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Biomedical subjects

H Ueo

Publications and source records attributed to H Ueo.

At least 145 records · Page 8Linked to original sources

Mammary carcinoma induced by oral administration of ethyl methanesulphonate. Determination of some of the parameters affecting tumor induction.

The carcinogenic activity of ethyl methanesulphonate (EMS), an alkylating agent and a potent mutagen, was examined in Wistar King A and Sprague Dawley rats following oral administration. In the Wistar King A rats, mammary carcinomas were detected in all of the young female rats by the 32nd week after initiation of the experiment. To determine the optimal experimental conditions for the rapid and invariable induction of mammary carcinomas, the relationship among age, sex, strain of the rats and concentration and duration of EMS administration, and tumor production was investigated. The tumor incidence was higher in the younger female rats and the Wistar rats were more susceptible than Sprague-Dawley rats. Mammary carcinomas were also induced in the younger male rats. In addition, concommitant production of renal tumors occurred by the 40th week in young rats administered 10(-2) M or 2 x 10(-2) M of EMS solution, while renal and uterine tumors developed concommitantly in the older female rats given 3 x 10(-3) EMS by the 56th week. Histologically, the prevailing features of tumors were infiltrating ductal adenocarcinoma in the mammary glands, mesenchymal tumor in the kidney, and leiomyosarcoma in the uterus. Methyl methanesulphonate, an analogue of EMS, did not induce tumors in any organs.

Aging↗

A safer and more reliable operative technique for esophageal reconstruction using a gastric tube.

A safer and more reliable method of esophageal reconstruction, using a gastric tube, is described. Th procedure to create an elongated gastric tube involves separate cutting of the seromuscular and mucosal layer along the line extending parallel to and 4 cm from the greater curvature of the stomach. The end of the cervical esophagus is anastomosed to the posterior wall of the gastric tube in end-to-side fashion. In addition, circumferential cutting of the seromuscular layer of the gastric tube about 5 cm from the anastomotic line is performed to avoid tension resulting from postoperative shrinkage of the gastric tube due to muscle contraction. Combination of these methods resulted in compete elimination of anastomotic leakage.

Esophageal Neoplasms↗

High incidence of rat mammary carcinoma by oral administration of ethyl methanesulphonate.

Ethyl methanesulphonate (EMS), one of the alkylating agents, is known to be a potent mutagen. We tested EMS for its carcinogenicity in female rats by oral administration. EMS was dissolved in drinking tap water at a concentration of 10(-3) M and was given for the first 12 weeks. The subcutaneous tumors were noticed as early as 16 weeks after initiating the experiment. At the 32nd week, all the surviving rats produced tumors; the majority were multiple tumors in the neck, axillar and inguinal areas corresponding to bilateral mammary glands. Histologically, the prevailing feature of the tumors was infiltrating medullary adenocarcinoma consistent with carcinoma of mammary duct origin. Neither regional lymph node involvement nor distant metastases were shown, but intraductal spread of carcinoma was a marked finding during the 32-week period.

Adenocarcinoma↗

Prognosis in gastric cancer associated with pregnancy.

Gastric cancer concomitant with pregnancy is rare. In order to determine the clinical problems and practical guidelines on this particular subject, 61 Japanese patients were analyzed for clinical features and the results of obstetric and surgical treatment corresponding to the time of detection of the gastric cancer during the gestational period. The data indicated a limitation in diagnostic approaches caused by pregnancy and difficulty in saving both the mother and the fetus. Only 20 (58.8%) of the pregnant women underwent both obstetric treatment for the fetus and surgical treatment for gastric cancer. Fifty-nine of the gastric cancer cases (96.7%) were advanced and resectability was consistently low (47.5%). The patients who received gastrectomy had a high incidence of hospital death (22.7%) and a poor prognosis--21.1% 3-year survival. Based on the authors' cases of both early and advanced gastric cancer associated with pregnancy, the importance of early detection by gastroendoscopy is emphasized.

Adenocarcinoma↗

Surgery for gastric carcinoma is feasible for patients over 80 years of age.

We report here the outcome of surgical treatment for gastric cancer in 54 patients over 80 years of age presenting from 1967 to 1989. The mean observation interval of the postoperative period was 24 days. In most cases, preoperative examinations revealed pulmonary, renal or cardiac disturbances. The postoperative morbidity rate was 40.7%, most commonly as a result of pulmonary complications. In the 2 patients with multiple organ disturbances, 1 died 1 day after operation following myocardial infarction and the other died of pneumonia 12 days postoperatively. Intensive care treatments were needed in the early postoperative period. The increased morbidity rate proved to be related to wide resectional procedures such as total gastrectomy, operative time in excess of 3 hours, and intraoperative blood loss greater than 300 ml (p less than 0.05). When adjustment for confounding variables was made in the multivariate discriminant analysis, the type of surgery proved to be a major independent risk factor related to postoperative complications. The majority of tumors (92.6%) could be removed by standard resectional procedures and curative operation was feasible for 36 (66.7%) patients. There were 24 deaths due to progression of the cancer. The crude overall 5-year actuarial survival rate was 23.8%, while the rate was 36.9% when correction was made for sex and age. The probability of long-term survival for patients in a relatively early stage of disease (T1-2, N0-1) was statistically better than for those with a more advanced disease (T3-4, N2, M1). Thus, even for patients in the 8th decade of life, gastric surgery can be considered, for carefully selected patients.

Aged↗

Evaluation of MTT assay in agarose for chemosensitivity testing of human cancers: comparison with MTT assay.

The MTT assay in agarose, a simple colorimetric test performed in double-layer agarose, has been evaluated for chemosensitivity testing of fresh tumor samples from human cancers in comparison with the MTT assay. The absorbance of cells from fibroblast cell lines or normal tissues was markedly reduced in agarose. The chemosensitivity of cells from a carcinoma cell line or fresh tumor tissues was not apparently affected by the presence of almost 50% of fibroblast or nonmalignant cells in the MTT assay in agarose, whereas it did so in the MTT assay. The frequency of the differences between chemosensitivity of fresh tumor samples in both assays was increased, when the tumor tissue cells contained a higher proportion of nonmalignant cells, i.e. vimentin-positive cells. In 173 patients with various carcinomas, in vitro sensitivity to 7 drugs in the MTT assay in agarose was significantly greater than that in the MTT assay. Further, the MTT assay in agarose had a higher accuracy for prediction of either sensitivity or resistance than the MTT assay in a total of 38 in vitro-in vivo correlations. These results indicated that the MTT assay in agarose was a more suitable technique for the application to chemosensitivity of fresh tumor samples from patients with various carcinomas as compared to the MTT assay.

Adult↗

Antitumor effects of intraarterial infusion of tumor necrosis factor/lipiodol emulsion on hepatic tumor in rabbits.

Human recombinant tumor necrosis factor (TNF) suspended in lipiodol (TNF/lipiodol emulsion) was injected via the hepatic artery, and its antitumor effects on VX2 tumor inoculated into the liver were evaluated. In TNF/lipiodol-treated rabbits, soft-X-ray study revealed an accumulation of lipiodol in the liver tumor and the TNF concentration in the tumors was significantly higher than in rabbits treated with free TNF. 7 days after the various treatments, the tumor growth ratio evaluated macroscopically was found to be significantly lower in TNF/lipiodol emulsion-treated rabbits compared to rabbits treated with either free TNF or lipiodol (p < 0.05). Microscopically, the necrotic-area ratio of the tumors in the TNF/lipiodol emulsion-treated group was also significantly greater than in any other group (p < 0.01). Pathohistologically, liver tumors treated with TNF/lipiodol emulsion revealed massive necrosis associated with occlusive thromboangitis in the tumor vessels and fibrous capsule formation around the tumor. In these rabbits, the elevation of serum transaminase after the treatment was transient and tissue damage in the surrounding noncancerous liver tissue was minimal. These findings therefore suggest that the intraarterial infusion of TNF/lipiodol emulsion may produce prominent antitumor effects, possibly due to the retention of TNF in the tumors, which causes damage to the endothelium of the tumor vessels.

Animals↗

Rapid hyperthermic cell sensitivity test measured by RNA synthesis using contact-sensitive plates of confluent Balb/c 3T3 cell monolayers.

We have developed a hyperthermic sensitivity test for human neoplastic cells using contact-sensitive confluent monolayers of BALB/c 3T3 cells designated as 'contact-sensitive plates (CSP)', which almost completely inhibited the growth of normal cells without influencing the growth of the human neoplastic cells. On 'CSP', the relative [3H]uridine incorporation into RNA of the hyperthermic cultures showed an excellent correlation with the relative clonogenic efficiency of the treated cultures. Since 'CSP' allows for only contact-insensitive tumour cells to proliferate, our assay will predict the hyperthermic sensitivity of only the neoplastic cells. Moreover, even 2 x 10(3) cells derived from clinical tumour tissues can be assayed within only 3 days. This assay system is potentially used as a rapid in vitro hyperthermic sensitivity test for human carcinoma.

Animals↗

Expression of tissue inhibitor of matrix metalloproteinase-1 in human breast carcinoma.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an inhibitor of matrix metalloproteinase (MMP) in human carcinomas. TIMP-1 is thus considered to inhibit carcinoma invasion and metastasis. On the other hand, recent reports have disclosed that TIMP-1 also possesses a growth-promoting function. The clinical significance of TIMP-1 expression has not been fully determined in breast carcinoma. We thus examined the expression of TIMP-1 mRNA in tumor tissues of 100 breast carcinoma cases by a reverse transcriptase-polymerase chain reaction assay. The expression of TIMP-1 mRNA in each case was evaluated semi-quantitatively with adjustment for the TIMP-1 expression in a control breast carcinoma cell line, MCF7. There was a significant inverse correlation between the TIMP-1 expression and lymph node metastasis (p<0.05). A multivariate analysis disclosed that TIMP-1 expression status was an independent determinant factor for lymph node metastasis. In addition, the tumors with positive estrogen or progesterone receptors showed a higher TIMP-1 mRNA expression than those without the receptors, but this did not reach statistical significance. The findings suggest that the breast tumors with high TIMP-1 expression might show less malignant potential than those with low TIMP-1 expression.

Adult↗

Clinical significance of MT1-MMP mRNA expression in breast cancer.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is known as an activator of MMP-2. We reported that the expression of MT1-MMP is a powerful indicator of lymph node metastasis in gastric cancers. We now examined the possibility that MT1-MMP expression also is an indicator of lymph node metastasis in breast cancer. We examined the clinicopathologic significance of the expression of MT1-MMP mRNA in 53 breast cancer specimens by the semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay. The highest expression of MT1-MMP was found in those specimens showing lymph node metastasis and/or lymph vessel invasion. Therefore, an analysis of MT1-MMP can predict the presence of lymph node metastasis in breast cancer patients by RT-PCR assay in minute amounts of tissue. We believe this is an objective assay for determining the role of MT1-MMP for metastasis in patients with breast cancer.

Adult↗

Heparanase expression in clinical digestive malignancies.

Recently, mammalian heparanase was cloned, and its probable function in tumor progression was reported. However, its expression in human clinical cancers has not been fully studied. Thus we determined the heparanase mRNA expression in 30 esophageal cancer cell lines and 144 clinical samples including 38 esophageal squamous cell carcinomas, 71 gastric adenocarcinomas, and 35 colorectal adenocarcinomas. The fresh surgical specimens of cancer tissue (T) and its paired normal tissue (N) were used. The heparanase mRNA was evaluated by reverse transcriptase-polymerase chain reaction, and the T/N expression ratio was determined in clinical cases. All 30 esophageal cancer cell lines expressed heparanase mRNA. The T/N ratio was determined as high (> or =1.3), equal (0.8 approximately 1.2) or low (< or = 0.7) in each clinical case. In cases of esophageal cancer, 7 showed high, 10 equal and 21 low expression. In cases of colorectal cancer, 3 showed high, 16 equal and 16 low expression. On the other hand, 42 showed high, 22 equal and 7 low expression in cases of gastric cancer. The frequency of high expression cases was greater in gastric cancer than in esophageal or colorectal cancers (p < 0.05). There were no differences in clinicopathologic factors including prognosis between high and low expression cases of each cancer. Our mRNA study of heparanase indicated that its expression status was different among gastrointestinal cancers. The clinical and pathological impact was low compared to other proteinases, although further studies are recommended for final conclusion.

Adenocarcinoma↗

An effective pre-operative chemoimmunotherapy regimen against advanced gallbladder carcinoma: a case report.

We designed a chemoimmunotherapy regimen with a single dose of mitomycin C (MMC) followed by subsequent OK-432 injections, since the ability of peripheral blood mononuclear cells (PBM) to generate OK-432 activated killer cells had previously been shown to be augmented by MMC in cancer patients. We herein report on a case with far advanced gallbladder carcinoma who demonstrated a remarkable response to this chemoimmunotherapy, and thus underwent a curative resection. A 67 year-old Japanese woman was diagnosed as having gallbladder carcinoma with invasion to the liver and portal vein, as well as obvious lymph node metastasis. Since these findings suggested the tumor to be unresectable at that time, our chemoimmunotherapy regimen with MMC and OK-432 was administered. After four courses of therapy, a computed tomography (CT) scan revealed the disappearance of both tumor invasion to the surrounding organs and lymph node metastasis, which therefore prompted us to attempt a radical tumor resection. The histology of the resected specimen revealed that the majority of cancer cells had been killed by the pre-operative therapy and that only remnants of viable cancer cells were found in a part of the neck of the gallbladder and in 2 regional lymph nodes. This experience thus suggests the effectiveness of our chemoimmunotherapy regimen against gallbladder carcinoma.

Aged↗

Mutation analysis of hBUB1, human mitotic checkpoint gene in multiple carcinomas.

hBUB1 is a human homolog of yeast mitotic check point gene that plays an important role in chromosome segregation. Recently mutations of hBUB1 were reported in colorectal cancer cell lines, indicating that inactivation of this gene could be directly involved in aneuploidy in human carcinoma cells. To obtain information of the magnitude of hBUB1 inactivation in multiple carcinomas, we examined mutations in 59 multiple carcinoma cell lines showing single base alteration, however, there was no mutation of hBUB1 with amino acid change in these carcinomas. There were four silent mutations at codon 93, codon 735, codon 430 and codon 98 in KYSE190, TE8 esophageal carcinoma cells, KATOIII gastric carcinoma cells and 697 B cell leukemia cells, respectively. Two candidates of mutation were identified in TE3 esophageal carcinoma cells and 697 B cell leukemia cell line at codon 9 and codon 285, respectively. This result suggests that the inactivation of hBUB1 may be very rare in human carcinomas, or restricted to certain cell lines of colorectal carcinomas.

Aged↗

Enhancement of cytotoxicity by hyperthermia after a long-term culture with 5-fluorouracil in transformed cells.

The cytotoxic effect of 5-FU (5-fluorouracil) was demonstrated to be enhanced by hyperthermia after treatment with 5-FU at even a comparatively low dose over fairly long periods. The cytotoxic effect of the combined treatment with 42 degrees C-hyperthermia and 1 microgram/ml 5-FU for 48 hrs, the cytotoxic effect of 42 degrees C-hyperthermia and 5 micrograms/ml 5-FU for 24 hrs, and the cytotoxic effect of 43 degrees C-hyperthermia and 1 and 5 micrograms/ml 5-FU for 8 hrs were studied. The maximally enhanced rate of 42 degrees C-hyperthermia after 5-FU treatment for 96 hrs was 48% after a 1 microgram/ml 5-FU treatment and 150% after 45 hrs with the 5 micrograms/ml 5-FU treatment. The maximally enhanced rate of 43 degrees C-hyperthermia after 5-FU treatment was 170% after 45 hrs with 1 microgram/ml 5-FU treatment and 180% after 24 hrs with 5 mg/ml 5-FU treatment. When V-79 cells were treated at the same temperature, the maximally enhanced rate with 1 microgram/ml 5-FU was almost equal to that of 5 micrograms/ml. Moreover, when each maximally enhanced rate was equalized, each concentration of FU (RNA)/RNA practically became equal, i.e., when the maximally enhanced rates were approximately 150 and 170-180%, FU (RNA)/RNA concentrations were about 40 and 15 ng/mg RNA, respectively. We thus concluded that FU (RNA)/RNA concentration might play an important role as an indicator of the effect of the combined treatment of 5-FU and hyperthermia.

Animals↗

Effect of heparin on unidentified fever after hepatectomy.

The antipyretic effects of heparin on fever of unknown origin were investigated in three patients after hepatectomy. The elevated temperatures in these patients seemed to be due to a pyrogen as no definite evidence of infection was obtained. Heparin (100-150 IU per kg of body weight) was given every eight or 12 hours subcutaneously, and fever disappeared in all three patients. This antipyretic effect of heparin was considered due to the acceleration of the pyrogen clearing system. The major thrust of this report is the clinical usefulness of heparin for the management of pyrexia of unknown origin.

Adult↗

The feasibility of epidural anesthesia without endotracheal intubation for abdominal surgery in patients over 80 years of age.

To evaluate the efficacy of a single application of epidural anesthesia without endotracheal intubation for elderly patients over 80 years of age, the data on 108 patients who underwent abdominal surgery were analyzed for the occurrence of postoperative complications. These patients were classified into two groups according to the type of anesthesia performed: 66 received epidural anesthesia alone (Group I) and 42, general anesthesia under endotracheal intubation (Group II). There were no lethal pulmonary complications in Group I, whereas 2 patients (4.8%) died of respiratory failure resulting from pulmonary complications in Group II. The incidence of postoperative pulmonary complications in Group I was 6.1%, which was significantly lower than the 28.6% observed in Group II (p < 0.005). The occurrence of pulmonary complications in Group I was not related to the operating time, while pulmonary complications frequently occurred in patients who underwent lengthy operations in Group II. These findings suggest that a single application of epidural anesthesia would improve the overall safety in performing abdominal surgery in elderly patients over 80 years of age.

Abdomen↗

Pancreaticoduodenectomy under epidural anesthesia without endotracheal intubation for the elderly.

To evaluate the efficacy of a single application of epidural anesthesia without endotracheal intubation for pancreaticoduodenectomy (PD), the data on 30 patients who underwent PD were analyzed for their operative morbidity and mortality. These patients were classified into two groups according to the type of anesthesia performed: 15 received epidural anesthesia alone (Group I) and 15, general anesthesia under endotracheal intubation (Group II). The clinical characteristics of the patients in both groups were comparable at the time of operation, except that Group I included a significantly larger proportion of elderly patients than Group II (p < 0.05). Postoperative pulmonary complications (PPCs) occurred in 5 (33.3%) of the Group II patients, especially in elderly patients who underwent lengthy operations, whereas no such complications occurred in the Group I patients (p < 0.05), even in elderly patients with a long operating time. The curability of the malignant tumors and the incidences of other complications were not significantly different between the two groups. These findings suggest that a single application of epidural anesthesia is effective in preventing PPCs when performing a time-consuming PD, especially in elderly patients.

Aged↗