Suppression of apoptosis by bcl-2 does not prevent p53-mediated control of experimental metastasis and anchorage dependence.

Mutations in the p53 tumor suppressor gene are frequently associated with the metastatic stage of tumor progression. Inactivation of p53 was shown to promote metastasis under experimental conditions. To determine the p53 functions that are involved in the control of tumor metastasis, we compared properties of three types of transformed mouse fibroblasts: with intact p53, with p53-mediated apoptosis suppressed by bcl-2 and with p53 inactivated by dominant negative mutants. Although expression of bcl-2 blocked apoptosis in detached cells and increased tumor cell survival in the blood circulation, it was insufficient to affect the ability of p53 to cause cell cycle arrest in detached cells and suppress experimental metastasis. For the suppression of metastasis complete inactivation of p53 was required. We conclude that the apoptotic function of p53 is dispensable for the p53-dependent suppression of experimental metastasis that is presumably achieved by controlling anchorage dependence. These data provide a possible explanation to dramatic differences in values of bcl-2 and mutant p53 as prognostic markers in human cancer.

Expression of sarcoma-associated antigens p102 and p200 in human sarcoma cell lines.

BACKGROUND: Understanding tumor antigen expression and its correlation with the cell cycle may help in designing immunotherapy by monoclonal antibodies. Therefore, we studied the in vitro expression of sarcoma-associated antigens p102 and p200 in the G, S, and G2/M phases of sarcoma cell lines. METHODS: The expression of human cell surface sarcoma-associated antigens p102 and p200 was studied in 13 human sarcoma cell lines, using flow cytometry. RESULTS: p102 was detected by monoclonal antibody 19-24-6 in all 13 sarcoma cell lines, and p200 was detected by monoclonal antibody 29-13-17 in five of 13. p102 antigen expression was 1.4- to 3.4-fold higher (p < 0.001) than p200 expression. Although sarcoma cell lines showed a wide range of p102/p200 antigen expression, over 99% of the entire in vitro and in vivo cell population was found to be p102- and/or p200-positive. In three cell lines, p102 expression was cell cycle-dependent, with relative fluorescence intensity ranging from 13.8% to 23.9% higher at the G1 phase than at the G2/M phase. In three cell lines, the expression of p200 at the GI phase was 22.4% to 40.9% percent higher than at the G2/M phase. CONCLUSIONS: The heterogeneity and cell cycle dependence of p102/p200 antigen expression in sarcoma cells suggest that monoclonal antibodies 19-24-6 and 29-13-17 might be applied to the immunotherapy of sarcoma.

Dual use of silver for management of chronic bone infections and infected non-unions.

Broad spectrum antibacterial effect of electrically generated silver ions has been fully established. Present work consists of clinical evaluation of beneficial antibacterial effect of silver ions liberated electrically with the help of locally manufactured power pack in 920 proved cases of chronic osteomyelitis with or without pathological fractures and septic non-unions. Wound debridement, silver iontophoresis, proper immobilisation and subsequent wound care yielded not only control of bone infections in 85% cases, but also produced healing of pathological fractures in 83% patients. Results remained unaffected by age or sex of patient, type of bone involved, duration of previous illness or type of previous treatment. Follow-up varied from 6 months to 10 years. This technique is likely to open a new chapter in treatment of chronic resistant bone infections and septic non-unions due to open fractures particularly in developing countries of the world.

Comparative study of bone growth by pulsed electromagnetic fields.

Pulsed electromagnetic fields have been widely used for treatment of non-united fractures and congenital pseudarthrosis. Several electrical stimulation systems such as air-cored and iron-cored coils and solenoids have been used the world over and claimed to be effective. Electrical parameters such as pulse shape, magnitude and frequency differ widely, and the exact bone-healing mechanism is still not clearly understood. The study attempts to analytically investigate the effectiveness of various parameters and suggests an optimal stimulation waveform. Mathematical analysis of electric fields inside the bone together with Fourier analysis of induced voltage waveforms produced by commonly used electrical stimulation wave-forms has been performed. A hypothesis based on assigning different weightings to different frequencies for osteogenic response has been proposed. Using this hypothesis astonishingly similar effective values of electric fields have been found in different systems. It is shown that effective electric field rather than peak electric field is the main parameter responsible for osteogenesis. The results are in agreement with experimental findings made on human beings by different investigators.