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T Aikou

Publications and source records attributed to T Aikou.

At least 163 records · Page 9Linked to original sources

[Evaluation of tissue oxygenation utilizing a tonometer in the stomach tube or colon used in substitutive esophagus after surgery for esophageal cancer].

We measured serial changes in mucosal pH (pHi) as an index of blood flow of the stomach tube or the colon in a substitutive esophagus using a tonometer in 18 patients following surgery for esophageal cancer. The pHi showed the lowest level at the postoperative 1 hr (PO 1 hr) and increased significantly at PO 6 hr. At PO 12 hr, pHi showed the level of more than pHi 7.3 which increased significantly compared with PO 6 hr. The oxygen delivery and oxygen consumption increased significantly from PO 1 hr at PO 6 hr but not changed between 6 and 12 hr. It was suggested that the blood flow was inadequate in the stomach tube or the colon as a substitutive esophagus within PO 12 hr following operation despite of adequate oxygen delivery systemically. In this series, the decreased pHi were shown in 2 patients with minor leakage of anastomosis and in one patients with the perforation of stomach tube. The correlation between pHi and modified respiratory index was recognized at PO 12 hr and 24 hr suggesting that pHi was associated with the pulmonary dysfunction. Therefore, it was suggested that the value and change of pHi is an useful predicting index of occurrence of anastomotic leakage or respiratory failure which may be a fatal postoperative complication after surgery for esophageal cancer.

Aged↗

The correlation of thymidine phosphorylase activity with the expression of interleukin 1 alpha, interferon alpha and interferon gamma in human colorectal carcinoma.

Thymidine phosphorylase (dThdPase) is an angiogenic enzyme and seems to be related to an angiogenesis in human colorectal carcinoma. The incidence of dThdPase-positive cells was significantly correlated with microvessel count in 21 human colorectal carcinomas. Interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), interferon alpha (IFN-alpha) interferon gamma (IFN-gamma) induce dThdPase activity in human cancer cell lines. To study whether this phenomenon occurs in the human colorectal carcinomas, we examined the correlation between dThdPase activity and the expression levels of IL-1 alpha, TNF-alpha, IFN-alpha and IFN-gamma in colorectal carcinoma tissues. dThdPase activity was assayed by the methods of Friedkin and Robert, and the expression level of IL-1 alpha, TNF-alpha, IFN-alpha and IFN-gamma was determined by ELISA. dThdPase activity was significantly correlated with the amount of IL-1 alpha (n = 19, r = 0.347, P = 0.0001), INF-alpha (n = 18, r = 0.717, P = 0.008), and IFN-gamma (n = 4, r = 0.9777, P = 0.0234) in human colorectal carcinomas. However, the dThdPase activity was not correlated with the amount of TNF-alpha (n = 21, r = 0.235, P = 0.2682). These results suggested that the expression levels of IL-1 alpha, IFN-alpha and IFN-gamma are correlated with dThdPase activity in human colorectal carcinomas and that these cytokines may cause angiogenesis by inducing the expression of dThdPase.

Carcinoma↗

The expression of thymidine phosphorylase and thrombomodulin in human colorectal carcinomas.

Thymidine phosphorylase (dThdPase) is an enzyme involved in pyrimidine nucleoside metabolism. dThdPase activity is increased in several types of malignant tumors. Recently, we demonstrated that dThdPase is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and that dThdPase has angiogenic activity. We measured dThdPase activity and the level of thrombomodulin (TM) as a marker for endothelial cells in colorectal carcinomas and adjacent normal tissues from 21 patients, and in adenomas from 13 patients. The average dThdPase activity of colorectal carcinomas (11.58 +/- 6.30 nmol/100 micrograms protein/h) was significantly higher than that of adenomas (8.57 +/- 4.14 nmol/100 micrograms protein/h) or normal tissues (4.89 +/- 3.16 nmol/100 micrograms protein/h). In immunohistochemical study, the expression of dThdPase was observed more frequently in colorectal carcinomas than in adenomas or normal mucosas. The amount of TM in colorectal carcinomas (8.32 +/- 5.07 ng/100 micrograms protein) was significantly higher than that of adenomas (4.51 +/- 4.49 ng/100 micrograms protein) or normal tissues (3.51 +/- 2.78 ng/100 micrograms protein). dThdPase activity in human colorectal carcinomas, adenomas and normal tissues was significantly correlated with the expression of TM in these tissues. These results indicate that the expression levels of both dThdPase and TM in colorectal carcinomas are higher than those in colorectal adenomas and normal tissues and suggest that dThdPase may be involved in angiogenesis in human colorectal carcinomas, adenomas and normal tissues.

Colorectal Neoplasms↗

Flow cytometric analysis of DNA heterogeneity in superficial carcinoma of the esophagus.

BACKGROUND: There are few studies of flow cytometric analysis for DNA heterogeneity of patients with superficial carcinoma of the esophagus limited to the epithelium or superficially invading the lamina propria or submucosa. METHODS: Flow cytometric analysis of cellular DNA content was performed on superficial carcinomas of the esophagus using paraffin embedded blocks of the surgically resected specimens from 56 patients. To evaluate the intratumoral DNA heterogeneity, a total of 141 samples of the 56 tumors were analyzed, depending upon the tumor size. RESULTS: One or two of the samples was available from 18 of 19 patients with tumors 2 cm or less in greatest dimension, whereas more than three of the samples were available from 22 of 37 patients with tumors 2.1 cm or greater in dimension (P < 0.003). Of 56 tumors, 40 (71.4%) exhibited DNA aneuploidy; DNA heterogeneity was found in 26 tumors (46.4%). The remaining 16 tumors exhibited DNA diploidy. Two of the five tumors that were limited to the epithelium had DNA heterogeneity. The mean dimension of the tumors with DNA heterogeneity was significantly greater (5.8 +/- 2.8 cm) than those exhibiting DNA diploidy (2.3 +/- 1.1 cm) and DNA aneuploidy without heterogeneity (2.9 +/- 2.4 cm). Recurrences after esophagectomy were detected in 6 of the 56 patients; the DNA ploidy pattern of these six patients exhibited DNA heterogeneity. CONCLUSION: The incidence of DNA heterogeneity increases as tumor size increases and is associated with an increased risk of tumor recurrence after esophagectomy in patients with superficial carcinoma of the esophagus.

Adult↗

Expression of HGF and TGF-beta 1 mRNA after partial hepatectomy in rats with liver cirrhosis.

Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-beta 1 (TGF-beta 1) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-beta 1 in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18h after a 70% hepatectomy. The expression of TGF-beta 1 mRNA peaked at 18h after partial hepatectomy in the LC group and at 48h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-beta 1.

Animals↗

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs.

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n = 5), an 84% Hx group (n = 5) and an 84% Hx+PSS group (n = 5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immunohistochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.

Animals↗

Controlled release of poly-D,L-lactic acid containing bleomycin.

By use of four types of in vivo degradable polylactic acid (PLA), i.e. PLA with an average molecular weight of 1500 (1500DL), 2200 (2200DL), 2800 (2800DL) and 3500 (3500DL), preparations of bleomycin (BLM)-containing solid forms (polymers) were tested. The in vitro release of BLM from the polymers was also examined in an immersion system. By the melt-pressing technique, five types of BLM (2.5 mg) containing solid forms, i.e. 1500DL polymer, 2200DL polymer, 2800DL polymer, 3500DL polymer and 1500DL + 3500DL (a mixture of 1500DL and 3500DL) polymer were prepared. In all five types of polymers, cumulative BLM release was controlled to less than 5% by the third day and no initial burst of the release was observed. BLM release from the polymer continued for 3 weeks at the shortest and 6 weeks at the longest. Various polymers containing BLM could be useful for the site of drug administration or anti-cancer release pattern.

Bleomycin↗

Lymph node metastasis of early stage carcinoma of the esophagus and of the stomach.

We undertook a comparative histologic study of early stage carcinoma of the esophagus and stomach, with tumor invasion limited to the submucosa. Here we analyze lymph node metastasis, lymphatic invasion, and vascular invasion. Our study is based on a retrospective review of 77 patients with early stage carcinoma of the esophagus and 192 patients with early stage carcinoma of the stomach treated during the period from 1973 through 1991. The incidence of lymph node metastasis and lymphatic invasion was significantly higher in intramucosal or submucosal esophageal cancer than in intramucosal or submucosal gastric cancer. However, there was no significant difference between intramucosal esophageal cancer and submucosal gastric cancer. The metastatic site of lymph nodes in esophageal cancer tended to be distant from the location of primary tumor compared with lymph nodes invaded by gastric cancer. Lymphatic invasion and vessel invasion between submucosal esophageal cancer and submucosal gastric cancer was statistically significant. From these results, we conclude that intraepithelial or intramucosal esophageal cancer is comparable to early stage carcinoma of the stomach, whereas submucosal esophageal cancer is actually an advanced lesion.

Adenocarcinoma↗

Increased midkine gene expression in human gastrointestinal cancers.

Midkine (MK) is a product of a retinoic acid-responsive gene, and is a novel growth differentiation factor. We examined the expression of the MK gene in specimens of 47 surgically removed human carcinomas of the gastrointestinal organs, namely, gastric, colorectal, hepatocellular, pancreatic, esophageal, ampullary duodenal and bile duct carcinomas. In most cases, the MK mRNA level was higher in cancer specimens than in the corresponding non-cancerous tissues. Furthermore, MK mRNA was more highly expressed in the colon adenocarcinoma lesion than in the adenoma lesions, in the two familial polyposis cases. While MK mRNA was not detected in the normal liver, it became detectable in cirrhotic tissues in 2 of 4 cases, and its expression was increased in the cancerous tissues. Thus, the increase of MK mRNA level is a phenomenon seen in many human gastrointestinal carcinomas. The increased expression of the MK gene in gastric carcinoma was significantly more prominent in well and moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas and signet ring cell carcinomas.

Adult↗

[Molecular biological mechanism of cancer metastasis and the prediction of metastasis in clinical cases].

An outline of the mechanism of cancer metastasis is presented from a molecular biological point of view, and the present state and future possibility of prediction about cancer metastasis in clinical cases is described. Cancer metastasis is developed through multiple steps. With the progress of studies on the mechanism of metastasis, the effort to predict cancer metastasis in clinical cases has progressed. Metastasis is formed in concern with many factors, so it may be highly difficult to explain clinical metastasis by a single factor. It will be important to comprehensively put many factors into consideration. For the preoperative diagnosis of the potential of metastasis, examination of specimens from endoscopic biopsy or blood serum will become more important.

Cell Adhesion Molecules↗

A modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay for quantitating tumor cell invasion.

Reconstituted basement membrane matrix (Matrigel) has been utilized for in vitro assay of tumor cell invasion in recent years. In the conventional chamber for the invasion assay, however, a large number of cells passed easily through the center of the Matrigel-coated filter because the Matrigel layer could not be completely uniform by the meniscus formation. To prevent the meniscus phenomenon of the Matrigel layer, we devised a water-repellent treatment of the inside wall of the assay chamber with paraffin. Consequently, very few erythrocytes passed through the Matrigel-coated filter of this modified chamber with the erythrocyte assay, which was used to demonstrate the evenness and uniformity of the Matrigel layer on the filter. For quantitating a small number of cells which invaded through the Matrigel-coated filter by the invasion assay, a tetrazolium-based colorimetric 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay was used. The invasive abilities of the eight different cells were determined by this invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay using the modified chamber with a filter coated with 70 microliters of the 0.2-mg/ml Matrigel. After 72 h of incubation, the malignant cell lines significantly exceeded the normal cell lines in the percentage of invasion (P < 0.01). Therefore, the modified invasion-3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium+ ++ bromide assay provides a simple, easily reproducible in vitro assay for quantitating tumor cell invasion.

Animals↗

Expression of desmoglein I in squamous cell carcinoma of the esophagus.

Desmoglein I (DGI) is major component of the desmosomal membrane core that plays an important role in epithelial cell adhesion. The aim of this study was to explore the correlation between the expression of DGI and the clinicopathological findings of esophageal cancer. DGI expression was immunohistochemically examined using an anti-DGI monoclonal antibody in 139 patients with squamous cell carcinoma of the esophagus. Normal squamous epithelial cells strongly expressed DGI at their cell-cell boundaries. According to the intensity and pattern of DGI expression, the cancerous tissues were divided into three groups: DGI (++), DGI (+), and DGI (-). Of the 139 tumors, 35 (25%) were DGI (++), 65 (47%) were DGI (+), and 39 (28%) were DGI (-). A good inverse correlation between DGI expression and tumor invasion, lymph node metastasis, lymphatic invasion, and vessel invasion was observed. These results indicate that DGI expression may be a significant factor for invasion, metastasis, and prognosis of human esophageal cancer.

Adult↗

In vivo activity of bleomycin incorporated with biodegradable poly-d,l-lactic acid and implanted in the mediastinum of dogs.

The possible usefulness of bleomycin incorporated with biodegradable poly-d, l-lactic acid (BLM-PLA) for targeting chemotherapy for esophageal cancer was studied in vivo. Local levels of BLM after administration were compared with those after injection of BLM-SOL, an aqueous solution of BLM. BLM-PLA or BLM-SOL was administered into the upper mediastinum under a right thoracotomy in 36 mongrel dogs. On days 10, 20, and 30 after administration, connective tissues, lymph nodes, lung, liver, kidney, and spleen were removed, and BLM activity was measured. High activity of BLM was detected for 30 days after BLM-PLA administration in both the connective tissues and the lymph nodes, compared with BLM-SOL administration. BLM activity was low in the other organs after BLM-PLA administration. BLM in the blood was significantly lower after administration of BLM-PLA than BLM-SOL. The results indicate that BLM-PLA may become a useful tool in targeting chemotherapy for esophageal cancer.

Animals↗

Occult lymph node metastasis in gastric cancer with submucosal invasion.

To evaluate more precisely the incidence of lymph node metastasis in patients with submucosally invaded (sm) gastric cancer, three additional sections were made from the remaining half of 1,794 lymph nodes taken from 57 patients, for a detailed reexamination. Lymph node metastasis was demonstrated in 19 nodes from 11 patients by the initial routine examination; however, the detailed reexamination showed cancer involvement in a further nine lymph nodes from eight patients. Of these eight patients, metastasis had not been detected in any lymph nodes by routine examination in six. Macroscopically, the lesion was of the depressed or mixed type in six of the eight patients. From the intranodal location and growth pattern of the cancer foci, lymph nodes with occult metastasis were divided into the marginal sinus type, the medullary sinus type, and the mixed type, with the marginal type being found most frequently. The overall incidence of lymph node metastasis in patients with sm gastric cancer was as high as 29.8% (17/57) in this series. Moreover, a follow-up study revealed that two patients with occult metastasis died of cancer recurrence postoperatively. Accordingly, systematic regional lymph node dissection should be carried out at the time of surgery for sm gastric cancer.

Adenocarcinoma↗

Inhibition of the increase of intrahepatic Ca2+ by diltiazem in rats with liver ischemia.

The effects of a continuous infusion of a calcium entry blocker, 1, 5-benzothiazepine derivative (diltiazem), on ischemic liver cell damage were studied using quantitative 45Ca-autoradiographic and liquid scintillation techniques. The drug was administered to male Wistar rats as a continuous infusion for 3 h, beginning 30 min before ischemia. Autoradiographic studies showed that 45Ca accumulated in the liver lobuli after 1 h of liver ischemia and 3 h of reperfusion, but the level of 45Ca accumulation was significantly lower in drug-treated rats than in untreated animals. In addition, liquid scintillation studies showed significant differences in the intrahepatic 45Ca contents. These results suggest that diltiazem may inhibit the rise of intracellular Ca2+ due to the flow of extracellular Ca2+ into the cytosol, and may protect the ischemic liver from damage.

Animals↗

Long-term results of subtotal esophagectomy with three-field lymphadenectomy for carcinoma of the thoracic esophagus.

OBJECTIVE: This study evaluated the impact of aggressive surgery on survival in patients with carcinoma of the thoracic esophagus. SUMMARY BACKGROUND DATA: Prognostic value of lymph-node status for patients with esophageal carcinoma was emphasized, although it is currently under debate whether extensive lymph node dissection improves survival. METHODS: Two hundred ninety-five patients with thoracic esophageal carcinoma were admitted to Kagoshima University Hospital from December 1982 to December 1990. Esophagectomy was performed on 244 (82.7%) of these patients; 106 of whom underwent three-field lymphadenectomy (bilateral cervical, mediastinal, and abdominal regions) were analyzed regarding lymph-node status, tumor recurrence, and the effect of prognostic factors on survival using Cox's proportional hazards model. RESULTS: Hospital mortality and morbidity were 10.4% (11/106) and 65.1%, respectively. Seventy-eight patients (73.6%) had nodal involvement, including 49 patients with abdominal lymph-node metastases and 46 patients with recurrent nerve-node metastases. Five-year survival rates were 54.5% for 16 patients with a solitary nodal metastasis, 30.3% for stage III, 17.4% for stage IV, and 7.2% for 28 patients with six or more metastatic nodes. The most frequent sites of recurrence were the upper mediastinal region and the lung--its incidence increased significantly as the number of positive nodes increased. The most unfavorable prognostic factors included regional or recurrent nerve-node metastasis and patient age of more than 71 years. CONCLUSIONS: Three-field lymphadenectomy, including especially the removal of bilateral recurrent nerve nodes in the cervical region, is essential for improving the survival of patients with carcinoma of the upper two thirds of the thoracic esophagus.

Adult↗

Active efflux system for cisplatin in cisplatin-resistant human KB cells.

Mutants, KCP-4 and PC-5, resistant to an anticancer agent, cisplatin, were selected in multiple steps from human epidermoid KB carcinoma cells and human prostate PC-3 carcinoma cells, respectively. KCP-4 and PC-5 were 63 and 10 fold more resistant to cisplatin than the parental cells, respectively. KCP-4 cells exhibited increased resistance to cisplatin analogues and were also slightly cross-resistant to melphalan, cyclophosphamide, mitomycin C and methotrexate. KCP-4 cells were not cross-resistant to doxorubicin, daunorubicin, vincristine or CdSO4. The accumulations of cisplatin in KCP-4 cells and PC-5 in medium containing 50 microM cisplatin were approximately 20% of those in the parental cells. Revertant analysis suggested that a defect in cisplatin accumulation may be related to cisplatin resistance in PC-5 cells. The uncoupling agent of oxidative phosphorylation, 2,4-dinitrophenol, increased the accumulation of cisplatin in KCP-4 and cisplatin-resistant human prostate carcinoma PC-5 cells to nearly the same level as in their parental KB-3-1 and human prostate carcinoma PC-3 cells without 2,4-dinitrophenol, but did not increase accumulation in KB-3-1 and PC-3 cells. Addition of glucose in the medium inhibited the enhancement of cisplatin accumulation in KCP-4 cells by 2,4-dinitrophenol. Enhanced active efflux of cisplatin from KCP-4 cells was observed. A cell-cell hybridization test showed that the cisplatin resistance and the accumulation defect behaved as codominant traits. These data suggest that an active efflux system for cisplatin exists in cisplatin-resistant KCP-4 cells.

Biological Transport, Active↗