Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

Combined chemotherapy and radiation for bulky stages I-II cervical cancer: comparison of concurrent and sequential regimens.

Based on analysis of 5-year survival rates among 386 patients with carcinoma of the cervix treated between 1976 and 1984 at Yonsei University College of Medicine, high risk factors have been defined which identify patients with a poor prognosis when treated with radiation alone. Among patients with FIGO Stages I-II disease, lesions > or = 4 cm were indicative of a higher risk of treatment failure. Between 1984 and 1991, 39 patients with Stages I-II large cell squamous cancers > or = 4 cm in diameter were treated with radiation alone. Between 1984 and 1989, 19 comparable patients were treated with sequential chemotherapy consisting of two or three cycles of cisplatin at 100 mg/m2 and a 5-day infusion of 5-fluorouracil at 1000 mg/m2/24 hr. Between 1988 and 1991, 37 comparable patients were treated with concurrent radiation and one to six cycles of chemotherapy employing the same or equivalent drug and dose schedule. The radiation techniques, dose, and fractionation employed were similar in the three groups. The 30-month survival rate was 100, 89.5, and 79.5% (P < 0.05) following concurrent treatment, sequential treatment, and radiation alone, respectively. Response to chemotherapy administered in cycles was evaluated before instituting radiotherapy in the patients treated with sequential chemotherapy and radiation. In conclusion, the combination of radiotherapy and chemotherapy appeared superior to radiation alone, and the toxicity of combined modality therapy is manageable. Also concurrent chemotherapy may be slightly better than sequential chemotherapy and radiation, and given the lesser overall treatment time and expense, this has become the preferred mode of treatment in our institution.