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Biomedical subjects

M Yuan

Publications and source records attributed to M Yuan.

At least 73 records · Page 4Linked to original sources

Monoclonal antibody directed against colon cancer mucin has high specificity for malignancy.

Exposure of core carbohydrate structures such as NeuAc alpha2-6GalNAc-Ser/Thr (sialosyl-Tn) in mucus glycoproteins is often associated with malignant transformation in a number of different tissues. Reagents that specifically identify such structures would be useful in the diagnosis of cancer. Monoclonal antibody JT10e has been produced against mucins from xenografts of LS174T colon cancer cells but also reacts with mucins of pancreatic cancer xenografts. The following data suggest that JT10e reacts with sialosyl-Tn: (I) reactivity with bovine and ovine submaxillary mucins; (2) reactivity sensitive to neuraminidase or mild acid; (3) inhibition of reactivity by NeuAc and NeuAc alpha2-6 lactose; and (4) lack of reactivity with other glycoproteins with related carbohydrate structures but no sialosyl-Tn. JT10e is distinguishable from 2 other antibodies which react with sialosyl-Tn, B72.3 and TKH2 because JT10e: (a) did not react with normal gastric tissue while B72.3 and TKH2 did; (b) was only partially inhibited by TKH2 and not at all by B72.3; (c) did not react with Tn antigen while B72.3 did; and (d) bound more strongly to pancreatic cancer mucins than did either B72.3 or TKH2. JT10e reacted with a high percentage of malignant colonic, pancreatic, gastric and mammary tissues but not with the corresponding normal tissues. A high percentage of patients with colonic, pancreatic, gastric, mammary and lung cancers had elevated blood levels of JT10e antigen. A number of colonic cancer patients had elevated JT10e antigen levels without corresponding elevations in CA19-9 levels. These results suggest that JT10e antibody could be used in conjunction with other mucin markers to improve the identification of malignancy in colon, and to study the structure of oligosaccharides in cancer mucins.

Animals↗

Multiple forms of intracellular and secreted mucins in a pancreatic cancer cell line.

Mucins have been implicated in circumventing the defenses of the body against tumorigenesis. A better understanding of the structures of mucins may assist in the development of new therapeutic approaches. Monoclonal antibody Ea6, developed against mucins purified from xenografts of the pancreatic cancer cell line SW1990, was used to identify a new type of pancreatic cancer mucin. The following characteristics suggest that Ea6 antibody reacts with the core structure of O-linked oligosaccharides, the Tn antigen (N-acetylgalactosamine-serine/threonine): (a) increased reactivity with ovine and bovine submaxillary mucins after desialylation; (b) reactivity was inhibitable by N-acetylgalactosamine; and (c) no reactivity with blood group A oligosaccharides. Ea6 mucins from cultured SW1990 cells had lower buoyant densities (1.36 versus 1.44 g/ml) than mucins identified by another monoclonal antibody directed against SW1990 mucins, SPan-1, and were less acidic. High density and molecular mass (> or = 400 kD) secreted antigens were unaffected by sulfhydryl bond reduction. After partial deglycosylation secreted SPan-1 antigens reacted with MUC1 peptide specific antibodies, SM-3 and HMFG-2, as well as polyclonal antisera directed against deglycosylated xenograft mucins. However, Ea6 antigens did not. SW1990 cytosol also contained SPan-1 antigens with apparent molecular weights of 160,000 and 210,000 and low buoyant densities (< or = 1.22 g/ml). These reacted with monoclonal antibodies specific for the MUC1 apomucin with no prior treatment. No Ea6 reactivity was detected with this fraction. These results suggest that Ea6 antibody identifies a new population of mucins that is distinct from SPan-1 mucins.

Animals↗

[Characterization and detection of cancer-associated antigens in patients with gastric cancer].

Six monoclonal antibodies reacted with different cancer-associated antigens were studied. In which, CL-2 reacts with carcinoembryonic antigen (CEA), CL-3: CEA and S-Tn, CL-4: glycosphingolipid, PS-7: S-Tn. PS-10: S-Tn Tn, and glycosphingolipid, all weakly, and GS-2: CEA, Tn, S-Tn, glycolipid, all strongly. All of the monoclonal antibodies expressed strongly in gastric cancer tissues, the positive rate are 62%-91.6%, but none are expressed in normal gastric tissues, except PS-7 (35% weakly expressed). The cancer-associated antigens in gastric juice, serum and feces were detected by binding inhibition ELISA and SDS-PAGE; Western blot methods. The results showed that: (1) The positive rates in gastric cancer are all over 90%, when detected by cock-tail monoclonal antibodies of any three. The false positive rates are 8%- 14%. (2) Detection of cancer-associated antigens in gastric juice and feces gives higher positive rates than in serum, it shows the carbohydrate antigens is relatively more stable than the protein when it passes through the gastrointestinal canal. (3) The monoclonal antibodies against S-Tn, Tn, and glycosphingolipid antigens are good markers for the diagnosis of gastric cancer.

Antibodies, Monoclonal↗

Differences in expression of SPan-1 and CA15-3 antigens in blood and tissues.

Pancreatic and mammary cancer cells are reported to have different oligosaccharides on the same apomucin, the MUCI gene product. A better understanding of the tissue specificity of these sugar structures may help in identifying the source of mucins when they are found in the sera. Serum levels of 3 pancreatic-cancer-associated carbohydrate epitopes identified by monoclonal antibodies (MAbs) SPan-1, 19-9 and DU-PAN-2, were compared to those of CA15-3 in a variety of malignant conditions. CA15-3 identifies both carbohydrate and peptide determinants associated with the MUC1 apomucin in breast tissues. SPan-1 antigen was elevated in a high percentage of patients with pancreatic, gastric and colorectal cancer but in only a few of the patients with malignancies of non-GI origin such as breast, ovary and lung. The 19-9 and DU-PAN-2 antigens had a similar pattern of much greater sensitivity for pancreatic cancer than for these non-gastrointestinal cancers. The levels of these 3 markers showed significant correlations in pancreatic cancer. In contrast, CA15-3 was elevated in a large number of patients with breast, lung, ovarian and pancreatic cancers. There was no correlation of CA15-3 with the 3 other markers in pancreatic cancer. SPan-1 and DF3/115D8 antigens in blood have different mobilities in SDS-PAGE and buoyant densities. Moreover, SPan-1 and DF3 antigenic determinants are localized in different regions of the same normal and malignant pancreas and breast tissues. Thus the SPan-1 determinant can be dissociated from the breast peptide and/or carbohydrate determinants.

Antigens, Neoplasm↗

In vitro susceptibility of Haemophilus influenzae to cefaclor, cefixime, cefetamet and loracarbef.

The susceptibility of 2,212 Haemophilus influenzae isolates cultured in UK clinical laboratories in 1991 was determined for four orally-administered beta-lactam drugs. These isolates included 1,893 ampicillin-susceptible, 191 beta-lactamase-positive and 128 ampicillin-resistant, beta-lactamase-negative Haemophilus influenzae. While 150 (6.8%) isolates were resistant to cefaclor (MIC > or = 16 mg/l) and 85 (3.8%) to loracarbef, all were inhibited by < or = 2 mg/l cefetamet and < or = 1 mg/l cefixime and were therefore susceptible to these agents. Ranges and modes of inhibition zone diameters and MICs indicated that the susceptibility of a variable proportion of the 191 beta-lactamase-positive isolates to cefaclor, loracarbef and cefetamet was reduced compared with the fully susceptible population. In contrast, a major reduction in susceptibility to all four antimicrobial agents was seen among the 128 ampicillin-resistant (MIC 1-64 mg/l) beta-lactamase-negative isolates such that these accounted for 53% and 67% of the total number of organisms resistant to cefaclor and loracarbef respectively. In addition, 23 of 25 isolates inhibited only by > or = 1 mg/l cefetamet and all eight inhibited only by > or = 0.5 mg/l cefixime showed this type of resistance to ampicillin. Results indicate the importance of detecting non-beta-lactamase-mediated resistance to ampicillin and any concomitant diminished susceptibility to other beta-lactam drugs.

Ampicillin Resistance↗

Antimicrobial resistance in Haemophilus influenzae from England and Scotland in 1991.

Twenty-two laboratories in England and Scotland sent 2212 clinical isolates of Haemophilus influenzae to The London Hospital Medical College (LHMC) between 1 January and 31 March 1991. After confirmation of identity, the prevalence of resistance was determined and compared with results from previous similar surveys. beta-Lactamase was produced by 8.3% of non-capsulate isolates and 21% of 52 type b isolates; both figures were higher than the 6% and 18% figures recorded, respectively, in 1986. There was an increase in the prevalence of non-beta-lactamase-mediated diminished susceptibility to ampicillin (5.8%) and co-amoxiclav (6.1%) compared with 1986 (4%). Whereas fewer H. influenzae isolates were resistant to tetracycline (1.4%) or chloramphenicol (0.8%), there was an increase in resistance to trimethoprim (6.8%) and to sulphamethoxazole (16.9%) compared with 1986 (4.2% and 3.5% respectively). In addition, 95 isolates (4.3%) were resistant to both of these anti-folate antimicrobials. Six isolates (one type b from CSF) were resistant to all drugs tested, except for co-amoxiclav. Overall, the results demonstrated that changes have occurred in the last decade in England and Scotland, such that H. influenzae isolates are increasingly likely to be resistant to ampicillin, co-amoxiclav and co-trimoxazole.

Chloramphenicol Resistance↗

The antimicrobial susceptibility of Moraxella catarrhalis isolated in England and Scotland in 1991.

Between 1 January and 31 March 1991, 20 laboratories in England and Scotland sent a total of 413 consecutive clinical isolates of Moraxella catarrhalis to The London Hospital Medical College (LHMC). After confirmation of identity, the susceptibility of all isolates to 11 antimicrobial agents was determined. Of the 375 (90.8%) isolates which were found at LHMC to be beta-lactamase-positive, 174 produced zones of inhibition around 2 micrograms ampicillin disc which were greater than or equal to 20 mm in diameter and 252 were inhibited by less than or equal to 0.5 mg/L of ampicillin. However, 71 of these 375 had been reported to be ampicillin-susceptible by peripheral centres. While beta-lactamase had not been detected in 35 of these 71 isolates, the other 36 had been reported to be ampicillin-susceptible and beta-lactamase-positive. All 38 beta-lactamase-negative isolates produced zones greater than or equal to 30 mm in diameter and were inhibited by less than or equal to 0.06 mg/L of ampicillin. No M. catarrhalis isolate was found to be resistant to co-amoxiclav, tetracycline, chloramphenicol or cefaclor. Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition. Resistance to trimethoprim was uniform (MICs 2-128 mg/L). Two isolates showed intermediate susceptibility to cefixime (MIC 2 mg/L) but none was resistant to the new oral cephalosporin cefetamet or to the oral carbacephem loracarbef.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Detection of antigens associated with lung carcinoma in sera by monoclonal antibodies WLA-2C4 and CL-3.

The levels of tumor-associated antigens (TAAS) corresponded to monoclonal antibodies WLA-2C4 and CL-3 in sera of 57 lung cancer patients, 100 healthy adults and 50 non-tumor disease patients were assayed with SABC-ELISA of immunobinding inhibition test. The threshold values of WLA-2C4 and CL-3 (RBI) were 12% and 36%, respectively. The positive results of lung carcinomas with at least one of the two TAAS were as follows: squamous cell carcinoma 89%; adenocarcinoma 83%; small cell carcinoma 67% and their mean positive rate was 79%. Whereas the positive rate in healthy adults and non-tumor disease patients was only 6%. These results indicate that using monoclonal antibodies WLA-2C4 and CL-3 simultaneously may be helpful to the serological diagnosis of lung carcinoma.

Adenocarcinoma↗

[Mucin core peptide expression in malignant and non-malignant colorectal tissues].

Three human mucin cDNAs (Muc-1, Muc-2, Muc-3) have recently been cloned and sequenced. The major portion of each mucin consists of sequences repeated in tandem along the protein. Three mucins are distinct due to differences in tandem repeat length, lack of sequence homology and different chromosomal locations of their genes. Since altered mucin glycosylation occurs in cancer resulting in exposure of core carbohydrate, we postulated that increased exposure or other alteration of core peptide structure may occur in cancerous tissues. Antibodies against Muc-1, Muc-2, Muc-3 tandem repeats were used for immunohistochemical analysis of normal, non-malignant and cancer tissues. The results indicate that in normal tissues, only Muc-2 expressed, while in cancerous tissues all three mucin core peptides were significantly accumulated, All of the three mucin core peptides increasingly expressed in adenoma, dysplasia epithelium and active ulcerative colitis (pre-malignant lesions), but not in the hyperplastic polyps, ischemic colitis and quiescent ulcerative colitis (non-malignant diseases).

Adenocarcinoma, Mucinous↗

[Histological localization of mucin core polypeptide MUC-2 in application to the differential diagnosis of adenocarcinoma].

Human mucin core cDNA-MUC-2 has been cloned and sequenced. Its major portion consists of amino acids tandem in arrangement with repetition in its sequence, locating at the 11th chromosome. Antibody against polypeptide MUC-2 was used for immunohistochemical SABC staining in order to investigate the expression of MUC-2 in human normal and cancerous tissues. The results revealed that MUC-2 was expressed in normal intestine and prostate, and accumulated in the colorectal cancer tissues, but not in other normal tissues or only weakly expressed in a few cases of pancreas, lung and breast cancers. If used in combining with monoclonal antibody against MUC-1, which is known to be expressed in normal and cancer tissues of pancreas, lung and breast, it is considered to be valuable for the differential diagnosis in detecting the origin of metastatic adenocarcinoma.

Adenocarcinoma↗

Characterization of new pancreatic cancer-reactive monoclonal antibodies directed against purified mucin.

Although mucins have been found to be useful in the diagnosis of pancreatic cancer, the carbohydrate and peptide structures of pancreatic mucins are still not well characterized. Monoclonal antibodies were produced using mucins purified from xenografts of a human pancreatic cancer cell line as the immunogen. One of these, Ia3, reacted with almost all pancreatic, gastric, and colorectal carcinomas examined by immunoperoxidase staining, but with few normal tissues. Ia3 antigen was elevated in sera of 50.4% of individuals with gastrointestinal tumors, but its levels did not correlate with those of CA15-3, CA19-9, or DU-PAN-2. Serum Ia3 antigens migrated more slowly in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the polymorphic epithelial mucins recognized by DF3 or 115D8. Ia3 reacted only with native, and not with partially deglycosylated, pancreatic cancer xenograft mucins. Periodate or neuraminidase treatment destroyed this reactivity, but protease had little effect. The antigen recognized by another antibody, Nd2, was not detected in normal pancreatic, colonic, or gastric tissues but was present in approximately 60% of the pancreatic and gastric carcinomas examined. Nd2 reactivity with native and partially deglycosylated mucin was lost after pretreatment with protease and beta-mercaptoethanol. We conclude that, while Ia3 reacts with carbohydrates, Nd2 reactivity appears to be dependent on the integrity of the mucin protein core. The antigenic determinants of Ia3 and Nd2 are different from those of B72.3, CA19-9, DU-PAN-2, SPan-1, and several breast cancer mucin-directed antibodies. These results suggest that the malignancy-associated structures identified by Ia3 and Nd2 may provide new information on the carbohydrate and peptide structure of pancreatic cancer mucins.

Antibodies, Monoclonal↗

Radioimmunolocalization of human malignant tumors with In-111 labeled monoclonal antibody.

An anti-human colon carcinoma monoclonal antibody 2C10 was radiolabeled with In-111 and studied in 15 patients with gastrointestinal and ovarian carcinoma. The labelling efficiency approached 100% and immunoactivity of the labeled antibody was over 75%. 2-3 mCi (1 mg) In-111-2C10 was given to the patients intravenously and scintigraphy was performed 72 hours after administration with a gamma camera. Specimens were also scanned in some of the patients. The resected tumors and remote margin were examined immunohistochemically. Positive scintigraphic images were obtained in 12/15 patients with colorectal cancer (10) and ovarian cancer (2). Negative results were seen in the two patients with gastric cancer. The scintigraphic results of 10 patients were confirmed surgically and pathologically. The remaining 5 were confirmed by endoscopy, B-ultrasonography or X-ray CT. Most patients had been definitely diagnosed before imaging except one patient with metastatic focus from ovarian cancer to colon and one with recurrent colon cancer were first detected with RIAD, showing the unique advantage the latfer. The high background radioactivity in the liver, however, is a conspicuous problem to be solved.

Adult↗

[Detection of cancer-associated antigen in feces of patients with gastric cancer by monoclonal antibodies].

Detection of cancer-associated antigen in feces was performed by ELISA binding inhibition method using monoclonal antibody in 25 patients with gastric cancer, 70 with non-malignant gastrointestinal diseases and 100 healthy individuals. Monoclonal antibodies used were CL-4, PS-9, PS-10 and a "cocktail" of the three. The level of cancer-associated antigens detected in feces was significantly higher in patients with gastric cancer than in healthy individuals. PS-9 and PS-10 were also significantly higher in gastric cancer than in non-malignant gastrointestinal diseases. The positive rates of CL-4 were 62.5% vs 7.0%, PS-9 44.0% vs 3% and PS-10 64.0% vs 7.0% in patients with gastric cancer and healthy individuals. When the cocktail of the three was used, the positive rates increased to 88.0% and 14% in the above two groups and 26.6% in gastritis group. These results indicate that the detection of cancer-associated antigen in feces is of value in diagnosis of gastric cancer.

Antibodies, Monoclonal↗

[Value of fecal detection of cancer-associated antigens using monoclonal antibodies in the diagnosis of colorectal cancer].

Detection of cancer-associated antigens in feces by the method of binding inhibition ELISA using monoclonal antibodies were performed in sixty patients with colorectal cancer; seventy with non-malignant gastrointestinal diseases: and one hundred healthy individuals. Monoclonal antibodies used were: anti-colonic cancer CL-2, CL-3, and anti-pancreatic cancer PS-9, PS-10. The level of cancer-associated antigens detected in feces were significantly higher in patients with colorectal cancer than that of non-malignant GI diseases or healthy individuals. The positive rate of the antigens in colorectal cancer patients and normal individuals were: 61.1% vs. 7% as detected by CL-2; 53.4% vs. 9% by CL-3; 55% vs. 8% by PS-9; and 53.3% vs. 8% by PS-10. When a "cocktail" of CL-2, PS-9, and PS-10 was used, the positive rate was 92.5% in cancer patients, and 14% in control group. Cancer-associated antigens were found to be positive in all seven early staged (Duke's A) colorectal cancer patients. These results indicate the value of assaying cancer-associated antigen in feces as an aid to the diagnosis of colorectal cancer, especially in the early stage.

Antibodies, Monoclonal↗

[Synthesis of 4-[(4-chlorophenyl) (5-fluoro-2-hydroxyphenyl) methylene amino]butyrates and its anticonvulsant activity].

It is known that gamma-aminobutyric acid (GABA) plays an important role in the pathophysiology of epilepsy. Under physiological conditions it is very difficult for GABA to cross the blood-brain barrier. It is likely that the esters of GABA, Which easily enter the brain, will have useful therapeutic properties. With this in mind, we have designed and synthesized 8 derivatives (IVa to IVh) of gamma-aminobutyric acid with an imine to link a lipophilic carrier in order to facilitate the passage of gamma-aminobutyric acid to cross the blood-brain barrier. All the eight synthesized title compounds were evaluated as anticonvulsants in mice via the Antiepileptic Drug Development Program of NIH. The compounds IVb and IVf showed anticonvulsant activity.

Aminobutyrates↗

[Pharmacological study of Rubus parvifolius L].

Aqueous extracts of Rubus parvifolius have been proved useful in shortening bleeding time and coagulation time in mice, shortening euglobulinlysis time in rabbits, inhibiting platelet thrombosis in rabbits in vivo, Rubus parvifolius increasing coronary flow in isolated rat heart, preventing rats from pituitrin induced changes of ECG and Rubus parvifolius increasing the tolerance of mice to hypoxia. The toxicity of Rubus parvifolius is small.

Animals↗

Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer.

Mucin glycoproteins are major secretory products of the colon and contain O-linked oligosaccharides synthesized on a polypeptide backbone. The initial step in the synthesis of O-linked oligosaccharides is the addition of N-acetylgalactosamine to serine or threonine residues forming the Tn antigen. This substance can then receive additional carbohydrate residues such as sialic acid to form sialosyl-Tn antigen, or galactose to form T antigen. In the colon, the T antigen is an oncodevelopmental cancer-associated antigen but little is known about Tn and sialosyl-Tn expression. The present comparative immunohistochemical study was performed to analyze the expression of these antigens in fetal, normal adult, and malignant colorectal tissues with an aim toward elucidating whether Tn and sialosyl-Tn are also oncodevelopmental colon cancer-associated antigens and to gain insight into the earliest steps of mucin glycosylation in colonocytes. We used three reagents to detect Tn antigen (two monoclonal antibodies ETn1.01 and CU-1, and one lectin Vicia villosa), two reagents to detect sialosyl-Tn (monoclonal antibodies TKH2 and B72.3) and one to detect T antigen (monoclonal antibody AH9-16). Except for occasional reactivity with VVA and CU-1, cells of normal colonic mucosa did not express Tn, sialosyl-Tn, or T antigens. However, in the transitional mucosa immediately adjacent to cancer, all three antigens were expressed (ranging from 35 to 67% of cases depending upon the reagent). In colon cancers, the percentage of cases expressing each antigen were as follows: Tn 72-81%, sialosyl-Tn 93-96%, and T 71%. Unlike T antigen, which was preferentially expressed by moderately well- and well-differentiated adenocarcinomas, both Tn and sialosyl-Tn antigens were expressed by most histological subsets of colon cancers, including poorly differentiated adenocarcinomas and mucinous (colloid and signet ring cell type) carcinomas. The majority of cancers expressed both Tn and sialosyl-Tn, usually in association with T antigen. Only one cancer lacked all three antigens. Fetal colonic mucosal cells expressed all three antigens, particularly in goblet cell mucin. These results indicate that like T antigen, Tn and sialosyl-Tn are oncodevelopmental cancer-associated antigens in the colon. Moreover, Tn and sialosyl-Tn antigens appear to be useful markers of poorly differentiated adenocarcinomas and mucinous carcinomas: two histological subsets that often fail to express other cancer-associated antigens and that are often associated with a poor clinical outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗