Role of confluent monolayer surfaces on the growth of a newly established human esophageal carcinoma cell line.
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Biomedical subjects
Publications and source records attributed to H Ueo.
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Primary cultures of 9-d-gestation Syrian hamster embryo (E9) cells are distinct from primary cultures of later gestational age in terms of their growth and differentiation. First, primary E9 cell cultures express multiple mesenchymal differentiation lineages (e.g., adipocyte, myoblast) only rarely seen in cultures of 13-d-gestation fetal (F13) cells. Second, although most primary E9 cultures have a limited in vitro proliferative life span and exhibit cellular senescence similar to primary cultures of F13 cells, E9 cultures seem to have higher frequency of escape from senescence and conversion to continuous cell lines compared to F13 cells. Moreover, this frequency can be further increased 4- to 5-fold by continuous exposure of the E9 cells to tumor promoters or epidermal growth factor. Eleven continuous cell lines have been isolated from untreated, promoter-treated, or epidermal growth factor-treated primary E9 cultures. Seven of these are neoplastic or preneoplastic. However, the remaining four do not show any evidence of being in neoplastic progression and three of these continue to express the same differentiated phenotype observed in ther parental primary cell cultures.
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Hyperthermia alone had a lethal effect on V-79 cells. Temporary exposure to hyperthermia resulted in substantial decreases in cell growth, in a time (20-120 min)- and temperature (39-44 degrees C)-dependent manner. A precipitous fall in cell growth occurred when cells were incubated at temperatures between 42 and 43 degrees C. Concomitant application of hyperthermia, bleomycin and irradiation (hyperthermochemoradiotherapy) led to a maximal effect, compared with findings in cells treated with a single or two modalities, in vitro as well as in vivo and in clinical cases. To produce a similar situation of tumor cell growth in vivo, multicellular tumor spheroids (MTS) were developed by culturing tumor cells on soft agar. The effect of various treatments on the cells was then determined. Hyperthermia had a greater effect on the inner layer (hypoxic state) of MTS than on the outer layer, while radiotherapy was more effective on the outer layer (aerobic state). The synergistic effect of the combination with hyperthermia and irradiation was exhibited in all layers of MTS. Hyperthermochemoradiotherapy may prove to be an effective and safe form of adjuvant therapy for treating clinical carcinoma.
Biopsy tissues from a 68-year-old Japanese man with metastases to axillary lymph nodes of a recurrent esophageal carcinoma were adapted to cell culture conditions and a continuously growing tumor cell line was developed. Immunohistochemical staining revealed that these cells contained keratinous material and the electron microscopic study revealed the presence of tonofilaments. Thus, this line, designated the KSE-1 line, was considered to have originated from metastatic squamous cell carcinoma of the esophagus. This line has a binding content of 4.2 fmol/mg protein for the estrogen receptor and 2.2 fmol/mg protein for the testosterone receptor. By measurement of cell number and thymidine incorporation, the growth rate of this line was found to be moderately responsive to these hormones, being inhibited by estrogen and enhanced by testosterone at concentration levels between 10(-13) and 10(-8) and 10(-13) and 10(-6) mg/ml, respectively.
Eighteen cases of mesenteric panniculitis of the colon collected from the literature, together with two cases from the authors' source, were reviewed. The disease occurred most often in late adult life, with a male predominance. Symptoms were abdominal pain, diarrhea, constipation, and a lower abdominal mass in most patients. Barium enema disclosed narrowing, shortening, and poor extensibility of the colon, and ultrasonography and computed tomography showed thickening of the mesocolon and colonic wall with soft-tissue density. Exploratory laparotomy was done in all patients, and colectomy, colostomy, or other surgical treatments were performed in 17 (85 percent). Gross appearance at the time of surgery was characterized by a marked thickening or a firm mass of the mesocolon with a puckered surface involving the appendices epiploicae of the colon. Microscopically, degeneration of the adipose tissue, revealed by aggregates of lipid-laden macrophages, was diagnostic. Inflammatory infiltration and fibrosis also were present in many patients. Mesenteric panniculitis of the colon seems to be a lesion more advanced than the same condition of the small intestine, and colostomy or bypass surgery may be needed for alleviation of severe symptoms.
Gastric cancer associated with pregnancy is most often associated with a poor prognosis because the cancer stage is usually advanced at the time of diagnosis. The symptoms are frequently masked by factors related to the normal pregnancy and diagnostic approaches are restricted by physical and psychological clinical events. The authors treated a 30-year-old woman at 35 weeks of gestation. She had episodes of hematemesis and a prompt diagnosis of early gastric cancer was made following observations using a gastroduodenal fiberscope. A living normal child was delivered following oxytocin-induced labor and, 18 days later, curative resection for the gastric cancer was done. The patient has been doing well for over 16 months at this writing, with no evidence of recurrence. Based on the author's experience and a review of the literature, they conclude that early gastric cancer detected during pregnancy has a satisfactory prognosis and that use of the gastrofiberscope facilitates an early diagnosis in a pregnant subject with untoward symptoms of the GI tract.
The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoting phorbol diester, were determined with regard to the induction of esophageal cancer in Wistar rats following a low-dose initial administration of the esophageal carcinogen N-amyl-N-methylnitrosamine [(AMN) CAS: 13256-07-0]. The induction of esophageal cancer was enhanced by TPA given in drinking water after AMN administration; i.e., the incidence of developing esophageal cancers and the multiplicity (number of esophageal cancers per rat) were significantly higher in groups given TPA solution orally after an oral administration of AMN than in those given the AMN solution alone. The enhancement of carcinogenesis with TPA was not affected by the interval between the administration of AMN and the administration of TPA. However, pretreatment with TPA before AMN administration did not enhance the induction of esophageal cancer. Neoplasms were not detected in groups given only TPA or tap water. Because this approach is similar to the phenomenon of two-stage carcinogenesis in the skin, it should provide a meaningful experimental model for studying two-stage carcinogenesis in the esophagus.
Cell nuclear deoxyribonucleic acid (DNA) content was microspectrophotometrically determined in biopsy specimens from 75 patients with squamous cell carcinoma of the esophagus. The relationships among DNA distribution patterns, pathohistologic features, and prognosis were investigated. In patients with a high hyperploid DNA content (type IV), there was a high frequency of lymph node metastasis and lymphatic invasion, as compared with those exhibiting the near diploid DNA content (type II). In the type IV group, 22 of 23 patients died within 2 years, whereas patients with type II had a good clinical course and the 5-year survival rate was 60%. The DNA distribution pattern, determined by a multivariate Cox model analysis, was one of independent and significant prognostic variables. As these findings suggest that the DNA distribution pattern reflects the malignant potentiality of the tumor, the preoperative determinations of the DNA pattern in biopsy specimens of the esophageal carcinoma should provide a valuable parameter for predicting the prognosis.
The effectiveness of preoperative hyperthermo-chemo-radiotherapy for 25 patients with carcinoma of the esophagus was histopathologically compared with findings in 104 patients treated preoperatively with irradiation only. The preoperative hyperthermo-chemo-radiotherapy increased the rate of "markedly effective" in the resected tissue, when compared with findings in cases of irradiation only. With regard to long survival rates, the 5-year survival rates of patients classed as "markedly effective" with preoperative combined therapy exceeded events in patients classed as "moderately effective," and "ineffective," with statistical significance. Preoperative hyperthermo-chemo-radiotherapy is the recommended treatment for patients with carcinoma of the esophagus.
The therapeutic effects of combined treatment with hyperthermia (HT) and temperature-sensitive liposomes (TSL) containing Bleomycin (BLM) were evaluated in metastatic lymph nodes of AH-66 ascites tumor in rats. As a model for metastatic lymph nodes, 4 X 10(6) cells of AH-66 were inoculated into the right popliteal lymph nodes of rats. Seven days after inoculation, when the tumor in popliteal lymph nodes was approximately 8 mm in diameter, TSL-BLM was injected subcutaneously into the right foot pad, and local hyperthermia at 43 degrees C was applied for 20 minutes. The most obvious suppression of tumor growth and excellent survival rate were obtained in rats which received both TSL-BLM and HT, compared with groups receiving HT or TSL-BLM alone. These findings suggest that the combination of TSL-BLM and HT provides an effective cancer chemotherapy for patients with metastatic lymph nodes.
The combined effects of hyperthermia, chemotherapy with bleomycin and irradiation (hyperthermo-chemo-radiotherapy) on the growth of transformed cells, spontaneously established from Chinese hamster fibroblasts, were studied in vitro. Concomitant application of the 3 modalities with hyperthermia at 42 degrees C for 30 minutes, treatment with 0.02 microgram/ml of bleomycin for 60 minutes and 2-Gy irradiation led to the best effect with an 89% cytotoxicity, compared with those in cells treated with a single modality or 2 modalities. To determine the role of hyperthermia and irradiation in this enhanced cytotoxicity, the response of the cells to each modality was compared between hypoxic cells in the inner layer and aerobic cells in the outer layer of multicellular tumor spheroids. The hypoxic cells were very sensitive to hyperthermia and also the aerobic cells were very sensitive to irradiation, which appeared to be one of the mechanisms for the enhanced effects obtained with these 2 modalities.
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An interview was conducted to determine the quality of life, both objectively and subjectively, in 64 patients without a recurrence of the disease more than one year after esophageal resection and reconstruction with a gastric tube for carcinoma of the thoracic esophagus. Despite the decrease in body weight, the patients appeared to be well adjusted and had a most optimistic attitude toward their illness. The laboratory data showed normal values, postoperatively. As there was no evidence of a diminished quality of life in these patients, we consider that physicians should recommend surgical therapy for patients with carcinoma of the esophagus.
Preoperative irradiation for carcinoma of the esophagus is tentatively recommended in many, but not all, institutes. For precise appraisal of the effect of preoperative irradiation for carcinoma of the esophagus, the effects of preoperative irradiation, as related to mortality and the long term results, were evaluated in 167 patients who underwent subtotal esophagectomy. Although postoperative pulmonary complications occurred at a higher rate in patients given irradiation preoperatively, the mortality was much the same in irradiation and nonirradiation groups. In 15 (14.4 per cent) of 104 patients given radiation therapy preoperatively, no viable cancer cells were present in the resected tissues and the five year survival rate of these patients was 45.1 per cent. Thus, when the cancer cells are completely damaged, the survival time is extremely enhanced. The findings of our study suggest that the aim of preoperative irradiation should be a complete destruction of the cancer cells.
A review of 195 patients with carcinoma of the esophagus disclosed 41 cases (21.0%) with glandular and/or mucus-secreting components, in addition to the ordinary component of squamous cell carcinoma. These tumors could be grouped into three types according to representative histologic features of glandular and mucus-secreting portions: glandular type (23 cases), cribriform type (11 cases), and mucoepidermoid type (7 cases). The histologic features of the three types were reminiscent of those of adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands, respectively. Moreover, areas showing glandular or mucus-secreting differentiation were in greater part located in the submucosa and the lamina propria mucosae, thereby suggesting that such differentiation had arisen in the esophageal glands or their ducts. In all 41 cases, the ordinary element of squamous cell carcinoma, invasive, or noninvasive, was admixed in various proportions with the glandular components, indicating that this type of esophageal tumor had originated not only from the covering squamous epithelium but also from esophageal mucous-gland or ductal epithelium. The findings also support the concept of the field origin of carcinogenesis in esophageal carcinoma.
The results of 231 oesophageal resections and reconstruction in 395 patients with thoracic oesophageal carcinoma presenting in the last 20 years are reported. In patients over 70, the incidence of multiple pathology and postoperative complication was high. The most frequent causes of death after surgery were pulmonary complications, and anastomotic leakage. As the mortality rate in the aged group exceeded that of the younger groups, careful pre-operative assessment, the indication for surgery and postoperative care should be carefully considered, even though only surgery offers a hope of cure for patients with oesophageal carcinoma. If the elderly can tolerate the surgical procedures, the 5 year survival rate equals that of the younger patients.