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Biomedical subjects

N Nagasue

Publications and source records attributed to N Nagasue.

At least 19 recordsLinked to original sources
PubMed1992

Xenotransplantation of alpha-fetoprotein-producing gastric cancers into nude mice. Characteristics and responses to chemotherapy.

Three human alpha-fetoprotein (AFP)-producing gastric cancers (AFPGC) were xenotransplanted into the lateral abdominal wall of nude mice. Two tumors were established and passed over ten generations. These tumors retained their ability to secrete AFP and their characteristic hepatoid features microscopically. Serum levels of AFP in the mice were elevated as the tumors grew. Through serial transplantation, the degree of differentiation was not altered. Neither local invasion nor distant metastasis were encountered during the observation periods. Both strains had an aneuploid pattern of DNA by flow cytometric examinations. The responses of these tumors to five chemotherapeutic agents were investigated using various doses. The high AFP-titer strain (AFPGC-2) showed a marked regression or suppression of tumor growth after administration of both mitomycin C (MMC) and cisplatin (CDDP). The low-titer strain (AFPGC-1) had substantial sensitivity only to MMC. The growth of both tumors was not suppressed by 5-fluorouracil, doxorubicin, or epirubicin. These findings suggest that the characteristics of AFPGC are preserved in the xenograft model of nude mice. In addition, MMC and CDDP may be active to some extent against this rare, but highly malignant cancer.

Animals↗
PubMed1992

Comparison between diploid and aneuploid hepatocellular carcinomas: a flow cytometric study.

Nuclear DNA content of hepatocellular carcinoma (HCC) was estimated by flow cytometry after hepatic resection in 91 patients during the past 5 years. There were 53 diploid and 38 aneuploid tumours. Clinicopathological features were compared retrospectively between the patients with diploid and those with aneuploid HCC. DNA ploidy did not show any correlation with age, sex, alcohol abuse, hepatitis B virus, serum alpha-fetoprotein level or underlying liver disease. Histopathologically, the incidence of HCC less than 2 cm in diameter tended to be higher in the diploid group but no difference was seen for large tumours (greater than 5 cm). The grade of tumour differentiation also tended to be higher in this group of small HCC. The ploidy pattern did not influence the rate of capsule or daughter nodule formation, or venous invasion. There were no significant differences in survival rate or in the incidence and time of intrahepatic tumour recurrence between the two groups. This study may indicate that nuclear DNA ploidy is not a particularly predictive factor for the surgical treatment of HCC.

Aneuploidy↗
PubMed1992

DNA ploidy pattern in synchronous and metachronous hepatocellular carcinomas.

DNA ploidy of hepatocellular carcinoma (HCC) was studied in 28 patients using a flow cytometric method. Fourteen patients had two HCCs synchronously, and the remaining 14 had tumor recurrence in the remnant liver 3-41 months after curative resection of primary HCCs. DNA ploidy pattern and histopathologic parameters were compared between the synchronous and metachronous HCCs. Among those with synchronous HCCs, both tumors were diploid in 7 cases and aneuploid in 2 instances. Five patients had HCCs of different DNA ploidy pattern. On the other hand, 5 of 14 patients with metachronous HCCs had a consistent DNA ploidy between primary and recurrent tumors. In 4 cases, the first tumor was diploid whereas the recurrent HCC was aneuploid or tetraploid. In the remaining 5 cases, the primary HCC was aneuploid, but the recurrent tumor was diploid. Assuming that the difference in DNA ploidy pattern indicates a different clonal origin, the current results indicate that at least 36% of synchronous HCCs and 64% of recurrent HCCs develop in a multicentric fashion.

Adult↗
PubMed1992

The salutary effect of FK506 in ischemia-reperfusion injury of the canine liver.

The present study was designed to elucidate the effect of FK506 on 90 min of warm ischemia of the liver and reperfusion in 30 dogs. Three groups of animals were studied. Group 1 animals received FK (0.15 mg/kg/day) for three days prior to the ischemia and group 2 animals got 2 ml of saline solution for three days instead of FK and were considered controls. In group 3 FK (0.15 mg/kg/day) was injected immediately upon reperfusion and two days thereafter. Evaluation of the effectiveness of the drug was monitored by measuring the serum activities of AST, ALT, LDH, serum total bilirubin, malondialdehyde, and by histopathological examinations of the liver specimens and survival of the animals for 7 days after reperfusion. The 7 day survival of the animals in group 1 (80%) was significantly (P < 0.05) improved compared with those in group 2 (30%) and group 3 (20%). The serum activities of AST, ALT, and LDH and total bilirubin were significantly lower in group 1 than in group 2 and group 3. FK pretreatment significantly prevented hepatocellular necrosis and neutrophilic infiltration in group 1 in comparison with those in group 2 and group 3. Although the malondialdehyde level in hepatic venous blood was relatively lower in group 1, this difference was not statistically significant. Three days FK pretreatment prevented hepatocellular injury and enzyme leakage after 90 min of hepatic ischemia, whereas FK treatment immediately upon reperfusion failed to do so. In conclusion, donor organ pretreatment with FK may become a promising strategy for improved allograft survival in liver transplantation.

Animals↗
PubMed1992

Hepatocellular carcinoma and sex hormones.

The liver is morphologically and functionally modulated by sex hormones. Long-term use of oral contraceptives and androgenic steroids can induce benign and malignant hepatocellular tumors. Hepatocellular carcinoma (HCC) is more prevalent in men than in women. The role of sex hormones and their receptors in the development of HCC was reviewed. Some HCCs may be androgen dependent but others may be estrogen or even both dependent. Further studies are mandatory in order to utilize such characteristics of HCC for an effective prophylaxis and therapy of this tumor.

Animals↗
PubMed1992

Androgen receptor in cirrhotic liver, adenomatous hyperplastic nodule and hepatocellular carcinoma in the human.

Androgen receptors (AR) were assayed for cirrhotic liver, adenomatous hyperplastic nodule (AHN), and hepatocellular carcinoma (HCC) which were removed by partial hepatic resection from five patients. There were three men and two women. Age ranged from 59 to 68 years. Underlying cirrhosis was macronodular in three and micronodular in two. AHN was present within HCC in two patients, but these two lesions were found in different lobes of the same liver in another two patients. Only AHN was seen in the last patient. ARs in the cytosol of cirrhotic liver ranged from nil to 12.8 fmol/mg of protein with the dissociation constant (Kd) of 3.2-20.3 x 10(-10) M. AHNs possessed ARs ranging from 4.0 to 27.6 fmol/mg of protein (Kd values, 7.4-21.0 x 10(-10) M. All HCC nodules had ARs ranging from 11.8 to 72.8 fml/mg of protein with Kd values of 5.3-27.1 x 10(-10) M. Thus, cytosolic AR concentrations were highest in HCC, lowest in cirrhotic liver, and intermediate in AHN. The present study seems to indicate that AHN may be a precancerous lesion and that androgen and its receptor play an important role in human hepatocarcinogenesis.

Aged↗
PubMed1992

Comparison between the clinicopathologic features of AFP-positive and AFP-negative gastric cancers.

We compared 27 cases of alpha-fetoprotein (AFP)-positive gastric cancer with 478 cases of AFP-negative gastric cancer in our department. The incidences of AFP-positive gastric cancer were 5.4% (27/505), 7.2% (23/218), and 2.1% (4/187) for overall, advanced, and early cases of gastric cancer, respectively. Sex, age distribution, pathologic type, and serum carcinoembryonic antigen levels were similar between these two groups. Borrmann III type cancer, lymph node metastasis, lymphatic and venous microinvasion of the gastric wall, and incidence of synchronous and metachronous liver metastasis occurred more often in the AFP-positive group. It was suspected that the character of early venous invasion contributed to the high incidence of liver metastasis. Liver metastasis occurred in 72% of AFP-positive patients, all of whom died within 2 yr. Long-term survival of the AFP-positive group was worse than that of the negative group. The 1-, 3-, 5-, and 7-yr survival rates of both groups were 38.7%, 11.6%, 11.6%, 11.6%, and 71.3%, 57.8%, 52.8%, 49.6%, respectively (p less than 0.001).

Female↗
PubMed1992

[Evaluation of repeated hepatic dearterialization combined with intra-arterial infusion chemotherapy of unresectable primary or secondary cancer of the liver].

Repeated hepatic dearterialization combined with intra-arterial infusion chemotherapy was performed in 29 patients with unresectable primary or secondary cancer of the liver. Partial Response (PR) was obtained in 4 cases (1 hepatocellular carcinoma and 3 gastric secondaries), when evaluated by measuring the regression rate radiologically. The most remarkable effect was found in those with metastases from gastric cancer. A satisfactory result was not obtained for hepatocellular carcinoma with liver cirrhosis because of frequent associated complications. A strategy to modulate the resistance of tumors to ischemia and anticancer drugs should be considered in order to obtain a better clinical result by this method.

Catheterization↗
PubMed1992

Long-term results after modified distal splenorenal shunt with expanded PTFE interposition.

Forty consecutive patients with esophagogastric varices underwent a modified distal splenorenal shunt with expanded polytetrafluoroethylene (PTFE) interposition and were followed up for 12 to 66 months (mean 44.7). The operations were urgent in 9, elective in 14, and prophylactic in 17 patients. There were 24 males and 16 females. Age ranged from 32 to 76 years with an average of 53.8. The causes of portal hypertension were liver cirrhosis in 32, chronic hepatitis in 4, idiopathic portal hypertension in 3, and primary biliary cirrhosis in 1. Twenty-six patients were in Child's class A, 6 in class B, and 8 in class C. The operative death rate within 1 month was 2.5% and the overall in-hospital mortality rate was 5%. The shunt patency rate was 97.2% at early and 100% at late examinations. Only one patient (2.5%) had upper gastrointestinal bleeding. Hepatic encephalopathy was seen in 8 (20.5%) of 39 surviving patients. Six patients died of liver failure and another six died from various causes during the follow-up period. Twenty-six patients (65%) are alive at present. The 1-, 3-, and 5-year cumulative survival rates were 87.4%, 73.3% and 48.8%, respectively. The current modified shunt can be carried out more safely and easily and yield a similar result to that with the original Warren shunt. In order to avoid hepatic encephalopathy and liver failure, however, it is not wise to persist in this procedure.

Adult↗
PubMed1991

Progesterone receptor in hepatocellular carcinoma. Correlation with androgen and estrogen receptors.

Progesterone receptors (PgR), estrogen receptors (ER), and androgen receptors (AR) were assayed consecutively for hepatocellular carcinoma (HCC) that was surgically removed from 19 men and three women. The methods of receptor assay were the enzyme immunoassay (EIA) for PgR and the dextran-coated charcoal (DCC) technique for ER and AR. The patients ranged in age from 32 to 77 years (average, 60.3 years). No patients had received any specific anti-cancer therapy before tissue collection. All patients but one had underlying liver disease: cirrhosis in 13 and chronic hepatitis in eight. The positive rate of each receptor was 18% for PgR, 48% for ER, and 82% for AR. The titer was highest for AR, intermediate for ER, and lowest for PgR. The titers of PgR in four PgR-positive patients ranged from only 1.1 to 3.0 fmol/mg of protein. There was no relationship between PgR, ER, and AR in terms of positivity and titer. Also, other clinical and histopathologic data did not influence the positivity or concentration of these three sex hormone receptors. It can be concluded that no or little PgR exists in the cytosol of untreated HCC.

Adult↗
PubMed1991

Effect of 17 beta-estradiol on the growth of an estrogen receptor-positive human esophageal carcinoma cell line.

Receptors for estrogen and for androgen in the nucleus and cytosol (ERn, ERc, ARn, and ARc, respectively) were studied on two newly established human esophageal carcinoma cell lines, ES-25C and ES-8C. ES-25C was ERn+ (the binding content 4.0 fmol/mg protein, Kd 0.09 nM), ERc-, ARn-, and ARc-. No receptors were found in ES-8C. Various doses of 17 beta-estradiol (E2) were added in vitro to investigate its effect on the growth of these cell lines. No effect of E2 was observed on ER--ES-8C cell line. The growth of ES-25C cell was significantly inhibited at the doses of 10(-10) and 10(-12) mol/l E2 compared with the control. The doubling time of 10(-12) mol/l E2-treated cells was 32 hours whereas that of control was 20 hours. This slower growth was reflected in the deduction of cells in S-phase utilizing 5-bromo 2'-deoxyuridine (BrdU) labeling. The current results strongly suggest that the growth inhibition of ER+ esophageal cancer cell by E2 is mediated by signal transduction induced by the estrogen-estrogen receptor system.

Aged↗
PubMed1991

Attenuation of ischemia-reperfusion injury of the liver in dogs by cyclosporine. A comparative study with allopurinol and methylprednisolone.

The effects of pretreatment with cyclosporine, allopurinol, or methylprednisolone on ischemia-reperfusion injury of the liver were investigated. A total of 32 adult mongrel dogs that received one of the pretreatments were divided into four groups and were subjected to 90 min liver ischemia. Serum activities of aspartate aminotransferase (s-AST) and lactate dehydrogenase, (s-LDH) as well as animal survivals were used as indicators of liver injury. The elevation of both s-AST and s-LDH was significantly suppressed by pretreatment with cyclosporine as much as by allopurinol. However a significant improvement in animal survival was obtained only in the cyclosporine-pretreated group. Pretreatment with methylprednisolone did not affect either the activities of s-AST and s-LDH or animal survivals when compared with the control group. These data suggest that cyclosporine is a potent protector against ischemic liver injury--as effective as allopurinol or methylprednisolone. Although the precise mechanism of the effect of cyclosporine on liver ischemia still remains unknown, these observations may be of use in liver transplantation.

Allopurinol↗
PubMed1991

Beneficial effect of cyclosporine pretreatment in canine liver ischemia. Enzymatic and electronmicroscopic studies.

The effect of cyclosporine on hepatic ischemia was investigated. Hepatic ischemia was produced for 90 min in mongrel dogs. Experimental dogs were divided into three groups as follows: group A (control group), group B (CsA pretreatment group), group C (CsA posttreatment group). CsA was administered at a dose of 10 mg/kg body weight/day for 3 days in the pre- or postoperative period. Survival rates were 61.5% in group A, 84.6% in group B, and 30.8% in group C. Enzymatic activity such as aspartate aminotransferase and lactate dehydrogenase was highest in group C, lowest in group B, and intermediate in group A. Opposite results were obtained for serum albumin concentrations. The mechanisms of the effect was investigated using a 60-min hepatic ischemia model. Serum levels of beta-glucosidase and beta-galactosidase in group B were lower than those in group A and group C. Electronmicroscopic specimens taken at 16 h after 60-min hepatic ischemia demonstrated that the extent of ischemic injury was mildest in group B. The present study demonstrated a beneficial effect on hepatic ischemia of CsA administered for 3 days prior to the ischemia. One of the mechanisms for this beneficial effect could be the stabilization of lysosomal membranes. These results suggest that CsA should be administered to a donor before organ harvesting for liver transplantation because of this beneficial effect.

Animals↗
PubMed1991

alpha Fetoprotein producing early gastric cancer with liver metastasis: report of three cases.

Three cases of alpha fetoprotein producing early gastric cancer are presented. Liver metastases occurred in all patients shortly after curative gastrectomy and all died within two years. The incidence of liver metastasis was significantly higher than that in alpha fetoprotein negative early gastric carcinoma (p less than 0.001). The incidences of lymph node metastasis and invasion in lymph vessels and veins were also substantially higher in this group of patients. Two radical hepatic resections, including extended right lobectomy, were performed on one patient but the tumour recurred immediately.

Adenocarcinoma↗
PubMed1991

Plasma lysosomal enzymes after liver transplantation in the pig.

During liver transplantation in the pig, the plasma activities of beta-galactosidase, beta-glucuronidase and beta-glucosidase were elevated as early as 15 min after establishing the hepatic circulation. The enzyme activities peaked at 3 h and returned to the initial level within 2-3 days. However, such substantial alterations were not observed in other enzymes, alpha-mannosidase and alpha-glucosidase. Similar reactions to those of the first three enzymes were found in aspartate aminotransferase and lactate dehydrogenase but with later peaks and slower eliminations. In light of the current study, the serial estimation of acid hydrolases may be useful to discover the extent of tissue injury and also to evaluate the effectiveness of various organ-preservation methods.

Animals↗