chondroitin-sulfates and Uterine-Cervical-Neoplasms

We studied the feasibility and efficacy of intravesical instillations with 40 ml chondroitin sulfate 0.2% solution to prevent or reduce acute radiation cystitis in women undergoing pelvic radiotherapy.. In a comparative pilot study in 20 patients, half of the patients received instillations. Instillations' bother was measured with visual analog scores (VAS, 0-10); bladder pain, with VAS; micturition-related quality of life, with the urogenital distress inventory (UDI).. One of the instilled patients discontinued the instillations. The first median "acceptability"-VAS was 0 (range, 0-3); the last median was 1 (range, 0-3). "Bladder pain"-VAS peaked halfway in the treatment among controls (median, 1; range, 0-5) and after treatment in the instilled patients (median, 1; range, 1-3). UDI scores showed over time median follow-up scores at or above median baseline scores in controls and at or below median baseline scores in instilled patients.. Intravesical instillations with chondroitin sulfate 0.2% solution may decrease the bother related to bladder symptoms and are well tolerated.

Topics: Acute Disease; Administration, Intravesical; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Cystitis; Female; Humans; Middle Aged; Pain Measurement; Patient Acceptance of Health Care; Pilot Projects; Quality of Life; Radiation Injuries; Radiotherapy; Surveys and Questionnaires; Urination; Urination Disorders; Uterine Cervical Neoplasms; Uterine Neoplasms

Cancer has the second-highest mortality rate worldwide after cardiovascular disease. In addition, breast and cervical cancer are two of the leading causes of cancer-related deaths among women. The tumor microenvironment, which consists of fibroblasts, immune cells, cells that form blood vessels, and proteins, is a therapeutic target for cancer therapy. As part of the cellular microenvironment, glycosaminoglycan chondroitin sulfate is associated with various aspects of tumor progression and metastasis depending on the sulfate pattern of chondroitin sulfate. This study evaluated the roles of Microbial Chondroitin Sulfate (CS) and Commercial CS in tumor growth and metastasis comparatively using MDA-MB-231 metastatic breast cancer cells, HeLa cervical cancer cells, and normal fibroblasts. In addition, the role of CS types in wound healing was also assessed comparatively.  Microbial CS was more cytotoxic in MDA-MB-231 cells than HeLa compared to Commercial CS. Although both CS reduced cell viability in normal cells, the selective index of Microbial CS in MDA-MB-213 cells was higher than its commercial counterpart. In addition, the role of CS types in wound healing was also assessed comparatively. Both types of CS decreased the cell migration in MDA-MB-231 cancer cells, but HeLa cells were more sensitive to Microbial CS than Commercial CS to heal the wound. The wound healing of NIH3T3 cells after Microbial CS was similarly high to the healing after Commercial CS. This preliminary study shows that microbial CS produced by biotechnological methods from a recombinant source created by our team can be an effective therapeutic agent in various types of cancer.

Topics: Animals; Antineoplastic Agents; Chondroitin Sulfates; Female; HeLa Cells; Humans; Mice; NIH 3T3 Cells; Tumor Microenvironment; Uterine Cervical Neoplasms; Wound Healing

The aim of this work was to prepare polysaccharide-based nanoparticles (NPs) sensitive to glutathione (GSH), and to elucidate the effect of the concentration of glucose used as cryoprotectant during freeze-drying on the GSH-responsiveness. NPs were obtained via ionic interaction between negatively charged polysaccharides, chondroitin sulfate and dermatan sulfate, and the positively charged thiolated chitosan (CSSH), and crosslinking of CSSH before or after the nanoparticles formation with a disulfide-bond containing crosslinker, N,N'-bis(acryloyl)cystamine (BAC). NPs were freeze-dried with glucose at two different concentrations (0.5 and 5.0%w/w) and then characterized as methotrexate delivery systems, studying the effect of GSH concentration on drug release, efficacy against tumor cells and cellular internalization. Non-loaded NPs were highly compatible with murine fibroblasts and showed a suitable size for being used in anticancer therapy. When methotrexate-loaded NPs were freeze-dried with the highest glucose concentration, they lost their responsiveness to GSH concentration in vitro. Drug-loaded NPs were shown to inhibit the growth of tumor cells (HeLa and CHO-K1) with greater efficiency than free methotrexate, disregarding the concentration of glucose used for freeze-drying. Nevertheless, confocal microscopy studies revealed that cellular internalization of NPs freeze-dried with 5.0% glucose is more difficult than for NPs freeze-dried with lower glucose concentration. Thus, concentration of glucose cryoprotectant should be taken into account during development of NPs intended to release the drug as a function of GSH levels, due to the specific interactions of glucose with GSH.

Topics: Animals; Antimetabolites, Antineoplastic; BALB 3T3 Cells; Cell Survival; Chemistry, Pharmaceutical; Chitosan; CHO Cells; Chondroitin Sulfates; Cricetulus; Cross-Linking Reagents; Cryoprotective Agents; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Carriers; Female; Freeze Drying; Glucose; Glutathione; HeLa Cells; Humans; Kinetics; Methotrexate; Mice; Microscopy, Confocal; Nanomedicine; Nanoparticles; Polymethacrylic Acids; Polysaccharides; Solubility; Technology, Pharmaceutical; Uterine Cervical Neoplasms

The aim was to develop a long-term delivery system for Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) without chemical modification (such as pegylation).. A nanocomplex system between the positively charged TRAIL and the negatively charged chondroitin sulfate (CS) (CS/TRAIL) was designed and applied in poly(lactide-co-glycolide) (PLGA) microspheres (MSs).. A nanocomplex of approximately 200 nm was easily formed in a weight ratio of 2 TRAIL to CS (TC2) at pH 5.0. The cytotoxicity of CS/TRAIL against HeLa cells was similar to that of native TRAIL. The complex also had higher loading efficiency (above 95%) in PLGA MSs prepared by the multi-emulsion method than that of native TRAIL. The release behaviour of TRAIL from the PLGA MSs was monitored. Although the release of TRAIL from native TRAIL-loaded PLGA MSs (TMS0) was almost complete after 3 days, TC2-loaded PLGA MSs (TMS2) showed sustained TRAIL release without an initial burst for 10 days. The released TRAIL from TMS2 led to cytotoxicity accompanied by massive apoptosis of cancer cells. TMS2 significantly inhibited tumour growth in an in-vivo xenograft model in mice, without any loss of body weight after treatment.. From the results, we concluded that TC-loaded PLGA MSs have the potential for long-term delivery of TRAIL without side effects.

Topics: Animals; Antineoplastic Agents; Apoptosis; Chondroitin Sulfates; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Drug Stability; Female; HeLa Cells; Humans; Lactic Acid; Male; Mice; Mice, Inbred ICR; Microspheres; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Recombinant Fusion Proteins; Solubility; TNF-Related Apoptosis-Inducing Ligand; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays

Human carcinoma cells cultured in serum free medium produced an enzyme present as two different isoforms of 62 and 59 kDa which was found to degrade hyaluronan and chondroitin sulfate, with optimum activity at pH 4.0 and 0.03 M NaCl. The activity was suppressed by treatment with 250 mM apigenin and 1 mM DTT. The one-dimensional and two-dimensional gel patterns of tumor hyaluronidase differed from those of human serum hyaluronidase. Deglycosylation of tumor hyaluronidase caused nearly complete elimination of activity, suggesting the importance of sugar chains in enzymatic function. The results of treatment with neuraminidase, in addition to the findings for the enzyme mentioned above, suggest hyaluronidase from carcinoma cells and serum hyaluronidase to differ in sugar chains and/or the core protein. Tumor hyaluronidase was shown to be endo-beta-N-acetyl-D-hexosaminidase and tetrasaccharide was identified as the major product, thus indicating the tumor hyaluronidase to be a testis-type hyaluronidase.

Topics: Blood Proteins; Carcinoma; Chondroitin Sulfates; Electrophoresis, Gel, Two-Dimensional; Female; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Isoenzymes; Lung Neoplasms; Neoplasm Proteins; Substrate Specificity; Tumor Cells, Cultured; Uterine Cervical Neoplasms

The important components of mucopolysaccharides and collagen have been analyzed in tissues of control and carcinoma of uterine cervix. Among these components hyaluronic acid and chondroitin sulphate levels were found to be increased, whereas decreased level of collagen was observed in uterine cervical carcinoma. Serum cathepsin B, D and acid and alkaline phosphatases have also been analyzed in controls and carcinoma patients before and after treatments. The activities of these enzymes have been found to increase prominently in advanced stages. Among these enzymes cathepsin B and alkaline phosphatase have exhibited remarkable increase in activity in uterine cervical carcinoma. Different modes of treatment exerted reversion of the elevated activities of these enzymes. However, combined therapy type II (radiation combined with cisplatin and cyclophosphomide) seems to be more effective in reverting the activities of these enzymes to normal levels.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Cathepsins; Chondroitin Sulfates; Collagen; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Middle Aged; Pepsin A; Peptide Hydrolases; Uterine Cervical Neoplasms