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Biomedical subjects

X T Chen

Publications and source records attributed to X T Chen.

At least 19 recordsLinked to original sources
PubMed2002

The value of MG7 antigen in predicting cancerous change in dysplastic gastric mucosa.

The aim of this study was to ascertain whether MG7Ag is a useful predictor of evolution of gastric dysplasia to carcinoma. A total of 1090 patients with confirmed dysplasia were stained immunohistochemically with MG7 monoclonal antibody by the ABC method. A prospective follow-up study was undertaken on 19 patients with MG7Ag positive staining and 16 with MG7 negative staining over a period of 10-78 months. The expression of MG7Ag was also compared in another two groups by conducting retrospective studies. One group showed an evolution into gastric cancer over 2-4 years, the other did not. Quantitative analysis of MG7Ag expression was carried out on the last two groups. The receiver operating characteristic curve and Youden index were used to assess the best critical value for MG7Ag. MG7Ag was found positive in 456/1090 cases (41.8%) with dysplasia. Prospective follow-up of 35 patients showed that 6/19 patients with MG7Ag positive staining developed gastric cancer, but there were no carcinomatous changes in 16 patients with MG7 negative staining. The results of MG7Ag expression in 72 cases with retrospective follow-up showed there were 24 with positive immunostaining among 34 cancerous cases (70.6%), and only 7 in 38 non-cancerous cases (18.4%) (p<0.01). Image analysis showed that an average MG7Ag density index ++0.19 could be regarded as the critical value for high risk of gastric mucosa with dysplasia evolving to cancer. Positive MG7Ag expression in gastric mucosa of patients with dysplasia, especially in cases with a density index ++0.19, was an indicator of high risk of malignant change.

Adult↗
PubMed2000

IMDA/aldol strategy for transforming carbohydrates into functionalized trans-decalins.

L-Rhamnal is readily converted into an allyl 2, 3-unsaturated-C-glycopyranoside. The (S) configuration of the alphaL-anomer defines the stereochemical outcome of the future IMDA reaction, leading to the absolute stereochemistry for the trans-decalin moiety in naturally occurring terpenoids. Selective cleavage of the terminal double bond of the allyl group provides an aldehydo function which serves for an aldol/Claisen addition with ethyl sorbate. Of the four possible diastereomers, one is obtained in pure form and processed to give the IMDA precursor. Cyclocondensation is achieved by heating in xylene to give a tricyclic trans-decalin whose structure is established by NMR and X-ray analysis.

Carbohydrates↗
PubMed1999

Probing cell-surface architecture through synthesis: an NMR-determined structural motif for tumor-associated mucins.

Cell-surface mucin glycoproteins are altered with the onset of oncogenesis. Knowledge of mucin structure could be used in vaccine strategies that target tumor-associated mucin motifs. Thus far, however, mucins have resisted detailed molecular analysis. Reported herein is the solution conformation of a highly complex segment of the mucin CD43. The elongated secondary structure of the isolated mucin strand approaches the stability of motifs found in folded proteins. The features required for the mucin motif to emerge are also described. Immunocharacterization of related constructs strongly suggests that the observed epitopes represent distinguishing features of tumor cell-surface architecture.

Antigens, CD↗
PubMed1999

Structure-activity profiles of eleutherobin analogs and their cross-resistance in Taxol-resistant cell lines.

PURPOSE: Eleutherobin, a natural product, is an antimitotic agent that promotes the polymerization of stable microtubules. Although its mechanism of action is similar to that of Taxol, its structure is distinct. A structure-activity profile of synthetic eleutherobin derivatives that have modifications at C3, C8 and C15 was undertaken to define the structural requirements for microtubule stabilization and cross-resistance in Taxol-resistant cell lines. METHODS: The biological activity of five eleutherobin analogs was assessed using three techniques: (1) cytotoxicity and drug-resistance in three paired Taxol-sensitive and -resistant cell lines; (2) polymerization of microtubule protein in vitro in the absence of GTP and (3) induction of microtubule bundle formation in NIH3T3 cells. RESULTS: Eleutherobin had an IC50 value comparable to that of Taxol, whereas neoeleutherobin, which has a carbohydrate domain that is enantiomeric with that of the parent compound, was less cytotoxic and had 69% of the maximum microtubule polymerization ability of eleutherobin. Both of these compounds exhibited cross-resistance in MDRI-expressing cell lines. Removal or replacement of the C15 sugar moiety resulted in reduced microtubule polymerization and cytotoxicity compared to eleutherobin and loss of cross-resistance in the cell lines SKVLB and J7-T3-1.6, both of which express high levels of P-glycoprotein. By contrast, removal of the urocanic acid group at C8 resulted in virtually complete abrogation of biological activity. The compound lost its ability to polymerize microtubules, and its cytotoxicity was reduced by a minimum of 2000-fold in lung carcinoma A549 cells. CONCLUSIONS: Removal or modification of the sugar moiety alters the cytotoxic potency of eleutherobin and its pattern of cross-resistance in Taxol-resistant cells, although such compounds retain a small percentage of the microtubule-stabilizing activity of eleutherobin. The N(1)-methylurocanic acid moiety of eleutherobin, or perhaps some other substituent at the C8 position, is essential for Taxol-like activity. These findings will be important for the future design and the synthesis of new and more potent eleutherobin derivatives.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Convergent total synthesis of a tumour-associated mucin motif.

Synthetic glycoconjugates that mimic cell-surface tumour antigens (glycolipids or glycoproteins with unusual carbohydrate structural motifs) have been shown to trigger humoral responses in murine and human immune systems. This raises the exciting possibility of inducing active immunity with fully synthetic carbohydrate vaccines, particularly if vaccine compounds can be synthesized that resemble the surface environment of transformed cells even more closely. Glycopeptides seem particularly suitable for this purpose. In contrast to most glycolipids and the carbohydrates themselves, glycopeptides bind to major histocompatibility complex molecules, and, in favourable cases, can stimulate T cells and lead to the expression of receptors that recognize the carbohydrate part of a glycopeptide with high specificity. The preparation of glycopeptides and glycoproteins remains, however, a difficult challenge: earlier synthesis methods have been inefficient, and established cloning approaches that allow engineering of global glycopatterns produce only heterogeneous glycoproteins. Here we report an efficient strategy of the synthesis of tumour-associated mucin glycopeptides with clustered trisaccharide glycodomains corresponding to the (2,6)-sialyl T antigen. Our approach involves construction of the complete glycodomain in the first stage, followed by convergent coupling to amino acid residues and subsequent incorporation of the glycosyl amino acid units into a peptide chain. This general strategy allows the assembly of molecules in which selected glycoforms can be incorporated at any desired position of the peptide chain. The resultant fully synthetic O-linked glycopeptide clusters are the closest homogeneous mimics of cell-surface mucins at present available, and so are promising compounds for the development of anticancer vaccines.

Carbohydrate Sequence↗
PubMed1993

[Effect of targeting treatment of mitomycin C immunoconjugate on stomach neoplasm].

An anti-gastric cancer monoclonal antibody MGb2-mitomycin C conjugate via dextran T-70 as intermediate (MGb2-PAD-MMC) was produced, and 28-30 g molecules of MMC were introduced into 1 g molecule of MGb2. Ninety-six hours after ip of 125I-MGb2-PAD-MMC (1.48 MBq/22 micrograms MGb2 per mouse) to nude mice bearing human gastric cancer SGC-7901, the tumor tissue:blood (T/NT) radioactivity ratio was 2.6, very much higher than that of the control 125I-normal IgG-PAD-MMC group (T/NT = 0.20). Single photo computed tomography imaging confirmed the results of biodistribution study. MGb2-PAD-MMC exhibited selective killing action on the SGC-7901 cells in vitro, which was considered to be mediated by monoclonal antibody MGb2. Nude mice inoculated with SGC-7901 xenograft in bilateral subrenal capsule were treated by MMC (ip), human recombinant interferon-alpha (Hu-IFN-alpha im), MGb2-PAD-MMC (ip) and MGb2-PAD-MMC+Hu-IFN-alpha daily for 5 d beginning 4 h after inoculation. The efficacy of the reagents estimated by the reduction of tumor size and calculated by T/C (%), was 28.3%, 16.4%, 47.8%, and 83.1%, respectively. These results demonstrated that the antitumor effect of MGb2-PAD-MMC was superior to free MMC, and that the Hu-IFN-alpha might further enhance the action of MGb2-PAD-MMC.

Adenocarcinoma↗
PubMed1992

Enhanced antitumor activity of daunomycin conjugated with antigastric cancer monoclonal antibody MGb2.

In the present study, an antigastric cancer monoclonal antibody, MGb2, was chosen to prepare an antibody-daunomycin conjugate. Daunomycin was modified by cis-aconitic anhydride, and the derivative was linked to antibody, a carbodiimide reagent being used to produce peptide bonding. Four to five molecules of daunomycin were specifically bound per molecule of antibody, without severely impairing the pharmacological activity of daunomycin and with minimal loss of antibody activity. A tetrazolium dye colorimetric assay indicated that the MGb2-daunomycin conjugate exhibited selective cytotoxicity against human gastric cancer cells SGC-7901 in vitro. The tumor localization in BALB/c nude mice showed that the specific conjugate could recognize the tumor as efficiently as the unconjugated antibody. MGb2-daunomycin conjugate could significantly suppress the growth of human gastric carcinoma GAII inoculated under the renal capsules of BALB/c nude mice. Intraperitoneal injection of MGb2-daunomycin conjugate twice a week for 3 weeks at a dose of 1 mg/kg of drug gave a tumor inhibition rate of 91.58%, far more effective than free daunomycin or an irrelevant conjugate.

Animals↗
PubMed1991

Specific targeting of mitomycin C to tumors by anti-gastric cancer monoclonal antibody.

In the present study, an anti-gastric cancer monoclonal antibody, MGb2, was chosen to prepare antibody-mitomycin C (MMC) conjugate with dextran T-40 as intermediary. Twenty molecules of MMC were introduced into each molecule of antibody while the antigen-binding capacity of the antibody was kept well. The conjugate showed selective cytotoxicity upon human gastric cancer cell line SGC-7901. Radioimmunoimaging and biodistribution studies indicated that after conjugation with MMC via dextran T-40 as intermediary, the tumor localization capacity of the antibody was well retained. When tested in nude mice, inoculated with human gastric carcinoma SGC-7901 in bilateral subrenal capsules, intraperitoneal injection of the conjugate daily for 6 days at a dose of 1 mg/kg gave a tumor inhibitory rate of 68.67%, which was far better than that of free MMC or irrelevant conjugate. No synergetic effect was found in regard to the mixture of MGb2 with MMC.

Animals↗
PubMed1991

Purification and partial characterization of a new group of gastric cancer associated antigens.

The corresponding antigens of MG series monoclonal antibodies (MG5, MG9, MGd1 and MGe1) against gastric cancer were purified and partially characterized. Each of these monoclonal antibodies was purified by passing through a DEAE-52 cellulose columns and covalently coupled with CNBr-activated sepharose 4B successively. By means of concanavalin A and antibody affinity chromatography, the corresponding antigens of MG series McAb were extracted from gastric cancer tissue respectively. Immunological and biochemical studies confirmed that the corresponding antigens of MG series McAb were a new group of gastric cancer associated neutral glycolipid and glycoprotein antigens.

Antibodies, Monoclonal↗
PubMed1991

Diagnostic significance of gastric cancer associated antigens (MG-AGS) in serum, ascitic fluid and gastric juice.

A group of monoclonal antibodies against gastric cancer, pooled in equal proportions, was used to investigate their corresponding antigens (MG-Ags) in serum and body fluid of patients with gastrointestinal cancer and benign diseases using microsphere-ELISA method. The mean serum level (plus 3 standard deviations) in 59 normal subjects was arbitrarily set as the positive threshold value. The positive rate was found to be 68.8% (135/196) in sera of patients with gastric cancer, 70% (14/20) in colonic cancer, 72.2% (24/33) in rectal cancer, 43.8% (7/16) in esophageal cancer, 45.5% (5/11) in cholecystic cancer and 34.9% (15/43) in lung cancer, which, however, was not found in primary liver cancer, pancreatic cancer and ovarian cancer. In 214 patients with benign diseases, a false positive rate was 7.48%. In gastric juice and ascitic fluid of patients with gastric cancer, the positive rates were found to be 61.7% (27/44) and 83.3% (20/24) respectively. These antigens were also determined repeatedly in sera of patients with gastric cancer who had undergone gastrectomy. It was found that the level of MG-Ags in sera began to decrease at 8-10 days after operation. These results suggest that the determination of MG-Ags is useful in the diagnosis of gastrointestinal cancer and evaluation of the treatments.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Studies on gastrin in duodenal ulcer.

By immunocytochemical method and radioimmunoassay, the gastrin secreting cells (G cells) and gastrin concentration in antral mucosa, gastric juice and serum in 20 patients with duodenal ulcer (DU) were studied. The number of G cells and gastrin concentration in antral mucosa showed no significant difference as compared with normal control. The number of G cells in patients with DU and antral atrophy was much higher than those with antral atrophy but with DU. It indicated that G cells were increased in number in DU, and the gastrin concentration in gastric juice (271.11 +/- 255.25 pg/ml) was much higher than in sera (74.71 +/- 43.07 pg/ml). G cells were distributed in different parts of pyloric glands, showing that gastrin in gastric juice should come directly from G cells. The disturbance of feedback mechanism in regulating gastric acidity might be an important role in hypersecretion of gastric acid in DU. The increase of gastrin concentration in gastric juice might be closely related to hyperplasia of parietal cells.

Adult↗
PubMed1990

Targeted anti-tumor agents and their cytotoxicity on gastric cancer cells in vitro.

Several chemotherapeutic drugs including methotrexate, daunomycin, mitomycin C and toxin such as ricin, A chain of ricin were chosen to conjugate with murine monoclonal antibodies MGb2 and MG11. The drugs were linked to antibody directly or through human serum albumin as intermediary. The ELISA results showed that the antibody retained well the antigen-binding capacity during conjugation. These conjugates showed highly selective cytotoxic effect on target cells. In chronic cytotoxicity tests, the cytotoxic effect of these conjugates on human gastric cancer cells KATOIII was quite similar to that of free drugs or ricin, but greater than that of irrelevant conjugates, while they had a little effect on non-target cells, suggesting that the selective cytotoxicity on target cells of the conjugates be mediated by antibodies.

Animals↗
PubMed1990

Selective cytotoxicity against human tumor cells by an anti-gastric cancer monoclonal antibody-mitomycin C conjugate.

An anti-gastric cancer monoclonal antibody, MGb2, was chosen to prepare MGb2-mitomycin C (MMC) conjugate. Four to five molecules of MMC were introduced into each molecule of antibody with the antibody activity well retained. The conjugate showed a highly selective cytotoxicity upon human gastric cancer cells KATO-III. In the 48-h exposure test, the cytotoxic effect of MGb2-MMC upon target cells was similar to that of free MMC, but much greater than that of normal mouse immunoglobulin-MMC conjugate. Instead, the MGb2-MMC showed a statistically less cytotoxic effect upon non-target cells. Imaging and biodistribution studies indicated that the MGb2 was still well localized in tumor tissue after its conjugation with MMC.

Animals↗
PubMed1990

[Effects of immuno-drug conjugates on growth of human gastric cancer xenograft in subrenal capsule of nude mice].

A conjugate of an anti-gastric cancer monoclonal antibody and mitomycin C linked by polyaldehyde dextran T-40 (MGb2-PAD-MMC) was prepared. Nude mice inoculated with human gastric cancer (SGC-7901) xenograft in bilateral subrenal capsule were treated ip with the conjugate at a daily dose containing MGb2 22.4 mg/kg and MMC 1 mg/kg for 6 d since 4 h after inoculation. The efficacy of the conjugate was estimated by the reduction of tumor size which calculated by T/C (%) was 32.2%. If MGb2 in the conjugate was replaced by a normal nude mice IgG (NIgG-PAD-MMC) or the nude mice were treated ip with the dose of MMC alone, the tumor T/C (%) were 58 and 87%, respectively. It was statistically significant between MGb2-PAD-MMC and NIgG-PAD-MMC or MMC treatment. When the above mentioned nude mice with SGC-7901 were treated ip with thrice dose of the conjugate (MGb2 67.2 mg/kg and MMC 3 mg/kg) for 6 d, the tumor growth was inhibited completely. Nevertheless, the same dose of MMC was given to the nude mice resulted in toxic appearance included anorexia, weight loss or even death. Furthermore, when the nude mice were treated ip with MGb2-PAD-MMC 24 h after inoculation, no apparent therapeutic effect was seen. In some experiments, nude mice inoculated with another human transplanted gastric tumor (GA II) xenograft treated ip with a conjugate of MGb2 and MMC or daunorubcin (Dau) 1 day after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1990

Changes and significance of immunoreactive beta-endorphin in gastric mucosa of patients with benign and malignant gastric diseases.

RIA method was used in this study to determine immunoreactive beta-endorphin (ir-beta-EP) in gastric mucosa of patients with benign and malignant gastric diseases. The results showed that the content of ir-beta-EP in gastric mucosa in the peptic ulcer group was the highest (68 +/- 9.5 pg/mg wet weight tissue, P less than 0.01), while its content in gastric carcinoma was closely related to the degree of differentiation of the tumor, that is, in poorly differentiated carcinoma it was lower than that in well differentiated carcinoma (P less than 0.02), and was also lower than that in gastritis (P less than 0.05). At the same time, we found that beta-endorphin can markedly augment the 3H-TdR incorporation of lymphocytes (P less than 0.01). This effect was not blocked by naloxone.

Gastric Mucosa↗
PubMed1989

[Detection of gastric cancer associated antigens in ascitic and pleural fluid for ascertaining the nature of the exudate].

A new group of gastric cancer associated antigens (MG-Ag) in ascitic fluid and pleural effusion was detected. First of all, the monoclonal antibodies (MG series) were purified and coupled to the miniglobules. The samples to be examined were then mixed with the MG-miniglobules to react. After being blocked by serum of normal mouse, the MG-miniglobules were mixed and made to react with the monoclonal antibodies labeled with HRP. With ELISA method, the MG-Ag levels in ascitic and pleural fluid were determined in 171 patients. The mean value of 87 non-malignant patients plus 3 standard deviations was arbitrarily set as the highest normal limit. Values above this limit were found in 39 (75%) of 52 patients with lung cancer and 20 (83%) of 24 patients with gastric cancer. The MG-Ag level was elevated in 4 (4.6%) of 87 patients with benign diseases. It is not elevated in 8 patients with ovarian cancer. It is suggested that determination of MG-Ag in ascitic and pleural fluid can be used for ascertaining the nature of ascites and pleural effusion.

Antigens, Tumor-Associated, Carbohydrate↗