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Carbohydrate Antigen (carbohydrate + antigen)
Selected AbstractsSynthesis of Non-Natural Glycosylamino Acids Containing Tumor-Associated Carbohydrate Antigens.CHEMINFORM, Issue 48 2003Stacy J. Keding No abstract is available for this article. [source] Original Article: Relationship between the serum CA-125 level and bone mineral density in healthy pre- and post-menopausal womenAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2010Ki Hoon AHN Background:, Osteoporosis and tumour-associated antigen (TAA) levels are associated with inflammatory processes, but little remains known about TAA levels and bone mineral density (BMD). Aims:, We determined whether or not high-normal TAA levels are associated with a lower BMD in healthy women. Methods:, A total of 3769 healthy women were enrolled from the health screening programme over 5 years. Each participant had undergone a basic health examination. Serum carbohydrate antigen (CA)-125, CA-19-9, carcinoembryonic antigen (CEA) and alpha-fetoprotein levels were evaluated as tumour markers. The correlations between serum TAA levels and BMD were analysed. Results:, Carbohydrate antigen 125 and CEA levels were positively associated with a higher BMD in the pre-menopause. In the post-menopause, the CA-125 level was positively associated with BMD. In the pre-menopause, CA-125 (r = 0.102; P < 0.001) and CEA levels (r = 0.134; P < 0.001) had a significant correlation with BMD. In the post-menopause, CA-125 was negatively associated with alkaline phosphatase (r = ,0.298; P < 0.001). Conclusions:, There was a significant positive association between CA-125 and BMD in healthy women. Additional basic and clinical studies on the relationship between CA-125 and bone are needed. [source] Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinomaCANCER, Issue 12 2009Michele Reni MD Abstract BACKGROUND: Radiologic assessment of tumor response in pancreatic cancer is complicated by desmoplastic reactions within or around the tumor. The objective of this study was to evaluate the correlation between a decline in carbohydrate antigen 19-9 (CA 19-9) and survival in patients with advanced pancreatic cancer who received upfront chemotherapy. METHODS: CA 19-9 serum basal values were measured in 247 patients with advanced pancreatic cancer who were enrolled in 5 consecutive trials between 1997 and 2007. Survival curves were compared among patients who had a predefined CA 19-9 nadir variation (<50%. Group 1; 50% to 89%, Group 2; or >89%, Group 3). To eliminate guarantee-time bias, survival analysis was repeated using the landmark method. RESULTS: In both univariate and multivariate analysis, the basal CA 19-9 value significantly predicted survival. The median survival was 15.5 months for 34 patients who had normal basal CA 19-9 values, 11.9 months for 108 patients who had basal values between 38 U/mL and 1167 U/mL, and 8 months for 105 patients who had basal values >1167 U/mL. At least 1 CA 19-9 follow-up value was available for 204 patients who had baseline values greater than normal. A significant difference in overall survival was observed in univariate and multivariate analyses between Groups 1 and 2, between Groups 1 and 3, and between Groups 2 and 3. The results were confirmed using the landmark method. CONCLUSIONS: In this study, baseline CA 19-9 was confirmed as an independent prognostic factor for survival, and it may be considered as a stratification factor in trials in patients with advanced pancreatic cancer. Biochemical response may be used as a complementary measure to radiologic response to provide a better assessment of chemotherapy activity and to drive treatment decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society. [source] Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis,HEPATOLOGY, Issue 1 2010Sanjay Y. Bangarulingam Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51%) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH polysomy were 46% and 88%, and for trisomy/tetrasomy they were 25% and 67%, respectively. Survival analysis showed that patients with FISH polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures. Conclusion: In PSC patients, the presence of a dominant stricture plus FISH polysomy has a specificity of 88% for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). (HEPATOLOGY 2009.) [source] Intra-abdominal sequestration of the lung and elevated serum levels of CA 19-9: a diagnostic pitfallHPB, Issue 1 2004C Armbruster Background Extralobar pulmonary sequestration is an uncommon congenital abnormality that is rarely diagnosed after the age of 40 years. We describe a 64-year-old woman with an intra-abdominal sequestration of the lung and elevated carbohydrate antigen (CA) 19-9 serum levels. Case outline On abdominal ultrasound a semi-solid cystic tumour was demonstrated that showed tight connection to the tail of the pancreas according to computed tomography. Cytological examination of the percutaneous biopsy did not lead to a definitive diagnosis. CA 19-9 serum levels were repeatedly elevated >250 IU/ml. With a tentative diagnosis of a tumour of the tail of pancreas the semi-solid cystic mass was resected. Frozen section histology suggested the diagnosis of pulmonary sequestration, which was confirmed by definitive histological examination. Immunohistochemical staining of the specimen with a specific monoclonal antibody against CA 19-9 showed strong immunoreactivity. Three months later the elevated CA 19-9 serum levels returned to normal. Discussion Elevated CA 19-9 serum levels have been described in benign pulmonary and mediastinal cystic lesions and in one case of extralobar intrathoracic lung sequestration. Although there is evidence that malignancies may arise in congenital lung cysts, CA 19-9 serum levels have not been investigated in such cases. Based on our results elevated serum values of CA 19-9 in combination with a cystic semi-solid mass in the left subphrenic space should include the differential diagnosis of extralobar pulmonary sequestration. [source] A carbohydrate neoepitope that is up-regulated on human mononuclear leucocytes by neuraminidase treatment or by cellular activationIMMUNOLOGY, Issue 2 2001Mark T. Quinn Summary The expression of cell-surface antigens can delineate specific leucocyte developmental or functional stages. For example, certain membrane glycoproteins are expressed selectively on leucocyte subsets only after activation. Leucocyte activation can also induce changes in carbohydrate epitopes expressed on surface antigens. In the present studies, we report on a novel monoclonal immunoglobulin M antibody (mAb 13.22) that recognizes a unique carbohydrate epitope expressed on human leucocyte membrane proteins. Characterization of mAb 13.22 specificity by immunoblotting showed that it recognized proteins of MW ,95 000 and 150 000, including both CD18 and CD11b. The mAb 13.22 epitope was removed by N -glycosidase F but not by endoglycosidase H or fucosidase, demonstrating that it is an N-linked carbohydrate antigen. Interestingly, immunoblot staining was enhanced after neuraminidase treatment, suggesting that the antibody epitope might also be partially masked by sialic acid. In resting leucocytes, the mAb 13.22 antigen was expressed strongly on neutrophils, while dull staining was present on monocytes, and no lymphocyte staining was observed. In marked contrast, treatment of leucocytes with neuraminidase resulted in exposure of a mAb 13.22 neoepitope on a subset of lymphocytes (primarily T lymphocytes and natural killer cells) as well as up-regulated staining more than 18-fold on monocytes. Activation of lymphocytes in culture with phytohaemagglutinin or concanavalin A also unmasked the mAb 13.22 neoepitope on ,37% of the CD45RO+ lymphocytes. Furthermore, analysis of leucocytes collected from the synovial fluid of patients with rheumatoid arthritis showed that ,18% of the lymphocytes present expressed the mAb 13.22 neoepitope. Taken together, our results suggest that the mAb 13.22 carbohydrate neoepitope could represent a physiologically relevant marker that is up-regulated on leucocyte subsets during the inflammatory response. [source] RM2 antigen (,1,4-GalNAc-disialyl-Lc4) as a new marker for prostate cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Seiichi Saito Abstract Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, ,1,4-GalNAc-disialyl-Lc4, defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and ,4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern ,4, high Gleason score (,8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer. © 2005 Wiley-Liss, Inc. [source] Low-grade renal epithelial tumor originating from the distal nephronINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2004NOBORU HARA Abstract, There are few published reports of low-grade renal epithelial tumor originating from the distal nephron. However, it should not be disregarded clinically, because the actual number of patients with such tumors may be higher than expected. We investigated the immunohistochemical profile of a histologically distinct subtype of such a tumor in detail, in addition to the clinical course and imaging studies. The present study demonstrated that both glandular and spindle cell components of this tumor have a persistent characteristic of an epithelial tumor arising from the distal tubule or collecting duct. This tumor is a benign complex neoplasm that can be treated successfully with radical surgery. Beta-catenin and E-cadherin are suggested to play a crucial role in tumorigenesis and the biphasic arrangement of this neoplasm, concerning the expression of epithelial membrane antigen and carbohydrate antigen 19-9. We suggest that the term ,distal nephron epithelioma' is appropriate for classifying such rare but clinicopathologically distinct tumors. [source] Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic populationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2004JEE-EUN KIM Abstract Background and Aim:, Although the prognosis for pancreatic cancer is generally poor, it is well known that the survival rate for resected pancreatic cancer is much higher than that for more conservative treatment. The importance of early detection is emphasized for resection of pancreatic cancer. Measurement of serum carbohydrate antigen (CA) 19-9 has shown satisfactory sensitivity and predictive value in symptomatic patients, but no available data has been found on healthy asymptomatic subjects. Thus, the authors aimed to determine the clinical usefulness of CA 19-9 as a screening tool for pancreatic cancer in asymptomatic subjects. Methods:, From December 1994 to November 2000, 70 940 asymptomatic persons visiting the Health Promotion Center at the Samsung Medical Center, Seoul, Korea, participated. All subjects underwent abdominal ultrasonography and serum CA 19-9 measurement. The authors analyzed the sensitivity, specificity, and predictive values of CA 19-9 for detecting pancreatic cancer. Also, those subjects who had a serum CA 19-9 level above the cut-off value were followed up using a serial check of CA 19-9, computed tomography, or endoscopic retrograde cholangiopancreatography. Results:, The number of subjects with a level of CA 19-9 above the cutoff of 37 U/mL was 1063 (1.5%), including four cases diagnosed with pancreatic cancer. The prevalence of pancreatic cancer over the age of 30 years is 13.66 per 100 000 population in Korea. Therefore, the sensitivity is 100% and the specificity 98.5%. However, the positive predictive value of CA 19-9 for detecting pancreatic cancer is only 0.9% in the asymptomatic population. Conclusion:, Mass screening for pancreatic cancer using CA 19-9 levels in asymptomatic subjects is ineffective because of a very low positive predictive value, despite its high sensitivity and specificity. [source] Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2006Mitsuhiro Nakae Abstract Aim:, New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high-throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125. Methods:, Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125. Results:, Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone. Conclusion:, Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed. [source] Gallbladder adenocarcinoma arising in Rokitansky,Aschoff sinusPATHOLOGY INTERNATIONAL, Issue 12 2008Tadashi Terada Carcinoma arising from Rokitansky,Aschoff sinus (RAS) is extremely rare; only eight cases have been reported in the literature. Herein is reported a case of minute adenocarcinoma arising in RAS. A 77-year-old Japanese man with gallbladder stones underwent cholecystectomy. A tiny submucosal tumor (1 cm × 1 cm) was incidentally recognized. Histologically, the submucosal tumor was located in the subserosa and, to a lesser extent, in the fibromuscular layer. It was adenocarcinoma. RAS were recognized within the tumor, and there was a gradual transition between RAS and the adenocarcinoma. Mucin histochemistry indicated neutral and acidic mucins in the cytoplasm and lumens of the adenocarcinoma cells. Immunohistochemistry showed that the adenocarcinoma cells were positive for cytokeratin, epithelial membrane antigen, carbohydrate antigen 19-9, K-i67 (labeling = 80%), MUC1, MUC5AC and MUC6. In contrast, the adenocarcinoma cells were negative for CEA, c-erbB2, p53 protein, MUC2 and CD10. In summary, minute subserosal adenocarcinoma, which arose in RAS, was found incidentally; therefore careful examination of resected gallbladders is necessary. [source] Immunohistochemistry and K-ras sequence of pancreatic carcinosarcomaPATHOLOGY INTERNATIONAL, Issue 10 2008Takumi Nakano Herein is presented a case of carcinosarcoma of the pancreas in an 82-year-old woman, analyzed on immunohistochemistry and K-ras sequence. The tumor, which arose in the pancreas head, was removed on pancreaticoduodenectomy. The patient died, however, of disseminated intravascular coagulation syndrome from postoperative sepsis 13 days later. Microscopically, the tumor consisted of malignant epithelial (well-differentiated adenocarcinoma cells) and mesenchymal (spindle-shaped tumor cells) components. The adenocarcinoma cells had positive immunostaining for cytokeratin AE1/AE3, cytokeratin 7, epithelial membrane antigen (EMA), CEA and carbohydrate antigen 19-9 (CA 19-9), while focal staining of these proteins was observed in the sarcomatous cells. In contrast, the sarcomatous cells had diffuse immunostaining for vimentin, CD10 and p53, while these proteins were not expressed in the ductal adenocarcinoma cells. These findings support the dual characteristics of a carcinosarcoma. DNA sequencing of the present case indicated point mutations of K-ras in both codons 12 and 34 on exon 2. The latter mutation is likely to correlate with the sarcomatous characteristics of this tumor. The tumor cells had specific and diffuse positive staining for CD10 and p53, with features characteristic of rapid growth. [source] Aberrant expression of pyloric gland-type mucin in mucin-producing bile duct carcinomas: A clear difference between the core peptide and the carbohydrate moietyPATHOLOGY INTERNATIONAL, Issue 8 2005Masamichi Goto The authors have recently defined the clinopathological entity of a mucin-producing bile duct tumor (MPBT), and divided MPBT into two distinct subtypes: ,columnar-type' and ,cuboidal-type' MPBT. Mucin core protein 6 (MUC6), which is present in normal pyloric glands, had higher expression levels in cuboidal-type tumors than in columnar-type tumors. In the pyloric glands, a carbohydrate antigen detected by monoclonal antibody HIK1083 (CA/HIK1083) is also expressed. In order to evaluate the coexpression pattern of MUC6 and CA/HIK1083 in MPBT, expression profiles were evaluated in 38 surgically excised mucin-producing bile duct carcinomas (MPBC; cuboidal-type, n = 15; columnar-type, n = 23), using immunohistochemistry. The staining rate was graded as follows: ,, <5% of neoplastic cells stained; +, 5% to <20%; +,+, 20% to <50%; +,+,+, ,50%. In cuboidal-type MPBC, MUC6 was positive in all cases (+,+,+, 13/15; +,+, 1/15; +, 1/15), whereas CA/HIK1083 was negative in all cases (,, 15/15; P < 0.0001). In columnar-type MPBC, MUC6 was positive in 65% of cases (+,+,+, 6/23; +,+, 8/23; +, 1/23; ,, 8/23), and CA/HIK1083 was positive in 52% (+,+, 3/23; +, 9/23; ,, 11/23; not significant). Our results clearly demonstrate that cuboidal-type MPBC have an aberrant pyloric glandular phenotype, that is, MUC6+/CA/HIK1083,. This unique profile may be related to different outcomes of patients with MPBC. [source] Antibody microarray analysis of serum glycans in esophageal squamous cell carcinoma cases and controlsPROTEOMICS - CLINICAL APPLICATIONS, Issue 8 2009Changxia Shao Abstract The objective of this study was to characterize specific serum glycan profile in esophageal squamous cell carcinoma (ESCC) cases and matched controls. A recently developed lectin-based antibody array was applied to detect various cancer-associated glycotopes in sera from 23 cases and 23 controls. Glycan levels were highly expressed in sera of ESCC patients as compared with controls. These included fucosylation level on interleukin (IL) 8; mannose level on haptoglobin; N-acetylglucosamine levels on IL6, mucin (MUC)1, and von Willebrand factor (vWf); sialyl Lewis a (sLea) levels on blood group Lewis X, IL6, IL10, MUC1, and serum amyloid A (SAA); sialyl Tn antigen (sTn) levels on cathepsin D, gelsolin, IL10, and vWf; T antigen levels on IL8, IL10, blood group Lewis X, vitronectin, and vWf (p<0.05). In addition, receiver-operating characteristics (ROC) analysis showed significantly discriminal improvement between cases and controls as measured by area under ROC curve. The highest sum of sensitivity and specificity was 1.52 for carbohydrate antigen 19-9 detection on both MUC1 and SAA, with area under ROC curves of 0.73 and 0.71, respectively. Taken together, this lectin-based antibody microarray allows efficient profiling of variations in specific glycans on proteins in ESCC cases as compared with controls, some of which might be useful for clinical diagnosis, early detection, and/or treatment. [source] CA19-9 as a predictor of tumor response and survival in patients with advanced pancreatic cancer treated with gemcitabine based chemotherapyASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2010Nazik HAMMAD Abstract Aims: The aim of this study was to determine the predictive role of pretreatment carbohydrate antigen 19-9 (CA19-9) measurement and its change after one cycle of gemcitabine-based therapy for response, time to progression (TTP) and overall survival (OS). Methods: Analyses were derived from three consecutive gemcitabine-containing phase II clinical trials between 1997 and 2004. Results: A total of 111 patients with pancreas cancer was studied. Baseline CA19-9 concentrations were dichotomized near the median. Lower baseline CA19-9 levels were positively associated with OS (median 9.1 vs 6.1 months, P = 0.0057) and TTP (median 6.4 vs 4.2 months, P = 0.0044). The covariate adjusted hazard ratio (HR) for progression among patients with baseline CA19-9 , 1000 ng/mL was HR = 1.94 (95% CI 1.24,3.02), with P = 0.0035. The covariate adjusted risk of death among patients with baseline CA19-9 , 1000 ng/ml was similarly elevated: HR = 1.90 (95% CI 1.23,2.94), with P = 0.0039. Change in CA19-9 levels from baseline to the end of treatment cycle 1 did not predict objective response (P = 0.75). There was somewhat longer OS (median 8.7 vs 7.1 months) and TTP (median 7.1 vs 5.4 months) in patients with ,50% reduction in serum CA19-9 concentrations, but this was not statistically significant (P = 0.74 and 0.81, respectively). Conclusion: Baseline CA19-9 levels may predict survival in patients with advanced pancreas cancer. The change in CA19-9 levels determined within 1 month of the initiation of therapy did not predict treatment outcome. [source] Original Article: Relationship between the serum CA-125 level and bone mineral density in healthy pre- and post-menopausal womenAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2010Ki Hoon AHN Background:, Osteoporosis and tumour-associated antigen (TAA) levels are associated with inflammatory processes, but little remains known about TAA levels and bone mineral density (BMD). Aims:, We determined whether or not high-normal TAA levels are associated with a lower BMD in healthy women. Methods:, A total of 3769 healthy women were enrolled from the health screening programme over 5 years. Each participant had undergone a basic health examination. Serum carbohydrate antigen (CA)-125, CA-19-9, carcinoembryonic antigen (CEA) and alpha-fetoprotein levels were evaluated as tumour markers. The correlations between serum TAA levels and BMD were analysed. Results:, Carbohydrate antigen 125 and CEA levels were positively associated with a higher BMD in the pre-menopause. In the post-menopause, the CA-125 level was positively associated with BMD. In the pre-menopause, CA-125 (r = 0.102; P < 0.001) and CEA levels (r = 0.134; P < 0.001) had a significant correlation with BMD. In the post-menopause, CA-125 was negatively associated with alkaline phosphatase (r = ,0.298; P < 0.001). Conclusions:, There was a significant positive association between CA-125 and BMD in healthy women. Additional basic and clinical studies on the relationship between CA-125 and bone are needed. [source] Single-molecule pair studies of the interactions of the ,-GalNAc (Tn-antigen) form of porcine submaxillary mucin with soybean agglutininBIOPOLYMERS, Issue 9 2009Marit Sletmoen Abstract Mucins form a group of heavily O -glycosylated biologically important glycoproteins that are involved in a variety of biological functions, including modulating immune response, inflammation, and adhesion. Mucins are also involved in cancer and metastasis and often express diagnostic cancer antigens. Recently, a modified porcine submaxillary mucin (Tn-PSM) containing GalNAc,1- O -Ser/Thr residues was shown to bind to soybean agglutinin (SBA) with ,106 -fold enhanced affinity relative to GalNAc,1- O -Ser, the pancarcinoma carbohydrate antigen. In this study, dynamic force spectroscopy is used to investigate molecular pairs of SBA and Tn-PSM. A number of force jumps that demonstrate unbinding or rebinding events were observed up to a distance equal to 2.0 ,m, consistent with the length of the mucin chain. The unbinding force increased from 103 to 402 pN with increasing force loading rate. The position of the activation barrier in the energy landscape of the interaction was 0.1 nm. The lifetime of the SBA,TnPSM complex in the absence of applied force was determined to be in the range 1.3,1.9 s. Kinetic parameters describing the rate of dissociation of other sugar lectin interactions are in the range 3.3 × 10,3,2.5 × 10,3 s. The long lifetime of the SBA-TnPSM complex is compatible with a binding model in which lectin molecules "bind and jump" from ,-GalNAc residue to ,-GalNAc residue along the polypeptide chain of Tn-PSM before dissociating. These findings have important implications for the molecular recognition properties of mucins. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 719,728, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Adenocarcinoma of the prostate immunostained for carbohydrate antigen 125 and carcinoembryonic antigenBJU INTERNATIONAL, Issue 3 2003H. Kiyokawa No abstract is available for this article. [source] Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinomaCANCER, Issue 12 2009Michele Reni MD Abstract BACKGROUND: Radiologic assessment of tumor response in pancreatic cancer is complicated by desmoplastic reactions within or around the tumor. The objective of this study was to evaluate the correlation between a decline in carbohydrate antigen 19-9 (CA 19-9) and survival in patients with advanced pancreatic cancer who received upfront chemotherapy. METHODS: CA 19-9 serum basal values were measured in 247 patients with advanced pancreatic cancer who were enrolled in 5 consecutive trials between 1997 and 2007. Survival curves were compared among patients who had a predefined CA 19-9 nadir variation (<50%. Group 1; 50% to 89%, Group 2; or >89%, Group 3). To eliminate guarantee-time bias, survival analysis was repeated using the landmark method. RESULTS: In both univariate and multivariate analysis, the basal CA 19-9 value significantly predicted survival. The median survival was 15.5 months for 34 patients who had normal basal CA 19-9 values, 11.9 months for 108 patients who had basal values between 38 U/mL and 1167 U/mL, and 8 months for 105 patients who had basal values >1167 U/mL. At least 1 CA 19-9 follow-up value was available for 204 patients who had baseline values greater than normal. A significant difference in overall survival was observed in univariate and multivariate analyses between Groups 1 and 2, between Groups 1 and 3, and between Groups 2 and 3. The results were confirmed using the landmark method. CONCLUSIONS: In this study, baseline CA 19-9 was confirmed as an independent prognostic factor for survival, and it may be considered as a stratification factor in trials in patients with advanced pancreatic cancer. Biochemical response may be used as a complementary measure to radiologic response to provide a better assessment of chemotherapy activity and to drive treatment decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society. [source] A novel algorithm to improve pathologic stage prediction of clinically organ-confined muscle-invasive bladder cancerCANCER, Issue 7 2009David Margel MD Abstract BACKGROUND: An algorithm was created to predict pathologic stage in patients with clinically organ-confined muscle-invasive bladder cancer. METHODS: The sample consisted of 133 consecutive patients scheduled to undergo cystectomy. To develop a tool to predict nonorgan-confined disease before surgery, principal component analysis (PCA) was applied. Patients were stratified into a training set (n = 89) and a validation set (n = 44), and 7 parameters were evaluated: levels of carcinoembryonic antigen, cancer antigen (CA) 125, and carbohydrate antigen (CA) 19-9; clinical stage; presence of hydronephrosis; presence of carcinoma in situ; and initial tumor size >3 cm. PCA was applied to the training set to determine the weight of each parameter. A PCA score was generated for each patient in the set, and a cutoff defining nonorgan-confined disease was established. The accuracy of the cutoff was quantified by the area under the receiver operator characteristics curve (AUC). The model was then applied to the validation set without recalculation; the AUC and the positive and negative predictive values of the validation set were calculated. RESULTS: On pathologic evaluation, 71 patients (53%) were found to have organ-confined tumors and 62 patients (47%) had extravesical disease. The AUC was 0.85 in the training group (95% confidence interval [95% CI], 0.71-0.97) and 0.84 in the validation group (95% CI, 0.75-0.93). The positive and negative predictive values in the validation group were 88% (95% CI, 71%-96%) and 94% (95% CI, 71%-99%), respectively. CONCLUSIONS: The newly devised, internally validated, algorithm was 85% accurate in predicting nonorgan-confined bladder disease before cystectomy. Further external validation in a large cohort was recommended as still necessary. Cancer 2009. © 2009 American Cancer Society. [source] Clinical significance of tumor markers and an emerging perspective on colorectal cancerCANCER SCIENCE, Issue 2 2009Keishi Yamashita Serum carcinoembryonic antigen (CEA) and CA19-9, a carbohydrate antigen recognized by the monoclonal antibody NS19-9, are commonly used as classical tumor markers in colorectal cancer (CRC) clinics. The roles of tumor markers include: (1) diagnostic screening (diagnostic markers); (2) prediction of prognosis after treatment (prognostic markers); and (3) judgment tools for treatment effect (surveillance markers). Tumor markers can be evaluated in serum, stools, or even in tissues depending on the clinical purpose. The American Society for Clinical Oncology recommends that CEA is the only marker of choice for monitoring the response of metastatic disease to systemic therapy at present. In the present paper, we are the first to review the clinical significance of the classical tumor markers CEA and CA19-9 in serum, allowing for our original data, and present our view on the newly emerging biomarkers in CRC. Novel promising biomarkers for diagnostic, prognostic, and surveillance purposes are reviewed and considered, some of which are anticipated for further validation. For diagnostic markers, urine or serum might replace fecal samples in the near future. On the other hand, prognostic or predictive markers for treatment sensitivity may be identified from the molecular profiles of primary cancer tissues. Selection of patients who are sensitive to chemotherapy will reduce the number of patients who undergo harmful chemotherapy with no effectiveness. The optimal tumor markers would be generalized, easy to assess, and accurate, and such markers are eagerly anticipated to enable personalized tailored therapy for CRC patients. (Cancer Sci 2009; 100: 195,199) [source] IgG2 containing IgM,IgG immune complexes predominate in normal human plasma, but not in plasma of patients with warm autoimmune haemolytic anaemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2006Dorothea Stahl Abstract:, The different physicochemical and sterical properties of IgG subclasses may favour a selective enrichment of defined IgG subclasses in IgM,IgG immune complexes (IC) of human plasma under physiological conditions. Such enrichment of IgG subclasses in IgM,IgG IC of plasma may differ from the normal IgG subclass distribution in plasma itself, and contribute to the physiological functions of IgM,IgG IC. Systematic studies on the IgG subclass distribution in IgM,IgG IC in humans are lacking. Using specific analytical techniques to characterise IgM,IgG IC in human plasma (i.e. fast protein liquid chromatography, enzyme-linked immunosorbent assay, affinity biosensor technology), and taking warm autoimmune haemolytic anaemia (WAIHA) of humans as a disease model, we here demonstrate that: (i) IgG2 is the predominant IgG subclass in IgM,IgG IC under physiological conditions, (ii) the predominance of IgG2 within IgM,IgG IC may get lost in polyclonal IgG-mediated autoimmune disease and (iii) the IgG subclass distribution in IgM,IgG IC influences the interaction between IC and blood cells involved in antigen presentation. The data presented here therefore extend the physiological function of IgG2, which is the protective immune response towards carbohydrate antigens in bacterial infections, and suggest IgG2-dependent regulation of immune responses to self-immunoglobulin in humans. The disturbed IgG subclass distribution in IgM,IgG IC of patients with WAIHA might influence activity of self-reactive B cells involved in the pathophysiology of the disease. [source] O-linked ,-N-acetylglucosaminylation in mouse embryonic neural precursor cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 16 2009Makoto Yanagisawa Abstract In neural stem cells (NSCs), glycoconjugates and carbohydrate antigens are known not only to serve as excellent cell surface biomarkers for cellular differentiation and development but also to play important functional roles in determining cell fate. O-linked ,-N-acetylglucosamine (O-GlcNAc), which modifies nuclear and cytoplasmic proteins on the serine and threonine residues, is also expected to play an important regulatory role. It is not known, however, whether O-GlcNAc is expressed in NSCs or what the function of this expression is. In this study, we evaluated the patterns and possible functions of O-GlcNAcylation in mouse embryonic neuroepithelial cells (NECs), which are known to be rich in NSCs. We confirmed the expression of O-GlcNAc transferase, O-GlcNAcase, and several O-GlcNAcylated proteins in NECs. Treatment of NECs with O-GlcNAcase inhibitors, PUGNAc and streptozotocin, induced robust accumulation of O-GlcNAc in NECs and reduction of number of NECs. In O-GlcNAcase inhibitor-treated NECs, the Ras-mitogen-activated protein kinase pathway and the phosphatidylinositol 3-kinase-Akt pathway, important for proliferation and survival, respectively, were intact, but caspase-3, an executioner for cell death, was activated. These results suggest the possibility that O-GlcNAc is involved in cell death signaling in NECs. Furthermore, in NECs, we identified an O-GlcNAc-modified protein, Sp1 transcription factor. Our study is the first to evaluate expression and functions of O-GlcNAc in NECs. © 2009 Wiley-Liss, Inc. [source] Serum carbohydrate antigen elevations in endometrial adenocarcinomas: Characterization of DU-PAN-2 expression as a tumor markerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2004Masanori Yasuda Abstract Aim:, To characterize serum elevations of carbohydrate antigens; DU-PAN-2, CA19-9, sialyl Lewisx and CA125 in endometrial adenocarcinomas (EMACs), particularly focusing on the clarification of DU-PAN-2 expression profiles. Methods:, Sixty-four resected EMACs of endometrioid type were used. The preoperative serum values of four markers were measured and comparatively analyzed regarding the relationship between histological grade and clinicopathological stage. Results:, The overall ratios of positive cases were 26.2% for DU-PAN-2, 25.0% for CA19-9, 13.6% for sialyl Lewisx, and 35.5% for CA125. DU-PAN-2 decreased as the grading went up (G1: 410.3 ± 243.8 to G3: 246.7 ± 90.0 U/mL), however, the reverse was true with CA19-9 (G1: 123.9 ± 147.4 to G3: 320.0 ± 180.0 U/mL). Sialyl Lewisx showed a strong tendency towards high elevation in G1 (346.3 ± 102.6 U/mL), compared to G3 (<2.5 U/mL). CA125 increased markedly as the grading went up (G1: 43.5 ± 6.3 to G3: 578.0 ± 10.0 U/mL). During staging-up from I + II to III + IV, the positive ratios inclined in all four markers as follows: DU-PAN-2, 18.4,53.3%; CA19-9, 20.4,40.0%; sialyl Lewisx, 11.4,22.2%; CA125, 31.8,44.4%. Serum elevations and positive ratios were correlated for DU-PAN-2, CA19-9 and CA125, while the reverse relationship was found for sialyl Lewisx. Conclusion:, It is suggested that DU-PAN-2 tends to be produced more in well-differentiated components of EMACs than in poorly differentiated ones. Since approximately half the cases with EMAC were serologically positive for DU-PAN-2 in stage III + IV, the marker is believed to be of much use for monitoring the cases with an extrauterine extent. [source] Characterization of a new serotype g isolate of Aggregatibacter actinomycetemcomitansMOLECULAR ORAL MICROBIOLOGY, Issue 3 2010K. Takada Summary Aggregatibacter actinomycetemcomitans is usually isolated from the oral cavity where it is associated with active periodontitis. The species can be divided into six serotypes (a,f) according to their surface carbohydrate antigens. However, some clinical isolates cannot be grouped within these six serotypes. Gram-negative, facultative anaerobic, catalase-positive coccobacilli were isolated from a patient with periodontitis and identified by employing genetic, biochemical and serological analyses. Phenotypic data identified the isolate as A. actinomycetemcomitans. Serotype-specific polysaccharide antigen from the isolate was untypeable by immunodiffusion testing in comparison with reference A. actinomycetemcomitans serotype a to f strains. Biofilm formation by the isolate was strong but cytotoxic activity was low. Gas chromatography/mass spectroscopy analysis of partially methylated alditol acetates from surface polysaccharide showed the presence of 2,4-di- O -methyl-rhamnose and 2,3,6-tri- O -methyl-glucose, with a 1 : 1 m ratio. The 1H- and 13C-nuclear magnetic resonance spectra of the antigen showed that both constituent glycoses had ,-anomeric configuration. It is proposed that the untyped strain is a new A. actinomycetemcomitans serotype, designated serotype g. [source] Structural analysis of ,-Gal and new non-Gal carbohydrate epitopes from specific pathogen-free miniature pig kidneyPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 13 2008Yun-Gon Kim Abstract The major barrier in transplantation of pig organs into humans is the presence of surface carbohydrate antigens (e.g., the Gal,1-3Gal,1-4GlcNAc-R (,-Gal) epitope) expressed on pig endothelial cells. In this study, total N -glycans from membrane glycoproteins derived from specific pathogen-free miniature pig kidney are identified by MALDI-TOF, negative ion ESI MS/MS and normal-phase HPLC (NP-HPLC) combined with exoglycosidase digestion. Over 100 N -glycans, including sialylated and neutral types, were identified. As well as the known ,-Gal antigens, some of these glycans contained novel non-Gal carbohydrate antigens such as (Neu5Gc-Gal-GlcNAc) and Gal,1-3Lewisx (Gal-Gal-(Fuc)GlcNAc) which have not been reported before in N -glycans from pig organs. The ability of MALDI, ESI, and HPLC to measure the relative proportions of the glycans was evaluated. The HPLC resolution was insufficient for accurate work and some minor differences were noted in the ionization efficiencies of different glycan groups when measured by the two mass spectrometric techniques. However, the results indicated that the relative quantity of ,-Gal epitope was in the region of 50% of the complex glycans. High-mannose type glycans were also abundant (35,43%) but appeared to be ionized more efficiently than the complex glycans by ESI than by MALDI. [source] Tissue distribution of histo-blood group antigens.APMIS, Issue 1 2000Vibeke Ravn The introduction of immunohistochemical techniques and monoclonal antibodies to specific carbohydrate epitopes has made it possible to study in detail the tissue distribution of histo-blood group antigens and related carbohydrate structures. The present paper summarizes the available data concerning the histological distribution of histo-blood group antigens and their precursor structures in normal human tissues. Studies performed have concentrated on carbohydrate antigens related to the ABO, Lewis, and TTn blood group systems, i.e. histo-blood group antigens carried by type 1, 2, and 3 chain carrier carbohydrate chains. Histo-blood group antigens are found in most epithelial tissues. Meanwhile, several factors influence the type, the amount, and the histological distribution of histo-blood group antigens, i.e. the ABO, Lewis, and saliva-secretor type of the individual, and the cell-and tissue type. Oligosaccharides with blood-group specificity are synthesized by the stepwise action of specific gene-encoded glycosyltransferases. In general, this stepwise synthesis of histo-blood group antigens correlates with cellular differentiation. The H and the Se genes both encode an ,1,2fucosyltransferase, which is responsible for the synthesis of blood group antigen H from precursor disaccharides. A new model for the participation of the Se/H-gene-encoded glycosyl transferases in synthesis of terminal histo-blood group antigens in human tissues is proposed; the type and degree of differentiation rather than the embryologic origin determines whether it is the H or the Se gene-encoded transferases that influence expression of terminal histo-blood group antigens in tissues. [source] Humanized immunotoxins: A new generation of immunotoxins for targeted cancer therapyCANCER SCIENCE, Issue 8 2009Mrudula Mathew Chemotherapy, radiation, and surgery are the conventional treatment modalities for cancer. The success achieved with these approaches has been limited due to several factors like chemoresistance to drugs, non-specificity leading to peripheral toxicity, and non-resectable tumors. To combat these problems, the concept of targeted therapy using immunotoxins was developed. Immunotoxins are chimeric proteins with a cell-selective ligand chemically linked or genetically fused to a toxin moiety and can target cancer cells overexpressing tumor-associated antigens, membrane receptors, or carbohydrate antigens. Ligands for these receptors or monoclonal antibodies or single chain variable fragments directed against these antigens are fused with bacterial or plant toxins and are made use of as immunotoxins. Pseudomonas exotoxin, anthrax toxin, and diphtheria toxin are the commonly used bacterial toxins. Ricin, saporin, gelonin, and poke weed antiviral protein are the plant toxins utilized in immunotoxin constructs. Several such fusion proteins are in clinical trials, and denileukin difitox is a FDA-approved fusion protein. In spite of the promise shown by bacterial- and plant toxin-based chimeric proteins, their clinical application is hampered by several factors like immunogenicity of the toxin moiety and non-specific toxicity leading to vascular leak syndrome. In order to overcome these problems, a novel generation of immunotoxins in which the cytotoxic moiety is an endogenous protein of human origin like proapoptotic protein or RNase has been developed. This review summarizes the advances in this new class of fusion protein and the future directions to be explored. (Cancer Sci 2009) [source] Induction of carbohydrate-specific antibodies in HLA-DR transgenic mice by a synthetic glycopeptide: a potential anti cancer vaccine for human useCHEMICAL BIOLOGY & DRUG DESIGN, Issue 3 2003S. Vichier-Guerre Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor-associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte-associated antigens (HLA). In order to stimulate a T-cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B-cell epitope (Tn antigen: , -GalNAc-Ser) covalently linked to peptides corresponding to the Pan DR ,universal' T-helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA-DR1, and HLA-DR4). A strong T-cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use. [source] Chemical and Chemoenzymatic Synthesis of S-Linked Ganglioside Analogues and Their Protein Conjugates for Use as ImmunogensCHEMISTRY - A EUROPEAN JOURNAL, Issue 3 2006Jamie R. Rich Abstract Analogues of the tumor-associated gangliosides GM3 and GM2 containing terminal S-linked neuraminic acid residues and an amino terminated, truncated ceramide homologue have been synthesized and conjugated to a protein. The synthesis involved coupling of a S-linked sialyl ,(2,3) galactose disaccharide with a glucosyl sphingosine analogue, followed by elaboration and deprotection to give amino-terminated glycosyl ceramide 1. Glycosyltransferase-catalyzed extension of the trisaccharide 1 provided access to the modified GM2 tetrasaccharide 2 or sulphur-containing GD3 analogue 30. Owing to their potentially enhanced resistance to endogenous exo- glycoside hydrolases and their inherent non-self character, carbohydrate antigens containing non-reducing terminal thioglycosidic linkages may be more immunogenic than O -linked antigens and may stimulate the production of antibodies capable of recognizing naturally occurring oligosaccharides. Our initial results suggest that in fact these antigens are viable immunogens and furthermore, that immune sera cross reacts with O -gangliosides in the context of a heterologous glycoprotein conjugate. [source] | ||||||||||||||||||||||||||||||||||