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Haruhiko Sugimura

Publications and source records attributed to Haruhiko Sugimura.

68 records · Page 4Linked to original sources
PubMed2002

hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese.

Oxidative stress is involved in many types of DNA damage, e.g., resulting in 8-hydroxyguanine adducts. Since a human counterpart exists for the yeast gene OGG1 (hOGG1) encoding an enzyme that repairs 8-hydroxyguanine, its polymorphism, Ser(326)Cys, might have potential as a genetic marker for cancer susceptibility. To investigate its association with stomach cancer risk and possible interactions with environmental factors, we conducted a case-control study of 101 stomach cancer cases and 198 controls using PCR-single-strand conformation polymorphism and a questionnaire approach. The proportional distribution of the Cys/Cys alleles did not differ between stomach cancer cases and controls, but subgroup analyses revealed that a frequent drinking habit elevated the odds ratio (OR) for stomach cancer in Cys/Cys compared to Ser/Ser and Ser/Cys carriers. The ORs with frequent consumption of pickled vegetables and meat tended to be higher in Cys/Cys than in Ser/Ser and Ser/Cys carriers, these interactions being on the borderline of statistical significance. Our findings suggest that the hOGG1 Ser(326)Cys polymorphism may alter the impact of some environmental factors on stomach cancer development. For confirmation, an additional study with a larger number of subjects is now required.

Adult↗
PubMed2002

Genomic structure of the human beta-PIX gene and its alteration in gastric cancer.

beta-PIX, a newly identified p21-activated kinase (PAK)-interacting exchange factors (PIX), encodes a guanine nucleotide exchange factor for Rho guanosine triphosphatases. Characterization of beta-PIX gene was performed using the BAC Library method. The beta-PIX gene has 17 exons and an A/T polymorphism at the 32nd base upstream of the intron/exon junction of exon 7. The frequencies of genotypes A/T, A/A and T/T were 23.6% (13/55), 72.7% (40/55) and 3.6% (2/55), respectively; these frequencies are in Hardy-Weinberg equilibrium. Two out of 14 informative tumors (14.3%) were shown to have lost their heterozygosity at this locus, but no mutations in the remaining alleles were detected. In addition, we examined the gene-expression profile in another set of 30 gastric samples, but no significant over-expression of either the beta-PIX gene or the alpha-PIX gene was found. Though the beta-PIX gene has been speculated to potentially have tumor-related biological characteristics, the findings of the present study suggest that the involvement of beta-PIX gene in human gastric carcinogenesis is minimal.

Alleles↗
PubMed2002

Diverticulitis causing a high serum level of carbohydrate antigen 19-9: report of a case.

We report herein a rare case of diverticulitis causing a high serum level of carbohydrate antigen (CA) 19-9. A 52-year-old man was admitted to our hospital with lower abdominal pain. Laboratory data showed evidence of inflammation and a high serum level of CA 19-9 (370 U/ml). Computed tomography demonstrated thickening of the wall of the sigmoid colon. He was diagnosed as having diverticulitis of the sigmoid colon and was treated with antibiotics. Although his symptoms improved, the presence of a malignancy such as colorectal cancer could not be completely ruled out because of the persistently high serum level of CA 19-9. A laparotomy was performed and the sigmoid colon was found to be adherent to the bladder. Under a diagnosis of diverticulitis, a sigmoidectomy was performed. Pathological examination revealed diverticulitis of the sigmoid colon, but there was no evidence of malignancy in the resected specimen. The serum CA 19-9 level decreased to normal postoperatively and immunohistochemical staining revealed CA 19-9 antigen in the cytoplasm of the diverticular epithelium. Therefore, a possible explanation for the high level of this tumor marker was diverticulitis of the sigmoid colon.

CA-19-9 Antigen↗
PubMed2002

Gastrojejunocolic fistula after gastrectomy with Billroth II reconstruction: report of a case.

We herein report the case of a 65-year old man with gastrojejunocolic fistula. The patient was admitted to our hospital because of edema of the lower limbs, diarrhea, and weight loss. His history included a distal gastric resection and Billroth II reconstruction for a duodenal ulcer 20 years previously. The laboratory data on admission revealed hypoproteinemia and hypoalbuminemia. An upper gastrointestinal X-ray series revealed a fistula between the transverse colon and upper jejunum. After improving his state of malnutrition, a partial resection of the remnant stomach, transverse colon, and jejunum, which were involved in the fistula, was performed. The postoperative course was uneventful and the patient was discharged on the 26th postoperative day. Gastrojejunocolic fistula is one of the severe complications of a stomal ulcer after a gastric resection with Billroth II reconstruction, which is considered to be induced by an inadequate resection of the stomach. As a result of the recent development of improved agents for the treatment of peptic ulcers, the occurrence of gastrojejunocolic fistula has decreased remarkably. However, gastrojejunocolic fistula should be recognized as one of the late severe complications observed after a gastrectomy with Billroth II reconstruction, since this disease may occur even 20 years after the first operation for peptic ulcer.

Aged↗
PubMed2002

Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan.

BACKGROUND & AIMS: Interleukin-1 beta (IL-1beta) polymorphisms are associated with increased risk of gastric cancer in whites. This study aimed to examine effects of these polymorphisms on gastric acid secretion, atrophic gastritis, and risk of peptic ulcer in Japan. METHODS: We determined IL-1B-511/-31 and IL-1RN genotypes and measured gastric juice pH, serum pepsinogen (PG) I and II levels, and gastritis and atrophy scores in Helicobacter pylori-positive patients with gastritis only, gastric ulcers, or duodenal ulcers (DUs), and H. pylori-negative controls. RESULTS: In the H. pylori-positive group, subjects with the proinflammatory IL-1B-511 T/T genotype had the highest atrophy and gastritis scores, the highest median gastric juice pH, and the lowest median serum PG I/PG II ratios. Although gastric juice pH significantly increased and serum PG I and PG I/PG II ratios significantly decreased in the IL-1B-511 T/T genotype group with age, no such age-dependent changes were observed in the C/C genotype group. Changes in the C/T genotype group were intermediate. In the H. pylori-negative group, the IL-1 loci had no effect on any of the physiologic or morphologic parameters. Carriage of IL-1RN allele 2 significantly protected against DU disease while the IL-1B-511 T/T genotype significantly protected against DU recurrence in patients older than 60 years. CONCLUSIONS: Proinflammatory IL-1beta polymorphisms are associated with hypochlorhydria and atrophic gastritis in Japan. The effects are dependent on H. pylori infection and become more significant with advancing age. This may explain the high incidence of gastric cancer in Japan and also the age-dependent decrease in DU recurrence in infected subjects.

Achlorhydria↗
PubMed2002

Total gastrectomy is not always necessary for advanced gastric cancer of the cardia.

BACKGROUND: It is unclear whether total gastrectomy (TG) is always necessary for gastric cancer of the cardia. We therefore investigated whether cardiac cancers treated by TG would have been cured by proximal gastrectomy (PG). METHODS: Photocopies of the resected stomachs of 55 patients who had received TG for cardiac cancer were reviewed. A simulated resection line for PG was drawn connecting a point 5 cm from the pyloric ring on the lesser curvature with a point 15 cm from the pyloric ring on the greater curvature. The distal surgical margin between the tumor edge and the simulated resection line was measured, and lymph nodes (LN) dissected surgically were examined for tumor involvement. RESULTS: Tumor location fell into three categories, upper-middle (UM, n = 28), upper (U, n = 18), and upper-esophagus (UE, n = 9). The means of the simulated surgical margins were 1.0 cm for UM, 4.7 cm for U, and 5.7 cm for UE tumors. UE tumors had no metastasis to No. 4d, 5, or 6 LN, and only one U tumor showed metastasis to No. 4d and 5 LN. In contrast, UM tumors had a higher incidence of these nodes involved. CONCLUSION: Advanced gastric cancer located in the U or UE regions is mostly curable by PG.

Carcinoma↗
PubMed2002

Bilateral cavernous sinus actinomycosis resulting in painful ophthalmoplegia. Case report.

The authors report the successful treatment of a 42-year-old man who suffered from recurrent painful ophthalmoplegia caused by bilateral cavernous sinus (CS) actinomycosis. A presumptive diagnosis of Tolosa-Hunt syndrome was made when he presented with left painful ophthalmoplegia. Recurrent ophthalmoplegia on the opposite side when steroid medications were tapered led to repeated imaging and a pterional craniotomy and biopsy sampling of the CS. These tests demonstrated acute inflammation and sulfur granules, which responded clinically and radiologically to parenterally administered penicillin therapy. Actinomycosis may present as a painful ophthalmoplegia with involvement of one or both CSs. Repeated imaging and possibly surgical exploration may be necessary to make a definitive diagnosis.

Actinomycosis↗
PubMed2002

Interaction between cytochrome P-450 2E1 polymorphisms and environmental factors with risk of esophageal and stomach cancers in Chinese.

Because cytochrome P-450 2E1 (CYP2E1) is involved in metabolic activation of environmental chemical carcinogens, gene polymorphisms that alter its functions may be associated with cancer susceptibility. However, previous studies have revealed disconcordant results with regard to cancer risk. To investigate gene-environment interactions with the RsaI polymorphism of CYP2E1 in terms of risk of esophageal and stomach cancers, we conducted a case-control study with 93 esophageal and 98 stomach cancer cases and 196 population-based controls in a high-endemic area for these cancers of China. We assayed genomic DNA samples for RFLPs in the CYP2E1 by PCR amplification, followed by digestion with RsaI, and collected information on environmental factors by a questionnaire approach. Odds ratios were estimated with an unconditional logistic model, after adjustment for potential confounding factors. The proportional distribution of the homozygous common RsaI alleles did not differ between cancer cases of the esophagus (59.1%) and stomach (59.2%), and controls (61.7%). However, we found a significant positive interaction between the heterozygous and homozygous RsaI rare alleles and ever-smoking in the odds ratio for stomach cancer (P = 0.015). The interaction between the gene polymorphism and dietary factors, such as garlic consumption, was not observed in both cancer cases. These results suggest that gene-environment interactions between the CYP2E1 polymorphism and smoking may have the potential to alter the susceptibility for cancer development in the stomach.

Adult↗
PubMed2002

Contribution of the NQO1 and GSTT1 polymorphisms to lung adenocarcinoma susceptibility.

Lung adenocarcinoma has replaced squamous cell lung carcinoma as the most frequent histological subtype in lung cancers. However, genetic factors that affect cancer susceptibility are much less understood in adenocarcinoma than in squamous cell carcinoma. In this study, polymorphisms in five genes involved in the metabolism of carcinogens or in the repair of damaged DNA in lung cells, NQO1-Pro187Ser, GSTT1-positive/null, GSTM1-positive/null, CYP1A1-Ile462Val, and OGG1-Ser326Cys, were examined for association with lung adenocarcinoma risk in a case-control study of 198 patients and 152 control subjects. The NQO1 and GSTT1 polymorphisms were associated with lung adenocarcinoma risk with adjusted odds ratio of 2.15 for the NQO1-Pro/Pro genotype versus the Ser/Ser genotype and adjusted odds ratio of 1.61 for the GSTT1-null genotype versus the positive genotype, respectively. Furthermore, individuals with the combined genotype of NQO1-Pro/Pro and GSTT1-null showed greater risk compared with those of NQO1-Ser/Ser and GSTT1-positive. In contrast, significant association was not observed for the GSTM1, CYP1A1, and OGG1 polymorphisms with lung adenocarcinoma risk, although several studies have shown their implication in the risk for squamous cell lung carcinoma. The result indicates that the NQO1-Pro/Pro and GSTT1-null genotypes are risk factors for lung adenocarcinoma development, and that the genetic factors for susceptibility to adenocarcinoma are different from those to squamous cell carcinoma. The enhanced risk of the NQO1-Pro/Pro genotype combined with the GSTT1-null genotype was more evident in smokers than in nonsmokers. Therefore, carcinogens in tobacco smoke, which are activated by NQO1 and detoxified by GSTT1, could have a role in lung adenocarcinoma development.

Adenocarcinoma↗
PubMed2002

Centromere numerical abnormality in the papillary, papillotubular type of early gastric cancer, a further characterization of a subset of gastric cancer.

Papillary adenocarcinoma of the stomach is a relatively uncommon histological type, and it is often detected in the early stage. We recently characterized the papillary type of gastric cancer and found frequent microsatellite instability and associated mutations. In this study we analyzed the centromere numerical abnormality (CNA) of 18 chromosomes (chromosomes 1-4, 6-12, 15-18, 20, X, and Y) in the papillary and papillotubular types of gastric cancer by a modified fluorescence in situ hybridization technique with microwave treatment. All 3 cases (100%) of papillary adenocarcinoma had high microsatellite instability (MSI-H), and low CNA, and 41% (7 cases) of the 17 cases of papillotubular adenocarcinoma exhibited MSI-H and all 7 cases had low CNA. Further 8 cases (47%) had extensive CNA. In these 15 cases, all the MSI-H cases had lower CNA, and low microsatellite instability (MSI-L) and MSS cases had higher CNA. The remaining two cases showed low CNA and MSI-L and MSS. These profiles were different from those of tubular type gastric cancer, which always had extensive CNA and no MSI. Although the numbers of the cases in this series are limited, our data may suggest that a modest CNA may be another characteristic of gastric cancer with papillary structure.

Adenocarcinoma, Papillary↗
PubMed2002

[An autopsy case of cor pulmonale due to a pulmonary tumor embolism as the first clinical manifestation of occult gastric cancer].

A 47-year-old man was admitted to our hospital because of progressive dyspnea and cough. Physical examination and chest radiographs showed the signs of cor pulmonale. A lung scan using perfused radionuclide revealed multiple peripheral perfusion defects and catheterization of the right heart showed severe pulmonary hypertension. A diagnosis of severe pulmonary embolism was made. Despite intensive care with anti-coagulation therapy, the patient died on the third-hospital day. Autopsy disclosed gastric cancer in the pylorus with metastases to the regional lymph nodes. There were no macroscopic pulmonary artery emboli or parenchymal lesions, but more than 60% of the small arteries and arterioles were occluded by casts of tumor cells. Cor pulmonale due to a pulmonary tumor embolism is a rare complication of cancer. This case is particularly unusual because the embolus-caused cor pulmonale was the initial manifestation of clinically occult, but pathologically advanced, gastric cancer.

Adenocarcinoma↗
PubMedDate not supplied

Development of the adductome approach to detect DNA damage in humans.

The development of new strategies designed to detect DNA damage caused by oxidative stress and other means may advance our understanding of the roles of such types of damage in the etiology of cancers, in aging processes, and as biomarkers of exposure. A DNA adduct detection method that uses liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) to detect multiple DNA adducts in human lung tissue is reported herein. This adductome analysis strategy is designed to detect the neutral loss of 2 -deoxyribose from positively ionized 2 -deoxynucleoside adducts in multiple reaction ion monitoring mode (MRM) transmitting the [M + H](+) > [M + H - 116](+) transition over a total of 374 transitions in the mass range from m/z 228.8 to m/z 602.8. Data analysis is optimized and coupled with a comprehensive manual screening process designed to minimize the number of artifactual adducts appearing in the final analysis. In the final analysis, putative adducts were organized into an adductome map and unambiguous confirmation of selected oxidative adducts were made by stable isotope dilution and comparison to authentic standards. The future applications of this method are discussed.

Aged↗
PubMedDate not supplied

Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with smoking.

Thymidylate synthetase (TS) and methylenetetrahydrofolate reductase (MTHFR) are major enzymes in the metabolism of folates, involved in DNA 'breaks', instability and hypomethylation. To investigate the possible relations between the TS 3'-UTR and MTHFR C677T polymorphisms and environmental factors impacting on risk of esophageal and stomach cancers, we conducted a case-control study in a high incidence region of China for these cancers. We recruited 138 esophageal and 155 stomach cancer cases, and 223 controls. The TS 3' -UTR and MTHFR C677T genotypes were detected by RFLP assay, using PCR products. The frequency of the -6 bp homozygous TS 3' -UTR genotype was 37.7 % in controls, higher than in Caucasians, although the present distribution was not in Hardy-Weinberg equilibrium. Ever-smoking with the -6 bp/-6 bp TS genotype elevated the ORs (2.61, 1.24-5.49; 3.54, 1.60-7.82) for cases of esophageal and stomach cancers, respectively, when compared with never-smoking with the +6 bp/+6 bp and +6 bp/-6 bp genotypes. No combination between the TS and MTHFR genotypes gave increased ORs. The present results suggest that TS polymorphism may modify the risk of esophageal and stomach cancer with smoking, pointing to the necessity for further investigations with information on folate and methionine intake with a larger population.

Adult↗