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1.
Background: The expression of inducible nitric oxide synthase (iNOS) has been reported to be altered in a number of tumours, but its role in tumour biology is still unclear. Methods: iNOS was studied in a series of 157 colorectal carcinoma patients and its relation to tumour grade, stage, cell cycle regulators, cell proliferation as well as survival was assessed. Results: iNOS intensity was moderate or intense in 37% of the tumours. iNOS intensity and percentage of positive cells were higher in Dukes A and B tumours than in Dukes C and D tumours, and low iNOS expression intensity was related to high histological grade. iNOS expression correlated positively with cell cycle regulators p21 and AP-2. There was also a high iNOS expression intensity and high fraction of iNOS positive cells in tumours with a high amount of tumour infiltrating lymphocytes (TILs). The cancer related survival was significantly lower among patients with a low signal for iNOS and low iNOS percentage in tumour epithelium. In multivariate analysis iNOS was not an independent prognostic factor. Conclusions: These results suggest that iNOS has a protective role in colorectal carcinogenesis, but further studies are required to establish the clinical significance of iNOS in colorectal cancer.  相似文献   

2.
Morris EJ  Maughan NJ  Forman D  Quirke P 《Gut》2007,56(10):1419-1425
OBJECTIVE: To identify by routine pathology which Dukes B colorectal cancer patients may benefit from chemotherapy. METHOD: Retrospective study of the five year survival of colorectal cancer patients for whom colorectal pathology minimum datasets had been collected between 1997 and 2000 in the Yorkshire region of the UK. The study population consisted of 1625 Dukes B and 480 Dukes C patients who possessed one positive node treated between 1997 and 2000. The predictive ability of the Petersen prognostic model was investigated and survival of Dukes B patients with potentially high risk pathological features was compared to that of Dukes C patients with one positive node. RESULTS: Only 23.3% of patients had all the pathological variables required for the application of Petersen's index reported. The index offered a statistically significant survival difference of 24.3% and 30.3% between high and low risk colon (p<0.01) and rectal cancer patients (p<0.01). The size of these effects was smaller than predicted by the original model. Survival of Dukes B patients with any of the high risk pathological factors or low nodal yields was lower than that of Dukes C patients who possessed one positive node. CONCLUSION: Petersen's index discriminated between high and low risk Dukes B colorectal tumours, but inadequate pathological reporting diminished its ability to identify all high risk patients. The survival of patients with any high risk feature was lower than the threshold for adjuvant therapy of one lymph node positive Dukes C colorectal cancer. Chemotherapy may benefit patients with such features. Improving the quality of pathological reporting is vital if high risk patients are to be reliably identified.  相似文献   

3.
Survivin基因在大肠癌中的表达与生物学特性的关系   总被引:1,自引:0,他引:1  
目的 研究Survivin基因在大肠癌中的表达与生物学特性的关系。方法 免疫组织化学法检测 83例大肠癌组织及癌旁正常组织Survivin的表达。结果 Survivin在大肠癌组织中阳性表达率为 68.7% ,而在癌旁正常组织不表达 ,按Dukes分期 ,C、D期阳性率高于A、B期 (P <0 .0 5) ,低分化、中分化、高分化癌组织阳性率无差异 (P >0 .0 5) ,肿瘤直径大于 5cm与小于 5cm者阳性率无差异 (P >0 .0 5)。结论 Survivin基因在大肠癌中高表达 ,与Dukes分期相关 ,但与癌组织分化程度、肿瘤大小无关  相似文献   

4.
M Yukawa  T Fujimori  S Maeda  M Tabuchi    K Nagasako 《Gut》1994,35(9):1258-1261
Mutations in oncogenes and tumour suppressor genes may have an important oncogenic role. Although flat type tumours have been frequently detected in recent years, ras and p53 expressions have not been studied in these tumours. Using a monoclonal and polyclonal antibody to the ras p21 and p53 product, paraffin wax embedded sections of 98 colorectal tumours (43 cases of the flat type colorectal tumour and 55 cases of polypoid type tumour) were stained using the immunoperoxidase technique. Staining was evaluated by light microscopic examination. Positive staining rate of ras p21 for the flat type was 0%; for the polypoid type, it was 60% in cancer with submucosal invasion, 82% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The positive staining rate of p53 for the flat type was 50% in submucosal cancer, 9% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. For the polypoid type, it was 40% in submucosal cancer, 12% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The intermediate staining rate of p53 in the polypoid type was 20% in submucosal cancer and 41% in adenoma with high grade dysplasia. It was seen that p53 was commonly expressed in both flat and polypoid lesions, p21 was not expressed in flat lesions, whereas it was commonly expressed in polypoid neoplasms. In the flat type cancer, a genetic change different from that of the polypoid type cancer is suggested.  相似文献   

5.
The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.  相似文献   

6.
A series of 161 bladder cancer biopsy specimens (survival data available in 122 cases) was analysed immunohistochemically for the expression of E-cadherin (E-CD), the most important cell-to-cell adhesion molecule in epithelial cells. Altogether, 81% of the tumours were E-CD-positive, the staining being heterogeneous in nearly all tumours. Normal transitional epithelium was positive for E-CD while in carcinomas the expression was reduced or even absent (18%). Lower levels of E-CD were detected in rapidly proliferating high-grade muscle-invasive tumours. Reduced expression of E-CD was related to a dense inflammatory cell reaction in tumour stroma. The median clinical follow-up was 12.0 years. Short recurrence-free survival of Ta-T1 tumours (P=0.02) was related to expression of E-CD fewer than 50% of cancer cells. In survival analysis the fraction of E-CD-positive cells (P=0.1) and the expression intensity of E-CD (P=0.09) showed a non-significant association to prognosis. Multivariate survival analysis indicated that expression of E-CD has no independent prognostic value over grade or stage while recurrence-free survival was related to E-CD expression.  相似文献   

7.
Apoptosis is a frequent phenomenon in breast cancer and it can be detected by light microscopy in conventional histopathological sections or by special staining techniques. The number of apoptotic cells as a percentage of cells present, or the number of apoptotic cells per square millimetre of neoplastic tissue, is usually described as the apoptotic index (AI). In breast cancer, the AI is not related to tumour size, axillary lymph node metastasis or distant metastasis at diagnosis. It is greater in invasive ductal carcinomas than in other histological types. High AI is also related to high histological grade, high nuclear grade, comedo-type necrosis, lack of tubule formation, and dense infiltration of the tumour by lymphocytes. Sex steroid receptor-negative tumours have greater AIs than the sex steroid receptor-positive ones. Aneuploid breast cancers with high S-phase fractions (SPFs) also have high AI values compared with diploid tumours with low SPFs. p53-Positive breast cancers have high AIs, whereas tumours that are Bcl-2 positive have low AIs. The AI shows a strong positive correlation to all direct or indirect indicators of cell proliferation, such as mitotic index and Ki67 immunolabelling. Univariate survival analyses show that a high AI is linked with unfavourable disease outcome in axillary lymph node-negative and -positive breast cancer, but multivariate analyses indicate that AI is not an independent prognostic factor. In conclusion, a high AI is related to malignant cellular features and indicators of invasiveness and cell proliferation in breast cancer.  相似文献   

8.
BackgroundThe overexpression of p53 protein and the expression of Ki-67 antigen may affect the survival of patients with gallbladder carcinoma. This association has been tested in a series of 41 patients with relatively early carcinoma of the gallbladder.MethodsForty-one surgical specimens from patients with a postoperative histological diagnosis of gallbladder carcinoma were studied. All patients were operated by simple cholecystectomy only because the tumours were not advanced and/or their general condition was poor. Patients submitted to radical operations were excluded. p53 expression was calculated from nuclear staining according to the intensity and extent of positive cells, as graded on a scale from 1 to 3; a combined score of >3 was considered as overexpression. Ki-67 expression was calculated by the MIB-I index: the percentage of positively stained tumour cell nuclei out of the total tumour cells counted (n = 1000); >20% of stained cells was considered positive.ResultsTwenty-nine gallbladder carcinomas (71%) overexpressed p53 protein in the cell nuclei. No significant differences were found in relation to cell differentiation on the level of tumour infiltration through the gallbladder wall. Five-year survival of patients with gallbladder carcinoma overexpressing p53 was 17.2%, while survival of patients without p53 overexpression was 30% (not significant). Twenty-four cases (58.5%) were considered positive for the MIB-I index. There were no differences between the grade of cell differentiation and wall infiltration. Five-year survival of the patients with a MIB-I positive index was 9.2% as opposed to 27.7% for those with a negative index (not significant).Conclusionsp53 protein nuclear overexpression and Ki-67 protein expression in gallbladder carcinoma were not related to histological differentiation, level of gallbladder wall invasion or patient survival.  相似文献   

9.
BACKGROUND/AIMS: The factors predicting recurrence and survival were evaluated using a computer-generated database to identify the independent predictors of survival of colorectal cancer in patients under 50 years of age. METHODOLOGY: One hundred and two patients under the age of 50 years with colorectal cancer who had been admitted into our hospital during the 20-year period of 1980-1999 were identified from a computer database. The factors possibly predicting recurrence were compared by bivariate analysis and the predictors of long-term survival by both univariate and multivariate analysis. RESULTS: A family history of colorectal cancer was present in 14% of all patients and in 15% of the patients aged under 40 years. Overall 5-year survival after radical resection was 59% and median survival 47 months. The recurrence rate after radical resection was 40%, being 13%, 35%, 55% and 80% in Dukes classes A, B, C and D, respectively. The risk of recurrence was most closely related to lymphatic invasion, vascular invasion and Dukes stage. Kaplan-Meier estimates showed that Dukes stage, grade of tumor, venous invasion, lymphatic invasion, perineural invasion and radicality of resection were the best predictors of survival, but in multivariate analysis only the radicality of operation, venous invasion and tumor grade retained their significance. CONCLUSIONS: Young age is not a poor prognostic marker in colorectal cancer. In addition to radical operation, venous invasion and tumor grade are good predictors of survival in patients under the age of 50 years.  相似文献   

10.
BACKGROUND/AIMS: Ku protein stimulates DNA repair and signals the damage/stress responses, which may affect apoptosis and cell proliferation. The expression of Ku70 has been reported to be related to cell proliferation in a human gastric cancer cell line. However, in colorectal carcinoma, the clinical significance of Ku70 expression remains unclear. We examined the expression pattern of Ku70 in sporadic colorectal cancer and its relation to clinicopathological parameters and survival. METHODOLOGY: We studied 101 consecutive cases of advanced colorectal carcinoma. In resected specimens, the number of cells stained positive for Ku70 protein was evaluated by immunohistochemistry. RESULTS: The percentage of cells expressing Ku70 in different tumors ranged from 4.2-99.7%. The elevated Ku70 expression group comprised 52 of 101 cases (52%). No significant correlation was seen between Ku expression pattern and the clinical parameters except depth of invasion. pTNM stage, histopathological grade and Ku70 were significant variables for prognosis of survival in the multivariate analysis. CONCLUSIONS: This is the first report correlating reduced survival with elevated expression of Ku protein in colorectal adenocarcinoma. Ku may be a new prognostic marker useful for selecting adjuvant treatment strategies.  相似文献   

11.
目的检测survivin基因在老年人大肠癌、正常大肠黏膜组织上的表达,探讨其临床意义。方法采用免疫组化S-P法对56例老年人大肠癌和33例正常大肠黏膜组织检测survivin基因的表达。结果survivin基因在老年人大肠癌与正常黏膜组织中的表达率分别为48.2%(27例)和12.1%(4例),差异有统计学意(P<0.05),而与组织学分级、Dukes分期、有无淋巴结转移差异无统计学意义。在随访组中,5年存活27例,survivin蛋白阳性表达6例,阳性表达率22.2%;死亡15例中,阳性表达12例(80.0%),差异有统计学意义(P<0.001)。结论survivin基因表达上调可能促进了老年大肠癌的发生,临床上通过检测survivin基因阳性表达率对患者预后可能有临床意义。  相似文献   

12.
The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I–II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I–II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value. Received: 2 February 1998 / Accepted: 16 June 1998  相似文献   

13.
14.
The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I–IIIb/Dukes classification A–C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.  相似文献   

15.
OBJECTIVE: To determine the prognostic relevance of neuroendocrine differentiation in colorectal cancer. METHODS: The survival of 116 patients with colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were used as neuroendocrine markers. Based on the degree of immunoreactivity for these markers, tumours were classified as 0 (no expression of neuroendocrine markers), 1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells staining positive for neuroendocrine markers). Patients were followed up for more than 5 years or until death. RESULTS: Seven of 59 (11.8%) stage III cancers and 13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0 and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only 18.6 months (Kaplan-Meier survival curves, P < 0.001). The difference was most striking in stage III disease with 79.4 months' survival for combined groups 0 and 1, and 38.9 months' survival for group 2 (P < 0.01). Using the multivariate Cox regression model, the presence of more than 2% of cells with neuroendocrine differentiation was found to be an independent prognostic parameter for stage III and IV disease. No correlation was observed between neuroendocrine differentiation and tumour location, grade, depth of invasion or stage. CONCLUSION: Neuroendocrine differentiation is often seen in colorectal cancer. It is an independent prognostic factor in stage III-IV colorectal cancer.  相似文献   

16.
Expression of survivin protein in human colorectal carcinogenesis   总被引:29,自引:0,他引:29  
AIM: To identify the role of survivin in colorectal carcinogenesis and the relationship between Survivin and histological differentiation grade of colorectal carcinoma. METHODS: Immunohistochemical staining of survivin by using the monoclonal antibody was performed by the standard streptavidin-peroxidase (SP) technique for the 188 paraffin sections which included 30 normal colorectal mucosas, 41 adenomas with low grade dysplasia, 30 adenomas with high grade dysplasia, and 87 colorectal carcinomas which were classified as high, middle and low differentiated subgroups which included 33, 28, 26 cases respectively. RESULTS: Expression of survivin was observed in the cytoplasm of adenoma with dysplasia and colorectal carcinoma cells. No immunoreactivity of survivin was seen in normal mucosas. The positive rate of survivin increased in the transition from normal mucosas to adenomas with low grade dysplasia to high grade dysplasia/ carcinomas (0.0 %, 31.7 %, 56.7 % and 63.2% respectively). But the difference between high grade dysplasia and carcinomas had no statistical significance. Positive rate was not related to histological differentiation grade of colorectal carcinoma. Moreover, there was no correlation between histological differentiation grade of colorectal carcinoma and immunoreactive intensity of survivin. CONCLUSION: The expression of survivin is the essential event in the early stage of colorectal carcinogenesis and plays an important role in the transition sequence and it is not related to histological differentiation grade of colorectal carcinoma. It thus may provide a new diagnostic and therapeutic target in colorectal cancer.  相似文献   

17.
OBJECTIVE: Fas ligand (FasL) is an important mediator of immune function and induces apoptosis by binding to its receptor Fas on sensitized cells. It has recently been shown that malignancies may express FasL and acquire immune privilege by inducing apoptosis of lymphocytes. Acquired resistance to Fas mediated apoptosis is known to be an early event in carcinogenesis. The aim of this study was to determine the extent of FasL expression in patients with colorectal cancer and examine its relationship with several prognostic pathological features and survival. DESIGN AND METHODS: Sixty-eight patients (median age 66 years) with colorectal cancer, whose diagnosis was made between 1988 and 1991 and in whom long-term follow-up was available, were evaluated. The tumours were of varying stages at diagnosis (eight Dukes' A, 28 Dukes' B, 23 Dukes' C and nine Dukes' D). The expression of FasL was detected immunohistochemically with a rabbit polyclonal IgG using the DAKO EnVision+ System. The specificity of FasL binding was confirmed by pre-incubation of the antibody with the immunizing peptide prior to staining. The relationship with several pathological features was determined using Kendall's tau-b correlation. Overall survival was estimated using the Kaplan-Meier product limit curves. Differences in observed survival were tested for statistical significance using the Mantel-Haenszel log rank test. Both the extent and intensity of staining were graded by a blinded observer. RESULTS: FasL was predominantly expressed in tumour epithelial cells in 88% of the cases. The positive staining of tumours varied in extent. FasL staining was higher in earlier Dukes' stage tumours in that the extent of FasL staining negatively correlated with Dukes' stage (Kendall tau-b = -0.22, P = 0.038). Consistent with this, the overall survival was better with a greater extent of FasL expression (log rank chi2 = 5.68, P = 0.017). There was a lower extent of FasL expression in mucinous adenocarcinomas (Kendall tau-b = 0.288, P = 0.01) and in those tumours with neural invasion (Kendall tau-b = -0.26, P = 0.03). No relationship was detected between FasL and tumour site, size, margin, differentiation, vascular invasion, necrosis or Crohn's-like reaction. CONCLUSIONS: FasL is widely expressed in colorectal cancers. This finding suggests that the extent of FasL expression in colorectal tumours is directly related to patients' survival.  相似文献   

18.
Purpose The aims of this study were to investigate the expression levels of proteins involved in cell cycle regulation in specimens of bladder cancer and to correlate them with the clinicopathological characteristics, proliferative activity and survival.Methods Eighty-two specimens obtained from patients affected by muscle-invasive bladder cancer were evaluated immunohistochemically for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation index, Ki-67. The statistical analysis included Kaplan–Meier curves with log-rank test and Cox proportional hazards models.Results In univariate analyses, low Ki-67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04) were associated to patient’s overall survival (OS), but in multivariate models p21 did not reach statistical significance. When the combinations of the variables were assessed in two separate multivariate models that included tumour stage, grading, lymph node status, vascular invasion and perineural invasion, the combined variables p21/Ki-67 or p21/cyclin D1 expression were independent predictors for OS; in particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome.Conclusions Important alterations in the cell cycle regulatory pathways occur in muscle-invasive bladder cancer and the combined use of cell cycle regulators appears to provide significant prognostic information that could be used to select the patients most suitable for multimodal therapeutic approaches.  相似文献   

19.
AIM To characterize the expression of toll-like receptors(TLR) 2 and 4 in colorectal cancer(CRC) and in normal colorectal mucosa.METHODS We analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed.RESULTS Normal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancerspecific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression(P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours.CONCLUSION Tumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease.  相似文献   

20.
目的探讨在大肠癌癌变过程中,即大肠正常组织、大肠增生性息肉、大肠腺瘤和大肠癌中PTEN的表达及意义。方法应用免疫组织化学SP法检测122例大肠组织标本中PTEN蛋白的表达,应用等级相关的秩和检验分析PTEN在大肠组织中表达的意义及其与临床病理特征间的关系。结果PTEN蛋白在正常大肠组织、大肠增生性息肉、大肠腺瘤、大肠癌中表达差异有明显统计学意义(P=0.000)。大肠癌中PTEN蛋白表达与肿瘤分化程度、临床肿瘤分期及性别无关(P〉0.05),但与患者的年龄相关(P=0.002)。结论PTEN蛋白在大肠癌癌变过程中存在异常表达,PTEN蛋白的低表达与大肠癌的发生和浸润转移相关。  相似文献   

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