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Biomedical subjects

H Konno

Publications and source records attributed to H Konno.

At least 109 records · Page 6Linked to original sources
PubMed1997

Regression of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP-470: occurrence of apoptosis and necrosis.

To clarify the mechanism of the reduction of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP-470, the death of tumor cells was examined pathologically and ultrastructurally. Liver metastases were developed by intravenous injection of AH-130 cells. TNP-470 was given subcutaneously after tumor cell injection. Alterations in the size and number of metastatic tumors were examined at various time points, in association with the analysis of cell death pattern. The metastatic nodules were divided into 4 groups according to the morphological patterns of cell death; no cell death, scattered apoptosis, central necrosis, and diffuse necrosis. The number and size of the metastatic tumors at 2 weeks in untreated rats were larger than those in treated rats. The number of tumors in untreated rats decreased, but the tumor size increased. All rats treated with TNP-470 were alive and free from tumors after 4 weeks, whereas all the untreated rats died of liver metastases. The percentages of the tumors with necrosis in untreated rats (61.2% at 2 weeks and 100% at 4 weeks) were significantly higher than that (31.8% at 2 weeks) in treated rats (P < 0.01). The percentage of the tumors containing apoptotic cells in treated rats was significantly higher than that in untreated rats (54.5% vs. 30.6%; P < 0.05). The growth of metastatic tumors without treatment might be faster than the growth of vessels in untreated tumors, resulting in central necrosis due to ischemia. On the other hand, the reduction of metastatic liver tumors treated with TNP-470 might be caused by inhibition of angiogenesis, providing a weak ischemic stimulus which triggers apoptosis, rather than by a direct cytotoxic effect on tumor cells, because previous in vivo experiments demonstrated that TNP-470 affected endothelial cells but not tumor cells.

Animals↗
PubMed1997

p53 overexpression and proliferative activity do not correlate with lymph node metastasis in early gastric cancer.

We investigated p53 overexpression and the proliferative activity of the primary lesion as well as the clinicopathological features of 75 patients with gastric cancer invading the submucosa (sm cancer), of whom 14 (18.7%) had lymph node metastasis. Among the clinicopathologic features studied, only lymphatic invasion by the primary tumor was related to lymph node metastasis. There was no relationship between immunohistochemical staining for p53 protein or Ki-67 and lymph node metastasis. The p53-positive rate was 35.7 and 57.1% in patients with and without metastasis, respectively, while the mean Ki-67 labeling index was 38.9 and 38.1%, respectively. Our results suggest that p53 mutation or the proliferative activity of sm cancer do not influence lymph node metastasis, even though p53 mutation may enhance the proliferative activity and metastatic potential of advanced gastric cancer.

Adenocarcinoma↗
PubMed1997

Measurement of pancreatic blood flow to prevent pancreatic juice leakage after pancreas-preserving total gastrectomy for gastric cancer.

In patients with gastric cancer, distal pancreatectomy was frequently performed for complete removal of the lymph nodes along the splenic artery, but this procedure sometimes induced pancreatic juice leakage, subphrenic abscess, and postoperative diabetes. To avoid these complications, pancreas-preserving total gastrectomy (PP) was developed by Maruyama et al. [World J Surg 1995; 19:552-536], with which the spleen, splenic artery, and fatty connective tissue including lymph nodes could be removed completely without distal pancreatectomy. From 1988 to 1995, 36 patients underwent PP in our department. Although there were no operative deaths and no patient developed postoperative diabetes, pancreatic juice leakage was observed in 4 patients (11.1%). We assumed that ischemia of the distal pancreas may have caused this pancreatic juice leakage and investigated the relationship between pancreatic blood flow (PBF) and this complication in 12 recent patients. A significant negative correlation between PBF in the pancreatic tail and the peak amylase level (PAL) in the drain fluid was demonstrated. Two patients with PBF values of 4.5 and 5.2 ml/min/100 g tissue, respectively, and a PAL of more than 2 x 10(5) U/l developed pancreatic juice leakage, whereas the 10 patients without this complication had PBF values above 6 ml/min/100 g tissue and a PAL of less than 2 x 10(4) U/l. These results suggest that measurement of PBF may be useful to predict the leakage of pancreatic juice after PP and that distal pancreatectomy may be preferable when PBF is extremely low.

Adult↗
PubMed1997

[Mechanism of regression of metastatic liver tumors in rats treated with angiogenesis inhibitor with special reference to apoptosis].

We examined the mechanism of the reduction of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP-470 on the histological basis of patterns of tumor cell death. Metastatic tumors were developed by intravenous injection of AH-130 cell line, followed by a dose of TNP-470. Alteration in the size and number of metastatic liver tumors and its cell death pattern were analyzed. The number and size of the metastatic tumors at 2 weeks in untreated rats were larger than those in treated rats. The number of tumors in untreated rats decreased, whereas their size increased. All rats treated were alive and free from tumors after 4 weeks, although all untreated rats died of metastatic tumors. Necrosis was predominant in the tumors of untreated rats, while most tumors in treated rats showed apoptosis. Consequently, the metastatic tumor in untreated rats might grow faster than its angiogenesis, suggesting the occurrence of central necrosis due to apparent ischemia. On the other hand, the tumor in treated rats might be reduce a by weak ischemic stimulus, which triggers apoptosis.

Animals↗
PubMed1996

Surgical treatment of patients with mixed hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUND: The results of treatment of mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) remain unclear because of the rarity of this disease. METHODS: Of 218 patients with primary liver carcinoma treated from 1979 to 1995, 6 had a histologic diagnosis of mixed HCC and CC (MHC). Five had chronic liver disease. Serum carcinoembryonic antigen (CEA), CA 19-9, and alpha-fetoprotein (AFP) levels were determined and hepatic angiography was performed preoperatively. Left trisegmentectomy (with portal vein reconstruction) and extended right lobectomy were performed in one patient each, whereas selective subsegmentectomy was done in three patients, and partial resection of segment 3 in one patient. Hilar lymphadenectomy was performed in two patients. RESULTS: Mild liver dysfunction was observed in two patients. The resected tumors ranged from 2.7 to 12 cm in size and all showed intermingling of HCC and CC elements. A preoperative diagnosis of MHC was possible in one patient because of a high AFP level and hypovascularity, whereas a high CEA level and hypervascularity led to the diagnosis in another patient. High levels of AFP, CEA, and CA 19-9 were observed in three, one, and three patients, respectively. There were no metastases in the dissected lymph nodes. Although 2 patients had died by 2 years after surgery, the 5-year survival rate was 60% and there were 2 long term survivors for more than 10 years. CONCLUSIONS: A hypervascular tumor with high CEA and CA 19-9 levels or a hypovascular tumor with a high AFP level may suggest a preoperative diagnosis of MHC in patients with suspected HCC. Extensive surgery is an effective treatment for this disease, except in patients with satellite nodules. Hilar lymphadenectomy may not be necessary in selected patients.

Adult↗
PubMed1996

The angiogenesis inhibitor TNP-470 (AGM-1470) improves long-term survival of rats with liver metastasis.

An excellent therapeutic effect of angiogenesis inhibitors on tumor growth or metastasis has been reported, but the sustained antimetastatic effect of these agents has not been studied. We investigated the sustained effect of TNP-470, an angiogenesis inhibitor, in rats with hepatic metastasis following intraportal implantation of rat ascites hepatoma AH-130 cells. TNP-470 was administered subcutaneously at 15 mg/kg (L-TNP) or 30 mg/kg (H-TNP) on alternate days for 2 weeks. The number of liver metastases was significantly reduced in both the L-TNP (85.1 +/- 77.6) and H-TNP (31.7 +/- 49.6) groups compared to the control group (300.7 +/- 100.7) (P < 0.01) at 14 days after the start of treatment. Although all rats in the control group died within 1 month of massive liver metastasis, the L-TNP and H-TNP, respectively, had a survival rate of 82 and 60%, at 4 months (P < 0.001). Absence of toxicity of TNP-470 at the lower dose, as evidenced by the absence of intraperitoneal or intrapleural bleeding, contributed to a better prognosis in the L-TNP group. Interestingly, a small dormant metastatic focus was found in only 1 of 15 rats surviving for 4 months, whereas metastatic foci were observed in all rats at the end of treatment. These results suggest that the sustained cytostatic effect of TNP-470 on vascular endothelial cells may help to improve long-term survival by reducing the metastatic burden.

Animals↗
PubMed1996

Efficacy of an angiogenesis inhibitor, TNP-470, in xenotransplanted human colorectal cancer with high metastatic potential.

BACKGROUND: The summation of gene mutations increases the metastatic potential of colorectal cancer. The genetic characterization and hepatic metastatic potential of five xenotransplanted human colon carcinoma strains were investigated. Furthermore, the therapeutic effect of the angiogenesis inhibitor, TNP-470, was evaluated. METHODS: The correlation between gene mutation and rate of hepatic metastases of five colon cancer strains transplanted orthotopically or subcutaneously was evaluated. The strain with the highest hepatic metastatic rate from orthotopical tumors, TK-4, was used in the experiment with TNP-470 treatment. Mice were given tumor transplants orthotopically or subcutaneously followed by 30 mg/kg of TNP-470 on alternate days from Day 10 or Day 21 after transplantation, respectively. RESULTS: The rate of hepatic metastases from orthotopically transplanted tumors of 5 strains was 38 to 79%. Interestingly, TK-4 with K-ras and p53 mutations and overexpression of p53 protein induced hepatic metastases from both orthotopical (79%) and subcutaneous tumors (44%). Although TNP-470 only significantly inhibited subcutaneous tumor growth, its antimetastatic effect was significantly demonstrated on the hepatic metastases of both orthotopical and subcutaneous tumors. CONCLUSION: p53 mutation is thought to enhance angiogenesis, favoring the growth of the hepatic metastases. TNP-470 proved the excellent antimetastatic effect of TK-4 on hepatic metastases. TK-4 has the highest metastatic potential and p53 mutation. An antiproliferative effect was observed on the rapidly growing primary tumors in which angiogenesis may be dominant.

Animals↗
PubMed1996

Synchronous lymphoma and adenocarcinoma occurring as a collision tumor in the stomach: report of a case.

We report herein the rare case of a 71-year-old man who was initially operated on under the diagnosis of advanced gastric cancer, but was subsequently found to have synchronous lymphoma and early adenocarcinoma of the stomach, confirmed by postoperative pathological examination. The patient had a history of lymphoma of the left tonsil, and histologically the gastric lymphoma was observed to be of the non-Hodgkin's, diffuse, large-cell type. Conversely, the gastric cancer was early well-differentiated tubular adenocarcinoma of type 0-IIa, according to the Japan Gastroenterological Endoscopy Society classification. The two tumors had collided at the fornix. The relationship between these two tumors is analyzed and the most appropriate methods of diagnosis and treatment are discussed.

Adenocarcinoma↗
PubMed1996

Hepatic angiomyolipoma developing during the follow-up of ulcerative colitis: report of a case and review of the literature.

Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5 x 7.5 x 7 cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.

Adult↗
PubMed1996

Second cancer during long-term survival after resection of biliary tract carcinoma.

Curative surgery for biliary tract malignancy has improved the prognosis of patients; however, during long-term follow up after extensive surgery, four of our patients (two with gallbladder carcinoma and two with bile duct carcinoma) developed a second primary cancer (one each in the duodenum, skin, descending colon, and lung). Regular examination of the upper gastrointestinal tract, colorectum, and lungs, and testing for tumor markers (carcinoembryonic antigen and CA19-9) were performed as follow-up studies. As a result, the second cancers were all found at a relatively early stage and all four patients are still alive 6-14 years after the initial operation. A review of the annual autopsy reports over the last 5 years in Japan showed that the incidence of second cancer was 14.8% in patients with gallbladder carcinoma and 13.5% in those with bile duct carcinoma. Furthermore, the rate of second gastric and colorectal carcinoma was significantly higher in patients with primary bile duct cancer than in those with primary gallbladder cancer. In conclusion, the incidence of a second cancer after resection of biliary tract malignancy is more than 10%, but this second cancer can be detected relatively easily and treated at an early stage during the course of regular long-term follow up for the first cancer.

Adult↗
PubMed1996

Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy.

The hypothesis that both activated Kupffer cells and the spleen may be responsible for endotoxin-induced liver injury following partial hepatectomy was investigated. Male rats were divided into a sham group receiving laparotomy alone and three groups receiving a two-thirds hepatectomy; one group was given normal saline (NS) solution as a vehicle control, one group received intravenous gadolinium chloride (GC group) (7 mg/kg body weight) for 2 days before intravenous injection of endotoxin to inhibit Kupffer cell phagocytosis, and the third group simultaneously underwent splenectomy and partial hepatectomy (SH group). As endotoxin, lipopolysaccharide (LPS) (1 mg/kg body weight) was administered intravenously 2 days after surgery. In the GC and SH groups, phagocytic activity was reduced to approximately 40% of that in the sham group. The highest plasma tumor necrosis factor alpha (TNF-alpha) level (8,544 +/- 1,223 pg/mL) was observed in the NS group at 1 hour after LPS administration, and the level was significantly reduced by GdCl3 or splenectomy (P < 0.05). Inhibition of Kupffer cell function and splenectomy attenuated functional and structural liver damage associated with the decreased hepatic infiltration of polymorphonuclear leukocytes (PMNs) and reduced priming of circulating PMNs in the early stage of endotoxemia following partial hepatectomy. Consequently, the 24-hour survival rate of the SH and GC groups was significantly improved to 50% and 80%, respectively (P < .05), while that of the NS group was 12.5%. These findings indicate that the modification of inflammatory mediator generation by splenectomy or inhibition of Kupffer cell function may be beneficial for the prevention of endotoxin-induced liver injury after partial hepatectomy.

Animals↗
PubMed1996

Liposomal ATP protects the liver from injury during shock.

Liposomes are useful drug carriers. In this study, adenosine triphosphate (ATP) was entrapped in liposomes (Lip-ATP). Anesthetized rats were given Lip-ATP (5 mg/kg as ATP), free ATP (5 mg/kg) or saline (control group) during stabilization. Then, the rats were exposed to 30 min of hypovolemic shock and 30 min of reperfusion. Administration of Lip-ATP significantly improved hepatic blood flow during shock (13.2 +/- 1.7 ml/min/100 g tissue in the Lip-ATP group vs. 9.4 +/- 2.2, in the control group, and 8.9 +/- 2.9 in the free ATP group) and during reperfusion (20.9 +/- 2.3, 16.3 +/- 2.2, and 16.2 +/- 1.8 ml/min/100 g tissue, respectively). The serum levels of hepatic enzymes (ALT, AST and LDH) were significantly lower in the Lip-ATP group after reperfusion when compared with the control and free ATP groups. Administration of Lip-ATP also produced the best recovery of hepatic ATP level. These findings indicate that Lip-ATP increased hepatic blood flow during shock and reperfusion, presumably by improving the energy charge and metabolism of the hepatocytes. Thus, Lip-ATP appears to be a useful agent for liver injury induced by hypovolemic shock.

Adenosine Triphosphate↗
PubMed1996

Ice nucleus production of Fusarium moniliforme var. subglutinans in relation to its growth characteristics.

The effects of culture conditions on the ice nucleus production of Fusarium moniliforme var. subglutinans isolated from the gut of larvae of the rice stem borer (Chilo suppressalis Walker) were examined. The ice nucleus production was only affected by cultivation temperature and pH: the optimum temperature and pH were 15 degrees C to 20 degrees C and 4.0 to 6.0, respectively.

Asparagine↗
PubMed1996

Two forms of alpha-glucosidase from Mucor javanicus produced by culture with castanospermine.

When Mucor javanicus was cultured with castanospermine, two alpha-glucosidases (CS-I, II) were produced. The two enzymes were purified by two CM-cellulofine column chromatographies, and compared with the alpha-glucosidase (C) from a culture without castanospermine. The molecular weights of the three enzymes were calculated to be 97,000 (CS-I, II) and 94,000 (C) from SDS-PAGE. CS-II was similar in hydrolysis of alpha-1,4-linkage to C, but hydrolyzed alpha-1,2-, alpha-1,3-, and alpha-1,6-linkages at a lower rate than C. The Michaelis constant of CS-I for malto-oligosaccharides was several times as high as the constants of CS-II and C, but CS-I hydrolyzed nigerose at a faster rate than maltose.

Carbohydrate Sequence↗
PubMed1995

Decrease in cerebellin and corticotropin-releasing hormone in the cerebellum of olivopontocerebellar atrophy and Shy-Drager syndrome.

Four neuropeptides; cerebellin, corticotropin-releasing hormone (CRH), neuropeptide Y and somatostatin were studied by radioimmunoassay in the postmortem human brains obtained from three patients with olivopontocerebellar atrophy (OPCA) and one with Shy-Drager syndrome. Significant decreases in cerebellin and CRH concentrations were found in the cerebellar hemisphere of these diseases compared with controls. These findings suggest important pathophysiological roles of cerebellin and CRH in these cerebellar diseases. Such significant decreases were not found in neuropeptide Y and somatostatin.

Adult↗
PubMed1995

Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP-470, and mitomycin C on the growth and liver metastasis of human colon cancer.

Angiogenesis inhibitors have attracted considerable interest. The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti-neoplastic agent, were investigated using a xenotransplanted human colon cancer, TK-4. Suturing of small pieces of TK-4 tumors to the cecal wall in nude mice (orthotopic transplantation) induced liver metastasis. Mice were randomly divided into 3 groups; a control group given saline solution, a group receiving TNP-470 and a group receiving MMC. TNP-470 was given s.c. on alternate days for 5 weeks from day 10 after cecal transplantation and MMC was administered intraperitoneally (i.p.) once a week from day 10 after cecal transplantation. MMC significantly inhibited cecal tumor growth. In the control group, liver metastases developed in 9 out of 10 mice, including 3 with more than 20 metastatic foci. Liver metastasis also developed in 8 out of 10 mice receiving MMC, 2 of which had many metastases. In contrast, liver metastasis developed in only 2 out of 8 mice in the TNP-470 group and neither of these animals had numerous metastases.

Animals↗
PubMed1995

Hepatic release of endothelin-1 after warm ischemia. Reperfusion injury and its hemodynamic effect.

This study investigated the release of endothelin (ET)-1 from the liver after warm ischemia/reperfusion (I/R) injury. Wistar rats were subjected to 120 min of warm hepatic ischemia by clamping the hepatic hilum under porto-jugular shunting. Reperfusion was performed by unclamping. The rats were divided into 2 groups receiving intravenous treatment with an anti-ET-1 mAb before ischemia (AET group) and with mouse immunoglobulin G (sham group). Hepatic blood flow was assessed by laser-Doppler flowmetry and reflectance spectrophotometry and was compared between the 2 groups along with the bile flow rate. The ET-1 concentrations of hepatic venous and portal blood were determined in the sham group, and the portal blood endotoxin levels were assayed in both groups. Both groups developed transient hypotension after reperfusion, but hepatic blood flow subsequently showed a significant improvement in the AET group. Hepatic congestion was detected in the sham group by both reflectance spectrophotometry and histological examination. After reperfusion, bile flow was significantly greater in the AET group. The portal endotoxin concentration showed no increase in both groups, and the hepatic venous blood ET-1 level in the sham group was significantly higher until 3 hr after reperfusion compared to the portal blood level. The 30-day survival rate was 50% in the AET group, whereas all the sham rats died within 12 hr. ET-1 was released from the liver after I/R injury and apparently participated in systemic and local hemodynamic changes that affected survival.

Animals↗