294, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31646558

RESUMO

OBJECTIVE: The aim of this study was to investigate the exact role of long non-coding RNA (lncRNA) RUNX1-IT1 in regulating the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells, and to explore the possible underlying mechanism. PATIENTS AND METHODS: LncRNA RUNX1-IT1 expressions in paired HCC tissues (cancer and paired non-cancer tissues) (n=80) and HCC cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The effects of lncRNA RUNX1-IT1 on the proliferation and apoptosis of HCC cells were estimated by cell counting kit-8 (CCK-8) and tunnel assay, respectively. Furthermore, the association between lncRNA RUNX1-IT1 expression and the overall survival of patients was analyzed by the survival curve. RESULTS: The expression level of lncRNA RUNX1-IT1 significantly decreased in HCC tissues. The overexpression of lncRNA RUNX1-IT1 remarkably inhibited the proliferation and induced the apoptosis of HCC cells. On the contrary, the knockdown of lncRNA RUNX1-IT1 remarkably enhanced the ability of proliferation and repressed the apoptosis of the HCC cells. In addition, lower expression of lncRNA RUNX1-IT1 indicated the worse prognosis of HCC patients. CONCLUSIONS: We found that lncRNA RUNX1-IT1 played an important role in the development of HCC by participating in cell proliferation and apoptosis. Thus, lncRNA RUNX1-IT1 might be a powerful candidate as a prognostic biomarker and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas de Fusão Oncogênica/metabolismo , RNA Longo não Codificante/metabolismo , Apoptose , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Células Cultivadas , Humanos , Fígado/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 45(6): 519-525, 2017 Jun 24.
Artigo em Chinês | MEDLINE | ID: mdl-28648030

RESUMO

Objective: To explore the effect and possible mechanisms of intermittent alkaline on rat vascular smooth muscle cells (VSMCs) calcification induced by high phosphorus. Methods: VSMCs were isolated from rat thoracic aorta and cultured in vitro. The fourth generation VSMCs were randomly divided into control group, high phosphorus+ pH7.4, high phosphorus+ pH7.5, high phosphorus+ pH7.6 and high phosphorus+ pH7.7 group with random number table. The control group was cultured in DMEM with 10% fetal bovine serum. Other groups were cultured in DMEM with 10 mmol/L ß-glycerophosphate and alkalized by 7.4% NaHCO(3) to adjust the pH respectively. After the intervention of 4 hours, the control group was replaced with the normal medium containing 10% fetal bovine serum, the other 4 groups were replaced with high phosphorus based on the pH value of the culture medium, and then replaced the culture medium every other day. After 4 days intervention, the mRNA and protein expression of L type calcium channel ß(3) subunit(LTCC ß(3)) and Runt related transcription factor 2 (Runx2) were detected by RT-PCR and Western blot. After 4 days intervention, the level of VSMC calcium ion was detected by Fluo-3/AM. After 14 days intervention, alkaline phosphatase (ALP) activity was measured by enzyme linked immunosorbent assay (ELISA) and the calcification was observed by measuring calcium content. Results: (1) Compared with control group, the gene and protein expressions of LTCC ß(3) were higher in high phosphorus+ pH7.4 group (0.49±0.03 vs. 0.23±0.02 and 0.45±0.03 vs. 0.26±0.02 respectively, all P<0.05). Compared with high phosphorus+ pH7.4 group, the mRNA(0.86±0.05) and protein(0.62±0.04) expressions of LTCC ß(3) were higher in high phosphorus+ pH7.5 group (P<0.05). Compared with high phosphorus+ pH7.5 group, the mRNA(0.99±0.05) and protein(0.80±0.03) expressions of LTCC ß(3) were higher in high phosphorus+ pH7.5 group (all P<0.05). Compared with high phosphorus+ pH7.6 group, the mRNA(1.16±0.05) and protein(0.93±0.03) expressions of LTCC ß(3) were higher in high phosphorus+ pH7.7 group (all P<0.05). (2) Compared with control group, calcium ion influx were higher in high phosphorus+ pH7.4 group (124.61±6.06 vs. 75.68±7.82, P<0.05). Compared with high phosphorus+ pH7.4 group, calcium ion influx was higher in high phosphorus+ pH7.5 group(210.85±9.75, P<0.05). Compared with high phosphorus+ pH7.5 group, calcium ion influx was higher in high phosphorus+ pH7.6 group(298.44±11.42, P<0.05). Compared with high phosphorus+ pH7.6 group, calcium ion influx was higher in high phosphorus+ pH7.7 group(401.13±11.41, P<0.05). (3) Compared with control group, the mRNA and protein expressions of Runx2 and ALP were higher in high phosphorus+ pH7.4 group (0.60±0.04 vs. 0.34±0.03, 0.42±0.04 vs. 0.21±0.02, 67.2±4.3 vs. 23.2±2.3 respectively, all P<0.05). Compared with high phosphorus+ pH7.4 group, the mRNA(0.76±0.05) and protein(0.68±0.03) expressions of Runx2 and ALP(102.1±5.4) were higher in high phosphorus+ pH7.5 group (all P<0.05). Compared with high phosphorus+ pH7.5 group, the mRNA(0.90±0.05) and protein(0.90±0.05) expressions of Runx2 and ALP(139.3±4.9) were higher in high phosphorus+ pH7.6 group (all P<0.05). Compared with high phosphorus+ pH7.6 group, the mRNA(1.11±0.05) and protein(1.08±0.06) expressions of Runx2 and ALP(197.0±6.7) were higher in high phosphorus+ pH7.7 group (all P<0.05). (4) Compared with control group, the calcium content were higher in high phosphorus+ pH7.4 group ((75.4±4.3)mg/g pro vs.(25.2±2.1)mg/g pro, P<0.05). Compared with high phosphorus+ pH7.4 group, the calcium content were higher in high phosphorus+ pH7.5 group ((100.8±5.7) mg/g pro, P<0.05). Compared with high phosphorus+ pH7.5 group, the calcium content were higher in high phosphorus+ pH7.6 group ((143.5±6.1) mg/g pro, P<0.05). Compared with high phosphorus+ pH7.6 group, the calcium content were higher in high phosphorus+ pH7.7 group ((205.1±8.2) mg/g pro, P<0.05). Conclusion: Intermittent alkaline stimulation can promote high phosphorus induced rat VSMCs calcification possibly through upregulating LTCC ß(3) subunit gene and protein expression, increasing calcium ion influx and enhancing VSMCs phenotypic transformation.


Assuntos
Glicerofosfatos , Músculo Liso Vascular , Fósforo , Calcificação Vascular , Compostos de Anilina , Animais , Aorta Torácica , Calcinose , Cálcio , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core , Miócitos de Músculo Liso , Ratos , Regulação para Cima , Xantenos
7.
Zhonghua Yi Xue Za Zhi ; 97(6): 451-456, 2017 Feb 14.
Artigo em Chinês | MEDLINE | ID: mdl-28219134

RESUMO

Objective: To explore the role of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) on vascular calcification in chronic renal failure rats. Methods: Nineteen male Sprague-Dawley (SD) rats were randomly divided into three groups: sham-operated group (n=6), 5/6 Nephrectomy (Nx) group (n=6), 5/6 Nx+ calcitriol group (n=7). Vascular calcification was determined by von Kossa staining and orthocresolphthalein complexone (OCPC) method. Protein expressions of NFATc1 and runt-related transcription factor 2 (Runx2) in aortas were measured by immunohistochemistry.In vitro, vascular smooth muscle cells (VSMCs) were primarily cultured and calcification was induced by ß-glycerophosphate (ß-GP). These cells were then randomly divided into control group, calcification group (10 mmol/L ß-GP) and cyclosporin A (CsA) intervention group (10 mmol/L ß-GP+ 1 µg/ml CsA). Calcium deposition was measured by Alizarin red staining and OCPC method; alkaline phosphatase (ALP) activity was measured by enzyme-linked immunosorbent assay. RT-PCR and Western blotting were used to observe the mRNA and protein expression of VSMCs NFATc1 and Runx2 respectively. Results: Compared to that in sham-operated and 5/6 Nx group, the expression of NFATc1 was obviously up-regulated in 5/6 Nx+ calcitriol group (7.20±0.46 vs 1.52±0.77, 2.04±1.31, P<0.05). In vitro, VSMCs calcification was successfully induced by high phosphorus environment, and RT-PCR and Western blotting showed that the expressions of NFATc1 and Runx2 were up-regulated (P<0.05). The calcification level in CsA intervention group was lower than that in calcification group [(60.86±7.95) vs (107.20±11.07) mg/g, P<0.05], and expression of Runx2 (mRNA and protein level) and ALP activity [(48.63±3.02) vs (98.75±3.46) U/g, P<0.05] decreased as well. Conclusion: NFATc1 contributes to accelerating vascular calcification in rat with chronic renal failure, the possible mechanism of which is that NFATc1 promotes VSMCs transformation to osteogenic phenotype.


Assuntos
Músculo Liso Vascular , Linfócitos T , Animais , Aorta , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core , Citoplasma , Glicerofosfatos , Falência Renal Crônica , Masculino , Miócitos de Músculo Liso , Osteogênese , Fósforo , Ratos , Ratos Sprague-Dawley , Regulação para Cima , Calcificação Vascular
8.
Artigo em Chinês | MEDLINE | ID: mdl-28104014

RESUMO

Objective: To investigate individualized therapeutic strategy for bilateral carotid body tumors. Methods: Clinical data of 16 patients with bilateral carotid body tumor treated from January 2003 to August 2016 were retrospectively studied. Of the 16 patients, 9 were males and 7 were females; 5 were sporadic and 11 were familial; 8 cases were observed, 1 cases was malignant and treated with chemotherapy, and 7 cases were treated with surgery. The treatment course, perioperative complications and clinical efficacy were assessed. Comprehensive evaluation of bilateral carotid body tumors was performed based on the size of bilateral tumor, clinical manifestations, genetic tests and other indicators. Individual treatment strategies included observation, surgery and observation, bilateral surgery, radiotherapy or chemotherapy. Surgical resection of carotid body tumor was unilateral in 3 cases and bilateral in 3 cases; removal of bilateral carotid body tumors plus unilateral jugular bulb in 1 case; and the internal carotid artery was reconstructed with autologous greater saphenous vein in 1 case. Results: All patients were followed up for 3 months to 12 years. There was no patient death during perioperative period. Superior laryngeal nerve injury occurred in 2 case. Baroreceptor failure syndrome occurred in one patient, but it gradually recoverd with medical treatments. Conlusion: It is important to identify whether bilateral carotid body tumors are hereditary and to make an individualized therapeutic strategy for each patient with bilateral carotid body tumors, focusing on the improvement in the quality of life of patient.


Assuntos
Tumor do Corpo Carotídeo/tratamento farmacológico , Tumor do Corpo Carotídeo/cirurgia , Artéria Carótida Interna/cirurgia , Tumor do Corpo Carotídeo/etiologia , Tumor do Corpo Carotídeo/patologia , Feminino , Humanos , Traumatismos do Nervo Laríngeo/etiologia , Masculino , Complicações Pós-Operatórias/etiologia , Pressorreceptores/fisiopatologia , Qualidade de Vida , Estudos Retrospectivos
9.
Zhonghua Xin Xue Guan Bing Za Zhi ; 44(6): 536-41, 2016 Jun 24.
Artigo em Chinês | MEDLINE | ID: mdl-27346269

RESUMO

OBJECTIVE: To observe the role of TRAM-34 (1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole), the blocker of intermediate conductance calcium-activated potassium channel (KCa3.1), on ß-glycerophosphate induced vascular calcification in vitro. METHODS: Vascular smooth muscle cells(VSMCs) were obtained from rat thoracic aorta, and VSMCs after the fourth passage and aortic rings were divided into control group (cultured in DMEM with 10% fetal bovine serum), high phosphorus group (cultured in DMEM with 10% fetal bovine serum and 10% ß-glycerophosphate) and TRAM-34 group(20 nmol/L TRAM-34 was added into high phosphorus DMEM). Calcium deposition of VSMCs and aortic rings were measured by o-cresolphthalein complexone method.Calcium influx of VSMCs was measured by immunofluorescence probe Fluo-3 AM.The expression of runt-related transcription factor 2(Runx2)was detected by RT-PCR and Western blot for cells and immunohistochemistry for aortic rings.ALP activity was measured by alkaline phosphatase activity detection kit. RESULTS: (1) Compared with control group, calcification was significantly increased in high phosphorus group ((121.67±6.17) mg/g vs. (84.38±8.17) mg/g, P<0.05) and this effect could be attenuated by TRAM-34 ((93.31±11.36) mg/g, P<0.05 vs. high phosphorus group) after 12 days culture. Similar results were found in aortic rings cultured for 12 days-high phosphorus group: (7.17±0.57) mg/g vs. CONTROL: (1.18±0.13) mg/g (P<0.05) and TRAM-34: (4.71±0.42) mg/g, P<0.05 vs. high phosphorus group.(2) Compared with control group, the calcium influx was higher in high phosphorus group (349.22±40.47 vs. 151.67±16.94, P<0.05) and reduced in TRAM-34 group (194.67±22.21, P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days. (3) Both mRNA and protein expressions of Runx2 in high phosphorus groups were higher than in control group (0.630±0.033 vs.0.340±0.058 and 0.865±0.031 vs.0.414±0.011, both P<0.05) and lower in TRAM-34 group (0.399±0.023 and 0.575±0.014, both P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days.Besides, compared with high phosphorus group, the expression of Runx2 was decreased in control group(0.113±0.010 vs.0.067±0.008, P<0.05) and TRAM-34 group (0.069±0.006, P<0.05) after aortic rings were cultured for 4 days. (4) Compared with control group, the activity of ALP was significantly increased in high phosphorus group (96.56±9.84 vs.46.92±4.60, P<0.05) and decreased in TRAM-34 group(70.20±8.41, P<0.05 vs. high phosphorus group) in VSMCs simulated for 12 days. CONCLUSION: KCa3.1 blocker TRAM-34 can inhibit ß-glycerophosphate induced VSMCs and aortic ring calcification through inhibiting calcium influx, downregulating Runx2 expression and attenuating osteogenic differentiation.


Assuntos
Calcinose/patologia , Cálcio/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Canais de Potássio Cálcio-Ativados/antagonistas & inibidores , Pirazóis/farmacologia , Animais , Aorta Torácica/citologia , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Glicerofosfatos/efeitos adversos , Músculo Liso Vascular/citologia , Osteogênese , Ratos , Calcificação Vascular/patologia
10.
Zhonghua Zhong Liu Za Zhi ; 38(6): 476-80, 2016 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-27346408

RESUMO

OBJECTIVE: To investigate the relationship between single nucleotide polymorphism of SET8 gene and the risk of clear cell renal cell carcinoma (CCRCC). METHODS: We selected 140 CCRCC patients and 130 healthy controls in this case-control study.Genotype of single nucleotide polymorphism (rs16917496) at the miR-502 binding site in the 3'UTR of SET8 mRNA in the CCRCC patients and healthy controls was tested and the association between genotype and risk of cancer was assessed. The expression of SET8 was determined by immunohistochemistry and the relationship between expression of SET8 and genotype of rs16917496 was analyzed. RESULTS: In the control group, CC, CT and TT genotypes were found in 30, 32 and 68 persons, respectively, while in the CCRCC patients, CC, CT and TT genotypes were found in 14 , 47 and 79 cases, respectively.The frequencies of rs16917496 CT and TT genotypes in the CCRCC group were significantly higher than those in the control group (P<0.05). Compared with the CC genotype, patients with CT and TT genotypes were more susceptible to develop CCRCC (P<0.05). CT and TT genotypes of rs16917496 at the miR-502 binding site of the SET8 gene were associated with expression of SET8. CONCLUSIONS: Genotype of the SNP rs16917496 at the miR-502 binding site in the 3' untranslated region of the SET8 gene is associated with the expression of SET8 protein. Analysis of genetic polymorphisms in miRNA binding sites may help to identify the subgroups of population susceptible to CCRCC.


Assuntos
Regiões 3' não Traduzidas , Carcinoma de Células Renais/genética , Histona-Lisina N-Metiltransferase/genética , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , Sítios de Ligação , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Fatores de Risco
11.
Scand J Immunol ; 79(5): 292-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24498941

RESUMO

We aimed to construct the DNA vaccine encoding Mycobacterium Tuberculosis (Mtb) dormancy antigen Rv1733c and investigate its immunogenicity in mice. The recombinant plasmid pcDNA-Rv1733c was transfected into P815 cells and its product was detected by indirect immunofluorescence. The mice were immunized once every 2 weeks by intramuscular injection of pcDNA-Rv1733c plasmid for a total of three times. The specific antibodies in the serum of the immunized mice were detected by enzyme-linked immunosorbent assay at the indicted time. Enzyme-linked immunosorbent spot was applied to determine the levels of IFN-γ, IL-2 and IL-4 secreted by splenic lymphocytes. Total cytotoxicity T lymphocyte (CTL) active of the splenic lymphocytes was detected by lactate dehydrogenase assay. Additionally, we analysed the percentages of CD4⁺ and CD8⁺ T cells in splenic lymphocytes using flow cytometry. The specific antibody was detected at 2 weeks after the first immunization, and the antibody titre was increased with time which was reached to 1:1600 at 8 weeks. The stimulation index of spleen lymphocytes and the levels of IFN-γ, IL-2 and IL-4 of pcDNA-Rv1733c-immunized mice were both higher than those of saline-immunized mice (P < 0.05). However, no difference was found in the percentages of CD4⁺ and CD8⁺ T cells and the activity of CTL between the pcDNA-Rv1733c- and saline-immunized mice (P > 0.05). So we got the conclusion that the plasmid pcDNA-Rv1733c DNA could induce specific humoral and cellular immunity in mice. Improving the immune effect of Rv1733c by several strategies, such as choosing appropriate immunization route and adjuvant, would be significant for Rv1733c as new tuberculosis vaccine.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/prevenção & controle , Vacinas de DNA/imunologia , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Linhagem Celular Tumoral , Citocinas/metabolismo , Citotoxicidade Imunológica , Humanos , Imunização Secundária , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/genética , Vacinas contra a Tuberculose/genética , Vacinas de DNA/genética
12.
Nucleic Acids Res ; 19(21): 5991-7, 1991 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-1945883

RESUMO

The transcriptional activator LEU3 of Saccharomyces cerevisiae belongs to a family of lower eukaryotic DNA binding proteins with a well-conserved DNA binding motif known as the Zn(II)2Cys6 binuclear cluster. We have constructed mutations in LEU3 that affect either one of the conserved cysteines (Cys47) or one of several amino acids located within a variable subregion of the DNA binding motif. LEU3 proteins with a mutation at Cys47 were very poor activators which could not be rescued by supplying Zn(II) to the growth medium. Mutations within the variable subregion were generally well-tolerated. Only two of seven mutations in this region generated poor activators, and both could be reactivated by Zn(II) supplements. Three of the other five mutations gave rise to activators that were better than wild type. One of these, His50Cys, exhibited a 1.5 fold increase in in vivo target gene activation and a notable increase in the affinity for target DNA. The properties of the His50Cys mutant are discussed in terms of a variant structure of the DNA binding motif. During the course of this work, evidence was obtained suggesting that only one of the two LEU3 protein-DNA complexes routinely seen actually activates transcription. The other (which may contain an additional protein factor) does not.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas Fúngicas/genética , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Transativadores , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação/genética , Cisteína/genética , Regulação Fúngica da Expressão Gênica/genética , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Plasmídeos/genética , Conformação Proteica , Saccharomyces cerevisiae/efeitos dos fármacos , Ativação Transcricional , Transformação Genética/genética , Zinco/metabolismo , Zinco/farmacologia , beta-Galactosidase/genética
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