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T Demura

Publications and source records attributed to T Demura.

At least 19 recordsLinked to original sources
PubMed1995

[5-Fluorouracil and alpha-2a interferon in patients with hormone-refractory prostate cancer].

BACKGROUND: Hormone-refractory metastatic prostate cancer remains a disease for were limited therapeutic options are available. Therefore, the establishment of newly, more effective chemotherapy is expected. Experimental data suggest that PC-3, a human hormone refractory prostate cancer cell line, showed a 2-fold increase in 5-Fluorouracil (5FU) sensitivity in the presence of alpha-2a Interferon (IFN alpha 2a) at 100 IU/ml, compared to that without IFN alpha 2a. Based on this data, we treated 11 patients with 5FU and IFN alpha 2a in order to determine the clinical response and toxicity of this combination chemotherapy. METHODS: One course of this combination chemotherapy consisted of a continuous intravenous infusion of 5FU at 600 mg/m2/day for 5 days (D1-D5) with IFN alpha 2a 3 million units (MU) intramuscularly 3 times weekly (D1, D3, D5) followed by a bolus injection of 5FU at 600 mg/m2 and IFN alpha 2a at 3 MU/day on D15 and D22. RESULTS: Based on the Response Criteria for Prostate cancer Treatment, one of 9 patients with bony metastasis had partial response, 2 patients with nodal disease on the CT scan obtained partial response. Six of 11 patients had more than 50% decrease in post-therapy prostatic antigen levels, 3 of whom obtained complete response. Significant myelosuppression did not occur. There were no chemotherapy-related deaths. CONCLUSION: These results suggest that the combination of 5FU and IFN alpha 2a, although preliminary, is an active regimen against hormone-refractory metastatic prostate cancer.

Aged↗
PubMed1995

[Prostate specific antigen (PSA)/gamma-seminoprotein ratio in the cases with PSA levels less than or equal to 10.0 ng/ml].

Prostate specific antigen (PSA) and gamma-seminoprotein (gamma-Sm) have been revealed to be the same protein and used as tumor markers for prostate cancer (CaP). However, it seems impossible to detect prostate cancer in the cases with PSA levels of 10.0 ng/ml or less. We now report on PSA/gamma-Sm ratio in the cases with PSA levels of 10.0 ng/ml or less, and on the relation between PSA and gamma-Sm in those cases. Serum samples were obtained from the patients with no cancer (NC) (n = 118) and CaP (n = 39). In the cases with PSA ranging from 4.1 to 10.0 ng/ml, gamma-Sm levels in the patient with CaP were significantly lower than in those with NC (3.744 +/- 2.481 (mean +/- SD, n = 27) VS. 7.573 +/- 4.182 (n = 41), p < 0.0001) though PSA levels in both groups were not significantly different, and consequently, PSA/gamma-Sm ratio in the patients with CaP were significantly higher than in those with NC (2.181 +/- 0.802 VS. 1.095 +/- 0.804, p < 0.0001). In the cases with PSA levels of 4.0 ng/ml or less, gamma-Sm levels in the patient with CaP were significantly lower than in those with NC (1.600 +/- 0.705 (n = 12) VS. 3.243 +/- 2.456 (n = 77), p = 0.0064), while PSA levels in the patients with CaP were not significantly different from those in the patients with NC, and consequently, PSA/gamma-Sm ratio in the patients with CaP were significantly higher than in those with NC (1.762 +/- 0.544 VS. 0.808 +/- 0.330, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1994

[Mucinous adenocarcinoma of the prostate. A case report and analysis of the literature].

An 80-year-old man, who had been treated for colon cancer 25 years ago, presented with gross hematuria. Rectal examination revealed a soft nodule in the right lobe. The serum prostatic specific antigen (PSA) was elevated to 5.2 ng/ml, while prostatic acid phosphate (PAP) was normal. Transrectal ultrasound revealed a hypoechoic mass in peripheral zone of the prostate and dilated seminal vesicle. A needle biopsy of the prostate showed mucinous adenocarcinoma. Under the diagnosis of prostatic tumor with seminal vesicle involvement, radical prostatectomy was performed. Histological findings showed organ confined cancer, of which most was composed of extracellular mucin lakes. Immunohistochemical study revealed the tumor cells positive for PSA and PAP. Mucinous adenocarcinoma of the prostate has been known to be clinically different from non-mucinous adenocarcinoma, in that the former is insensitive to hormonal therapy, is rarely associated with elevated PAP and rarely metastasize to the bone. But our analysis of the literatures is Japan showed no significant difference clinically between mucinous and non mucinous prostatic adenocarcinoma. However mucinous adenocarcinoma with signet ring cell rarely responds to hormonal therapy, which should not be classified to true mucinous adenocarcinoma in the current criteria. True mucinous adenocarcinoma could be a variant of prostatic adenocarcinoma, which is peripheral origin and should be treated like non-mucinous adenocarcinoma.

Acid Phosphatase↗
PubMed1994

[Diagnosis of prostate cancer by means of the ratio of prostate specific antigen/gamma-seminoprotein (P/S ratio)].

Prostate specific antigen (PSA) and gamma-seminoprotein (gamma-Sm) are revealed to be the same protein. However, the serum concentrations of PSA and gamma-Sm in the same samples are frequently different. We previously measured a ratio of serum PSA concentration and gamma-Sm concentration (P/S ratio), and evaluated its usefulness for diagnosis of prostate cancers. In this paper, we tried to determine the cutoff value which brings better efficiency and diagnose prostate cancer by means of P/S Ratio. Between April 1988 and September 1992, 221 men underwent prostatic biopsy and/or TUR-P, and were diagnosed pathologically. Of 221 patients, 130 were diagnosed as BPH, prostatis or normal prostate (no cancer; NC) and 91 were diagnosed as prostate cancer (CaP). 1) The mean +/- SD of P/S ratio in 130 patients with NC was 0.919 +/- 0.563. While, the mean +/- SDs of P/S ratio were 12.447 +/- 44.353 in 91 patients with CaP and 2.052 +/- 0.751 in 39 Cap patients with serum PSA level of < or = 10 ng/ml. The mean P/S Ratios in CaP patients with serum PSA of < or = 10 ng/ml as well as in all CaP patients were significantly higher than those in NC patients (p < 0.0001). 2) When the cutoff value of P/S Ratio was determined to be 1.45, the highest efficiency (= sensitivity x specificity divided by 100), 83.4, was obtained. The sensitivity and specificity were 91.2% and 91.5%, respectively as a cutoff value of 1.45.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1993

Measurement of prostate specific antigen and gamma-seminoprotein ratio: a new means of distinguishing benign prostatic hyperplasia and prostate cancer.

We measured a ratio of serum prostate specific antigen (PSA) and gamma-seminoprotein concentrations (referred to as the PSA/gamma-seminoprotein ratio) and evaluated its usefulness for the diagnosis of prostate cancer. Between April 1988 and October 1992, 214 men underwent prostatic biopsy and/or transurethral resection of the prostate, and the disease was diagnosed pathologically. Of 214 patients 127 were diagnosed as having benign prostatic hyperplasia, prostatitis or a normal prostate (no cancer), while 87 had prostate cancer. Of 61 patients with a serum PSA level greater than 10 ng./ml. 50 (82.0%) had prostate cancer, compared to 31 of 84 (36.9%) with a serum PSA level of 3.0 to 10 ng./ml. Of 113 patients with a serum gamma-seminoprotein level greater than 4.0 ng./ml. 52 (46.0%) had prostate cancer. The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratio for 127 patients without cancer was 0.942 +/- 0.564, while that for 87 prostate cancer patients was 12.840 +/- 45.327 (Wilcoxon p < 0.0001). The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratios for 37 prostate cancer patients with a PSA level of 10 ng./ml. or less and for 50 prostate cancer patients with a PSA level of more than 10 ng./ml. were 2.044 +/- 0.767 and 20.829 +/- 58.757, respectively. Even the mean PSA/gamma-seminoprotein ratio for prostate cancer patients with a PSA level of 10 ng./ml. or less was significantly greater than that for patients without cancer (Wilcoxon p < 0.0001). The sensitivities for PSA (cutoff value 3.0 ng./ml.), gamma-seminoprotein (cutoff value 4.0 ng./ml.) and PSA/gamma-seminoprotein ratio (cutoff value 1.45) were 93.1%, 59.8% and 92.0%, respectively, and the specificities were 49.6%, 52.0% and 91.3%, respectively. Of 91 patients with a PSA/gamma-seminoprotein ratio of 1.45 or more 80 (87.9%) had prostate cancer, while 116 of 123 (94.3%) with a PSA/gamma-seminoprotein ratio of less than 1.45, had no cancer. These results suggest that PSA/gamma-seminoprotein ratio yields the same sensitivity as PSA and more specificity than PSA levels, offering significant advantage over PSA in detecting prostate cancer. The mean plus or minus standard deviations of PSA/gamma-seminoprotein ratios for stages A, B, C and D prostate cancer were 1.847 +/- 0.786 (11 patients), 2.740 +/- 1.536 (30), 7.626 +/- 9.140 (12) and 27.149 +/- 70.500 (34), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Neoplasm↗
PubMed1993

[Usefulness of prostate specific antigen/gamma-seminoprotein ratio for diagnosis of prostate cancer].

Prostate specific antigen (PSA) and gamma-seminoprotein (gamma-Sm) are used as tumor markers of the prostate cancer. However, the serum concentrations of PSA and gamma-Sm are frequently increased in patients with benign prostatic hypertrophy (BPH). We measured the ratio of serum PSA to gamma-Sm concentration (P/S ratio), and evaluated its usefulness for diagnosis of prostate cancers. Between April 1988 and July 1992, 162 men underwent prostatic biopsy and/or TUR-P, and were diagnosed pathologically. Of 162 patients, 112 were diagnosed as BPH and 50 were diagnosed as prostate cancer. Of 24 patients with serum PSA level of > 20 ng/ml, 23 (95.8%) were prostate cancer, while, of 79 patients with serum PSA level of 3.0-20 ng/ml, 23 (29.1%) were prostate cancer. The sensitivity and the specificity for PSA were 92.0% and 49.1%, respectively. Of 85 patients with serum gamma-Sm level of > 4.0 ng/ml, 30 (35.3%) were prostate cancer. The sensitivity and the specificity for gamma-Sm were 60.0% and 50.9%, respectively. A mean +/- SD of P/S ratio in 112 patients with BPH was 0.954 +/- 0.591. While, the mean +/- SD of P/S ratio was 16.295 +/- 58.584 in all prostate cancer patients, and 2.031 +/- 0.654 in 27 prostate cancer patients with serum PSA level of < or = 20 ng/ml. P/S Ratio in prostate cancer patients with serum PSA of < or = 20 ng/ml as well as in all prostate cancer patients were significantly higher than P/S Ratio of BPH patients (p < 0.0001). Of 55 patients with P/S Ratio of > or = 1.50, 45 (81.8%) were prostate cancer and 10 (18.2%) were BPH. While, of 107 patients with P/S Ratio of < 1.50, 102 (95.3%) were BPH and 5 (4.7%) were prostate cancer. The sensitivity and the specificity for P/S Ratio were 90.0% and 91.1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

[Localization of androgen receptor in male sex organ, accessory sex organs and external genital skin].

Previously, we established an anti-androgen receptor (AR) monoclonal antibody. Using the antibody, we investigated immunohistological AR localization in human testes, epididymides, seminal vesicles and scrotal skins. The testes, epididymides and scrotal skins were obtained from a prostate cancer patient without pre-hormonal therapy undergoing bilateral orchiectomy. The seminal vesicles were obtained from a bladder cancer patient undergoing radical cystectomy. The tissues were immediately frozen in liquid nitrogen and kept at -80 degrees C until used. Cryostat-frozen sections were cut at 5 microns and stained by an indirect method. We obtained the following results. 1) In the testes, nuclei of Leydig cells were stained though Sertoli cells were not stained. AR localization in Leydig cells which produce testosterone suggests autocrine or intracrine mechanism in the testis. 2) In the epididymides, nuclei of epithelial cells of epididymal ducts were stained, while muscles and connective tissues were not stained. In the seminal vesicles, nuclei of glandular epithelial cells were stained. 3) In the scrotal skins, the cells of squamous cell layer have positive stainings. The cells in the upper portion of squamous cell layer were stained more intensely than the cells in the lower portion. The basal layer was not stained. The cells of the outer root sheath of hair follicles in the scrotal skins were also stained. 4) In androgen target organs, AR-positive cells and AR-negative cells were mixed in the epithelium of a glandular duct, which suggests heterogeneity of AR localization in the androgen target organs.

Animals↗
PubMed1992

[Undiversion in a patient with ileal conduit using cecoileal urinary reservoir, a case report].

A case of urinary undiversion in a 19 year old man with high ileal loop, who at the age of 1 year was inadvertently cystectomized for probable acute urinary retention masquerading as acute abdomen, is reported. The ileo-ceco-colonic segment was isolated and the colon was partially detubularized. After ileocecal intussusception and stabilization to the cecal wall (Hendren), a segment of ileal patch was applied to form an Indiana type pouch. The ileal loop was free from the abdominal wall and its distal end was anastomosed to the terminal ileum of the pouch. Undiversion was completed by connecting the pouch at its dependent portion with the remnant prostatic urethra. At 4 months postoperatively the pouch functions quite satisfactorily as a low pressure and good volume reservoir that empties well without reflux. His erectile and ejaculatory function have also been maintained.

Adult↗
PubMed1991

Autoradiographic localization of alpha 1-adrenoceptors in human prostate: special reference to zonal difference.

Using autoradiography, localization of alpha 1-adrenoceptor in human prostate was examined with particular reference to zonal difference. Prostatic tissues were obtained from total cystoprostatectomy specimens of six male bladder tumor patients. Peripheral zone (PZ), central zone (CZ) and preprostatic region which contained preprostatic sphincter and periurethral gland were dissected from the tissues. [125I]-HEAT was used as radioligand for autoradiography. Autoradiographic distribution of alpha 1-adrenoceptor was quantitated by grain counting using a light microscope equipped with a micrometer. Specific binding was demonstrated predominantly in fibromuscular stroma of PZ, fibromuscular stroma of CZ and preprostatic sphincter. No specific binding was demonstrated in glandular epithelium of PZ and periurethral gland. Glandular epithelium of CZ showed a few specific bindings. Among fibromuscular portion, specific bindings in both CZ and preprostatic sphincter were significantly higher than in PZ. Specific binding in glandular epithelium of CZ was significantly less than in fibromuscular stroma of PZ. These results show that the human prostate has a zonal difference in the distribution of alpha 1-adrenoceptors, probably reflecting some functional difference in these regions.

Aged↗
PubMed1991

Adrenocortical nuclear progesterone-binding protein: identification by photoaffinity labeling and evidence for deoxyribonucleic acid binding and stimulation by adrenocorticotropin.

Nuclei of the guinea pig adrenal cortex contain a protein that specifically binds progesterone and that, biochemically, is clearly distinct from the classical progesterone receptor. The adrenocortical nuclear progesterone-binding protein has now been purified more than 2000-fold by steroid-affinity chromatography with a 75% yield. The purified protein preparation demonstrated three major bands on sodium dodecyl sulfate-polyacrylamide gel of 79K, 74K, and 50K. To determine which of the three might represent the progesterone-binding protein, steroid photoaffinity labeling was performed which resulted in the specific and exclusive labeling of a 50K band. Thus, the adrenocortical nuclear progesterone-binding protein appears to be distinct from the classical progesterone receptor not only biochemically, but also on the basis of molecular size. To test whether the adrenocortical nuclear progesterone-binding protein can be hormonally stimulated, guinea pigs were treated with ACTH. The chronic administration of ACTH caused a 4- to 6-fold increase in the specific progesterone binding capacity without a change in the binding affinity. There appeared to be no significant difference in nuclear progesterone binding between the zona fasciculata and zona reticularis. This finding suggests a mediating role for the progesterone-binding protein in ACTH action. In addition, the nuclear progesterone-binding protein bound to nonspecific DNA sequences, further suggesting a possible transcriptional regulatory role.

Adrenal Cortex↗
PubMed1990

Androgen binding activity in the spongy tissue of mammalian penis.

The binding of [3H]R1881 to cytosol fractions was determined for the spongy tissues of horse, porcine and human penis. Binding of [3H]R1881 to cytosol fractions from these spongy tissues was found to be specific with high affinities (mean of Kd; 1.8 X 10(-10) M) but with equally low binding capacities (mean of 4.66 fmol/mg. protein). Saturation analysis revealed that the binding capacity was similar for both corpus cavernosum and corpus spongiosum of horse penis. We conclude that a trace amount of androgen receptor is present in spongy tissue of the penis and that there is no difference in cytosolic receptors between corpus cavernosum and corpus spongiosum in adult mammalian penis.

Androgens↗
PubMed1990

The nuclear conversion of pregnenolone to progesterone and subsequent binding to the nuclear progesterone-binding protein in the guinea pig adrenal cortex: a possible regulatory role for the pregnenolone-binding protein.

Progesterone, which is normally produced in the endoplasmic reticulum, was found to be rapidly degraded in the cytosolic fraction of the guinea pig adrenal cortex in vitro. Assuming this finding reflects what happens in vivo raises a question as to the source of progesterone for interacting with a nuclear progesterone-binding protein (P4-BP) that exists in this model system. It was subsequently found that pregnenolone, which in contrast to progesterone is relatively stable in the cytosol, was converted to progesterone by endogenous nuclear 3 beta-ol dehydrogenase. It was also determined that the nuclear-derived progesterone specifically bound to the nuclear P4-BP which is distinct from the classical progesterone receptor. The guinea pig adrenocortical cytosol contains a specific pregnenolone-binding protein (P5-BP) that could be virtue of its pregnenolone binding activity regulate the conversion of pregnenolone to progesterone in the nuclear compartment and thereby reduce the binding of progesterone to the nuclear P4-BP. A partially purified P5-BP preparation markedly inhibited the nuclear conversion of pregnenolone to progesterone and reduced the binding of progesterone to the nuclear P4-BP (P5-BP did not directly inhibit binding of progesterone to the nuclear P4-BP). The ability of P5-BP to inhibit the conversion of pregnenolone to progesterone was destroyed by heat and alkaline phosphatase treatment. The binding of pregnenolone to the P5-BP, as previously reported, is regulated by phosphorylation/dephosphorylation, and alkaline phosphatase-treated P5-BP loses the ability to bind pregnenolone; this process can be reversed by a cytosolic kinase. This provides a mechanism for controlled release of bound steroid. These results suggest that P5-BP regulates the nuclear conversion of pregnenolone to progesterone and thus the binding of progesterone to the nuclear P4-BP.

Adrenal Cortex↗
PubMed1989

Establishment and characterization of monoclonal antibody against androgen receptor.

Hybrid cell lines were prepared by the fusion of BALB/c myeloma NS-1 cells with the lymphocytes of BALB/c mice that were immunized with partially purified androgen receptor (AR) from human prostates. Nine clones of the hybrid progeny were determined for the production of antibodies against AR by immunoprecipitation assay. One of the clones, referred to as "5F4", was chosen for analysis of the detailed specificity. The clone "5F4" secreted IgM class antibodies against AR. Competition study demonstrated that "5F4" antibody inhibited androgen binding of AR, suggesting that the antibody identifies androgen binding site of AR. Immunoblotting analysis showed that the antibody identified the ARs as two proteins, 95 kD and 41 kD proteins, on a sodium dodecyl sulfate polyacrylamide gel. It is suspected that a 95 kD protein should be a monomeric AR and a 41 kD protein is a proteolytic fragment of AR. Immunohistochemical analysis demonstrated that androgen-dependent tissues--human prostatic hypertrophy tissues, an AR abundant prostatic cancer tissue and fibroblast cells from human genital skin--were stained intensely with "5F4" monoclonal antibody, while androgen-independent tissues--fibroblast cells from lymph nodes, an AR deficient prostatic cancer tissue and human prostatic cancer cell line, PC-3--showed no staining. These results also support the specificity of the antibody for AR.

Androgens↗
PubMed1989

Nuclear progesterone-binding protein in the guinea pig adrenal cortex: distinction from the classical progesterone receptor.

Nuclei purified from the guinea pig adrenal cortex contain a specific progesterone-binding activity which, based on enzyme degradation studies, appears to be proteinaceous. Saturation analysis revealed a Kd of about 15 nM and a binding capacity of about 33 pmol/mg DNA. The activity of the nuclear binding protein was specific essentially for progestational steroids; the two most potent progesterone competitors were 5 alpha-pregnane-3,20-dione and medroxyprogesterone (17 alpha-hydroxy-6 alpha-methylprogesterone), while 17 beta-estradiol, testosterone, cortisol, and other related steroids were poor competitors. The adrenocortical nuclear progesterone-binding protein was present to an equal extent in both male and female guinea pigs. The adrenocortical nuclear progesterone-binding protein differed from the classical progesterone receptor in that 1) the affinity of the adrenocortical binding protein for progesterone is an order of magnitude lower; 2) the potent synthetic progestin R5020 binds less tightly to the adrenocortical progesterone-binding protein; 3) the adrenocortical progesterone-binding protein is not modulated by estrogenic activity; 4) the adrenocortical progesterone-binding protein is more stable at 37 C; 5) the adrenocortical nuclear progesterone-binding protein is not salt extractable; and 6) Western blot analysis has revealed that an antiprogesterone receptor monoclonal antibody, which recognizes the guinea pig uterine classical nuclear progesterone receptor, does not recognize the adrenocortical nuclear progesterone-binding protein. Thus, the guinea pig adrenocortical nucleus contains a type of progesterone-binding protein that appears to be clearly different from the classical progesterone receptor.

Adrenal Cortex↗
PubMed1988

Postoperative reduction of serum beta-HCG in testicular seminoma.

Serum beta-HCG and urinary HCG were measured in 17 patients with histologically proved pure seminoma of the testis. The patients have been followed to date for 10 to 74 months after orchiectomy, and have no residual disease or recurrence of their disease. Preoperative urinary HCG levels were abnormal in 9 patients (53%). Serum beta-HCG levels were slightly elevated in 6 out of 12 patients evaluated, and were reduced after orchiectomy even in patients with preoperative normal beta-HCG levels (P less than 0.05). Preoperative levels of the tumour marker in seminoma were far lower than in patients with non-seminomatous germ cell tumours, but it would not be rare to see a small amount of HCG produced by the tumour cells in the seminoma.

Adult↗
PubMed1988

Establishment of monoclonal antibody to human androgen receptor and its clinical application for prostatic cancers.

Hybrid cell lines were prepared by the fusion of BALB/c myeloma NS-1 cells with the lymphocytes of BALB/c mice that were immunized with partially purified androgen receptor (AR) from human prostates. One of the clones, 5F4, was chosen for detailed specificity analysis. The avidin-biotin-peroxidase complex (ABC) procedure was used for immunohistochemical staining of the 5F4 monoclonal antibody. In human benign prostatic hypertrophy (BPH) tissues, cytoplasm and nuclei were stained. Of 16 prostatic cancer tissues, 2 were composed of AR-positive cells exclusively, 7 were composed of AR-negative cells, and 7 contained both AR-positive cells and AR-negative cells (mixed). Of nine cases that were AR-positive or mixed, seven cases responded to the hormone therapy, and two were not determined for responsiveness because the patients died early of other diseases. Of seven AR-negative cases, all but one inestimable case had no response to the hormone therapy. Immunohistochemical analysis of AR by using the monoclonal antibody 5F4, was a useful tool for determining androgen dependency of prostatic cancers.

Animals↗