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Biomedical subjects

D Toya

Publications and source records attributed to D Toya.

At least 37 records · Page 2Linked to original sources

Characterization of gamma-glutamyltranspeptidase from human pancreatic cancer.

To elucidate the specific changes of pancreatic gamma-glutamyl-transpeptidase (gamma-GTP) associated with malignant transformation, some properties of gamma-GTP purified from pancreatic cancer were compared with those of gamma-GTPs from normal pancreas and other tissues. Four of five pancreatic cancer gamma-GTPs showed distinctly slower electrophoretic mobility than normal pancreatic enzymes. Isoelectric points of pancreatic cancer gamma-GTPs varied in each case, but they were all higher than those of normal pancreatic enzymes. This difference in isoelectric points of gamma-GTPs between cancerous tissue and normal tissue was reduced by neuraminidase treatment. Lectin affinity chromatography revealed two of five pancreatic cancer gamma-GTPs with a greater affinity to concanavalin A (Con A) than normal pancreas gamma-GTPs. Four of five pancreatic cancer gamma-GTPs had a greater affinity to Lens culinaris agglutinin (LCA) than normal pancreas gamma-GTPs. Normal pancreas gamma-GTPs had little affinity to Phaseolus vulgaris erythroagglutinating (E-PHA), but two of five pancreatic cancer gamma-GTPs had an apparent affinity to E-PHA and one of them had a slight affinity to E-PHA. These results indicate that the transformational changes of pancreatic cancer gamma-GTP are mainly induced in the sugar chains of the enzyme molecule, resulting in lower content of sialic acid and higher content of fucose and bisecting GlcNAc residue (the beta-N-acetylglucosamine residue linked at the C-4 of the beta-mannosyl residue of the trimannosyl core of the asparagine-linked sugar chain) as compared with the normal pancreatic enzyme.

Carcinoma, Hepatocellular↗

Measurement of a pancreatic cancer-associated antigen (DU-PAN-2) detected by a monoclonal antibody in sera of patients with digestive cancers.

DU-PAN-2 is a high-molecular-weight glycoprotein defined by a murine monoclonal antibody (MAb) against a pancreatic ductal adenocarcinoma cell line. In order to evaluate the usefulness of this antigen as a tumor marker, we determined the serum level of the antigen by competitive inhibition radioimmunoassay in sera from 139 patients with various malignant tumors, chiefly digestive cancers, 98 patients with different benign diseases and 11 healthy subjects. Values in the healthy subjects were less than 100 U/ml. Levels above 100 U/ml were frequently observed in sera from benign diseases, but levels above 400 U/ml were found in only 6 of the patients with benign diseases. In contrast, levels exceeding 400 U/ml were detected in 72% of patients with pancreatic cancer, 44% of patients with hepatocellular cancer and 40% of patients with biliary tract cancer. The positivity was low in other cancers such as gastric cancer (19%) and colorectal cancer (7%). Serum levels of CEA and CA 19-9 were also determined in cancer patients. Among the pancreatic cancer patients studied, values above 400 U/ml were found in 5 of the 8 CEA-negative patients (less than 5 ng/ml) and 2 of the 3 CA 19-9 negative patients (less than 37 U/ml). These results indicate that determination of the serum DU-PAN-2 can aid in serological diagnosis of cancer of the digestive tract, more particularly of the pancreas.

Adenocarcinoma↗

Factors affecting serum levels of CA 19-9 with special reference to benign hepatobiliary and pancreatic diseases.

In order to elucidate the factors affecting the serum levels of CA 19-9, we analyzed sera of 79 patients with pancreatic cancer and 169 with non-malignant diseases, chiefly consisting of hepatobiliary and pancreatic diseases. Serum CA 19-9 values in patients with pancreatic cancer had no relation to the location of the tumor or presence of jaundice. Similarly, no tendency was observed as to the location and size of tumor or to the grade of differentiation in 12 CA 19-9-negative patients with pancreatic cancer. Serum levels of CA 19-9 in patients with cholelithiasis complicated by cholangitis frequently showed markedly high values, but then rapidly normalized in parallel with the subsiding of inflammation. The behaviour of serum CA 19-9 showed little relation to renal or hepatic failures or to intrahepatic cholestasis. However, slightly elevated levels of the antigen were found in more than half of those patients with fulminant hepatitis showing massive necrosis. In chronic pancreatitis, the prevalence was only 8%; however, an increase was observed at the time of exacerbation in 2 of 5 positive patients. There was hardly any increase in serum levels of CA 19-9 after endoscopic retrograde cholangiopancreatography (ERCP), although serum levels of pancreatic enzymes rose after ERCP in almost all patients. Thus, it appears that CA 19-9 does not easily escape into the bloodstream, unlike pancreatic enzymes.

Antigens, Neoplasm↗

Serum tumor markers in patients with hepatocellular carcinoma: diagnosis of alpha-fetoprotein -low or -negative patients.

The presence of specific gamma-glutamyl transpeptidase isoenzyme (gamma-GTPI) and variant alkaline phosphatase (VAALP) were concurrently determined, and levels of basic fetoprotein (BFP) and carcinoembryonic antigen (CEA) in addition to alpha-fetoprotein (AFP) were measured in 144 hepatocellular carcinoma (HCC) patients in order to evaluate the diagnostic value of these tumor markers with respect to AFP-low or -negative patients and the tumor stage. Serum AFP levels below 400 ng/ml, commonly seen in sera of hepatobiliary diseases other than HCC, were noted in 42% of the patients. The diagnostic usefulness was increased by combination assay of these markers except for CEA. A definitive diagnosis of HCC could be made in 78% of the patients by a combination of gamma-GTPI, VAALP and AFP. Moreover, a diagnosis of malignancy could be made in 87% of cases by the inclusion of BFP. The prevalence of BFP and CEA increased in proportion to the tumor stage, whereas that of AFP and gamma-GTPI were independent of stage and were high even in patients in comparatively early stages. Furthermore, secreting type markers such as AFP and gamma-GTPI were relatively useful for diagnosis of HCC when the lesions were still small.

Alkaline Phosphatase↗

[Evaluation of the measurement of serum carcinoembryonic antigen (CEA) levels using monoclonal antibody].

We measured serum carcinoembryonic antigen (CEA) levels in 164 cancer patients, 153 patients with benign diseases and 45 healthy controls using monoclonal antibody and compared CEA levels by monoclonal antibody (m-CEA) with those by polyclonal antibody (p-CEA). There was a good correlation between m-CEA and p-CEA, especially in cancer patients. The positively of m-CEA was almost the same as that of p-CEA in cancer patients. But, false-positive cases by m-CEA were less common than by p-CEA in non-cancerous patients. Thus, the measurement of m-CEA was not less useful than that of p-CEA.

Antibodies, Monoclonal↗

[Novel gamma-GTP isoenzyme and hepatocellular carcinoma].

The authors discussed the clinical significance and some properties of the novel gamma-GTP isoenzyme (novel gamma-GTP) which was reported to be specific for sera of hepatocellular carcinoma (HCC) in our previous publications. One or more of specific bands (novel gamma-GTP) such as bands II, II' and I' were electrophoretically detectable in 109 (55%) of 200 patients with HCC, but only in 3% of 279 patients with other hepatobiliary diseases. Novel gamma-GTP was found in 38% of HCC patients with AFP levels below 400 ng/ml. The incidence of novel gamma-GTP was independent of the clinical stage as classified by liver scanning. Even in stage I, where filling defects were not seen, the incidence was 52%. It is concluded that novel gamma-GTP is useful in diagnosis of HCC patients with low levels of AFP or at a relatively early stage. Some properties of gamma-GTP purified from HCC tissues were investigated and compared with those of the normal kidney enzyme. The enzymes from HCC and kidney were identical in enzymatic and immunological properties, whereas a considerable difference was observed in electrophoresis, Con A affinity, effect of neuraminidase and isoelectric point. Respective bands II, II' and I' could be differentiated in Con A affinity and neuraminidase reaction. These results support the possibility that novel gamma-GTP in sera of HCC patients is largely due to a difference in carbohydrate moiety of gamma-GTPs.

Carcinoma, Hepatocellular↗

[Evaluation of CA 19-9 radioimmunoassay].

A carbohydrate antigenic determinant (CA 19-9) which monoclonal antibody (1116 NS-19-9) recognizes was found by Koprowski et al in 1979. Recently DelVillano et al have developed a forward sandwich radioimmunoassay (RIA) for quantitative measurement of CA 19-9. This CA 19-9 RIA Kit (CENTOCOR) was examined both experimentally and clinically. In the basic study, the standard curve obtained from this assay showed liniality, and the reproducibility of Intra-assay and Inter-assay was good. In the clinical study, using 37 U/ml as the reference value, the CA 19-9 RIA provided excellent sensitivity for pancreatic cancer (84%) and cancer of the biliary tract (69%), and excellent specificity, even among patients with benign gastrointestinal disorders. Moreover, CA 19-9 was suggested to be useful for monitoring of pancreatic cancer. Thus, the data indicate that CA 19-9 RIA can be a useful tumor marker for pancreatic cancer.

Antibodies, Monoclonal↗

Clinical evaluation of specific gamma-GTP isoenzyme in patients with hepatocellular carcinoma.

The authors evaluated specific gamma-GTP isoenzyme (specific gamma-GTP) found in sera of patients with hepatocellular carcinoma (HCC). In addition to band II and II' which had been reported in our previous publication, band I' also had a high specificity for HCC. One or more of these bands were detectable in 109 (55%) of 200 patients with HCC, but only in seven (3%) of 279 patients with other hepatobiliary diseases. Specific gamma-GTP was found in 38% of HCC patients with alpha-fetoprotein (AFP) levels below 400 ng/ml. The incidence of this isoenzyme was independent of the clinical stage as classified by liver scanning. Even in Stage I, where filling defects were not seen, the incidence was 52%. We conclude that the specific gamma-GTP is useful in diagnosis of HCC patients with low levels of AFP or at a relatively early stage.

Carcinoma, Hepatocellular↗

Purification of gamma-glutamyltranspeptidase (gamma-GTP) from human hepatocellular carcinoma (HCC), and comparison of gamma-GTP with the enzyme from human kidney.

In order to elucidate the characteristics of novel gamma-GTP, which was reported in our previous publications to be specific to sera of HCC, gamma-GTP was purified from HCC tissues, and its physicochemical and immunologic properties were compared with those of the normal adult kidney enzyme. The enzyme from HCC tissue and from normal kidney were found to be similar or identical with respect to the Km value for substrate, optimal pH, thermostability, effect of various amino acids as acceptors, behavior to cations or ethylendiaminetetraacetate, and immunologic properties. However, the HCC tissue enzyme was distinguishable from the normal kidney enzyme with respect to molecular weight, electrophoretic mobility before and after neuraminidase treatment, Con-A-affinity, sensitivity to neuraminidase, and isoelectrophoretic point. These results support the conceivability that novel gamma-GTP in the sera of HCC patients is largely due to structural differences in the carbohydrate moieties.

Carcinoma, Hepatocellular↗

[A new tumor marker--novel gamma-GTP isoenzyme].

The authors discussed the clinical significance and some properties of the novel gamma-GTP isoenzyme (novel gamma-GTP) which was reported to be specific for sera of hepatocellular carcinoma (HCC) in our previous publications. One or more of specific bands (novel gamma-GTP) such as bands II, II' and I' were electrophoretically detectable in 109 (55%) of 200 patients with HCC, but only in 3% of 279 patients with other hepatobiliary diseases. Novel gamma-GTP was found in 38% of HCC patients with AFP levels below 400 ng/ml. The incidence of novel gamma-GTP was independent of the clinical stage as classified by liver scanning. Even in stage I, where filling defects were not seen, the incidence was 52%. It is concluded that novel gamma-GTP is useful in diagnosis of HCC patients with low levels of AFP or at a relatively early stage. Some properties of gamma-GTP purified from HCC tissues were investigated and compared with those of the normal kidney enzyme. The enzymes from HCC and kidney were identical in enzymatic and immunological properties, whereas a considerable difference was observed in electrophoresis, Con A affinity, effect of neuraminidase and isoelectric point. Respective bands II, II' and I' could be differentiated in Con A affinity and neuraminidase reaction. These results support the possibility that novel gamma-GTP in sera of HCC patients is largely due to a difference in carbohydrate moiety of gamma-GTPs.

Biliary Tract Diseases↗

[Tumor markers of hepatocellular carcinoma with special reference to diagnostic efficacy of combination of these markers and relation to its stages].

The authors concurrently determined four markers consisting of novel gamma-GTP isoenzyme (Novel gamma-GTP), variant alkaline phosphatase (VAALP), basic fetoprotein (BFP) and CEA in addition to AFP in 144 patients having HCC. Serum AFP levels below 400ng/ml, a condition commonly seen in sera of hepatobiliary diseases other than HCC were obtained in 60 our of patients, or 42%. There was little correlation among positivities of these markers, and the diagnostic usefulness was increased by combination assay of these markers, except in the case of CEA. Specific diagnosis of HCC could be made in 78% by a combination of Novel gamma-GTP and VAALP in addition to AFP. Moreover, diagnosis of an existing malignancy could be made in 87% by BFP in addition to AFP, Novel gamma-GTP and VAALP. Positive ratios of BFP and CEA increased in proportion to staging, whereas those of AFP and Novel gamma-GTP were independent of the stage and relatively high even in patients within the early stage. In general, incidences of these markers were relatively lower in patients having small HCC, however, markers of a secreting type such as AFP and Novel gamma-GTP were relatively useful for early diagnosis of HCC.

Alkaline Phosphatase↗

Novel gamma-GTP isoenzyme as diagnostic tool for hepatocellular carcinoma.

Out of 13 bands of gamma-GTP isoenzymes which were separated by our method, band II, II' and I' were specifically found in sera of patients with hepatocellular carcinoma (HCC), and therefore were called HCC specific novel gamma-GTP isoenzyme (novel gamma-GTP). One or more of these bands were detectable in 95 out of 178 patients with HCC. The positive ratio of novel gamma-GTP was 53% in total patients of HCC, and corresponded to 71% in patients whose serum activity of gamma-GTP was more than 100 mu/ml. In general, there was significant correlation between positivity of the novel gamma-GTP and titer of AFP. However, it was found in 33% of patients with AFP levels below 400 ng/ml which were frequently encountered in liver diseases other than HCC. From these results novel gamma-GTP can be useful also in diagnosis of HCC patients in whom serum AFP is lower or negative.

Carcinoma, Hepatocellular↗

Subsegmental transcatheter arterial embolization for hepatocellular carcinoma in the caudate lobe.

PURPOSE: To clarify the effectiveness of transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) in the caudate lobe of the liver. MATERIALS AND METHODS: Thirteen patients with HCC in the caudate lobe underwent TAE. TAE was performed by injection of the mixture of anticancer drugs (mitomycin C and doxorubicin or epirubicin) and iodized oil, followed by gelatin sponge particles. Arterial anatomy of the caudate branch, local recurrence rate, and survival rate were evaluated. RESULTS: From 31 TAEs for the caudate lobe, 22 subsegmental TAEs were successfully performed (71%). Local recurrence in the caudate lobe was seen in 10 patients (77%). Subsegmental TAE for the caudate lobe was repeated one to five times. Cumulative local recurrence rates were 33% and 75% within 3 and 6 months, respectively. Survival rates after first TAE for HCC in the caudate lobe were 89% and 74% for 1 and 3 years, respectively. CONCLUSION: Local recurrence rate after subsegmental TAE for HCC in the caudate lobe was high. However, repeated subsegmental TAE possibly improves the prognosis of HCC in the caudate lobe.

Aged↗