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Biomedical subjects

H Ueo

Publications and source records attributed to H Ueo.

At least 91 records · Page 5Linked to original sources

Prognostic factors in Japanese patients with colorectal cancer: the significance of large bowel obstruction--univariate and multivariate analyses.

In order to define prognostic factors in colorectal carcinoma, univariate and multivariate analyses were carried out on data from 113 Japanese patients treated in a typical general hospital in Japan. In the univariate analysis, a poor prognosis was seen in those with poorly differentiated adenocarcinoma, in tumors that perforated the visceral peritoneum or that invaded directly other organs or structures (T4), in metastasis to the nodes along the main vascular pedicle (N3), in lymphatic permeation, in blood vessel invasion, in peritoneal dissemination, in Dukes C stage, and in those with lesions presenting with large bowel obstruction. Of these, only lymph node metastasis and peritoneal dissemination had an independent prognostic significance when a multivariate Cox analysis was performed. The significant risk factors related to an obstructing tumor were determined by multivariate logistic regression analysis. The significant variables were patient's age, nodal involvement and peritoneal dissemination. Since lymph node metastasis and peritoneal dissemination proved significant in both multivariate analyses, we propose that the presence of large bowel obstruction is not an independent prognostic factor in patients with colorectal carcinoma. In poor-risk patients who have an obstructing tumor, a staged operation should be attempted for definitive curative surgery.

Adenocarcinoma↗

Inhibitory effects of prostaglandin F2 alpha on mammary carcinogenesis induced by ethyl methanesulphonate in rats.

The effect of prostaglandin F2 alpha (PGF2 alpha) on mammary carcinogens was examined for a new system in female rats, using ethyl methanesulphonate (EMS). The rats were given EMS orally for a period of 12 weeks starting at age 4 weeks. Mammary carcinomas were first detected at the 16th week and were found in all surviving rats at the 32nd week. The concomitant administration of PGF2 alpha for 8 weeks made the development of tumor retarded; i.e., the carcinomas were first detected at the 30th week and final tumor incidence at the 44th week was 61.1%. The incidence of developing mammary carcinomas and multiplicity (number of mammary carcinomas per rat) were significantly lower in PGF2 alpha treated rats than in those given EMS alone. The inhibitory effect of PGF2 alpha on tumor development was apparent when PGF2 alpha was concomitantly given to the rats with EMS at age 4 weeks, while PGF2 alpha injections after oral administration of EMS at age 16 weeks did not significantly retard tumor development. Histologically, no significant difference in morphology was observed between PGF2 alpha-treated and PGF2 alpha-non-treated rats in either the cancerous or noncancerous mammary tissues. The finding demonstrates that PGF2 alpha inhibits the development of EMS-induced mammary carcinomas when given to younger rats, presumably by affecting the hormonal status rather than by direct action on the mammary glands.

Animals↗

Characterization of human esophageal carcinoma cell line established on confluent monolayer, and advantage of confluent monolayer surface structure for attachment and growth.

Biopsy tissue from a 72-year-old Japanese woman with metastasis to the cervical lymph nodes of recurrent esophageal carcinoma was adapted for culturing on the surface of lethally X-irradiated confluent monolayers of Balb/c 3T3 cells, and a continuous-growing tumor cell line was developed. These cells were found to contain keratinous material by immunohistochemical staining. We confirmed that these cells were of human origin by performing chromosome analysis. Thus, this line, designated as KSE-2 line, was considered to have originated from metastatic squamous-cell carcinoma of the human esophagus. When the attachment and growth of KSE-2 was examined on various culture surfaces, the confluent monolayers of Balb/c 3T3 cells were found to be more suitable than other substrata, such as plastic and collagen-coated dishes. The fixation of confluent monolayers of 3T3 cells with 3% glutaraldehyde had almost no affect on the colony-forming efficiency of the KSE-2 cells. In addition, the period of lag phase after inoculation of KSE-2 cells on fixed as well as nonfixed monolayers was shorter than that on plastic dishes. The conditioned medium from lethally X-irradiated 3T3 cells did not enhance the attachment and proliferation of KSE-2 cells on both nonfixed and fixed confluent monolayers. From these results, the surface structure itself of the 3T3 confluent monolayer was considered to play an important role in the favorable attachment and proliferation of KSE-2 cells.

Aged↗

Human colon cancer tissues are more sensitive than rectal cancer tissues to antitumor drugs in vitro.

The chemosensitivities of 62 human colon cancer tissues, 67 rectal cancer tissues and 31 tumor-adjacent normal mucosal tissues were determined using the in vitro succinate dehydrogenase inhibition (SDI) test. These tissues obtained at the time of surgery were exposed to carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was considered as positive when succinate dehydrogenase (SD) activity of the drug-treated cells decreased to below 50% of that of control cells, on day 3 of exposure. Decrease in the SD activity was noted in the colon cancer tissues, compared to the rectal cancer tissues, exposed to six antitumor drugs and in particular, to CQ (p less than 0.05), DDP (p less than 0.01) and ACR (p less than 0.05, one-sided paired t test). Decrease in the SD activity was noted in the tumor tissues, compared to the tumor-adjacent normal tissues, exposed to CQ, MMC and ACR (p less than 0.01). The sensitive rates were higher in the colon cancer tissues than the rectal cancer tissues, against all six antitumor drugs. Our findings show that the rectal cancer tissues are resistant to antitumor drugs, compared to the colon cancer tissues in vitro. When selecting antitumor drugs to treat patients with a rectal cancer, the assessment for chemosensitivity of the related tissues is crucial.

Antineoplastic Agents↗

Inhibitory effects of estrogen on the growth of a human esophageal carcinoma cell line.

In order to accurately determine sex hormone dependency and hormone responsiveness in human esophageal carcinoma, the effects of sex hormones on the growth of esophageal carcinoma cell lines, KSE-1 and KSE-2 cells, were examined in vitro and in vivo. Cell proliferation of cultured KSE-1 cells was inhibited by treatment of estradiol and enhanced by dihydrotestosterone (DHT), whereas KSE-2 cells were unaffected by these sex hormones. The heterotransplanted tumors of KSE-1 cells in nude mice possessed estrogen receptor (ER) and androgen receptor (AR), while the tumors of the KSE-2 cells had neither ER nor AR. When the tumor growth rates and serum hormone levels were monitored during the continuous administration of either estradiol or DHT, no significant differences were observed in either the serum hormone levels or tumor growth rates between male and female mice. The administration of estradiol significantly inhibited the growth of ER-positive and AR-positive KSE-1 tumors in both males and females in conjunction with an increase in the estradiol levels and a decrease in the DHT levels in the serum. However, the growth of ER-negative and AR-negative KSE-2 tumors was not influenced by either estradiol or DHT administration. These results suggest that the in vivo growth of human esophageal carcinoma cells with sex hormone receptor is influenced by circulating hormone levels and can be manipulated by systemic estradiol administration.

Animals↗

Estrogen receptor status and effects of endocrine ablative surgery in ethyl methanesulphonate-induced rat mammary carcinoma.

An experimental model of rat mammary carcinoma induced by oral administration of ethyl methanesulphonate (EMS) was characterized with reference to estrogen receptors (ER) and hormone dependency. After the administration of EMS, the mammary carcinomas developed more rapidly in the 4-week old rats than in the 16-week old rats. The developed mammary carcinomas were related to the ER status. Tumor development was prevented by ablative oophorectomy prior to EMS administration, but only partially, by adrenalectomy. These inhibitory effects on tumor development were more obvious when ablative surgery was performed on younger rats at age 4 weeks. In rats subjected to oophorectomy at after EMS administration at age 16 weeks, tumor induction was retarded but not completely prevented. Thus, it appears that mammary tumors induced by EMS are dependent on ovarian hormones and that mammary glands of the younger female rats are more sensitive to carcinogenic actions of EMS.

Adrenalectomy↗

Estradiol sensitivity test using contact-sensitive plates of confluent BALB/c 3T3 cell monolayers.

We have attempted to develop an in vitro assay system for predicting estradiol sensitivity of clinical cancer cells by measuring the effects of estradiol on the net DNA synthesis of primary culture cells. Superinoculation of neoplastic and normal cells onto confluent monolayers of a contact-sensitive cell line, which have been designated as contact-sensitive plates (CSPs), resulted in both the specific growth of the neoplastic cells and the growth inhibition of contact-sensitive normal cells. The applicability of CSPs to an estradiol sensitivity test was examined in the known estradiol-sensitive, estrogen receptor-possessing cell lines, MCF-7 breast cancer and KSE-1 esophageal cancer cells. The responses of each cancer cell to estradiol were sufficiently evaluated in this assay and clearly demonstrated stimulative and inhibitive growth regulatory effects of the estradiol in MCF-7 and KSE-1 cells, respectively. A total of 38 clinical carcinomas (33 of the breast and 5 of the esophagus) were tested for their estradiol sensitivity. A statistically significant increase of cancer cell growth (P less than 0.1) in nontreated culture from the 48th to the 96th h of the primary culture on CSPs was observed in 28 of 38 overall cases (73.7%), and the evaluable data were obtained within 5 days by a sampling of 5 X 10(3) cancer cells. Most of the breast carcinomas exhibited a positive correlation between the growth-stimulative effect of estradiol in this assay and the estrogen receptor levels in the resected specimens. On the other hand, a clinical case of esophageal cancer with an estrogen receptor showed a growth inhibition of primary carcinoma cells by estradiol treatment. These results therefore indicate the feasibility of predicting individual tumor response to estradiol by using a rapid sensitivity test in vitro.

Animals↗

Tumor promoters retard the loss of a transient subpopulation of cells in low passage Syrian hamster cell cultures.

Early passage normal diploid Syrian hamster (SH) fetal cell cultures contain a transient subpopulation of contact-insensitive (CS-) cells which lack density-dependent inhibition of cell division. The size of this CS- subpopulation decreases during in vitro passage by conversion of the CS- cells to contact-sensitive (CS+) cells. Approximately 10-15 population doublings after the frequency of the CS- cells has declined to below 0.001%, mass cultures cease proliferating and exhibit cellular senescence. Cultures with higher initial numbers of CS- cells exhibit longer in vitro proliferative life spans than cultures with smaller initial numbers of CS- cells. Active tumor promoting phorbol esters (12-O-tetra-decanoyl-phorbol-13-acetate [TPA] and phorbol-12,13-didecanoate [PDD]) retard the decline in the proportion of CS- cells during in vitro passage, while the inactive tumor promoting phorbol ester, 4 alpha-phorbol-12,13-didecanoate (4 alpha PDD) has no effect on the rate of loss of the CS- cells. In addition, continuous treatment from secondary culture with TPA or PDD extends by approximately twofold the in vitro proliferative life span of SH fetal cell cultures. Treatment must, however, begin at passage 1 or 2 when the CS- cells are still present. After the proportion of the CS- cells has decreased to less than 0.001% as in passage 6 cultures, promoters have no effect on the life span of the culture. This finding that exposure to promoters results in both a prolonged maintenance of the CS- cellular subpopulation, as well as an extension of in vitro proliferative life span, suggests that the conversion of CS- cells to CS+ cells is involved in the mechanism of in vitro senescence.

Animals↗

Safety of EEA staplers for anastomosis between upper esophagus and the gastric tube.

The EEA stapling devices used for intrathoracic anastomosis between the upper esophagus and the gastric tube in patients with carcinoma of the thoracic esophagus were evaluated, and the results were compared with those of an antesternally reconstructed esophagus. These approaches were both used by the same surgical team. An intrathoracic anastomosis using the EEA stapler was made in 53 patients with carcinoma of the thoracic esophagus. Minor anastomotic leakage occurred in five patients (9.4%). Good results were obtained with total parenteral nutrition for 2 weeks. Intrathoracic anastomotic complications were never fatal. Among another 106 patients with antesternally reconstructed esophagus, with the EEA stapler there were 28 patients with anastomotic leakage (26.4%) and two operative mortalities (1.9%). Intrathoracic anastomosis with the EEA stapler is recommended because it is secure and the operative procedure is simple and time-saving. For successful use of the instrument, proper technical procedures must be followed.

Adult↗

Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma.

The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (greater than or equal to 43%) was significantly better, as compared to that of patients with low cytotoxicity (less than 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL2 (greater than or equal to 1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection.

Cytotoxicity, Immunologic↗

Preoperative hyperthermochemoradiotherapy for patients with esophageal carcinoma or rectal carcinoma.

Hyperthermia is effective for the treatment of carcinoma when applied concomitantly with chemotherapy and irradiation. However, it is difficult to heat deep portions of the body, such as the esophagus and the rectum. We therefore devised an electrode for radio frequency, and we have been successfully using this electrode in the treatment of both esophageal and rectal carcinoma. The 5 yr survival rates of patients with esophageal carcinoma, given either preoperative hyperthermochemoradiotherapy or chemoradiotherapy, were 43.2 and 14.7%, respectively. On the other hand, 11 patients with rectal carcinoma underwent radical surgery after preoperative hyperthermochemoradiotherapy. In the histologic studies of in the resected specimens, patients classified as marked, moderate, mild, and no effectiveness were seen in six, three, two, and zero cases, respectively. Since there were no severe side effects in patients given hyperthermia, this treatment deserves serious consideration when treating patients with malignant lesions in the esophagus or rectum.

Adult↗

Estrogen enhances cytotoxicity of hyperthermia on cultured transformed cells.

The synergistic cytotoxicity of the combined treatment of hyperthermia and estradiol was demonstrated. This effect was measured for both clonogenic efficiency and membrane function, whose function was expressed as the initial rate of thymidine (dThd) incorporation. V-79 cells in a suspension culture were simultaneously treated with 10(-9)-10(-4) mg/ml estradiol at temperatures of 41-43 degrees C in a water bath. The survival rate of the V-79 cells decreased as the temperature increased. However, there was little decrease from treatment by estradiol alone. The survival rate for combined treatment by both heat and estradiol was lower than that of the separate treatment by either hyperthermia or estradiol alone, and the results were statistically significant. The values for Vmax (maximum reaction velocity) of hyperthermia decreased as the temperature increased, although the Vmax value of estradiol treatment alone changed little. The 1/Vmax value for the combined treatment of heat and estradiol increased in comparison with that of heat treatment alone. However, the Km (Michaelis constant) value showed little correlation with the survival rate. Based on these results, we propose that estradiol enhances cell membrane damage by hyperthermia.

Animals↗

Growth of cells superinoculated onto irradiated and nonirradiated confluent monolayers.

We prepared confluent monolayers of normal BALB/c 3T3 cells and compared differences in the growth of four types of cells superinoculated onto these nonirradiated and irradiated monolayers. The test cells were normal BALB/c 3T3 A31 cells, a squamous cell carcinoma from a human esophageal cancer (KSE-1), human fetal fibroblasts, and V-79 cells from Chinese hamster lung fibroblasts. Cell growth was checked by counting the cell number, determining [3H]thymidine incorporation and assessing colony formation. We found that on nonirradiated monolayers, colony formation of human fetal fibroblasts and normal BALB/c 3T3 cells was completely inhibited. On irradiated cells, test cells did exhibit some growth. KSE-1 cells, which had a low clonogenic efficiency on plastic surfaces, formed colonies on both irradiated and nonirradiated cells. On these monolayers, the clonogenic efficiency of V-79 cells was also higher than that on plastic surfaces. We conclude that the nonirradiated monolayer of BALB/c 3T3 cells completely inhibits the growth of superinoculated normal BALB/c 3T3 and human fetal fibroblasts, while on the other hand, they facilitate the growth of neoplastic KSE-1 and V-79 cells by providing a surface for cell adherence and growth, without affecting the presence of normal cells in co-cultures.

Animals↗

Duodenal obstruction caused by acute appendicitis with intestinal malrotation in an adult. A case report.

A 55 year old man with a short history of continuous vomiting and recent episodes of midabdominal pain and high fever was discovered to have a complete duodenal obstruction caused by acute appendicitis and intestinal malrotation. A fibrous adhesion caused by the inflamed appendix in the high caecum involved the duodeno-jejunal junction. This case is unique in that the onset of acute appendicitis triggered duodenal obstruction in the presence of an asymptomatic malrotation.

Acute Disease↗