Modified tumor-associated carbohydrate antigens could be used to develop anti-cancer vaccines.Carbohydrate antigens in which thioglycosidic linkages are used instead of O-glycosidic linkages may be more immunogenic an...Modified tumor-associated carbohydrate antigens could be used to develop anti-cancer vaccines.Carbohydrate antigens in which thioglycosidic linkages are used instead of O-glycosidic linkages may be more immunogenic and may stimulate the production of antibodies capable of recognizing naturally occurring carbohydrates due to their enhanced resistance to endogenous glycosidases and their inherent non-self antigen character.For this purpose,a new S-linked tumor-associated carbohydrate antigen STn has been successfully synthesized for the first time.展开更多
The serum of 40 normal subjects, 61 cases of various malignant diseases except pancreatic cancer,53 cases of various benign diseases and 33 cases of pancreatic cancer was examined with ELISA to determine the serum lev...The serum of 40 normal subjects, 61 cases of various malignant diseases except pancreatic cancer,53 cases of various benign diseases and 33 cases of pancreatic cancer was examined with ELISA to determine the serum level of pancreatic cancer-associated ant展开更多
INTRODUCTIONCarcinoembryonic antigen ( CEA) , originally described by Gold and Freedman [1] in 1965, is now an acknowledged member of immunoglobulin superfamily[2],with a role as an intracellular adhesion molecule[3]....INTRODUCTIONCarcinoembryonic antigen ( CEA) , originally described by Gold and Freedman [1] in 1965, is now an acknowledged member of immunoglobulin superfamily[2],with a role as an intracellular adhesion molecule[3].Carbohydrate antigen 19-9(CA19-9), obtained with a monoclonal antibody produced by immunizing a monoclonal antibody produced by immunizing a mouse with a colonic cancer cell line in 1979[4],is a ligand for E-selectin that plays an important role in the addhesion of cancer cells to endothelial cells [5,6].展开更多
AIMS The CAS0 and CEA are well-described human tumor-as- sociated antigens most useful clinically in gastrointestinal cancer. In this study we compared these markers in sera from patients with malignant and benign dig...AIMS The CAS0 and CEA are well-described human tumor-as- sociated antigens most useful clinically in gastrointestinal cancer. In this study we compared these markers in sera from patients with malignant and benign digestive tract diseases. METHODS Using a side-phase radioimmunoassay,CA50 and CEA serum levels were measured in 33 control subjects and 86 patients with gastric cancer(n=34),gastric ulcer(n=27)and chronic atrophic gastritis(n=25).Carcinoma of the stomach was found in the antrum(n=22),in the body(n=3),and the fundus(n=9),and histopathologically,was divided into adeno- carcinoma(n=21),squamous cancer(n=4)and not divided (n=9).Gastric ulcer,when present,appeared in the antrun(18 patients),the body(3)and the fundus(9)and chronic atrophic gastritis was all associated with intestinal metaplasia(IM). RESULTS The normal ranges established for CA50 and CEA in the control group were 16.26+6.14 kU/L and 3.12±1.03/μg/L respectively.In the patients with gastric cancer,serum levels of CA50(112.67±38.36 kU/L)and CEA(10.28±3.76μg/L) were elevated significantly(P<0.01,respectively),the former being>22 kU/L in 18 of 34 patients(53%;range,5-1 550 kU/ L),and the latter>5 μg/L in 19 of 34 patients(55.8%,range, 0.5-17.4 μg/L).A statistically significant correlation was found between the levels of CA50 and GEA(r=0.648,P<0.01). The serum levels of CA50(46.4±25.9 kU/L,P<0.01 )and CEA(6.85±2.43 μg/L,P<0.01)were much lower in patients with gastric ulcer or chronic atrophic gastritis(P>0.05). CONCLUSIONS Based on these results,it is concluded that CA50 and CEA are indicators for advanced gastric cancer,and af- ter surgery,their serum levels may decrease considerably. Overall,there is such a close correlation between them that in clinical practice they might be of great value to the diagnosis of gastric cancer.展开更多
Carcinoembryonic antigen (CEA) is frequently used in the diagnosis of the colorectal carcinoma. CA242 is a novel unique tumor-associated antigen characterized by higher tumor specificity and sensitivity for colorectal...Carcinoembryonic antigen (CEA) is frequently used in the diagnosis of the colorectal carcinoma. CA242 is a novel unique tumor-associated antigen characterized by higher tumor specificity and sensitivity for colorectal cancer, as compared with other mucin antigens. In this study, preoperative levels of serum CEA and CA242 were measured in 63 cases of colorectal carcinoma. It was disclosed that the positive rate of CA242 was higher than that of CEA, particularly in patients with colon cancer.The combined determination of CEA and CA242 significantly increased the sensitivity and accuracy in the detection of colorectal cancer as compared with the use of CEA alone (P<0.o1). In patients with advanced disease the positive rate was markedly elevated, especially in patients with liver metastasis. The results indicate that the combined use of CEA and CA242 assays is an useful adjunct diagnostic measure for colorectal carcinoma, and is helpful in the assessment of the stage of the disease as well as in making treatment Plan.展开更多
Tumor-associated carbohydrate antigens （TACAs）, important molecular markers on tumor cells, are major targets for the development of anti-cancer vaccines. However, due to the immunotolerance and weak immunogenicity,...Tumor-associated carbohydrate antigens （TACAs）, important molecular markers on tumor cells, are major targets for the development of anti-cancer vaccines. However, due to the immunotolerance and weak immunogenicity, native TACAs cannot induce powerful immune response. The use of modified TACAs such as N-glycosides could be an alternative strategy to overcome this problem. Herein, the synthesis of N（OMe）-linked analogue of tumor-associated disaccharide antigen Thomsen-Friedenreich （TF） by the glycosylation reaction is described.展开更多
Tumor-associated carbohydrate antigens(TACAs)provide a special class of tumor-specific antigens that show promising applications in cancer immunotherapy.However,the weak immunogenicity and structural complexity of TAC...Tumor-associated carbohydrate antigens(TACAs)provide a special class of tumor-specific antigens that show promising applications in cancer immunotherapy.However,the weak immunogenicity and structural complexity of TACAs are obstacles to their clinical application.Here,based on a fast and low-cost purification strategy for oligosaccharide synthesis,the synthesis of tumour-associated carbohydrate antigens Globo H and mannobiose which resembles repeat unit of mannan was achieved.To enhance the immunogenicity and multivalent effect,Globo H and mannobiose were covalently attached to degradable polymer backbones.2D spindle-like lamellar micelle and globular micelle were obtained from glycopolymer through a solvent-exchange method of self-assembly.The glyconanoparticle showed good biocompatibility and degradability.Immunological functions of these glyconanoparticles such as stimulation of BMDC to cause upregulation of inflammatory factors were preliminarily explored.展开更多
Tumor-associated carbohydrate antigens(TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2...Tumor-associated carbohydrate antigens(TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2,4-ditrophenyl(DNP)-modified GM3 intermediate was synthesized chemoenzymatically and conjugated to keyhole limpet hemocyanin(KLH), and the resulting bioconjugate was tested for its potential as a vaccine candidate. Mice immunological studies revealed that the DNP-modified GM3(GM3-NHDNP) analog elicited strong and rapid immune responses by recruiting anti-DNP antibodies to facilitate the targeted delivery of the vaccine construct to antigen processing cells(APCs). Moreover, the endogenously produced anti-DNP antibodies, together with the elicited antibodies against GM3-NHDNP, may synergistically promote tumor binding and cancer cell death when the cancer cell surfaces are glycoengineered to express the GM3-NHDNP antigen.展开更多
基金National Natural Science Foundation of China(Grant No.20732001).
文摘Modified tumor-associated carbohydrate antigens could be used to develop anti-cancer vaccines.Carbohydrate antigens in which thioglycosidic linkages are used instead of O-glycosidic linkages may be more immunogenic and may stimulate the production of antibodies capable of recognizing naturally occurring carbohydrates due to their enhanced resistance to endogenous glycosidases and their inherent non-self antigen character.For this purpose,a new S-linked tumor-associated carbohydrate antigen STn has been successfully synthesized for the first time.
文摘The serum of 40 normal subjects, 61 cases of various malignant diseases except pancreatic cancer,53 cases of various benign diseases and 33 cases of pancreatic cancer was examined with ELISA to determine the serum level of pancreatic cancer-associated ant
基金This study was supported by the research grant from Administration of Key Disciplines for"Project 211"of Sun Yat-Sen University of Medical Sciences,Grant No.98097.
文摘INTRODUCTIONCarcinoembryonic antigen ( CEA) , originally described by Gold and Freedman [1] in 1965, is now an acknowledged member of immunoglobulin superfamily[2],with a role as an intracellular adhesion molecule[3].Carbohydrate antigen 19-9(CA19-9), obtained with a monoclonal antibody produced by immunizing a monoclonal antibody produced by immunizing a mouse with a colonic cancer cell line in 1979[4],is a ligand for E-selectin that plays an important role in the addhesion of cancer cells to endothelial cells [5,6].
文摘AIMS The CAS0 and CEA are well-described human tumor-as- sociated antigens most useful clinically in gastrointestinal cancer. In this study we compared these markers in sera from patients with malignant and benign digestive tract diseases. METHODS Using a side-phase radioimmunoassay,CA50 and CEA serum levels were measured in 33 control subjects and 86 patients with gastric cancer(n=34),gastric ulcer(n=27)and chronic atrophic gastritis(n=25).Carcinoma of the stomach was found in the antrum(n=22),in the body(n=3),and the fundus(n=9),and histopathologically,was divided into adeno- carcinoma(n=21),squamous cancer(n=4)and not divided (n=9).Gastric ulcer,when present,appeared in the antrun(18 patients),the body(3)and the fundus(9)and chronic atrophic gastritis was all associated with intestinal metaplasia(IM). RESULTS The normal ranges established for CA50 and CEA in the control group were 16.26+6.14 kU/L and 3.12±1.03/μg/L respectively.In the patients with gastric cancer,serum levels of CA50(112.67±38.36 kU/L)and CEA(10.28±3.76μg/L) were elevated significantly(P<0.01,respectively),the former being>22 kU/L in 18 of 34 patients(53%;range,5-1 550 kU/ L),and the latter>5 μg/L in 19 of 34 patients(55.8%,range, 0.5-17.4 μg/L).A statistically significant correlation was found between the levels of CA50 and GEA(r=0.648,P<0.01). The serum levels of CA50(46.4±25.9 kU/L,P<0.01 )and CEA(6.85±2.43 μg/L,P<0.01)were much lower in patients with gastric ulcer or chronic atrophic gastritis(P>0.05). CONCLUSIONS Based on these results,it is concluded that CA50 and CEA are indicators for advanced gastric cancer,and af- ter surgery,their serum levels may decrease considerably. Overall,there is such a close correlation between them that in clinical practice they might be of great value to the diagnosis of gastric cancer.
文摘Carcinoembryonic antigen (CEA) is frequently used in the diagnosis of the colorectal carcinoma. CA242 is a novel unique tumor-associated antigen characterized by higher tumor specificity and sensitivity for colorectal cancer, as compared with other mucin antigens. In this study, preoperative levels of serum CEA and CA242 were measured in 63 cases of colorectal carcinoma. It was disclosed that the positive rate of CA242 was higher than that of CEA, particularly in patients with colon cancer.The combined determination of CEA and CA242 significantly increased the sensitivity and accuracy in the detection of colorectal cancer as compared with the use of CEA alone (P<0.o1). In patients with advanced disease the positive rate was markedly elevated, especially in patients with liver metastasis. The results indicate that the combined use of CEA and CA242 assays is an useful adjunct diagnostic measure for colorectal carcinoma, and is helpful in the assessment of the stage of the disease as well as in making treatment Plan.
基金Grant from the Ministry of Science and Technology of China(Grant No.2012ZX09502001-001)the National Natural Science Foundation of China(Grant No.81172916)
文摘Tumor-associated carbohydrate antigens （TACAs）, important molecular markers on tumor cells, are major targets for the development of anti-cancer vaccines. However, due to the immunotolerance and weak immunogenicity, native TACAs cannot induce powerful immune response. The use of modified TACAs such as N-glycosides could be an alternative strategy to overcome this problem. Herein, the synthesis of N（OMe）-linked analogue of tumor-associated disaccharide antigen Thomsen-Friedenreich （TF） by the glycosylation reaction is described.
基金supported by the National Key Research and Development Program of China(No.2023YFA0915300)the National Natural Science Foundation of China(Nos.52125303 and 92356305)Innovation Program of Shanghai Municipal Education Commission(No.2023ZKZD02)。
文摘Tumor-associated carbohydrate antigens(TACAs)provide a special class of tumor-specific antigens that show promising applications in cancer immunotherapy.However,the weak immunogenicity and structural complexity of TACAs are obstacles to their clinical application.Here,based on a fast and low-cost purification strategy for oligosaccharide synthesis,the synthesis of tumour-associated carbohydrate antigens Globo H and mannobiose which resembles repeat unit of mannan was achieved.To enhance the immunogenicity and multivalent effect,Globo H and mannobiose were covalently attached to degradable polymer backbones.2D spindle-like lamellar micelle and globular micelle were obtained from glycopolymer through a solvent-exchange method of self-assembly.The glyconanoparticle showed good biocompatibility and degradability.Immunological functions of these glyconanoparticles such as stimulation of BMDC to cause upregulation of inflammatory factors were preliminarily explored.
基金supported by the National Natural Science Foundation of China (Nos. 21907038, 32000904)the Natural Science Foundation of Jiangsu Province (No. BK20200601, China)+4 种基金the National Postdoctoral Program for Innovative Talents of China (No. BX20200153)the Health and Family Planning Commission of Wuxi, China (No. Z202005)the Social Development Key Project of Jiangsu Province (No. BE2019632, China)partly supported by the 111 Project (No. 111-2-06, China)the National First-class Discipline Program of Food Science and Technology (No. JUFSTR20180101, China)。
文摘Tumor-associated carbohydrate antigens(TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2,4-ditrophenyl(DNP)-modified GM3 intermediate was synthesized chemoenzymatically and conjugated to keyhole limpet hemocyanin(KLH), and the resulting bioconjugate was tested for its potential as a vaccine candidate. Mice immunological studies revealed that the DNP-modified GM3(GM3-NHDNP) analog elicited strong and rapid immune responses by recruiting anti-DNP antibodies to facilitate the targeted delivery of the vaccine construct to antigen processing cells(APCs). Moreover, the endogenously produced anti-DNP antibodies, together with the elicited antibodies against GM3-NHDNP, may synergistically promote tumor binding and cancer cell death when the cancer cell surfaces are glycoengineered to express the GM3-NHDNP antigen.
