Search PubMed⌕ Search

Biomedical subjects

J Shimazaki

Publications and source records attributed to J Shimazaki.

At least 91 records · Page 5Linked to original sources

Influence of osteoarthritis on serum marker levels of bone formation and resorption in patients with benign prostatic hypertrophy.

BACKGROUND: The aim of this study was to investigate the influence of osteoarthritis of lumbar vertebrae on serum bone formation and resorption marker levels of patients with benign prostatic hypertrophy (BPH). METHODS: Serum levels of carboxyterminal propeptide of type I procollagen (PICP), alkaline phosphatase (ALP), carboxyterminal telopeptide of type I collagen (ICTP), and prostate-specific antigen (PSA) were examined in 40 patients with BPH, and the presence of osteoarthritis at the lumbar vertebrae of the patients was evaluated by plain x-ray-p. RESULTS: Findings of osteoarthritis were observed in 23 of the 40 patients (58%), and 10 of the patients had severe osteoarthritis (involving at least 2 lumbar vertebral bodies). The serum levels of PICP, ALP, ICTP, and PSA of the patients without osteoarthritis findings were not different from those of the patients with osteoarthritis or severe osteoarthritis. CONCLUSION: The influence of osteoarthritis on serum bone formation and resorption marker levels of patients with BPH appears to be rather slight, if there is any influence at all.

Aged↗

[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group].

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.

Administration, Oral↗

[Effect of estramustine phosphate on hormone refractory prostate cancer].

Clinical effects of estramustine phosphate (EMT) on hormone refractory prostate cancer were studied. Prostate cancer relapsed in 70 of the 259 patients with stage C and D diseases who had initially responded to endocrine therapy. After cancer relapse, endocrine therapy was changed to oral administration of EMT in 21 patients, while initial endocrine therapy was continued in 14 and additional radiation therapy was given in 35. A partial response or no change was observed in 11 of the 21 patients (52%) given EMT therapy, the mean duration of the response being 14.2 months. The 21 patients given EMT therapy survived significantly longer than the 14 patients with continued on endocrine therapy, and those responding to EMT therapy tended to have a better survival than those unresponsive. Side effects of EMT included loss of appetite in 2 patients and edema of the lower limb in 1, but they were not severe enough to require discontinuation of the drug. EMT may be a useful drug for patients with advanced prostate cancer with relapse after endocrine therapy.

Administration, Oral↗

[Mechanism on androgen-independent progression of prostate cancer].

Eighty percent of prostate cancer with metastasis respond to androgen ablasion, showing initial androgen-sensitive growth. However, more than half of responders gradually loses dependency up to 5 years. Animal experiments reveal that loss of androgen sensitivity is attributable to complex reasons; adaptation, paracrine control by other androgen-independent tissues, genetic changes and mutation of androgen receptor. Most important event is explained from alteration of expression on oncogenes and suppressor genes. Counterplan of the progression was discussed.

Androgen Antagonists↗

[Androgen receptor].

Explore the source record for details and available documents.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

[Prostate cancer].

Up to stage B1 or prostate cancer with N0-1 positive lymph node may be curable by monotherapy of either radical prostatectomy or irradiation. Localized but more advanced stages (B2 and C), however, are difficult to cure. To further improve the prognosis in these stages, a new treatment modality is proposed; pelvic lymphadenectomy, followed by irradiation with neoadjuvant and adjuvant endocrine therapy. An average 2-year followup is favorable. Further studies is awaited to make conclusion.

Androgen Antagonists↗

Effects of artificial tear temperature on corneal sensation and subjective comfort.

PURPOSE: Cooling reduces acute inflammation and local nerve sensation. We investigated the relationship between artificial tear temperature, ocular surface sensation, and patient comfort. METHODS: We placed preservative-free artificial tears and eye mask stored at four temperatures (36 degrees C, 25.2 degrees C, 4 degrees C, and -10 degrees C) in the right eyes of 24 normal subjects, whose left eyes served as controls. Corneal and conjunctival sensations were measured and corneal temperature was recorded. Comfort was reported on a 7-point scale. RESULTS: Corneal temperature was significantly lowered with all temperature artificial tears and frozen eye mask (p < 0.001 for each temperature relative to the previous one). Aesthesiometer readings were inversely correlated with corneal temperature (r = -0.45, p = 0.0005), decreasing with lower temperatures, reaching 2.0 +/- 1.3 g/mm2 (p = 0.001) for the mask. Conjunctival sensation reacted similarly and was well correlated with both corneal temperature (r = 0.43, p = 0.0009) and corneal sensation (r = 0.39, p = 0.006). Treatments provided relief, with the 4 degrees C tears being the most comfortable (p = 0.0001). CONCLUSION: Although there may still be some biases, cooled artificial tears provide relief to the eye by the mechanism of reduced corneal and conjunctival sensation.

Administration, Topical↗

[Free/total ratio of prostate-specific antigen (PSA) for prostate cancer detection in patients with gray zone PSA level].

Thirty seven patients complaining of voiding disturbance who showed gray zone total prostate-specific antigen (t-PSA) level (upper limit of normal approximately 10 ng/ml) but did not reveal apparent cancerous findings in the prostate were examined for free PSA (f-PSA) and prostate volume. According to histological diagnosis, 9 were cancer cases and the other 28 were non-cancer cases. The free/total (F/T) ratio was 0.10 and 0.16 in the cancer and non-cancer groups, respectively (t-PSA; DPC kit, p = 0.03). The t-PSA (DPC and Dinabott kits), f-PSA and PSA density alone did not distinguish these two groups. For diagnosis of cancer, the ratio seemed to be F/T, the most reliable followed by PSA density and t-PSA. When using a 13% F/T, the sensitivity and specificity for cancer detection were 88.9 and 70.8%, respectively. t-PSA measured with the Dinabott kit, showed a similar tendency except that the F/T ratio showed a slight variation. Prostate volume and patient age influenced the F/T slightly, but these factors may not impair the usefulness of F/T.

Aged↗

Identification of histone H2A.X as a growth factor secreted by an androgen-independent subline of mouse mammary carcinoma cells.

Shionogi carcinoma 115 (SC 115) cells and Chiba subline 2 (CS 2) cells are clones of an androgen-responsive mouse tumor cell line and its autonomous subline, respectively. We have shown previously that CS 2 cells produce a heparin-binding growth factor that stimulates the growth of SC 115 cells as well as the growth of themselves. In this study, a growth factor was purified from serum-free conditioned media of CS 2 cells cultured without testosterone. A heparin-binding fraction showed growth- promoting activity on SC 115 cells and BALB/3T3 cells. The amino acid sequence analysis revealed that the components were identical to histones H2A.1 and H2A.X. Since histone H2A purified from bovine thymus had almost no growth-promoting activity on SC115 cells, histone H2A.X was assumed to be a growth factor. cDNA of histone H2A.X was cloned from a library of CS 2 cells, and its sequence was confirmed. The expressed product of histone H2A.X cDNA in Escherichia coli showed remarkable stimulatory effects on growth of SC 115 cells cultured in the absence of testosterone. These results indicate that histone H2A.X is secreted from CS 2 cells cultured without testosterone and plays a role as a growth factor.

3T3 Cells↗

Induction of apoptosis in androgen-independent mouse mammary cell line by 1, 25-dihydroxyvitamin D3.

Androgen-dependent tumors eventually progress to independent tumors after androgen withdrawal. Effective treatment for hormone-independent tumors is therefore needed. Androgen-independent CS-2 cells could grow in serum-free culture whether androgen is present in the medium or not. In the present study, the mechanism of cell death in CS-2 cells was examined after 1, 25-dihydroxyvitamin D3[1, 25(OH)2D3] treatment. 1, 25(OH)2D3 has been examined as an anti-tumor agent, but its role in promoting cell death is poorly understood. Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, the cells underwent apoptosis with 1, 25(OH)2D3 treatment. Northern-blot analysis was used to identify a series of genes whose expression per cell is enhanced during the apoptotic pathway. In the apoptotic process induced by 1, 25(OH)2D3, mRNA expression of testosterone-repressed prostatic message 2, transforming growth factor beta1, glucose-regulated 78-kDa protein and calmodulin increased. Flow-cytometric analysis showed that 1, 25(OH)2D3 treatment resulted in a block in G0/G1 of the cell cycle. These results demonstrate that androgen-independent CS-2 cells retain the ability to undergo apoptosis by 1, 25(OH)2D3. This system appears to be a good model for investigating apoptosis of hormone-independent cancer.

Actins↗

Androgen receptor content of prostate carcinoma cells estimated by immunohistochemistry is related to prognosis of patients with stage D2 prostate carcinoma.

BACKGROUND: Patients with prostate carcinoma generally respond to androgen withdrawal therapy, but subsequent progression to androgen-independence is frequently observed. Since androgen receptors play a key role in androgen action, the ratio of androgen receptor-containing cells in cancerous tissues was determined by immunohistochemical staining of prostate biopsy specimens for comparison with the outcome. METHODS: Sixty-two patients with untreated Stage D2 prostate carcinoma who received endocrine therapy between 1986 and 1992 were included in the present study. Biopsy tissue was stained with anti-human androgen receptor antibody, and the ratio of positively stained cells was estimated by counting 700 to 1000 cancer cells from each patient. Histologic grade, extent of bone metastases, clinical response to endocrine therapy, and outcome, were compared with androgen receptor content. RESULTS: Cancers with a low Gleason score had a significantly higher androgen receptor content than those with a high Gleason score. Androgen receptor content was not significantly correlated with extent of disease or tumor marker response at three months. Patients with 48% or more androgen receptor positive cells had a statistically significant better outcome, in terms of both progression free and cause-specific survival, than patients with less than 48% androgen receptor content. Multivariate analysis demonstrated that androgen receptor content, extent of disease and tumor marker response at three months were significant predictors of outcome. CONCLUSIONS: Androgen receptor content measured immunohistochemically is a useful prognostic indicator for patients with Stage D2 prostate carcinoma treated with endocrine therapy.

Aged↗

Detection of human papillomavirus DNA and p53 gene mutations in human prostate cancer.

The relationship between integration with human papillomavirus (HPV) and p53 gene mutations in tissues of prostate cancer were examined. Tissue samples analyzed were obtained by total prostatectomy (29 stage B cancer cases) and from autopsy (22 endocrine therapy-resistant metastatic disease cases). HPV DNA was detected in 8 of 51 (16%, 5 in stage B and 3 in autopsy cases) by polymerase chain reaction (PCR) using consensus primers on L1 region. Genotypes of HPV were entirely type 16. Structural abnormalities of p53 gene were detected in 7 of the 22 autopsy cases (32%) by PCR-single-strand conformation polymorphism analysis and direct sequencing. No p53 gene mutation was found in stage B cancer cases. Analysis of mutation spectra revealed clear differences between Japanese and Westerners. There was a significant difference in the mutation frequency between stage B and autopsy cases (p < 0.01, Fisher's exact test). One case showed both integration of HPV and p53 gene mutation in different cancer foci. However, the other cases revealed an inverse correlation between the presence of HPV DNA and p53 gene mutations. These data show that p53 genetic alteration is correlated with the progression of prostate cancer, in contrast to the integration of HPV that may occur in a relatively early stage. In conclusion, this study may indicate that either p53 gene mutation or the presence of HPV's oncogenic protein E6 is involved in the development of prostate cancer.

Adenocarcinoma↗

Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancers.

Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyzed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stage C, 10 cases; cancer death, 18 cases) for allelic loss on 16q, using either restriction fragment length polymorphism (RFLP)- or polymerase chain reaction (PCR)-based methods. Allelic losses were observed in 20 (42%) of 48 cases, all of which were informative with at least one locus. Detailed deletion mapping identified three distinct commonly deleted regions on this chromosome arm: q22.1-q22.3, q23.2-q24.1, and q24.3-qter. On the basis of a published sex-averaged framework map, the estimated sizes of the commonly deleted regions were 4.7 (16q22.1-q22.3), 17.2 (16q23.2-q24.1) and 8.4 cM (16q24.3-qter). Allelic losses on 16q were observed more frequently in the cancer-death cases (11 of 18; 61%) than in early-stage tumor cases (9 of 30; 30%; P < 0.05). In 7 of 11 patients from whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 16q, but the metastatic tumors showed LOH. These results suggest that inactivation of tumor suppressor genes on 16q plays an important role in the progression of prostate cancer. We also analyzed exons 5-8 of the E-cadherin gene, located at 16q22.1, in tumor DNA by means of PCR-single strand conformation polymorphism and direct sequencing, but we detected no somatic mutations in this candidate gene.

Adenocarcinoma↗

Allelic losses at loci on chromosome 10 are associated with metastasis and progression of human prostate cancer.

DNA samples from tumors and paired normal tissues from 48 patients with prostate cancer (stage B, 16 cases; stage C, 14 cases; stage D, 18 cases) were examined with 26 polymorphic markers spanning chromosome 10. Allelic losses were observed in 17 of the 46 cases (37%) that were informative with at least one of the markers. Detailed deletion mapping identified two distict commonly deleted regions on the long arm of chromosome 10 (10q22-q24:7 cM and 10q25.1:17 cM) and one on 10p, suggesting that at least three tumor suppressor genes associated with prostate cancer are present on this chromosome. We observed loss of heterozygosity more frequently in tumors from fatal cases (stage D, 8/16, 50%) than in localized tumors (stage B, 0/16, 0%; P = 0.001 or stage B + C, 5/30, 17%; P = 0.02 Fisher's exact test). All metastatic tissues showed allelic loss at one or more loci on 10q. In five of the nine patients from whom DNAs were available from both metastatic and primary tumors, the primary cancer foci had no detectable abnormality of chromosome 10, while the metastatic foci showed allelic loss on chromosome 10. These results suggested that inactivation of one or more tumor suppressor genes on chromosome 10 plays an important role in late stages of prostate cancer.

Adenocarcinoma↗