RESUMEN
CD24, which is upregulated in several human malignancies, is related to Epithelial-mesenchymal-transition (EMT) and has characteristics of cancer stem-like cells, especially in cisplatin-resistant ovarian carcinoma cells. Drug delivery systems represent a promising therapeutic approach for diseases with treatment resistance, and the present study investigated a novel CD24-targeted drug delivery system for advanced ovarian carcinoma. We produced liposomal cisplatin with a red fluorescent substance - cyanine 5.5 (GL-CDDP-Cy5.5). In order to target CD24-positive cells, an anti-CD24 monoclonal antibody was modified to the above drug (CD24-GL-CDDP-Cy5.5). Specific uptake of CD24-GL-CDDP-Cy5.5 was confirmed using a therapeutically resistant ovarian cancer cell line, Caov-3 cells. Antitumor effects of CD24-GL-CDDP-Cy5.5 were then evaluated in Caov-3 ×enograft mice. CD24-GL-CDDP-Cy5.5 showed more specific uptake by flow cytometry than GL-CDDP-Cy5.5. In xenograft mice, GL-CDDP-Cy5.5 and CD24-GL-CDDP-Cy5.5 treatment had significantly higher platinum concentration in disseminated tumor cells than cisplatin (P<0.05). Moreover, CD24-GL-CDDP-Cy5.5 suppressed tumor growth and prolonged survival time compared with other treatments. Median survival times of the control, cisplatin, GL-CDDP-Cy5.5 and CD24-GL-CDDP-Cy5.5 groups were 37, 36, 46 and 54 days after inoculation, respectively. Immunohistochemical analysis showed that CD24-GL-CDDP-Cy5.5 treatment, compared with GL-CDDP-Cy5.5, decreased the number of CD24-positive cells and suppressed the EMT phenomenon significantly (P<0.05). The present study demonstrated that CD24-GL-CDDP-Cy5.5, compared with other treatments, improved therapeutic efficacy. The present results suggested the potential for targeting anticancer therapeutics for CD24-positive cells to prevent disease progression.
RESUMEN
OBJECTIVE: Although surgical menopause may increase the risks of osteoporosis, few studies have investigated the influence of chemotherapy and radiation therapy. The aim of this study is to evaluate the effects of treatments for gynecological malignancies on bone mineral density (BMD). METHODS: This study enrolled 35 premenopausal women (15 ovarian cancers (OCs), 9 endometrial cancers (ECs), and 11 cervical cancers (CCs)) who underwent surgical treatment that included bilateral oophorectomy with or without adjuvant platinum-based chemotherapy in OC and EC patients, or concurrent chemo-radiation therapy (CCRT) in CC patients according to the established protocols at the Osaka Medical College Hospital between 2006 and 2008. The BMD of the lumbar spine (L1-L4) was measured by dual-energy X-ray absorptiometry, and urine cross-linked telopeptides of type I collagen (NTx) and bone alkaline phosphatase (BAP) were assessed for evaluation of bone resorption and bone formation respectively. These assessments were performed at baseline and 12 months after treatment. RESULTS: Although the serum BAP was significantly increased only in the CC group, a rapid increase in the bone resorption marker urinary NTx was observed in all groups. The BMD, 12 months after CCRT was significantly decreased in the CC group at 91.9±5.9% (P<0.05 in comparison to the baseline). CONCLUSION: This research suggests that anticancer therapies for premenopausal women with gynecological malignancies increase bone resorption and may reduce BMD, particularly in CC patients who have received CCRT. Therefore, gynecologic cancer survivors should be educated about these potential risks and complications.
