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Biomedical subjects

S Noguchi

Publications and source records attributed to S Noguchi.

At least 541 records · Page 30Linked to original sources

Degradation of a cAMP-binding protein is inhibited by human c-Ha-ras gene products.

Incubation of the particulate fraction of cell extract prepared from NIH3T3 mouse fibroblasts resulted in preferential proteolytic degradation of a cAMP-binding protein. The proteolysis was inhibited by human c-Ha-ras gene products produced by Escherichia coli. The proteolysis was observed at pH 6 to 7, and inhibited by antipain and leupeptin. These results suggest that cAMP-binding proteins might be cleaved by thiol proteinases. In fact, c-Ha-ras gene products were proved to inhibit the cathepsin B-like activity present in the particulate fraction.

Animals↗

c-Ha-ras gene products are potent inhibitors of cathepsins B and L.

c-Ha-ras proteins produced by Escherichia coli inhibited the activities of cathepsins B and L which had been partially purified from rat kidney. Furthermore, amino acid sequence homology between c-Ha-ras proteins and thiol proteinase inhibitors has been found.

Amino Acid Sequence↗

Growth-stimulating effect of pharmacological doses of estrogen on androgen-dependent Shionogi carcinoma 115 in vivo but not in cell culture.

Shionogi carcinoma 115 (SC115) had been accepted for 20 years as an androgen-dependent mouse mammary tumor, the growth of which is stimulated only by androgen. However, we very recently found that the growth of SC115 tumors in vivo is stimulated not only by physiological doses of androgen but also by pharmacological doses of estrogen through the estrogen receptor system. In the present study, the growth-stimulative effect of estrogen on an androgen-dependent cloned cell line (SC-3) derived from SC115 cells, which showed androgen- and estrogen-dependent growth in vivo, was examined in vitro. In serum-supplemented medium (Eagle's minimum essential medium containing 2% steroid-free fetal calf serum), testosterone or 5 alpha-dihydrotestosterone (10(-9)-10(-6) M) significantly stimulated the growth of SC-3 cells (3.2-fold increase in cell number at day 10 in culture containing 10(-8) M androgens) and changed the shape of SC-3 cells from epithelial to spindle (fibroblast-like), whereas 17 beta-estradiol (10(-12)-10(-6) M) even in high concentrations had no such effects on SC-3 cells. Contrary to the effect of 17 beta-estradiol in vivo, 17 beta-estradiol as well as cyproterone acetate (10(-8)-10(-6) M) inhibited the growth-stimulative effect of testosterone (10(-8) M) on SC-3 cells in a dose-dependent manner in the serum-supplemented medium. The anti-androgen and 17 beta-estradiol also showed comparable competitive effects on [3H]testosterone binding to androgen receptor in SC-3 cells. In serum-free medium [Ham's F-12:Eagle's minimum essential medium (1:1, v/v) containing 0.2% bovine serum albumin], testosterone [10(-8) M] also markedly stimulated the growth of spindle-shaped SC-3 cells, and epidermal growth factor (1 ng/ml) enhanced the growth-stimulative effect of testosterone, whereas 17 beta-estradiol (10(-8)-10(-6) M) in the absence or presence of epidermal growth factor had no growth-stimulative effect on SC-3 cells. We conclude that the growth of SC115 cells is stimulated by either physiological doses of androgen or pharmacological doses of estrogen in vivo but only by androgen in cell culture.

Androgens↗

Preoperative doxorubicin instillation in recurrent superficial bladder cancer.

Further recurrence of superficial bladder cancer after transurethral resection is frequent in patients who have already experienced recurrence. In an attempt to prevent or delay further recurrences in such patients, the effect of preoperative doxorubicin instillation was investigated. A total of 51 patients with recurrent superficial bladder cancer were randomized to receive either TUR alone or TUR with preoperative doxorubicin instillation. Doxorubicin was administered twice a week for 3 weeks before TUR surgery. An objective response (CR + PR) of the tumors was observed at operation in 12 of 25 (48%) evaluable doxorubicin-treated patients. Chemical cystitis was seen in 32% of the patients. Further recurrence after TUR was observed in 13 of 25 (52%) patients in the doxorubicin group, as against 15 of 23 (65%) evaluable patients in the control group. The mean disease-free interval was significantly longer (11.8 as against 7.1 months) in the doxorubicin group. These preliminary results suggest that preoperative doxorubicin instillation might be effective for prolongation of the disease-free interval in patients with recurrent bladder cancer.

Administration, Intravesical↗

Action mechanisms of physiological doses of androgen or pharmacological doses of estrogen in growth stimulation of Shionogi carcinoma 115 in mice.

Shionogi carcinoma 115 (SC115) had been accepted for 20 yr as an androgen-dependent mouse mammary tumor. However, we recently found that the growth of SC115 tumors in vivo is also stimulated by pharmacological doses of estrogen through estrogen receptor. In the present study, action mechanisms of androgen or high doses of estrogen in the growth stimulation of SC115 were examined using a cloned cell line (SC-3) derived from the SC115 tumor. In serum-supplemented [2% steroid-free fetal calf serum-Eagle's minimum essential medium (MEM)] and serum-free [HAM F-12: MEM (1:1, v/v) containing 0.1% bovine serum albumin] media, testosterone (Test, 10(-9)-10(-6) M) significantly increased both cell number and DNA synthesis of SC-3 cells (by up to 10-fold), whereas oestradiol-17 beta (10(-12)-10(-6) M) had no such effects; the Test-induced growth was completely inhibited by the addition of a 100-fold molar excess of cyproterone acetate (CA). The serum-free medium cultured with SC-3 cells in the presence or absence of 10(-8) M Test was collected [conditioned medium (CM) or conditioned medium without Test (CM-)], and then Test in CM was removed by Gel filtration using Sephadex G-100 or inactivated by the addition of a 100-fold molar excess of CA. In the serum-free culture system, the addition of the CM without Test activity significantly enhanced both number of SC-3 cells and DNA synthesis in the cells, whereas CM(-) had no such effects. The present findings suggest that growth-stimulatory activities of androgen and high doses of estrogen on SC115 cells are mediated by growth factor(s), secreted from SC115 cells through androgen receptor and from some of nontransformed cells through estrogen receptor, respectively.

Animals↗

The value of lymph-node dissection in patients with differentiated thyroid cancer.

The perithyroidal and ipsilateral cervical lymphatic system not only is commonly involved by thyroid cancer but also is a common site of recurrence. Modified radical neck dissection, with preservation of the sternocleidomastoid muscle and spinal accessory nerve, is the treatment of choice for patients with clinically evident lymph node metastases due to differentiated thyroid cancer. It is also recommended, by us, for patients over 40 years of age who have primary thyroid tumors greater than 1.5 cm in size whether or not nodes are clinically palpable. This is because at least 75 per cent of these patients have metastases, and their discernment at operation is unreliable. With more aggressive surgery, the recurrence-free survival rate can be improved substantially without cosmetic deformity or postoperative dysfunction.

Age Factors↗

Loss of intracellular peroxidase and anaplastic change of differentiated carcinoma of human thyroid gland.

Ultrastructural localization of endogenous peroxidase (peroxidase) in differentiated thyroid carcinoma was studied in 2 cases of follicular carcinoma and 12 of papillary carcinoma. The reaction product for the enzyme was observed in cancer cells which had a round and smoothly-contoured nucleus and rather few number of microvilli (positive cells) and the product localized mainly in the rough-surfaced endoplasmic reticulum and perinuclear cisternae. The positive cells resembled normal follicular cells in localization sites of the reaction product and ultrastructural features. On the contrary, in cancer cells having an irregularly-outlined nucleus with or without intranuclear cytoplasmic inclusion and many microvilli, no reaction product was visualized (negative cells). The positive cells were frequently found in 2 follicular carcinomas and 2 papillary carcinomas. Only a few number of positive cells presented in 2 papillary carcinomas. The remaining 8 papillary carcinomas were composed only of negative cells. Histologically, follicles with colloid were frequently found in carcinomas with abundant positive cells, whereas they were few in number in carcinomas containing only negative cells. These findings suggest that loss of peroxidase activity in cancer cells of follicular cell origin correlates with anaplastic change of the cancer cells.

Carcinoma↗

Ultrastructural localization of endogenous peroxidase activity in benign thyroid diseases.

Ultrastructural localization of endogenous thyroid peroxidase under benign pathological conditions such as toxic diffuse goiter, non-toxic multinodular goiter, and adenoma, and in normal tissue was studied. Peroxidase activity was visualized by a cytochemical reaction for electron microscopy. In toxic diffuse goiters and most non-toxic multinodular goiters, reaction product for peroxidase was observed not only in the cytoplasm but also at the external surface of microvilli of follicular cells. In normal thyroid tissues and adenomas, peroxidase was visualized only in the cytoplasm. Peroxidase activity at the external surface of microvilli of the follicular cells was found in the tissues obtained from the goiters which showed "hot" radioiodine scintigram. These findings suggest that follicles with peroxidase activity at the external surface of microvilli in non-toxic multinodular goiter are "autonomous follicles" and that peroxidase at the external surface of microvilli plays some role in active iodine uptake.

Adenoma↗

Temporal increase of two proteins in PC-12 pheochromocytoma cells induced by nerve growth factor.

Two-dimensional gel electrophoresis revealed two protein spots, a (molecular weight 70,000, pI 4.6) and b (molecular weight 69,000, pI 4.4) in PC-12 cells (rat pheochromocytoma cells). When the cells were induced to differentiate with nerve growth factor, the amount of protein in spot a, and later spot b increased with time, then the amount in both spots gradually decrease to undetectable level. These spots were not detected in adult rat brain nor in other cell lines of rat and mouse. Thus, these proteins can be used as markers to follow the differentiation of PC-12 cells.

Animals↗

Human serum thyroglobulin determination with monoclonal antibody one-step assay: minimum interference of autoantibody.

Combination of two thyroglobulin monoclonal antibodies (monoAbs) recognizing epitopes which are rarely recognized by an antibody enabled us to develop a rapid one-step enzyme immunoassay of serum Tg. Of 87 monoclonal antibodies, 20 were selected for the purpose. The method is a sandwich technique employing a monoAb covering microplate and horse-radish peroxidase monoAb conjugate. A combination of monoAb 7A7A solid phase and 31A2E for the conjugate gave the best results. The assay takes 60 min and the minimal detectable amount is 2 ng/ml. Intraassay variation is from 4 to 7%. Interassay variation is 5 to 12%. The recovery rate for Tg added to normal sera is between 89 and 111%. The correlation coefficient with the polyclonal antibody method in Tg hemagglutination negative sera is 0.98. The presence of autoantibody in sera up to 10 X 2(4) hemagglutination titer does not affect the recovery rate to a statistically significant extent.

Antibodies, Monoclonal↗

[Hormone therapy--recent advances].

Inhibitory effects of hormone therapy on the growth of cancer can be found only in cancers whose growth is stimulated by hormones. Among the various kinds of steroid-or peptide-dependent (or responsive) tumors, estrogen-dependent breast and endometrial cancers and androgen-dependent prostate cancer have been shown to have high incidences. Therefore, the suppression or disappearance of the production or action of estrogens or androgens has been used as a common form of hormone therapy. Although surgical therapies such as removal of the ovaries, adrenals, hypophysis or testes have been used as the major hormone therapies, medicinal therapies such as the administration of antiestrogen, aminoglutethimide, medroxyprogesterone acetate, antiandrogen and/or high doses of LHRH have recently become the major types of hormone therapy. Fortunately, hormone therapy produces very few side effects compared with various other therapies for cancer. However, hormone therapy has been shown to be effective only in 30% of breast cancers or endometrial cancers, and 70% of prostate cancers. Furthermore, loss of hormone dependency generally occurs during hormone therapy. Therefore, useful methods for the growth inhibition of hormone-independent recurrent tumors should be developed. Various kinds of chemotherapies combined with hormone therapies have recently been used. Although these chemoendocrine therapies have resulted in an increase in response rate, overall survival has not been significantly improved in comparison with endocrine therapy alone. Since recent findings have shown that the growth of sex steroid-dependent cancer is mediated by sex steroid-induced growth factor (s) secreted by the cancer cells(autocrine control), suppression of the production or action of such growth factor (s) should be investigated as a future form of endocrine therapy; a loss of hormone dependency might occur through the production of such growth factor (s) without hormone stimulation.

Breast Neoplasms↗

Both androgen and glucocorticoid induce identical secretory proteins in serum-free culture of Shionogi carcinoma 115 cells.

The effects of androgen or glucocorticoid on the induction of secretory proteins in SC-3 cells (a cloned cell line from Shionogi carcinoma 115) were examined in a serum-free medium [Ham's F-12: Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin]. Through analysis of [35S]methionine-labeled proteins by one-dimensional (sodium dodecyl sulfate polyacrylamide) gel electrophoresis, we successfully demonstrated the production of a testosterone (10(-9)-10(-6) M)- or dexamethasone (10(-8) M)-induced secretory protein with a molecular weight of 24,000 in SC-3 cells. However, 17 beta-estradiol (10(-8) M) or progesterone (10(-8) M) had no such effect. The production of the secretory 24K protein increased slightly within 2 hr after the addition of 10(-8) M testosterone and increased further thereafter. The addition of tunicamycin to the incubation mixture with [35S]methionine resulted in the identification of a testosterone- or dexamethasone-induced secretory protein with a molecular weight of 20,000. By the use of two-dimensional gel electrophoresis, we could demonstrate that both testosterone (10(-8) M) and dexamethasone (10(-8) M) added to the serum-free medium stimulate the secretion from SC-3 cells of the same 5 proteins (30-40K, 39K, 30K, 27K proteins and the secretory 24K glycoprotein). The present findings show that physiological concentrations of both androgen and glucocorticoid induce the secretion of the same 5 proteins from SC-3 cells.

Animals↗

Low-dose irradiation to head, neck, or chest during infancy as a possible cause of thyroid carcinoma in teen-agers: a matched case-control study.

A matched case-control study was performed to identify the etiologic factors for thyroid carcinoma in teen-agers. Twenty-seven cases and 69 controls were investigated to assess the significance of various maternal and subject factors. Irradiation during infancy was the only factor which showed a statistically significant association with the incidence of thyroid cancer in teen-agers (summary X2 = 8.040; d.f. = 1; P less than 0.005). The estimated dose ranged from 0.2 to 40 rads on the head, neck, or chest during infancy.

Female↗

Monoclonal antibody highly sensitive for the detection of ras p21 in immunoblotting analysis.

Four murine monoclonal antibodies (NCC-RAS-001, -004, -005, -017) reactive with ras p21 were produced by using recombinant c-Ha-ras p21 as an immunogen. Among these antibodies, NCC-RAS-004 was extremely sensitive when used in immunoblotting analysis, facilitating semiquantitative detection of c-Ha-, c-Ki- and N-ras p21 in cell and tissue lysates. In cells carrying a point-mutationally activated ras, p21 with abnormal mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis was clearly detected.

Antibodies, Monoclonal↗