Prevention of multidrug resistance (MDR) in osteosarcoma by NSC23925.

BACKGROUND: The major limitation to the success of chemotherapy in osteosarcoma is the development of multidrug resistance (MDR). Preventing the emergence of MDR during chemotherapy treatment has been a high priority of clinical and investigational oncology, but it remains an elusive goal. The NSC23925 has recently been identified as a novel and potent MDR reversal agent. However, whether NSC23925 can prevent the development of MDR in cancer is unknown. Therefore, this study aims to evaluate the effects of NSC23925 on prevention of the development of MDR in osteosarcoma. METHODS: Human osteosarcoma cell lines U-2OS and Saos were exposed to increasing concentrations of paclitaxel alone or in combination with NSC23925 for 6 months. Cell sublines selected at different time points were evaluated for their drug sensitivity, drug transporter P-glycoprotein (Pgp) expression and activity. RESULTS: We observed that tumour cells selected with increasing concentrations of paclitaxel alone developed MDR with resistance to paclitaxel and other Pgp substrates, whereas cells cultured with paclitaxel-NSC23925 did not develop MDR and cells remained sensitive to chemotherapeutic agents. Paclitaxel-resistant cells showed high expression and activity of the Pgp, whereas paclitaxel-NSC23925-treated cells did not express Pgp. No changes in IC50 and Pgp expression and activity were observed in cells grown with the NSC23925 alone. CONCLUSIONS: Our findings suggest that NSC23925 may prevent the development of MDR by specifically preventing the overexpression of Pgp. Given the significant incidence of MDR in osteosarcoma and the lack of effective agents for prevention of MDR, NSC23925 and derivatives hold the potential to improve the outcome of cancer patients with poor prognosis due to drug resistance.

Surgical management of malignant soft tissue tumours in patients aged 65 years or older.

OBJECTIVE: With the aim to determine the most effective treatment for primary malignant musculoskeletal tumours in patients aged 65 years or older, we reviewed cases of low- and high-grade neoplasms, surgical margins, surgical methods, and the prognoses of elderly and aged patients at our institution. METHODS: Records of 25 patients aged 65 years or older who had malignant soft tissue tumours from December 1986 to February 1997 were reviewed. Low- and high-grade neoplasms accounted for 8 and 17 patients, respectively. 11 patients were aged 65 to 69 years, while 14 were 70 years or older. Surgical margins were wide in 19 cases, marginal in 4, and intralesional in 2. Reconstruction was done using 6 musculocutaneous flaps and/or 4 vessel grafts. As adjuvant therapy, radiotherapy was used in 5 cases and chemotherapy in 3. There was no recurrence in patients with wide surgical margins (determined on the basis of gross inspection of the excised tumour and the cut surface); but there was recurrence in 4 patients with marginal margins, and one patient with intralesional margin. Two patients with intralesional, 4 with marginal, and 2 with wide margins, died from recurrence at the primary site and metastasis, or from metastasis without recurrence at the primary site. RESULTS: Follow-up periods ranged from 4 months to 180 months (mean, 91.6 months). The overall 5-year survival rate was 79.6%; for low- and high-grade neoplasms, the figures were 100% and 69.7%, respectively; for those aged 65 to 69 years and in their 70's or older, the figures were 90.9% and 70.1%, respectively. CONCLUSION: For geriatric patients, wide surgical margins are required to manage both low- and high-grade neoplasms, in order to avoid multiple surgeries.

Clinical and immunohistochemical characteristics of benign giant cell tumour of bone with pulmonary metastases: case series.

PURPOSE: Giant cell tumour of bone with pulmonary metastases is rare. However, some patients die of pulmonary metastases, and histological examination cannot distinguish between benign tumour and malignant metastases. In this study, we present clinical and immunohistochemical findings associated with giant cell tumour of bone with pulmonary metastases. METHODS: Five patients with benign giant cell tumour of bone with pulmonary metastases (one man and 4 women) were studied. Patients' ages ranged between 20 and 23 years (mean age, 21.8 years). Tumours were in the distal femur in 2 cases, and in the proximal tibia, distal tibia, and lumbar spine in one case each. The tissue specimens from primary tumours, recurrent tumours, and pulmonary metastases were studied using immunohistochemical techniques. RESULTS: Three of the 5 primary tumours were of the spontaneous regression or growth cessation type, or the continuously slow-growing type, showing 4.2% to 6.2% of positive cells for Ki-67 after immunohistochemical staining. However, 2 patients with the rapid-growing type of disease died of pulmonary metastases; their primary, recurrent, and metastatic tumour specimens contained 9.0% to 11.5% of positive cells for Ki-67. CONCLUSION: Three of the 5 primary tumours had a benign clinical pattern and immunohistochemistry. Two of the 5 patients died of pulmonary metastases, which had an aggressive clinical pattern and a high prevalence of positive cells in Ki-67. Examination of Ki-67 should be carried out for aggressive type of giant cell tumour.