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AIM:To investigate the mechanism of the radiosensitizing effect of maximum non-cytotoxic doses of tetrandrine (Tet) on nasopharyngeal carcinoma cell lines CNE1 and CNE2.METHODS:The cells were treated with maximum non-cytotoxic doses of Tet (for CNE1 cells at 1.5 μmol/L and for CNE2 cells at 1.8 μmol/L),irradiation at 4 Gy,or combination of irradiation and maximum non-cytotoxic doses of Tet.The cell cycle distribution was analyzed by flow cytometry.The protein levels of γ-H2AX,cleaved caspase-3,p-CDC25C,CDK1,p-CDK1,cyclin B1,ERK and p-ERK were determined by Western blot.RESULTS:The expression of γ-H2AX was increased in CNE1 cells and CNE2 cells after combined treatment with irradiation and maximum non-cytotoxic doses of Tet.The percentages of CNE1 cells and CNE2 cells at G2/M phase in irradiation group were (18.09 ±0.42)％ and (18.48 ± 1.32)％,respectively,which were decreased to (15.88 ± 1.04) ％ and (13.80 ± 0.82) ％ in combined treatment group,respectively (P ＜ 0.05).Combined treatment enhanced the increase in the protein level of cleaved caspase-3 caused by irradiation.The protein levels of pCDC25C and p-CDK1 were increased in a dose-dependent manner by Tet treatment (P ＜ 0.05),while the expression of CDK1 showed no difference among different doses of Tet treatments.The protein levels of p-CDC25C,p-CDK1 and CDK1 showed no difference after the treatment with maximum non-cytotoxic doses of Tet.The combined treatment with irradiation and the maximum non-cytotoxic doses of Tet decreased the protein levels of p-CDC25C and p-CDK1 (P ＜0.05),increased the expression of cyclin B1,and had no influence on the expression of CDK1 （ P ＜0.05).The combined treatment resulted in an increase in the protein level of p-ERK1 (P ＜ 0.05).CONCLUSION:The maximum non-cytotoxic doses of Tet enhance the DNA damage and apoptosis in CNE1 cells and CNE2 cells caused by irradiation,and the mechanism might be associated with ending of G2/M arrest via activation of ERK/CDC25C/CDK1/cyclin B1 pathways.
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Aim To investigate the effect of hesperidin on human lung cancer cell A549 and the possible mechanism.Methods The cell apoptosis and necrosis of A549 treated with hesperidin were measured by the Hoechst 33342/PI fluorescent dye based on microfluidic chip technology.Cell cycle and apoptosis rate were evaluated by flow cytometry(FCM).The expressions of the related genes were detected through the real-time fluorescent quantitative PCR technology(RT-PCR) including VEGF, PI3K and PTEN.The protein expressions of Bcl-2, Cyclin B1, PI3K, Akt and PTEN were detected by Western blot after hesperidin intervention.Results The proliferation of A549 cells was significantly inhibited by hesperidin in a dose-dependent manner.FCM results showed that hesperidin could not only influence the G0/G1 phase and S phase, but also promote the apoptosis of lung cancer cells.Meanwhile, the apoptosis and necrosis rate was increased from(6.7±0.6)% to(27.9±1.1)% compared with that of control group(P<0.05).From the level of molecular, the gene expressions of VEGF and PI3K were decreased, while the PTEN was increased after hesperidin stimulation.Western blot results showed that the expression of protein Bcl-2, Cyclin B1 and Akt were decreased, which all showed close relationship with cell apoptosis, cell cycle and PI3K-Akt signaling pathway.The expression of PI3K was increased, but the change of PTEN was not statistically significant compared with that of control group.Conclusion Hesperidin induces lung cancer cell apoptosis through PI3K-Akt signaling pathway, which blocks cancer cell division and destroys the balance of related protein expression.
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AIM:To investigate the mechanism of the radiosensitizing effect of maximum non-cytotoxic doses of tetrandrine (Tet) on nasopharyngeal carcinoma cell lines CNE1 and CNE2.METHODS:The cells were treated with maximum non-cytotoxic doses of Tet (for CNE1 cells at 1.5 μmol/L and for CNE2 cells at 1.8 μmol/L),irradiation at 4 Gy,or combination of irradiation and maximum non-cytotoxic doses of Tet.The cell cycle distribution was analyzed by flow cytometry.The protein levels of γ-H2AX,cleaved caspase-3,p-CDC25C,CDK1,p-CDK1,cyclin B1,ERK and p-ERK were determined by Western blot.RESULTS:The expression of γ-H2AX was increased in CNE1 cells and CNE2 cells after combined treatment with irradiation and maximum non-cytotoxic doses of Tet.The percentages of CNE1 cells and CNE2 cells at G2/M phase in irradiation group were (18.09 ±0.42)％ and (18.48 ± 1.32)％,respectively,which were decreased to (15.88 ± 1.04) ％ and (13.80 ± 0.82) ％ in combined treatment group,respectively (P ＜ 0.05).Combined treatment enhanced the increase in the protein level of cleaved caspase-3 caused by irradiation.The protein levels of pCDC25C and p-CDK1 were increased in a dose-dependent manner by Tet treatment (P ＜ 0.05),while the expression of CDK1 showed no difference among different doses of Tet treatments.The protein levels of p-CDC25C,p-CDK1 and CDK1 showed no difference after the treatment with maximum non-cytotoxic doses of Tet.The combined treatment with irradiation and the maximum non-cytotoxic doses of Tet decreased the protein levels of p-CDC25C and p-CDK1 (P ＜0.05),increased the expression of cyclin B1,and had no influence on the expression of CDK1 （ P ＜0.05).The combined treatment resulted in an increase in the protein level of p-ERK1 (P ＜ 0.05).CONCLUSION:The maximum non-cytotoxic doses of Tet enhance the DNA damage and apoptosis in CNE1 cells and CNE2 cells caused by irradiation,and the mechanism might be associated with ending of G2/M arrest via activation of ERK/CDC25C/CDK1/cyclin B1 pathways.
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Purpose To investigate the expression of polo-like kinase 1 (Plk1) and Cyclin B1, p21WAF1in cervical carcinoma, and to determine the relationship between the expression of the three proteins and tumor clinicopathological features. Methods The expres-sion of Plk1, Cyclin B1 and p21WAF1 was detected in 102 cases of cervical carcinoma, 20 cases of (cervical intraepithelial neoplasia, CIN) , and 20 cases of nomal cervical tissues by the technique of tissue chip and immunohistochemical staining of EliVision. Statistical analyses of the data were performed with SPSS 19. 0 software. Results The positive rates of Plk1 in cervical carcinoma and CIN were 70. 5%, 55. 0%, respectively, which were significantly higher than normal cervical tissues (10%) (P<0. 01);The positive rates of Cyclin B1 in cervical carcinoma and CIN were 52. 9% and 30. 0%, respectively, which were significantly higher than normal cervical tissues (10%)(P <0.01); The positive rates of p21WAF1 in cervical carcinoma and CIN were 23.5% and 10.0%, respectively, which were significantly higher than normal cervical tissues ( 0 ) ( P<0. 01 ) . There were no significant differences between cervical carcinoma and CIN in the positive rates of Plk1, Cyclin B1 and p21WAF1. The expression of Plk1 was associated with the depth of carci-noma invasion (P<0. 05), that of Cyclin B1 was associated with lymph node metastases and the depth of carcinoma invasion (P<0. 05)and that of p21WAF1 in cervical carcinoma was associated with histological grade (P<0. 05). In cervical carcinoma, the expres-sion of Plk1 was positively correlated with Cyclin B1 (rs =0. 297, P=0. 002) and negatively correlated with p21WAF1(rs = -0. 403, P<0. 001). Conclusion The expression of Plk1, Cyclin B1 and p21WAF1 is involved in the occurrence and development of cervical carcinoma, and the former two are also related with prognosis of cervical carcinoma. The combination of the three would provide a new target for clinical treatment.
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Objective: To observe the effect of monocrotaline (MCT) extract from Crotalaria sessiliflora on inducing human pancreatic cancer cell BxPC-3 into polyploid giant cells in vitro. Methods: BxPC-3 cells (1 × 104/mL) were inoculated with MCT (0, 5, 10, and 20 μg/mL) in RPMI-1640 for 72 h, respectively, then the cell morphology was observed by Giemsa staining, and the DNA content was measured by flow cytometry; BxPC-3 cells-induced apoptosis was checked by AnnexinV-FITC/PI double staining using flowcytometry, BxPC-3 polyploid giant cell genome was checked by chromosome spreading assay, and Cyclin B1 expression also was analysed by Western blotting. Results: Giemsa staining and DNA content by flow cytometry showed that MCT induced BxPC-3 cell into polyploid giant cells in vitro. MCT treatment for 72 h appeared 4N, and 8N polyploid giant of BxPC-3 cells, induction of apoptosis, decreased the expression of cyclin B1 in a dose dependent manner. Chromosome analysis demonstrated once again that polyploid giant cell was mainly in 8N. Conclusion: Monocrotaline might exert its antitumor effect by blocking the cell cycle, inducing apoptosis, and down-regulating Cyclin B1 protein.
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Objective To investigate the effect of artesunate on the cell cycle of human multiple myeloma RPMI8226 cells and explore the related molecularmechanisms. Methods RPMI8226 cellswere treated with 0, 25, and 50 pg/mL artesunate. The morphology change of cells was observed under transmission electron microscope, the cell cycle distribution was detected by flow cytometry, and the expression of cyclin B1 and p34cdc2 protein was examined by Western blotting analysis. Results After treated with 50 pg/mL artesunate for 48 h, most RPMI8226 cells showed characteristic morphology of apoptosis. With the increase of artesuate concentration, the proportion of RPMI8226 cells in G0/G1 phase was significantly decreased (P<0. 05) and that of cells in G2/M phase was significantly increased (P<0.05), suggesting that artesunate induced noticeable G2/M arrest. Cyclin B1 level was increased and the p34cdc2 level was decreased with the increase of artesuate concentration. Conclusion Artesunate can induce G2/M arrests in RPMI8226 cells, which may be related to the increasedcyclin B1 expression and decreased p34cdc2 expression.
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Objective To observe the differences of the radio-biological characteristics between the human malignant glioma cell line SHG-44 and its progeny cells SHG-4410 Gy and to probe the underlying mechanism.Methods The SHG-4410 Gy cells were the progeny of SHG cells that had been irradiated with 10 Gy X-rays and then passaged for 15 generations.The radiosensitivity of SHG-44 and SHG-4410 Gy wre measured by clonogenic assay and the multi-target single-hit model was used to fit the survival curve.The cell cycle redistribution and apoptosis were analyzed by flow cytometry assay.Quantitative Real Time-PCR (qRT-PCR) was used to determine the relative levels of cyclin B1 mRNA and miR-21.Stat3 protein levels were detected by Western blot.Results The values of D0,Dq and SF2 of SHG-4410 Gy cells were significantly higher than those of SHG-44 cells.Flow cytometric analysis showed that there was less G2/M phase arrest in SHG-4410 Gy (F =22.21,P ＜ 0.05).Radiation-induced early apoptotic population was increased from (17.60 ± 0.26) ％ to (28.00 ± 0.36) ％ for SHG-44 cells,but increased from only (4.20 ± 0.30)％ to (5.17 ± 0.65)％ for SHG-4410 Gy.miR-21 in SHG-4410 Gy cells were increased by 1.44 fold of SHG-44 cells,which was associated with the increase of Stat3 protein expression.Conclusions Radioresistance is observed in the progeny of human malignant glioma cell line SHG-44 which had been irradiated with 10 Gy X-rays.The underlying mechanisms may be relative to the upregulation of cyclin B1 that acts as a key downstream gene in the signaling pathway of G2/M phase transition.In addition,the upregulation of miR-21 may be involved in the apoptosis of SHG-4410 Gy cells.
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PURPOSE: The molecular mechanisms that are responsible for the initiation and progression of breast cancers are largely unknown. This study was to analyze the cyclin B1, cdc2, p53 and p16 tumor suppressor genes in human breast cancer. MATERIALS AND METHODS: To investigate the role of cyclin B1, cdc2, p53 and p16 in the pathogenesis and progression of breast carcinomas, 98 cases of breast cancers were examined by immunohistochemical method. The correlations of cyclin B1, cdc2, p53 and p16 expression with various clinico-pathologic findings were analysed. RESULTS: In the normal breast tissues, cyclin B1, cdc2 and p16 were weakly expressed, while p53 was not expressed. On the other hand, cyclin B1, cdc2, p53 and p16 were overexpressed in breast cancer, showing correlation between the expression of cyclin B1 and cdc2 and breast cancers (p=0.00). The overexpressions of cdc2 and p16 were correlated with an infiltrative tumor border pattern and this was statistically significant (p<0.05). In addition, the overexpression of cdc2 was correlated with histologic high grade carcinomas (p=0.00). CONCLUSION: Cyclin B1 and cdc2 appeared to be involved in the genesis or progression of breast cancers. In addition, the overexpressions of p16 and p53 may play important roles in more aggressive tumor and the overexpression of cdc2 is associated with progression of tumor to a higher grade of breast carcinomas. The deranged overexpressions of cyclin B1, cdc2, p16 and p53 may play an important role in human breast carcinogenesis.
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Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/genética , Ciclina B/genética , Ciclina B1/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Inmunohistoquímica , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Objective To explore the role of Cyclin B1 and Cyclin D1 on Barrett esophagus,Barrett's esophagus mixed with atypical dysplasia and esophageal adenocarcinoma.Methods Cyclin B1 and Cyclin D1 were examined with immunohistochemistry.76 esophageal tissues of patients werB collected,including severe reflux esophagitis(RE,25 cases),Barrett esophagus(BE,35 cases),Barrett esophagus mixed with atypical dysplasia(DY,8 cases),esophageal carcinoma(CA,8 cases).Ten cases with normal esophageal mucosa were examined as the control. Results Cyclin B1 and Cyclin D1 were high expression in the specimens of the BE,DY and CA groups and very low expression in the control and RE group.Statistieal difference Was showed(P<0.01).Expression of Cyclin D1 was increasing gradually from the tissues of intestinal metaplasia,atypical dysplasia to adenocarcinoma(50.04 vs 67.94 vs 74.31).There Was significant difference among these three groups(P<0.01).Conclusion Cyclin B1 and Cyclin D1 as markers of tumour development could evaluate the risk from Barrett esophagus to adenocarcinoma.Perhaps it is the earlv event in the development of esophageal carcinoma.
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Objective: To study the expression of p34cdc2 and cyclin B1 in human cervical carcinoma, and the relationship between their expression and clinicopathologyical features of cervical cancer. Methods: A quantitative real-time reverse transcription polymerase chain reaction and Western blotting assay were used to analyze the expression levels of p34cdc2 and cyclin B1 mRNA and protein, respectively, in fresh invasive cervical cancer (n = 62) and control cervical tissues (n = 15). Results: The expression levels of p34cdc2 and cyclin B1 mRNA and protein were significantly higher in cancer tissues than those in control cervical tissues (P = 0.004, P = 0.013; P = 0.016, P = 0.029), and mainly displayed overexpression. Significant positive correlation was found between the expression of p34cdc2 and cyclin B1 mRNA (r = 0.527, P = 0.001) and protein (r = 0.432, P = 0.022) in cervical cancer tissues. A statistical significance was found between the expressions of p34cdc2/cyclin B1 mRNA and lymphatic metastasis in cervical cancer (P = 0.038, P = 0.001). No statistically significant association was found between the age, histological types, the differentiation degree, clinical stages and expression of p34cdc2/cyclin B1 (P > 0.05). Conclusion: p34cdc2 and cyclin B1 are important molecules in regulation of cervical carcinogenesis. Over-expression of p34cdc2/cyclin B1 stimulates cervical cancer cells to overcome G2/ M checkpoint and enter M phase in cell cycle. The high-expression of p34cdc2/ cyclin B1 might become a novel biomarker for studying the mechanism underlying the tumorigenesis and lymphatic metastasis of cervical cancer.
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PURPOSE: Cell cycle progression is regulated by interactions of specific cyclins and cyclin dependent kinases (CDKs) at the G1-S and G2-M checkpoints and cell cycle deregulation plays a major role in carcinogenesis of human cancers. PATIENTS AND METHODS: To investigate the role of cell cycle regulators in the pathogenesis and progression of human gastric cancers, 23 cases of gastric carcinomas were examined for the expression of cyclin B1, p34cdc2, p27(Kip1) and p53 by immunohistochemical methods, and gene expression was correlated with various clinicopathologic findings. RESULTS: Out of 23 cases studied, cyclin B1 was diffusely expressed in 20 cases (87.0%), p34cdc2 in 14 cases (60.9%) and p53 in 12 cases (52.2%), whereas in normal gastric tissues, cyclin B1 and p34cdc2 were weakly expressed and p53 was not expressed. In contrast, p27(Kip1) was expressed in only 8.7% of gastric carcinomas compared with 78.3% of normal gastric tissues. There was correlation between the expression of cyclin B1 and expression of p34cdc2 (p=0.002), between the expression of cyclin B1 and loss of p27(Kip1) (p=0.025), and between the expression of p34cdc2 and loss of p27(Kip1) (p=0.065). In addition, expression of cyclin B1 was correlated with regional lymph node metastasis (p=0.032). CONCLUSION: Our results indicate that cyclin B1 and p34cdc2 are involved in the genesis or progression of gastric cancers. Furthermore, overexpression of cyclin B1 may play an important role in lymph node metastatic potential of gastric cancer. Thus, abnormal expression of cyclin B1 and CDKs, overexpression of p53 and loss of p27(Kip1) expression may play important roles in human gastric carcinogenesis.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína Quinasa CDC2/metabolismo , Ciclina B/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Pronóstico , Neoplasias Gástricas/diagnóstico , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
0.05).The mRNA expression of Cyclin B1 of IMRT group was significantly higher than that of ART group at each dose point(P
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OBJECTIVE: Cyclin is a family of regulatory proteins that play a key role in controlling the cell cycle. Abnormalities of cell cycle regulators, including cyclins and cyclin dependent kinases (CDKs), have been reported in malignant tumors. This study was undertaken to quantitatively detect cyclin B1 and D1 in cervical cancer. METHODS: A quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to analyze the expression of cyclin B1, D1 mRNA and proteins, respectively, in fresh invasive cervical cancer (n=41) and normal cervix tissue (n=10). RESULTS: There was significantly greater cyclin B1 expression in invasive cervical cancer than in normal cervix tissue (p=0.019). However, cyclin D1 expression was not significantly different (p=0.967). A Western blot analysis yielded similar results. CONCLUSION: Our results were consistent with the concept that up-regulation of cyclin B1 expression occurred in cervical cancer and an aberrant expression of cyclin B1 might play an important role in cervical carcinogenesis.
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Femenino , Humanos , Western Blotting , Carcinogénesis , Ciclo Celular , Cuello del Útero , Ciclina B1 , Ciclina D1 , Ciclina I , Quinasas Ciclina-Dependientes , Ciclinas , ARN Mensajero , Regulación hacia Arriba , Neoplasias del Cuello UterinoRESUMEN
OBJECTIVE: The objective of this study was to evaluate the relationship between the expression of cyclin B1, D1 and the various prognostic factors in ovarian carcinoma. METHODS: In this study, fresh ovarian tissue samples were obtained from 41 patients treated surgically at our institute from March of 2002 to February of 2005. These included 36 ovarian carcinomas and 5 normal ovarian tissues that were served as the control. Quantitative real-time RT-PCR and Western blot analysis were used in detecting the expression of mRNA and protein of cyclin B1, D1, respectively. RESULTS: The mean 2(-delta delta CT) values of cyclin B1 and D1 mRNA in ovarian carcinoma tissues obtained through quantitative real-time RT-PCR were 5.83+/-12.03, 17.60+/-22.20, respectively, and the mean values in the control were 0.55+/-0.35, 0.50+/-0.26, respectively. The results showed difference in the expression, but were not statistically significant (p=0.67, 0.07, respectively). If the mean densitometer value of cyclin B1 and D1 protein in the control obtained by Western blot analysis was 1, the mean values in ovarian carcinoma tissues were higher, but were not statistically significant (1.30+/-0.73, 1.81+/-1.28, respectively) (p=0.76, 0.06, respectively). The expression of cyclin B1, D1 and various prognostic factors was not statistically related. CONCLUSION: Our results showed that the expression of cyclin B1 and D1 in ovarian carcinoma tissues was higher than in the normal control. This suggested that cyclin B1, D1 and the tumorigenesis and the degree of malignancy was closely related. But the expression of cyclin B1, D1 and various prognostic factors was not statistically related. Further studies based on the correlation between cyclin and response to treatment or survival rate are needed to support cyclin as a prognostic factor of ovarian carcinoma.
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Humanos , Western Blotting , Carcinogénesis , Ciclina A , Ciclina B1 , Ciclina D1 , Ciclinas , ARN Mensajero , Tasa de SupervivenciaRESUMEN
BACKGROUND: Oncogene expression in Paget's disease of the breast is not well known. To characterize invasive ductal carcinoma associated with Paget's disease, we studied expression of anaphase promoting complex (APC) with its regulatory proteins. METHODS: Immunohistochemical stainings were done with 10 cases of invasive ductal carcinoma associated with Paget's disease for APC, pituitary tumor transforming gene (PTTG), cyclin B1, p53, cyclin D1, and c-erbB-2. The expressions of these markers in Paget's disease were compared with those in the associated with carcinoma. RESULTS: APC, PTTG, cyclin B1, and c-erbB-2 were positive in all of the cases with both Paget's disease and underlying carcinoma. p53 was expressed in Paget's disease of 6 cases (60%) and in carcinoma of 7 cases (70%). Cyclin D1 was positive in Paget's disease of 8 cases (80%) and in carcinoma of 9 cases (90%). CONCLUSIONS: Breast carcinomas with Paget's disease seem to be distinguished by the high expression of APC, cyclin B1, PTTG, c-erbB2, and cyclin D1 in contrast to breast cancers without Paget's disease. Furthermore, the similar expression patterns of APC and APC regulatory proteins in both Paget's disease and underlying breast cancer support the epidermotropic theory as its pathogenetic mechanism.
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Anafase , Ciclosoma-Complejo Promotor de la Anafase , Mama , Neoplasias de la Mama , Carcinoma Ductal , Ciclina B1 , Ciclina D1 , Oncogenes , Enfermedad de Paget Mamaria , Neoplasias HipofisariasRESUMEN
PURPOSE: Disturbance in normal cell cycles by cell cycle control factors is an important process of cancer carcinogenesis. The aims of this dissertation were identify the influence of cyclin B1 and D1 on the growth and expression of gastric cancer and their effects on the prognosis. METHOD: The subjects were 128 patients selected from those who underwent gastric surgery for their gastric cancer between January 1995 and December 1998. Immunohistochemical staining was conducted for cyclin B1 and D1 using paraffin embedded tissues, followed by analysis of their protein expressions, possible prognostic factors and survival rate. RESULTS: Cyclin B1 expression was founded in 48 of the 128 patients (37.5%), and that of cyclin D1 in 96 (75%). Both cyclin B1 and D1 showed no statistical significance with T-stage, location of tumors or histologic types. However, for the case of any significance with lymph node metastasis, the higher the N-stage, the greater was the expression of cyclin B1 (P=0.014). For the case of any significance with life term, the Kaplan-Meier method showed the greater the expression of cyclin B1, the shorter the life term (P=0.042). CONCLUSION: An association was indicated between cyclin B1 and lymph node metastasis in gastric cancer, but has no relation with the T-stage, histologic type or location of tumors. Cyclin D1 shows no association with lymph node metastasis, T-stage, histologic type or location of tumors. However, cyclin B1 showed a significant association with the survival rate.
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Humanos , Carcinogénesis , Ciclo Celular , Puntos de Control del Ciclo Celular , Ciclina B1 , Ciclina D1 , Ciclinas , Ganglios Linfáticos , Metástasis de la Neoplasia , Parafina , Pronóstico , Neoplasias Gástricas , Tasa de SupervivenciaRESUMEN
Objective:To investigate the mechanisms of genistein (GEN) affecting the chemosen- sitivity of human breast cancer cell line MDA-MB-453 to paclitaxel (PTX) in vitro. Method:HER2/neu- overexpressing breast cancer cells MDA-MB-453 were treated by GEN, PTX alone or combined in vitro. Cell cycle was measured by flow cytometry. The expression of HER2/neu protein was observed by immunocytochemistry and. Akt, p-Akt, cyclin B1 and CDK1 protein by Western blot. Results:Cell cycle of MDA-MB-453 cells was blocked at G1/S after treatment of GEN, while at G2/M after treatment with PTX alone. Both GEN and PTX did not change the expression of HER2/neu, total Akt and CDK1 in MDA-MB-453 cells, but GEN significantly decreased p-Akt and cyclin B1 level, and PTX obviously increased cyclinB1 level. GEN antagonized the effects of PTX on level of cyclin B1 protein and blockage of G2/M in MDA-MB-453 cells after treatment with GEN and PTX in combination. Conclusion:The antagonism effects of GEN on the increase of cyclin B1 and blockage of G2/M induced by PTX may be one of the mechanisms of GEN affecting the chemosensitivity of MDA-MB-453 cells to PYX.
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Objective:To study the expression of livin and its correlation with cyclin B1 in breast cancer.Methods:The expressions of livin and cyclin B1 in breast cancer paraffin embedded specimens were detected by immunohistochemical technique.The relationship between livin and cyclin B1 and clinicopathological characteristics was analyzed.Results:The rates of positive expression of livin and cyclin B1 protein in breast cancer were 77.2%and 68.4%,respectively,and the correlation was psitive(?=0.701,P
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To investigate the role of cyclin B1 and cdc2 in the pathogenesis and progression of malignant lymphoma, 68 cases of nodal non-Hodgkin's lymphoma were examined about the expression of cyclin B1 and cdc2 along with p53 and Ki-67 by immunohistochemical method. The correlation of their expression with various clinicopathologic findings was also analyzed. Cyclin B1 and cdc2 were diffusely expressed in 39 cases (57.4%) and 54 cases (79.4%) out of 68 cases studied, respectively. The mean labeling indices of cyclin B1 and cdc2 in malignant lymphoma were 31.9% and 68.0%, respectively. In normal lymphoid tissues, cyclin B1 and cdc2 were expressed predominantly in the germinal center with mean labeling indices of 13.9% and 28.3%, respectively. The correlation between the expression of cyclin B1 and cdc2 was noted (p=0.013). The expression of Ki-67 was correlated with that of cyclin B1 (p=0.023) and marginally correlated with that of cdc2 (p=0.056). The expression of cdc2 and p53 in complete remission group to chemotherapy was lower than that of progressive disease group (p=0.047, p=0.049). In multivariate analysis, the clinical stage alone showed significance on overall survival (p=0.049). In conclusion, cyclin B1 and cdc2 appeared to be involved in the genesis or progression of malignant lymphoma and cdc2 can be a useful marker for response to chemotherapy.
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Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína Quinasa CDC2/biosíntesis , Ciclina B/biosíntesis , Ciclina B1 , Inmunohistoquímica , Antígeno Ki-67/biosíntesis , Ganglios Linfáticos/metabolismo , Linfoma no Hodgkin/metabolismo , Tonsila Palatina/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
PURPOSE: It has been demonstrated that PLC-gamma1 is overexpressed in many tumor cells, and that overexpression of Phospholipase C (PLC)-gamma1 is associated with tumor progression. In order to understand the effect of the PLC-gamma1 overexpression on the regulation of cell cycle regulators following DNA damage, we analyzed the expression level of PCNA, cyclin B1, and p21 Waf1 after ultraviolet C (UVC) irradiation in PLC-gamma1-transfected PC12 cells. MATERIALS AND METHODS: PC12 and 3Y1 cells, transfected with empty vector or rat PLC-gamma1 cDNA, were used for this study. Following UVC irradiation, cell cycle progression was analyzed by flow cytometry and protein expression was detected by Western blotting. RESULTS: Waf1 protein was markedly down-regulated, whereas PCNA and cyclin B1 was up-regulated in PLC-gamma1 overexpressed-cells as compared to the vector transfected-cells. When the cells were irradiated with UVC, PCNA was slightly increased within 3-hours of the UV irradiation and then was markedly decreased in Vector/ PC12 cells, while it remained high until 37 hour after UVC in PLC-gamma1/PC12 cells. In contrast, cyclin B1 was gradually decreased following UVC irradiation in both cells. CONCLUSION: The overexpression of PLC-gamma1 affects the expression level of PCNA after UVC irradiation. We proposed that the overexpression of PLC-gamma1 may contribute to the UV-induced genomic instability by up-regulating the expression of PCNA.