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Biomedical subjects

K Inokuchi

Publications and source records attributed to K Inokuchi.

At least 73 records · Page 4Linked to original sources
PubMed1987

Site-specific demethylation and normal chromatin structure of the human dihydrofolate reductase gene promoter after transfection into CHO cells.

The effect of in vitro methylation on the function and chromatin structure of the human dihydrofolate reductase (DHFR) promoter linked to the DHFR coding sequences (minigene) was studied after DNA-mediated gene transfer into DHFR- CHO cells. Methylation of HhaI sites reduced the transforming frequency to about 10% of control, whereas methylation of HpaII sites had a less significant effect. The integrated genes were demethylated at specific sites in the promoter sequence, namely, HpaII sites around -57 base pairs from the major start site for transcription and HhaI sites around +9, +24, or both. All other HpaII or HhaI sites in the DHFR coding region or in the plasmid sequences remained consistently methylated. The DHFR minigene, after methylation with HhaI methylase, was also introduced without selection by cotransfection with pSV2neo and selection for neor clones in G418. Preferential demethylation of the same sites was observed even without selection for the DHFR+ phenotype. Analysis of the chromatin structure of the integrated minigene revealed characteristic proximal and distal hypersensitive regions of the promoter, as previously observed in human cells. Correctly initiated DHFR mRNA was detected in all of the transformants studied. These results suggest that formation of the characteristic chromatin structure is an intrinsic property of the DHFR promoter sequence and that demethylation of specific sites accompanies gene expression.

Animals↗
PubMed1987

Identification of sequence elements that confer cell-type-specific control of MF alpha 1 expression in Saccharomyces cerevisiae.

The MF alpha 1 gene of Saccharomyces cerevisiae, a major structural gene for mating pheromone alpha factor, is an alpha-specific gene whose expression is regulated by the mating-type locus. To study the role of sequences upstream of MF alpha 1 in its expression and regulation, we generated two sets of promoter deletions: upstream deletions and internal deletions. By analyzing these deletions, we have identified a TATA box and two closely related, tandemly arranged upstream activation sites as necessary elements for MF alpha 1 expression. Two upstream activation sites were located ca. 300 and 250 base pairs upstream of the MF alpha 1 transcription start points, which were also determined in this study. Each site contained a homologous 22-base-pair sequence, and both sites were required for maximum transcription level. The distance between the upstream activation sites and the transcription start points could be altered without causing loss of transcription efficiency, and the sites were active in either orientation with respect to the coding region. These elements conferred cell type-specific expression on a heterologous promoter. Analysis with host mating-type locus mutants indicates that these sequences are the sites through which the MAT alpha 1 product exerts its action to activate the MF alpha 1 gene. Homologous sequences with these elements were found in other alpha-specific genes, MF alpha 2 and STE3, and may mediate activation of this set of genes by MAT alpha 1.

Base Sequence↗
PubMed1987

[Cooperative study of surgical adjuvant chemotherapy of colorectal cancer (first report): Investigation of background factors and adverse effects. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

In order to evaluate the efficacy of surgical adjuvant chemotherapy in patients undergoing gross curative resection for colorectal cancer (excluding m and sm cancer), a randomized controlled study was conducted from January, 1982 to October, 1983. Four hundred and ninety-one institutions participated in this study. The schedules for drug administration differed according to each district. In the Hokkaido and Shikoku districts, the patients were divided into the following two groups, one was a combination of ACNU and Futraful (FT) and the other was FT only. In the Chubu and Kinki districts, three groups were studied, namely those receiving a combination of ACNU and FT, those receiving FT only and those given no adjuvant chemotherapy. In the Tohoku and Kanto districts, a combination of MMC and FT and administration of FT only were studied. In the Chugoku and Kyushu districts, the patients were divided into a combination of ADM and FT, and FT only group. Among the 3,926 registered cases, 3,421 cases were valid for the study. As to the background factors, there were no significant differences among the groups in each district. There were no significant differences in one-year survival rates and one-year disease-free rates. No serious adverse effects were observed in any of the groups.

Alopecia↗
PubMed1987

[A multi-institutional study on postoperative adjuvant immunochemotherapy of gastric cancer (II)].

A multi-institutional cooperative study of postoperative immunochemotherapy for gastric cancer was studied using PSK and/or OK-432 combined with Tegafur (FT) and/or MMC. A total of 3,630 gastrectomized patients from 412 institutions were entered into the study using 6 randomly assigned protocols. Unbiased background cases were analyzed by 4-year or 5-year survival rates (SVR) for each protocol. The efficacy of combined PSK with FT was noticed in all cases of curative operation macroscopically and in n(-) X ps(+) cases (4-y SVR). The combination of MMC, FT and PSK produced better survival than MMC with FT or PSK administration in all cases of macroscopic curative operation (5-y SVR) and in non-curative operation (4-y SVR). The combination of MMC, FT, PSK and OK-432 was effective for poorly differentiated cancer (4-y SVR). Immunochemotherapy with MMC, FT, PSK and OK-432 was more effective in patients with preoperative positive PPD skin test than in those with negative PPD skin test. These results suggested that adjuvant immunochemotherapy using PSK and/or OK-432 combined with MMC and FT is effective for the improved survival of gastrectomized patients with gastric cancer.

Biological Products↗
PubMed1987

[Prospectives on cancer treatment in the future--from its clinical aspects].

Remarkable progress has been achieved in the treatment of gastric cancer during these three decades, the late survival rate being increased twice or more. The factors attributing to this result were analyzed and prospect for further progress was discussed. One of the most promising ways for this purpose lies in the development of multidisciplinary treatment. So far the mode of thinking has been placed on the organ-oriented basis. However, the search should be directed to the treatment specifically effective to each biological type involved in the tumor. A concept of "Type-Oriented Treatment" was proposed herein.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Effectiveness of multidisciplinary treatment combined with immunotherapy in esophageal cancer--analysis of 287 cases of carcinoma of the thoracic part of the esophagus in Kyushu and Yamaguchi districts].

The effectiveness of surgical adjuvant immunochemotherapy was studied on 287 patients with thoracic esophageal cancer in the Kyushu and Yamaguchi districts. Pre- and postoperative subcutaneous administrations of BCG, 10 mg once a week and an oral administration of PSK, 3 g a day, for as long as possible after surgery were instituted. The control group was designated as the one which neither PSK nor BCG was given. Most patients received chemotherapy and/or radiotherapy. Significant elongation of survival time was observed in immunotherapy patients with stage III and in those with non-curative resection, both having no lymph node metastasis.

Adult↗
PubMed1986

Chromatin structure of the human dihydrofolate reductase gene promoter. Multiple protein-binding sites.

The chromatin structure of the promoter region of the human dihydrofolate reductase gene was determined using a variety of nucleases including DNase I, micrococcal nuclease, several restriction endonucleases, exonuclease III, and Bal31. Two separate regions from -670 to -340 (the distal hypersensitive region) and from -170 to +150 (the proximal hypersensitive region) were shown to be essentially free of proteins as indicated by their accessibility to both endo- and exonucleases. Within the proximal hypersensitive region, one protein appears to be bound at the start site for transcription. A 170-base pair fragment between the two hypersensitive regions was highly resistant to all nucleases tested. Multiple barriers against exonuclease digestion and resistance to dissociation by high salt concentrations suggest that more than one protein is tightly bound to this region. The upstream sequence from -670 and the downstream sequence from +150 were shown to be packaged into nucleosomes. The selective accessibility of certain sites to micrococcal nuclease cutting indicates that the initial nucleosomes are phased upstream from the distal hypersensitive region. There appears to be a protein bound between the phased nucleosomes and the upstream boundary of the distal hypersensitive region. These results suggest that the normal nucleosome array is interrupted by about 900 base pairs of nucleosome-free DNA to which several nuclear proteins bind in a DNA sequence-specific manner.

Chromatin↗
PubMed1986

Prognostic factors of esophageal carcinoma: univariate and multivariate analyses.

The correlation of 5-year survival rate with various clinical and histopathological factors was studied using univariate and multiple analyses of 128 patients who had undergone resection for esophageal carcinoma between 1965 and 1978 in the Department of Surgery, Kyushu University Hospital. The depth of penetration, lymph node metastasis, lymphatic or vascular invasion, and INF had a significant correlation with 5-year survival in the univariate analysis; however, only depth of penetration and lymph node metastasis were prognostic factors with a significant difference, in the multivariate analysis. In 55 patients in whom the cell nuclear DNA content had been determined, the DNA pattern was the greatest prognostic factor (p less than 0.01), in multivariate analysis. We propose that the DNA distribution in the malignant cells should be examined as a most pertinent prognostic factor.

Adult↗
PubMed1986

Superficial spreading esophageal cancer controlled by hyperthermo-chemo-radiotherapy: a case report.

Hyperthermo-chemo-radiotherapy (HCR) was prescribed for a patient with superficially spreading esophageal cancer, since severe lung dysfunction presented too great a surgical risk. Viable cancer cells completely disappeared after HCR and 8 months later, at this writing, the patient is living in good condition. Conservative treatment with HCR for patients with esophageal cancer is effective for carefully selected patients.

Aged↗
PubMed1986

Histopathological evaluation of hyperthermo-chemo-radiotherapy for carcinoma of the esophagus.

The effectiveness of preoperative hyperthermo-chemo-radiotherapy for 25 patients with carcinoma of the esophagus was histopathologically compared with findings in 104 patients treated preoperatively with irradiation only. The preoperative hyperthermo-chemo-radiotherapy increased the rate of "markedly effective" in the resected tissue, when compared with findings in cases of irradiation only. With regard to long survival rates, the 5-year survival rates of patients classed as "markedly effective" with preoperative combined therapy exceeded events in patients classed as "moderately effective," and "ineffective," with statistical significance. Preoperative hyperthermo-chemo-radiotherapy is the recommended treatment for patients with carcinoma of the esophagus.

Aged↗
PubMed1986

Hyperthermochemoradiotherapy and esophageal carcinoma.

Cancer of the esophagus still poses considerable treatment problems, with a poor 5-year survival rate after surgery, an even worse outlook after radiation and surgery, and a not very satisfactory response to chemotherapy. After several years of continued research, in 1983 we developed a Radio Frequency System with endotract electrode and thermosensors for administering hyperthermochemoradiotherapy to patients with carcinoma of the esophagus. Results in 129 patients are discussed. Immediate improvement of subjective complaints and decrease or elimination of the cancer lesion are so distinct that this treatment, by means of an endotract antenna, shows promise as a modality for esophageal lesions and may find application in diseases such as colorectal cancer or carcinoma of the uterine cervix.

Bleomycin↗
PubMed1986

Preoperative detection of a highly malignant type of early gastric carcinoma by cytophotometric DNA analysis.

A cytophotometric DNA analysis was made of gastroendoscopically biopsied materials of 43 patients with early gastric carcinoma and the data were compared with the DNA patterns of the resected specimens of these patients. The DNA patterns could be classified into two types, Low Ploidy and High ploidy, according to the degree of dispersion of the DNA value. The Ploidy to Ploidy coincidence of the DNA patterns between biopsied material and the resected specimen in the same lesion was noted in 93 per cent (39/42). The DNA patterns of the resected specimens were consistent in the majority of cases, regardless of the areas examined, center or periphery, and mucosa or submucosa of the same lesion. This study provides evidence that a highly malignant type of early gastric carcinoma, Pen A type, could be differentiated in gastroendoscopically biopsied materials by a cytophotometric DNA analysis.

Biopsy↗
PubMed1986

Postoperative adjuvant chemotherapy for gastric cancer, the second report. Analysis of data on 2873 patients followed for five years.

The effectiveness of combination chemotherapy with mitomycin-C (MMC) plus futraful (N1-(2'-tetrahydrofuryl)-5-fluorouracil), as an adjunct to surgery for gastric cancer was investigated in a prospective randomized controlled study. Three thousand and thirty-three Japanese patients in 344 hospitals were entered and 2873 could be followed for 5 years. All patients had undergone gastrectomy from April 1977 to May 1979 and were assigned, at random, to either Groups A, B or C. In Group A, bolus MMC was administered with no further treatment. In Group C, oral futraful was given for one year, without MMC induction. In Group B, both a bolus MMC injection and oral futraful were prescribed. This randomized study showed no statistical difference in the 5 year survival rate among the three groups. However, in patients given MMC and put on oral futraful for one year, the 5 year survival rate for those with stage III gastric cancer or for those with positive lymphnode metastasis plus obvious serosal invasion seemed to be improved.

Adult↗
PubMed1986

Development of erosive gastritis in a canine model of esophageal varices.

We designed a reproducible canine model of esophageal varices, based on the concept of a regional hyperdynamic state in the upper stomach. Arterialization of the left gastric vein concomitant with the distal splenorenal shunt led to a stable hyperdynamic state and reproducible esophageal varices occurred. In the long-term follow-up of these dogs with varices, the erosive gastritis seen in the upper stomach clearly resembled clinically observed lesions. Hemodynamic and morphological studies revealed that gastric mucosa of these animals was in an ischemic state, even though there was a remarkable increase in blood flow in the submucosal area. It is suggested that the decrease in mucosal blood flow, as induced by the hyperdynamic state caused erosive gastritis.

Animals↗
PubMed1986

Acute liver failure in rats inhibited by intrasplenic administration of OK-432.

Intrasplenic administration of OK-432, an immunostimulant derived from Streptococcus, prevented hepatic failure induced in rats by D-galactosamine. When OK-432 was given 1.0 K.E. (Group I) or 0.1 K.E. (Group II) into the subcutaneously transpositioned spleen three times prior to dosing with D-galactosamine, survival rates were 100 and 87%, respectively. On the contrary, with a splenic injection of saline (Group III), the survival rate was 47 and 32% in rats given OK-432 1.0 K.E. intraperitoneally (Group IV). The poisoned rats given no pretreatment (Group V) survived at a rate of 26%. These results show that intrasplenic administration of OK-432 leads to a significant enhancement of survival. Metabolic data and histological findings were compatible with survival rates, in each group. Activation of the reticuloendothelial function by the intrasplenic administration of this immunostimulant seems to have prevented acute liver failure.

Acute Disease↗
PubMed1986

Combined effects of hyperthermia, bleomycin, and X rays on Ehrlich ascites tumor.

The combined effects of water-bath hyperthermia at 42.5 degrees C for 30 min, 1/10 LD50 Bleomycin iv, and 200 rad x irradiation were studied in DDD strain male mice with Ehrlich ascites tumor. The objective was to acquire data on the optimum regimen for a combined administration of these three modalities. The treatments were given 10 days after the inoculation of 2 X 10(6) of the cells into the right hind limb. Concomitant application of the three modalities led to an 80% regression. A single modality produced no significant effect and a 30-50% regression occurred when only two modalities were combined. To assess the influence of timing and sequence, hyperthermia was applied at 1, 2, 4, and 6 hr before, after, or simultaneously with the combination of Bleomycin and 200 rad X ray. A significant effect was obtained in the case of concomitant application of the three and hyperthermia was effective when applied within 2 hr before or after administration of Bleomycin plus irradiation. This enhancement disappeared at 4-hr intervals.

Animals↗