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Biomedical subjects

T Shimano

Publications and source records attributed to T Shimano.

At least 55 records · Page 3Linked to original sources
PubMed1992

A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient reactive to a sulfated glycolipid.

A human monoclonal antibody, BMMK-33G, was established by a fusion of human B-lymphoblastoid cells, HO-323, with lymphocytes of axillary lymph nodes obtained from a breast cancer patient. High-performance thin-layer chromatography (HPTLC)-immunostaining and enzyme-linked immunosorbent assay (ELISA) revealed that BMMK-33G was interestingly directed to enough sulfatide (Galactosylceramid-I2-sulfate), which is one of the sulfate ester containing glycolipids. By immunohistochemical staining, BMMK-33G intensely reacted to breast cancer, pancreatic cancer and gastric cancer. It also reacted to many normal human tissues including mammary glands, but these stainings were weaker than those for cancer. This report describes BMMK-33G, a human monoclonal antibody against sulfatide which may be very useful for studying not only tumor immunology but also autoimmune diseases.

Antibodies, Monoclonal↗
PubMed1992

Immunohistochemical study of p53 expression in microwave-fixed, paraffin-embedded sections of colorectal carcinoma and adenoma.

Expression of p53, a tumor-suppressor gene product, was studied immunohistochemically in microwave-fixed, paraffin-embedded sections of 84 colorectal carcinomas and 44 adenomas. Using a monoclonal antibody (PAb1801), nuclear p53 was detected successfully in 51 of 84 (60.7%) cases of carcinomas, and no stain for p53 was demonstrated in the adjacent normal mucosa. The results in the microwave-fixed, paraffin-embedded sections correlated with those in the frozen sections. The incidence of p53 expression in colorectal carcinomas was high in the cases with distant metastasis, but it was not affected by clinicopathologic features such as tumor size or depth of invasion. In colorectal adenomas, only 4 of 44 (9%) adenomas expressed p53. This expression of p53, however, was restricted to only a few glands within tubular adenomas with mild dysplasia. Thus, p53 protein was expressed preferably by malignant tumors of the colorectum. The present study demonstrated the usefulness of microwave fixation to preserve p53. The immunohistochemical detection of p53 in microwave-fixed, paraffin-embedded sections of colorectal carcinoma and adenoma can provide valuable information about the mechanism of carcinogenesis in colorectal epithelium.

Adenoma↗
PubMed1992

Use of a local immunotherapy as an adjunctive tool for the generation of human monoclonal antibodies from regional lymph nodes of colonic cancer patients.

Human hybridomas were generated through the fusion of the human B-lymphoblastoid cell line HO-323 with the regional lymph node lymphocytes of colonic cancer patients who had received a local immunotherapy. A total of 353 hybridomas were obtained from 4 patients and 116 of these were found to secrete greater than or equal to 100 ng/ml human immunoglobulin. The efficiency was remarkably high as compared with that from patients without the local immunotherapy. Further immunohistological examination showed that 5 hybridomas secreted IgM which selectively reacted with colonic cancers. The results indicate that local immunotherapy could be an adjunctive tool for the generation of highly potent human hybridomas through augmenting the host's immunity.

Antibodies, Monoclonal↗
PubMed1992

[Effect of intratumoral injection of the mixture of OK-432 and fibrinogen (OK/fbg) on gastric cancer].

We have reported the intratumoral injection of OK/fbg is a very effective immunotherapy for colorectal cancer. In this study, we injected OK/fbg into gastric cancer. Histopathological examinations revealed the formation of fibrin fibers, marked infiltration of inflammatory cells and regression of tumor tissue. Seven days after injection, cytotoxicity of splenic lymphocytes was significantly high and HLA-DR, CD25+ splenic lymphocytes were increased. But there was no significant change in peripheral blood and lymph node lymphocytes. On the contrary, several hours after injection, cytotoxicity and surface markers were changed in peripheral blood and lymph node lymphocytes. However, there was no change in splenic lymphocytes. We suppose that activation of splenic lymphocytes was caused by activation of peripheral blood and regional lymph nodes.

Chemotherapy, Adjuvant↗
PubMed1991

A novel point mutation at codon 146 of the K-ras gene in a human colorectal cancer identified by the polymerase chain reaction.

In this report, point mutations of the K-ras gene at codon 146 were analyzed in 25 cases of colon cancer, 4 cases of lung cancer, and 41 cases of lymphoid malignancy. A codon 146 mutation substituting threonine (ACA) for alanine (GCA) was detected in the tumor tissue of a patient with colon cancer and was not detected in the normal tissue of the same patient. Any additional mutations of the ras gene family were not detected in this patient. These results suggest that the codon 146 mutation of the K-ras gene could be involved in the development of naturally occurring human malignancies.

Antisense Elements (Genetics)↗
PubMed1991

The partial characterization and clinical evaluation of pancreas cancer-associated antigen from the ascites fluid of a patient with pancreatic cancer.

Monoclonal antibodies against pancreas cancer-associated antigen (PCAAp) were produced by established hybridoma cells. Two monoclonal antibodies, 3F1 and 3B6, were selected and these two monoclonal antibodies were found immunohistologically to react strongly with cancer cells and intraductal mucin-like products in well-differentiated pancreatic cancer tissues, but weakly, if at all, with gastric, colorectal and other cancers and at all not with normal adult or fetal pancreatic tissue. PCAAp is usually expressed in normal colonic mucosa (PCAAc), but the two monoclonal antibodies scarcely reacted with normal colonic mucosa. A sandwich enzyme immunoassay was developed to measure circulating PCAAp. Thirty-two normal subjects and 271 patients comprised of 210 with malignant disease and 61 with benign disease were surveyed. The cut-off value of PCAAp levels in the 32 normal subjects was 2.06 micrograms/ml, being the mean + 2SD, while PCAAp levels of more than this were observed in 72 per cent of the patients with pancreatic cancers, 65 per cent of those with bile duct cancers, 60 per cent of those with hepatomas, 0-30 per cent of those with other malignant diseases, and 10 per cent of those with benign hepatobiliary diseases. The susceptibility of isolated PCAAp and PCAAc to various enzymes and chemical reagents were also studied. The results of this study suggest that the assay for PCAAp might be useful in the diagnosis of pancreatic cancer.

Adult↗
PubMed1991

Perforin expression in lymphocytes infiltrated to human colorectal cancer.

Perforin (PFP) is a cytotoxic protein released from killer cells. PFP immunoreactivity in human peripheral blood lymphocytes (PBL) and tumour infiltrating lymphocytes (TIL) was investigated immunocytochemically with the aid of an anti-PFP monoclonal antibody. PFP was detected in the cytoplasm of 10% of PBL. We performed a double staining of PFP+ cells with Leu11b/CD16, Leu2a/CD8, or Leu3a/CD4 and showed that PFP was produced by 9% of CD8+ cells and 18% of CD16+ cells but not by CD4+ cells. In 28 colorectal cancer tissues, PFP immunoreactivity was observed in the lymphocytes infiltrating to the tumour stroma. The PFP+ cells were most numerous in Dukes A and decreased in number according to the progression of tumours. The PFP+ cells in TIL exhibited the same phenotypes as those in PBL but the PFP+ cells were more numerous in CD8+ cells than in CD16+ cells at all stages. This study represents the first evidence that PFP is mainly secreted from CD8+ cells in tumour tissues. It is hypothesised that the decrease in the number of PFP+ cells in accordance with tumour progression may reflect the suppression of the hosts local immunity.

Antibodies, Monoclonal↗
PubMed1991

Immunohistochemical analysis of amylase isoenzymes in thyroid cancer.

The expression of amylase in various histological types of thyroid cancer was studied by an immunohistochemical technique, using a polyclonal antiamylase antiserum and two monoclonal antibodies specific for salivary and pancreatic-type amylases, respectively. Amylase was expressed in 21 of 24 (88%) thyroid cancers by polyclonal antiserum analysis. Analysis by monoclonal antibodies, however, showed that only 13 (54%) cases and three (13%) cases contained salivary-type and pancreatic-type amylases, respectively. Moreover, immunoreactivity for pancreatic-type amylase was detected only in medullary carcinoma; other histological types were positive for salivary-type amylase. These results show that thyroid cancer frequently expresses amylase, and suggest that the differences between amylase isoenzymes in thyroid cancer may correlate with those found between cellular origin of tumour.

Amylases↗
PubMed1991

Production of three monoclonal antibodies specifically reactive respectively with the ductal, acinar and islet cells of the human pancreas.

Three monoclonal antibodies, designated FP-1, FP-2 and FP-3, were obtained by immunizing a BALB/c mouse with dispersed human fetal pancreatic cells and using hybridoma technology. FP-1, FP-2 and FP-3 reacted specifically, respectively, with the ductal epithelial, acinar and islet cells, of the fetal pancreas as well as with adult human pancreatic tissue, suggesting a use in the discrimination of pancreatic cell types. Upon screening various tumor tissues, FP-1 was found to react with adenocarcinomas of the pancreas (16/23), stomach (7/8), colon (4/6) and gall bladder (2/2) as well as with the three malignant cell lines, PANC-1 (pancreas), HT-29 (colon) and LoVo (colon). In contrast to FP-1, FP-2 and FP-3 reacted with only 5% (2/39) and 0% (0/39), respectively, of these adenocarcinomas. Although FP-3 did not react with any of these adenocarcinomas, it did react with various APUDoma cells such as islet cell tumors of the pancreas (3/5), pheochromocytomas (2/2), medullary thyroid carcinomas (2/3) and gastrointestinal carcinoids (1/3). FP-3 thus appears to be the first monoclonal antibody with extremely high endocrine cell specificity.

Animals↗
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

Preparation and characterization of monoclonal antibodies to an N-linked oligosaccharide.

Two monoclonal antibodies to an N-linked oligosaccharide, MT-5 and MT-9, have been prepared by immunization with a pyridylaminated, asialylated, galactosylated, fucosylated, bisected biantennary sugar. The reactivity of these antibodies was monitored by their reaction with human asialoglycophorin in a solid-phase enzyme-linked immunosorbent assay. Both antibodies reacted with the sugar chains of various human glycoproteins such as immunoglobulin G, transferrin, gamma-glutamyl transpeptidase, alpha 1-acid glycoprotein, and alpha-fetoprotein. Treatment of asialoglycophorin with beta-N-acetylhexosaminidase or alpha-mannosidase resulted in reduction of the binding to these antibodies. The reactivity of MT-5 to asialoglycophorin was slightly inhibited by D-mannose and N-acetylglucosamine, whereas that of MT-9 was inhibited by D-mannose, N-acetyl-D-glucosamine, chitobiose, and L-fucose. The epitope specificity of MT-5 appears to be a sugar chain containing biantennary N-acetyl-D-glucosamine residues, the bisected N-acetyl-D-glucosamine residue, and a trimannosyl core. The epitope to which MT-9 is directed may be a complex made up of beta-mannose, chitobiose, and L-fucose. These studies indicate that immunization with pyridylaminated sugars can produce antibodies that recognize N-linked oligosaccharides. Monoclonal/polyclonal antibodies to the N-linked sugar chains of glycopeptides would be useful in such studies of proteins.

Antibodies, Monoclonal↗
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

Immunohistochemical study on pancreatic secretory trypsin inhibitor (PSTI) in gastric carcinomas.

The expression of pancreatic secretory trypsin inhibitor (PSTI) was studied immunohistochemically in 106 cases of gastric carcinoma. Of the 45 intestinal-type carcinomas, 34 cases (76%) expressed PSTI: 15 (63%) of 24 early carcinomas and 19 (90%) of 21 advanced carcinomas, the incidence being significantly different (P less than 0.05). Furthermore, in the intestinal-type carcinomas, a significant correlation was observed between PSTI expression and clinical stage or nodal involvement. On the other hand, of the 61 diffuse-type carcinomas, including 27 early and 34 advanced carcinomas, 54 cases (89%) were positive for PSTI; a high incidence of the PSTI expression was observed in both early and advanced carcinomas, being 93% and 85%, respectively. Moreover, PSTI-positive cells were localized in more than half of the early diffuse-type gastric carcinomas at the invading zone of the surrounding tissues. The incidence of PSTI expression in advanced scirrhous-type carcinomas (100%) was significantly higher than that (76%) in medullary-type ones (P less than 0.05). Thus, the present findings, together with the previous reports that PSTI stimulates 3H-thymidine incorporation into DNA in human fibroblasts, suggest that the PSTI expressed in gastric carcinomas may possibly possess a biologic function responsible for the tumor growth and progression and for the stromal proliferation of fibrous tissues.

Adenocarcinoma↗