No abstract

Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P ‫؍‬ .03) and more advanced tumor stages (P ‫؍‬ .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P ‫؍‬ .001). Tumors that were positive for both p53 and MDM2 were larger (P ‫؍‬ .003) and of more advanced stage (P ‫؍‬ .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P ‫؍‬ .046), and the apoptotic index was lower among p53-positive tumors (P ‫؍‬ .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.

We analyzed independent treatment variables (age, sex, signs and symptoms, site, size, histopathologic findings, grade, and clinical presentation) and treatment-dependent variables (resectability, type of operation, surgical margins, surgical boundaries, microscopic margins, adjuvant radiotherapy, and adjuvant chemotherapy) in 80 patients with primary retroperitoneal soft-tissue sarcomas admitted from 1982 through 1988. Both univariate and multivariate analysis of survival and disease-free survival were performed. The major factor in survival outcome was the ability to completely resect the lesion. When the 62 patients who underwent complete resection were examined, the only independent prognostic factor for both survival and disease-free survival was grade. We conclude that completeness of resection and grade of the lesion are primary determinants of survival. Once all tumor is macroscopically removed, no advantage could be demonstrated by more extensive surgical resection or current adjuvant therapy.

Hyperthermia, either alone or combined with radio-, immuno-or chemotherapy, can control tumor growth, but its effect on metastasis is still controversial. In the present study, we investigated the influence of hyperthermia on the metastatic potential of B16-F10 murine melanoma cells. Incubation of melanoma cells at 43 o C for 30 min led to a significant decrease in cell viability. About half of the cells survived the acute exposure to heat. These thermoresistant cells displayed a longer lag phase as compared to control unheated B16-F10 melanoma cells. Other parameters of cell growth such as doubling time and saturation density were equivalent in both control and thermoresistant cells. Both control and treated cells were adherent, but thermoresistant cells failed to spread during the first 48 h after heat exposure. B16-F10 cells colonize the lungs of C57BL/6J mice when injected intravenously; the number of lung colonies is a measure of the metastatic potential of injected cells. Median values of 22, 10.5 and 31 colonies per injected mouse were observed for control cells, cells heated to 43 o C for 30 min and thermoresistant cells, respectively, with statistically significant differences between groups (Mann-Whitney test, P<0.02). Thus, despite its cytotoxic action, heat exposure induced the acquisition of a more metastatic phenotype in a subpopulation of B16-F10 cells.

No abstract

The apolipoprotein E gene, which is located on chromosome 19, has three alleles (epsilon2, epsilon3, and epsilon4). Several recent publications associate the presence of the apolipoprotein E epsilon4 allele with the occurrence of neurologic diseases, and consider it a risk factor for the development of central nervous system affections. A group of 40 patients with cerebral palsy was studied and compared to a control group of 40 subjects, and higher occurrence of the allele epsilon4 in the group of subjects with cerebral palsy was observed. A significantly higher risk of developing cerebral palsy was demonstrated among those subjects with the apolipoprotein E epsilon4 allele.

Objective. Our aim was to study the effects of the gonadotropin releasing hormone agonist on the uterine leiomyoma of infertile women. Material and methods. Sixty-seven nulliparous women (aged 24-39 years) with uterine leiomyomas, underwent ultrasonographic study of leiomioma volume, and were divided in two groups. Thirty-one had nodes greater than 300 cm 3 and were treated with goserelin 3.6 mg every 28 days for 6 months (group I); the other 36 patients did not receive medication (group II or control group). Sixteen patients from group I had 436 (median) reduction of the leiomyoma volume (subgroup Ia) and the other 15 women had reduction >36 (subgroup Ib). All women underwent myomectomy.Results. The group with the greater leiomyoma reduction after treatment with goserelin (group Ib) showed a significantly lower percentage of ER+ when compared with group Ia and the control group. Group Ib had a significantly higher percentage of PR+ in relation to the control group, but not to group Ia. The number of blood vessels, AgNOR dots, and cells, and the amount of collagen were not different between the three groups studied. Leiomyomata reduction correlated negatively with the percentage ER+ cells, but positively with the PR+ cells, amount of collagen and number of blood vessels. No correlation was found between the number of AgNOR dots and cellularity. Conclusion. Our data strengthen the hypothesis that the uterine leiomyoma response to steroid hormones results from the presence of specific hormone receptors, and progesterone receptors may also play a role in the development of leiomyoma.

A follow-up of 363 cranial bone grafts for nasal reconstruction is presented. The main indications for the surgery were congenital, posttraumatic, or postrhinoplasty deformity. The results were satisfactory in the vast majority of cases. The complications associated with the grafts and with the donor site are discussed, as are the methods to treat and prevent these complications from occurring.