Effect of combined tigason and selenium treatment on colon carcinogenesis

Summary The modifying effect of an aromatic retinoic acid analog, Tigason, alone or in a combined regimen with selenium on the incidence of colon tumors induced by 1,2-dimethylhydrazine was investigated in BD rats. Treatment with the carcinogen alone resulted in induction of colon adenocarcinomas in 29 rats (92%). In comparison to the 1,2-dimethylhydrazinetreated group, administration of Tigason or Tigason plus selenium reduced tumor incidence (71% and 68%, respectively). The effect of combined treatment with Tigason and selenium, however, was not additive. Although some researchers have been unable to demonstrate any protective effect of different synthetic retinoids against 1,2-dimethylhydrazine or N-methyl-N-nitrosourea-induced colon tumors, our findings suggest that the process of tumor initiation in colon mucosa can be significantly influenced by the aromatic retinoid Tigason or by simultaneous administration of Tigason and selenium.     

Androgen receptors in experimentally induced colon carcinogenesis

Summary Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with ³H-methyltrienolone as the ligand.Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P<0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P<0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations.Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.Supported by a grant of the Deutsche Forschungsgemeinschaft Grant No. Iz 1/1-1, by the Ministry for Science and Research NRW, and by the Julia Baker Fund     

Oxidative DNA damage accumulation in gastric carcinogenesis

Background—Gastric carcinogenesis is amultifactorial, multistep process, in which chronic inflammation playsa major role.
Aims—In order to ascertain whether freeradical mediated oxidative DNA damage is involved in such a process,concentrations of 8-hydroxydeoxyguanosine (8OHdG), amutagenic/carcinogenic adduct, and thiobarbituric acid reactivesubstances (TBARS), as an indirect measure of free radical mediateddamage, were determined in biopsy specimens from patients undergoing endoscopy.
Patients—Eighty eight patients were divided intohistological subgroups as follows: 27 with chronic non-atrophicgastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaffected controls.
Methods—Intestinal metaplasia,Helicobacter pylori infection, and disease activity weresemiquantitatively scored. 8OHdG concentrations were assessed by HPLCwith electrochemical detection, and TBARS concentrations werefluorimetrically assayed.
Results—8OHdG concentrations (mean number ofadducts/10⁵ dG residues) were significantly higher inchronic atrophic gastritis (p=0.0009). Significantly higherconcentrations were also detected in the presence of severe diseaseactivity (p=0.02), intestinal metaplasia (p=0.035), and Hpylori infection (p=0.001). TBARS concentrations were alsohigher in atrophic gastritis, though not significantly so. In amultiple logistic regression analysis, 8OHdG concentrations correlatedbest with the presence and severity of H pylori infection(r=0.53, p=0.002).
Conclusions—Chronic gastritis is characterised bythe accumulation of oxidative DNA damage with mutagenic andcarcinogenic potential. H pylori infection is the majordeterminant for DNA adduct formation.

Keywords:free radicals; oxidative DNA damage; gastriccarcinogenesis; precancerous changes; peroxidative damage

     

Estrogens,androgens, and EGF receptor expression in gastric carcinoma induced byN-methyl-N'-nitro-N-nitrosoguanidine

Complex and conflicting relationships between epidermal growth factor (EGF), estrogens (E), androgens (A), and related receptors (EGF-R, E-R, A-R) have been reported in different biological situations associated with cell proliferation. There is also evidence that EGF and sex hormone receptors may be involved in normal and neoplastic growth of the gastrointestinal mucosa. In this study, we investigated the behavior of EGF receptors and sex hormone and related receptors, duringN-methyl-N'-nitro-N-nitrosoguanidine (NG) -induced gastric carcinogenesis in Sprague-Dawley male rats. Four groups of 15 rats each (10 NG-treated and five controls) were sacrificed after 1, 20, 30, and 40 weeks of treatment. Gastric tissue from each rat was processed for receptor status (number and affinity) and proliferative activity. A significant and progressive decrease of A-R and EGF-R was observed starting from the 20th week, while no change of E-R occurred throughout the experiment. Cell proliferation in the gastric mucosa of NG-treated rats increased after 30 weeks of treatment. These data indicate that NG treatment is able to modify the receptor status of gastric mucosa in rats.This work was supported by Grants from the Ministry of Education (MPI).     

MYC and gastric adenocarcinoma carcinogenesis

MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacterpylori （Hpylon] and clinical applications.     

Role of prostaglandins in the early phases of experimental gastric carcinogenesis in the rat

Summary The study was initiated to evaluate the effect of N-methyl-N-nitro-N-nitrosoguanidine (NG) on gastric intraluminal prostaglandin release during a 30-day treatment period and to investigate the effect of a stable prostaglandin E¹ analogue (misoprostol) on NG-induced gastric mucosal damage during the same time period. Samples of gastric juice (1 h) were obtained from 40 male Sprague-Dawley rats with chronic gastric fistulas, in basal conditions and after 5, 15 and 30 days of continuous oral administration of NG (120 mg/l) or tap water. Aliquots of gastric juice were titrated with 0.1 M NaOH. Other aliquots were extracted with ethyl acetate and subjected to specific radioimmunoassay for prostaglandin E₂. The severity of gastric mucosal lesions was evaluated in 60 rats after 5 days and 30 days of continuous oral administration of NG (120 mg/l) or NG plus misoprostol (200 g/kg^-1/day^-1) or tap water, and a histological study was carried out. Administration of NG induced a significant decrease of gastric intraluminal prostaglandin E₂ concentration at 15 and 30 days. Oral administration of misoprostol, at non-antisecretory doses, protected the rats against NG-induced gastric mucosal damage. Prostaglandins may be involved in the early phases of experimental gastric carcinogenesis.This work was supported by grants from the Ministry of Education (MPI)     

Role of metallothionein in Helicobacter pylori-positive gastric mucosa with or without early gastric cancer and the effect on its expression after eradication therapy

Background and Aim:  Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori ( H. pylori ) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori -induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy.
Methods:  Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori -negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years.
Results:  MT expression was higher in H. pylori -negative patients than in positive patients ( P  < 0.01). Moreover, in the corpus it was higher in H. pylori -positive patients without ECG compared to those with ECG ( P  < 0.05). The MT labeling index had a negative correlation with the severity of gastritis ( P  < 0.01). A positive correlation was shown between the MT labeling index and apoptosis: proliferation ratio ( r  = 0.41, P  < 0.01). The MT labeling index in H. pylori -positive patients was gradually recovered after eradication ( P  < 0.05).
Conclusion:  The decrease of MT expression cannot prevent tissue damage in H. pylori -positive gastric mucosa and leads to more severe gastritis. This phenomenon may be attributed to gastric carcinogenesis. H. pylori eradication increases MT expression and may reduce the risk of ECG.     

低硒与低营养复合因素致大鼠心肌损伤的实验研究

目的 探讨长期低硒与低营养复合因素膳食对大鼠心肌损伤的作用。方法 将Wistar大鼠40只随机分成2组，实验组用低硒、低蛋白、低维生素E饲料喂养，对照组用常硒、常蛋白、常维生素E饲料喂养，至第26周处死大鼠。测定全血谷胱甘肽过氧化物酶（GSH-Px）活性，血清肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）水平和心脏质量与体质量比值。光镜、电镜下观察心肌结构改变。结果 实验组大鼠全血GSH墩活性水平显著低于对照组（t=58．79，P〈0．01）；实验组与对照组大鼠血清CK分别为（1．456±0．291）、（1．057±0．251）kU／L，CK—MB分别为（1．138±0．215）、（0．722±0．130）kU／L，LDH分别为（864．96±137．57）、（404．65±72．49）U／L，组间比较差异有统计学意义（t=4．71、7．46、13.42，P〈0．01）。大鼠心脏质量与体质量比值，实验组[（3．608±0．166）g／kg]显著高于对照组[（3．140±0．114）g／kg]，组间比较差异有统计学意义（t=10．62，P〈0．01）。光镜下实验组大鼠心肌出现散在小灶状坏死，检出率为66．67％，两组心肌病变检出率差异有统计学意义（χ^2=7．25，P〈0．01）。电镜下实验组大鼠部分心肌细胞线粒体嵴断裂，基质密度下降，细胞核固缩，早期凋亡形成，肌丝走行紊乱甚至溶解；对照组大鼠心肌细胞膜结构完好，线粒体嵴清晰，基质密度适中。结论 长期低硒、低营养复合因素膳食可引起大鼠心肌组织出现损伤。     

阿霉素致大鼠心肌线粒体DNA突变及硒的保护作用

采用ＰＣＲ方法对大鼠心肌ｍｔＤＮＡ特异片段进行扩增，用ＰＣＲ－ＳＳＣＰ和薄层扫描方法检测其片段的缺失突变和点突变。阿霉素组大鼠心肌ｍｔＤＮＡ特异片段出现缺失突变（６０．５％），并有点突变（２／６）。Ｓｅ保护组检出部分缺失突变（３０．０％），未检出点突变。阿霉素可以导致大鼠心肌ｍｔＤＮＡ突变热点区域发生缺失突变和点突变。ｍｔＤＮＡ损伤可能是阿霉素致心肌损伤的重要机制之一。Ｓｅ可以降低阿霉素对ｍｔＤＮＡ的损伤，对阿霉素性心肌损伤有明显地保护作用。     

MNNG加吐温20和维生素D3对大鼠前胃的影响

目的　研究胃癌发生、发展过程中，间质组织中血管反应与肿瘤的关系．方法　经水摄入Ｎ－ 甲基－ Ｎ１ － 基－ Ｎ － 亚硝基胍（ ＭＮＮＧ）和表面活性剂（ 吐温２０） 诱发大鼠肿瘤，饲料中添加维生素Ｄ３（ＶｉｔＤ３） 对肿瘤进行预防． 每８ ｗｋ 处死大鼠７ 只，３２ ｗｋ 实验结束．结果　ｗ ｋ １６ 实验组大鼠前胃鳞状上皮形态主要以血管密度增加、血管内皮细胞增生，３２ ｗｋ（ ＭＮＮＧ） ＋ 表面活性剂和ＶｉｔＤ３ 组肿瘤发生率高于ＭＮＮＧ 组（１０ ％ ） ，肿瘤发生率为６５ ％ ．结论　该组动物诱癌实验表明，肿瘤形成前主要以血管新生、血管ＥＣ 增生为主的病理性变化．     

Features of early gastric cancer and gastric adenoma by enhanced-magnification endoscopy

Background Changes to the mucosal surface of early gastric carcinomas and gastric adenomas as viewed by enhanced-magnification endoscopy with acetic acid have not been investigated thoroughly. Using this technology, we investigated the appearance of the gastric surface patterns of neoplastic and surrounding nonneoplastic mucosa. Methods Forty-seven consecutive patients with early gastric carcinomas or gastric adenomas underwent enhanced-magnification endoscopy following 1.5% acetic acid instillation. All biopsy specimens were taken from the area at which the enhanced-magnified endoscopic image was obtained. Results Surface patterns of gastric tumors and the surrounding mucosa were classified into five types: type I, small round pits of uniform size and shape; type II, slit-like pits; type III, gyrus and villous patterns; type IV, irregular arrangements and sizes of pattern types I, II and III; type V, destructive patterns of types I, II and III. The predominant pattern of the surrounding mucosa was type III, and most type III mucosa had characteristics of intestinal metaplasia. Although all elevated adenomas showed type II or type III surface patterns, both depressed adenomas showed type IV. Elevated carcinomas showed type III (42.9%) or type IV (57.1%) surface patterns, while depressed carcinomas showed type IV (70%) or type V (30%). Although differentiated tubular adenocarcinomas showed type III (10.3%), type IV (86.2%), or type V (3.5%) surface patterns, all of the signet-ring cell carcinomas and poorly differentiated tubular adenocarcinomas showed type V. Conclusions Enhanced-magnification endoscopy may be useful for identifying gastric tumors and determining the extent of horizontal spread, especially in tumors of the depressed type.     

硒与维生素E的协同影响对心肌损伤保护的研究

通过在低硒富锰饲料中联合补充硒及ＶＥ喂养大鼠，并以亚硝酸钠作为诱发因素建立大鼠心肌损伤模型，观察硒与ＶＥ的协同作用对心肌损伤的保护效果。结果表明，在低硒环境下，富锰能显著提高心肌坏死检出率及降低机体抗氧化能力。单纯补充硒及ＶＥ均可对抗富锰的影响，但硒与ＶＥ的联合补充效果更佳。     

Ear tumours induced by experimental carcinogenesis in the rat: excision prevents early death

1,2-dimethylhydrazine (DMH) is widely used to induce colorectal tumours in rodents. Some of the animals develop ear as well as colorectal tumours. Rats with large, ulcerated ear tumours are usually sacrificed before the completion of the experiment. In this experiment, fourty-six male Spraque-Dawley rats were injected with 1,2-dimethylhydrazine (21 mg/kg body weight) once a week for 27 weeks to study the histogenesis of colorectal carcinoma. Thirty-six developed ear tumours. Fourteen of the 36 tumours were larger than 2 cm in diameter. These developed between 20–26 weeks and were surgically excised 1–5 weeks later. Four rats died postoperatively. The surgical removal of large ear tumours permitted the completion of the large bowel experiment on schedule (i.e. 27 weeks) in 10 (28%) of the 36 rats with ear tumours.

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Résumé La 1,2 dimethylhydrazine (DMH) est largement utilisée pour induire des tumeurs colo-rectales chez les rongeurs. Quelques animaux développent des tumeurs de l'oreille au même titre que des tumeurs colo-rectales. Les rats porteurs de larges tumeurs exulcérées de l'oreille sont sacrifiés habituellement avant la fin de l'expérimentation. Dans cette étude, 46 rats mâles Spraque-Dawley ont reçu par injection de la 1,2 dimethylhydrazine (21 mg/kg de poids corporel) une fois par semaine durant 27 semaines afin d'étudier l'histo-génèse des cancers colo-rectaux. Trente-six ont développé des tumeurs de l'oreille, 14 de ces 36 tumeurs mesuraient plus de 2 cm de diamètre. Elles se développent entre la 20 et la 26e semaine et ont été excisées chirurgicalement 1 à 5 semaines plus tard. Quatre rats sont morts dans la période post-opératoire. L'excision chirurgicale des larges tumeurs de l'oreille a permis de compléter le programme d'expérimentation colique (sur 27 semaines) chez 10 (28%) des 36 rats porteurs des tumeurs de l'oreille.

     

The tumor-protective effect of selenium in an experimental model

Summary The possibility of a tumor-protective effect of selenium on the growth of benzpyrene-induced sarcoma was studied in an assay with Balb/c mice. The animals received 4 parts/10⁶ selenium in their drinking water for 12 months prior to subcutaneous injection of benzpyrene to induce sarcomas. In contrast to unpretreated controls, the selenium-exposed animals developed significantly less and smaller tumors in a given time. These results are compared to those of other authors. Several mechanisms fo selenium influence on benzpyrene metabolism are discussed.     

Dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress in rats

AIM: To investigate the dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress (WRS) in rats. METHODS: WRS model of Sprague-Dawley (SD) rats was established. Fifty-six male SD rats were randomly divided into control group, stress group and post-stress group. The stress group was divided into 1, 2 and 4 h stress subgroups. The post-stress group was divided into 24, 48 and 72 h subgroups. The pH value of gastric juice, ulcer index (UI) of gastric mucosa and H , K -ATPase activity of gastric parietal cells were measured. Ultrastructural change of parietal cells was observed under transmission electron microscope (TEM). RESULTS: The pH value of gastric juice decreased time-dependently in stress group and increased in post-stress group. The H , K -ATPase activity of gastric parietal cells and the UI of gastric mucosa increased time-dependently in stress group and decreased in post-stress group. Compared to control group, the pH value decreased remarkably (P = 0.0001), the UI and H , K -ATPase activity increased significantly (P = 0.0001, P = 0.0174) in 4 h stress subgroup. UI was positively related with stress time (r = 0.9876, P < 0.01) but negatively with pH value (r = -0.8724, P < 0.05). The parietal cells became active in stress group, especially in 4 h stress subgroup, in which plenty of intracellular canalicular and mitochondria were observed under TEM. In post-stress group, the parietal cells recovered to resting state. CONCOUSION: The acid secretion of parietal cells is consistent with their ultrastructural changes during the development and healing of stress ulcer induced by WRS and the degree of gastric mucosal lesions, suggesting gastric acid play an important role in the development of stress ulcer and is closely related with the recovery of gastric mucosal lesions induced by WRS.     

The effect of antioxidants on MNNG-induced stomach carcinogenesis in rats

Summary The effect of vitamins A, C and E, butylated hydroxytoluene (BHT) and glutathione (GSH) on gastric carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was investigated. Male and female BD-VI rats 2–3 months old received a single oral application of MNNG dissolved in corn oil. The male rats were divided into four groups: Group-I: MNNG 250 mg/kg by intubation; Group-II: MNNG+ vitamin C daily in the drinking water (400 mg/l); Group-III: MNNG+vitamin C (400 mg/1) +100 g of milk broth (for each of 10 rats) containing vitamin A (40 000 IU), vitamin E (0.5 g) and BHT (0.1 g) three times a week. The treatment with antioxidants started 7 days before the MNNG administration and continued until the end of experiment. Group-IV rats received MNNG+oxyferriscorbone, i.p. as a single dose of 1.0 mg/kg, daily during the week before and the week after MNNG exposure and than 3 times a week till the end of the experiment. Female rats were divided into two groups: Group-I: MNNG 333 mg/kg by intubation; Group-II: MNNG +GSH orally at a dose of 100 mg/rat 1 h before and 5, 24, 48, and 72 h after MNNG intubation.The incidence of gastric tumors after 15 months of treatment was as follows: male rats, 82.4% in Group-I, 40.0% in Group-II, 40.7% in Group-III, and 50.0% in Group-IV; female rats; 72.7% in Group-I, and 36.0% in Group-II.     

生长抑素的表达与胃黏膜上皮癌变的关系

[目的]探讨生长抑素（ss）在胃黏膜上皮癌发生、发展中的作用及地位，从而为胃癌的诊断、治疗及预后判断提供一个新的途径。[方法]应用免疫组化SABC（Strept Avidin Biotin Complex）法检测78例胃癌组织和20例正常胃黏膜、53例胃黏膜上皮各级癌前病变标本中SS的表达。[结果]SS在正常胃黏膜中阳性表达率为85．0％，癌前病变组织中阳性表达率为43．4％，胃癌组织中阳性表达率为24．3％；高／中分化组和低分化组中的阳性表达率分别为34．2％、13．5％，随分化程度减低呈下降趋势；浸润黏膜层或黏膜下层和浸润肌层或浆膜层两组的阳性表达率分别为64．3％、15．6％，随浸润程度的加深其阳性表达率呈下降趋势；无淋巴结转移组和有淋巴结转移组的阳性表达率分别为38．7％、14．9％；TNMⅠ～Ⅱ期和Ⅲ～Ⅳ期的阳性表达率分别为45．5％、8．9％。以上两组间比较差异均有统计学意义（P〈0．05）。[结论]SS的低表达与胃癌的组织学分级、浸润深度、淋巴结转移及TNM分期密切相关。SS的失表达可能是胃黏膜上皮癌变过程中的重要机制之一。     

黄绿青霉素对低硒低蛋白大鼠心肌组织形态结构的影响

目的 观察黄绿青霉素(CIT)对低硒低蛋白大鼠心肌组织形态结构的影响.方法 将48只Wistar 雄性大鼠按2×2析因设计分为4组:低硒低蛋白加毒素组、低硒低蛋白无毒素组、常硒常蛋白加毒素组和常硒常蛋白无毒素组,每组12只.首先用常硒常蛋白或低硒低蛋白饲料喂养大鼠2个月,然后加毒素各组饲料中另加入8 mg·kg-1·d-1 CIT喂养2个月,再以加入10 mg·kg-1·d-1 CIT的饲料喂养2周,而无毒素各组继续喂饲原饲料.在实验终期将大鼠麻醉后进行股动脉放血处死,称量心脏质量,计算心脏质量指数,光镜下观察心肌组织病理学变化.结果 低硒低蛋白加毒素组、低硒低蛋白无毒素组、常硒常蛋白加毒素组和常硒常蛋白无毒素组心脏质量指数分别为( 3.65±0.45)×10-3、(3.05±0.19)×10-3、(3.83±1.06)×10-3、(3.31±0.52)× 10-3.析因分析结果显示,CIT因素对大鼠心脏质量指数有明显影响作用(F=8.524,P＜0.05),而“硒+蛋白”因素未见明显影响作用(F=1.347,P＞0.05),且二者间不存在交互作用(F=0.048,P＞0.05).光镜下低硒低蛋白加毒素组大鼠心肌细胞血管周围出现纤维组织增生,细胞中出现明显的收缩带;低硒低蛋白无毒素组大鼠出现少量心肌细胞固缩;常硒常蛋白加毒素组大鼠心肌细胞出现坏死灶,并伴有炎性细胞浸润,出现较多固缩细胞;常硒常蛋白无毒素组大鼠心肌细胞群排列整齐,层次清晰,结构完好.结论 CIT可引起大鼠心肌组织变性坏死,低硒低蛋白也可造成大鼠心肌组织轻微损伤,而两因素叠加在一起时心肌损伤较严重.     

Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study

BACKGROUND AND AIMS: Infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. However, most patients with H. pylori infection will not develop gastric cancer. The aims of the present study were to examine which histological features, including H. pylori infection, would increase the risk of gastric cancer using a case-control study. METHODS: Three gastric biopsy specimens were taken from 72 patients with early gastric cancer and 72 age- and sex-matched control subjects. The grade of gastritis was examined according to the updated Sydney System. The presence of H. pylori infection was determined by serology and histology. Odds ratio (OR) of developing gastric cancer was calculated for H. pylori positivity and histological features using conditional logistic regression. For patients with H. pylori infection, histological features in cancer patients and control subjects were compared. RESULTS: The OR of the presence of mononuclear cell infiltration in the corpus and intestinal metaplasia in the angulus were significantly elevated. The grade of mononuclear cell infiltration in the corpus and antrum was significantly higher in both types of cancer patients than controls. Glandular atrophy and intestinal metaplasia were increased in patients with intestinal-type cancer in the angulus and antrum. Bacterial density in the corpus and polymorphonuclear cell infiltration in the antrum were increased in patients with diffuse-type cancer. CONCLUSIONS: Severe chronic gastritis induced by H. pylori infection seems to be associated with diffuse-type gastric cancer. Glandular atrophy and intestinal metaplasia, which occur in gastric mucosa with chronic inflammation, are significantly associated with intestinal-type cancer.