(ZrB2+Al2O3+Al3Zr)/A356 composites were synthesized by melt direct reaction from A356-(K2ZrF6+KBF4+Na2B4O7) system.The phase compositions and the microstructures of the as-prepared composites were investigated...(ZrB2+Al2O3+Al3Zr)/A356 composites were synthesized by melt direct reaction from A356-(K2ZrF6+KBF4+Na2B4O7) system.The phase compositions and the microstructures of the as-prepared composites were investigated by XRD,SEM and TEM.The results show that the reinforcements are composed of ZrB2 and Al2O3 ceramic phase particles and Al3Zr intermetallic particles.The ZrB2 particulates are easy to join together to form some particle clusters and distribute along the α(Al) grain boundary.The morphologies of the ZrB2 particulates are in hexagon-shape with the size of about 50 nm.The TEM investigation results of Al3Zr indicate that Al3Zr grows in the form of facet with the length-diameter ratio of about 20.The morphologies of Al2O3 particles are in rectangular-shape and ellipsoidal-shape,with the size of about 0.1 μm.In addition,the interfaces of the matrix and particles are net and no interfacial outgrowth is observed.展开更多
OBJECTIVE To assess the functional change of SFRP1 (secreted frizzled-related protein1), in colorectal tumorigenesis. METHODS Immunohistochemical investigation and the semiquantitative reverse transcription-polymera...OBJECTIVE To assess the functional change of SFRP1 (secreted frizzled-related protein1), in colorectal tumorigenesis. METHODS Immunohistochemical investigation and the semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to assess the expression of SFRP1, β-catenin (β-cat) and E-caderin (E-cad) in matched samples of normal colorectal mucosa, adenomas and cancers. RESULTS SFRP1 mRNA expression was down-regulated in the neoplasms, and abnormal expressions of β-cat and E-cad were found in colorectal adenomas and colorectal cancers. CONCLUSION Down-regulation of SFRP1 observed is consistent with its acting as a tumor suppressor gene in colorectal tumorigenesis.展开更多
AIM: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-l) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer.METHODS: Eighty...AIM: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-l) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer.METHODS: Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining.RESULTS: WISP-1 gene overexpression was found in 65% (56/86) primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues (P = 0.001). The mRNA expression level was correlated with Duke's staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group (1.40±0.35) was different from that in control group (1.04± 0.08, P 〈 0.001). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (1.46 ±0.37, n = 56) was higher than that in low-level mRNA (1.28 ± 0.28, n = 30, P = 0.018).CONCLUSION: Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer.展开更多
AIM: To assess the incidence of MLH1 (the human MutL homologue) and MSH2 (the human MutS homologue) protein expression in Turkish patients with sporadic colorectal cancers and to compare their survival and clinic...AIM: To assess the incidence of MLH1 (the human MutL homologue) and MSH2 (the human MutS homologue) protein expression in Turkish patients with sporadic colorectal cancers and to compare their survival and clinicopathological features. METHODS: We validated the tissue microarray technology in 77 colorectal carcinomas by analyzing the immunohistochemical expression of proteins involved in two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors; MLH1 and MSH2 proteins for microsatellite instability (MSI). RESULTS: Our analysis showed that 29 (39.2%) had loss of MLH1 expression, 5 (6.8%) had loss of MSH2 expression and 2 cases had loss of expression of both proteins. We found that 60% of MSH2-negative tumors were located in the right side of the colon; all MSH2-negative cases were women. In addition, the loss of MSH2 expression was correlated with low p53 expression. Neither MLH1 nor MSH2 expressions were associated with prognosis, although there seemed a tendency of longer survival (71.7 ± 8.65 mo vs 47.08± 5.26 too) for the patients with MLHl-negative versus MLHl-positive carcinomas. There were not significant differences in overall and recurrence-free survival among MLH1/MSH2-positive and -negative cases.CONCLUSION: Our data supports that Turkish patients with MLH1- and MSH2-defective tumors have some distinct features from each other. Although prognostic importance remains controversial, immunohistochemical analysis of mismatch repair genes may be used as a routine histopathological examination of sporadic colorectal carcinomas.展开更多
AIM: To explore the expression of BAG1 and tissue inhibitor of metalloproteinase 3 (TIMP3) in colon carcinoma and their correlation and clinicopathologic significance. METHODS: SABC immunohistochemistry was used to de...AIM: To explore the expression of BAG1 and tissue inhibitor of metalloproteinase 3 (TIMP3) in colon carcinoma and their correlation and clinicopathologic significance. METHODS: SABC immunohistochemistry was used to detect the expression of BAG1 and TIMP3 in 80 colon carcinoma tissues and 20 normal colonic mucosa. RESULTS: Positive rate of BAG1 in colon carcinoma tissue (80%) was notably higher compared to normal colonic mucosa (10%) (P < 0.05). However, no significant difference was observed in positive rate of TIMP3 in colon carcinoma tissue (43.75%) as compared with normal colonic mucosa (60%) (P > 0.05). Expression of BAG1 and TIMP3 was strongly associated with colon carcinoma differentiation, Duke's staging, lymph node metastasis and survival rate (P < 0.05), but not associated with gender and age. Moreover, BAG1 expression was not correlated with TIMP3. CONCLUSION: Our results suggest that over-expression of BAG1 or attenuated expression of TIMP3 may play an important role in genesis and development of colon carcinoma. The protein expression levels of BAG1 and TIMP3 are related to the malignant degree, infiltration and metastasis of colon carcinoma. BAG1 and TIMP3 might be new biological parameters in predicting invasion and metastasis of colon carcinoma.展开更多
The origin of myofibroblasts or myofibroblastic cells in the desmoplastic stroma associated with carcinoma invasion has been controversial. In the early invasive area of a rectal adenocarcinoma reported here, an obvio...The origin of myofibroblasts or myofibroblastic cells in the desmoplastic stroma associated with carcinoma invasion has been controversial. In the early invasive area of a rectal adenocarcinoma reported here, an obvious transition between the muscularis mucosa and the bundles of eosinophilic stromal cells observed in the carcinomatous stroma was demonstrated both in morphology and in their cytoskeletal phenotype, which conceivably suggests that the smooth muscle cells of the muscularis mucosa could convert to the eosinophilic stromal cells, namely myofibroblasts. Moreover, type I procollagen was demonstrated in both protein and mRNA levels in the areas of eosinophilic stromal cells with a lesser degree of differentiated smooth muscle phenotype that showed a transition from the muscularis mucosa, implying that the myofibroblastic cells converted from smooth muscle cells of the muscularis mucosa could be responsible for type I collagen production. These findings suggest that the muscularis mucosae may not be a passive barrier through which colorectal carcinomas infiltrate into the submucosa, but may play an active role in the formation and remodeling of tumor stroma.展开更多
AIM: To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor samples were analyzed for β-catenin using immunohistochemist...AIM: To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor samples were analyzed for β-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC. RESULTS: Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 too) than those with a NI below the median (15.5 too) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted diseasespecific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046). CONCLUSION: Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.展开更多
AIM: To investigate the in situ expression of suppressionof tumorigenecity 13 (ST13) mRNA in both colorectal cancer and adjacent normal tissues.METHODS: Colorectal cancer cell lines SW1116, SW620and CoLo205 were enrol...AIM: To investigate the in situ expression of suppressionof tumorigenecity 13 (ST13) mRNA in both colorectal cancer and adjacent normal tissues.METHODS: Colorectal cancer cell lines SW1116, SW620and CoLo205 were enrolled to confirm the feasibility of the in situ hybridization procedure. Seven colorectal cancer and adjacent normal tissues were included for RNA-RNA in situ hybridization.RESULTS: The expression of ST13 in the seven normal colon tissues was positive and the positive signals appeared in mucosal cells. Only three of the seven colorectal cancer tissues had positive hybridization signals that appeared in adenocarcinoma cells.CONCLUSION: The expression of ST13 decreases in colorectal cancer tissue compared with that in adjacent normal tissue. ST13 is mostly expressed in colorectal epithelia and adenocarcinoma cells.展开更多
AIM: To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tis- sue from 49 C...AIM: To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tis- sue from 49 CRC patients were analyzed. Mononuclear cells were isolated by FicolI-Hypaque density gradient centrifugation and were subjected to a flow cytometry- based immunophenotypic analysis. RESULTS: A considerable increase in the percentage of CD33+HLA-DR MDSCs was observed in the periph- eral blood (1.89% :1= 0.75%) and tumor tissues (2.99%±1.29%) of CRC patients as compared with that in theperipheral blood of healthy controls (0.54%±0.35%). This expanded CD33+HLA-DR subset exhibited imma- ture myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Fur- ther studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis (P = 0.023), whereas that in tumor tissues was cor- related with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION: Characterization of MDSCs in CRC sug- gests the clinical significance of circulating and tumor- infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.展开更多
AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coil (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of th...AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coil (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential, location of adenomas, macroscopic appearance and age of the patients. RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5± 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 ±15.5 mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P =0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas. CONCLUSION: Most adenomas expressed full-length APC protein, suggesting that protein expression is not a reliable marker for assessment of APC gene mutation. Complete loss of APC protein did not influence morphology, location, or appearance of adenomas, nor was it affected by the patient's age.展开更多
AIM: To assess the usefulness of two independent histopathological classifications of rectal cancer regression following neo-adjuvant therapy. METHODS: Forty patients at the initial stage cT3NxM0 submitted to preope...AIM: To assess the usefulness of two independent histopathological classifications of rectal cancer regression following neo-adjuvant therapy. METHODS: Forty patients at the initial stage cT3NxM0 submitted to preoperative radiotherapy (42 Gy during 18 d) and then to radical surgical treatment. The relationship between "T-downstaging" versus regressive changes expressed by tumor regression grade (TRG 1-5) and Nasierowska-Guttmejer classification (NG 1-3) was studied as well as the relationship between TRG and NG versus local tumor stage ypT and lymph nodes status, ypN. RESULTS: Complete regression (ypT0, TRG 1) was found in one patient. "T-downstaging" was observed in 11 (27.5%) patients. There was a weak statistical significance of the relationship between "T-downstaging" and TRG staging and NG stage. Patients with ypT1 were diagnosed as TRG 2-3 while those with ypT3 as TRGS. No lymph node metastases were found in patients with TRG 1-2. None of the patients without lymph node metastases were diagnosed as TRG 5. Patients in the ypT1 stage were NG 1-2. No lymph node metastases were found in NG 1. There was a significant correlation between TRG and NG. CONCLUSION: Histopathological classifications may be useful in the monitoring of the effects of hyperfractionated preoperative radiotherapy in patients with rectal cancer at the stage of cT3NxM0. There is no unequivocal relationship between "Todownstaging" and TRG and NG. There is some concordance in the assessment of lymph node status with ypT, TRG and NG. TRG and NG are of limited value for the risk assessment of the lymph node involvement.展开更多
AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after rad...AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.展开更多
基金Project(50971066) supported by the National Natural Science Foundation of ChinaProject(20070299004) supported by Research Fund for the Doctoral Program of Higher Education of China+1 种基金Project(2008-46) supported by Jiangsu Provincial '333' Project of training the High-level Talents Foundation,ChinaProject(BE2009127) supported by Jiangsu Provincial Science Supporting Item,China
文摘(ZrB2+Al2O3+Al3Zr)/A356 composites were synthesized by melt direct reaction from A356-(K2ZrF6+KBF4+Na2B4O7) system.The phase compositions and the microstructures of the as-prepared composites were investigated by XRD,SEM and TEM.The results show that the reinforcements are composed of ZrB2 and Al2O3 ceramic phase particles and Al3Zr intermetallic particles.The ZrB2 particulates are easy to join together to form some particle clusters and distribute along the α(Al) grain boundary.The morphologies of the ZrB2 particulates are in hexagon-shape with the size of about 50 nm.The TEM investigation results of Al3Zr indicate that Al3Zr grows in the form of facet with the length-diameter ratio of about 20.The morphologies of Al2O3 particles are in rectangular-shape and ellipsoidal-shape,with the size of about 0.1 μm.In addition,the interfaces of the matrix and particles are net and no interfacial outgrowth is observed.
文摘OBJECTIVE To assess the functional change of SFRP1 (secreted frizzled-related protein1), in colorectal tumorigenesis. METHODS Immunohistochemical investigation and the semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to assess the expression of SFRP1, β-catenin (β-cat) and E-caderin (E-cad) in matched samples of normal colorectal mucosa, adenomas and cancers. RESULTS SFRP1 mRNA expression was down-regulated in the neoplasms, and abnormal expressions of β-cat and E-cad were found in colorectal adenomas and colorectal cancers. CONCLUSION Down-regulation of SFRP1 observed is consistent with its acting as a tumor suppressor gene in colorectal tumorigenesis.
基金The Key Project of National Outstanding Youth Fund of China, No.39925032
文摘AIM: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-l) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer.METHODS: Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining.RESULTS: WISP-1 gene overexpression was found in 65% (56/86) primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues (P = 0.001). The mRNA expression level was correlated with Duke's staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group (1.40±0.35) was different from that in control group (1.04± 0.08, P 〈 0.001). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (1.46 ±0.37, n = 56) was higher than that in low-level mRNA (1.28 ± 0.28, n = 30, P = 0.018).CONCLUSION: Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer.
基金the Research Foundation of Istanbul University,No T-493/25062004
文摘AIM: To assess the incidence of MLH1 (the human MutL homologue) and MSH2 (the human MutS homologue) protein expression in Turkish patients with sporadic colorectal cancers and to compare their survival and clinicopathological features. METHODS: We validated the tissue microarray technology in 77 colorectal carcinomas by analyzing the immunohistochemical expression of proteins involved in two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors; MLH1 and MSH2 proteins for microsatellite instability (MSI). RESULTS: Our analysis showed that 29 (39.2%) had loss of MLH1 expression, 5 (6.8%) had loss of MSH2 expression and 2 cases had loss of expression of both proteins. We found that 60% of MSH2-negative tumors were located in the right side of the colon; all MSH2-negative cases were women. In addition, the loss of MSH2 expression was correlated with low p53 expression. Neither MLH1 nor MSH2 expressions were associated with prognosis, although there seemed a tendency of longer survival (71.7 ± 8.65 mo vs 47.08± 5.26 too) for the patients with MLHl-negative versus MLHl-positive carcinomas. There were not significant differences in overall and recurrence-free survival among MLH1/MSH2-positive and -negative cases.CONCLUSION: Our data supports that Turkish patients with MLH1- and MSH2-defective tumors have some distinct features from each other. Although prognostic importance remains controversial, immunohistochemical analysis of mismatch repair genes may be used as a routine histopathological examination of sporadic colorectal carcinomas.
文摘AIM: To explore the expression of BAG1 and tissue inhibitor of metalloproteinase 3 (TIMP3) in colon carcinoma and their correlation and clinicopathologic significance. METHODS: SABC immunohistochemistry was used to detect the expression of BAG1 and TIMP3 in 80 colon carcinoma tissues and 20 normal colonic mucosa. RESULTS: Positive rate of BAG1 in colon carcinoma tissue (80%) was notably higher compared to normal colonic mucosa (10%) (P < 0.05). However, no significant difference was observed in positive rate of TIMP3 in colon carcinoma tissue (43.75%) as compared with normal colonic mucosa (60%) (P > 0.05). Expression of BAG1 and TIMP3 was strongly associated with colon carcinoma differentiation, Duke's staging, lymph node metastasis and survival rate (P < 0.05), but not associated with gender and age. Moreover, BAG1 expression was not correlated with TIMP3. CONCLUSION: Our results suggest that over-expression of BAG1 or attenuated expression of TIMP3 may play an important role in genesis and development of colon carcinoma. The protein expression levels of BAG1 and TIMP3 are related to the malignant degree, infiltration and metastasis of colon carcinoma. BAG1 and TIMP3 might be new biological parameters in predicting invasion and metastasis of colon carcinoma.
文摘The origin of myofibroblasts or myofibroblastic cells in the desmoplastic stroma associated with carcinoma invasion has been controversial. In the early invasive area of a rectal adenocarcinoma reported here, an obvious transition between the muscularis mucosa and the bundles of eosinophilic stromal cells observed in the carcinomatous stroma was demonstrated both in morphology and in their cytoskeletal phenotype, which conceivably suggests that the smooth muscle cells of the muscularis mucosa could convert to the eosinophilic stromal cells, namely myofibroblasts. Moreover, type I procollagen was demonstrated in both protein and mRNA levels in the areas of eosinophilic stromal cells with a lesser degree of differentiated smooth muscle phenotype that showed a transition from the muscularis mucosa, implying that the myofibroblastic cells converted from smooth muscle cells of the muscularis mucosa could be responsible for type I collagen production. These findings suggest that the muscularis mucosae may not be a passive barrier through which colorectal carcinomas infiltrate into the submucosa, but may play an active role in the formation and remodeling of tumor stroma.
基金Grants from the Special Government Funding (EVO) allocated to Turku University Central Hospital and Cancer Society of South-West Finland (Turku)
文摘AIM: To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor samples were analyzed for β-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC. RESULTS: Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 too) than those with a NI below the median (15.5 too) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted diseasespecific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046). CONCLUSION: Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.
基金Sapported by the National Natural Science Foundation of China, No. 39770818
文摘AIM: To investigate the in situ expression of suppressionof tumorigenecity 13 (ST13) mRNA in both colorectal cancer and adjacent normal tissues.METHODS: Colorectal cancer cell lines SW1116, SW620and CoLo205 were enrolled to confirm the feasibility of the in situ hybridization procedure. Seven colorectal cancer and adjacent normal tissues were included for RNA-RNA in situ hybridization.RESULTS: The expression of ST13 in the seven normal colon tissues was positive and the positive signals appeared in mucosal cells. Only three of the seven colorectal cancer tissues had positive hybridization signals that appeared in adenocarcinoma cells.CONCLUSION: The expression of ST13 decreases in colorectal cancer tissue compared with that in adjacent normal tissue. ST13 is mostly expressed in colorectal epithelia and adenocarcinoma cells.
文摘AIM: To investigate the frequency and clinical signifi- cance of the myeloid-derived suppressor cells (MDSC) in human colorectal carcinoma (CRC). METHODS: Samples of peripheral blood and tumor tis- sue from 49 CRC patients were analyzed. Mononuclear cells were isolated by FicolI-Hypaque density gradient centrifugation and were subjected to a flow cytometry- based immunophenotypic analysis. RESULTS: A considerable increase in the percentage of CD33+HLA-DR MDSCs was observed in the periph- eral blood (1.89% :1= 0.75%) and tumor tissues (2.99%±1.29%) of CRC patients as compared with that in theperipheral blood of healthy controls (0.54%±0.35%). This expanded CD33+HLA-DR subset exhibited imma- ture myeloid cell markers, but not lineage markers, and showed up-regulation of CD18/CD11b expression as compared with the MDSCs from healthy donors. Fur- ther studies showed that the MDSC proportion in CRC peripheral blood was correlated with nodal metastasis (P = 0.023), whereas that in tumor tissues was cor- related with nodal/distant metastasis (P = 0.016/P = 0.047) and tumor stage (P = 0.028), suggesting the involvement of MDSCs in CRC tumor development. CONCLUSION: Characterization of MDSCs in CRC sug- gests the clinical significance of circulating and tumor- infiltrating MDSCs and may provide new insights into the CRC immunotherapy targeting MDSCs.
基金Supported by the research project MSM 0021620808
文摘AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coil (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential, location of adenomas, macroscopic appearance and age of the patients. RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5± 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 ±15.5 mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P =0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas. CONCLUSION: Most adenomas expressed full-length APC protein, suggesting that protein expression is not a reliable marker for assessment of APC gene mutation. Complete loss of APC protein did not influence morphology, location, or appearance of adenomas, nor was it affected by the patient's age.
文摘AIM: To assess the usefulness of two independent histopathological classifications of rectal cancer regression following neo-adjuvant therapy. METHODS: Forty patients at the initial stage cT3NxM0 submitted to preoperative radiotherapy (42 Gy during 18 d) and then to radical surgical treatment. The relationship between "T-downstaging" versus regressive changes expressed by tumor regression grade (TRG 1-5) and Nasierowska-Guttmejer classification (NG 1-3) was studied as well as the relationship between TRG and NG versus local tumor stage ypT and lymph nodes status, ypN. RESULTS: Complete regression (ypT0, TRG 1) was found in one patient. "T-downstaging" was observed in 11 (27.5%) patients. There was a weak statistical significance of the relationship between "T-downstaging" and TRG staging and NG stage. Patients with ypT1 were diagnosed as TRG 2-3 while those with ypT3 as TRGS. No lymph node metastases were found in patients with TRG 1-2. None of the patients without lymph node metastases were diagnosed as TRG 5. Patients in the ypT1 stage were NG 1-2. No lymph node metastases were found in NG 1. There was a significant correlation between TRG and NG. CONCLUSION: Histopathological classifications may be useful in the monitoring of the effects of hyperfractionated preoperative radiotherapy in patients with rectal cancer at the stage of cT3NxM0. There is no unequivocal relationship between "Todownstaging" and TRG and NG. There is some concordance in the assessment of lymph node status with ypT, TRG and NG. TRG and NG are of limited value for the risk assessment of the lymph node involvement.
基金Supported by Grants from the Major State Basic Research Development Program of China, 973 Program No. 2004CB518707the Zhejiang Provincial Natural Science Foundation of China,No. R2090353the Fundamental Research Funds for the Central Universities, No. KYJD09007
文摘AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.