Biomedical subjects

T Aikou

Publications and source records attributed to T Aikou.

At least 145 records · Page 8Linked to original sources

PubMed1997

[Treatment of thoracic esophageal carcinoma which invades adjacent structure--significance of resection and combined therapy].

From January 1980 to December 1994, a total of 64 cases of thoracic esophageal carcinoma which invaded adjacent structure (A3) were resected and 35 cases were unresected in Kagoshima University Hospital. Adjacent structures were mainly trachea/bronchus, aorta or pulmonary vein. Combined resections were performed in 22 cases (34.4%), and no tumors remained in 12 cases (18.8%). One year survival rates and 50% survival time of the no residual tumor group were 25.7% and 8.5 months, while the rates of the residual tumor group were 15.7% and 5.1 months. But, there was no significant difference of survival rates according to the amount of residual tumor. On the other hand, 1-year survival rates and 50% survival time of unresected group were 3.1% and 4.5 months. As a postoperative adjuvant therapy, radiation was the most effective modality. As a result, operations should be done at first for the A3 carcinoma in which a complete combined resection is expected. On the other hand, radiation or chemotherapy should be selected for the cases in which the tumor may remain, even though combined resection is done.

Adult↗

PubMed1997

[A case of advanced lung cancer with long time survival, involving direct invasion to the liver].

A 64-year-old male was admitted to our hospital complaining of right back pain. He had squamous cell carcinoma located at lower lobe of right lung involving the diaphragm and liver, pointed out by chest CT. Main tumor, the lateral chest wall, the posterior side of the diaphragm and the posterior side of the liver (S7) were resected. This patient has survived without any recurrences for 5 years and 10 months after operation. It is important not to hesitate in performing combined resections, even if the advanced lung cancer has invaded into the liver. Because the long-term survival might be achieved.

Carcinoma, Squamous Cell↗

PubMed1997

[Rational lymphadenectomy in patients with cervical nodes metastasis for carcinoma of the lower third esophagus].

Prognostic value of removing cervical nodes in patients with carcinoma of the lower third esophagus is extremely controversial. Of 93 patients with curative esophagectomy via trans-thoracic approach, cervical nodes were involved in five patients (13%), upper mediastinal nodes in 12 patients (30%), and para-aortic nodes in only one patients (3%) for 40 patients whose proximal part of the tumor invading the mid-esophagus from below. Of the remaining 53 patients with tumor extent confined to the lower third esophagus, cervical nodes were involved in only one patients (2%), upper mediastinal nodes in five patients (9%), and paraaortic nodes in six patients (11%). Three of the five patients with cervical metastasis whose proximal part of the tumor invading the mid-esophagus survived for at least 22 months or more following three-field lymphadenectomy. Removing the cervical nodes in patients with carcinoma of the lower third esophagus may have some role to improve the survival if the tumor invades the mid-esophagus from below.

Carcinoma, Squamous Cell↗

PubMed1997

MTT-hybrid assay incorporates the advantages of both clonogenic and MTT assay radiosensitivity testing for fresh tumor samples.

After devising a 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-Hybrid assay that incorporates the advantages of both the clonogenic and standard MTT assays, we evaluated the validity of this system using a malignant fibrous histiocytoma (MFH) cell and four xenografted tumors. In the MFH cells the surviving fractions were correlated with radiation dose at three assays. In xenografted tumor cells, the surviving fractions determined by the MTT assay did not show a similar dose response, possibly because of contamination by normal cells. Changes in the surviving fraction of the xenografted cells were correlated to the radiation dose as determined by the clonogenic assays, but this assay took longer performance times and was not useful for evaluating tumors with a low planting efficiency. With the MTT-hybrid assay, changes in fractions of the four xenografted tumor cells were correlated to radiation dose. The MTT-hybrid assay required a smaller optimal number seeding cells and shorter assay time than those of the clonogenic assay. Therefore, the MTT-Hybrid assay can be used successfully to assess the radiosensitivity of both established tumor cell lines and fresh tumor samples.

Animals↗

PubMed1996

Characterization of the ATP-dependent LTC4 transporter in cisplatin-resistant human KB cells.

An active efflux pump for cis-diamminedichloroplatinum(II) (cisplatin) has been identified in cisplatin-resistant KCP-4 cells isolated from human epidermoid carcinoma KB-3-1 cells. The adenosine triphosphate(ATP)-dependent transport of leukotriene C4 (LTC4), an endogenous substrate for the glutathione S-conjugate export pump(GS-X pump), has been found in membrane vesicles prepared from KCP-4 cells. Multidrug resistance-associated protein (MRP) has also been identified as an ATP-dependent LTC4 transporter. To examine whether the GS-X pump expressed in KCP-4 cells in MRP, we investigated the expression of MRP in KCP-4 cells and compared the LTC4 transporting activity of GS-X pump expressed in KCP-4 cells with that of MRP. The level of MRP gene expression in KCP-4 cells was low and similar to that in KB-3-1 cells. MRP was not detected in membrane vesicles prepared from KB-3-1 and KCP-4 cells by immunoblot analysis. The ATP-dependent transport of LTC4 in KCP-4 and C-A120 vesicles showed saturable kinetics with an apparent Km of 0.18 microM and 0.25 microM, respectively. [3H]LTC4 transport in KCP-4 vesicles was more inhibited by 2,4-dinitrophenyl-S-glutathione(DNP-SG), bis-(glutathionato)-platinum(II) (GS-platinum) complex and glutathione disulfide(GS-SG) and less by LTD4 compared with that in C-A120 vesicles. The character of the LTC4 transporter expressed in KCP-4 vesicles is similar but not identical to that of MRP. Our results suggest that a glutathione S-conjugate export pump which is different from MRP exists in cisplatin-resistant KCP-4 cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma.

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We previously found that thymidine phosphorylase (dThdPase) and PD-ECGF are the same protein. PURPOSE: We retrospectively examined the expression of dThdPase in primary colorectal carcinomas, its association with angiogenesis and clinicopathologic findings, and its prognostic value. METHODS: Tissues were obtained from the tumors of 163 patients whose colorectal carcinomas were completely removed by surgery. Microvessels assessed by immunostaining endothelial cells for factor VIII were counted on a 400x field in the most active areas of neovascularization within the tumor. We purified the monoclonal antibody against dThdPase and studied the expression of dThdPase in the same serial sections used for the detection of factor VIII. Those who carried out microvessel counting and dThdPase expression assessment had no knowledge of clinicopathologic findings. The significance of dThdPase in the prognosis of patients with colorectal carcinomas was also examined in the survival analysis of mortality follow-up data covering the period between 1984 through 1991. Reported P values are from two-sided tests of statistical significance. RESULTS: The mean microvessel count (+/- standard deviation) in dThdPase-positive colorectal carcinoma specimens (17.5 +/- 7.2) was higher (P < .001) than that in dThdPase-negative carcinoma specimens (9.3 +/- 5.5). The dThdPase positivity was in accordance with the microvessel count. dThdPase positivity showed highly significant statistical associations with tumor size, extent of invasion, lymph node metastasis, lymphatic invasion, and venous invasion. Cox regression analysis revealed that dThdPase expression was prognostic for poor disease outcome after adjustment for Dukes' stage and microvessel count. CONCLUSIONS: These findings suggest that higher levels of dThdPase expression in colorectal carcinomas are associated with more extensive angiogenesis, poor clinical and laboratory findings, and unfavorable clinical outcome. IMPLICATIONS: Inhibition of dThdPase in human colorectal carcinomas might improve prognosis for some patients.

Colorectal Neoplasms↗

PubMed1996

Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma.

BACKGROUND: Angiogenesis is reportedly correlated with metastasis, relapse, and prognosis in some types of tumors. Hematogenous or lymph node metastasis and local recurrence are the main elements related to the death of patients with colorectal carcinoma. Thus, the authors examined the microvessel count in colorectal carcinoma to determine how angiogenesis correlates with clinicopathologic factors and prognosis. METHODS: Paraffin embedded sections from 166 patients with primary colorectal carcinomas that had been completely removed were analyzed for angiogenesis. Vessels were stained with anti-factor VIII polyclonal antibody, and areas with the most discrete microvessels were counted in a 400x field. RESULTS: Tumor size was significantly correlated with microvessel count. Microvessel counts from patients with lymph node metastasis, lymphatic vessel invasion, venous vessel invasion, or relapse were significantly higher than those without. Furthermore, microvessel count was an independent prognostic factor (P = 0.007), whereas the Dukes stage had more significant prognostic value (P < 0.001) according to the multivariate Cox hazard analysis. CONCLUSIONS: This study suggested that angiogenesis assessed by the microvessel count was a marker of relapse and prognosis of patients with colorectal carcinoma.

Adenocarcinoma↗

PubMed1996

Expression of the multidrug-resistance-associated protein (MRP) gene in human colorectal, gastric and non-small-cell lung carcinomas.

MRP has been identified as another multidrug-resistance (MDR) gene and may be involved in an alternative MDR mechanism in some solid tumors. We investigated the expression of MRP mRNA in multidrug-resistance KB sublines (KB-8-5, KB-C2, C-A40 and C-A120), human non-small-cell lung carcinomas (NSCLC), gastric and colorectal carcinomas, and compared it with that in drug-sensitive human KB cells. MRP gene expression was elevated in 8 of 9 (89%) squamous-cell carcinomas of the lung. Furthermore, MRP expression in 4 squamous-cell carcinomas (L13, 18, 19 and 20) was more than 3.6 times higher than in KB-3-1 cells, and the average MRP mRNA expression level of all squamous-cell carcinomas was significantly higher than that of adenocarcinoma of the lung and of colorectal and gastric carcinomas. These results suggested that the MRP is responsible, at least in part, for drug resistance in some squamous-cell carcinomas of the lung.

ATP-Binding Cassette Transporters↗

PubMed1996

Induction of hepatocyte growth by intraportal infusion of HGF into beagle dogs.

Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature parenchymal hepatocytes, is a hepatotrophic factor involved in liver regeneration and is even essential for development of the liver. We report here that human recombinant HGF at a very low concentration and given intraportaly stimulated liver regeneration in dogs. In vitro, HGF dose-dependently stimulated DNA synthesis of primary cultured hepatocytes isolated from a dog. The maximal activity was twofold higher than that of epidermal growth factor, and insulin potentiated the mitogenic activity of HGF. When human recombinant HGF was infused through the portal vein into 30% partially hepatectomized dogs at 0.25 microg/kg body weight in order to directly target the liver, HGF stimulated DNA synthesis of hepatocytes and liver weight at 72 h after the operation; labeling indices in saline- and HGF-injected groups were 0.75 and 1.82%, respectively, and the liver weights in saline- and HGF-injected groups were 302 and 374 g, respectively. Since HGF exerts potent antihepatitis activity as well as mitogenic activity, these results indicate that intraportal administration of HGF may be particularly important to enhance liver regeneration and prevent the severe hepatic insufficiently after hepatic surgery.

Animals↗

PubMed1996

Gastric acid secretion and gastroduodenal pH after pancreaticogastrostomy in dogs.

Pancreaticogastrostomy has been reintroduced as a useful alternative procedure to pancreaticojejunostomy after Whipple resection or pylorus-preserving pancreaticoduodenectomy because of the very low incidence of leakage and disruption. In this study, gastric acid secretion, serum gastrin level, and 24-hr dual gastroduodenal pH after pancreaticogastrostomy were examined on the assumption that a canine model was a pylorus-preserving pancreaticoduodenectomy. Basal acid output (BAO), maximal acid output (MAO), and dual gastroduodenal pH were measured in eight dogs with gastric fistula. After pancreaticogastrostomy, BAO levels showed a slight increase significantly, but MAO levels showed no change. Serum gastrin levels in the fasting and postprandial states showed the similar patterns between before and after surgery. In the 24-hr dual gastroduodenal pH monitoring, gastric pH and duodenal pH also did not change in the fasting and postprandial states. These results suggested that the maintenance of the normal gastric pH after pancreaticogastrostomy was caused by a little increase of BAO, and the neurohumoral relationship between the stomach, duodenum, and pancreas was preserved even after pancreaticogastrostomy. Therefore, the pancreaticogastrostomy is a recommendable reconstructive procedure physiologically after pylorus-preserving pancreaticoduodenectomy.

Anastomosis, Surgical↗

PubMed1996

High serum alpha-fetoprotein concentration associated with pseudoinfarction of a cirrhotic liver: report of a case.

We report herein the case of a 65-year-old man with cirrhosis of the liver in whom a portal vein thrombus was found to be the cause of a marked elevation in serum alpha-fetoprotein (AFP). The patient presented with fever and abdominal pain, and a diagnostic work-up revealed a liver mass and an increased serum AFP concentration of 91,000 ng/ml. The mass gradually regressed, and the AFP concentration simultaneously decreased to 163 ng/ml. However, because hepatocellular carcinoma (HCC) could not be ruled out, a partial hepatectomy was performed. Histological examination of the resected specimen revealed a thrombus of the portal vein surrounded by the fibrosis associated with liver cirrhosis, but no neoplastic lesion was found. Thus, portal thrombus associated with liver cirrhosis might induce an extremely high level of AFP production.

Aged↗

PubMed1996

Exogenous hepatocyte growth factor markedly stimulates liver regeneration following portal branch ligation in dogs.

Portal branch ligation (PBL) or embolization prior to extensive hepatectomy has been employed to increase the functional reserve of the remaining liver. This study investigated the effects of human recombinant hepatocyte growth factor (rh-HGF) on liver regeneration following PBL in dogs. Beagle dogs were subjected to PBL and were divided into two groups, a control group (n = 11) without rh-HGF and a treated group (n = 12) receiving postoperative rh-HGF at 250 ng/kg via the portal vein. Dogs were killed 72 h or 14 days following PBL. We studied the changes in serum HGF level, DNA synthesis of the liver, hepatocyte size, liver weight, and liver function tests. In the HGF group, the ratio of whole liver weight to body weight increased significantly, and both ligated and nonligated lobes showed marked increases in weight. The nonligated lobes in the HGF group showed significant increases in both DNA synthesis and hepatocyte size. Moreover, ligated lobes in the HGF group showed an increase in DNA synthesis without hypertrophy compared with the control group. Administration of rh-HGF did not significantly affect liver function tests. Ligation of the portal branch supplying the portion of liver to be resected, coupled with the administration of rh-HGF, is a useful strategy to increase hepatic reserve in advance of major hepatectomy.

Animals↗

PubMed1996

The activity and expression of thymidine phosphorylase in human solid tumours.

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. Since dThdPase seems to have an important role in angiogenesis of tumours, we measured the activity and expression of dThdPase in various tumours and the adjacent non-neoplastic tissues. We assayed dThdPase activity by spectrophotometric means, and the expression of dThdPase was examined by immunoblotting and by immunohistochemical staining using a monoclonal antibody against dThdPase. In the oesophagus, stomach, colorectum, pancreas, and lung, dThdPase activity in carcinomas was significantly higher (P < 0.05) than that in the adjacent non-neoplastic tissues. The expression level of dThdPase detected by immunoblotting correlated well with the activity of dThdPase. In the oesophagus, stomach, colorectum, gall bladder, pancreas and lung, the proportion of dThdPase-positive tumours was significantly higher (P < 0.05 or 0.01) than that of the dThdPase-positive adjacent normal tissues. In oesophageal, gastric colorectal and lung carcinomas, the proportion of dThdPase positivity in advanced carcinomas was significantly higher (P < 0.01) than that in early carcinomas. Tumour-infiltrative macrophages or lymphocytes in the lymph node, alveolar macrophages and Kupffer cells expressed high levels of dThdPase. The results indicate that dThdPase activity and expression level in many tumours are higher than those in the adjacent non-neoplastic tissues, and that dThdPase may have an important role in the proliferation of these solid tumours.

Digestive System Neoplasms↗

PubMed1996

Ultrasonographic detection of lymph-node metastases in superficial carcinoma of the esophagus.

BACKGROUND AND STUDY AIMS: The presence or absence of lymph-node metastasis is the single most important factor in determining the strategy for treating superficial carcinoma of the esophagus. In this study, ultrasound (US) and endoscopic ultrasonography (EUS) were used in the diagnosis of lymph-node metastases, and the accuracy and limitations of these methods were assessed. PATIENTS AND METHODS: Prospectively, 37 patients with superficial esophageal cancer were studied by US and EUS before surgery, and the results were compared with the histological findings. Twelve of the patients had histologically confirmed lymph-node metastases. Ultrasonographic images of the lymph nodes were classified into three types, based on their boundaries and internal echoes. RESULTS: The sensitivity, specificity, and accuracy of predicting mediastinal lymph-node metastasis by EUS diagnosis were 80.0%, 87.5%, and 86.5%, respectively. The sensitivity, specificity, and accuracy of US in the assessment of cervical and abdominal lymph-node metastasis were 71.4%, 86.7%, and 83.3%, respectively. In cases in which there was a solitary metastatic lymph node, the detection rate was higher than in cases with two or more positive nodes. Most metastatic lymph nodes correctly diagnosed by US and EUS were larger than 6 mm and had tumor involving more than one-third of their cross-sectional area. CONCLUSIONS: In patients with superficial esophageal carcinomas, US is accurate in staging cervical and abdominal lymph nodes. EUS is accurate in staging mediastinal lymph nodes.

Carcinoma, Squamous Cell↗

PubMed1996

Assessment of tumor invasion of the distal esophagus in carcinoma of the cardia using endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: Esophageal invasion by carcinoma of the cardia may affect the surgical approach. Accurate assessment of esophageal invasion is difficult using endoscopy, computed tomography, or barium contrast radiography. The aim of the present study was to evaluate the use of endoscopic ultrasonography (EUS) in the prediction of esophageal invasion by carcinoma of the cardia. PATIENTS AND METHODS: EUS (using a linear-array scanner) was carried out prospectively in 47 patients with carcinoma of the cardia who underwent subsequent surgical resection. The findings were correlated with the histopathological assessment of tumor infiltration in the esophagus in the resected specimen. RESULTS: An absence of esophageal invasion was correctly predicted by EUS in 12 of 13 patients. Histopathologically confirmed invasion of the esophagus was correctly predicted in 32 of 34 patients. With a margin of error of 10 mm, the accuracy of EUS in predicting or excluding histologically confirmed invasion of the esophagus was 85.1% (40 of 47 patients). False-positive results with EUS occurred in patients with prominent edematous or fibrous changes in the distal esophagus; false-negative results with EUS were seen in patients with scattered infiltration of a small number of tumor cells into the mucosal or submucosal layer. CONCLUSIONS: EUS can provide the surgeon with additional information on the extent of esophageal infiltration in patients with carcinoma of the gastric cardia, and can therefore assist in the selection of the surgical approach.

Adult↗

PubMed1996

Prophylactic action of allopurinol against chemotherapy-induced stomatitis--inhibition of superoxide dismutase and proteases.

The activities of superoxide dismutase (SOD) and several proteases were measured in kidney of mice treated with allopurinol in order to elucidate the mechanism of prophylactic action of allopurinol against chemotherapy-induced stomatitis. The following results were obtained. Following 3 day administration of allopurinol 20 mg/day per os (Group C), the concentrations of allopurinol and oxipurinol in the renal tissue were 203.9 +/- 52.1 and 1141.7 +/- 194.8 micrograms/g, respectively. The SOD activity was significantly lower in Group C than in the untreated control group (p < 0.01). The enzyme activities of papain and trypsin were suppressed in Group C. However, the other proteases tested were not affected by the administration of allopurinol, indicating only weak anti-protease action of allopurinol. These results suggest that allopurinol may be effective to prevent chemotherapy-associated stomatitis via both direct and indirect actions to oral mucosa, that include inhibitory actions on xanthine oxidase as well as protease.

Allopurinol↗

PubMed1996

Expression of thymidine phosphorylase in human gastric carcinoma.

The activity of thymidine phosphorylase (dThdPase) has been reported to increase in several types of malignant tumors. Experimental evidence has shown that dThdPase is identical to platelet-derived endothelial cell growth factor, and that dThdPase has angiogenic activity. We examined the expression of dThdPase to investigate whether the expression of dThdPase correlates with angiogenesis, clinicopathologic features and the prognosis of patients with human gastric carcinomas. Microvessels were assessed by immunostaining endothelial cells for factor VIII. We counted microvessels in the tumors of 158 patients whose tumors were completely removed surgically. Microvessels were counted in a x400 field in the most active areas of neovascularization. We purified a monoclonal antibody (TMA-1) against dThdPase and studied the expression of dThdPase using TMA-1 in the same serial sections as those used for the detection of factor VIII. The correlation between angiogenesis and dThdPase, and the clinicopathological significance of dThdPase, in patients with gastric carcinoma were examined. The positive expression of dThdPase was more frequent (P < 0.001) in gastric carcinomas (67/158, 43.4%) than that in normal tissues (12/158, 7.6%). The average microvessel count in dThdPase-positive gastric carcinomas was higher (P < 0.001) than that in dThdPase-negative carcinomas. The percentage of gastric carcinoma cells expressing dThdPase was significantly correlated with the microvessel count (P < 0.001). Further, the average size of dThdPase-positive carcinomas was significantly larger (P < 0.001) than that of negative carcinomas and the mean microvessel count in dThdPase-positive gastric carcinomas was also significantly higher (P < 0.001) than that in dThdPase-negative carcinomas. There was a significant correlation between the positive expression of dThdPase and microvessel count (P < 0.001) or lymph node metastasis (P = 0.013) by multivariate logistic analysis. Further, patients with dThdPase-positive carcinoma showed a significantly worse prognosis than those with dThdPase-negative carcinoma overall and in stage III. These findings indicate that the expression of dThdPase in gastric carcinomas is related to progression and metastasis, and this enzyme affects the prognosis of some patients with the disease.

Adult↗

PubMed1996

Hepatic hemodynamics in a patient with nodular regenerative hyperplasia.

Nodular regenerative hyperplasia of the liver is an uncommon condition. Approximately 50% of these patients develop portal hypertension. Few previous reports document the site of increased resistance to blood flow within the liver in this disorder. We measured Doppler waveform patterns of the right hepatic vein by pulsed Doppler ultrasonography and portal, wedged hepatic, and free hepatic venous pressure by intravenous catheter before and after splenectomy in a 47-yr-old woman with nodular regenerative hyperplasia who presented with portal hypertension and pancytopenia. Nodular regenerative hyperplasia was histologically confirmed. Pre- and postoperative measures indicated a marked difference between wedged hepatic venous pressure and free hepatic venous pressure, whereas there was little difference between portal venous pressure and wedged hepatic venous pressure. Doppler waveform patterns of the right hepatic vein showed an unclear pulsatile flow pattern with a decreasing reversed phase. The above data suggest that portal hypertension in nodular regenerative hyperplasia is primarily sinusoidal, similar to that seen with cirrhosis.

Female↗