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Biomedical subjects

E Uchida

Publications and source records attributed to E Uchida.

At least 145 records · Page 8Linked to original sources
PubMed1987

Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer.

Carbohydrate antigen (CA) 19-9 identified by a murine monoclonal antibody against a colorectal carcinoma antigen is thought to be a sialylated Lewis (Le)a blood group antigen and occurs in high concentration in serum of patients with pancreatic carcinoma. This study was designed to identify the relationship between Lewis antigens and CA 19-9 in patients with pancreatic cancer. The following analyses were performed in 20 pancreatic cancer patients: Lea and Leb antigen phenotype in saliva (modified enzyme-linked immunosorbent assay) or on red cells (hemagglutination); CA 19-9 levels (radioimmunoassay) in serum; and CA 19-9 and Lea and Leb expression (immunoperoxidase assay) on tumor tissue. Lea-b- patients based on salivary phenotype failed to express CA 19-9 in tumor tissue and had normal or low levels of CA 19-9 (less than 37 units/ml) in serum (P = 0.0011, versus Lea+b- and Lea-b+ patients). Eighty-eight % of Lea+b- and Lea-b+ patients had elevated serum CA 19-9 levels (greater than 37 units/ml). All Lea+b- and Lea-b+ patients expressed both Lea and Leb antigens in tumor tissue. These results support the view that Lea-b- pancreatic cancer patients cannot manufacture CA 19-9. Surprisingly, Lea-positive patients express Leb antigen in tumor tissue; in this subgroup, Leb antigen may be a tumor-specific biomarker.

Adenocarcinoma↗
PubMed1987

Preparation and antitumor effect of macrophage activating factor (MAF) encapsulated in liposomes bearing a monoclonal anti-human melanoma (A375) antibody.

We prepared large unilamellar vesicles containing the cell-free culture supernatant of a human T cell hybridoma rich in macrophage activating factor (MAF) and bearing monoclonal antibodies against human melanoma A375 tumor cells; their antitumor activity against A375 cells was examined in vitro and in vivo. Both MAF-immunoliposomes (bearing antibodies) and MAF liposomes (not bearing antibodies) showed macrophage-mediated cytotoxicity in vitro at a high E/T ratio (about 40). But at a low E/T ratio (about 15), only MAF-immunoliposomes showed tumoricidal activity, their activity being more than ten thousand-fold stronger compared with a soluble MAF preparation (MAF solution). MAF-immunoliposomes not only showed tumor neutralization mediated by macrophages in vivo when a mixture of tumor cells, macrophages, and MAF-immunoliposomes was locally injected, but also showed significant inhibition of tumor growth on repeated i.v. systemic administration of them. On the other hand, other samples (MAF-liposomes without the antibody, a MAF solution, and immunoliposomes without MAF) were not significantly effective against tumor growth. These results may constitute evidence that the delivery of lymphokines to the tumor sites is important or even critical when an attempt is made to treat cancer with lymphokines with the expectation of the potentiation of the host's immune system.

Animals↗
PubMed1987

Correlative studies on antigenicity of pancreatic cancer and blood group types.

Blood group-related antigenicity in 14 pancreatic cancer patients was examined by immunohistological method using monoclonal antibodies (MoAbs) against A, B, H, Lea, Leb, and CA 19-9 and compared with the phenotypic expression of the individuals' blood groups. MoAb-A reacted strongly with tumor tissue in four of five blood group A patients. Two of two patients with blood type B showed a weak, focal reactivity of their cancer with MoAb-B. H antigen was found in four of five patients from blood group A, while it was present in only one blood group O person and absent in B-type individuals. B antigen was inappropriately expressed in one person with type A blood and in two with type O. Lea antigen was expressed in all but two tumor tissues and Leb antigen in all tumorous tissues, irrespective of Le blood group status. MoAb 19-9 reacted with 11 of 14 cases.

ABO Blood-Group System↗
PubMed1986

Presence of two distinct acinar cell populations in human pancreas based on their antigenicity.

The immunohistochemical localization of ABH- and Lewis (Le)-related blood group antigens, including CA 19-9, a sialylated Lea antigen, was examined using monoclonal antibodies (MoAbs) in 18 normal human pancreases and compared with ABH blood group antigenicity of the individuals. Acinar cells expressed ABH, Leb, Ley, and in some cases, Lex antigen in various proportions, but not Lea and CA 19-9. The reactivity of Leb and Ley was similar with regard to cellular localization and specificity. In all specimens but one, the distribution of Leb (and Ley) and H antigens on the one hand, and of A or B antigens on the other, showed a reciprocal relationship, in that one group of acini expressed Leb (and Ley) and H antigens, but lacked any A or B antigens (type 1 acinar cell); another group of acinar cells had A or B antigens, but expressed neither Leb (Ley) or H antigens (type 2 acinar cell). In ductal cells, four of eight individuals with blood group A, two of three with blood group B, and five of six with blood group O expressed the appropriate antigen, while the remainder did not. Lea antigen was expressed primarily by centroacinar and terminal ductular and ductal cells of medium-sized ducts of all specimens, whereas Leb was present in the cells of small and large ducts in all but four cases. The reactivity of ductal and ductular cells to Lex was negative, except for one case. MoAb-Ley and MoAb 19-9 reacted only with a few ductal cells in six (33%) and 12 cases (67%), respectively. There was no relationship in the expression of Le-related antigens between acinar and ductal/ductular cells; nor were there any sex difference with regard to the binding patterns of any antibodies. However, age appeared to influence the reactivity of some antibodies with acinar cells. Islet cells did not react with any of the antibodies. The results indicate that, although the antigenicity of epithelial cells can be affected by the host blood group types, there might be several regulatory systems for expression of blood group antigens in a cell-specific pattern.

Adolescent↗
PubMed1986

Blood-group antigen expression during pancreatic cancer induction in hamsters.

The expression of blood group-related and tumor-associated antigens was examined in pancreatic adenocarcinomas and in the normal pancreas of hamsters to determine if this expression correlated with the host blood group and/or stage of carcinogenicity, respectively. Pancreatic tumors were induced by 4 weekly treatments of hamsters with N-nitrosobis(2-oxopropyl)amine (BOP) and analyzed immunohistochemically during different stages of tumor progression with polyclonal antibodies (PoAbs) and monoclonal antibodies (MoAbs) against A, B, O and Lewis (Le) isoantigens, including X, Y and CA 19-9 monosialoganglioside (gastrointestinal cancer antigen, GICA), as well as with PoAbs detecting human carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and the beta-subunit of human chronic gonadotropin (beta-HCG). The red blood cells of both control and tumor-bearing hamsters expressed AB and Le(a+b+)-like blood group types, as detected by polyvalent antisera. However, none of the MoAbs reacted with the hamster red blood cells. In the pancreas, all PoAbs against blood group antigens reacted with hyperplastic ducts and ductules at very early stages of carcinogenesis, as well as with neoplastic lesions, but not with normal pancreatic cells, except for the acinar cells, which were stained with PoAb-B, PoAb-Lea and PoAb-Leb. None of the MoAbs showed any affinity for the normal pancreatic cells; however, they reacted to various degrees with induced hyperplastic and neoplastic tissue. Reactivities of several MoAbs with malignant cells were greater than those with hyperplastic lesions: MoAb-B was highly reactive with all induced lesions, MoAb-A less reactive, and MoAb-H and MoAb-Ley (which has 6 sugar chains) detected only some cancer cells. Neither of the two MoAb-Lex (with 5 carbohydrate chains) reacted with carcinoma cells, although they did bind to a few hyperplastic cells. Neither MoAb-Lea and MoAb CA 19-9, nor PoAbs against CEA, AFP and beta-HCG, reacted with any normal, hyperplastic or malignant cells. These results demonstrate the differential reactivity of these PoAbs and MoAbs in normal and malignant pancreatic tissue and show that blood group antigens, especially the B isoantigens, are specific markers for induced pancreatic duct tumors in hamsters.

Adenocarcinoma↗
PubMed1986

Monoclonal antibody CO17-1A and leukapheresis in immunotherapy of pancreatic cancer.

Eighteen patients with measurable or evaluable advanced (metastatic or unresectable) adenocarcinoma of the pancreas were treated with a single infusion of monoclonal antibody CO17-1A in autologous leukocytes. No toxicity was experienced with treatment. Three of seventeen patients evaluable for response demonstrated unusually stable disease and a decrease in serum CA 19-9 antigen in two patients who expressed this biomarker. Human anti-mouse antibody developed in 81% of these patients. Monoclonal antibody CO17-1A may have a cytostatic effect in a small fraction of patients. Future clinical trials will focus on enhancing this effect with other immune modulators.

Adenocarcinoma↗
PubMed1985

Purification and properties of H+-translocating, Mg2+-adenosine triphosphatase from vacuolar membranes of Saccharomyces cerevisiae.

H+-translocating, Mg2+-ATPase was solubilized from vacuolar membranes of Saccharomyces cerevisiae with the zwitterionic detergent N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate and purified by glycerol density gradient centrifugation. Partially purified vacuolar membrane H+-ATPase, which had a specific activity of 18 units/mg of protein, was separated almost completely from acid phosphatase and alkaline phosphatase. The purified enzyme required phospholipids for maximal activity and hydrolyzed ATP, GTP, UTP, and CTP, with this order of preference. Its Km value for Mg2+-ATP was determined to be 0.21 mM and its optimal pH was 6.9. ADP inhibited the enzyme activity competitively, with a Ki value of 0.31 mM. The activity of purified ATPase was strongly inhibited by N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, tributyltin, 7-chloro-4-nitrobenzoxazole, diethylstilbestrol, and quercetin, but was not affected by oligomycin, sodium azide, sodium vanadate, or miconazole. It was not inhibited at all by antiserum against mitochondrial F1-ATPase or mitochondrial F1-ATPase inhibitor protein. These results indicated that vacuolar membrane H+-ATPase is different from either yeast plasma membrane H+-ATPase or mitochondrial F1-ATPase. The vacuolar membrane H+-ATPase was found to be composed of two major polypeptides a and b of Mr = 89,000 and 64,000, respectively, and a N,N'-dicyclohexylcarbodiimide binding polypeptide c of Mr = 19,500, whose polypeptide composition was also different from those of either plasma membrane H+-ATPase or mitochondrial F1-ATPase of S. cerevisiae.

Adenosine Triphosphate↗
PubMed1985

Lectin binding affinities of induced pancreatic lesions in the hamster model.

We examined the binding pattern of nine lectins to N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic lesions in Syrian hamsters. These lectins were Arachis hypogaea (PNA), Dolichos biflorus (DBA), Griffonia simplicifolia I (GS-I), Helix aspersa (HAA), Helix pomatia (HPA), Sophora japonica (SJA), Ricinus communis I (RCA-I), Triticum vulgaris (WGA) and Ulex europaeus I (UEA-I). All of the lectins reacted in untreated control hamsters to varying intensities with cytoplasmic components of acinar cells. GS-I, HPA, RCA-I and UEA-I bound to the basolateral surface and PNA, HAA and HPA to the luminal surface of these cells. All but GS-I, RCA-I and UEA-I stained the cytoplasm of islet cells diffusely. In untreated control hamsters, some ductal cells bound PNA, HAA and RCA-I, whereas these cells reacted negatively to the remaining six lectins. Ductular cells did not bind any of the nine lectins. Hyperplastic ductal cells in untreated hamsters were reactive with all nine lectins; however the intensity of the reactivity, cellular localization and extent differed for each lectin. In carcinogen-treated hamsters, the binding pattern of the lectins to acinar and islet cells did not differ significantly from that in untreated hamsters, whereas cells of induced ductal and ductular lesions bound each of the lectins in different patterns and intensities. The reaction of UEA-I to induced lesions was most consistent, specific and strong, thereby indicating the presence of L-fucose in glycoproteins produced by altered cells. Although the binding affinity of the lectins to induced hyperplastic lesions differed in both a quantitative and qualitative fashion, all dysplastic and malignant lesions were reactive to each lectin. This result indicates a heterogeneity in the carbohydrate structure of the glycoproteins produced by pancreatic cells during carcinogenicity.

Animals↗