AIM： To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma （ICC）. Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fl...AIM： To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma （ICC）. Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined. METHODS： The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87 cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated. RESULTS： Fifty-two patients （60%） exhibited both MUC1 and MUCSAC expressions, whereas 31% expressed either MUC1 or MUC5AC, and 9% expressed neither. High MUC1 immunoreactivity displayed a significant correlation wibh tumor progression as reflected by vascular invasion （P〈0.001）, whereas high expression of MUC5AC significantly correlated with neural invasion （P = 0.022） and advanced ICC stage （P = 0.008）. Patients with high expression of MUC1 had a significantly shorter survival （P = 0.0002）. According to multivariate analyses, MUC1 reactivity （P = 0.026）, histological grading and stage of tumor represented the least probability of survival. CONCLUSION： MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.展开更多
AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells. METHODS: Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were per...AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells. METHODS: Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were performed to measure the adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with different VNTR lengths. RESULTS: Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher (P < 0.05) adhesion to all the cell lines and clones tested, when compared to the non-pathogenic strain HPTx30a. Bacteria showed a significantly higher (P < 0.05) adhesion to the GP202 cell line, when compared to the MKN45 cell line. Furthermore, both strains showed a significantly higher (P < 0.05) adhesion to GP202 clones with larger MUC1 VNTR domains. CONCLUSION: This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells. The extent of bacterial adhesion depends on the size of theMUC1 VNTR domain. The adhesion is further dependent on bacterial pathogenicity and the gastric cell line. MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.展开更多
AIM:To explore useful prognostic factors for mucinous adenocarcinoma(MAC) in the colon and rectum.METHODS:MAC was divided into low-and high-grade types based on the degree of structural differentiation;low-grade MAC a...AIM:To explore useful prognostic factors for mucinous adenocarcinoma(MAC) in the colon and rectum.METHODS:MAC was divided into low-and high-grade types based on the degree of structural differentiation;low-grade MAC arisen from well to moderately differentiated adenocarcinoma and papillary carcinoma,and high-grade MAC from poorly differentiated adenocarcinoma and signet ring cell carcinoma.Immunohistochemically,the expression of 2 types of MUC1(MUC1/DF and MUC1/CORE),MUC2,2 types of MUC5AC(MUC5AC/CHL2 and HGM),MUC6,CDX2,and CD10 was examined in 16 cases of MAC consisting of 6 low-and 10 high-grade types.RESULTS:MUC1/DF3 was expressed in 3 of 6 low-grade MAC(50) and 10 of 10 high-grade MAC(100).MUC1/CORE was expressed in 1 of 6 lowgrade MAC(16.7) and 7 of 10 high-grade MAC(70).MUC2 was expressed in all MAC regardless of the grade.MUC5AC was expressed in 6 of 6 low-grade MAC(100) and 4 of 10 high-grade MAC(40).HGM was expressed in 5 of 6 low-grade MAC(83.3) and 6 of 10 high-grade MAC(60).Expression of MUC6 and CD10 was undetected in all MAC regardless of the grade.CDX2 was expressed in 5 of 6 low-grade MAC(83.3) and 7 of 10 high-grade MAC(70).Taken together,MUC1/DF3 was expressed significantly more frequently in high-grade MAC than in low-grade,and MUC5AC/CHL2 was expressed significantly more frequently in low-grade MAC than in high-grade.CONCLUSION:It is proposed that MUC1/DF3 and MUC5AC/CHL2 immunostaining is useful to discriminate high-grade MAC from low-grade MAC.展开更多
BACKGROUND Pancreatic mucinous cystadenocarcinoma(MCAC)is a rare malignancy with a poor prognosis when it presents metastases at diagnosis.Due to its very low incidence,there are no clear recommendations for the treat...BACKGROUND Pancreatic mucinous cystadenocarcinoma(MCAC)is a rare malignancy with a poor prognosis when it presents metastases at diagnosis.Due to its very low incidence,there are no clear recommendations for the treatment of advanced disease.Olaparib(an oral PARP inhibitor)has been approved for the maintenance treatment of patients with metastatic pancreatic adenocarcinoma harbouring germline BRCA1/2 mutations.Herein,we report the first case of a germline BRCA1 mutated unresectable MCAC which was effectively treated with olaparib.CASE SUMMARY A 41-year-old woman,without personal or family history of cancer,was diagnosed with ovarian and peritoneal metastases of MCAC.She underwent 12 cycles of gemcitabine plus oxaliplatin(GEMOX)obtaining a partial response and allowing radical surgery.One year later,local recurrence was documented,and other 12 cycles of GEMOX were administered obtaining a complete response.Seven years later,another local recurrence,not amenable to surgical resection,was diagnosed.She started FOLFIRINOX(oxaliplatin,irinotecan,leucovorin and fluorouracil),obtaining a partial response after 8 cycles.Given the excellent response to platinum-based chemotherapy,BRCA testing was performed,and a BRCA1 germline mutation was detected.She was switched to maintenance olaparib due to chemotherapy-related toxicities and achieved an almost complete metabolic response,with a reduction in the diameter of the lesion,after three months of therapy.CONCLUSION The current case suggests the beneficial effect of olaparib in BRCA mutated MCAC.However,further studies are required.展开更多
Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and ...Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and coinvestigators showed recently that MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through β-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-β-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound.展开更多
目的研究异黏蛋白(Metadherin,MTDH)、转酮醇酶样基因1(transketolase Like Protein 1,TKTL1)在喉癌组织中的表达及其与相关肿瘤标志物及癌细胞增殖活力的相关性。方法选取2013年1月~2016年12月于我科治疗的70例确诊为喉鳞状细胞癌(简...目的研究异黏蛋白(Metadherin,MTDH)、转酮醇酶样基因1(transketolase Like Protein 1,TKTL1)在喉癌组织中的表达及其与相关肿瘤标志物及癌细胞增殖活力的相关性。方法选取2013年1月~2016年12月于我科治疗的70例确诊为喉鳞状细胞癌(简称喉癌组)患者为研究对象,另选70例同期于我院诊断为声带息肉患者为对照组,测定癌组织和息肉组织中MTDH、TKTL1的阳性表达率及MTDH、TKTL1的mRNA表达量,检测两组患者血清鳞状细胞癌抗原(squamous cell carcinoma related antigen,SCCAg)、癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原199(carbohydrate antigen,CA199)含量,检测组织中癌基因信号传导及转录激活因子3(signal transducers and activators of transcription,STAT3)、原癌基因c-myc的mRNA含量,采用Pearson法检测MTDH、TKTL1与血清SCCAg、CEA、CA199及STAT3、c-myc表达量的相关性。结果喉癌组织中MTDH与TKTL1阳性率分别为58.57%、64.29%,均高于对照组的20%、12.86%(P均<0.01)。喉癌组MTDH与TKTL1的mRNA表达量分别为1.78±0.45、1.97±0.62,均显著高于对照组的0.19±0.03、0.21±0.07(P均<0.01);喉癌组的血清肿瘤标志物SCCAg、CEA、CA199水平分别为6.75±2.74、9.36±2.73、31.54±10.36,显著高于对照组的1.34±0.83、3.21±1.36、12.42±4.13(P均<0.01);喉癌组织中的STAT3、c-myc mRNA表达量分别为2.36±0.75、1.99±0.51,显著高于对照组的0.67±0.12、0.71±0.15(P均<0.01)。M T DH、T KT L1表达量与血清SCCAg、CEA、CA199含量及STAT3、c-myc均呈正相关。结论 MTDH、TKTL1在喉癌组织中的表达显著增加,与癌症发生发展密切相关,且与肿瘤标志物、促癌基因的表达呈正相关,有促进癌细胞增殖的作用。展开更多
基金Supported by the Thailand Research Fund, No. BRG/06/2544Royal Golden Jubilee PhD Program Grant, No. PHD/0045/2542 to Boonla C and Wongkham S
文摘AIM： To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma （ICC）. Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined. METHODS： The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87 cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated. RESULTS： Fifty-two patients （60%） exhibited both MUC1 and MUCSAC expressions, whereas 31% expressed either MUC1 or MUC5AC, and 9% expressed neither. High MUC1 immunoreactivity displayed a significant correlation wibh tumor progression as reflected by vascular invasion （P〈0.001）, whereas high expression of MUC5AC significantly correlated with neural invasion （P = 0.022） and advanced ICC stage （P = 0.008）. Patients with high expression of MUC1 had a significantly shorter survival （P = 0.0002）. According to multivariate analyses, MUC1 reactivity （P = 0.026）, histological grading and stage of tumor represented the least probability of survival. CONCLUSION： MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.
基金Portuguese Foundation for Science and Technology(FCT)Project POCTI/CBO/44812/2002+1 种基金Project POCTI/SAU-IMI/56895/2004 National Institutes of Health, R01-CA57362
文摘AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells. METHODS: Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were performed to measure the adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with different VNTR lengths. RESULTS: Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher (P < 0.05) adhesion to all the cell lines and clones tested, when compared to the non-pathogenic strain HPTx30a. Bacteria showed a significantly higher (P < 0.05) adhesion to the GP202 cell line, when compared to the MKN45 cell line. Furthermore, both strains showed a significantly higher (P < 0.05) adhesion to GP202 clones with larger MUC1 VNTR domains. CONCLUSION: This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells. The extent of bacterial adhesion depends on the size of theMUC1 VNTR domain. The adhesion is further dependent on bacterial pathogenicity and the gastric cell line. MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.
基金Supported by Grants-Aid for Researchers,Hyogo College of Medicine and Grants-in Aid for Scientif ic Research and Hitec Research Center Grant from the Ministry of Education,Science,Sports,Culture,and Technology of Japan
文摘AIM:To explore useful prognostic factors for mucinous adenocarcinoma(MAC) in the colon and rectum.METHODS:MAC was divided into low-and high-grade types based on the degree of structural differentiation;low-grade MAC arisen from well to moderately differentiated adenocarcinoma and papillary carcinoma,and high-grade MAC from poorly differentiated adenocarcinoma and signet ring cell carcinoma.Immunohistochemically,the expression of 2 types of MUC1(MUC1/DF and MUC1/CORE),MUC2,2 types of MUC5AC(MUC5AC/CHL2 and HGM),MUC6,CDX2,and CD10 was examined in 16 cases of MAC consisting of 6 low-and 10 high-grade types.RESULTS:MUC1/DF3 was expressed in 3 of 6 low-grade MAC(50) and 10 of 10 high-grade MAC(100).MUC1/CORE was expressed in 1 of 6 lowgrade MAC(16.7) and 7 of 10 high-grade MAC(70).MUC2 was expressed in all MAC regardless of the grade.MUC5AC was expressed in 6 of 6 low-grade MAC(100) and 4 of 10 high-grade MAC(40).HGM was expressed in 5 of 6 low-grade MAC(83.3) and 6 of 10 high-grade MAC(60).Expression of MUC6 and CD10 was undetected in all MAC regardless of the grade.CDX2 was expressed in 5 of 6 low-grade MAC(83.3) and 7 of 10 high-grade MAC(70).Taken together,MUC1/DF3 was expressed significantly more frequently in high-grade MAC than in low-grade,and MUC5AC/CHL2 was expressed significantly more frequently in low-grade MAC than in high-grade.CONCLUSION:It is proposed that MUC1/DF3 and MUC5AC/CHL2 immunostaining is useful to discriminate high-grade MAC from low-grade MAC.
文摘BACKGROUND Pancreatic mucinous cystadenocarcinoma(MCAC)is a rare malignancy with a poor prognosis when it presents metastases at diagnosis.Due to its very low incidence,there are no clear recommendations for the treatment of advanced disease.Olaparib(an oral PARP inhibitor)has been approved for the maintenance treatment of patients with metastatic pancreatic adenocarcinoma harbouring germline BRCA1/2 mutations.Herein,we report the first case of a germline BRCA1 mutated unresectable MCAC which was effectively treated with olaparib.CASE SUMMARY A 41-year-old woman,without personal or family history of cancer,was diagnosed with ovarian and peritoneal metastases of MCAC.She underwent 12 cycles of gemcitabine plus oxaliplatin(GEMOX)obtaining a partial response and allowing radical surgery.One year later,local recurrence was documented,and other 12 cycles of GEMOX were administered obtaining a complete response.Seven years later,another local recurrence,not amenable to surgical resection,was diagnosed.She started FOLFIRINOX(oxaliplatin,irinotecan,leucovorin and fluorouracil),obtaining a partial response after 8 cycles.Given the excellent response to platinum-based chemotherapy,BRCA testing was performed,and a BRCA1 germline mutation was detected.She was switched to maintenance olaparib due to chemotherapy-related toxicities and achieved an almost complete metabolic response,with a reduction in the diameter of the lesion,after three months of therapy.CONCLUSION The current case suggests the beneficial effect of olaparib in BRCA mutated MCAC.However,further studies are required.
文摘Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and coinvestigators showed recently that MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through β-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-β-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound.
文摘目的研究异黏蛋白(Metadherin,MTDH)、转酮醇酶样基因1(transketolase Like Protein 1,TKTL1)在喉癌组织中的表达及其与相关肿瘤标志物及癌细胞增殖活力的相关性。方法选取2013年1月~2016年12月于我科治疗的70例确诊为喉鳞状细胞癌(简称喉癌组)患者为研究对象,另选70例同期于我院诊断为声带息肉患者为对照组,测定癌组织和息肉组织中MTDH、TKTL1的阳性表达率及MTDH、TKTL1的mRNA表达量,检测两组患者血清鳞状细胞癌抗原(squamous cell carcinoma related antigen,SCCAg)、癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原199(carbohydrate antigen,CA199)含量,检测组织中癌基因信号传导及转录激活因子3(signal transducers and activators of transcription,STAT3)、原癌基因c-myc的mRNA含量,采用Pearson法检测MTDH、TKTL1与血清SCCAg、CEA、CA199及STAT3、c-myc表达量的相关性。结果喉癌组织中MTDH与TKTL1阳性率分别为58.57%、64.29%,均高于对照组的20%、12.86%(P均<0.01)。喉癌组MTDH与TKTL1的mRNA表达量分别为1.78±0.45、1.97±0.62,均显著高于对照组的0.19±0.03、0.21±0.07(P均<0.01);喉癌组的血清肿瘤标志物SCCAg、CEA、CA199水平分别为6.75±2.74、9.36±2.73、31.54±10.36,显著高于对照组的1.34±0.83、3.21±1.36、12.42±4.13(P均<0.01);喉癌组织中的STAT3、c-myc mRNA表达量分别为2.36±0.75、1.99±0.51,显著高于对照组的0.67±0.12、0.71±0.15(P均<0.01)。M T DH、T KT L1表达量与血清SCCAg、CEA、CA199含量及STAT3、c-myc均呈正相关。结论 MTDH、TKTL1在喉癌组织中的表达显著增加,与癌症发生发展密切相关,且与肿瘤标志物、促癌基因的表达呈正相关,有促进癌细胞增殖的作用。
