chondroitin-sulfates and Stomach-Neoplasms

The study was to construct reduction-responsive chondroitin sulfate A (CSA)-conjugated TOS (CST) micelles with disulfide bond linkage, which was used for controlled doxorubicin (DOX) release and improved drug efficacy in vivo.. CST and non-responsive CSA-conjugated TOS (CAT) were synthesized, and the chemical structure was confirmed by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, fluorescence spectrophotometer and dynamic light scattering. Antitumour drug DOX was physically encapsulated into CST and CSA by dialysis method. Cell uptake of DOX-based formulations was investigated by confocal laser scanning microscopy. In vitro cytotoxicity was studied in A549 and AGS cells. Furthermore, antitumour activity was evaluated in A549-bearing mice.. CST and CAT can form self-assembled micelles, and have low value of critical micelle concentration. Notably, DOX-containing CST (D-CST) micelles demonstrated reduction-triggered drug release in glutathione-containing media. Further, reduction-responsive uptake of D-CST was observed in A549 cells. In addition, D-CST induced stronger cytotoxicity (P < 0.05) than DOX-loaded CAT (D-CAT) against A549 and AGS cells. Moreover, D-CST exhibited significantly stronger antitumour activity in A549-bearing nude mice than doxorubicin hydrochloride and D-CAT.. The reduction-responsive CST micelles enhanced the DOX effect at tumour site and controlled drug release.

Topics: A549 Cells; alpha-Tocopherol; Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Chondroitin Sulfates; Delayed-Action Preparations; Disulfides; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Micelles; Neoplasms; Polymers; Stomach Neoplasms; Xenograft Model Antitumor Assays

To elucidate the stromal characteristics in gastric carcinoma, the localization of chondroitin sulfate proteoglycans (PGs), fibronectin (FN), and type IV collagen was observed by immunohistochemical methods in 46 surgically resected stomachs including 41 carcinomas, 2 adenomas, and 3 ulcers. Chondroitin 4-sulfate PG revealed by 9A2 antibody and FN were distributed abundantly in the stroma of gastric carcinoma. On the other hand chondroitin 6-sulfate PG revealed by 3B3 antibody and type IV collagen were located more broadly in the stroma of undifferentiated carcinoma, especially scirrhous carcinoma than differentiated carcinoma. Type IV collagen was ultrastructurally localized around smooth muscle cells, myofibroblasts, and capillaries. And Bromodeoxyuridine was labelled in the stromal cells including endothelial cells and smooth muscle cells whose proliferative activities were suggested. In addition to carcinoma, muscularis mucosae of adenoma and ulcer were stained by 3B3 antibody. In gastric carcinoma, extracellular matrix was more strikingly distributed compared with noncarcinomatous region and in particular, stromal changes may be promoted by cancer cells in scirrhous carcinoma. These results suggest that specific stromal changes in gastric carcinoma may be related with the histologic types and growth patterns.

Topics: Chondroitin Sulfates; Collagen; Fibronectins; Humans; Immunohistochemistry; Proteoglycans; Stomach; Stomach Neoplasms

The sulfated glycosaminoglycan (SGAG) composition of gastric mucosa from 24 patients with chronic superficial gastritis, 2 patients with adenocarcinoma and 36 normal subjects is reported. The mucosa was obtained by endoscopic biopsy and after histopathological examination the SGAG were extracted and characterized. Three different SGAG were isolated: chondroitin 4,6-sulfate, dermatan sulfate and heparan sulfate. Their relative concentrations for the different groups were submitted to analysis of variance by Scheffe's method. Different SGAG compositions were observed in two gastric regions (antrum and body), in chronic superficial gastritis, in adenocarcinoma and in two age groups (less than 40 years and greater than 40 years). These and other results suggest that these macromolecules might be involved in the processes of cell division and aging.

Topics: Adenocarcinoma; Adult; Aging; Chondroitin Sulfates; Dermatan Sulfate; Gastric Mucosa; Gastritis; Glycosaminoglycans; Heparitin Sulfate; Humans; Stomach Neoplasms

The influence of fixed fibroblasts on the glycosaminoglycan (GAG) synthesis of gastric carcinoma cells was examined by incubation along with [3H]glucosamine. In well-differentiated adenocarcinoma cells, the amount of 3H-GAG in the interface material between the carcinoma cells and the fixed fibroblasts was much larger (about twenty times) than in the interface between the carcinoma cells and the bare culture plates, and 3H-GAG consisted mainly of heparan sulfate, with a small amount of dermatan sulfate and chondroitin sulfate. On the other hand, in poorly differentiated carcinoma cells, the amount of 3H-GAG in the interface material produced by the carcinoma cells on the fibroblast was almost the same as on the bare culture dish. In a conventional monolayer culture, well-differentiated adenocarcinoma cells produced a much greater amount of GAG, consisting mainly of dermatan sulfate, chondroitin sulfate and heparan sulfate, than poorly differentiated carcinoma cells. Almost the same amount of hyaluronic acid was secreted into the medium by both types of carcinoma cells.

Topics: Adenocarcinoma; Cell Adhesion; Cell Communication; Cell Differentiation; Cell Division; Cell Line; Chondroitin Sulfates; Dermatan Sulfate; Fibroblasts; Glycosaminoglycans; Heparitin Sulfate; Humans; Stomach Neoplasms

The glycosaminoglycan (GAG) content of stomach carcinoma tissue was compared with that of non-neoplastic mucosa. GAG synthesis was also studied, by an analysis of 35S-labelled material after incubation of tissue segments in medium containing 35SO4. No significant difference was found between the amount of GAG and its components in the medullary carcinoma tissue and in non-neoplastic mucosa, but GAG synthesis of the carcinoma tissue was at a much higher rate than that of the non-neoplastic mucosa. In the autoradiograph, high 35S uptake in the carcinoma cells was observed. The GAG content of the scirrhous-carcinoma tissue was about twice that of medullary carcinoma.

Topics: Chondroitin Sulfates; Dermatan Sulfate; Gastric Mucosa; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Stomach Neoplasms

Topics: Chondroitin Sulfates; Gastric Mucosa; Glycopeptides; Glycosaminoglycans; Humans; Hyaluronic Acid; Metaplasia; Molecular Weight; Mucins; Stomach Neoplasms