Radioimmunoassay of serum pepsinogen I in chronic gastritis and stomach cancer

Blood serum in stomach cancer and chronic gastritis has been compared. A sharp decrease in pepsinogen 1 level both in cancer and gastritis patients was found as compared with healthy subjects. Pepsinogen 1 level in poorly-differentiated tumor (37.4 ng/ml) was lower than in well-differentiated one (58.2 ng/ml).     

人血清胃蛋白酶原含量的测定与胃癌的关系

胃癌是我国的主要恶性肿瘤之一。国外已有用放射免疫的方法检测人末稍血清中胃蛋白酶原Ⅰ型和Ⅱ型（ＰＧⅠ和ＰＧⅡ），用ＰＧⅠ及ＰＧⅡ的测值和ＰＧⅠ／ｐＧⅡ的比值预测胃癌和癌前病变。本研究是采用生物素、亲合素酶标的方法测定人末稍血中的ＰＧⅠ和ＰＧⅡ，并探讨用该方法预测胃癌和癌前病变的可能性。结果表明，ｐＧⅠ在胃癌和萎缩性胃炎组（包括胃粘膜上皮化生或不典型增生）中的平均值最低，慢性胃炎、胃十二指肠溃疡和胃息肉及其它病变者的均值偏高。各组中男女性别间均值差异没有显著性。ＰＧⅡ在胃癌组中的平均值最高，余者从高至低依次为胃十二指肠溃疡、萎缩性胃炎、慢性胃炎和胃息肉及其它病变者。各组中男女性别间均值差异没有显著性。ＰＧⅠ／ＰＧⅡ比值也是胃癌组和萎缩性胃炎组的最低。以病理学诊断的胃癌和萎缩性胃炎（包括胃粘膜上皮化生或不典型增生）为标准，以ｐＧⅠ／ＰＧⅡ≤３．Ｏ检出胃癌和萎缩性胃炎的灵敏度为６２．９６％，特异度为６２．００％，阳性预告值为４７．２２％，阴性预告值为７５．６１％，病理和胃蛋白酶原两种方法检查的一致率为６２．３１％，与胃镜检出的效果相接近。这种方法经济，便于基层应用，对胃癌和癌前病变的检测有意义。     

Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels

A total of 5,209 asymptomatic, middle-aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26-9.64). Risk of gastric cancer increased as the antibody level increased; the H. pylori-positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person-years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level or=30 ng/mL (HR = 3.81, 95% CI = 1.10-13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori-negative or indeterminate subjects with low PG level (PG I 500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person-years). In contrast, H. pylori-negative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylori-related gastritis from the general population.     

FACTORS INFLUENCING SERUM PEPSINOGEN LEVELS IN A CHINESE POPULATION AT HIGH RISK OF STOMACH CANCER

The relationships between serum pepsinogen (PG) levels and age, sex, ABO blood type, cigarette smoking and diet were studied among over 3, 000 residents selected at random in an area with high risk of stomach cancer in Shandong Province, China. Males had significantly higher median PG Ⅰ and Ⅱ levels than feamles. PG Ⅰ tended to decrease and PG Ⅱ to rise with age. Subjects with blood type A had a higher PG Ⅱ level than subjects with other blood types. Both PG Ⅰ and Ⅱ levels rose with dally consumption of cigarettes. Alcohol consumption was not related to PG levels. The PG Ⅰ/Ⅱ ratio declined with increasing consumption of sour pancakes, a fermented staple food found to contain N-nitroso compounds and to be a risk factor for stomach cancer in this population.     

Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis

This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach.     

Clinical significance of pepsinogen A isozymogens, serum pepsinogen A and C levels, and serum gastrin levels

Gastric mucosal pepsinogen A phenotype, serum pepsinogen A level, serum pepsinogen C level, serum pepsinogen A/pepsinogen C ratio, and serum gastrin level were evaluated as potential markers for gastric cancer or its precursors in 19 healthy volunteers and 341 patients from the gastroscopy program. Gastric cancer, atrophic gastritis, and intestinal metaplasia of the stomach were associated with pepsinogen A phenotypes, characterized by an intense fraction 5, and with a low serum pepsinogen A level (less than 25 micrograms/l), a low serum pepsinogen A/pepsinogen C ratio (less than 1.5), and a high serum gastrin level (greater than 79 ng/l). The specificity of pepsinogen A phenotypes with an intense fraction 5 for gastric cancer or its precursors was 95.1% with a sensitivity of 20.4%. The sensitivity and specificity of the noninvasive tests were evaluated with the receiver operating characteristic. For clinical purposes, a serum pepsinogen A/pepsinogen C ratio less than 1.8 is the most suitable test, with a sensitivity of 74% and a specificity of 76% for gastric cancer or its precursors, with a reference population of patients with benign gastric disorders. However, the sensitivity and specificity of the single or combined tests are too low for population screening purposes.     

O6-Methylguanine in blood leucocyte DNA: an association with the geographic prevalence of gastric cancer and with low levels of serum pepsinogen A, a marker of severe chronic atrophic gastritis

Using a competitive repair assay, 407 samples of peripheralblood leucocyte DNA from randomly selected subjects in 17 populationswere tested for the presence of the adduct O⁶-methylguanine.With a limit of assay sensitivity of 0.05 fmol/µg DNA,the adduct was detected in 21 samples (5%). Sixteen positivesamples came from 102 tested (16%) from two populations, inJapan and Portugal, with extremely high gastric cancer rates.This was significantly higher (P < 0.001) than the threepositive samples out of 216 tested (1%) from populations withlow or intermediate rates of gastric cancer. There was alsoan association between presence of the adduct and having a low(<25 ng/ml) level of serum pepsinogen A, a marker of severechronic atrophic gastritis. These results are consistent withthe general involvement of methylating agents in the pathogenesisof gastric cancer and with the model proposing formation ofsuch compounds by endogenous nitrosation in the hypochlorhydricstomach.     

Ethnic differences in serum pepsinogen levels among Japanese and non-Japanese Brazilian gastric cancer patients and controls

A low level of serum pepsinogen I (Pg I) is a risk factor for gastric cancer (GC); low levels of Pg I and the pepsinogen ratio (Pg I:Pg II) are correlated with chronic atrophic gastritis. We report serum Pg levels and compare the degree of association with GC among Japanese and non-Japanese Brazilians. Sera were cross-sectionally ascertained from 93 Japanese Brazilian patients category matched by age and sex with 110 controls, and 228 non-Japanese Brazilian patients individually matched by age and sex with one control. Among non-Japanese Brazilians, GC was associated with a Pg I level <30 ng/ml (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.8) and a Pg I:Pg II ratio < 3.0 (OR, 3.4; 95% CI, 2.2-5.3). However, among Japanese Brazilians, the association was present with a level of Pg I < 30 ng/ml (OR, 3.5; 95% CI, 1.9-6.3), and was weak with a Pg I:Pg II ratio < 3.0 (OR, 1.3; 95% CI, 0.73-2.4). Serum Pg I may be preferred to the Pg I:Pg II ratio to study the association between Pg and GC among Japanese Brazilians.     

Prognostic value of serum pepsinogen levels in patients with gastric-carcinoma

Serum pepsinogen levels were examined in 107 patients with gastric carcinoma, by immunoradiometric assay for evaluating its clinical usefulness in gastric cancer. The mean serum pepsinogen-I (PG-I) level and the pepsinogen-I/pepsinogen-II (PG-I/II) ratio decreased as the histologic stage increased. Also, serum pepsinogen-II (PG-II) correspondingly increased with the increase of histologic stage. Moreover, in patients with low PG-I/II (<2.0), prognosis was significantly poorer than in those with high PG-I/II (greater-than-or-equal-to 2.0). The rate of recurrence after a curative resection was significantly higher in patients with low PG-I/II. These results suggest that measurement of serum pepsinogens and calculation of PG-I/II are useful for prediction of the tumor stage, and PG-I/II may be a prognostic indicator for gastric carcinoma.     

A case of a gastric cancer patient with high serum pepsinogen levels at relapse

A rare case of a 68-year-old female cancer patient with an extremely high serum level of pepsinogens (PG) at relapse is presented. She had stage 3 Borrmann 3 type gastric cancer which was a poorly differentiated adenocarcinoma. Her postoperative serum PG levels had been within normal limits (23.0 ng/ml for PG-I and 3.2 ng/ml for PG-II), but at the time of the peritoneal relapse they were 5,630 ng/ml and 3,380 ng/ml, respectively. After was chemotherapy initiated, her serum PG levels decreased in parallel with an improvement of her clinical status. Immunohistochemical examination with monoclonal antibodies revealed PG-I and PG-II production in the primary and the metastatic lesions.     

Evaluation of pepsinogen A expression in stomach cancer]

The report deals with a molecular-genetic study of human pepsinogen A (PGA) genetic locus. EcoRI, HindIII and BamH 1 restriction endonuclease technique were employed. The investigation involving 58 patients with stomach cancer (SC) and 18 healthy donors failed to identify any significant PGA genetic restructuring in the blood of healthy donors. However, DNA sampled from tumor tissue showed lower expression and deletion of PGA fragments as compared with those of unaltered gastric mucosa in the same patients. Such changes were identified in 27 SC patients.     

Determinants of plasma pepsinogen levels in a population at high risk for stomach cancer in venezuela

Determinants of plasma pepsinogens (PG) levels were studied in 1365 participants in a chemoprevention trial for gastric pre-cancerous lesions being conducted in Venezuela. Gastric biopsies, plasma samples and information on smoking and dietary habits were obtained at baseline examination. Both PG-I and PG-II levels increased progressively with the level of Helicobacter pylori infection in gastric biopsies, resulting in no clear trend in the I/II ratio. Instead, there was a progressive decrease in the I/II ratio with increasing degrees of infiltration of polynuclear cells and monocytes, atrophy, intestinal metaplasia and the stage of pre-cancerous lesions. The mean I/II ratios for atrophic gastritis or more advanced lesions were less than 4.0. When subjects with the I/II ratio 4 or higher were used as controls, severe reduction in the I/II ratio (<2.0) was inversely associated with tobacco consumption. This may be due to a pharmacological effect of nicotine. The severe reduction of I/II ratio was also inversely associated with fresh fruit consumption. In addition, a decreased I/II ratio was positively associated with rice/pasta and arepas (tortilla made from corn) consumption and inversely associated with plantain consumption. Possible effects of vitamins and starchy food on the development of atrophic gastritis need to be studied further. © 1995 Wiley-Liss, Inc.     

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori‐associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori‐associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori‐negative/CAG‐negative), cancer incidence rate was low, at 16/100,000 person‐years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG‐free subjects (H. pylori‐positive/CAG‐negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7–54.7] to subjects with CAG (H. pylori‐positive/CAG‐positive) (HR = 17.7, 95% CI = 5.4–108.6) and finally to subjects with metaplastic gastritis (H. pylori‐negative/CAG‐positive) (HR = 69.7, 95% CI = 13.6–502.9). In H. pylori‐infected CAG‐free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation‐based high PG II level or potent immune response‐based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse‐type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person‐years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori‐infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis‐atrophy‐metaplasia‐cancer sequence and partly from active inflammation‐based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori‐infected subjects.     

Association of serum ferritin levels with the risk of stomach cancer.

A group of 5908 men provided serum samples during their study examination from 1967 to 1970. After a surveillance period of over 20 years, 121 incident cases of tissue-confirmed gastric cancer were identified. Their stored sera and those of 121 matched controls from the study population were tested for serum ferritin and transferrin levels. Because of the suggested effects of previous thawing on the serum results, detailed data analyses were limited to the 46 cases and matched controls whose sera were never thawed before this study. The mean serum levels (In ng/ml) were 5.26 for the 46 gastric cancer cases and 5.68 for their controls (P < 0.01). For serum transferrin, the mean levels (mg/dl) were 249.8 for cases and 254.1 for controls (P = 0.53). The inverse association with serum ferritin, which reflect total iron body stores, was stronger for the 21 cases diagnosed within 15 years of examination (P = 0.02) than for the 25 cases diagnosed after 15 years (P = 0.15). The limitations of the study and the implications of its findings are discussed.     

SOD在Hp感染阳性的胃癌、胃粘膜不典型增生及慢性胃炎中表达的研究

目的　观察 SOD在 Hp感染与胃癌、胃粘膜不典型增生及慢性胃炎之间所起的作用。方法　采用免疫组织化学方法观察 SOD在 Hp感染阳性胃癌、胃粘膜不典型增生及慢性胃炎组织中的表达。结果　 Hp感染的阳性胃癌、胃粘膜不典型增生及慢性胃炎组织中的 SOD表达无变化。而在胃癌、胃粘膜不典型增生及慢性胃炎三者之间 SOD的表达有差异。结论　胃癌、胃粘膜不典型增生及慢性胃炎组织中 SOD的表达不受 Hp感染的影响。监测胃粘膜中 SOD的变化 ,可为早期诊断胃癌提供帮助     

Clinical significance of serum tenascin-C levels in breast cancer

Tenascin-C (TNC) is a key molecule in tissue remodeling, and high levels are observed in many diseases, including heart failure, thrombosis, atherosclerosis, and cancer. High TNC expression by immunohistochemical analysis has been shown in invasive and metastasizing tissues from a variety of cancers, including colon, lung, brain, and breast. This study was conducted to investigate the serum level of TNC in breast cancer patients and its relationship with tumor progression and known prognostic parameters. Ninety-six breast cancer patients were enrolled into the study. Serum samples were obtained on first admission before adjuvant and metastatic treatments were given and at follow-up. Serum TNC levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) method. Median age of diagnosis was 48 years old (range, 29–80). Thirty-seven (39 %) patients had metastatic breast cancer. The mean TNC levels were found to be significantly higher in patients with breast cancer (344.1?±?42.4 pg/mL) compared to those in healthy controls (137.2?±?26.8 pg/mL) (p?=?0.005). Serum TNC level in grade 3 tumors was found to be significantly higher than in grades 1–2 tumors (p?=?0.04). No correlation was detected between serum TNC levels and other prognostic parameters analyzed, including presence of metastasis, lymph node involvement, and tumor size. Serum TNC level had no significantly adverse effect on survival in univariate and multivariate analyses (p?=?0.65 and p?=?0.85, respectively). In conclusion, although serum TNC levels are elevated, it has no predictive or prognostic roles on survival in breast cancer patients.     

Clinical significance of serum adipokines levels in lung cancer

Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients—mean age 62.9 ± 9.2 years—with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232–0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information.