Biomedical subjects

H Iishi

Publications and source records attributed to H Iishi.

At least 55 records · Page 3Linked to original sources

PubMed1998

Inhibition of experimental gastric carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats, by sodium nitroprusside, a nitric oxide generator.

The effects of prolonged administration of sodium nitroprusside (SNP), a generator of nitric oxide (NO), on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and the labelling index of the gastric mucosa were investigated in male Wistar rats. The rats received intra-peritoneal injections of 2 or 4 mg/kg body weight of SNP every other day after 25 weeks' oral treatment with the carcinogen. Prolonged administration of SNP at 4 mg/kg body weight, but not at 2 mg/kg body weight, significantly decreased the incidence of gastric cancers in experimental week 52. However, it did not affect the histological types or depths of involvement of gastric cancers. SNP at 4 mg/kg body weight, but not at 2 mg/kg body weight, also significantly decreased the bromodeoxyuridine labelling index of the antral epithelial cells. These findings indicate that SNP inhibits gastric carcinogenesis and suggest that this effect may be related to the suppression of proliferation of the antral epithelial cells.

Animals↗

PubMed1998

Low prevalence of Helicobacter pylori infection in patients with hamartomatous fundic polyps.

Helicobacter pylori infection of the gastric mucosal surface was investigated in patients with hamartomatous fundic polyps or hyperplastic polyps and in patients without endoscopic evidence of disease (healthy subjects). Presence of H. pylori infection was determined by culture, histologic examination, and the endoscopic phenol red test. Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral biopsy specimens. Both prevalence of H. pylori infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients with hamartomatous fundic polyps than in healthy subjects and patients with hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa that contained IgA and of gastric epithelial cells that expressed Lewis b did not differ significantly among the three groups. These findings suggest that defense mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen are present in patients with hamartomarous fundic polyps.

Biopsy↗

PubMed1998

Inhibition by transforming growth factor (34-43)-alpha, a TGF-alpha antagonist, of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged administration of transforming growth factor (34-43)-alpha, an antagonist of TGF-alpha, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labelling and apoptotic indices and TGF-alpha immunoreactivity of gastric mucosa and gastric cancers was examined in Wistar rats. The rats received intraperitoneal injections of 10 or 20 microg kg(-1) body weight of TGF(34-43)-alpha every other day after oral treatment with MNNG for 25 weeks. Long-term administration of TGF(34-43)-alpha at both doses significantly reduced the incidence of gastric cancers at the end of the experiment in week 52. However, TGF(34-43)-alpha had no significant effect on the number, histological type or depth of involvement of gastric cancers. Administration of TGF(34-43)-alpha also significantly decreased the bromodeoxyuridine labelling index and TGF-alpha immunoreactivity, and significantly increased the apoptotic index of antral mucosa and gastric cancers. These findings indicate that TGF(34-43)-alpha inhibits gastric carcinogenesis, and that its effects are mediated through decreased cell proliferation and TGF-alpha immunoreactivity and increased apoptosis induction in the gastric cancers.

Adenocarcinoma↗

PubMed1998

Suppression by pravastatin, an inhibitor of p21ras isoprenylation, of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of pravastatin, an inhibitor of p21ras isoprenylation, on hepatocarcinogenesis induced by N-nitrosomorpholine and on p21ras isoprenylation were investigated in male Sprague-Dawley rats. Rats received i.p. injections of pravastatin (10 and 20 mg kg(-1) body weight) every other day and, from the beginning of the experiment, were given drinking water containing N-nitrosomorpholine for 8 weeks. Visible white nodules and hepatic lesions staining positively for gamma-glutamyl transpeptidase or glutathione-S-transferase, placental type, were examined macroscopically or histochemically. In week 15, pravastatin at both dosages significantly reduced the incidence, number and volume of visible white nodules. Quantitative histological analysis also showed that prolonged administration of pravastatin at both dosages resulted in significant reductions in the number and percentage area of hepatic lesions positive for gamma-glutamyl transpeptidase and glutathione-S-transferase, placental type. Administration of pravastatin also significantly decreased the amount of membrane-associated p21ras in the tumour and the labelling index of neoplastic nodules and increased the apoptoic indices of neoplastic nodules. These findings indicate that pravastatin suppresses hepatocarcinogenesis and suggest that this effect might be related to pravastatin's inhibition of p21ras isoprenylation and its subsequent inhibition of cell proliferation and induction of apoptosis in neoplastic lesions.

Animals↗

PubMed1998

Prevention of gastric ulcer recurrence with tetraprenylacetone.

BACKGROUND: The role of cytoprotective agents in the treatment of ulcers remains unclear. In the present study we investigated the effect of tetraprenylacetone (TAP), a cytoprotective agent, on healing and recurrence of gastric ulcers infected with Helicobacter pylori and on the mucosal microvascular architecture of healed gastric ulcers. PATIENTS: Ninety-five gastric ulcer patients with H. pylori infection were studied. METHODS: Gastric ulcer patients with H. pylori infection received 20 mg omeprazole (44 patients) or 20 mg omeprazole and 150 mg TAP (46 patients) in random fashion. Ulcer healing was assessed with endoscopy 12 weeks after the start of treatment. The patients with healed ulcer were followed up for another 12 months without further therapy. During endoscopic examination at week 12, biopsy specimens were obtained from healed gastric ulcers, and the gastric mucosal microvascular architecture of the biopsy specimens was observed by means of the alkaline phosphatase staining method. RESULTS: The rate of ulcer healing at week 12 was similar in patients treated with omeprazole with and without TAP. However, at or within 12 months of the start of follow-up observation, ulcers recurred significantly less frequently in patients treated with both omeprazole and TAP than in those treated with omeprazole alone. Alkaline phosphatase staining methods showed that the mucosal microvascular architecture improved significantly more frequently in healed gastric ulcers that had been treated with both omeprazole and TAP than in those treated with omeprazole alone. CONCLUSIONS: Treatment with TAP plus omeprazole significantly decreases ulcer recurrence through TAP's improved mucosal restoration.

Adult↗

PubMed1998

Helicobacter pylori infection in patients with early gastric cancer by the endoscopic phenol red test.

BACKGROUND: An endoscopic procedure that uses a pH indicator called phenol red to assess Helicobacter pylori infected gastric mucosa has recently been developed. This test makes it possible to take biopsy specimens from H pylori infected areas. AIM: This test was applied to patients with early gastric cancers to clarify the role of H pylori in gastric carcinogenesis. SUBJECTS: Sixty five patients with early gastric cancer (50 with differentiated adenocarcinoma and 15 with undifferentiated adenocarcinoma). METHODS: Patients with early gastric cancer underwent the endoscopic phenol red test before their operation. In this test, areas infected with H pylori can be observed as "coloured" areas where phenol red was turned from yellow to red. RESULTS: H pylori infection was significantly (p < 0.001) more frequent in patients with differentiated adenocarcinomas than in those with undifferentiated adenocarcinomas. Differentiated adenocarcinomas were usually located in areas of mucosa infected with H pylori, but undifferentiated adenocarcinomas were frequently located in non-infected areas. CONCLUSION: H pylori may be a strong risk factor for differentiated early gastric cancer.

Adenocarcinoma↗

PubMed1997

Ornithine decarboxylase inhibitor lessens the rat gastric carcinogenesis enhancement caused by tyrosine methyl ester.

The effects of combined administration of a catecholamine precursor, tyrosine methyl ester (TME), and an ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the norepinephrine (NE) concentration and ODC activity of the gastric wall, and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received s.c. injections of TME, 512 mg/kg body weight, every other day and drinking water with or without 2.5 g/l of DAP after 25 weeks of oral administration of MNNG. At week 52, administration of TME resulted in significant increases in the incidence of gastric cancers, in the NE concentration and the ODC activity of the antral portion of the gastric wall, and in the labeling index of antral epithelial cells. Administration of both TME and DAP significantly reduced the enhancements by TME of gastric carcinogenesis, NE concentration and ODC activity of the antral wall, and the labeling index of the antral mucosa. Our results suggest that ODC inhibition lessens enhancement by TME of gastric carcinogenesis and that the enhancement by TME of gastric carcinogenesis is mediated in part by polyamine biosynthesis.

Animals↗

PubMed1997

Ha-ras mutations in N-nitrosomorpholine-induced lesions and inhibition of hepatocarcinogenesis by antisense sequences in rat liver.

To evaluate the application of Ha-ras mRNA antisense oligonucleotide therapy for liver tumors, we examined the frequency and types of mutation in codon 61 of the Ha-ras oncogene in preneoplastic lesions and hepatocellular carcinomas induced by N-nitrosomorpholine (NNM) in rats. Thirty-seven percent of preneoplastic lesions and 50% of hepatocellular carcinomas contained mutations, mostly CAA-CTA and CAA-AAA transversions. We also investigated the effects on NNM-induced lesions of an antisense oligonucleotide directed against a point mutation (CAA-CTA) in codon 61 of Ha-ras mRNA. In this experiment, Sprague-Dawley rats were given free access to water containing NNM for 8 weeks and received twice-weekly i.p. injections of a mutated Ha-ras antisense oligonucleotide with a 5' phosphorothioate linkage or a sense oligonucleotide in oligonucleotide-liposome complexes. At week 16, rats that had received the mutated Ha-ras antisense oligonucleotides had significantly fewer and smaller preneoplastic lesions positive for glutathione-S-transferase, placental type, and had smaller hepatocellular carcinomas than rats that had received the sense oligonucleotide. Mean cellular fluorescence in the liver was found to increase with higher doses of mutated, fluorescein-isothiocyanate-labeled antisense or sense oligonucleotides. Moreover, mutated Ha-ras antisense oligonucleotide decreased the expression of mutated Ha-ras mRNA (CAA-CTA). Our findings indicate that mutated Ha-ras antisense oligonucleotide significantly inhibits hepatocarcinogenesis in rats and could be an effective therapy against liver tumors.

Animals↗

PubMed1997

d-Limonene inhibits N-nitrosobis(2-oxopropyl)amine induced hamster pancreatic carcinogenesis.

The effect of d-limonene on pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (BOP) was investigated in Syrian golden hamsters. During and after 5 weekly injections of BOP, each hamster was fed diet containing d-limonene. In week 26, quantitative histological analysis showed that prolonged treatment with d-limonene significantly reduced the number of pancreatic carcinomas. Administration of d-limonene did not cause a significant increase in the apoptotic index, but caused a significant decrease in the BrdU labeling index of carcinoma. These findings indicate that d-limonene inhibits the development of pancreatic carcinoma not by enhancing tumor cell loss through apoptosis, but rather by inhibiting cell proliferation.

Animals↗

PubMed1997

Reduction in NaCl-enhanced gastric carcinogenesis in rats fed a high-protein diet.

The effect of a purified, high protein diet on enhanced gastric carcinogenesis induced by oral administration of NaCl was investigated in Wistar rats. Rats were fed on a purified diet with an equalized caloric content, containing 8% NaCl and 25% casein (normal protein diet), or 50% casein (high protein diet) after oral treatment with N-methyl-N'-nitro-N-nitrosoguanidine for 25 weeks. In week 52, oral administration of NaCl had significantly increased the incidence and size of gastric cancer in rats fed a normal protein diet. However, NaCl had no significant effect on gastric carcinogenesis in rats fed a high protein diet. Oral administration of NaCl also caused a significant increase in tissue norepinephrine concentrations in the antral portion of the gastric wall, and increased the labeling indices of the antral epithelial cells of rats fed on a normal protein diet. However, in rats fed a high protein diet, administration of NaCl had no significant influence on these two parameters. These findings indicate that a high protein diet attenuates enhanced gastric carcinogenesis induced by the administration of NaCl, and that this effect may be related to its ability to decrease norepinephrine concentrations in the gastric wall, which subsequently decreases the proliferation of antral epithelial cells.

Animals↗

PubMed1997

Enhancement by ethyl alcohol of experimental hepatocarcinogenesis induced by N-nitrosomorpholine.

The effects of ethyl alcohol (EtOH) during or after treatment with N-nitrosomorpholine (NNM) on hepatocarcinogenesis, ornithine decarboxylase (ODC) activity and the labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of 1 g EtOH/kg body weight every other day during or after treatment with NNM. Pre-neoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P), were examined immunohistochemically. At the end of experiment at week 16, administration of EtOH after NNM treatment had no significant effect on the number and size of GST-P-positive hepatic lesions, whereas administration of EtOH during NNM treatment significantly increased the number and percentage area but not the mean area of GST-P-positive hepatic lesions. EtOH caused significant increases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and the adjacent hepatocytes after the cessation of EtOH administration but not during EtOH treatment. Our findings indicate that EtOH enhances hepatocarcinogenesis and suggest that this effect may be closely related to the increases in ODC activity and cell proliferation in enzyme-altered lesions and the adjacent liver after EtOH treatment.

Animals↗

PubMed1997

Diagnosis of carcinoma in situ of the pancreas by peroral pancreatoscopy and pancreatoscopic cytology.

BACKGROUND: Most pancreatic carcinomas are unresectable at the time of diagnosis, but recently the diagnosis of carcinoma in situ of the pancreas has become possible. This diagnosis can be made by the detection of cancer cells in pancreatic juice and the radiographically demonstrated lack of a mass lesion. It has greatly improved the effectiveness of surgery. Carcinoma in situ remains within the pancreatic ductal epithelium and has not yet invaded the parenchyma. However, it has often been difficult to locate carcinoma in situ by conventional diagnostic methods, such as ultrasonography, endoscopic ultrasonography, computed tomography, and endoscopic retrograde pancreatography. METHODS: Peroral pancreatoscopy and a new method of cytodiagnosis, pancreatoscopic cytology, were used to analyze 11 patients with carcinoma in situ of the pancreas, 10 with disease in the main duct of the pancreas and 1 with disease in the branch ducts. The results of pancreatoscopic cytology were compared with those of conventional pancreatic juice cytology. RESULTS: Under peroral pancreatoscopy, carcinoma in situ of the pancreas in the main duct appeared as papillary mucosa, irregular mucosa, or nodular mucosa. Using pancreatoscopic cytology, cancer cells were obtained from all the lesions, allowing a more thorough analysis than pancreatic juice cytology. CONCLUSIONS: Peroral pancreatoscopy and pancreatoscopic cytology are useful for locating and diagnosing carcinoma in situ of the pancreas.

Aged↗

PubMed1997

Enhancement by monochloramine of the development of gastric cancers in rats: a possible mechanism of Helicobacter pylori-associated gastric carcinogenesis.

The effects of cytotoxic monochloramine on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. After oral administration of drinking water containing the carcinogen and regular chow pellets for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without s.c. injection of taurine, until the end of the experiment in week 52. Treatment with both ammonium acetate and sodium hypochlorite significantly increased the incidence of gastric cancers in week 52, while the concomitant use of taurine with ammonium acetate and sodium hypochlorite significantly attenuated the enhanced gastric carcinogenesis. Spectrophotometric examinations revealed that taurine scavenged monochloramine. These findings suggest that Helicobacter pylori-associated gastric carcinogenesis may be mediated by monochloramine.

Animals↗

PubMed1997

Clinicopathologic features and endoscopic resection of duodenal adenocarcinomas and adenomas with the submucosal saline injection technique.

BACKGROUND: Endoscopic resection with the submucosal saline injection technique has been used to treat early duodenal cancers and adenomas. However, indications for endoscopic treatment of these cancers have not been established. METHODS: We used the submucosal saline injection method to treat 14 early duodenal cancers and adenomas to evaluate its safety and effectiveness. A 0.9% NaCl solution was injected into the submucosal layer near the tumor through needle forceps to elevate the tumor, which was then resected with electrocoagulation. Resected specimens were examined to assess depth of involvement, completeness of resection, and histologic type. Reports of early duodenal cancers in the Japanese literature were reviewed to analyze the relationship among lymph node metastasis, submucosal invasion, and tumor size. RESULTS: All tumors were completely removed "en bloc" (12 tumors) or in a "piecemeal" fashion (two tumors). The largest tumor was 20 mm in diameter. No serious complications occurred during or after treatment. Review of Japanese literature showed that lymph node metastasis did not occur when protruding or elevated tumors were less than 50 mm in diameter but did occur when depressed tumors, with or without marginal elevation, were more than 10 mm in diameter. CONCLUSIONS: Endoscopic resection with the submucosal saline injection technique is a safe and effective treatment for early duodenal cancers and adenomas. Protruding or elevated tumors less than 50 mm in diameter can be removed completely. However, because of possible lymph node metastasis, depressed tumors with or without marginal elevation should be removed surgically.

Adenocarcinoma↗

PubMed1997

Inhibition by ginsenoside Rg3 of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats.

The effects of concomitant use of bombesin and ginsenoside Rg3 on the incidence of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane were investigated in male inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 microg/kg body weight) every other day, and from week 20, s.c. injections of ginsenoside Rg3 (2.5 or 5.0 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of a higher dose of ginsenoside Rg3 with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth pattern, labeling and apoptotic indices and tumor vascularity of intestinal cancers, it significantly decreased the incidence of cancer metastasis. These findings indicate that ginsenoside Rg3 inhibits cancer metastasis through activities that do not affect the growth or vascularity of intestinal cancers.

Adenocarcinoma↗

PubMed1996

Enhancement by neurotensin of hepatocarcinogenesis by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of neurotensin on hepatocarcinogenesis by N-nitrosomorpholine (NNM) was investigated in Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and alternate-day injections of neurotensin from the beginning until the end of the experiment. Preneoplastic and neoplastic lesions stained for placental type glutathione-S-transferase (GST-P) were examined histochemically. Administration of neurotensin significantly increased the percentage area and the number of GST-P-positive lesions, and the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that neurotensin enhances hepatocarcinogenesis and that this effect may be related to its effect in increasing cell proliferation in preneoplastic lesions.

Animals↗

PubMed1996

Inhibition by the calmodulin antagonist trifluoperazine of experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of the calmodulin antagonist trifluoperazine on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) and on the ornithine decarboxylase (ODC) activity and labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks, and from the beginning of the experiment, received s.c. injections of 15 or 30 mg/kg body weight of trifluoperazine in depot form every other day until the end of the experiment. Preneoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P) were examined histochemically. In week 16, quantitative histological analysis showed that prolonged administration of 30 mg but not 15 mg/kg body weight of trifluoperazine resulted in significant reductions in the number and percentage area of GST-P-positive hepatic lesions. Trifluoperazine also caused significant decreases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and their adjacent hepatocytes. These findings indicate that trifluoperazine inhibits carcinogenesis and suggest that this effect may be closely related to its effect in inhibiting ODC activity and cell proliferation in the enzyme-altered lesions and their adjacent liver.

Animals↗

PubMed1996

Inhibition by amiloride of experimental carcinogenesis induced by azaserine in rat pancreas.

The effects of prolonged administration of the diuretic amiloride on pancreatic carcinogenesis induced by azaserine and on the labeling index of carcinogen-induced pancreatic lesions were investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight azaserine and also 5 mg/kg body weight amiloride every other day until the end of the experiment at week 62. Carcinogen-induced pancreatic lesions were examined by histochemical techniques and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histologic analysis showed that prolonged administration of amiloride significantly reduced the number and size (as percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely correlated with the subsequent development of pancreatic cancer. Amiloride also significantly decreased the labeling index of carcinogen-induced pancreatic lesions, but not of the surrounding acinar cells. In contrast, amiloride has no significant influence on the number and size of ATPase-negative pancreatic lesions. These findings indicate that amiloride inhibits pancreatic carcinogenesis, and that this effect may be related to the reduction of ATPase-positive lesions and to amiloride's inhibition of cell proliferation in neoplastic lesions of the pancreas.

Adenosine Triphosphatases↗