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Biomedical subjects

J Shimazaki

Publications and source records attributed to J Shimazaki.

At least 127 records · Page 7Linked to original sources

Metastasis suppressor genes for prostate cancer.

To examine the role of human chromosomes in the development of metastatic prostate cancer, we introduced a copy of human chromosomes into highly metastatic Dunning R-3327 rat prostatic cancer cells by microcell-mediated chromosome transfer. Each microcell hybrid clones containing human chromosomes 8, 10, 11, and 17, respectively, showed decreased ability to metastasize to the lung, without any loss of tumorigenicity. This finding demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in human chromosome 10, 11, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained metastasis suppressor gene(s) for prostate cancer. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes 8, 10, and 11 were located on 8p23-q12, 10q, 11p13-11.2, respectively. Further analyses are proposed to confirm the potentially useful advantage of this assay system to identify metastasis suppressor gene(s) for prostate cancer.

Animals↗

[Prognostic factors in stage D2 prostate cancer: results of univariate and multivariate analyses].

To evaluate prognostic factors in stage D2 prostate cancer, 235 patients who had been treated with endocrine therapy were investigated. With univariate analysis, performance status, hemoglobin concentration, serum alkaline phosphatase, LDH, histological grade, extent of disease (EOD), and response of tumor markers at 3 months were shown to be significant prognostic factors. To compare these 7 factors, multivariate analyses was performed in 196 cases. Cox proportional hazard model demonstrated that LDH, followed by response of tumor markers at 3 months, histological grade, and EOD were significant for predicting prognosis. We concluded that the patients whose serum LDH was above the normal range and/or whose tumor markers were not or had not been normalized 3 months after the onset of endocrine therapy were in the high risk group, and should be given more aggressive treatment.

Aged↗

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral↗

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral↗

[Bilateral renal cell carcinoma with extension into the vena cava associated with von Hippel-Lindau disease: a case report and review of the literature].

We report a case of bilateral renal cell carcinoma with extension into the inferior vena cava associated with von Hippel-Lindau (VHL) disease. A 52-year-old woman was referred to our hospital for further examination of bilateral renal masses which were found on abdominal ultrasound examination. The diagnosis was confirmed with renal angiography, abdominal computed tomography (CT), abdominal magnetic resonance-CT (MRI), cavography and head MRI. Right adjunctive nephrectomy and removal of the tumor thrombus were performed. She has been treated with interferon-alpha after the operation. The analysis of her DNA by using single strand conformational polymorphism revealed a VHL gene abnormality.

Carcinoma, Renal Cell↗

Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.

The KAI1 gene, recently identified as a metastatic suppressor gene for prostate cancer, was cloned and was revealed to be identical to the C33/IA4/ R2/4R9 gene. The expression of KAI1 protein was examined immunohistochemically in the tissues from 14 cases of benign prostatic hyperplasia and 46 cases of prostate cancer using mouse monoclonal anti-human C33 antibody. In benign prostatic hyperplasia tissues, KAI1 protein was uniformly expressed in the glandular cell membrane at cell-to-cell borders. The KAI1 protein in the tissues of untreated prostate cancer was also located at similar sites to those of benign prostatic hyperplasia, but the percentage of strongly positive cancer cells was correlated inversely to the Gleason pattern (P < 0.0001, one-way analysis of variance). There was also a statistically inverse correlation between the percentage of KAI1-positive cancer cells and the clinical stage (chi 2 = 9.6; P = 0.0081). In 4 cancer death cases relapsed from endocrine therapy, KAI1 protein was not stained in either primary or metastatic foci. These results indicate that the expression of KAI1 protein correlates to tumor characteristics in prostate cancer.

Adenocarcinoma↗

[Cavernous hemangioma of urinary bladder: a case report and review of the literature].

We report a case of cavernous hemangioma of the urinary bladder treated with transurethral resection (TUR). A 58-year-old woman was admitted to our department with the chief complaint of macroscopic hematuria. Cystoscopy revealed a red sessile tumor 2 cm in diameter, at the internal urethral orifice. The tumor had a mostly low signal intensity, partly high signal intensity, on T1-weighted, coronal magnetic resonance (MR) images. Computed tomography and T2-weighted MR images did not delineate the tumor. TUR was performed, and the specimen was pathologically diagnosed as cavernous hemangioma of the urinary bladder. A brief description of the case is provided and the literature is reviewed.

Female↗

Limbal autograft transplantation for recurrent and advanced pterygia.

BACKGROUND AND OBJECTIVE: This study was conducted to examine the usefulness of limbal autograft transplantation in the treatment of recurrent and advanced pterygia. PATIENTS AND METHODS: Eleven patients with recurrent and 16 with advanced pterygia (a total of 27 pterygia) were treated with limbal autograft transplantation. Once a pterygium had been excised, superior limbal tissue was taken with conjunctival flap and transferred to the excised area. RESULTS: All the grafts were planted promptly, and donor sites were re-epithelialized with no excessive scar tissue formation. Although slight recurrence was noted in 2 eyes (7.4%), subconjunctival tissue invasions were limited to less than 1 mm, and no further surgical interventions were needed. CONCLUSION: These results indicate that limbal autograft transplantation may be effective for the treatment of recurrent and advanced pterygia.

Adult↗

[Mass screening for prostate cancer in Japan].

Since 1975 mass screening for prostate cancer has been performed in Japan. The Prostate Research Foundation has analysed the data every year that collected from all institutes performing a mass screening. Up to 1993, 67, 225 subjects were examined. The detection rate of prostate cancer was 0.69%. Approximately half of the cancer were stage B, and the subjects who have metastatic stage were only 20% and the pattern of stage seemed to be different from that of patients who visited hospitals. In Chiba prefecture the subjects lived in a district of south Boso peninsula received a mass screening for prostate cancer with total of 1,964 men from 1985, and 17 cancers were diagnosed (0.87%). The distribution of prostate-specific antigen (PSA) assayed with Tandem-R kit was examined using the stocked sera (n = 976) of the screening for prostate cancer in Chiba prefecture. The percentage of 0.05-4.0 ng/ml, 4.1-9.9 ng/ml, over than 10.0 ng/ml of the PSA, were 89.6%, 7.0%, 3.4%, respectively. This distribution is approximately as same as the previous reports by the United States and Canada.

Age Factors↗

Induction of apoptosis in an androgen-independent mouse cell line by transforming growth factor-beta 1.

Androgen-dependent tumors eventually progress to androgen-independent tumors after androgen withdrawal. Androgen-independent CS2 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 CS2 cells was examined after transforming growth factor-beta 1 (TGF-beta 1) treatment. Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, these cells underwent apoptosis with TGF-beta 1 treatment. During the apoptotic process induced by TGF-beta 1, mRNA expression of testosterone repressed prostatic message-2, glucose regulated 78 kDa protein, and calmodulin increased. Flow cytometric analysis showed that TGF-beta 1 treatment resulted in a block in the G0/G1 phase of the cell cycle. These results demonstrate that although androgen withdrawal could not induce apoptosis in androgen-independent CS2 cells, these cells retain the ability to undergo apoptosis induced by TGF-beta 1. This system should be a good model for investigating apoptosis of hormone-independent cancer.

Androgens↗

Ocular surface changes and discomfort in patients with meibomian gland dysfunction.

OBJECTIVE: To determine the importance of meibomian gland dysfunction (MGD) on the ocular surface. DESIGN: Prospective study. SETTING: A university-based referral practice. PATIENTS: Patients with ocular discomfort (147 eyes) and without ocular discomfort (54 eyes) were examined. In the total 201 eyes, MGD was defined as the presence of an obstruction of the meibomian orifices (obstruction group [n = 54]) or the absence of a gland structure (gland dropout group [n = 36]), or both of these findings (combined group [n = 38]). There were not any findings of MGD in 73 eyes (non-MGD group). MAIN OUTCOME MEASURES: Scores that were obtained from fluorescein and rose bengal staining, the breakup time of the tear film, the rates of tear evaporation and tear production, and meibography. RESULTS: Of the 147 eyes with ocular discomfort, 95 (64.6%) had either an obstruction of an orifice or gland dropout, or both. The combined group had higher scores for staining with fluorescein (P = .002) and rose bengal (P = .021) compared with that in the non-MGD group. The rate of tear production was increased more in the gland dropout group than in the non-MGD group (P = .002). The rate of tear evaporation was significantly increased in the gland dropout group (P = .017). CONCLUSION: Meibomian gland dysfunction is a major cause of ocular surface abnormalities and ocular discomfort.

Adult↗

Localization of a tumor suppressor gene associated with progression of human prostate cancer within a 1.2 Mb region of 8p22-p21.3.

Human prostate cancers frequently show loss of heterozygosity at loci on the short arm of chromosome 8. In order to take a step toward isolation of the putative tumor suppressor gene(s) on 8p via positional cloning, we performed high-resolution deletion mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8 cases; endocrine therapy-resistant cancer death, 18 cases) using new 12 restriction fragment length polymorphism markers for this chromosomal region. Allelic losses were observed in 25 of the 44 cases (57%) that were informative with at least one locus. Detailed deletion mapping defined a 1.2 Mb commonly deleted region at 8p22-p21.3 flanked by markers cMSR-32 and C18-1051. A second region of common deletion was identified between C18-1312 and C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor genes associated with prostate cancer are present on chromosome arm 8p. Allelic losses on 8p were observed more frequently in the cancer death cases (14/17, 82%) than in early-stage tumors (11/27, 40%; P < 0.01, Fisher's exact test). In two out of 7 patients for 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 8p, but the metastatic tumors showed loss of heterozygosity. These results suggest that inactivation of tumor suppressor genes on 8p plays an important role in the progression of prostate cancer.

Adenocarcinoma↗

Increased comfort and decreased inflammation of the eye by cooling after cataract surgery.

PURPOSE: Cooling can reduce clinical symptoms and pain caused by traumatic swelling or fracture of extremities. We obtained subjective and objective measures of the effects of cooling of the eyes after cataract surgery. METHODS: Twenty patients with bilateral cataracts were enrolled in this study. For each patient, an ice-cold eye mask was applied over gauze to one operated-on eye for two hours after the operation and was not applied after operation on the other eye. After each operation, the patient rated comfort on a five-point scale. The severity of inflammation associated with each procedure was evaluated by using an infrared radiation thermometer to determine the central corneal temperature and a laser flare-cell meter to determine the cell and flare count, at intervals up to 28 days after surgery. RESULTS: Cooling, applied after the first operation in ten patients and after the second operation in ten patients, statistically significantly increased the patients' comfort level and was associated with a significant decrease in central corneal temperature on days 0, 1, and 3; in cell counts on days 1, 3, 7, and 14; and in flare counts on days 1, 14, and 28. CONCLUSIONS: Cooling increased the comfort level and reduced inflammation after cataract surgery, with no adverse effects.

Aged↗

Antiandrogen withdrawal syndrome in prostate cancer after treatment with steroidal antiandrogen chlormadinone acetate.

OBJECTIVES: A case report is presented of 2 patients whose levels of serum prostate-specific antigen (PSA) improved after the withdrawal of a steroidal antiandrogen. METHODS: Two cases with prostate cancer had been treated with surgical castration and the steroidal antiandrogen chlormadinone acetate (CMA), and, on disease progression, the administration of CMA was terminated. RESULTS: Following withdrawal of CMA, a fall in PSA levels and remarkable clinical improvement were observed in both cases. One patient revealed a decrease and the other an increase in serum prostate acid phosphatase after the discontinuation of CMA. Serum levels of testosterone, prolactin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione were not significantly elevated after CMA withdrawal. CONCLUSIONS: Withdrawal of the steroidal antiandrogen CMA resulted in a decline in PSA levels and clinical improvement in prostate cancer patients with disease progression. Changes in testosterone, prolactin, or adrenal androgens were not a cause of the antiandrogen withdrawal syndrome.

Aged↗

Reconstruction of the corneal epithelium by limbal allograft transplantation for severe ocular surface disorders.

PURPOSE: Although penetrating keratoplasty is an established surgical procedure, it often is ineffective for severe ocular surface diseases such as alkali burns or limbal deficiency. The authors have performed limbal allograft transplantation for the reconstruction of the corneal epithelium. METHODS: A total of nine patients (3 with chemical injury, 3 with limbal deficiency with unknown etiology, 2 with moderate ocular pemphigoid [OCP], and 1 with traumatic limbal deficiency) were treated by limbal allograft transplantation. Penetrating keratoplasties were performed in all patients with the exception of one with OCP. Patients received cyclosporine both systemically (10 mg/kg) and topically (0.05%) as well as high-dose intravenous dexamethasone (8 mg). RESULTS: The corneal epithelium was reconstructed in all patients, although two showed partial increased fluorescein permeability and two others required a second surgery. The other five epithelia remained clear at mean follow-up of 12.3 months, with two episodes of graft rejection which were controlled successfully by medication. CONCLUSIONS: Limbal allograft transplantation with intensive immunosuppression by cyclosporine and high-dose steroids appears to be a promising surgical intervention for the reconstruction of corneas affected by severe ocular surface disease.

Adult↗

Dry eye with only decreased tear break-up time is sometimes associated with allergic conjunctivitis.

PURPOSE: The authors' clinical experience has suggested that there is a form of dry eye with only decreased tear break-up time, which is associated with allergic conjunctivitis. The current study was performed to verify this hypothesis. METHOD: The authors recruited patients with two types of dry eye syndrome, those with only decreased tear break-up (BUT type) and those with positive vital staining (staining type). Individuals without any symptoms or signs served as controls. All subjects were compared regarding symptoms, Schirmer and tear clearance test results, conjunctival papillary formation, antigen-specific serum-IgE level (s-IgE), and goblet cell density of the palpebral conjunctiva. Antigen-induced allergic conjunctivitis was produced in guinea pigs, and histopathologic changes of the conjunctiva were examined. RESULTS: Patients with the BUT-type dry eye syndrome were younger and their symptoms were as severe as the staining type. The Schirmer and tear clearance test results were better, and the papillary formation and s-IgE were observed more than in the BUT type. The average goblet cell density in the BUT-type syndrome was 625.4 +/- 193.2/mm2, which was significantly less than 1005.6 +/- 294.5/mm2 in the controls (P < 0.01). The average goblet cell density was significantly decreased in the allergic animals (10.40 +/- 1.11/0.2 mm) compared with that of the controls (16.21 +/- 0.26/0.2 mm) or the anti-allergic drug-treated group (13.69 +/- 0.30/0.2 mm) (P < 0.01). CONCLUSION: These results support the authors' hypothesis that decreased break-up time is in part associated with the decreased goblet cell density caused by allergic conjunctivitis.

Adult↗

Long-term follow-up of patients with familial subepithelial amyloidosis of the cornea.

PURPOSE: To investigate the clinical course of patients with familial subepithelial amyloidosis of the cornea (FSA). METHODS: The authors retrospectively investigated the clinical course of seven Japanese patients with FSA. Corneal specimens obtained at the time of keratoplasty were examined histopathologically. RESULTS: The mean follow-up period was 20.6 years, including four patients followed for more than 25 years. In all patients, the initial symptoms of photophobia and epiphora started in the first decade of life. All except one patient had their first keratoplasty before 30 years of age. The seven Japanese patients with FSA had a total of 35 keratoplasties, each of which was followed by a severe recurrence of disease. In each patient, subepithelial haziness developed in the graft within 1 year of keratoplasty (mean, 7.9 months). Amyloid deposition typically recurred within a few years (mean, 26.6 months) followed by a deterioration of vision. There was a high incidence of postkeratoplasty complications such as wound dehiscence, glaucoma, and cataract. Histopathologic findings demonstrated that, in the early phase of recurrence, amyloid was deposited between the basal cell of the epithelium and Bowman's layer. CONCLUSION: Patients with FSA have ocular symptoms with a deterioration in vision from an early decade of life. Conventional surgical approaches were complicated by subepithelial haziness in the first postoperative year, which was followed by a severe recurrence in each patient. New surgical approaches may be indicated in FSA.

Adult↗