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1.
AIM: The aim of the present study was to detect the methylation status of multiple genes (Syk, CDH1 and TIMP-3) in colorectal cancer (CRC) tissues, to investigate the roles in the pathogenesis of CRC, to investigate whether methylation of multiple genes was associated with recurrence and metastasis of CRC, and to evaluate its ability to predict the prognosis of CRC. METHODS: Nested methylation-specific PCR (n-MSP) were used to detect methylation status of spleen tyrosine kinase (Syk) from 120 CRC tissues and the methylation status of CDH1 and tissue inhibitor of metalloproteinase-3 (TIMP-3) from 100 CRC tissues. RESULTS: We found that methylation in one or more genes, co-methylation in two genes and three genes were detected in 74%, 21%, and 8% of CRC tissues. No significant correlation between three genes co-methylation and lymph node metastasis (2=0.725,P>0.05) was observed. The methylation of CDH1 gene, but not Syk or TIMP-3 gene, was significantly related with liver and lung metastasis of CRC (2=6.938,P<0.01). The methylation of Syk or TIMP-3, and co-methylation of CDH1 and TIMP-3 were risk factors in the prognosis of colorectal cancer after surgical treatment, and three genes co-methylation was not a risk factor. CONCLUSION: Our results indicate that methylation of multiple genes exists in CRC tissues. The methylation of multiple genes is not a necessary factor in the pathogenesis, metastasis and recurrence of CRC, and also it is not a necessary prognostic factor in CRC.  相似文献   

2.
AIM: To investigate the expression and promoter methylation of tazarotene-induced gene-1 (TIG1) in esophageal squamous-cell carcinoma (ESCC) tissues. METHODS: The methods of methylation-specific PCR and real-time fluorescence quantitative PCR were applied to examine the methylation and mRNA expression of TIG1, respectively, in 43 cases of ESCC tissues, 20 cases of paracancerous tissues and 15 cases of normal tissues. RESULTS: The frequency of promoter methylation of TIG1 gene in ESCC tissues was 25.6% (11/43), which was significantly higher than that in the paracancerous tissues (5.0%, 1/20) and normal tissues (0/20). The hypermethylation of TIG1 gene in these tissues had no correlation with sex, age and clinical stage of the patients. However, it was correlated with the pathological stage (P<0.01) and lymph node metastasis (P<0.05). The mRNA expression of TIG1 in ESCC tissues was significantly lower than that in paracancerous tissues (P<0.05) and normal tissues (P<0.01). However, the expression level of TIG1 mRNA in methylated tissues was significantly lower than that in unmethylated tissues (P<0.01). CONCLUSION: Promoter methylation may be an important mechanism of TIG1 gene inactivation in ESCC, which was related to lymph node metastasis and TNM stage of esophageal carcinoma.  相似文献   

3.
AIM: To detect the levels of tissue inhibitor of metalloproteinase-3 (TIMP-3) in both plasma and the tissue of hepatocellular carcinoma (HCC), and to elucidate their association with clinical features.METHODS: Plasma protein levels of TIMP-3 in 56 HCC patients and 30 cases of controls were detected by ELISA.The mRNA and protein levels of TIMP-3 in 30 HCC tissue samples with their portal vein tumor embolus and lymphatic metastasis tissues, and in normal liver tissues from 30 controls were detected by RT-PCR and Western blotting.The relationship between mRNA and protein levels and their clinic-pathological data were analyzed.RESULTS: The plasma TIMP-3 protein levels in the extrahepatic metastasis patients were obviously lower than those in the non-extrahepatic metastasis patients (P<0.05).The mRNA levels of TIMP-3 in normal liver, carcinoma in situ, portal vein tumor embolus and lymphatic metastasis tissues were 0.78±0.09, 0.52±0.09, 0.42±0.07 and 0.40±0.08, respectively, with significant differences among them (P<0.05).The protein levels of TIMP-3 in these 4 kinds of tissues were 115.08±8.60, 77.04±8.83, 64.43±3.80 and 62.80±3.73, respectively, also with significant differences among them (P<0.05).CONCLUSION: The expression of TIMP-3 significantly decreases in the carcinoma in situ tissues of HCC patients, and decreases more obviously in the portal vein tumor embolus and lymphatic metastasis tissues, indicating that low expression of TIMP-3 may play an important role in HCC invasiveness and metastasis.  相似文献   

4.
AIM:This study was to investigate the expression and significance of Bmi-1 in colorectal carcinoma (CRC), and to explore the effect of Bmi-1 on Ki67 expression in human CRC.METHODS:The samples from sixty CRC, thirty adenomas and twenty normal colorectal mucosal tissues were used in this study.The expression of Bmi-1 protein was detected by immunohistochemistry.The clinicopathological features and survival rate of patients were also analyzed.RESULTS:The overexpression of Bmi-1 was respectively 25.0%, 6.7%and 0% in CRC and adenomas as well as normal colorectal mucosal tissues.The results showed that the expression of Bim-1 was significantly higher in CRC, compared with that in adenomas and normal colorectal mucosal tissues (P<0.05).The overexpression of Bmi-1 protein in CRC was obviously associated with distant metastasis and TNM stage (P<0.05), but not with gender, age, tumor size, tumor site, histological type, differentiation degree and lymph node metastasis (P>0.05).Kaplan-Meier survival analysis showed that the overexpression of Bmi-1 reduced significantly survival of CRC patients (P<0.05).No statistical relation between expression of Bmi-1 and Ki67 in CRC was observed.CONCLUSION:The overexpression of Bmi-1 protein is significantly correlated with tumorigenesis, metastasis and prognosis of CRC.Bmi-1 might be regarded as a parameter in evaluating prognosis of CRC.  相似文献   

5.
AIM: To elucidate the correlation between the expression of aldehyde dehydrogenase 1 (ALDH1)/ATP-binding cassette subfaminly G member 2 (ABCG2) and microvessel density (MVD) in epithelial ovarian cancer (EOC).METHODS: In 198 specimens of EOC and 60 specimens of ovarian benign epithelial tumor tissues, the protein expression of ALDH1/ABCG2 and CD105 (microvessel marker) was detected by immunohistochemical staining.RESULTS: The positive rates of ALDH1 and ABCG2 in the EOC were 64.1% and 61.6%, respectively, while the positive rates in benign epithelial tumor tissues were 8.3% and 6.7%, respectively, and there were significant differences between them (P<0.05). In EOC and benign epithelial tumor tissues, the MVD were 22.6±9.7 and 5.03±3.35, respectively, and the difference was also significant (P<0.05). The expression of ALDH1 and ABCG2 in EOC was significantly related to differentiation, FIGO stage,and abdominal organ and lymph node metastasis (P<0.05). MVD had correlation with differentiation, FIGO stage, ascite, and abdominal organ and lymph node metastasis (P<0.05). MVD had positive correlation with the expression of ALDH1 and ABCG2 (P<0.01). There was also a positive correlation between the expression of ALDH1 and ABCG2 (P<0.01). Over-expression of ALDH1/ABCG2 and MVD≥23 were related to the poor prognosis. The survival rates in ALDH1/ABCG2 positive and MVD≥23 groups were significantly lower than those in ALDH1/ABCG2 negative and MVD<23 groups (P<0.05). The FIGO stage, the expression of ALDH1/ABCG2 and MVD were indepen-dent prognosis factors of EOC (P<0.05).CONCLUSION: The results suggest that the expression of ALDH1/ABCG2 and MVD in EOC are related to differentiation, lymph node metastasis, clinical stage and prognosis. Combined detection of these indexes may play an important role in predicting the progression and prognosis of EOC.  相似文献   

6.
AIM:To examine COX-2 expression in esophageal carcinoma, and to study relationships between COX-2 expression and clinicopathological features and prognosis of esophageal carcinoma patients. METHODS:89 paraffin - embedded tissue samples from patients with esophageal carcinoma were collected, its clinicopathological features such as tumour differentiation, depth of invasion, length and site of the tumor, regional lymph node metastases, distant metastasis were recorded. Survival time of 81 cases were also recorded. By SP immunohistochemistry method, the expression of COX-2 in tumor samples was examined. RESULTS:COX-2 expression in esophageal carcinoma was markedly higher than that in nomal esophagus, the expression was higher in less differentiated and deeper invaded cases (P<0.05), but it had no correlations with other clinicopathological features such as age,sex, length and site of the tumor, regional lymph node metastases, and distant metastasis (P>0.05). Cases of esophageal carcinoma with lower COX-2 expression had longer survival time than those with higher COX-2 expression (P<0.01). CONCLUSIONS:COX-2 expression is higher in esophageal carcinoma than normal esophagus. COX-2 expression of esophageal carcinoma is higher in less differentiated and deeper invaded cases, but it has no correlation with age, sex, length and site of the tumor, regional lymph node metastases, and distant metastasis. Patients with lower COX-2 expression have longer survival time than those with higher COX-2 expression.  相似文献   

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AIM: To investigate the expression and clinical significance of bone morphogenetic protein 3 (BMP3) in hilar cholangiocarcinoma tissues.METHODS: Thirty cases of hilar cholangiocarcinoma specimens were collected. The expression of BMP3 at mRNA and protein levels in the tumor tissues and paracancerous tissues was detected by real-time PCR and Western blot. The hilar cholangiocarcinoma paraffin-embedded specimens (n=103) were collected. The protein expression of BMP3 was determined by immunohistochemical method, and the relationship of BMP3 protein expression with clinical pathological characteristics was evaluated.RESULTS: In the 30 patients with hilar cholangiocarcinoma, the expressions of BMP3 protein and mRNA in 22 cases of tumor tissues were significantly decreased compared with the adjacent normal tissues. The results of immunohistochemistry showed that 87 cases were negative and 16 cases were weakly positive in all 103 cases of hilar cholangiocarcinoma. The expression of BMP3 protein was associated with the tumor TNM staging, lymph node metastasis and tumor differentiation (P<0.05).CONCLUSION: BMP3 gene might be inhibited in human hilar cholangiocarcinoma. The down-regulation of BMP3 gene might be associated with the carcinogenesis and development of hilar cholangiocarcinoma.  相似文献   

9.
AIM: To investigate the relationship between the expression of MMP-2, TIMP-2 and VEGF-C in hepatocellular carcinoma (HCC) with or without lymph node metastasis. METHODS: The expression of MMP-2, TIMP-2 and VEGF-C in 44 cases of HCC were examined using immunohistochemistry methods (SP).RESULTS: The positive expression of MMP-2, TIMP-2 and VEGF-C was associated with lymph node metastasis of HCC (P<0.05). CONCLUSIONS: There was a significant correlation between the high-expression of MMP-2 and VEGF-C, and the low-expression of TIMP-2 in lymph node metastasis of HCC. VEGF-C is an important factor promoting lymph node metastasis of HCC. The expression of MMP-2, TIMP-2 and VEGF-C may have important value in determining lymph node metastasis and prognosis of HCC.  相似文献   

10.
AIM: To analyze the relationship between Tpl-2 (tumor progression locus 2)expression and clinicopathological parameters of colorectal carcinoma by investigating the expression of Tpl-2 in adjacent normal mucosa, colorectal adenomas and colorectal carcinoma. METHODS: Tpl-2 expression in normal mucosa, adenoma and carcinoma was examined and compared in a set of tissue microarrays by immunohistochemistry. The potential relationship between Tpl-2 expression and clinicopathological features was analyzed. RESULTS: The expression of Tpl-2 in carcinoma was significantly increased compared to the adenoma and normal mucosa (P<0.01). No significant difference was detected between the adenoma and normal mucosa (P>0.05). Meanwhile, the correlation between Tpl-2 expression and lymph node metastasis (N stage) and TNM stage (P<0.05) was observed. However, the correlation between the Tpl-2 expression and clinicopathological features of colorectal cancer including sex, age, body mass index (BMI), tumor size, histological differentiation, invasive depth (T stage),distant metastasis(M stage) and K-ras mutation (P>0.05) was not found. CONCLUSION: Tpl-2 has a relevance to the development of colorectal cancer as a promotive factor in the colorectal carcinogenesis.  相似文献   

11.
AIM: To study the expression and clinical significance of T-cell immunoglobulin and ITIM domain (TIGIT) in colorectal cancer. METHODS: The patients with colorectal cancer (n=80) from January 2016 to June 2018 were selected. The expression of TIGIT and CD155 in the colorectal cancer tissues and adjacent normal tissues were detected by immunohistochemical staining method. The expression of TIGIT and CD155 was also determined by Western blot and ELISA. RESULTS: The positive expression rates of TIGIT and CD155 were 78.8% (63/80) and 83.8% (67/80) in the colorectal cancer tissues, significantly higher than that in the paracancerous tissues of 8.8% (7/80) and 18.8% (15/80), respectively (P<0.05). There was a positive correlation between TIGIT and CD155 expression (r=0.867, P<0.01). The expression levels of TIGIT and CD155 were increased as the stage evolved. The positive rates of TIGIT and CD155 in the colorectal cancer tissues were correlated with the degree of differentiation, pathological stage and lymph node metastasis (P<0.05). CONCLUSION: TIGIT and CD155 are correlated with the occurrence and development of colorectal cancer, and can be used as one of the prognostic indicators of colorectal cancer.  相似文献   

12.
AIM:To investigate the expression of KDM5B gene in breast cancer tissues and its relationship with clinical data and prognosis of the patients. METHODS:Data sets of breast cancer were collected from The Cancer Genome Atlas (TCGA) database, and KDM5B mRNA expression profiles were downloaded. The mRNA expression of KDM5B in breast cancer tissues and adjacent tissues was detected by real-time PCR. The cases were divided into high expression group and low expression group according to the median expression of KDM5B, and the relationship with clinical data and case characteristics were analyzed. The relationship between KDM5B and prognosis of breast cancer patients was analyzed by Kaplan-Meier plotter. RESULTS:The expression of KDM5B in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.01). In TCGA breast cancer data, the expression of KDM5B was significantly correlated with human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), age, histopathological type and lymph node metastasis (P<0.01), but not with progesterone receptor (PR), menopause and distant metastasis. The expression of KDM5B was significantly correlated with HER2, age and lymph node metastasis, but not with ER, PR, menopause, pathological type and distant metastasis. The higher the expression of KDM5B, the shorter the total survival time and the disease-free survival time of breast cancer patients. CONCLUSION:KDM5B is over-expressed in breast cancer tissues and correlated with prognosis of the patients. KDM5B expression is significantly correlated with HER2, age and lymph node metastasis. KDM5B may play an important role in the development of breast cancer.  相似文献   

13.
AIM: To investigate the expression and clinical significance of PAK4 in the cell lines and tissues of non-small cell lung cancer (NSCLC). METHODS: PAK4 expression in human bronchial epithelial (HBE) cells, NSCLC cell lines, NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR and Western blot. Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. RESULTS: PAK4 was over-expressed in the NSCLC cell lines at both mRNA and protein levels compared with HBE cells (P<0.05). PAK4 was over-expressed in the NSCLC tissues at both mRNA and protein levels compared with adjacent non-tumor tissues (P<0.05). PAK4 was over-expressed in the metastatic NSCLC tissues compared with the primary NSCLC tissues (P<0.05). Higher PAK4 staining scores were positively correlated with differentiation, lymph node metastasis, distant metastasis, and clinical stage. Kaplan-Meier analysis and log-rank test showed that overall survival was significantly different between the patients with up-regulated PAK4 and the patients with down-regulated PAK4(P<0.05). PAK4 over-expression was associated with NSCLC progression.CONCLUSION: Increased PAK4 expression was associated with tumor invasion, metastasis and prognosis in the patients with NSCLC. PAK4 is an important prognostic marker and potential therapeutic target in NSCLC.  相似文献   

14.
AIM: To study the mRNA and protein expression of Kang ai1 (KAI1) tumor suppressor gene and to determine the relationship between KAI1 and invasiveness and metastasis of cervical cancer. METHODS: The expression of KAI1 metastasis suppressor was detected by immunohistochemistry in paraffin slides and by real-time quantitative polymerase chain reaction (RT-PCR) in fresh tissue. The samples included 20 cases of normal cervical tissues, 20 cases of cervical intraepithelial neoplasia (CIN) and 40 cases of cervical carcinoma. The results of the gene expression combined with the pathological and clinical data were also analyzed. RESULTS: The expression of KAI1 protein and mRNA was related to the tissue differentiation of cervix. The positive rates of KAI1 expression were the highest in the normal cervical tissue, the middle in CIN and the lowest in cervical carcinoma with significant difference among three groups (P<0.01). The expression of KAI1 protein was not related with the grade of CIN (P>0.05). However, both mRNA and protein expression of KAI1 were related to the differentiation and the clinical stages of cervical cancer (P<0.01) and also related to the metastasis of the cancer. The positive rates between the non-lymphatic metastasis and lymphatic metastasis (P<0.05) were significant different. Cox regression and logistic regression showed that the tissue differentiation, clinical stages, lymphatic metastasis and expression of KAI1 were all related factors with recurrence and prognosis of cervical cancer. CONCLUSION: The down-regulation of KAI1 tumor suppressor gene at both mRNA and protein levels is related to the differentiation, clinical stages and metastasis of cervical cancer, indicating that the expression of KAI1 is a prognostic factor for cervical cancer.  相似文献   

15.
AIM: To investigate the relationship between expression of Bmi-1 (B cell-specific MLV integration site-1) in gastric cancer and its clinicopathologic significance.METHODS: 146 surgical patients with gastric carcinoma were followed up at least 2 years.Expression of Bmi-1 protein was examined by immunohistochemistry in their archival paraffin embedded tissue specimens.RESULTS: The intensive positive rate of Bmi-1 expression in gastric cancer was 67.8% (99/146).Expression of Bmi-1 was highly correlated with tumor size,clinical stage,lymph node metastasis and T classification (P<0.05),but not with sex,age,tumor differentiation,etc.(P>0.05).The survival rate in the patients with Bmi-1 expression was much lower than that in those patients without Bmi-1 expression (P<0.01).Multivariate analysis indicated that Bmi-1 expression,T classification,lymph node metastasis,distant metastasis,tumor size and postoperative chemotherapy were all significantly prognostic factors of gastric carcinoma.CONCLUSION: Overexpression of Bmi-1 in patients with gastric carcinoma enhances the possibility of invasion and metastasis,implying a poor prognosis.Bmi-1 may serve as fairly a good prognostic factor to indicate biologic behavior and prognosis in gastric carcinoma.  相似文献   

16.
AIM: To investigate the clinical significance of stathmin 1 (STMN1) expression in cervical cancer and the influence of its expression on the viability and apoptosis of cervical cancer cells. METHODS: Western blot was used to detect the protein expression of STMN1 in cervical cancer tissues, and the relationship between the expression and clinical characteristics of cervical cancer was analyzed. STMN1-siRNA was transfected into cervical squamous-cell carcinoma SiHa cells. The protein levels of STMN1, STAT3, p-STAT3 and survivin were determined by Western blot after transfection for 48 h. The cell viability was measured by MTT assay. The apoptosis was analyzed by flow cytometry. DCFH-DA probe was used to detect the level of reactive oxygen species (ROS). RESULTS: The protein expression of STMN1 in cervical cancer tissues was significantly higher than that in paracancerous tissues (P<0.01). The STMN1 protein expression level was not correlated with age and histological types of cervical cancer patients, but was related to clinical stage, histological differentiation and lymph node metastasis (P<0.01). Transfection with STMN1-siRNA significantly reduced the expression of STMN1 in SiHa cells. Compared with control group, the cell viability in STMN1-siRNA group was significantly decreased, the apoptotic rate and ROS content were increased, and the protein levels of p-STAT3 and survivin were down-regulated (P<0.01). However, no significant difference of the STAT3 protein level was observed between STMN1-siRNA group and control group. CONCLUSION: STMN1 is highly expressed in cervical cancer, and its expression is related to clinical stage, histological differentiation and lymph node metastasis. Inhibition of STMN1 expression reduces the viability and promotes apoptosis of cancer cells by down-regulating STAT3 signaling pathway.  相似文献   

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AIM: The aim of this study was to examine the microstatellite instability (MSI) and loss of heterozygosity(LOH) of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in hepatocellular carcinoma (HCC),which may provide experimental evidence for the mechanism of nm23H1 gene and tumor metastasis.METHODS: Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues,PCR-SSCP,ordinary silver stain were used to study MSI and LOH of locus D17S396.Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1.RESULTS: ① The frequency of heredity instability of HCCs was 35.42%.The frequency of LOH in the cases with lymph node or distant organs metastasis or not and with intrahepatic metastasis or embolus of portal vein or not was significantly different (P<0.01),it was higher in stage TNM Ⅲ than that in stageⅠ and Ⅱ.Moreover,it was higher in high tendency to invasion or metastasis cases than that in the low tendency cases (P<0.01).② The expression of nm23H1 was 56.25%.It was significantly different in Edmondson grade,TNM stage and in lymph node or distant organ metastasis cases (P<0.01).The cases with high tendency of invasion or metastasis exhibited lower nm23H1 expression compared with low tendency cases (P<0.01).③ The positive rate of nm23H1 protein in LOH positive group was lower than that in LOH negative group (P<0.05).CONCLUSION: The results indicate that both MSI and LOH of nm23H1 gene control the development of HCC independently in different pathways.LOH inhibits the expression of nm23H1,which endows it with high aggressive and poor prognosis.Increase in the amount of nm23H1 protein expression effectively restrains the tendency to invasion or metastasis of HCCs and improves prognosis of patients.  相似文献   

19.
AIM: To investigate the expression of miR-143 and its association with clinicopathologic features in gastric cancer.METHODS: The expression level of miR-143 in 32 cases of gastric cancer and matched non-tumor adjacent tissue specimens was examined using stem-loop real-time RT-PCR. The relationship between the expression of miR-143 and its clinicopathologic features of gastric cancer was analyzed.RESULTS: The expression level of miR-143 was significantly lower in the tumor tissues than that in the adjacent tissues (P<0.05). Down-regulated miR-143 expression was associated with the cell differentiation (P<0.05) and lymph node metastasis (P<0.05) in gastric cancer patients. No significant association was found between the expression of miR-143 and the status of gender, age, blood type, tumor location, tumor size, depth of tumor invasion and tumor node metastasis stage.CONCLUSION: It is possible that miR-143 plays an important role in the generation and progression of gastric cancer. The expression level of miR-143 may be a valuable adjuvant parameter for predicting the poorly differentiated gastric cancer.  相似文献   

20.
AIM: To investigate the expression of the red cell membrane integration protein SLP-2 (stomatin-like protein 2) in gastric cancer tissues and to analyze its correlation with clinicopathological manifestations and prognosis. METHODS: One hundred and ninety gastric cancer tissue samples with detailed clinical information were collected from the Department of Pathology, Sun Yat-sen University Cancer Center. The protein expression of SLP-2 in ganstric cancer was detected by the method of immunohistochemistry. The relationships between SLP-2 expression and the clinicopathological manifestations were evaluated. RESULTS: The positive rate of SLP-2 in gastric cancer tissue was 63.2% (120/190). SLP-2 expression was relevant to infiltration depth, TNM stage and lymph node metastasis (P<0.05). However, no statistical difference was observed in the SLP-2 expression associated with sex, age, differentiation, tumor size and distant metastases. Kaplan-Meier survival curves revealed that increased expression of SLP-2 was associated with poor prognosis in gastric adenocarcinoma patients (P<0.01). Based on the univariate analysis, 7 factors were found to have statistical significance of associations with overall survival, including SLP-2 expression, lymph node metastasis, histological grade, tumor size, invasive depth, distant metastases and the 7th edition of the UICC TNM classification. Only the tumor size and the 7th edition of the UICC TNM classification were independent prognostic factors for overall survival in the multivariate analysis. CONCLUSION: SLP-2 is highly expressed in gastric adenocarcinoma tissues and may play an important role in tumor progression and metastasis. Although SLP-2 is not an independent prognostic factor, it may influence the prognosis of gastric cancer. Increased expression of SLP-2 can be used for predicting unfavorable prognosis in gastric adenocarcinoma patients.  相似文献   

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