[Helicobacter pylori infection and gastroduodenal diseases. From the point of view of surgery].
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Gastric Mucosa↗
Biomedical subjects
M Onda
Publications and source records attributed to M Onda.
The effect of preoperative high dose methylprednisolone in attenuating the metabolic response after oesophageal resection.
OBJECTIVE: To evaluate the effect of giving glucocorticoids preoperatively for the prophylaxis of surgical stress. DESIGN: Prospective randomised study. SETTING: University hospital, Japan. SUBJECTS: 30 patients undergoing resection of oesophageal carcinoma. INTERVENTIONS: 15 patients (group 1) were randomised to be given methylprednisolone (30 mg/kg) and 15 patients (group 2) to be given saline intravenously before operation. MAIN OUTCOME MEASURES: Outcome, length of stay in the intensive care unit (ICU), metabolic response, and oxygenation. RESULTS: Patients given methylprednisolone had a mean stay in the ICU of 5.1 +/- 1.0 days compared with 8.2 +/- 4.5 days in the saline group (p < 0.01). 5 patients in the saline group compared with 0 in the methylprednisolone group developed postoperative complications (p = 0.02). Plasma norepinephrine and arginine vasopressin levels in methylprednisolone group were significantly lower than those in the saline group (p < 0.05). The PaO2:FiO2 ratio in the saline group was significantly lower than that in the experimental group (p < 0.01). CONCLUSIONS: Preoperative methylprednisolone may facilitate the postoperative management of surgical patients.
Adult↗
Detailed deletion mapping of chromosome arm 3p in breast cancers: a 2-cM region on 3p14.3-21.1 and a 5-cM region on 3p24.3-25.1 commonly deleted in tumors.
Loss of heterozygosity (LOH) on 3p is frequent in human renal cell carcinomas, lung cancers, and breast cancers. To define the region(s) on 3p that harbor presumptive tumor suppressor gene(s) for breast cancer, we examined 196 primary breast tumors for their patterns of LOH at 22 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 101 (52%) of these tumors. Detailed deletion mapping identified two distinct commonly deleted regions; one was localized to a 2-cM interval flanked by D3S1547 and D3S1295 at 3p14.3-21.1, and the other to a 5-cM interval flanked by D3S1286 and D3S1585 at 3p24.3-25.1. The FHIT gene lies in the vicinity of the proximal commonly deleted region. Attempts to correlate LOH on 3p to clinicopathological parameters detected an association with the absence of the progesterone receptor (P = 0.0096). The results suggest that inactivation of unidentified tumor suppressor genes on 3p plays a role in the mechanism whereby hormone dependency is lost in the course of breast carcinogenesis.
Breast Neoplasms↗
[Prospect of gene therapy for metastatic foci of gastric cancer].
Surgical excision of both primary and metastatic tumors is the recommended therapy for gastric cancer. There are many cases of multiple metastasis to lymph nodes, disseminated metastasis of peritoneum, and post-operative systemic metastasis for which no surgical treatment is available. Cancer gene therapy is one of the promising new techniques. We injected the suicide gene, herpes simplex virus thymidine kinase (HSV-tk), directly into the tumor using gastrofiberscopy. Following GCV treatment caused tissue degeneration at the injection site and lymph nodes. These findings show that suicide gene therapy for gastric cancer may be effective for a metastatic tumor along with the primary tumor.
Animals↗
[Effects of neoadjuvant intra-arterial infusion chemotherapy in patients with stage III breast carcinoma].
From 1991 to 1996, we performed neoadjuvant intra-arterial infusion chemotherapy in 5 eligible patients among 21 patients with Stage III breast carcinoma. The treatment regimen for neoadjuvant chemotherapy was intra-arterial Epirubicin (EPR) on Day 1, 3, 5, 7 combined with endocrine therapy (MPA 1,200 mg). The effects of the treatment were compared among 8 patients given adjuvant intravenous chemotherapy. The clinical response rate was 100% with all partial response and metastatic lymph nodes were disappeared histologically in 2 cases. The median disease-free interval and overall survivals are 44 months (range 28-64) and 48 months (range 28-64), respectively. Neoadjuvant (intra-arterial) group had a longer disease-free interval than the adjuvant (intravenous) group. We are applying this treatment for down staging, and it is possible to use minimal invasive surgery for cure of stage III breast carcinoma.
Adult↗
K-ras and p53 gene mutations in colorectal cancer in 57 Japanese patients.
Fifty-eight tissue specimens from 57 Japanese patients with colorectal cancer were analyzed for the K-ras and p53 gene mutations by polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing. K-ras mutations were detected in 21 cases (36.2%) and p53 mutations in 20 cases (34.5%). Eight specimens had both gene mutations. The K-ras mutation was associated with higher degrees of differentiation (p = 0.0019). The P53 mutation was associated with Duke B to D staging (p = 0.028), lymph vessel invasion (p = 0.021), and venous invasion (p = 0.03). Interestingly, a mutation in only exon 7 of the P53 gene was associated with lymph node metastasis. These results suggest the important effect of the mutations of the K-ras and p53 genes, especially p53 gene on colorectal carcinogenesis in Japanese patients. The grades of malignancy of the specimens with the mutations in both genes were not different significantly from those with a single (K-ras or p53) or no mutation, suggesting no cooperation between K-ras and p53 gene mutations on carcinogenesis or tumorigenesis.
Adenocarcinoma↗
Inhibitory effect of anti-epidermal growth factor receptor antibody on a human gastric cancer.
BACKGROUND: Blockading the putative epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha)/EGF receptor autocrine pathway with anti-EGF receptor monoclonal antibody (MoAb) might prevent the growth of tumor. METHODS: The present study was designed to examine the effect of MoAb 528 on the growth of an EGF receptor which was hyperproducing human gastric cancer cells in vitro and in vivo. RESULTS: Treatment with MoAb 528 inhibited the growth of cultured cells in a dose-dependent manner. Twenty micrograms of MoAb 528 given intraperitoneally after inoculation of 1 x 10(6) cells and 200 micrograms of the MoAb 528 given after inoculation of 1 x 10(7) cells to athymic mice inhibited the growth of the xenograft. Twenty micrograms of MoAb 528 from a miniosmotic pump, which releases its contents over 2 weeks, also prevented the growth of the xenograft when the treatment was started on the day after tumor inoculation. However, no inhibitory effect was observed when the treatment was started 3 weeks after inoculation. The binding capacity of 125I-EGF on the MoAb treated tumors was diminished in comparison with control tumors. CONCLUSIONS: The results suggest that MoAb 528 blocks the EGF or TGF-alpha/EGF receptor signal pathway, resulting in the inhibition of cancer cell growth. This MoAb 528 may therefore be an effective antitumor agent against human gastric cancer that shows expression of the EGF receptor.
Animals↗
Genetic polymorphisms of the cancer related gene and Helicobacter pylori infection in Japanese gastric cancer patients. An age and gender matched case-control study.
BACKGROUND: Gastric cancer is a multistage process, each caused by numerous factors. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiologic techniques and serum markers. METHODS: Serum pepsinogen I levels, pepsinogen I/pepsinogen II (I/II) ratios, serum IgG antibody against Helicobacter pylori (H. pylori), and genetic polymorphisms of cytochrome p450 2E1 (CYP2E1), glutathione-S-transferase M1 (GSTM1), and L-myc protooncogenes were analyzed in 82 persons with gastric cancer and in 151 age- and sex-matched controls, who were selected from 208 gastric cancer patients and 375 noncancer patients, respectively. Statistical analysis was performed to elucidate which risk factors for gastric cancer were contributing the most to gastric carcinogenicity. RESULTS: Serum pepsinogen I level (odds ratio [OR] = 1.81; 95% confidence interval [CI], 1.04-3.16) and pepsinogen I/II ratios (OR = 3.09; 95% CI, 1.74-5.49) were significantly associated with gastric cancer risk in a case-control study. Seropositivity of serum IgG antibody against H. pylori (OR = 1.25; 95% CI, 0.84-1.85) and specific genotypes of a L-myc genetic polymorphism (OR = 1.33; 95% CI, 0.59-2.99) were more commonly observed in gastric cancer cases, but this was not statistically significant. Specific genotypes of the CYP2E1 RsaI polymorphism and GSTM1 gene deletion were not associated with gastric cancer. CONCLUSIONS: Atrophic mucosal change, indicated by serum pepsinogen levels, is possible a risk factor for gastric cancer. H. pylori infection and genetic polymorphisms of CYP2E1, L-myc, and GSTM1 genetic polymorphisms were not risk factors in this study.
Adult↗
Tob, a novel protein that interacts with p185erbB2, is associated with anti-proliferative activity.
We have molecularly cloned a cDNA for a novel protein termed Tob (Transducer of ErbB-2) that interacts with the c-erbB-2 gene product p185erbB2. Nucleotide sequencing reveals that the Tob protein is a 45 kDa protein that does not contain either SH2 (Src Homology 2) or SH3 domain but is homologous to the previously characterized anti-proliferative gene product BTG-1 at its amino-terminal half. The carboxyl-terminal half of Tob is characterized by the presence of a sequence rich in proline and glutamine and shows no homology to known proteins. Like BTG-1, exogenously expressed Tob is able to suppress growth of NIH3T3 cells, but the growth suppression is hampered by the presence of kinase-active p185erbB2. By using the GST-Tob protein that contains either full length or amino-terminal half of Tob, we show that the carboxyl-terminal half of Tob is relevant to its interaction with p185erbB2. Furthermore, we could co-immunoprecipitate the Tob protein with anti-ErbB-2 antibody, and reciprocally the p185erbB2 with anti-Tob antibodies. These data suggest that p185erbB2 negatively regulates the Tob-mediated anti-proliferative pathway through its interaction with Tob, resulting possibly in growth stimulation by p185erbB2. Finally, expression of the Tob mRNA is observed in various cell types and is not correlated with expression of c-erbB-2, suggesting that other receptor-type protein-tyrosine kinases are also involved in the Tob-mediated regulation of cell growth.
3T3 Cells↗
ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma.
BACKGROUND: It has been reported that the c-erbB-2 protooncogene is frequently amplified and overexpressed in many types of cancers, except sarcomas and hematological malignancies. METHODS: Expression of ErbB-2 in the tumors of 26 patients with conventional osteosarcoma was evaluated by immunoblotting. DNA from osteosarcoma tissues that expressed ErbB-2 were analyzed by Southern blot hybridization to examine gross rearrangement of the gene. The DNA was also surveyed for the presence of genetic mutation in the transmembrane domain of ErbB-2 by polymerase chain reaction-single-stranded DNA conformation polymorphism analysis. In addition, possible correlation of ErbB-2 expression with gender, age, histopathologic subtype, and response to chemotherapy was analyzed. Survival analysis was performed by the Kaplan-Meier test using the approximate chi-square statistic for the log-rank test. RESULTS: The ErbB-2 protein was detected in 11 of 26 osteosarcoma tissues (42%) by immunoblot analysis. Expression of ErbB-2 was confirmed by immunohistochemical studies using specific anti-ErbB-2 monoclonal antibody. However, neither amplification of the c-erbB-2 gene nor evidence of significant genetic mutation was found in these osteosarcomas. Expression of ErbB-2 examined by immunoblotting was most strongly correlated with early pulmonary metastases (P < 0.05). Among the entire group of 26 patients in this study, Kaplan-Meier life table survival of the patients with apparent ErbB-2 expression was significantly worse than that of the patients with little ErbB-2 expression (P < 0.01). CONCLUSIONS: In 42% of the osteosarcomas, the tumor cells expressed ErbB-2. Expression of ErbB-2 was strongly correlated with early pulmonary metastasis and poor survival rate for the patient. These data suggest that ErbB-2 plays a significant role in aggressive tumor growth and in the promotion of metastatic potential in osteosarcomas. ErbB-2 in the osteosarcoma tissues would be a useful prognostic marker for patients.
Adolescent↗
Myoepithelial hamartoma of the small bowel: report of a case.
Benign small bowel tumors seldom cause symptoms, due to the fluid content and distensibility of the small bowel. We herein present the case of a solitary ileal hamartoma causing melena and abdominal pain in a 24-year-old man. The diagnosis of a submucosal ileal tumor was made after performing small bowel barium studies. Surgical treatment was undertaken, and a histological examination of the excised lesion, which showed a partially ulcerated tumor surface and extended from the submucosa to the subserosa, revealed numerous cystic glands of various sizes together with bundles of proliferating smooth muscle cells. Histochemical and immunohistochemical investigations were performed for differential diagnosis, and the tumor features were consistent with a diagnosis of ileal myoepithelial hamartoma. In the literature, small intestinal myoepithelial hamartomas are quite rare and this is the first report of a myoepithelial hamartoma causing melena.
Adult↗
Changes in urinary nitrate and nitrite during treatment of ulcerative colitis.
The urinary excretion rates of nitrate (NO3) and nitrite (NO2) were monitored in 14 patients with active ulcerative colitis during treatment using hydrocortisone and sulfasalazine. During the active phase of the disease, the NO3 excretion was significantly higher in the patients than in healthy controls (n = 6, p < 0.05), although it varied considerably among the patients. During the healing phase, the NO3 excretion decreased concurrently with improvement of symptoms and colorectal ulceration, but the NO2 excretion increased. During the inactive phase of the disease, the NO3 and NO2 excretions were significantly lower than during the active phase, and the NO2/NO3 ratio resembled that in the healthy controls. In contrast, a patient who failed to respond to treatment showed continuously high NO3 and NO2 excretion rates. These results indicate that urinary NO3 and NO2 excretions vary with the disease state in ulcerative colitis.
Adult↗
[Effect of green tea polyphenol fraction on 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in the rat].
We studied the anti-tumor effect of green tea polyphenol fraction (Sunphenon, SF: provided by Taiyo Kagaku Inc., Mie, Japan) on DMH-induced colorectal carcinogenesis in male Wistar rats. DMH was subcutaneously administered weekly at 20 mg/kg for 14 weeks. The rats in group I (20 rats) were given tap water for the whole of the study period. The rats in group II (15 rats) were given tap water from weeks 0-14, and 0.1% SF from weeks 15-35. The rats in group III (21 rats) were given 0.1% SF during the whole period. The rats were sacrificed at week 35. The cecal contents were aseptically removed and examined microbiologically to obtain the counts of four bacteria species (including Clostridium perfringens) per 1 g of cecal contents. The incidence of tumors production was significantly decreased (Group I: 100% vs Group II: 57.1%, Group III: 62.5%, p < 0.05), and the frequency of occurrence of C. perfringens (which is thought to yield harmful products which may be carcinogenic) was decreased in the SF-treated groups. These results suggest that SF prevents DMH-induced carcinogenesis in rats, and that its effect may be somehow related to its ability to preserve the composition of the colonic microflora.
1,2-Dimethylhydrazine↗
[The evaluation of therapeutic effect on partial splenic embolization (PSE) for liver cirrhosis patients].
Partial splenic embolization (PSE) was performed on fifty cases with liver cirrhosis underwent no therapy. We evaluated changes of platelet count, ICGR15, GPT and Child-Pugh score which were significantly recovered by PSE. About liver cirrhosis before PSE, K.ICG, GPT, Alb, platelet count and splenic volume were selected as total characteristic factors by principal component analysis. We showed predicting formulas after PSE by multiple regression analysis between five factors selected by principal component analysis and platelet count, HPT, PT, Alb, ICGR15, K.ICG, GOT, GPT and Child-Pugh score after PSE. In conclusion, it is suggested that PSE is useful for recovering of platelet count and liver function. We made it possible to estimate therapeutic effect by predicting formulas before PSE.
Aged↗
[K-ras gene mutations in adenomas from familial adenomatous polyposis].
A 18-year-old woman underwent total colectomy for familial adenomatous polyposis. In order to clarify the significance of K-ras mutations in early colorectal carcinogenesis, K-ras mutations were analyzed in multiple adenomas by PCR-SSCP method. A total of 256 adenomas were found throughout the entire colon and rectum, and the distribution was a sparse type. The correlation between K-ras gene and clinicopathological factors was examined in 90 adenomas. There was no correlation among K-ras mutations and anatomical distribution, or morphological classification, but K-ras mutation was more frequent in severe compared with slight atypia. We investigated the correlation between the size of adenoma in the horizontal and vertical directions and K-ras mutation. K-ras mutation was more frequent in the horizontal size greater than 6 mm in diameter, and also more frequent in vertical size greater than 20 mm in height. It was concluded that the adenomas detecting K-ras mutations might have proliferating potential, and would be applied to determine polypectomy.
Adenoma↗
[Mitomycin C-DNA adduct detection in rat organs and human liver].
Mitomycin C-DNA adduct formation was detected in rat organs and also in human tissues by 32P-postlabeling assay. The adduct levels were 1-4 adduct/ 10(8) nucleotides in the human liver after 20 mg of mitomycin C by intra-artery administration and which level was higher comparing with the levels in the rat liver after 10 times more dosages of mitomycin C administration by intra-venous injection. The levels in the human liver were maintained at least 56 days after administration. Organ-specific differences of adduct levels were observed in rat experiments: the adduct levels of liver, lung and kidney were stable but rapidly decreased in stomach and colon. These results, which were obtained from the experiments using the normal parts of each organs may indicate that the drug effectivity for adduct formation was sufficient with smaller dose in the stomach and colon, but disappeared quickly, mean while, the drug effectivity was undergoing in relatively high levels for longer periods in the liver lung and kidney. The analysis of human liver samples may suggest that the selective intra-artery injection induced stronger drug effectivity for adduct formation in human organs.
Adult↗
[Role of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].
Examinations of peritoneal lavage smears (LC) and gastric wall brushing smear cytology (BC) appear to be important for determining accurately the stage of gastric cancer. We have been carrying out such examinations during gastric cancer surgery for 7 years. In the present study, we evaluated the results obtained from 287 patients with gastric cancer. Tumor invasion and peritoneal dissemination were correlated with a positive incidence of cancer cells in LC and/or BC. Gastric cancer showing serosal invasion was classified into positive for LC and/or BC and negative for LC and/or BC. Patients positive for LC and/or BC had a poorer prognosis. For future gastric cancer treatment, patients positive for peritoneal cytology are expected to be targeted for intensive treatment during or before surgery.
Adenocarcinoma↗