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
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
The role of the transcription factor NF-κB in shaping the cancer microenvironment is becoming increasingly clear. Inflammation alters the activity of enzymes that modulate NF-κB function, and causes extensive change...The role of the transcription factor NF-κB in shaping the cancer microenvironment is becoming increasingly clear. Inflammation alters the activity of enzymes that modulate NF-κB function, and causes extensive changes in genomic chromatin that ultimately drastically alter cell-specific gene expression. NF-κB regulates the expression of cytokines and adhesion factors that control interactions among adjacent cells. As such, NF-κB fine tunes tissue cellular composition, as well as tissues' interactions with the immune system. Therefore, NF-κB changes the cell response to hormones and to contact with neighboring cells. Activating NF-κB confers transcriptional and phenotypic plasticity to a cell and thereby enables profound local changes in tissue function and composition. Research suggests that the regulation of NF-κB target genes is specifically altered in cancer. Such alterations occur not only due to mutations of NF-κB regulatory proteins, but also because of changes in the activity of specific proteostatic modules and metabolic pathways. This article describes the molecular mode of NF-κB regulation with a few characteristic examples of target genes.展开更多
Direct aminolysis of selenoester in aqueous media was investigated as a glycopeptide ligation strategy.This strategy allows the peptide and glycopeptide ligation to proceed smoothly(even with hindered amino acids) wit...Direct aminolysis of selenoester in aqueous media was investigated as a glycopeptide ligation strategy.This strategy allows the peptide and glycopeptide ligation to proceed smoothly(even with hindered amino acids) without the need of cysteine residue, N-terminal thiol auxiliary or coupling additive, and to afford the corresponding amide products in excellent yields. No epimerization was observed during ligation reations. In this work, the selenoester of unprotected glycopeptide was readily prepared, and the direct aminolysis of glycopeptide selenoester was successfully applied to synthesize MUC1 mucin sequence efficiently.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The role of the transcription factor NF-κB in shaping the cancer microenvironment is becoming increasingly clear. Inflammation alters the activity of enzymes that modulate NF-κB function, and causes extensive changes in genomic chromatin that ultimately drastically alter cell-specific gene expression. NF-κB regulates the expression of cytokines and adhesion factors that control interactions among adjacent cells. As such, NF-κB fine tunes tissue cellular composition, as well as tissues' interactions with the immune system. Therefore, NF-κB changes the cell response to hormones and to contact with neighboring cells. Activating NF-κB confers transcriptional and phenotypic plasticity to a cell and thereby enables profound local changes in tissue function and composition. Research suggests that the regulation of NF-κB target genes is specifically altered in cancer. Such alterations occur not only due to mutations of NF-κB regulatory proteins, but also because of changes in the activity of specific proteostatic modules and metabolic pathways. This article describes the molecular mode of NF-κB regulation with a few characteristic examples of target genes.
基金supported by the National Key Research and Development Program of China (No. 2017YFA0505200)the National Natural Science Foundation of China (No. 21772056)+2 种基金Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation Open Foundation (No. JXMS201701)the self-determined research funds of CCNU from the colleges' basic research and operation of MOE (No. CCNU18TS011)the Program of Introducing Talents of Discipline to Universities of China(111 program, No. B17019)
文摘Direct aminolysis of selenoester in aqueous media was investigated as a glycopeptide ligation strategy.This strategy allows the peptide and glycopeptide ligation to proceed smoothly(even with hindered amino acids) without the need of cysteine residue, N-terminal thiol auxiliary or coupling additive, and to afford the corresponding amide products in excellent yields. No epimerization was observed during ligation reations. In this work, the selenoester of unprotected glycopeptide was readily prepared, and the direct aminolysis of glycopeptide selenoester was successfully applied to synthesize MUC1 mucin sequence efficiently.
