Biomedical subjects

Y Koide

Publications and source records attributed to Y Koide.

332 records · Page 19Linked to original sources

PubMedDate not supplied

Potent and selective aromatase inhibitor: in vitro and in vivo studies with s-triazine derivative SEF19.

We found a potent aromatase inhibitor through the screening of agents for estrogen-dependent breast cancer. SEF19 (2-(imidazol-1-yl)-4,6-dimorphorino-1,3,5-triazine) decreased 50% of human placental aromatase activity in vitro at the concentration of 5.3 nM. In order to clarify the selectivity of SEF19 for enzyme inhibition, we determined the effect of SEF19 on the activities of four steroidogenic cytochrome P450 enzymes in porcine adrenal gland, P450SCC(side-chain cleavage of cholesterol), P450(11 beta) (11 beta-hydroxylase), P450(17 alpha)(17 alpha-hydroxylase/C17,20 lyase) and P450C21 (21-hydroxylase). SEF19 failed to inhibit the activities of porcine adrenal P450SCC, P450(17 alpha) and P450C21 up to the concentration of 100 microM and showed some inhibition on P450(11 beta) activity at 100 microM, while SEF19 completely nullified the aromatase activity at 1 microM. We also determined the potency of SEF19 for the suppression of aromatase activity in vivo. SEF19 suppressed dose-dependently the uterine hypertrophy of immature rats caused by administration of androstenedione (30 mg/kg, s.c.). The ED50 of SEF19 for the suppression of uterine hypertrophy was 0.8 mumol/kg. These results suggest that SEF19 may serve as a potent and selective agent for the treatment of estrogen-dependent breast cancer.

Androstenedione↗

PubMedDate not supplied

Follow-up study of the heart in acromegaly: pre- and post-operative evaluation.

Pre-operative and post-operative echocardiographic data were analyzed from 8 patients with acromegaly. Pre-operatively, end-diastolic diameter was greater than 55 mm in 5 patients (63%) and concentric left ventricular hypertrophy was observed in 3 patients (38%). However, left ventricular function was normal (fractional shortening of the left ventricle greater than 28%) in all patients except 1. All patients had increased left ventricular mass. There was no significant correlation between left ventricular mass and basal plasma growth hormone concentration. An average of 23.9 months after hypophysectomy, growth hormone concentration was significantly decreased. However, the abnormal echocardiographic findings remained. In conclusion, echocardiographic abnormalities (left ventricular dilatation and hypertrophy) are common in patients with acromegaly, but systolic function is, in general, maintained. These cardiac abnormalities persist after reduction of plasma growth hormone concentration.

Acromegaly↗

PubMedDate not supplied

Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers.

The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.

Aged↗

PubMedDate not supplied

Lymph node metastasis with adenocarcinoma of the gastric cardia: clinicopathological analysis and indication for D1 dissection.

PURPOSE: To establish the indications for proximal resection with dissection of perigastric lymph nodes in order to treat adenocarcinoma of the gastric cardia. METHODS: We analyzed the clinicopathological features of 110 resected adenocarcinomas of the gastric cardia with respect to the appropriate operative method and extent of lymphadenectomy for treatment. RESULTS: Of the 110 patients, 93 underwent curative resection. The D2 group (total gastrectomy with dissection of extended regional lymph nodes) revealed higher morbidity and mortality rates compared to the D1 group (proximal resection with dissection of perigastric lymph nodes). The risk of lymph node metastasis was determined by depth of invasion, size of tumors, and gross findings of tumors. CONCLUSION: The appropriate operative method for adenocarcinoma of the gastric cardia requires: (i) tumor size less than 4 cm; and (ii) gross findings indicating a superficial type of lesion, which are recommended for proximal resection with dissection of perigastric lymph nodes.

Adenocarcinoma↗

PubMedDate not supplied

Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells.

We examined the effect of herpes simplex virus-thymidine kinase gene (HSV-TK)-mediated suicide gene therapy on human esophageal cancer. Two human lines, T.Tn cells which bears truncated p53 and TE2 cells with wild-type p53, were transduced with the HSV-TK gene and tested for their sensitivities to a prodrug, ganciclovir (GCV). The transduced cells, T.Tn/TK and TE2/TK, increased in vitro sensitivity to GCV compared with that of respective wild-type cells. However, the growth suppression of T.Tn/TK tumors induced by GCV was marginal in nude mice and the tumors regrew thereafter. In contrast, the growth of TE2/TK tumors was significantly inhibited by GCV and all the tumors disappeared. The status of the p53 gene of tumor cells thereby may influence the efficacy of the HSV-TK/GCV system.

Animals↗

PubMedDate not supplied

Radiosensitivity of human breast cancer cells transduced with wild-type p53 gene is influenced by the p53 status of parental cells.

Induction of apoptosis with chemotherapeutic agents or radiation in tumours is frequently related to the status of those p53 gene of the tumours. To examine whether forced expression of the wild-type p53 gene in tumour cells can modulate their susceptibility to radiation and anti-cancer agents, we retrovirally transduced two types of human breast cancer cell lines, which respectively harboured a mutated p53 gene (OCUB-M) or wild-type p53 gene (YMB-1), with the wild-type p53 gene. Transduced cells which consistently expressed the wild-type p53 gene (OCUB-M/p53, YMB-1/p53) proliferated at the same rate as control cells which were transduced with the beta-galactosidase gene (OCUB-M/lacz, YMB-1/lacz). However, sensitivity to radiation was increased in OCUB-M/p53 cells but not in YMB-1/p53 cells. In vitro chemosensitivity to DNA-damaging anticancer agents such as cyclophosphamide and 5-fluorouracil was not influenced by the transduction of the wild-type p53 gene in either cells. Expression of the wild-type p53 gene in p53-mutated human breast cancer cells can therefore increase their sensitivity to radiation but not their chemosensitivity. Therapeutic effects following by the transduction of the wild-type p53 gene were not observed in breast cancer cells already bearing the wild-type p53 gene.

Antineoplastic Agents↗

PubMedDate not supplied

Electroporation-mediated transfer of cytokine genes into human esophageal tumors produces anti-tumor effects in mice.

Electroporation facilitates transfer of chemicals or plasmid DNA from extracellular milieu into cells by increasing the permeability of the cell membrane. Delivery of electric pulses to established tumors thereby can improve the susceptibility of tumors to an anti-cancer agent administered. We examined whether electroporation-mediated transfer of cytokine genes into solid tumors could produce anti-tumor effects in the tumor-bearing mice. Plasmid DNA containing cytokine genes were injected into human esophageal T.Tn tumors developed in nude mice and electric pulses were then delivered. Administration of murine GM-CSF or human IL-2 gene followed by electroporation significantly suppressed the subsequent growth of T.Tn tumors and prolonged the survival of the inoculated mice. In contrast, electroporation-mediated introduction of a control gene, human GM-CSF gene, whose products do not bind to murine GM-CSF receptors, did not achieve any anti-tumor effects. In vivo transfection of cytokine genes with electroporation could be a possible therapeutic strategy for established solid tumors.

Animals↗

PubMedDate not supplied

Study of irradiation effects on cytokine secretion from retrovirally-transduced tumor cells: a model for tumor vaccination.

We have examined the effects of irradiation on the cytokine secretion from genetically modified human esophageal and gastric carcinomas. Both cell lines were transduced retrovirally to secrete interleukin-2, interleukin-6 and granulocyte-macrophage colony-stimulating factor, respectively. The metabolism of all the transduced cells was partially inhibited by 6 Gy, and greatly inhibited by 20 Gy irradiation. Cytokine productions, however, was not affected by 6 Gy in many cases, and continued to be detected even after 60 Gy irradiation. The analysis of the dose and time of irradiation in each cytokine producer is useful for the designing of tumor vaccine using cytokine gene transfer.

Cell Division↗