Apoptosis in prostate carcinomas after short-term treatment with decapeptyl.

Altogether, 40 patients with advanced prostate cancer received the LH-RH analog, Decapeptyl (D), as monotherapy for 1 month. The dose of D was 3.75 mg/month, intramuscularly in microcapsules. Needle biopsy was taken from the prostate of 20 patients at 24 hours, of 10 patients at 7 days, and of 10 patients at 30 days after the injection. The biopsy samples were investigated for mitotic and apoptotic indices as well as expression of p53 and Ki67 in the tumor cells. The effect of the LH-RH analog was manifested in very low and even absent mitotic activity in all points in time. The expression of mutant p53 was high (above 80%) in all 1-day and 7-day samples and in 8 of 10 samples taken 30 days after the start of the therapy. In 2 cases, the ratio of p53-expressing tumor cells was 2% and 5%. At day 30, the previously high ratio of Ki67-positive tumor cells decreased to 2-10% in 8 cases and showed focally higher values (70-90%) in 2 cases. Extremely high (90-100%) apoptosis could be registered in scattered foci of the tumor tissue in all samples taken 1 and 7 days after D injection. The other parts of the tumor tissue showed lower (1-5%) apoptotic activity. At day 30 after the injection, the same phenomenon was observed in 4 cases, but in 6 cases the apoptotic ratio became diffusely low (1-2%). Focal increase of apoptosis observed in the 1- and 7-day samples may be attributed to the direct effect of the LH-RH analog on tumor cells. The findings at day 30 indicate a considerable decrease in proliferating activity and, in the majority of cases, also in apoptotic activity, reflecting the effect of D on the pituitary-gonadal axis.

bcl2, p53 and bax in thyroid tumors and their relation to apoptosis.

Twenty five thyroid tumors were investigated by immunohistochemistry for the presence of apoptosis, expression of p53, bax and bcl2. In nine adenomas (average age 40) the rate of p53 positive cells was 5.7%, while it was 13.3% for bax and 41.7% for bcl2 in the tumor cells. In six follicular carcinomas (average age 56) p53 positivity was obtained for 71.1%, while bax and bcl2 positivity constituted 3.4% and 2.5%, respectively. In ten papillary adenocarcinomas (average age 42) p53 was positive in 39.6%, but bax and bcl2 were positive in 3.4% and 3% of the tumor cells, respectively. Almost no signs of spontaneous apoptosis were found in any of the cases. Determination of p53, bax and bcl2 ratio in thyroid tumors may contribute to the differentiation between follicular adenomas and carcinomas.

Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants.

Apoptosis, the well-characterized form of active programmed cell death, is a physiologic phenomenon in embryonal and fetal life in developing organs. Severe hypoxia, which occurs in most preterm infants, also leads to cell death, which may be necrotic or apoptotic. The aim of our study was to examine the incidence of apoptosis in various organs (such as lung, kidney, and brain) of preterm infants who suffered from clinically proven respiratory distress causing infantile respiratory distress syndrome (IRDS), cardiac failure, and periventricular leukomalacia (PVL). Twenty-four autopsy cases were studied histologically to detect the apoptotic ratio, which was performed on the basis of hematoxylin and eosin staining and validated by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) reaction. Elevated apoptotic ratio was found in stages II, III, and IV of bronchopulmonary dysplasia (BPD) among alveolar and bronchiolar cells. The apoptotic activity was very low in stage I of BPD. High apoptotic ratio was detected in hypoxic injuries of the central nervous system (CNS) of preterm infants. Features of apoptosis were present in proximal and excreting tubules of the kidney. Significant elevation of apoptotic activity may play a role in the development of BPD, ischemic brain lesions, and renal failure.

Spontaneous apoptosis and retinoic acid receptor incidence in neuroblastomas and peripheral neuroectodermal tumors.

Twelve cases of neuroblastoma (NB) (7 boys and 5 girls) and 4 cases of primitive peripheral neuroectodermal tumor (PNET) (3 boys and 1 girl) were investigated for the presence of apoptosis and retinoic acid receptor (RAR) by immunhistochemical method. The apoptotic index in NB was zero or 1% in 8 children and relatively low (2-4.8%) in the other 4 cases, while it was higher (4.1-10.5%) in PNET. The RAR index determined by immunoperoxidase reaction in NB was zero or 3% in 5 cases and 9-34% in 7 children. RAR index in PNET was 16-68% in all the 4 cases. Good correlation (r = .47 according to Pearson-Bravis) was found between the number of RAR and spontaneous apoptosis. These results suggest that the RAR index in untreated NB and PNET shows great individual variation since its determination is necessary for the evaluation of the efficacy of retinoic acid treatment.

Buspirone use for smoking cessation.

The results of buspirone efficacy have been inconsistent and contradictory. The rate of smoking abstinence has been reported to range from 36% to 88% and 16% to 89% in buspirone and placebo treatment groups, respectively. Only one controlled study reported buspirone efficacy in reducing nicotine withdrawal symptoms, although it was based on a small sample population and only 4 weeks of follow-up. The most recent studies have been unable to demonstrate the efficacy of buspirone in smoking cessation or in the relief of withdrawal symptoms. A placebo-controlled, randomized trial with a large number of patients, relatively high doses of buspirone (30-60 mg/d), strict abstinence criteria, long-term follow-up, and the inclusion of smokers with general anxiety or anxiety reported in previous quit attempts is needed to further evaluate buspirone efficacy in smoking cessation and the reduction of nicotine withdrawal symptoms. The treatment effects of buspirone could then be specifically tested as a function of alleviating the anxiety component of the smoking withdrawal syndrome. Finally, buspirone may prove to be an alternative in patients unsuccessful with or unable to tolerate transdermal nicotine therapy. How buspirone compares with bupropion therapy for smoking cessation is also unknown.