Biomedical subjects

T Hida

Publications and source records attributed to T Hida.

At least 73 records · Page 4Linked to original sources

PubMed1996

PACAP stimulates c-fos mRNAs in small cell lung cancer cells.

The effects of PACAP on c-fos mRNA using small cell lung cancer (SCLC) cell was investigated. PACAP-27 (100 nM) increased c-fos mRNA 5-fold using NCI-N417 cells. The increase was concentration dependent with 0.1 nM PACAP-27 half maximally increasing c-fos mRNA. Also the increase in c-fos mRNA caused by PACAP was time dependent; being maximal after 1 hour and returning to basal values after 4 hours. PACAP-38 but not PACAP(28-38) increased c-fos mRNA. One uM PACAP(6-38), a PACAP receptor antagonist, inhibited the increase in c-fos mRNA caused by 1 nM PACAP. These data indicate that PACAP stimulates nuclear oncogene expression in SCLC cells.

Carcinoma, Small Cell↗

PubMed1996

Modification of chemo-radiosensitivity of a human lung cancer cell line by introduction of the glutathione S-transferase pi gene.

Recent studies have suggested that glutathione S-transferase pi (GST-pi) may play a role in determining tumor sensitivities to cytotoxic drugs. In order to better understand the role of this enzyme in chemo- and/or radioresistance of lung cancer cells, we examined whether introduction of GST-pi cDNA into a chemo- and radiosensitive lung cancer cell line altered its sensitivities to various chemotherapeutic agents and/or ionizing radiation, which are often used in the management of lung cancers. Modestly increased resistance of the GST-pi transfectants preferentially to sublethal damage caused by ionizing radiation as well as to adriamycin (ADM) was observed. In contrast, resistances to cisplatin (CDDP), etoposide (VP-16), irinotecan hydrochloride (CPT-11) and paclitaxel were virtually unaltered. These results suggest that GST-pi may not play a major role in chemo- and radioresistance of lung cancers, although it could afford selective and limited protection against ADM- and ionizing radiation-induced damage.

Antineoplastic Agents↗

PubMed1996

[Vitrectomy in Coats' disease].

Four eyes of four patients with Coats' disease underwent vitrectomy because of exudative or tractional detachments involving the macula or premacular fibrosis. All cases had gelatinous vitreous and had no complete posterior vitreous detachment. The exudates decreased and the retina reattached after removing vitreous traction and coagulating abnormal vessels with endodiathermy and not removing subretinal fluid in 3 eyes with retinal detachment. In one eye with tractional detachment, retinal breaks were found beneath the proliferative membrane during the initial vitrectomy procedure. This eye needed multiple operations because of recurrent traction by the remaining peripheral vitreous. Exudation into the vitreous and vitreous traction may cause mutual progression in these eyes, and vitrectomy is an effective treatment, although there are difficulties in removing vitreous traction completely.

Adolescent↗

PubMed1996

Reduced expression of DNA topoisomerase II confers resistance to etoposide (VP-16) in small cell lung cancer cell lines established from a refractory tumor of a patient and by in vitro selection.

Cell lines, LC-5 and LC-172, were established from tumors of a small cell lung cancer patient prior to and after combination chemotherapy including etoposide (VP-16), when drug-resistant tumors developed in relapse. A VP-16-resistant cell line, LC-172/VP, was selected from the LC-172 cells in culture in multiple steps with VP-16. LC-172 cells were 3.5-fold resistant to VP-16 in growth inhibition, and 3.3-fold resistant to adriamycin as compared with LC-5 cells. LC-172/VP cells showed large differences in cross-resistance to topoisomerase II-targeting drugs such as VP-16, 200-fold, adriamycin, 10-fold, and MST-16, 4.3-fold; the cells were moderately refractory, 5.5-fold, to vincristine. VP-16 accumulation in the cells was similar in three cell lines. Topoisomerase II unknotting activity was reduced 7- to 10-fold in LC-172/VP and 1.5- to 2-fold in LC-172 cells compared with LC-5 cells, while relaxing activity of topoisomerase I appeared to be unchanged. Topoisomerase II protein was also reduced 5- to 10-fold in LC-172/VP and marginally so in LC-172 cells. Topoisomerase II alpha and II beta were each reduced 10-fold and 2-fold, respectively, in LC-172/VP cells, while they were both slightly decreased (-1.5-fold), respectively, in LC-172 cells compared with LC-5 cells. No apparent alteration in ATP requirement for catalytic activity and in sensitivity to VP-16 was observed for topoisomerase II from the three cell lines. Taken together, these results suggested that resistance to VP-16 in LC-172 and LC-172/VP is associated with a quantitative reduction in expression of topoisomerase II alpha of the parental type.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

A novel type of retinoic acid receptor antagonist: synthesis and structure-activity relationships of heterocyclic ring-containing benzoic acid derivatives.

A new series of heterocyclic ring-containing benzoic acids was prepared, and the binding affinity and antagonism of its members against all-trans-retinoic acid were evaluated by in vitro assay systems using human promyelocytic leukemia (HL-60) cells. Structure-activity relationships indicated that both an N-substituted pyrrole or pyrazole (1-position) and a hydrophobic region, with these linked by a ring system, were indispensable for effective antagonism. Among the compounds evaluated, optimal antagonism was exhibited by 4-[4,5,7,8,9,10-hexahydro-7,7,10,-10-tetramethyl-1-(3- pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid (31), 4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)-5- thiaanthral[1,2-b]pyrrol-3-yl]benzoic acid (40), and 4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3- pyridylmethyl)anthra[2,1-d]pyrazol-3-yl]benzoic acid (55), all of which possess a 3-pyridylmethyl group at the five-membered ring nitrogen atom.

Benzoates↗

PubMed1995

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↗

PubMed1995

TAN-1323 C and D, new concanamycin-group antibiotics; detection of the angiostatic activity with a wide range of macrolide antibiotics.

We detected potent angiostatic activity in a MeOH extract from the mycelia of microbial strain S-45628 in the chick chorioallantoic membrane (CAM) assay. The producer was taxonomically characterized as Streptomyces purpurascens. Active principles designated TAN-1323 A-D were isolated and determined to be 18-membered macrolide antibiotics; components C and D are new members of this group, while components A and B are identical to concanamycins C and A, respectively. When tested in the CAM assay, components B and D gave huge avascular zones at the extremely low doses of 10-100 ng/disk, although components A and C showed far weaker activity due to their preferential tissue-damaging effect on the CAM. The discovery that these 18-membered macrolide antibiotics are angiostatic substances prompted us to examine other types of macrolide antibiotics, leading to the discovery that 16-membered macrolide antibiotics such as bafilomycin C1, tylosin and leucomycin also show angiostatic activity on the CAM. Thus, angiostatic potential is widely distributed among macrolide antibiotics. The mechanism of action of these macrolide antibiotics is also discussed.

3T3 Cells↗

PubMed1995

TAN-1511 A, B and C, microbial lipopeptides with G-CSF and GM-CSF inducing activity.

The microbial lipopeptides, TAN-1511 A, B and C, were isolated from the culture broth of Streptosporangium amethystogenes subsp. fukuiense AL-23456. Their structures were elucidated on the basis of their reactions and spectroscopic analyses. These lipopeptides were mixtures of molecules having different lengths of fatty acids. The metabolites stimulated the proliferation of bone marrow cells from BALB/c female mice at very low concentrations (concentration giving 30% increase: A and B, 0.313 ng/ml; C, 1.25 ng/ml). We confirmed that chemically synthesized TAN-1511 A analogue [(2R,6R)-2-tetradecanoylamino-6,7- bis(hexadecanoyloxy)-4-thiaheptanoyl-Gly-Gly-Gly-Glu-Thr-Thr -OH] stimulated the proliferation of bone marrow cells in a manner similar to that of natural TAN-1511 A. This analogue induced the secretion of both granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF), and potentiated the generation of Gr-1 positive cells in the bone marrow cell culture. Moreover, it effected the G-CSF mediated restoration of granulocytopoiesis in a murine leukopenia model.

Amino Acid Sequence↗

PubMed1995

Synthesis and biological activities of TAN-1511 analogues.

TAN-1511 analogues were synthesized and their effects on the proliferation of bone marrow cells were examined. To exert potent activity the following conditions are necessary: the configuration of the 2-amino-6,7-dihydroxy-4-thiaheptanoic acid moiety must be (2R,6R), long chain acyl groups (C14 to C18) must be bound to both hydroxyl groups, the amino group must be free or acylated with the long chain fatty acid (ca. C14) and the peptide moiety must have glutamic acid as a component. Among the synthesized compounds, trisodium (2R,6R)-2-amino-6,7-bis (hexadecanoyloxy)-4-thiaheptanoyl glycyl glutamyl glutamate, which has improved solubility, was effective in experimental leukocytopenia in mice.

Amino Acid Sequence↗

PubMed1994

Novel role of vitamin K2: a potent inducer of differentiation of various human myeloid leukemia cell lines.

When myeloblastic ML1 cells were cultured in the presence of Vitamin K2 (menaquinone, VK2), the population of cells capable of reducing NBT increased to 83.5% at low VK2 concentration of 1 microM, indicating VK2 induces cellular differentiation. VK2 also exerted differentiation-inducing action on histiocytic U937 and promyelocytic HL60 cell lines. None of these effects were observed with Vitamin K1 (phylloquinone, VK1), suggesting the geranylgeranyl group of the side chain of VK2 to be essential to these effects. Combinations of VK2 with other differentiation-inducers such as interferon-gamma, retinoic acid, or camptothecin additively or synergistically induced the differentiation of HL-60 cells. These results suggest that VK2 may safely be used in differentiation therapy in combination with other inducers.

Cell Differentiation↗

PubMed1994

Serum glutathione S-transferase-pi level as a tumor marker for non-small cell lung cancer. Potential predictive value in chemotherapeutic response.

BACKGROUND: Resistance to chemotherapeutic agents is a major problem in non-small cell lung cancer (NSCLC) chemotherapy, and recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents that include platinum compound. METHODS: GST-pi in serum of 121 patients with NSCLC was measured by a sandwich enzyme-linked immunosorbent assay, and the serum concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, and neuron-specific enolase (NSE) were also examined. Serum levels of these tumor markers were also evaluated in relation to therapeutic response in 69 patients who received combination chemotherapy with platinum compound. RESULTS: Fifty of 121 patients with NSCLC (41.3%) showed elevated serum GST-pi levels above a cutoff value of 34.8 ng/ml (mean + two standard deviations in 30 healthy control subjects). The positive rate of GST-pi in patients with NSCLC was higher than those of CEA (37.2%), SCC (15.7%), and NSE (14.9%). The mean pretreatment GST-pi level was significantly lower in patients with a partial response to chemotherapy than in those with no response (26.9 +/- 11.3 ng/ml versus 38.8 +/- 16.7 ng/ml; P < 0.003). Among patients with elevated levels of pretreatment serum GST-pi, only 13.8% (four of 29) responded to the combination chemotherapy, whereas partial response was observed in 40.0% of patients (16 of 40) with serum GST-pi concentration below the cutoff level (P < 0.02). Neither CEA, SCC, nor NSE showed such a relationship. CONCLUSIONS: The serum GST-pi level may have limited value as a tumor marker for NSCLC: Interestingly, pretreatment serum GST-pi levels may be a useful parameter for predicting therapeutic response to combination chemotherapy regimens that include platinum compound.

Adult↗

PubMed1994

Gomisin A, a lignan component of Schizandora fruits, inhibits development of preneoplastic lesions in rat liver by 3'-methyl-4-dimethylamino-azobenzene.

The effects of gomisin A, a lignan component of Schizandra fruits, on development of preneoplastic lesions in the liver after a short-term (3 weeks) feeding of 3'-methyl-4-dimethyl-aminoazobenzene (3'-MeDAB) to male Donryu rats were investigated, and compared with the effects of phenobarbital. Gomisin A inhibited both increases of the level of glutathione-S-transferase placental form (GST-P) and the number and size of GST-P positive foci in the liver increased after treatment with 3'-MeDAB. Moreover, although the population of diploid nuclei was increased and that of tetraploid nuclei was decreased by pretreatment with 3'-MeDAB, gomisin A returned this to near the normal ploidy pattern. But phenobarbital increased the level of GST-P and the number and size of GST-P positive foci with little affect on the ploidy population changed by 3'-MeDAB. Thus, the effect of gomisin A on hepatocarcinogenesis was inhibitory in contrast with that of phenobarbital. This study suggests that gomisin A is a candidate for a chemopreventive drug inhibiting the promotion process in hepatocarcinogenesis.

Animals↗

PubMed1994

Ectopic expression of c-kit in small-cell lung cancer.

Accumulating evidence suggests that c-kit plays an important role in the regulation of growth of at least 3 lineages of stem cells, while only very limited data are available on the development of human solid tumors. Our recent studies have shown that c-kit transcripts are expressed in a very restricted sub-set of human solid tumors such as small-cell lung cancer (SCLC). We have also conducted an immunohistological study on in situ localization of the c-kit protein in various human solid tumors as well as in corresponding fetal and adult normal tissues. No c-kit expression was detected in normal bronchial epithelial cells or pneumocytes in lung parenchyma of human fetal and adult specimens, indicating that the c-kit protein is aberrantly expressed in lung-cancer cells. We also found that significant chemotactic response as well as moderate in vitro cell growth occurred in SCLC cell lines upon addition of recombinant human stem-cell factor.

Adenocarcinoma↗

PubMed1994

Histochemical and immunohistochemical studies on keratan sulfate in the anterior segment of the developing human eye.

Changes in the distribution of keratan sulfate in the anterior segment of developing ocular tissue were investigated histochemically and immunohistochemically using human eyes from 5 weeks gestation to 2 years after birth. Enzyme digestion methods with streptomyces hyaluronidase, chondroitinase and keratanase showed that the main component of glycosaminoglycans in the cornea was hyaluronic acid at the early stage and chondroitin sulfate from the middle stage to the neonatal stage. Keratan sulfate was found at the neonatal stage. Immunohistochemical staining, however, showed that keratan sulfate was present from 6 weeks around mesenchymal cells which migrated into the anterior portion. The stroma and endothelial cells of the cornea, trabecular tissue, iris, choroidal tissue of the ciliary body and anterior tunica vasculosa lentis were the next tissues to show positive for immunostaining. Keratan sulfate became limited to the cornea and lumbus and mostly disappeared from the other anterior segment tissues after birth. These findings suggest that tissues which seem to originate from mesenchymal cells and surround the chamber space contain keratan sulfate during the developmental stage.

Adolescent↗

PubMed1994

Augmentation of host defense mechanisms against tumor by sperabillin polymers, new basic peptidyl biopolymers, in mice.

Sperabillin polymers, which have been shown recently to have antitumor activity, are new basic peptidyl polymers composed of a pseudo-peptide antibiotic, sperabillin A. The polymers, HP-2 (MW 9990), AP-2 (MW 20,100) and AB-2 (MW 35,000), were found to potently activate murine peritoneal macrophages. The phagocytosis-dependent respiratory burst and Fc gamma receptor expression of peritoneal macrophages from C57BL/6 mice were enhanced after in vitro cultivation with these polymers. When HP-2, a representative of these polymers, was intraperitoneally injected into mice, the number of peritoneal exudate cells increased and phagocytosis-dependent respiratory burst and class II (I-A) antigen expression of peritoneal macrophages were augmented. These macrophages showed strong inhibitory activity against the growth of murine tumor cell lines such as EL4 lymphoma and B16 melanoma. Nitrogen oxide, tumor necrosis factor (TNF) and interleukin 1 (IL-1) might be required for this inhibitory activity. Moreover, in mice treated with HP-2, splenocyte counts also increased and non-specific killer activity of the splenocytes was augmented. These results indicate that sperabillin polymers are new macrophage activators.

Adjuvants, Immunologic↗

PubMed1994

Inhibition by gomisin A, a lignan compound, of hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene in rats.

The effects of gomisin A, a lignan compound of Schizandra fruits, on hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in rats were investigated. Gomisin A inhibited both increases of the number and size of glutathione S-transferase placental form (GST-P)-positive foci, a marker enzyme of preneoplasm, and the population of diploid nuclei, as a proliferative state of hepatocytes, in the liver from rats simultaneously treated with 3'-MeDAB. Gomisin A increased GST activity in the liver, by raising the level of GST 1 and 2 isozymes. 3'-MeDAB increased GST activity and GST-P expression. This high level of GST-P induced by 3'-MeDAB was suppressed by additional treatment with gomisin A. In an experiment on simultaneous treatment, gomisin A increased the biliary excretion of 3'-MeDAB-related aminoazo dyes and decreased the content in the liver of rats fed with 0.06%-3'-MeDAB containing diet. In an experiment on pretreatment with 3'-MeDAB, even though no aminoazo dye was detectable in the liver or bile 2-weeks after cessation of 3'-MeDAB-feeding, gomisin A showed a tendency to reduce the preneoplastic changes of increases in GST-P positive foci and diploid nuclei in the liver. These results suggest that gomisin A inhibits the hepatocarcinogenesis induced by 3'-MeDAB by enhancing the excretion of the carcinogen from the liver and by reversing the normal cytokinesis.

Animals↗

PubMed1994

Novel retrovirus protease inhibitors, RPI-856 A, B, C and D, produced by Streptomyces sp. AL-322.

Four kinds of retrovirus protease inhibitors (RPI-856 A, B, C and D) were isolated as white powder from the culture filtrate of a soil isolate, Streptomyces sp. AL-322 by column chromatography using Diaion HP-20, Sephadex LH-20, ODS reversed phase HPLC and SP-2SW ion exchange HPLC. The structures of these inhibitors were elucidated by physico-chemical properties, chemical reactions and spectral analyses, as valyl-ADPAA-leucyl-AOPBA-valyl-valyl-aspartic acid (RPI-856 A and B) and valyl-ADPAA-leucyl-AOPBA-valyl-valine (RPI-856 C and D) [ADPAA = 2-amino-2-(3,5-dihydroxyphenyl)acetic acid, AOPBA = 3-amino-2-oxo-4-phenylbutyric acid]. RPI-856 A and B, and RPI-856 C and D were both determined to be diasteromers each other on the asymmetric carbon in AOPBA. These four inhibitors strongly inhibited in vitro HIV-1 protease and HTLV-I protease both derived from recombinant Escherichia coli with IC50 of 10(-7) approximately 10(-8) M.

Amino Acid Sequence↗

PubMed1994

Structures of dnacin A1 and B1, new naphthyridinomycin-type antitumor antibiotics.

Dnacin A1 and B1 were revealed to be new naphthyridinomycin-type antitumor antibiotics with formulae of C20H23N5O4 and C19H24N4O5, respectively. The gross structure of dnacin A1 was elucidated by the spectroscopic analyses. Conversion of dnacin B1 into A1 by treatment with potassium cyanide indicated the presence of an alpha-carbinolamine moiety in dnacin B1. The relative stereochemistry of dnacins was clarified by analysis of the NOESY spectra.

Antibiotics, Antineoplastic↗