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Biomedical subjects

R Nemoto

Publications and source records attributed to R Nemoto.

At least 19 recordsLinked to original sources

Numerical chromosome aberrations in bladder cancer detected by in situ hybridization.

OBJECTIVE: To investigate the relationship between interphase cytogenetics and the grade and stage of bladder cancer in patients with transitional cell carcinomas of the urinary bladder. PATIENTS AND METHODS: By use of in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 10, 11, 17, 18, X and Y was detected within interphase nuclei in formalin-fixed and paraffin-embedded sections of the routinely processed bladder cancers from 20 patients. The percentage of hyperdiploid cells (three or more spots) was estimated using light microscopy. RESULTS: The percentage of hyperdiploid cells for chromosomes 7, 11 and 17 was highly correlated with increasing tumour grade (P < 0.01, Spearman rank correlation) or increasing pathological stage (P < 0.01). The percentage of hyperdiploid cells for chromosome Y was not correlated with either grade or stage (P > 0.05). As high tumour grade and stage are both indicative of more aggressive tumour behaviour and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosomes 7, 11 and 17, may be highly predictive of bladder tumour aggressiveness. CONCLUSION: These preliminary results suggest that measurement of numerical chromosome aberrations using in situ hybridization in bladder cancer may offer a new objective and quantitative assay of the biological potential of individual tumours.

Aged

Proliferating cell nuclear antigen cyclin in human transitional cell carcinoma.

OBJECTIVES: To confirm the value of the proliferating cell nuclear antigen (PCNA) labelling index in relation to histological grade, stage and prognosis. MATERIALS AND METHODS: Tissue specimens from 56 patients (49 men, 7 women; mean age 65 years [range 34-86]) with newly diagnosed transitional cell carcinoma of the urinary bladder were stained by an avidin-biotin peroxidase method using an anti-PCNA monoclonal antibody. Immunohistochemical analysis was performed on ethanol-fixed, paraffin-embedded tissue sections obtained by endoscopic biopsy or transurethral resection (TUR). The PCNA labelling index was determined by counting the number of PCNA-labelled cells in the tissue sections. RESULTS: Grade 1 tumours averaged 5.1 +/- 3.0% labelling versus 10.9 +/- 5.2% in grade 2 tumours, and grade 3 tumours had a PCNA labelling index of 21.8 +/- 10.4%. The average labelling indices for superficial tumour (37 patients) and invasive tumour (19 patients) were 7.5 +/- 5.3% and 20.8 +/- 10.0%, respectively. A distant metastatic bladder tumour showed an average labelling index of 42.3%. To analyse survival, tumours with PCNA indices above and below the median level (12%) were compared. Those patients with an index of < 12% (the mean of all of the PCNA values) had a worse prognosis than those with an index of > 12%. The mean PCNA labelling indices in recurrent and non-recurrent tumours were 6.4 +/- 0.7% and 8.2 +/- 1.7%, respectively, statistically not significant. CONCLUSION: The higher PCNA labelling index may indicate biological malignancy. These results suggest that measurement of the PCNA labelling index in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, though it does not help to select patients at high risk of recurrence in superficial tumours.

Adult

[The role of the vertebral veins in the dissemination of prostate carcinoma].

A total of 75 prostate cancer and 67 lung cancer patients with positive bone scintigrams were studied. The patterns of spread of tumors to various bones were different between the 2 groups. The differences in the distribution of bony metastases between the prostate and lung are explained by the role of Batson's vertebral venous plexus.

Bone and Bones

[A comparative study of DNA measurement of bladder cancer from image cytometry and chromosome aberration in in situ hybridization].

The relationship between interphase cytogenetics and the DNA index measuring SCM of bladder cancer was investigated in 17 patients with bladder tumor. By in situ hybridization, the copy number of chromosomes 1, 7, 10, 11, 17, 18, X and Y was detected. The percentage of hyperdiploid cells for chromosomes 7 and 17 was highly correlated with the increasing DNA index. Since a high DNA index is both indicative of more aggressive tumor behavior and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosome 7 and 17, may be highly predictive of bladder tumor aggressiveness.

Carcinoma, Transitional Cell

[Detection of numerical chromosome aberrations in human sperm nuclei using in situ hybridization from formarin-fixed clot sections].

It has been shown that molecular cytogenetics in interphase nuclei is applicable to human sperm nuclei from formarin-fixed clot sections utilizing in situ hybridization (ISH). Ejaculates from a normal volunteer were studied utilizing biotinylated DNA probes specific for the alpha satellite region for numerical aberrations of chromosome 17 and Y. With respect to the appearance of the ISH signal, optical concentration and time for the digestion enzyme has to be established essentially. This allows precise identification of numerical abnormalities of chromosome in sperm nuclei without disruption of the morphology. This technique can now be applied to the detection of chromosomal aneuploidy in human sperm from patients with male infertility.

Aneuploidy

[Development of spinal bone metastasis by MBT-2 tumor in mice].

The biology of skeletal metastasis is poorly understood. In order to establish an animal model of spinal bone metastasis, we injected MBT-2 tumor cells into the tail vein of C3H/He mice while the inferior vena cava was occluded. By this technique, the tumor cells were transferred into the vertebral plexus. Spinal lesions developed in 12 of 15 (80%) experimental mice and in none of the control mice. All bone lesions resulted in local bone destruction. The predominant site of bone metastasis was lumbarvertebrae; other affected sites were thrpelvis and coccyges. This model should be of value in understanding the pathogenesis of spinal bone metastasis and in studying the effects of various agents on the prevention and control of spinal lesions.

Animals

[Treatment of prostatic carcinoma with UFT and leucovorin--basic study using SRCA].

Combination effect of UFT and leucovorin against the rat prostatic carcinoma (R-3327) was evaluated by the subrenal capsular assay (SRCA) using nude mice. Anticancer effect of UFT was augmented by co-administration of both low and high dose leucovorin. These results suggest a clinical usefulness of UFT administration with leucovorin for the patients with hormonally refractory advanced prostatic carcinoma.

Animals

Immunohistochemical detection of proliferating cell nuclear antigen (PCNA)/cyclin in human prostate adenocarcinoma.

Tissue specimens from 12 patients with adenocarcinoma of the prostate and 7 patients with benign prostate hypertrophy were stained by an indirect immunoperoxidase method using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody. The PCNA labeling index was determined by counting the number of PCNA-labeled cells in the tissue sections. Average PCNA labeling index of the benign prostate hypertrophy was 1.2 +/- 0.5%. Poorly differentiated tumors averaged 7.6 +/- 3.9% labeling versus 4.6 +/- 1.3% in moderately differentiated tumors, and well differentiated tumor in the series had a PCNA labeling index of 2.5 +/- 0.9%. The PCNA labeling indices for atypical hyperplasia were 1.9, and 4.1%, respectively. Our preliminary results suggest that the measurement of PCNA labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

Adenocarcinoma

Response of MBT-2 bladder carcinoma-induced osteolysis to various agents.

Tumor-bone interactions were experimentally studied using a bladder tumor in mice (MBT-2). The method consisted of subcutaneously inoculating tumor cells over the calvaria in nude mice after the periosteum was disrupted. This resulted in a local tumor that caused fragmentation of the bone. Bone destruction was found to increase in proportion to the number of osteoclasts in the earlier phase. The osteoclasts decreased in number when the tumors had grown large enough to envelop the residual bone. However, bone destruction continued and seemed to be mediated by the tumor cells by a mechanism that did not involve the osteoclasts. The effects of several agents were investigated in this model. High doses of calcitonin and cyclosporine reduced the bone resorption, and these agents may be effective in the early phase of bone destruction. A bisphosphonate derivative (AHBuBP) inhibited bone resorption markedly in the early and late phases of bone destruction. Autoradiography using carbon 14 (14C)-labeled AHBuBP showed that the isotope was concentrated at the surface of the bone adjacent to the MBT-2 tumors. These results suggest that bisphosphonates may make bone less susceptible to the actions of osteoclasts and tumor cells.

Alendronate

Role of the vertebral venous system in metastatic spread of cancer cells to the bone.

Bromodeoxyuridine (BrdU) labeled human prostatic cancer cells, PC-3, and murine osteosarcoma cells, POS-1 were injected into the tail veins of male mice under concomitant temporal occlusion of inferior vena cava. Five minutes after release of the venous occlusion, animals were sacrificed and various tissues, organs and the vertebral bones were examined immunohistochemically using an application of BrdU-anti-BrdU methods. Obvious BrdU labeled tumor cells, isolated or clumped, were demonstrated within the venous channels along the vertebral column, the epidural venous channels around spinal nervous tissues, in the bone marrow of lumbo-sacral vertebrae and intra- and peri-prostatic venous channels. The results suggest that a blockade of short duration of venous flow at the inferior vena cava can result in the bypassing of tumor cells through the vena cava to the vertebral venous system, which has a close connection with the peri-prostatic venous plexus. Thus, the vertebral venous system may play an important role in the metastasis of prostatic carcinoma to bone. In addition this experimental procedure is a very valuable model for studying mechanisms and prevention of bone metastases from prostatic carcinoma.

Adenocarcinoma

Clinical significance of the vertebral vein in prostate cancer metastasis.

A total of 75 prostate cancer and 67 lung cancer patients with positive bone scintigrams were studied. The patterns of spread in the axial skeleton and pelvis were different between the groups. The differences in the distribution of bony metastases between prostate and lung are explained by the role of Batson's vertebral venous plexus. We developed an animal model of spinal bone metastasis to prove this route. As suspension of tumor cells was injected into the tail vein of mice with vena caval occlusion. This procedure reproducibly resulted in metastatic tumor growth in the lumbar region of the vertebral column. The prevalence of spinal bone metastasis is attributed to passage of tumor cells via the vertebral venous plexus.

Adenocarcinoma

[Prostate cancer after subcapsular prostatectomy diagnosed as benign prostate hypertrophy--clinico-pathological analysis].

Of 160 newly diagnosed cases of prostate cancer during last 11 years, six (3.75%) had a prior subcapsular prostatectomy. Digital rectal examination in these six cases revealed a significant prostatic abnormality and multiple bone metastases were showed. Histological examination by step-section technique was done retrospectively using surgical materials from subcapsular prostatectomy. Two cases of incidental carcinoma were detected histologically. One showed stage A1 and another stage A2. Continuous observation should be performed after prostatectomy, even if the surgical specimens revealed no carcinoma.

Aged

[Effect of suppletory estrogen or 1,25(OH)D3 on bone mineral content].

Post-menopausal changes in bone mineral content (BMC) and the effect of suppletory estrogen or 1,25(OH)D3 was studied. BMC was evaluated by means of quantitative computed tomography. Post-menopausal BMC (age 45-49) was 158.4 +/- 42.0 mg/cm3 which was significantly lower than in other subjects in the same aged group (192.3 +/- 27.1 mg/cm3). At two years, ten years and more than ten years post-menopause it decreased significantly by 17%, 30%, 55% respectively, compared with that of pre-menopausal BMC. The administration of conjugated estrogen (0.625 mg) or 1,25(OH)D3 was effective in preventing bone loss, although a transient decrease in BMC was observed in some cases to which 1,25(OH)D3 was administered. In cases of pre-menopausal bilateral oophorectomy, BMC was found to decrease significantly to the post-menopausal level about two years after operation. However, long-term estrogen replacement therapy tends to inhibit the decrease.

Aged

Inhibition by a new bisphosphonate (AHBuBP) of bone resorption induced by the MBT-2 tumor of mice.

A new bisphosphonate, 4-amino-1-hydroxybuthylidene-1,1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) in terms of its effect on tumor-induced osteolysis using a bladder tumor in mice (MBT-2). Tumor cells were inoculated subcutaneously (SC) over the calvaria in mice, resulting in a local tumor causing fragmentation of the bone. The tumor-induced osteolysis associated with osteoclasts proliferation was accompanied with reactive new bone formation. This osteolysis was evaluated by measuring the increased area of bone resorption in reduced opacity to radiograph and histologic study. The results showed the following sequence of potency: AHBuBP greater than AHPrBP = HEBP. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumor. The authors conclude that AHBuBP appears to be an interesting new bisphosphonate with possible clinical application.

Alendronate

Urophonographic studies of benign prostatic hypertrophy.

The sonic detection and recording systems of urethral sounds generated during micturition were developed. This procedure was tentatively postulated as "urophonography" and its recording diagram as a "urophonogram". Classification of urophonograms was done on the basis of analyzing normal healthy male volunteers and patients with benign prostatic hyperplasia. Four types of urophonograms were demonstrated according to the shape and characteristics. Types 1, 2, 3 and 4 were characterized by a diamond shape, irregular occurrences of sound spikes, the mixture of Types 1 and 2 and no remarkable sound spikes respectively. Types 1, 2, and 3 were found in BPH, while Type 4 was demonstrated in normal healthy male volunteers. After prostatectomy a high percentage of Type 4 was demonstrated. The frequency (Hz) of these sounds was around 650. Diamond shape sound showed higher value of power gain (dB) than irregular type sound. The wave length was around 0.50 (m). Comparison of urophonographic studies with conventional uroflowmetric investigation was undertaken. Urophonography was useful for investigations of dysfunctional voiding and lower urinary tract obstruction.

Aged