[Eugonadotropic germinal cell failure (idiopathic germinal cell failure)].
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Chorionic Gonadotropin↗
Biomedical subjects
Yoshitatsu Fukabori
Publications and source records attributed to Yoshitatsu Fukabori.
Preparation of a single prostate needle biopsy specimen for histological diagnosis and RNA analysis.
PURPOSE: When a prostate needle biopsy specimen is used for molecular study, a second specimen from the same area as the first one has previously been required for pathological diagnosis. However, we developed a method for obtaining substances such as RNA and we also made pathological diagnosis possible from a single needle biopsy specimen, improving reliability. MATERIALS AND METHODS: Prostate needle biopsy specimens from 118 patients were frozen in optimal cutting temperature compound. Tissue from the upper part of the frozen specimen was sectioned longitudinally for histopathological examination. The remainder of the specimen was placed in TRIzol reagent to extract total RNA for molecular biological investigation. RESULTS: Pathological diagnosis and total RNA extraction (1.6 to 32.7 microg) could be obtained from 1 needle biopsy specimen. When 2 specimens were obtained from the same area of the prostate, pathological diagnoses were discordant in 19% of the cases. CONCLUSIONS: We established a method for histopathological diagnosis in the prostate needle biopsy specimen used for molecular investigation. This single specimen method may facilitate molecular research in prostate cancer.
Aged↗
Administration of extract of mushroom Phellinus linteus induces prostate enlargement with increase in stromal component in experimentally developed rat model of benign prostatic hyperplasia.
OBJECTIVES: To clarify the effect of the mushroom extract Phellinus linteus on noncancerous prostate cells using an experimentally developed rat benign prostatic hyperplasia model. A growing number of people take some natural herbal extracts for maintenance of their health. Among them, the extracts of certain mushrooms are believed to have a marked tumoricidal effect but low toxicity for normal tissues, and they are being drunk widely in Japan and Korea. However, until now, their effect on noncancerous benign prostate growth has not been examined. METHODS: The mushroom extract was administered daily for 5 weeks to experimentally developed benign prostatic hyperplasia rats. Prostate organ weight, histologic composition, and gene expression levels of sex hormone receptors, transforming growth factor-beta, vascular endothelial growth factor, and endothelial nitric oxide synthase were examined. RESULTS: Prostate weight increased significantly by 37% owing to treatment with the mushroom extract (P < 0.05). In particular, the stromal component of the prostate increased significantly by 80% (P < 0.05). A suppression of transforming growth factor-beta1 expression by 56% was observed with the mushroom extract treatment (P < 0.05). CONCLUSIONS: We found that the mushroom extract enlarged the prostate. The effect was suggested to be on the prostate stroma, which may be involved in transforming growth factor-beta1 regulation. Administration of mushroom extract should be considered carefully by those with an enlarged prostate.
Agaricales↗
Direct regulation of prostate blood flow by vascular endothelial growth factor and its participation in the androgenic regulation of prostate blood flow in vivo.
Previous studies on prostate blood flow regulation have indicated that androgen regulates prostate blood flow. However, the mechanism responsible for this regulation is unknown. In the present study, we focused on the effects of vascular endothelial growth factor (VEGF), a key factor responsible for angiogenesis and androgenic blood flow regulation. We examined in vivo the effect of VEGF on prostate blood flow and its participation in the androgenic regulation of this blood flow using a castrated rat model following subcapsular intraprostatic injection method. We found that VEGF is involved in blood flow regulation with an activity equal to that of dihydrotestosterone (DHT). The effect of VEGF on prostate blood flow was already seen at 30 min after the administration. The elevating effect of DHT on castrated rat prostate blood flow was abolished by coadministration of DHT with neutralizing anti-VEGF antibody. The change in VEGF-A mRNA expression in response to androgen stimulation was examined by double-fluorescent probe quantitative PCR (Taqman PCR). The results showed that androgenic regulation of VEGF gene expression occurred shortly after androgen stimulation. VEGF gene up-regulation was abolished or down-regulated by coadministration of neutralizing anti-VEGF antibody. This is the first report on the importance of VEGF in the androgenic regulation signaling pathway that affects prostate blood flow. Alternative treatment targeted toward anti-VEGF activity as a substitute for ordinary antiandrogenic therapy may be effective against prostate diseases, especially those with androgen-independent and hyperhemorrhagic status.
Androgens↗
Expression of bone morphogenetic protein-7 (BMP-7) in human prostate.
BACKGROUND: It is known that BMP is a factor that strongly induces bone formation in muscle tissue. However, the expression of BMP-7 is not detected in normal bone tissues. Recently, we reported that the level of BMP-7 expression was significantly higher in metastatic bone lesions than in normal bone and that the high expression of BMP-7 in metastatic bone lesions was related to osteoblastic metastasis. The aim of this study was to investigate the level of BMP-7 gene expression in normal prostate glandular tissues, newly diagnosed prostate cancer tissues, and local recurrent prostate cancer tissues. METHODS: Total RNA was extracted from 23 samples of normal prostate glandular tissues, 28 samples of newly diagnosed prostate cancer tissues, and 23 samples of local recurrent prostate cancer tissues. We also examined the expression of BMP-7 in human prostatic epithelial cells (HPECs) under conditions of androgen replacement. After reverse transcription of the RNA samples, the expression of BMP-7 was measured by real-time quantitative polymerase chain reaction (PCR). Glyceraldehyde phosphate dehydrogenase (GAPDH) was used as an internal standard. RESULTS: The level of BMP-7 expression was highest in the normal prostate glandular tissue (P < 0.05). The expression of BMP-7 tended to be lower during the development and progression of prostate cancer. The expression of BMP-7 in prostate epithelial cells treated with 10(-7) M dihydrotestosterone (DHT) was significantly higher than in the DHT-free control (P = 0.0285). CONCLUSIONS: It has been reported that the BMP-7 mRNA level is androgen-dependent in the mouse prostate. The present results suggest that the BMP-7 mRNA level is androgen-dependent in the human prostate, since the expression of BMP-7 was decreased in local recurrent prostate cancer tissues after hormonal therapy and was increased by DHT.
Aged↗
Androgen-dependent blood flow control and morphological changes of the capillaries in rat prostate.
To clarify the effect of androgens on the microcirculation of the prostate, organ blood flow and ultrastructural features of the capillaries were investigated. In the ventral prostate (VP) of adult Wistar rats, organ blood flow was measured using a laser Doppler flowmetry, and the morphological features of the subepithelial capillaries were investigated and their luminal area was measured using transmission electron microscopy and a computed image analyzer at 1, 2, 3, and 7 days after castration, and 2 days after castration and gradational testosterone supplementation. The capillaries of the VP were classified into three types; oval opened (type 1), intermediate (type 2) and collapsed (type 3). Organ blood flow reduced from 40.5 to 27.7 mL/min/100 g (p < 0.0001) and the luminal area of the capillaries reduced from 13.5 to 4.5 microm2 (p < 0.0001) 2 days after castration. These reductions of the blood flow and the luminal area were gradationally prevented by testosterone supplementation. In the morphological features of the capillary, type 1 had rapidly shifted to types 2 and 3 after castration, and the shift of the capillary type was significantly prevented by the testosterone supplementation. These results clearly demonstrated that the androgen-dependent ultrastructural and morphological features in subepithelial capillaries revealed local microcirculatory conditions correlating the organ blood flow changes in VP.
Animals↗
Role of androgen on blood flow and capillary structure in rat seminal vesicles.
To clarify the effect of androgen on the microcirculation in seminal vesicles of adult Wistar rats, we investigated the organ blood flow and morphological features in the capillaries after castration and subsequent testosterone supplementation. Testosterone (T) was subcutaneously injected every 12 hours after castration and its doses were set to 10(-2), 10(-1), 10(0) and 10(1) mg/kg-body weight (T10(-2), T10(-1), T10(0) and T10(1) groups, respectively). Organ blood flow was measured using laser Doppler flowmetry, and the subepithelial capillaries were analyzed using transmission electron microscopy. The capillaries were morphologically classified into 3 types; oval opened (type 1), intermediate (type 2) and collapsed (type 3), and their luminal areas were measured using a computed image analyzer. The organ blood flow was significantly reduced from 36.3+/-5.1 to 21.9+/-2.7 ml x min(-1)/100 g tissue, and the luminal area of the capillaries was significantly reduced from 9.02+/-1.28 to 4.85+/-0.82 microm2 with the shift of the type 1 and type 2 to type 3 after castration. The reduction of the luminal area and the blood flow reduction, and shift of the capillary type were significantly protected by gradated testosterone supplementation. These results indicate that the maintenance of the blood flow and morphological profiles in capillaries depend on androgen-supplementation levels in seminal vesicles.
Animals↗
[Acute scrotum from testicular involvement in acute lymphocytic leukemia: a case report].
A 8-year-old boy with acute lymphocytic leukemia (ALL) had received chemotherapy and a complete bone marrow remission was obtained. Then he underwent bone marrow transplantation. After 6 months, he suddenly got left flank-low abdominal pain. Sequentially, he had swelling and redness of left scrotum, left testicular swelling and tenderness. Incision was done and enlarged and hard testis was diagnosed as testicular tumor, left orchiectomy was performed. Histological diagnosis was involvement of ALL, so he received radiotherapy. He remains free of disease by the present after 7 months.
Bone Marrow Transplantation↗
[The evaluation of bladder outlet obstruction using the bladder weight calculation nomogram].
The ultrasound estimated bladder weight (UEBW) of 15 patients (13 male, 2 female; mean age 64.7 years) who underwent pressure flow study (PFS) were evaluated using the nomogram. In the nomogram, thickness of bladder wall (T) and bladder weight (BW) were plotted on the horizontal axis and on the vertical axis, respectively. BW points calculated from various values of T by the formula were plotted on the volume-fixed bladder capacity curve. BW of each case was estimated by the nomogram from echo-measured T at maximum bladder filling and injected volume (V) into the bladder. Bladder outlet obstruction (BOO): was evaluated from obtained results, and compared with the results of PFS. The features of the distribution on Schafer's nomogram were also investigated. It was possible to estimate BW immediately after ultrasonic examination. BW was under 35 g in one patient, and over 35 g in 14 patients. Obstruction grade on the Schafer's nomogram ranged from III to VI. BOO could be evaluated quantitatively with little invasion even in patients who could not undergo PFS for urinary retention and urge incontinence. In conclusion, the bladder weight calculation nomogram immediately showed the BOO information of the patient with neither invasive technique, complicated calculation, electronic calculator nor expansive computer. This nomogram may make a breakthrough for utilizing UEBW.
Adult↗
The evaluation of rat prostate blood flow using a laser speckle flowmetry: a comparative study using the microsphere method in castrated and androgen-replenished rats.
To evaluate the accuracy and reliability of laser speckle blood flowmetry in the measurement of prostate blood flow, we performed a comparative study with the ordinary intra-arterial radioactive microsphere injection method using the well-known castrate-rat model. Adult male Wistar strain rats were used for the study. The rats were either only castrated or subcutaneous testosterone replenishment was followed subcutaneously 6 h after castration. The prostate blood flow was measured at different time courses after castration. The effect of a single androgen replenishment on prostate blood flow was also evaluated. The measurement of prostate blood flow was performed by both the radioactive microsphere injection method and laser speckle blood flowmetry, and then the outcomes were compared. Rapid reduction in prostate blood flow to 30% of the normal level was observed 24 h after castration in the measurements with the microsphere injection technique. The prostate blood flow decreased gradually after 24 h post-castration to 23 and 21% of the normal level at 48 and 72 h after castration, respectively. The laser speckle blood flowmetry also detected the decrease in prostate blood flow well, but in a more gradual manner. The prostate blood flow was 70, 52 and 35% of the normal level at 24, 48 and 72 h after castration, respectively. The effect of a single administration of testosterone to castrated rats had recovered the prostate blood flow to 74 and 98% of the normal level by measurement with the microsphere injection technique and laser speckle blood flowmetry, respectively. The different outcome in blood flow rate change between the methods can be explained according to their different mechanism of measurement, thus suggesting the capillary vessels are the early and most responsive portion for hormonal manipulation. In conclusion, the laser speckle blood flowmetry is a convenient and reliable method for evaluating prostate blood flow, especially when the organ is required for other biological and molecular assays, since the method does not require the excision of the organ for the measurement.
Androgens↗
Increased expression of bone morphogenetic protein-7 in bone metastatic prostate cancer.
BACKGROUND: Prostate cancer frequently metastasizes to bone. The skeletal metastases of prostate cancer origin are osteoblastic rather than osteolytic. Recently, the expression of bone morphogenetic proteins (BMPs) in prostate cancer cell lines was detected. The present study indicated the existence of BMP-7 in normal prostate tissue, but its function has not been clarified. The mechanism by which prostate cancer causes osteoblastic metastasis is not clear. We investigated the expression of BMP-7 and -6 in normal and metastatic bone tissues to clarify the biological relationship between the expression of BMPs and bone metastasis in prostatic cancer. METHODS: Six samples of normal bone tissue and nine samples of bone metastasis tissue were collected during the autopsies of six patients with prostate cancer. Total RNA was extracted from these samples. After reverse transcription (RT) of the RNA samples, the expression of BMP-6 and -7 in each sample was measured by the real-time quantitative polymerase chain reaction (PCR). Glyceraldehyde phosphate dehydrogenase (GAPDH) was used as an internal standard. RESULTS: Although the expression of BMP-7 was detected in five out of seven (71%) metastatic bone lesions of prostate cancer, it was not detected in normal bone tissues. The expression level of BMP-7 was significantly higher in metastatic bone lesions than in normal bone (P < 0.05). There was no significant difference between the level of expression of BMP-6 in metastatic bone lesions from prostate cancer and the level in normal bone tissue (P = 0.81). CONCLUSIONS: These results suggest that high expression of BMP-7 in metastatic bone lesions of prostate cancer is related to osteoblastic metastasis. BMP-7 in the bone metastasis tissue indicates that the cells expressing BMP-7 probably originated from the prostate, because we have detected high expression of BMP-7 in the prostate. Prostate 54: 268-274, 2003.
Bone Morphogenetic Protein 6↗
Hormonal and morphologic evaluation of the effects of antiandrogens on the blood supply of the rat prostate.
OBJECTIVES: To clarify the basic aspects of the regulation of the prostatic blood supply by antiandrogens, their effect on the prostatic blood supply was studied for both androgen content and morphology of true capillaries in the rat ventral prostate. The effectiveness of antiandrogens on the control of hemorrhagic status in prostatic diseases has been previously reported. METHODS: Androgen concentrations in the prostate were quantified after administration of chlormadinone acetate (CMA), finasteride, or flutamide. The prostatic blood supplies were measured after administration of CMA, finasteride, flutamide, or bicalutamide. The alpha-blockers, terazosin and tamsulosin, were included in the study as negative controls. The histologic changes in the capillaries of the ventral prostate were observed, and the luminal area was measured. RESULTS: The prostate dihydrotestosterone concentrations were decreased by the administration of all antiandrogens. Treatment with CMA, finasteride, flutamide, or bicalutamide reduced the prostatic blood supply by 50% to 65%. The parallel reduction in luminal areas of the true capillaries was observed in rats treated with CMA. Treatment with alpha-blockers did not affect the prostate androgen content, prostatic blood supply, or capillary luminal area. CONCLUSIONS: The reduction of the prostatic blood supply was suggested to be the result of a decrease in dihydrotestosterone content and the reduction in the luminal area of capillaries. The early reductive effect of antiandrogens on the prostatic blood supply suggests an alternative use for antiandrogens independent of their typical use for prostate volume regression. The results support the basic aspects of the advantage of preoperative treatment with CMA, flutamide, and bicalutamide, similar to finasteride, in reducing perioperative hemorrhage.
5-alpha Reductase Inhibitors↗
Vitamin D receptor gene polymorphism in familial prostate cancer in a Japanese population.
AIM: Vitamin D acts as an antiproliferative agent against prostate cells. Epidemiological study has shown that a low level of serum vitamin D concentration is a risk factor for prostate cancer. Vitamin D acts via vitamin D receptor (VDR), and an association of genetic polymorphisms of the VDR gene has been reported. In the current study, we examined the association of VDR gene polymorphisms with familial prostate cancer in a Japanese population. METHODS: We performed a case-control study consisting of 81 familial prostate cancer cases and 105 normal control subjects. Three genetic polymorphisms (BsmI, ApaI and TaqI) in the VDR gene were examined by the restriction fragment restriction length polymorphism method. RESULTS: Overall, there was no significant association of the VDR gene polymorphisms with familial prostate cancer risk in the cases and control subjects. However, a weak association between BsmI or TaqI genotypes and cancer risk was observed in subjects under 70 years of age. Stratification of cases by clinical stage or pathological grade did not show significant association between the VDR gene polymorphisms and prostate cancer risk. CONCLUSION: In the present study, we could not confirm any significant association between VDR gene polymorphisms with familial prostate cancer risk in a Japanese population. Further large-scale case-control studies are warranted to confirm the importance of VDR gene polymorphisms in familial prostate cancer.
Adult↗
Ultrastructural changes in subepithelial capillaries and their surrounding stroma in rat prostate and seminal vesicle after castration.
The purpose of this study was to clarify the androgen-ablation-induced morphological changes in the capillaries and stroma near the epithelial cells in prostate and seminal vesicles (SV) using transmission electron microscopy (TEM). In ventral prostate (VP) and SV of immature male rats, the luminal areas of subepithelial capillaries and the width of the stromal layers between endothelia and epithelia were measured quantitatively after castration using TEM and a computed image analyzer. The luminal areas of the capillaries were significantly reduced in VP and SV in the short-term after castration. In the stromal layer, the width of the collagen layer surrounding the capillary significantly increased in VP and SV in the long-term after castration. These data suggest that the reduction of the capillaries and the thickening of collagen surrounding them are related to the involution of glandular epithelial cells in VP and SV after castration.
Animals↗
The diagnostic accuracy of the age-adjusted and prostate volume-adjusted biopsy method in males with prostate specific antigen levels of 4.1-10.0 ng/mL.
BACKGROUND: The authors evaluated a new age-adjusted and prostate volume-adjusted biopsy method for the detection of prostate carcinoma through the transperineal and the transrectal approaches in men with PSA levels of 4.1-10.0 ng/mL. METHODS: The value of the adjusted biopsy method was calculated by using the following four factors: 1) life expectancy in Japanese men in 1998, 2) prostate volume estimated by transrectal ultrasonography, 3) tumor doubling time (4 years), and 4) tumor volume that influenced death (20 cc). The number of biopsy sites was set at 8-20. Between August, 1999 and December, 2001, 100 men age or= 50 cc, and men with PSA density (PSAD) levels /= 50 cc), and patients with PSAD levels <or= 0.15 ng/mL/cc. The authors recommend that patients undergo an additional transition zone biopsy at the anterior aspect through the transperineal approach.
Age Factors↗
Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3.
Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.
Antineoplastic Agents↗
Tumor-associated tissue eosinophilia of penile cancer.
BACKGROUND: Tumor-associated tissue eosinophilia (TATE) occurs in many kinds of cancer. This study analyzed whether TATE improves the survival of penile cancer patients. METHODS: In 17 patients with penile cancer, survival was compared between the TATE-positive group and the TATE-negative group. Tissue eosinophils were observed by transmission electron microscopy. RESULTS: In all cases, 5-year survival was 72.9% in the TATE-positive group (n = 8) and 38.9% in the TATE-negative group (n = 9; P = 0.131). In stage III and IV, it was 60% in the TATE-positive group (n = 5) and 0% in the TATE-negative group (n = 5; P = 0.058). Transmission electron microscopy images revealed the vigorous infiltration of tissue eosinophils. CONCLUSIONS: It is suggested that TATE improves the survival of patients with advanced penile cancer. However, a greater number of subjects is needed to prove statistical significance.
Eosinophilia↗
Usefulness of prostate-specific antigen velocity in screening for prostate cancer.
BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.
Adult↗