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BACKGROUND Data supporting the differential activation of T helper (Th) 2 cells in transplantation acceptance/tolerance in rodents have been presented by several investigators. However, the differential activation of Th2 cells may be simply the result of allograft acceptance/tolerance induction instead of a contribution to the maintenance of grafts. METHODS Therefore, we established interleukin (IL)-4 transgenic mice under the control of a cardiac alpha-myosin heavy chain promotor and transplanted IL-4-expressing heart allografts into unmodified recipients to determine the actual contribution of the Th2 bias to allograft acceptance. RESULTS Among 16 newborn C57BL/6J (B6) mice, three were positive for the IL-4 transgene. Serum IL-4 levels of transgenic versus control B6xC3H F1 mice were not statistically different. Reverse-transcriptase polymerase chain reaction showed that the transgenic B6xC3H F1 mice expressed IL-4 mRNA in the heart and in the lung, whereas control mice did not express IL-4 in any organ. IL-4 mRNA expression in the transgenic but not in the control heart was also confirmed by RNAse protection assay and fluorescence in situ hybridization. The survival of IL-4 transgenic B6xC3H heart grafts heterotopically placed in C3H recipients was prolonged compared with that of nontransgenic grafts (19.0+/-9.1 vs. 6.8+/-2.2 days, P=0.003). Interferon-gamma mRNA expression in IL-4 transgenic heart grafts on the fifth posttransplant day as assessed by Northern blotting was suppressed compared with that in control grafts. Reverse-transcriptase polymerase chain reaction analysis showed that IL-2 mRNA was suppressed in the IL-4 transgenic grafts compared with that in control grafts, while IL-4 mRNA was observed only in IL-4 transgenic grafts. IL-10 mRNA was detected at similar levels in both transgenic and control grafts. CONCLUSIONS A Th2 bias may contribute to allograft acceptance in part by inducing the down-regulation of Th1-cytokine mRNAs, but it may not be sufficient to induce indefinite graft survival.

Using new criteria for histological effects of anti-cancer treatment, the effects of hormono-chemotherapy on 10 patients with prostatic cancer not previously treated were compared with those on 10 patients who received conventional hormone therapy. Marked effects were observed in 4 (40%) patients received hormono-chemotherapy but not observed in patients who received conventional hormone therapy (chi 2 test, p less than 0.05). All four cases who showed marked effects were in stage B at the beginning of treatment. Hormonal effects were more obvious in well differentiated cancer, and the effects of chemotherapy were observed in some cases with moderately and poorly differentiated cancer. Therefore, the addition of chemotherapy is recommended as the initial therapy on prostatic cancer to reduce the relapsing rate, especially for patients with poorly and moderately differentiated cancer.

Background: Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti-apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl-2 and its family members are best characterized. Methods: To investigate the effect of bcl-2-mediated anti-apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl-2 (LNCaP/bcl-2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl-2 was compared with the parental cell line in vitro and in vivo. Results: LNCaP/bcl-2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum-free or androgen-free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum-free or androgen-free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl-2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl-2-derived tumors showed resistance, as was previously reported. Conclusions: These data confirm the notion that anti-apoptotic function of bcl-2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.

The main purpose of this study was to compare semiquantitatively the amount of alpha1a-adrenoceptor subtype mRNA in urethral, central and peripheral areas in benign hypertrophied prostates and non-hypertrophied prostate by the competitive reverse transcriptase polymerase chain reaction (RT-PCR) method. Prostates from twenty cases of men with benign prostatic hypertrophy (BPH) and 5 cases of bladder tumor without BPH were obtained for this study. The mRNA was extracted from the urethral, central and peripheral areas of each prostate, and quantitative RT-PCR was performed using the ratio of PCR product of alpha1a-adrenoceptor mRNA/beta2-microglobulin mRNA. The ratio for the central area of the hypertrophied prostate was significantly greater than that for the same area of the non-hypertrophied prostate (p0.05). In contrast, the urethral area showed no significant difference between the two prostate conditions. The central area of the hypertrophied prostate showed the tendency to have an increased alpha1a-adrenoceptor mRNA level compared with the urethral area, though no statistical difference was recognized because of the high standard error. Regional differences in the alpha1a-adrenoceptor mRNA in the non-hypertrophied prostate were rarely observed. The present finding demonstrates that the increased alpha1a-adrenoceptor mRNA content found in the hypertrophied prostate (1) was due to that in the central area.

Fas/APO-1 is a cell-surface protein, a member of the TNF-receptor family, and it potentially induces apoptosis. In presence of an apoptosis-inducible anti-human Fas MAb, Fas-negative control PC-3 human prostate-cancer cells did not undergo morphological changes, while PC-3 human Fas transfectants showed apoptotic changes in vitro. However, LNCaP human Fas transfectants, as well as Fas-negative control LNCaP human prostate-cancer cells, were Fas-resistant. The growth of Fas-transfected PC-3 tumor was retarded compared with that of control PC-3 tumor in vivo without stimulation of anti-human Fas MAb. Anti-human Fas MAb administration in vivo caused macroscopic Fas-transfected PC-3 tumors formed in BALB/c nude mice to undergo apoptosis.

The histochemical detection of human papillomavirus (HPV) was performed using the technique of in situ hybridization from the formalin fixed paraffin embedded specimens of penile carcinoma and condylomata+ acuminata . One of 19 penile cancer cases (5.3%) revealed the positive staining on the nuclei of the tumors for HPV type 16/18. However, the positive nuclei were scattered and localized in small part of the tumor which showed no koilocytosis. On the contrary, 11 of 12 condyloma acuminata cases (91.7%) showed positive staining on the nuclei of the tumors for HPV type 6/11, also 5 of the 11 cases (45.5%) revealed cross reaction for other type of HPV. The HPV types 6/11, 16/18 and 31/33/35 may be unrelated to the pathogenesis of the Japanese penile carcinoma. However, further study is necessary to evaluate that the number of HPV-DNA copy in our cases is too small, or the other type of HPV is responsibility.

Twenty-three patients who underwent conventional total cystectomy were examined regarding postoperative potency. Two patients who were subjected to simple cystectomy and whose partial prostate and whole seminal vesicles were left showed full erection and normal ejaculation 1-2 months after surgery, thus giving 100% potency after simple cystectomy. In contrast, of 12 patients who underwent radical cystectomy alone, only 3 (25%) regained potency postoperatively, and the strength and duration of erection were not satisfactory for 1 of the 3 patients. Nine patients who received radical cystectomy and urethrectomy did not show signs of potency postoperatively. The sum total postoperative potency rate in the 21 patients subjected to radical cystectomy was 14.3% (3/21). The facts may indicate that urethrectomy is harmful for postoperative potency because damage of the cavernous nerves probably takes place during surgery. To avoid nerve damage, the urethra should be left intact during radical cystectomy employing the nerve-sparing technique developed by Walsh and Donker unless the posterior urethra is invaded by bladder carcinoma. In addition, it was demonstrated that pelvic irradiation might cause impotency as neither pelvic lymph node dissection nor cisplatin administration had any influence on postoperative potency.