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Biomedical subjects

N Miyoshi

Publications and source records attributed to N Miyoshi.

At least 91 records · Page 5Linked to original sources

Hormone-dependent changes of blood vessels in DMBA-induced rat mammary carcinoma and its regression studied by 3H-thymidine autoradiography.

Using DMBA-induced rat breast cancer, the changes in the histology and proliferative activity underlying the phenomenon of tumor regression by hormone therapy were studied by 3H-thymidine autoradiography. The control tumor was found to essentially consist of two histologically different areas, medullary (A area) and tubular or cystic (B area). The cancer cells in the A area were homogeneously proliferating with a cell cycle time of 51h, and among those in the B area, 65% were proliferating with a cell cycle time of 81h while 35% were non-proliferating. Among the various-kinds of hormone therapies, ovariectomy plus male sex hormone administration was most effective in inducing tumor regression. In the regressed tumor, the A area was greatly diminished due to central necrosis and replaced by cystic B area. In the remaining A area, the cell cycle time was lengthened to 97h, and that for the proliferating cells in the B area was as long as 118h. The most striking histological change after ovariectomy plus male sex hormone administration was the diffuse necrosis of the capillary endothelial cell within 24h, followed by hemorrhage, central necrosis in the A area (1W), and final stage of fibrosis (2W). The tumor administered with female sex hormone after ovariectomy showed a rebound growth from the regression, due to the initial reactivation of the endothelial cell proliferation and following stimulation of cancer cell mitotic activity. From these observations, it is concluded that the capillary endothelial cells in DMBA-induced rat breast cancer are estrogen dependent, and that the tumor regression induced by decreased estrogen-level is attributable to the massive necrosis from capillary insufficiency and anoxia.

9,10-Dimethyl-1,2-benzanthracene↗

Computer analysis of sub-parameters of depurination and depolymerization rate constants in Feulgen DNA hydrolysis.

Feulgen DNA hydrolysis curves derived from cytofluorometry at various temperatures and HCl concentrations were computer analyzed with least squares fit to Bateman function. By comparing the depurination (k1) and depolymerization (k2) rate constants at different hydrolysis conditions, it was found that the two parameters of temperature and HCl concentration can be expressed as k = AN2 X exp (-B/T), where A and B are constants, N is the HCl concentrations, and T is the absolute temperature. From the analysis of Feulgen hydrolysis curves with 2N HCl at various temperatures, it was calculated that A = 5.3590 X 10(14) and B = 12133.543, for k1, and A = 6.2401 X 10(14) and B = 12181.660, for k2 for mouse 4C hepatocytes fixed with absolute methanol. Computer generated theoretical hydrolysis curves using the above k1 and k2 values were compared with experimental curves at various temperatures and HCl-concentrations. The two types of hydrolysis curves coincided with each other when 1-3 N HCl was used at temperatures between 30-40 degrees C. The peak times of hydrolysis curves at different conditions determined by experimental analysis and theoretical estimations also coincided reasonably well with each other. The physico-chemical phenomena underlying the equation designating k1 and k2 values are discussed.

Animals↗

Cellular uptake of hematoporphyrin derivative in KK-47 bladder cancer cells.

The fluorescence emission spectra and degree of fluorescence polarization of hematoporphyrin derivative (HpD) have been investigated using HpD-containing KK-47 cells, PBS and cetyl trimethyl ammonium chloride (CTAC) micellar solutions. The fluorescence emission bands in the HpD-containing cell suspension were red-shifted and broadened as compared to those in the PBS solution. The degree of the polarization in the PBS and CTAC micellar solutions did not change with increasing incubation time, but in the cell suspension it increased temporarily and then decreased 4 h after incubation. These results suggest that HpD monomers and dimers may bind weakly to the outer cell membrane, and then slowly distribute throughout the intracellular loci in strong-binding form. In addition, the cellular uptake and/or binding loci of HpD were considered to be the mitochondria and nuclear membrane by subcellular fractionation and fluorescence microscopic studies.

Cell Line↗

Whole bladder wall photoradiation therapy for carcinoma in situ of the bladder: a preliminary report.

Whole bladder wall photoradiation therapy, using a hematoporphyrin derivative as a sensitizer, the red light (wavelength 630 plus or minus 1.6 nm.) of an argon dye laser as the source of excitation energy and a motor driven laser light scattering optic, was performed in 2 patients with multicentric carcinoma in situ of the bladder. The total light dose was 10 J. per cm.2. Acute vesical inflammatory changes developed in the bladder wall lining, associated with a reduction of bladder capacity, which, however, disappeared within 3 months after photoradiation therapy. The anticancer effect of photoradiation therapy was followed by urinary cytologic and cystoscopic examinations for 4 months. Occasional discharges of clusters of vacuolated cancer cells or sheets of vesical detached cells in the urine were observed for 2 weeks after photoradiation therapy but, thereafter, repeat urinary cytologic and cystoscopic examinations revealed no malignancy.

Adult↗

Photoradiation therapy of bladder tumours.

Photoradiation therapy (PRT), in which hematoporphyrin derivative (HpD) is activated by an argon-dye laser, was used on 46 superficial bladder tumours in 9 patients. It was suggested that there is little or no thermal cell killing effect of laser irradiation from study of the heating effect of the beam intensity. A fluorospectrophotometric study of biopsies from these tumorus and normal mucosa revealed preferential HpD localization in the malignant tissues. In tumours less than 1 cm diameter treated with 150 mwatts per cm2 for 5 minutes there were 2 CR and 5 NC, whereas with 200 mwatts per cm2 or more for the same time there were 15 CR and 5 PR. Concerning the accumulated energy intensity of the light, in tumours 1 cm in size or less, treatment with 100-250 joules per cm2 obtained CR in 5 of 6 tumours. From these results, it was suggested that the light intensity should be 300 mwatts per cm2 for 5-10 minutes or more and the total light dose should be 100 joules per cm2 or more in tumours up to 2 cm in size. There was no CR in tumours more than 2 cm in size. No early side effects were seen from the administration of HpD. Sensitivity to sunlight was seen in 4 cases.

Aged↗

A trial manufacture of a motor-driven laser light scattering optic for whole bladder wall irradiation.

The detection of CIS of the bladder by fluorescence endoscopy with hematoporphyrin derivative (HpD) and argon ion laser was performed using a video monitoring system coupling with an image intensifier; however, it was difficult because of the reflecting light of the excitation light. Whole bladder wall photoradiation therapy was carried out in 3 patients with multicentric CIS of the bladder, using argon-dye laser light (630 +/- 1.6 nm) of 5 to 25 J/cm2. The anticancer effect of this therapy was followed by urinary cytology and clusters of vacuolated cancer cells were observed for 2 days after the therapy.

Carcinoma in Situ↗

Cellular binding of hematoporphyrin derivative (HpD) in human bladder cancer cell line: KK-47.

In vitro cellular uptake or binding of hematoporphyrin derivative (HpD) was investigated by comparing the optical properties; absorption spectra, fluorescence spectra, fluorescence lifetime and fluorescence polarization, of HpD in KK-47 cells derived from a human bladder carcinoma, organic and micellar solutions. In addition, the relationship between the mode of cellular HpD uptake and photodynamic cellular inactivation by argon-dye laser was studied using a clonogenic assay system. HpD molecules may weakly bind to the cell membrane within approximately 2 hrs after incubation in HpD-containing medium, and then major HpD molecules may slowly be distributed throughout the cytoplasm as a dimer form for 4 hrs after incubation in HpD-free medium. The intracellular binding loci were found to be the mitochondria and nuclear membrane by subcellular fractionation and fluorescence microscopic studies. The loci may be relatively hydrophilic on the basis of the polarity-dependence data on the fluorescence polarization. An exponential cellular photoinactivation curve was observed in relation to increasing concentrations of HpD and to intracellular strong-binding of dimeric HpD.

Cell Line↗

Photoradiation therapy of bladder tumors.

Photoradiation therapy (PRT), in which hematoporphyrin derivative (HpD) is activated by an argon-dye laser, was performed on 46 superficial bladder tumors in 9 patients. It was suggested there is little or no thermal cell killing effect of laser irradiation from a study of the heating effect of the beam intensity. A fluorospectrophotometric study of biopsies from tumors and normal mucosa revealed preferential HpD localization in malignant tissues. In tumors less than 1 cm in diameter treated with 150 mwatts per cm2 for 5 minutes there were 2 with complete remission (CR) and 5 with no change (NC), whereas with 200 mwatts per cm2 or more for the same time there were 15 CR and 5 with partial remission (PR). Concerning the accumulated energy intensity of light, in tumors 1 cm in size or less, treatment with 100-250 joules per cm2 obtained CR in 5 of 6 tumors. From these results, it was suggested that the light intensity should be 300 mwatts per cm2 for 5-10 minutes or more and the total light dose should be 100 joules per cm2 or more in tumors up to 2 cm in size. There was no CR in tumors more than 2 cm in size. No early side effects were seen from administration of HpD. Sensitivity to sunlight was seen in 4 cases.

Cystoscopy↗