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Biomedical subjects

H Morimoto

Publications and source records attributed to H Morimoto.

At least 145 records · Page 8Linked to original sources
PubMed1991

The clinical status and histopathological factors affecting natural killer cells of peripheral blood lymphocytes in patients with gastric cancer.

The in vivo function of NK cells is still uncertain, and there are various contradictory reports on NK cells in gastrointestinal cancer. In the present study the activity and proportion of NK cells (Leu 11 + cells) in peripheral blood were assessed in 71 patients with gastric cancer, and analysed with respect to the clinical and histopathological factors, such as the clinical stage, tumor size, degree of invasion, metastasis, histology, etc. There were no differences in the proportions and activities of NK cells between normal volunteers and gastric cancer patients. A low NK cell activity was associated with early gastric cancers (carcinoma in the mucosa or submucosa) less than 2 cm in diameter, large advanced tumors (invasion beyond the muscularis propria) greater than 8 cm in diameter, and metastasis of adjacent regional (perigastric) nodes. Liver metastasis did not affect the NK cell activity, however a high NK activity was found in patients with peritoneal dissemination. The NK activity did not correlate with the proportion of Leu 11 + cells in normal volunteers or in patients with early gastric cancer, however the activity and proportion of NK cells correlated with each other in patients with advanced gastric cancer. These results suggest that the preoperative evaluation of circulating NK cells in gastric cancer patients may be beneficial to assess the extent of nodal metastasis, the degree of tumor invasion, and peritoneal dissemination.

Adult↗
PubMed1991

[Intratumoral injection of OK-432 in conjunction with fibrinogen greatly enhances antitumor effect on colorectal carcinomas].

We found that antitumor effect of OK-432, a lyophylized preparation of an attenuated strain of streptococcus pyogenes, on colorectal carcinoma was greatly augmented when it was injected intratumorally in conjunction with fibrinogen. Twenty cases of colorectal cancer received intratumoral injection of 5 KE of OK-432 mixed with 80mg of fibrinogen including factor-XIII and 1ml of aprotinin at the time of endoscopic examination. Changes in the shape of the tumors were observed endoscopically within a few days after injection, and in most cases, decrease in the height of tumor margin was noted. Histopathological findings on surgically resected specimens revealed that the fine meshwork of fibrin was formed at the injected site soon after the injection, and a marked infiltration of inflammatory cells including neutrophils, plasma cells, macrophages, eosinophils and lymphocytes. Such granulomatous changes developed over 7 days after injection, and the degradation of tumors were observed. By 14 days after the injection, tumor tissues were largely replaced with granulomas, and shrinkage of tissues were observed. These findings indicated that fibrinogen including factor-XIII and aprotinin has a potential ability to augment the immunoreaction induced by biological response modifiers, and intratumoral injection of OK-432 in conjunction with fibrinogen solution was superior to intratumoral injection of OK-432 alone as the local immunotherapy of colorectal cancer.

Aprotinin↗
PubMed1991

[The efficacy of intra-arterial infusion chemotherapy in patients with metastatic liver tumors].

The efficacy of intra-arterial infusion chemotherapy for the treatment of liver metastasis was investigated in 28 colorectal cancer patients, 3 gastric cancer patients and 5 breast cancer patients between April 1986 and May 1991. 1. The long-term intra-arterial infusion chemotherapy was a simple and safe method in cancer patients. 2. We examined the serial serum CEA level in cancer patients and found that the serial change in CEA level correlated well with response to chemotherapy. The efficacy of this treatment was approximately 60% in colorectal cancer, 30% in gastric cancer, 80% in breast cancer. Intra-arterial infusion chemotherapy may be an effective treatment for the patients with liver metastasis from colorectal cancers and breast cancers. 3. In 8 colorectal cancer patients, the serum CEA level decrease to half of the pretreatment level. However, in all cases it increased significantly within 6 months postoperatively. Almost the same trend was observed in two cases of breast cancer. Our results suggest that we should give careful consideration to the resistance to anti-cancer drugs and develop a new protocol in order to obtain further satisfactory results.

Administration, Oral↗
PubMed1991

[Expression of P53 and heat shock protein in colorectal tumors: an immunohistochemical study].

Abnormality of tumor suppressor gene p53 is supposed to be associated deeply with colon carcinogenesis. We have examined the aberrant expression of the p53 protein in human colorectal cancer or adenomatous tissues immunohistochemically using monoclonal antibody PAb 1801. In microwave-fixed colorectal tissues, p53 was successfully detected in more than 60% of carcinomas. Specific signal for p53 was restricted in the nuclei of cancer cells, while no staining was observed in adjacent normal mucosa. The incidence of p53 expression in colorectal carcinomas was not affected by pathological features such as tumor size, histological grade, nor depth of invasion. In about 10% of colorectal adenomas, weak signal was detected in a few adenomatous glands. Heat shock protein of 72 kDa (HSP72), known to form complex with the mutant-type of p53 in tumor cells, was also detected immunohistochemically in 25% of p53-positive cases. In these cases, high incidence of lymphnodal or distant metastasis was observed, which suggests that expression of both p53 and HSP72 may indicated biological malignancy of the colorectal carcinomas.

Biomarkers, Tumor↗
PubMed1990

Expression of pancreatic secretory trypsin inhibitor gene in human colorectal tumor.

Expression of pancreatic secretory trypsin inhibitor (PSTI) gene was examined by Northern blotting analyses in 31 human colorectal tumors that included two benign adenomas and 26 adenocarcinomas. Among the total of 28 cases which proved to be adequate for mRNA analyses, all but one showed the expression of PSTI at various levels. In contrast, PSTI expression was not detected in two malignant lymphomas of the rectum. The level of PSTI expression was not correlated with the patient's age, sex, tumor location or size, stage of differentiation, lymph node metastasis, or progression stage. Some colorectal adenocarcinomas were also shown to express genes that can hybridize with human trypsinogen cDNA probe. It looks as though in these tumors, a protease(s) and its inhibitor are produced simultaneously as part of a cellular self-defense mechanism.

Adenocarcinoma↗
PubMed1990

[A double blind study to evaluate the optimal dose and its frequency for oral administration of OK-432 (picibanil) by immunological parameters (the 2nd report)].

The present study was designed to determine the optimal dose and frequency of oral administration of a biological response modifier, OK-432 (Picibanil), which has been used for cancer immunotherapy by injection. Ninety one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40KE, once or 3 times a week before operation (5KE X 1/W, 20KE X 1/W, 40KE X 1/W, or X 3/W). Misregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. In the 1st report, we already showed that 5KE X 3/W might be the optimal regimen to augment the natural killer (NK) activity of regional lymph node lymphocyte (RNL). In the 2nd report, we searched for the optimal regimen to augment the antitumor immunity of T lymphocytes. The proliferative response of RNL to SuPR (protein derived from OK-432) was augmented in all the groups administered OK-432. The responsiveness of PBL to autologous tumor extract enhanced by IL-2 was augmented by 5KE X 1/W, and that of RNL was augmented by 5KE X 3/W. The killer/suppressor (Leu2+15-/Leu2+15+) ratio in RNL increased in all the groups administered OK-432 especially in 20KE X 3/W group. Oral administration of OK-432 augmented both non-specific and the specific antitumor immunity of PBL as well as RNL, and 5KE X 3/W may be the optimal regimen to augment the antitumor immunity, especially of RNL.

Administration, Oral↗
PubMed1990

[A double blind study of the evaluation of the optimal dose and its frequency in oral administration of OK-432 (Picibanil) by immunological parameters (the 1st report)].

A biological response modifier, OK-432 (Picibanil) administered by injection has been used for cancer immunotherapy. The present study was designed to determine the optimal dose and frequency of oral administration of OK-432. Ninety-one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40 KE, once or 3 times a week before their operation (5 KE X 1/W, 20 KE X 1/W, 40 KE X 1/W, or X3/W). ++Missregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. The NK activity of PBL was augmented by the administration of 40 KE X 1/W or 20 KE X 3/W and that of RNL was augmented by the administration of 5 KE X 3/W or 40 KE X 1/W, in conjunction with an increase in the number of % positive cells of leu 11a+ or leu 19+ analysed by flow cytometry. The killing activity of PBL, RNL, or MNL against allogeneic lined gastric cancer cells (KATO III) was not augmented by the oral administration of OK-432 for one week. The skin reactivity to Su-PS or PPD, serum levels of tumor markers, or serum levels of immunoglobulins did not help in determining the optimal dose or its frequency. These results suggest that 5 KE X 3/W may be the optimal regimen to augment the antitumor immunity of RNL.

Administration, Oral↗
PubMed1990

[Chemotherapy with fluoropyrimidines for MOPC-104E plasmacytoma transplanted in mice with CCl4 induced chronic liver dysfunction].

The masked compounds of 5-fluorouracil (5-FU) have been widely used for chemotherapy in digestive organ cancer. Among them it has been considered that FT (Tegafur) is metabolized into the active form by the drug-metabolizing enzyme P-450 in the microsomes of hepatocytes, and that their activation and anti-tumor activity may decrease under the condition of chronic liver dysfunction. However, this hypothesis has never been experimentally proved. In the present study the therapeutic effect and metabolism of 5-FU and its masked compounds: FT, UFT (uracil + FT), HCFU (Carmofur), 5'-DFUR (Doxifluridine) were assessed by using MOPC-104E plasmacytoma transplanted subcutaneously in BALB/c mice with CCl4-induced chronic liver dysfunction. Agents were administered daily directly into the stomach with stainless steel canule over days 7 to 13 after tumor transplantation, and the tumor weights, drug concentrations in the liver or the tumor, and serum levels of GOT, GPT and LDH were measured on day 14. In mice with chronic liver dysfunction the tumor-inhibitory effect of 5-FU, FT, UFT and HCFU did not necessarily decrease and serum levels of GOT, GPT and LDH of mice administered with 5-FU, FT, HCFU and 5'-DFUR were higher than in normal animals treated with them. By contrast UFT had no influence on them. The most remarkable difference was observed in uracil concentrations, which were significantly lower in the tumor and the liver of mice with chronic liver dysfunction than in those of normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Chemosensitivity correlation between the primary tumors and simultaneous metastatic lymph nodes of patients evaluated by DNA synthesis inhibition assay.

The chemosensitivities of primary tumors (PT) and simultaneous metastatic lymph nodes (MN) to mitomycin C (MMC), 5-fluorouracil (5-FU), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), carboquone (CQ), or cisplatin (CDDP) were assessed in a group of 29 patients (11 gastric, 8 colorectal, 4 breast, and 6 other cancers) by a DNA synthesis (3H-thymidine incorporation) inhibition assay. PT and MN from the same patient showed heterogeneity in chemosensitivity. MN were more sensitive to the agents than PT. PT were sensitive to 5-FU, whereas MN were sensitive to CDDP. An analysis of the sensitivity correlations showed that the sensitivities of PT to MMC, 5-FU, CQ, and CDDP correlated with each other, but ADR sensitivity correlated with only CQ sensitivity. The sensitivities of MN correlated with each other, except for those to ADR and CDDP. In contrast, MMC, ADR, or CQ sensitivity showed a correlation between PT and MN. These results suggest that patients should be treated according to the sensitivity of the target lesion. However, if the sensitivity assay is not available, the sensitivity correlation may be useful when choosing the agent. It also may be important that ADR sensitivity does not correlate with the sensitivities of other agents.

Breast Neoplasms↗
PubMed1990

Biologically active aromatic retinoids bearing azido photoaffinity-labeling groups and their binding to cellular retinoic acid-binding protein.

Retinoids bearing azido photoaffinity-labeling groups (azidoretinoids) have potential as probes for investigating the molecular mechanisms of action of all-trans-retinoic acid (RA) as mediated by its cellular retinoic acid-binding protein (CRABP) and nuclear receptor proteins. Two new azidoretinoids, 3-azido-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1E- propen-1-yl]-benzonic acid and 4-(4-azido-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)be nzoic acid were synthesized, and evaluated for their in vitro biological potency, and binding affinity for CRABP. Like RA, these aromatic azides had significant activity in modulating cell differentiation in retinoid-deficient hamster tracheal organ culture (ED500.02 nM and 0.03 nM, respectively) and in the inhibition of the induction of ornithine decarboxylase in mouse epidermis (ED50 7.0 nmol and 0.5 nmol, respectively). They also possessed high binding affinity for CRABP (ID50 0.9 microM and 0.85 microM, respectively). The tritiated aromatic azides were further evaluated for their ability to bind covalently to CRABP after photolysis. On photolysis at -78 degrees C, the two radiolabeled azidoretinoids formed stable adducts with CRABP. Treatment of the adducts with either RA or p-chloromercuriphenylsulfonic acid (CMPS) and subsequent dialysis did not cause any dissociation, indicating the formation of a covalent bond. In contrast, treatment of the unirradiated complexes with RA or CMPS led to dissociation of the complex. Synthesis of affinity labels and characterization of CRABP-retinoid complexes should provide useful information on the ligand-binding regions and insights into the mechanism of action of RA.

Affinity Labels↗
PubMed1990

Expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer.

We examined the expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer by immunohistochemical staining using an anti-PSTI antiserum, an in situ hybridisation technique utilising sulphonated PSTI cDNA probe, and a Northern blot hybridisation method, using a 32P-labelled PSTI cDNA probe. Immunohistochemically, PSTI was detected in 80 of 95 (84%) colorectal cancer cases. Analyses with in situ hybridisation as well as Northern blot hybridisation demonstrated PSTI mRNAs in immunohistochemically positive cases, showing PSTI could be produced in colorectal cancerous cells. Histologically well or moderately differentiated adenocarcinoma showed higher incidence of PSTI immunoreactivity than the other types. Furthermore, the intensity of the immunohistochemical staining for PSTI increased the more cases advanced, particularly in regard to depth of invasion and tumour size. Thus, PSTI expression is widespread in colorectal cancer, and occurs more commonly in advanced cases. Considering the suggestion that PSTI is a growth-stimulating factor as an well as inhibitor to proteolytic proteinase, the present findings may indicate that PSTI expressed in colorectal cancerous cells may play a role possibly closely associated with tumour development.

Adult↗
PubMed1990

3H nuclear magnetic resonance study of anaerobic glycolysis in packed erythrocytes.

The utility and power of 3H NMR spectroscopy as a technique for monitoring biological systems in vivo is illustrated with glucose metabolism in erythrocytes. Use of C-1-tritiated glucose allowed us to monitor the disappearance of the alpha and beta tritons, with the production of lactate and 1H3HO (HTO), as well as some intermediates. Spin lattice relaxation times (T1) were measured to avoid T1 distortion of the spectral intensities. Detection of the formation of 1 mM tritiated water in the presence of 110 M H2O protons and deuterons allows the eventual fate of the label in the pentose shunt to be observed in vivo.

Anaerobiosis↗
PubMed1990

Increased number of suppressor T-cells and impaired IL-2 mediated T-cell function in peripheral blood of gastric cancer patients.

The present study was designed to investigate the mechanisms responsible for suppressed T-cell immunity in gastric cancer patients. The peripheral blood T-cell functions in gastric cancer patients were evaluated by measuring responses to PHA and IL-2, and T-cell subpopulations were assessed by flow cytometry. Both the PHA and IL-2 responses decreased in patients with gastric cancer, although the proportions of CD3+ and CD25+ cells were the same for gastric cancer patients and healthy volunteers. The PHA response, but not that of IL-2, was lower in patients with liver metastasis or peritoneal dissemination than in patients without these conditions. Single regression analysis showed that with lymph node involvement in the disease the IL-2 response was more strongly suppressed than PHA response. The serum level of IAP did not correlate with the response to either PHA or IL-2. The proportion of CD4+ cells was not affected by any factor related to gastric cancer, although CD4+/CD8+ and CD8+11b-/CD8+11b+ ratios did decrease in patients with distant lymph node involvement. These changes may be due to a comparative increase in suppressor cells. These results suggest that gastric cancer patients exhibit impaired IL-2 mediated T-cell function and that the number of suppressor cells may increase with progressive lymph node involvement. These two serial effects may be indeed responsible for the impaired blood T-cell function in patients with gastric cancer.

Adult↗
PubMed1990

[The relation between serum carcinoembryonic antigen (CEA) and response to chemotherapy in patients with advanced colorectal cancer].

Prognostic factors from 22 cases of advanced colorectal carcinoma were examined with respect to age, the degree of cellular differentiation, pretreatment serum CEA and doubling time of circulating CEA. The prognoses were very poor for patients of younger age and poorly differentiated tumor. No correlations were observed between survival time and pretreatment serum CEA. A significant correlation of survival time and CEA doubling time was observed. The serial serum CEA levels were examined in the 11 colorectal cancer patients with unresectable multiple liver metastasis, who were treated with intraarterial selective chemotherapy. There were no significant differences between pretreatment serum CEA and survival time on response to chemotherapy. In 9 cases showing over 40 ng/ml of CEA before treatment, however, the serial change in CEA levels correlated well with response to chemotherapy. In four cases with recurrent liver metastasis, prolongation time could be predicted from the CEA induces with respect to the forward time earning and the alternation of the CEA doubling time. Furthermore, the two cases without any measurable lesions also showed the same trend. These results suggested that serial measurement of serum CEA were useful for monitoring the response to chemotherapy against advanced colorectal cancer when the pretreatment serum CEA was high (over 40 ng/ml).

Adenocarcinoma↗
PubMed1989

[Oral administration of OK-432 (picibanil). (8th report) clinical application: its immunomodulatory effects on the patients with gastrointestinal cancers].

A streptococcal preparation, OK-432 at a dose of 5 KE was orally administered to the patients with gastric or colorectal cancer for 7 approximately 14 days before operation, and its immunomodulatory effects on peripheral blood lymphocytes (PBL), regional lymph node lymphocytes (RLNL) and tumor infiltrating lymphocytes (TIL) were assessed. OK-432 treated group included 5 gastric and 6 colorectal cancers, and control group included 6 gastric and 8 colorectal cancers. After oral administration of OK-432 the proportion of Leu 7+ and Leu 11+ cells in PBL increased, and NK cell activity of PBL also was augmented. The proportion of OKT8+ cells increased in PBL and those of OKT3+ cells and OKT8+ cells decreased in RLNL after oral administration of OK-432. The responsiveness of TIL to autologous tumor extracts in the presence of interleukin-2 was enhanced in oral OK-432 group. These results indicate that oral OK-432 affects on NK and T cells and augments the antitumor immunity of the patients with gastrointestinal cancer.

Administration, Oral↗