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Biomedical subjects

K Inokuchi

Publications and source records attributed to K Inokuchi.

At least 91 records · Page 5Linked to original sources

Intimal hyperplasia: the permeation of serum-derived substance into the arterial autovein graft under abnormal blood flow.

The etiology of intimal hyperplasia in autogenous vein grafts used for arterial replacement was experimentally studied in dogs. We previously developed an experimental model, which mimicked a human extremity with poor run-off of peripheral arteries. This model characterized the abnormal flow by a weak fluctuation of wall shear stress at the site adjacent to the vessel wall. In this model we found that an autogenous vein implanted into the femoral artery under such abnormal flow conditions exhibited remarkable intimal thickening; 200-400 micron at 1 month and 300-500 micron at 6 months. A fluorescence microscopic study revealed that Evans blue-albumin complex entered the inner wall of vein grafts transplanted in abnormal flow conditions until about 2 weeks after implantation, after which further permeation was no longer observed. A similar observation was made in the fibrinogen distribution of subendothelial tissue. These results showed that abnormal flow conditions enhance the permeation of certain substances into immaturely repaired intimal tissues of autovein grafts. This phenomenon is thought to be responsible for the proliferation of smooth muscle cells, leading to hyperplasia of autovein grafts.

Animals

Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years.

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC + FT + PSK group showed a significant increase in 5 year survival from the other groups (p less than 0.05). Moreover the survival rate was significantly higher in the MMC + FT + PSK group than in the MMC + FT group (p less than 0.01). According to the analysis on stratification, the MMC + FT + PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p less than 0.01 or p less than 0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.

Adjuvants, Immunologic

[A cooperative study of surgical adjuvant chemotherapy of colorectal cancer (second report): 3-year survival rate. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan].

To evaluate the efficacy of surgical adjuvant chemotherapy for patients with curatively resected colorectal cancer (excluding m and sm cancer), a randomized controlled study was performed from January 1982 to October 1983. The schedules for drug administration were different in four districts, and four randomly assigned protocols were studied using tegafur (FT), ACNU, MMC and ADM. A total of 4,906 cases from 491 institutions were entered and 4,206 cases were varied for the study. There were no significant differences in 3-year survival rate in each district protocol. According to Dukes C for rectal cancer patients, ADM + FT group was higher than the FT only group in 3-year survival rate (p = 0.092) and had a significantly longer survival than FT only group in 3-year disease-free rate (p = 0.011). The rate of local recidivation in colon cancer resected curatively was higher in ACNU + FT group than in FT only group (p less than 0.05). A tendency for decreased liver metastasis was observed in FT group compared with the control group, and liver metastasis of ADM + FT group was lower than that of FT only group. No serious adverse effects were observed in any protocol.

Antineoplastic Combined Chemotherapy Protocols

[Long-term chemotherapy in patients with stage IV gastric cancer after surgical treatment--a randomized comparative study of FT-207 and UFT].

A prospective randomized and comparative study of FT-207 and UFT was performed for cases of Stage IV gastric cancer involving long-term cancer chemotherapy after surgery. Immediately after the surgery, the subjects were randomly divided into two groups: A group treated by MMC and FT-207: and B group treated by MMC and UFT. From a total of 54 cases, 8 cases were excluded, so that A group consisted of 24 subjects and B group of 22 subjects. There were no differences in background factors between the two groups. In a comparison of all the cases, B group revealed a significantly higher survival rate than A group. These results indicated that the simultaneous use of MMC and UFT was effective as a long-term cancer chemotherapy after surgery for patients with Stage IV gastric cancer.

Adult

An ultrasonic duplex system facilitates detection of portal hemodynamic changes following selective shunts for esophageal varices.

We used an ultrasonic duplex system (US system) to assess portal hemodynamics in 52 patients with liver cirrhosis and esophageal varices, who underwent 2 types of distal splenorenal shunt (DSRS), conventional DSRS (group A, 8 patients) or DSRS with splenopancreatic disconnection (group B, 44 patients). The portal blood flow rate (PBF) was determined in 64 out of 70 patients (91.4%) and the shunt flow rate (SVF) in 39 out of 42 patients (92.9%) who had angiographically confirmed patent portal vein and shunt vein, during the peri- and postoperative period. In group A, a remarkably small amount of postoperative PBF (193 ml/min) and a concomitant increase in SVF (1039 ml/min) were evident. Such ultrasonic findings were compatible with a reduction in portal vein diameter, in accordance with the poor portal perfusion grade of the liver, and a transpancreatic stealing of the portal blood flow to the shunt, as evidenced by postoperative angiography. In contrast, the reduction in PBF was minimal, that is 663 ml/min preoperatively to 562 ml/min at discharge, and 536 ml/min at late follow-up, in group B patients. Significant alterations in portal circulation of the group B patients were not evident angiographically. This US system is most useful to assess portal hemodynamics in patients with a selective shunt.

Adult

The clinical usefulness of preoperative CEA determination in gastric cancer.

Between 1980 and 1984, preoperative serum carcinoembryonic antigen (CEA) was determined in 468 patients with gastric cancer to evaluate its clinical usefulness. The positive rate of preoperative CEA was 20.9 per cent in these 468 patients. A significantly higher CEA positive rate was obtained in those patients with liver metastasis (69.2 per cent), n3-4 (40.0 per cent), stage IV gastric cancer (37.0 per cent) and Pap, Tub1 histological type (26.3 per cent) (p less than 0.01). It is interesting that the positive rate of the 49 unresectable patients was 51.0 per cent, which was significantly higher than 17.4 per cent of the 419 resectable cases (p less than 0.01). CEA levels in 16 of the 39 patients with liver metastasis were more than 100 ng/ml. In contrast, serosal invasion and peritoneal metastasis were less correlated to the CEA positive rate. In the 419 resected cases, the 5 year survival rate in the higher CEA group of more than 50 ng/ml (35 cases) was 4.4 per cent, which was significantly lower than 64.0 per cent in the negative group (346 cases) (p less than 0.01). These results show that CEA determination in patients with gastric cancer is useful for the prediction of prognosis, as well as for a diagnostic tool to discover the presence of liver or lymph node metastasis.

Adult

Mitomycin C plus carmofur (HCFU) adjuvant chemotherapy for noncuratively resected cases of colorectal carcinoma (interim report).

In order to examine the efficacy of adjuvant chemotherapy employing Mitomycin C (MMC) and carmofur (HCFU) for patients with noncuratively resected colorectal carcinoma, a cooperative study was performed by 54 institutions in the Kyushu and Chugoku areas in Japan. The prospective randomized controlled study consisted of two groups, one receiving only MMC and the other receiving MMC as well as HCFU. Out of an original total of 200, 170 cases were evaluable. Concerning the 30-month survival rate, a better result was observed in the MMC + HCFU group than in the MMC only group (Z-test: p less than 0.05). Significantly better survival rates were obtained in those cases with disseminating peritoneal metastasis, hepatic metastasis and Stage V cancer in the MMC + HCFU group as when compared with the MMC only group (generalized Wilcoxon test: p less than 0.05). No significant side effects due to the combined administration of HCFU were recognized. The combined administration of MMC and HCFU were recognized. The combined administration of MMC and HCFU was suggested to be a safe and effective adjuvant chemotherapy in noncuratively resected cases of colorectal carcinoma.

Aged

The usefulness of CEA as an indicator for early detection and a guide to the treatment of recurrent gastric cancer.

The usefulness of carcinoembryonic antigen (CEA) as an indicator for recurrence and a guide to the treatment was evaluated from a retrospective analysis of 88 patients with recurrent gastric cancer. Sixty-two of these patients (70.5 per cent), 25 of whom had a preoperative positive assay, and 37 a negative assay, had elevated levels of CEA after disease progression. Averaged CEA level in patients with liver metastasis was significantly higher (872 ng/ml) than in those with peritoneal metastasis (68 ng/ml), with lymph node metastasis (103 ng/ml) or with local metastasis (93 ng/ml) (p less than 0.01). An elevation of CEA was found prior to the clinical manifestation of recurrence, and the average lead time was 4 months. In 25 patients with a lead time of more than 4 months, survival time after CEA elevation was 13.3 months, which was longer than the 6.5 months of 28 patients with less than 4 months. Thirty-seven of the 88 patients were treated after recurrence. The average survival period after the detection of recurrence was 9.4 months in patients with surgical treatments followed by chemotherapy, 5.9 months in those with chemotherapy alone and 3.8 months in those with surgery alone. The average survival period of 26 patients with positive CEA assays in recurrence was 5.1 months longer than of patients with negative assays. This fact suggested that early detection of recurrence followed by various treatments, in the elevated CEA group, contributes to favorable results.

Adult

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

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

[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

[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

[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

[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