Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction

Changes in cell survival contribute to tumour development, influence tumour biology and its response to chemotherapy. p53 gene alterations should negatively affect apoptosis by impaired p53-dependent apoptotic response. We looked for associations between spontaneous apoptosis, p53 gene mutation, p53 protein accumulation, growth fraction, bcl-2 expression and histological parameters in 64 ovarian, four tubal and three peritoneal carcinomas. Apoptotic cells were detected with the TUNEL method. p53 gene variants were detected by the single-strand conformation polymorphism and were sequenced directly. P53, Ki-67 and bcl-2 protein expressions were detected immunohistochemically. A weighed multiple logistic regression model was applied. Apoptotic index (Al) ranged 0.02–0.18 (mean 0.11); proliferation index (PI) ranged 3–90% (mean 54%). p53 gene mutations were present in 51, p53 protein accumulation in 46, and diffuse bcl-2 expression in 29 of 71 tumours. The AI was positively associated with the presence of p53 gene mutation (P = 0.011). However, the PI included into the analysis did positively influence the AI (P = 0.02) and diminished the association with p53 gene mutation (P = 0.082). The AI was negatively associated with good histological differentiation (P = 0.0006), the serous tumour type (P = 0.002), and diffuse bcl-2 expression (P = 0.025). Strong bcl-2 expression was associated with endometrioid tumour type (P = 0.002). FIGO stage and p53 protein accumulation were the only parameters that influenced overall survival time. Thus, our results suggest that histological tumour type and grade are major determinants of spontaneous apoptosis in ovarian carcinomas;p53 alterations do not adversely but rather positively affect spontaneous apoptosis by increasing growth fraction. This, in turn, suggests p53-independency of spontaneous apoptosis in ovarian carcinomas. © 2000 Cancer Research Campaig

Cooperation in the snowdrift game on directed small-world networks under self-questioning and noisy conditions

Cooperation in the evolutionary snowdrift game with a self-questioning updating mechanism is studied on annealed and quenched small-world networks with directed couplings. Around the payoff parameter value $r=0.5$, we find a size-invariant symmetrical cooperation effect. While generally suppressing cooperation for $r>0.5$ payoffs, rewired networks facilitated cooperative behavior for $r<0.5$. Fair amounts of noise were found to break the observed symmetry and further weaken cooperation at relatively large values of $r$. However, in the absence of noise, the self-questioning mechanism recovers symmetrical behavior and elevates altruism even under large-reward conditions. Our results suggest that an updating mechanism of this type is necessary to stabilize cooperation in a spatially structured environment which is otherwise detrimental to cooperative behavior, especially at high cost-to-benefit ratios. Additionally, we employ component and local stability analyses to better understand the nature of the manifested dynamics.Comment: 7 pages, 6 figures, 1 tabl