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M Nakada

Publications and source records attributed to M Nakada.

At least 73 records · Page 4Linked to original sources
PubMed1986

Cell kinetics and chemosensitivity of human carcinomas serially transplanted into nude mice.

Six human carcinoma xenografts serially transplanted into nude mice were used for the study of chemosensitivity and cell kinetics. Three gastric carcinomas (St-4, St-40 and H-111), two colon carcinomas (Co-3 and Co-4) and one breast carcinoma (MX-1) were inoculated into the subcutaneous tissue of BALB/cA nude mice. The maximum tolerable doses of mitomycin C (MMC), adriamycin (ADM), cyclophosphamide (CPA) and 5-fluorouracil (5-FU) were administered when the tumor weights reached 100-300 mg. The response rates of the tumor to these drugs were found to be 3/6 for MMC, 2/6 for 5-FU and 1/6 for ADM and CPA. Percent labeled mitosis curves obtained from 3H-thymidine pulse labeling were analyzed by the method of Quastler and Sherman. It was found that the antitumor effect of MMC was closely correlated with the growth fractions of the tumors (r = -0.98, P less than 0.001), and it appeared that the tumor cells were more sensitive to MMC in the resting stages during the proliferating phase than in the other cell cycle phases. Cell kinetics is considered to be an important factor in determining chemosensitivity, and the system of human tumor xenografts-nude mice seems to be a suitable experimental model for investigating the correlation between cell kinetics and chemosensitivity in vivo.

Animals↗
PubMed1985

Biological activities and binding properties of 23,23-difluoro-25-hydroxyvitamin D3 and its 1 alpha-hydroxy derivative.

23,23-Difluoro-25-hydroxyvitamin D3 is 5-10 times less active than 25-hydroxyvitamin D3 in stimulating intestinal calcium transport, bone calcium mobilization, increasing serum phosphorus, mineralization of rachitic bone, and binding to the plasma transport protein in rats. It is converted to 23,23-difluoro-1 alpha, 25-dihydroxyvitamin D3 by chick renal 25-hydroxyvitamin D-1-hydroxylase. This compound is one-seventh as active as 1,25-dihydroxyvitamin D3 in binding to the chick intestinal receptor for 1,25-dihydroxyvitamin D3. Thus, fluoro substitution on carbon-23 of vitamin D has an unexpected and unexplained suppressive action on plasma binding and biological activity. However, since this substitution does not block the biological response of 25-hydroxyvitamin D3, these results provide additional evidence that 23-hydroxylation of vitamin D is not involved in biological function.

Animals↗
PubMed1985

Molybdate and the 1,25-dihydroxyvitamin D3 receptor from chick intestine.

The nature of the 1,25-dihydroxyvitamin D3 receptor from chick intestine was examined in regard to its response to sodium molybdate. Sodium molybdate (10 mM) stabilized the receptor from crude nuclear extract but not that from the supernatant or cytoplasmic fraction, suggesting the molybdate may act by binding to the DNA binding region of the receptor. At a concentration of 50 mM, sodium molybdate prevented aggregation of the nuclear receptor. This concentration of sodium molybdate also inhibited the receptor from binding to DNA cellulose while the same ionic strength KCl (90 mM) did not. These properties also suggest that molybdate interacts with the DNA binding region. Purification of the receptor using DNA cellulose chromatography has also been improved by using a sodium molybdate gradient (0-0.2 M) instead of the KCl gradient used previously.

Animals↗
PubMed1985

Significance of preoperative use of ultrasonography in parathyroid neoplasms: comparison of sonographic textures with histologic findings.

The sonographic textures of 10 parathyroid tumors in nine patients were examined and compared with their histologic features, particularly with the amount of fibrous trabeculae. The carcinomas containing a large amount of fibrous trabeculae, which is the most frequent finding in parathyroid cancer, were very echogenic. On the other hand, the adenomas without fibrous trabeculae showed a low echogenicity. These data suggest that the possibility of malignancy is high when the parathyroid tumor is found to be very echogenic.

Adenoma↗
PubMed1985

The appearance of 1,25-dihydroxyvitamin D3 receptor during chick embryo development.

The appearance of the 1,25-dihydroxyvitamin D3 receptor in intestine, kidney, and chorioallantoic membrane of chick embryo was followed by sucrose density gradient sedimentation analysis and Scatchard plot analysis. The receptor from each of these organs sediments as a single 3.7S component. At 19 days of embryonic life, intestine had the highest specific 1,25-dihydroxyvitamin D3 binding activity followed by kidney and chorioallantoic membrane. The 1,25-dihydroxyvitamin D3 binding activity increased gradually at 12-15 days and rapidly until 20 days in intestine. In kidney, this protein increased rapidly from 12 to 16 days and did not change subsequently. In chorioallantoic membrane, the receptor increased slowly from 8 through 15 days, rapidly until 19 days, and decreased at 20 days. The injection of hydrocortisone into the chick embryo at 10 days increased receptor number in intestine, kidney, and chorioallantoic membrane by a factor of 2 at 12 days. Injection of this hormone after this time had little or no effect.

Allantois↗
PubMed1985

Difference in arginine vasopressin responsive cAMP production between apical and basolateral membrane of cultured renal epithelial cells (MDCK).

It has been reported that vasopressin (AVP)-sensitive renal epithelial cell line (MDCK) forms morphologically polarized monolayers when cultured on plates. We studied whether the AVP-responsive cAMP production system would be located solely on the basolateral surface of these cells as has already been shown on the renal tubules. We used two methods to overcome the inaccessibility to the basolateral surface of the cultured cell layer and to study the apical and basolateral surfaces separately. One was culture on collagen sheet and the other was on Millipore filters. Our experiments showed that MDCK cell increased adenosine 3':5'-cyclic monophosphate (cAMP) content prominently only when vasopressin was accessible to the basolateral surface. Accordingly, MDCK cells were shown to have the AVP-responsive cAMP production system predominantly on the basolateral surface of the cell membrane.

Animals↗
PubMed1985

Calcitonin-responsive clonal cell line from porcine kidney (PK(15)) in serum-free medium.

PK(15), a homogeneous epithelial cell line from porcine kidney which was originally established through single cell cloning from PK-2a, was found to respond to [Asu1,7]eel calcitonin with an increase in adenosine 3':5'-cyclic monophosphate (cAMP) content, but do not respond to parathyroid hormone or arginine vasopressin. These cells were able to grow in a synthetic medium (a 1:1 mixture of Dulbecco's modified Eagle's MEM and Ham's F12 medium) without any supplementary factor. The medium supplemented with selenous acid, transferrin, and insulin permitted a growth rate equivalent to those in serum containing medium. When grown in the serum-free defined medium, these cells showed an increase in cAMP content in response to [Asu1,7]eel calcitonin to approximately the same degree as in the serum containing medium (10% fetal calf serum). Our present study first indicates that PK(15) cells are capable of growing in the serum-free defined medium retaining the calcitonin responsiveness of the original cells.

Alkaline Phosphatase↗
PubMed1985

Calcitonin stimulation of cyclic adenosine 3':5'-monophosphate production with growth inhibition in human renal adenocarcinoma cell lines.

Responsiveness of cyclic adenosine 3':5'-monophosphate (cAMP) to parathyroid hormone, calcitonin, and vasopressin was studied in six human renal adenocarcinoma cell lines. Four of six renal adenocarcinoma cell lines showed increased cAMP content in response to calcitonin while the other two did not. Neither parathyroid hormone nor vasopressin increased the concentration of cAMP in each of these cell lines. The growth rate of KU-2 cells, which responded to calcitonin with an increase of cAMP content, was inhibited by calcitonin. On the other hand the growth rate of calcitonin-nonsensitive KH-39 cells was unaltered. The growth inhibitory effect of the hormone on KU-2 cells could be considered to be mediated by the increased cAMP levels from the following results: (a) there was positive correlation between the cellular cAMP content and growth inhibition after various amounts of calcitonin addition; (b) KU-2 growth was also suppressed by N6,O2'-dibutyryl cAMP; and (c) a group of KU-2 cells which had become resistant to calcitonin-induced growth inhibition showed a diminished cAMP increase in response to calcitonin.

Adenocarcinoma↗
PubMed1985

[Cell kinetics of human lung small cell carcinomas transplanted into nude mice].

Three human lung small cell carcinoma (SCC) xenografts serially transplanted into BALB/c nude mice were used for cell kinetic analysis. SCC strains, Lu-24, Lu-130 and Lu-134, were inoculated into the backs of nude mice, and when each tumor reached more than 300 mg, 50 microCi of 3H-thymidine per mouse was administered ip. The percentage labeled mitosis curve was obtained from the autoradiographic specimens which were labeled by the pulse-chase method. Cell cycle phase, growth fraction (GF) and cell loss factor (CL) were assessed by the methods of Quastler, Fujita and Steel, respectively. These cell kinetic parameters were compared with those of six control human gastrocolic and breast carcinoma xenografts which were previously reported by us. It was noticed that the cell cycle times (Tc) of SCC were statistically shorter than those of controls and this short Tc was found to be dependent on their short post-mitotic resting phases. GFs and labeling indices of SCC were observed to be statistically lower than those of controls, suggesting an incomplete adaptation of SCC xenografts to the host nude mice. Whereas some modifications by the host mice on the cell kinetics were supposed, the characteristics of SCC cell kinetics were thought to be essentially preserved in nude mice and these kinetic parameters were observed to be stable throughout the serial transfers. Accordingly, the SCC xenograft-nude mouse system was considered to be useful as an experimental therapeutic model of human lung small cell carcinomas.

Animals↗
PubMed1984

Subcellular distribution of DNA-binding and non-DNA-binding 1,25-dihydroxyvitamin D receptors in chicken intestine.

A comparison of 1,25-dihydroxyvitamin D3 receptor concentration and equilibrium dissociation constants of whole tissue, nuclear, and cytosol extracts of vitamin D-deficient chicken intestine has been carried out. The extracts had the following order of receptor concentration: nuclei greater than whole tissue greater than cytosol. The receptors in each preparation had identical equilibrium dissociation constants (Kd) for 1,25-dihydroxyvitamin D3. However, the receptor in the cytosol fraction did not bind to DNA-cellulose, while a large fraction of the receptor population in crude nuclear extract and whole tissue extract bound to DNA-cellulose and could be eluted with 0.22 M KCl, suggesting that the cytosolic form of the receptor does not possess a DNA binding site.

Animals↗
PubMed1984

[Chemosensitivity to mitomycin C and cell kinetics of human tumor xenografts serially transplanted into nude mice].

Different chemosensitivity to mitomycin C (MMC) and cell kinetics were studied by using human tumor xenografts serially transplanted into nude mice. Two gastric adenocarcinomas (St-4; poorly differentiated, St-40; well differentiated) and two colon adenocarcinomas (Co-3; well differentiated, Co-4; poorly differentiated) were transplanted into the back of BALB/c nude mice subcutaneously. Three mg/kg of MMC was administered, q4d X 3, intraperitoneally. The effect of MMC in vivo was evaluated according to the protocol of Battelle Memorial Institute. The primary cultured tumor cells of the same strains were used for the chemosensitivity test in vitro, and the effect of MMC in vitro was tested by the inhibition rate of 3H-thymidine (3H-TdR) incorporation to cancer cells. Cell kinetics were analyzed by percent labeled mitosis curves obtained from 3H-TdR pulse labeling in vivo and by 3H-TdR incorporation to cancer cells in vitro. Although MMC suppressed the growth of St-40 and Co-4, it was found that St-4 and Co-3 were less sensitive to MMC in vivo. St-4, St-40 and Co-4 were observed to be sensitive to MMC in vitro. Growth fractions of transplanted tumors in vivo were correlated well to the chemosensitivity to MMC with statistical significance. St-4, which was insensitive to MMC in vivo and sensitive in vitro, showed low growth fraction in vivo and increased 3H-TdR incorporation in vitro, suggesting the recruitment of G0 cells to growth fraction in vitro. The chemosensitivity of 4 tumors to MMC was revealed to be correlated well to each growth fraction in vivo and in vitro.

Adenocarcinoma↗
PubMed1983

[Effect of chemotherapy on the interstitial tissue of a malignant human tumor transplanted into nude mice, with reference to microvessels].

Experimental chemotherapy of cyclophosphamide (CPA) was performed on a human malignant hemangiopericytoma serially transplanted into nude mice with a genetic background of BALB/c and the changes or histological findings and microangiograms (MAG) were investigated. The treatment was performed 2 weeks after tumor inoculation. Either 120 mg/kg or 240 mg/kg of CPA, dissolved in 0.2 ml of physiological saline, was administered once intraperitoneally. On days 1, 2, 4 and 7 after the treatment, mice were sacrificed and each tumor was examined in terms of histological findings and MAG. Although the tumors treated with 120 mg/kg of CPA were suppressed temporarily, the regrowth of the tumors were observed. The tumors treated with 240 mg/kg of CPA regressed without any regrowth. From the observations of MAG, the former showed an avascular area on day 4 after the treatment and the tumor vessels regenerated on day 7 after the treatment. On the other hand, in the latter group, it was found that the normal vascular network developed after the formation of an avascular area 2 days after the treatment. From the histological findings, the former showed to reduce mitotic indeces of 1 or 2 days after the treatment, however the mitotic indeces were found to recover 7 days after the treatment. Mitotic indeces of tumors treated with 240 mg/kg of CPA were observed to be depressed after the treatment. These results suggested that the changes of interstitial tissue were closely correlated well with the destruction and regrowth of tumor cells observed by the growth curve and histological findings. Tumor vessels were thought to play an important role in the cancer chemotherapy, not only as the transport systems of drugs but also as the target of antitumor agents.

Animals↗