Expression profile of prostate-specific antigen messenger RNA assessed by in situ hybridization is a novel prognostic marker for patients with untreated prostate cancer.

The present study was undertaken to define the relationship between histological grade (Gleason grade) and prostate-specific antigen (PSA) mRNA expression and to evaluate the level of PSA mRNA expression as a possible prognostic marker for untreated prostate cancers. The primary grade areas of 104 prostatic biopsy specimens were analyzed for the expression of PSA mRNA and its protein by nonradioactive in situ hybridization and immunohistochemistry, respectively. A multivariate survival analysis was performed to examine the correlation between PSA mRNA expression and several clinicopathological parameters, e.g., the immunostaining level of PSA protein in biopsy specimens. The percentage of specimens positive for PSA mRNA increased significantly with advanced histological grade. Image analysis of the signal intensity for PSA mRNA showed a significant correlation between the signal intensity in both primary and secondary grade areas of each specimen and the histological grade (P < 0.0001). Only 26.0% of specimens positive for PSA protein were also positive for PSA mRNA (and vice versa, 6.7%). Other tumors were either positive for both (66.3%) or negative for both (1.0%). When the Cox's proportional hazards regression model was used to analyze cancer-specific survival, untreated patients with higher levels of PSA mRNA expression in the higher grade (representing higher grade of either primary or secondary grade) area of tumors were at high risk for cancer-related death (P = 0.017). Furthermore, in cancer-specific survival curves based on PSA mRNA expression status, patients with high levels of PSA mRNA expression in the higher grade area of tumors had a significantly poorer prognosis (P = 0.001), compared with those with tumors expressing low levels of PSA mRNA. Our results suggested that analysis of PSA mRNA expression in specific areas in biopsy specimens of patients with untreated prostate cancer may provide a good assessment of prognosis of prostate cancers.

Steroid receptor levels and histology of endometriosis and adenomyosis.

Steroid receptors in endometriosis and adenomyosis were investigated to clarify their clinical significance. The receptor levels were determined by Scatchard plot analysis (4 degrees C, by dextran-coated charcoal). In the cytosols of both tissues, the 17 beta-estradiol-estrogen receptor (ER) complex demonstrated a dissociation constant (Kd) of 4.5 x 10(-10) M; the Kd of the progesterone-progesterone receptor (PR) complex was 1.5 x 10(-9) M; and the Kd of the dihydrotestosterone-androgen receptor (AR) complex was 4.0 x 10(-10) M. Seven cases of ovarian endometriosis were studied. The ER and PR levels in endometriosis seemed to be lower than those in the corresponding normal endometrium. AR was also present. There was a suggestion that most endometriosis is least responsive to progestogens. Ten cases of adenomyosis were studied. Histologic dating revealed a delay in the most aberrant endometrial tissue in adenomyosis, as compared with dating of corresponding normal endometrial tissue. ER and AR were detected in all cases. PR was not detected in some cases and, when detected, the content seemed to be lower, possibly suggesting the delayed dating.

Effect of ankle disk training combined with tactile stimulation to the leg and foot on functional instability of the ankle.

Twenty-two university students with unilateral functional instability of the ankle participated in this study. They were randomly assigned to one of two experimental groups. Subjects in both groups were trained to stand on the affected limb on an ankle disk. In group 1, two pieces of 1-cm wide nonelastic adhesive tape were applied to the skin around the lateral malleolus from the distal third of the lower leg to the sole of the foot before the training sessions. Subjects in group 2 participated in the training sessions without the application of the adhesive tape. Training was performed for 10 minutes a day, five times per week, for a period of 10 weeks. Subjects were tested for postural sway while standing on the affected limb before, during, and after the training period. In group 1, postural sway values decreased significantly after 4 weeks compared with the pretraining performance, and they were within the normal range after not more than 6 weeks of training. In group 2, the values did not improve significantly compared with the pretraining performance until after 6 weeks of training, and they were not within the normal range until after 8 weeks of training. The findings suggest that the 2-week earlier correction of postural sway in group 1 was due to an increased afferent input from skin receptors that were stimulated by the traction of the adhesive tape.

[Clinical evaluation of pivmecillinam in the maintenance therapy of chronic urinary tract infection (author's transl)].

In order to evaluate the efficacy and safety of pivmecillinam (melysin tablet, PMPC), PMPC was administered to 78 chronic UTI cases in the field of obstetrics and gynecology (posthysterectomy infection, chronic cystitis, chronic pyelonephritis and etc.). In principle, daily 400 mg of PMPC was administered for 2 weeks. (1) Overall clinical efficacy judged by doctor was evaluated in 78 cases and the result was; excellent in 17, good in 37, fair in 10, poor in 13 and unknown in 1 case with the effectiveness rate of 69.2%. (2) Overall clinical efficacy judged by 'criteria for clinical evaluation in complicated UTI' recommended by UTI study member was evaluated in 54 cases and the result was; excellent in 15, good in 20 and poor in 19 cases with the overall efficacy rate of 64.8%, the result of which was similar to that of doctor's judgement. (3) Efficacy on pyuria was evaluated in 72 cases and it was cleared in 27, decreased in 25, unchanged in 20 and unknown in 6 cases. Efficacy on bacteriuria was evaluated in 72 cases and it was eliminated in 44, decreased in 9, replaced in 8, unchanged in 8 and unknown in 9 cases. (4) Side effect, considered by doctors to be caused by PMPC administration, was noticed in 3 out of 78 cases (3.8%), all of which was mild gastrointestinal disturbance and the administration of PMPC was continued. Abnormal change of laboratory finding considered by doctors to be caused by PMPC administration was noticed in 1 out of 78 cases, which was slight elevation of GOT and GPT values. It is therefore considered that PMPC appear to be useful drug for the maintenance therapy of chronic UTI in the field of obstetrics and gynecology.

[Clinical evaluation of renal angiomyolipoma].

Between April 1980 and December 1999, 23 kidneys in 20 patients were diagnosed as having renal angiomyolipoma at our institution. The patients were 6 males and 14 females aged 24 to 79 years, with a mean age of 55.4 years. Two patients had associated tuberous sclerosis and 3 had bilateral disease. Of all patients the main clinical symptoms were pain (45%) and palpable mass (40%); 5 patients (25%) had asymptomatic lesions. The size of the tumor ranged from 1.3 to 24 cm (mean 7.7 cm). Treatment consisted of nephrectomy in 9 patients, partial nephrectomy in 6 and selective embolization in one. Pre-operative diagnosis was renal cell carcinoma in 5 of the 9 patients who underwent nephrectomy. Six patients with 7 diseased kidneys were followed radiologically. One patient underwent percutaneous biopsy to confirm the diagnosis. We suggest that nephron-sparing surgery for patients with renal angiomyolipoma should be the first step if tumor size is 4 cm < or = or increasing rapidly. Selective embolization is also a useful method. However, we need long-term follow-up to evaluate the effectiveness of embolization.

[Evaluation of bone metastases from renal cell carcinoma].

Forty-two cases of bone metastasis from renal cell carcinoma were examined. Thirty of the cases had bone metastases at the time of renal cell carcinoma. Bone metastasis appeared after treatment of the primary site in 12 cases. Fifteen cases had only bone metastasis and another 27 had metastasis in multiple organs. The total cause-specific survival curve of these patients was 10% at 5 years. All patients with bone metastases died of cancer within 5 years after the bone metastases had developed. There was no significant difference in the survival rate between patients with bone metastases and patients with lung metastases. We investigated the prognostic value of laboratory studies in bone metastases of renal cell carcinoma. However, no significant markers were detected for bone metastases. The 6 patients were treated with decompressed laminectomy (2), wide resection (3) and excision of the metastatic lesions (3). The quality of life was improved in all the patients although they died of cancer.

[Clinical examination and therapies of hydronephrosis after radical hysterectomy].

We investigated postoperative hydronephrosis in 50 patients (100 ureter) undergoing radical hysterectomy for uterine cervical cancer from Jan. 1989 to Dec. 1991 at Department of Obstetrics and Gynecology in Nagasaki University Hospital. The incidence of hydronephrosis was 68.1% of patients, and hydronephrosis was seen significantly more frequently and was of a higher grade on the right kidney than the left. After one year, hydronephrosis disappeared in 59.1% of patients (65.1% of right kidney, 88.2% of left kidney), and only 2 of 93 kidney have worsened. In cases without hydronephrosis, hydronephrosis developed in only 3 of 31 kidney after one year due to local recurrence or nodule metastasis of the original disease. We compared therapeutic effects of 3 methods (ureteral stent, PNS, no treatment). But there was no significant difference between these methods, we could not determine which was the best treatment. And we observed that indwelling ureteral stent might interrupt spontaneous healing of ureter. Radiotherapy didn't significant influence hydronephrosis after radical hysterectomy; Therefore, we suggest that, in patients with hydronephrosis without other severe urological complications after radical hysterectomy, clinical course should be observed for at least one year, first and them some treatments should be applied if cases worsen gradually than before.

Implications of subcellular steroid binding sites in endometrial cancer, determined by an immunofluorescent steroid-antibody technique and biochemical assay.

A discrepancy has been found between the progestogen level necessary for treatment of endometrial cancer and the steroid receptor level detected for the response indicator. Therefore the relationships between the steroid binding quantity detected biochemically and the steroid reactivity determined immunofluorescently was evaluated subcellularly in the endometrial cancers. Estradiol-17 beta and progesterone fluorescences were not always related to the classical steroid receptor binding quantities. These two steroids bound to the nuclear components directly, but heterogeneously. In the biochemical method using fractionated dispersed cancer cells, cellular heterogeneity of the steroid receptor mechanism in a given endometrial cancer tissue was proved. Steroid fluorescence was not related to the steroid-receptor complex quantity in the normal endometrial nucleus. This suggests that the binding of steroid antibody to the steroid-receptor bound already to the nucleus seems to be inhibited due to steric hindrance. Therefore the nuclear steroid fluorescence did not always give the nuclear steroid-receptor complex quantity. These results indicate heterogeneity in the estrogen and progestogen receptor mechanism in endometrial cancer, when studied by the biochemical and immunofluorescent techniques, and that these steroids bind to the nucleus directly and may influence the nuclear mechanism. Therefore, in endometrial cancer progestogen does not always have a therapeutic effect through the progestogen receptor and does not affect the therapeutic effect on any of the cells.

Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis.

Lymph node dissemination is a major prognostic factor in human cancer. However, the molecular mechanisms underlying lymph node metastasis are poorly understood. Recently, vascular endothelial growth factor-C (VEGF-C) was identified as a ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and the expression of VEGFR-3 was found to be highly restricted to the lymphatic endothelial cells. In this report, we investigated the expression of VEGF-C and VEGFR-3 in human prostatic carcinoma tissue by using in situ hybridization and immunohistochemical staining respectively. Expression of VEGF-C mRNA in prostatic carcinoma was significantly higher in lymph node-positive group than in lymph node-negative group. In addition, the number of VEGFR-3-positive vessels was increased in stroma surrounding VEGF-C-positive prostatic carcinoma cells. These results suggest that the expression of VEGF-C in prostatic carcinoma cells is implicated in the lymph node metastasis.

Chromatin transcription by progesterone-receptor complex in rabbit uterus.

This study was designed to investigate the chromatin transcription in vitro by progesterone-receptor complex in the estrogen-primed rabbit uterus. RNA synthesis by the uterine chromatin was stimulated when progesterone-uterine cytosol complex was bound to the chromatin and the stimulation was dependent upon the dose of the bound progesterone-cytosol 8S complex and upon the incubation time of the complex in the presence of the chromatin. Either norethindrone- or dydrogesterone-uterine cytosol complex also stimulated the uterine chromatin transcription but the extent was less than that of progesterone complex. These results indicate that progesterone as well as synthetic progestogens can directly regulate chromatin transcription via progesterone receptor in the rabbit uterine cells.

Prognostic significance of beta-microseminoprotein mRNA expression in prostate cancer.

BACKGROUND: Human beta-microseminoprotein (beta-MSP or PSP94) is a small protein secreted by prostatic epithelial cells. We recently reported the presence of low levels of beta-MSP mRNA expression and protein in most prostate cancer tissues. METHODS: Beta-MSP and mRNA expression was examined by in situ hybridization in biopsy specimens obtained from 92 patients with prostate cancer. All tissue specimens were obtained by needle biopsies prior to treatment. All patients subsequently received endocrine therapy. To estimate the influence of beta-MSP mRNA expression and three possible prognostic factors, i.e., patient age, clinical stage, and Gleason score, on time to progression under endocrine therapy, univariate and multivariate analyses were performed using Cox's proportional hazards regression model. RESULTS: Multivariate survival analysis showed that clinical stage was the strongest prognostic factor (P = 0.006) and that beta-MSP mRNA expression was the second strongest factor (P = 0.038) in 92 patients with stage B-D disease. Analysis of only 51 patients with stage D disease showed that beta-MSP mRNA expression was the only significant prognostic indicator for progression under endocrine therapy (P = 0.003). CONCLUSIONS: The presence of cells that express the beta-MSP transcript may be a novel indicator of potentially aggressive prostate cancer.

Cellular expression of beta-microseminoprotein (beta-MSP) mRNA and its protein in untreated prostate cancer.

BACKGROUND: Previous studies have shown that beta-microseminoprotein (beta-MSP) may be used as a diagnostic marker for prostate cancer. However, the level of expression of beta-MSP in prostate cancer detected by immunohistochemistry (IHC) has varied from one study to another. METHODS: We analyzed the expression of both beta-MSP mRNA and its protein in a large sample of prostate tumors from 104 patients with untreated prostate cancer, using both nonradioactive in situ hybridization (ISH) and IHC. RESULTS: Our results showed that 72 and 96 of 104 specimens were negative for beta-MSP mRNA (69.2%) and beta-MSP (92.3%), respectively. Furthermore, a reduced expression of both beta-MSP mRNA and its protein was detected in all malignant epithelial tissues compared with benign epithelia. Not all malignant tissue samples negative for beta-MSP mRNA were negative for beta-MSP (6.7%), and vice versa (29.8%). Other tissue samples were either negative for both (62.5%) or positive for both (1.0%). CONCLUSIONS: Our results showed a lower level of expression of beta-MSP in prostate cancer tissue, compared with benign prostate tissue. This phenomenon may be mainly due to the presence of reduced levels of beta-MSP mRNA.

Nuclear translocation of progesterone receptor--progestogen complex in vitro.

The nuclear translocation of receptor-progestogen complex was investigated in the estrogen-primed rabbit uterus. To avoid the influence of the in vivo steroid metabolism, the incubation of cytosol with progestogens, and that of the nuclear suspension with steroid-cytosol complex were performed in the in vitro systems. The quantity of the steroid receptor translocated by progestogens to the nucleus was measured using the [3H]-progesterone exchange assay. [3H]-progesterone-receptor complex in the cytosol was exchanged for cytosolic receptor sites by progesterone, dydrogesterone or norethindrone effectively. When the steroid receptors translocated to the nucleus by such steroids in the in vitro system were determined using exchange assay, progesterone translocated the receptor to the nucleus much more than did dydrogesterone or norethindrone. It was suggested that progesterone was potent in the ability of the nuclear translocation of its own receptor. The highly potent biological activities of norethindrone and dydrogesterone in vivo must be explained in the other way.