chondroitin-sulfates and Uterine-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

Gestational trophoblastic neoplasia (GTN) can result from the over-proliferation of trophoblasts. Treatment of choriocarcinoma, the most aggressive GTN, currently requires high doses of systemic chemotherapeutic agents, which result in indiscriminate drug distribution and severe toxicity. To overcome these disadvantages and enhance the chemotherapeutic efficacy, chondroitin sulfate A (CSA)-binding nanoparticles were developed for the targeted delivery of doxorubicin (DOX) to choriocarcinoma cells using a synthetic CSA-binding peptide (CSA-BP), derived from malarial protein, which specifically binds to the CSA exclusively expressed in the placental trophoblast. CSA-BP-conjugated nanoparticles rapidly bonded to choriocarcinoma (JEG3) cells and were efficiently internalized into the lysosomes. Moreover, CSA-BP modification significantly increased the anti-cancer activity of the DOX-loaded nanoparticles in vitro. Intravenous injections of CSA-BP-conjugated nanoparticles loaded with indocyanine green (CSA-INPs) were rapidly localized to the tumor. The CSA-targeted nanoparticles loaded with DOX (CSA-DNPs) strongly inhibited primary tumor growth and, more importantly, significantly suppressed metastasis in vivo. Collectively, our results highlight the potential of the CSA-BP-decorated nanoparticles as an alternative targeted delivery system of chemotherapeutic agents for treating choriocarcinoma and for developing new GTN therapies based on drug targeting.

Topics: Animals; Antibiotics, Antineoplastic; Binding Sites; Cell Line, Tumor; Cell Survival; Chondroitin Sulfates; Choriocarcinoma; Dose-Response Relationship, Drug; Doxorubicin; Drug Delivery Systems; Female; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Pregnancy; Treatment Outcome; Uterine Neoplasms; Xenograft Model Antitumor Assays

Topics: Chondroitin Sulfates; Cystitis; Female; Humans; Radiation Injuries; Uterine Neoplasms

In many tumors, the amount of chondroitin sulfate in the extracellular matrix has been shown to be elevated when compared to the corresponding normal tissue. Nevertheless, the degree of chondroitin sulfate increase varies widely. In order to investigate a possible correlation between the amount of chondroitin sulfate and tumor size, several individual specimens of human leiomyoma, a benign uterine tumor, were analyzed. The glycosaminoglycans from eight tumors were extracted and compared with those from the respective adjacent normal myometrium. The main glycosaminoglycan found in normal myometrium was dermatan sulfate, with small amounts of chondroitin sulfate and heparan sulfate. In leiomyoma, both dermatan sulfate and chondroitin sulfate were detected and the total amounts of the two galactosaminoglycans was increased in all tumors when compared to normal tissue. In contrast, the heparan sulfate concentration decreased in the tumor. To assess the disaccharide composition of galactosaminoglycans, these compounds were incubated with bacterial chondroitinases AC and ABC. The amounts of L-iduronic acid-containing disaccharides remained constant, whereas the concentration of D-glucuronic acid-containing disaccharides increased from 2 to 10 times in the tumor, indicating that D-glucuronic acid-containing disaccharides are responsible for the elevation in galactosaminoglycan concentration. This increase is positively correlated with tumor size.

Topics: Chondroitin Sulfates; Densitometry; Dermatan Sulfate; Female; Humans; Leiomyoma; Myometrium; Polysaccharides; Uterine Neoplasms

The basal lamina components laminin, heparan sulfate proteoglycan (HSPG), and type IV collagen were synthesized and codeposited in the extracellular matrix (ECM) by a cultured human cell line from gestational choriocarcinoma (JAR). Laminin and HSPG formed a noncovalent complex detected by the coimmunoprecipitation of HSPG with laminin from cell lysates and culture media. The complex was stable in the cell lysis buffer that contained detergents (1% Triton X-100, 0.5% deoxycholate, and 0.1% sodium dodecyl sulfate) and sodium chloride (from 0.15 to 1.0 M), but was dissociated by adding 8 M urea to the detergent lysates. Even though JAR cells produced roughly equal amounts of HSPG and chondroitin sulfate proteoglycan, only HSPG complexed with laminin, suggesting a specific interaction between these basal lamina components. The laminin-HSPG complex was deposited and retained in the ECM. This was shown biochemically by isolating an enriched fraction of ECM from JAR cells cultured on native type I collagen gels. At steady state, more than half (52%) of the laminin-HSPG in the culture was recovered in the ECM fraction, in contrast to 16% of the total laminin and 29% of the total type IV collagen, which were secreted to a greater extent than laminin-HSPG into the culture medium. The retention of the laminin-HSPG complex in the ECM suggests that it may participate in the assembly of the basal lamina-like extracellular matrix deposited by JAR cultures. Omission of ascorbate from the culture medium abolished the ECM deposition of type IV collagen but had little effect on the deposition of laminin or laminin-HSPG. This demonstrates that the stable deposition of laminin-HSPG and laminin in the collagen-based choriocarcinoma cultures is not dependent on an assembled network of type IV collagen.

Topics: Basement Membrane; Chondroitin Sulfates; Choriocarcinoma; Collagen; Detergents; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix; Female; Glycosaminoglycans; Heparin; Humans; Immunosorbent Techniques; Kinetics; Laminin; Macromolecular Substances; Pregnancy; Pronase; Proteoglycans; Sodium Chloride; Tumor Cells, Cultured; Urea; Uterine Neoplasms