Gene expression in gastric carcinoma tissues

In gastric cancer, the expression of c-myc protein and mRNA were investigated to determine the mechanism of inappropriate expression of c-myc gene. Correlation between clinical findings and the gene was also studied. Forty-six lesions of 43 patients were investigated by immunohistochemical staining technique. The expression of c-myc mRNA in the small fresh tissues of the same patients was detected by Northern blot hybridization. Results were as follows: 1) c-myc protein was detected in 20 lesions. The expression of c-myc protein was not differed in histological types ans stages of the lesions. 2) The level of c-myc mRNA expression was increased. In 34 cancer lesions than normal mucosa of the same patients. The overexpression of c-myc mRNA in the cancer lesion was more frequently found in early-stage cancer than in advanced-stage cancer. However, no difference was seen in histological types. 3) c-myc protein expression was correlated with mRNA overexpression. 4) In early-stage cancer, the rate of the lesions found to express excess c-myc protein was not so frequent as that of mRNA overexpression. In conclusion, c-myc mRNA overexpression was thought to cause inappropriate protein expression in gastric cancer and c-myc gene overexpression might happen already in the early-stage of gastric cancer suggesting it had a role in carcinogenesis.     

Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma

Previous studies have shown that tumour-suppressor genes play an important role in the progression of solid tumours. Recently, the p21WAF1/CIP1 tumour-suppressor protein has been reported to work as a critical downstream effector of p53 and a potent inhibitor of cyclin-dependent kinases. Thus, the p21WAF1/CIP1 gene is thought to play a central role in tumour suppression. In this study we investigated p21 protein expression in gastric carcinomas. A total of 172 primary gastric carcinoma specimens were immunohistochemically stained for p21 protein expression. Correlations between p21 expression and clinicopathological features were examined. Loss of p21 expression was observed in 104 of 172 tumour tissues (60.4%), and the frequency of p21 loss increased as the stage progressed. Expression of p21 in the primary tumour was frequently lost in patients with either lymph node, liver or peritoneal metastases as compared with patients without metastases. In patients with p21-negative tumours, the risk of recurrence following curative surgery was significantly higher, and the prognosis was significantly poorer than in patients with p21-positive tumours. Loss of p21 expression in primary gastric carcinoma correlates with disease progression. The status of p21 gene expression may have prognostic value in this disease.     

Loss of alpha-v integrin expression and recurrence in node-negative lung carcinoma

BACKGROUND: Despite "curative" resection, metastases develop in many patients with node-negative (N0) non-small cell lung carcinoma. Alternative biologic markers for this tumor would be useful. Integrins are cell adhesion molecules that are thought to be important in tumor progression, and expression of these molecules previously has been shown to be altered in non-small cell lung carcinoma. We evaluated alterations in integrin expression and clinical outcome. METHODS: Immunohistochemical staining of tumor specimens was performed, and clinical data were reviewed retrospectively. RESULTS: Data were complete for 42 patients. Half of all patients (21/42) and 9 of 26 patients with negative nodes experienced tumor recurrence during follow-up. Neither histologic type nor tumor differentiation status correlated with recurrence. However, loss of the alpha v integrin subunit was associated significantly with recurrence in the N0 group. Seventy-five percent of patients with negative nodes who exhibited recurrence lost alpha v expression, compared with only 10% of patients with negative nodes who did not exhibit recurrence (p = 0.012). Alterations of other integrin subunits did not correlate significantly with prognostic follow-up variables. CONCLUSIONS: Loss of alpha v expression may serve as a marker for patients with node-negative non-small cell lung carcinoma who are at high risk for recurrence, potentially directing additional therapies.     

Loss of heterozygosity and loss of expression of the DCC gene in gastric cancer

Even with a good surveillance program, nosocomial infections may be not recognized because of several reasons: absence of symptoms or prolonged incubation period (eg, viral bloodborne infections, tuberculosis); problems with the microbiological diagnosis, because adequate specimens may be difficult to obtain or special methods should be used (eg, fungal infections, virus, new agents); shorter hospital stays (eg, surgical-site infections); difficulty in distinguishing between nosocomial and community-acquired infections (eg, influenza); and failure to detect clinically relevant colonization (eg, multiresistant microorganisms). Because of the important potential consequences of occult nosocomial infections, specific surveillance programs should be designed to address these problems.     

Enhanced expression of initiator TRNA(Met) in human gastric and colorectal carcinoma

Transfer RNA isoaccepting species are differentially expressed at different times during development, differentiation, growth, aging, and carcinogenesis processes. It has been suggested that alterations in tRNA patterns might be mechanistically important in modulating gene expression during the various physiological/pathological cellular stages. As part of a study to investigate the possible mechanisms by which alterations of translational machinery can start and/or sustain carcinogenic cell proliferation, in this communication we report analysis of tRNA distribution in two gastro-intestinal human tumors. The qualitative and quantitative data obtained for cellular tRNA distribution put into evidence a shift in the tRNA population with increased level of initiator tRNA(Met) in the malignant tissues. This observation confirms previous data obtained on experimental carcinogenesis models and suggests the possibility of specific involvement of tRNA changes in protein synthesis initiation during tumorigenesis.     

Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma

BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS: The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS: In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized.     

p21 expression and mutation in gastric carcinoma: analysis by immunohistochemistry and PCR-SSCP

The biopsy of the temporal artery is a necessary procedure in order to gain a certain diagnosis of temporal arteritis. Is an easy method and customarily sure, but needing a knowledge of the clinical picture of this arteritis and of it surgical anatomy. The AA. explain the technique they follow.     

Diagnostic confusion between gastric carcinoma and gastric tuberculosis

Developing countries like developed ones need highly skilled medical personnel, referred to as 'specialists'. In the case of developing countries, the training of these specialists abroad is expensive to the sponsoring governments, imposes a lot of hardship on the doctors and, above all, the course-content of such training takes little or no cognizance of the environment in which these doctors would later practise. The developing countries also cannot afford the loss of years in valuable services which the training abroad entails. Attempts are now being made to train specialists wholly or partly at home, in some developing countries. The approach is still not much divorced from what obtains in Britain and North America, that is, one of being trained on the job, with the onus for self-education being placed on the prospective students. Such students in most developing countries of tropical Africa have little or no facilities for further education outside their places of work. It is proposed that purpose-designed postgraduate medical schools may provide a temporary solution to specialist training in developing countries of tropical Africa. Such schools would in addition provide highly skilled medical service as well as obviate the need and the expense for the setting up of government sponsored medical research and training institutes.     

Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii

Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with six antigens in 107 patients, 94 of whom were age, sex, and race-matched with healthy individuals or patients with diseases unrelated to immunological abnormalities. 20% of RA patients were anergic. Impaired cell-mediated immunity in the RA patients was manifested by a decrease in the magnitude of skin reactivity as well as a decrease in the incidence of positive reactions to multiple antigens. Depression in cell-mediated immunity was related to age but not to sex, duration of disease, or disease activity. A slight correlation was found between absolute peripheral lymphocyte counts and the number of positive skin tests, and was confirmed by finding an association between lymphocyte counts and the size of skin reactions. A correlation was also found between lymphocyte counts and disease activity. Four explanations of the observed depression in cell-mediated immunity in RA were considered: (1) a preoccupation of the immune mechanism of the host with cell-mediated immunity reactions related to the pathogenesis of the disease; (2) a depression of cell-mediated immune reactivity by a virus infection; (3) depression of cell-mediated immunity by therapy; and (4) immune complex suppression of cell-mediated immunity. No effect of gold therapy was found. The near universal use of salicylates or other anti-inflammatory drugs did not permit investigation of the effect of these drugs on cell-mediated immunity.     

Dimeric sialyl-Le(x) expression in gastric carcinoma correlates with venous invasion and poor outcome

BACKGROUND & AIMS: High expression of sialyl-Le(x) in tumors of different organs correlates with hematogenous metastasis and adverse outcome. Dimeric sialyl-Le(x) expression in gastric carcinoma was evaluated, and its prognostic significance within this setting was determined. METHODS: Dimeric sialyl-Le(x) immunohistochemical expression in 97 gastric carcinomas was analyzed using the FH6 monoclonal antibody. Scoring was based on the percentage of immunoreactive cells: negative, low expression (< or = 25%), and high expression (> 25%). RESULTS: Immunoreactivity was observed in 45 cases (46.4%), encompassing 27 and 18 cases with low and high expression, respectively. Significant relationships were found between dimeric sialyl-Le(x) expression and venous invasion (P = 0.0025) and histological classification (P = 0.05). No correlation was observed with other clinicopathologic features. Patients with tumors showing high expression of dimeric sialyl-Le(x) had a significantly shorter survival time than those with low or no expression (P = 0.03). By multivariate analysis, pathological TNM (pTNM) staging and venous invasion emerged as independent prognostic factors in the whole series. Within the group of patients with tumors in pTNM stages II and III, dimeric sialyl-Le(x) was the only independent prognostic factor. CONCLUSIONS: High expression of dimeric sialyl-Le(x) correlates with venous invasion and poor outcome in gastric carcinoma.     

New molecular prognostic markers in gastric carcinoma

Many molecular events have been reported as prognostic factors in gastric cancer. Amplifications of K-sam and c-met genes are often associated with poorly differentiated adenocarcinoma, while ERBB2 genes are amplified in well--differentiated adenocarcinomas of the stomach. Alterations of tumor suppressor regulators confer progression of gastric cancer. On the other hand, multi autocrine loops of growth factors/receptors in gastric cancer cells play a key role in the progression and metastasis of cancer cells. The overexpression of K-sam gene, occurs in 31.9% of gastric cancers, and the prognosis of patients with overexpression of K-sam gene is poorer than those without it. Multivariate analysis reveals that the overexpression of K-sam gene is an important factor for prognosis, lymphnode metastasis and the depth of tumor invasion of gastric carcinomas.     

Epstein-Barr virus and gastric carcinoma

Immunohistopathological staining for p53, PCNA and Ki67 was performed in 120 specimens from previously untreated laryngeal carcinomas using the avidin-biotin method with peroxidase as a marker enzyme and diaminobenzidine as a chromogen. A 5-grade staining score system was used. Statistically significant correlations (Chi-square) were seen between T- and N-stage and histopathological grading. p53 and Ki67 scoring correlated with T- and N-stage whereas PCNA with T-stage. All staining correlated with histopathological grading. The score of staining for p53, PCNA and Ki67 correlated with each other. The patients with recurrences within 3 years had mainly carcinomas with higher staining scores. Using Chi-square analysis the p53, PCNA and Ki67 staining scores were also independent prognostic indicators.     

The role of microsatellite instability in gastric carcinoma

Hernia repair may involve the use of an implant to augment or replace autologous tissue, but the best material for use in this application has not been established. We developed a dog model to evaluate the mechanical strength of fascial defects repaired using carbon fibers, compared with the strength of similar defects repaired using polypropylene mesh (Marlex). Unrepaired defects were included as an additional control. Bilateral defects (1 cm square) were made in the fascia of the back, and the ultimate mechanical strength and stiffness at the repair sites were measured 3-12 months after operation. Defects repaired with carbon fibers were significantly stronger 12 months after operation compared with defects repaired with polypropylene mesh and compared with unrepaired defects. It is concluded that carbon fibers are biocompatible and significantly increase mechanical strength at the repair site. A randomized clinical trial involving patients undergoing hernia repair seems justified to determine whether carbon fibers are superior to standard therapy.     

Loss of ovarian function promotes angiogenesis in human ovarian carcinoma

We show here that elevated levels of gonadotropins (luteinizing hormone and follicle stimulating hormone), as found in menopause or after ovariectomy, promote growth of human ovarian carcinoma by induction of tumor angiogenesis. Human epithelial ovarian cancer tumors progressed faster in ovariectomized mice. This induced growth could be attributed to the elevated levels of gonadotropins associated with loss of ovarian function because direct administration of gonadotropins also was effective in promoting tumor progression in vivo. On the other hand, gonadotropins had no direct effect on the proliferation of human ovarian cancer cells in vitro. Using MRI, we demonstrated that ovariectomy significantly (P < 0.02) induces neovascularization of human ovarian carcinoma spheroids implanted in nude mice. Moreover, conditioned medium of gonadotropin-treated human ovarian carcinoma cells showed increased mitogenic activity to bovine endothelial cells, and this activity could be blocked by neutralizing antibodies against luteinizing hormone and against vascular endothelial growth factor. Accordingly, gonadotropin stimulation resulted in a dose-dependent-induced expression of vascular endothelial growth factor in monolayer culture as well as in the outer proliferating cells of human ovarian cancer spheroids. These results demonstrate the significance of the elevated levels of gonadotropins, as found in menopause and in all ovarian cancer patients, on the progression of ovarian cancer and could explain the protective effect of estrogen replacement therapy. Based on these results, we suggest that hormonal therapy aimed at lowering the circulating levels of gonadotropins may possibly prolong remission in ovarian cancer by extending tumor dormancy.     

Epstein-Barr virus associated gastric carcinoma: the genetic alteration and the expression of CD44 variant

BACKGROUND: Chronic symptomatic gastroparesis occurs in 3-5% of patients following vagotomy and antrectomy. Erythromycin, a macrolide antibiotic, improves gastric emptying in patients with idiopathic and diabetic gastroparesis. Erythromycin's effect on gastric emptying in patients with post-vagotomy-antrectomy gastroparesis is unknown. The aim of this study was to determine if a single dose of intravenous erythromycin (1 mg/kg or 6 mg/kg) accelerates solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomy gastroparesis. METHODS: Six patients were entered into the study, three males and three females, with a mean age of 50 years. Four patients were randomized to receive erythromycin 6 mg/kg and two patients 1 mg/kg. The mean time since initial surgery was 9.2 years (range 1-16 years) with five patients having undergone a Roux-en-Y revision. RESULTS: Intravenous erythromycin significantly lowered percentage gastric retention at 120 min, from a baseline of 90.5 +/- 6% (S.E.M.) to 40.1 +/- 4.8% after erythromycin (P = 0.0002). Erythromycin improved gastric emptying in each patient by at least 40%. Intravenous erythromycin significantly accelerated the rate of gastric emptying in the first 30 min after meal ingestion from a baseline rate of 0.072 +/- 0.06%/min to 0.96 +/- 0.31%/min after erythromycin (P = 0.028). For each of the subsequent 30 minute time periods, erythromycin had no significant effect on the rate of gastric emptying. CONCLUSION: Intravenous erythromycin significantly improves the initial phase of solid meal gastric emptying in patients with chronic symptomatic post-antrectomy-vagotomy gastroparesis.     

Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils

Helicobacter pylori is classified by IARC/WHO as a definite human gastric carcinogen, despite "inadequate experimental evidence." To obtain direct evidence concerning this relationship, we investigated the histopathological findings of gastric mucosa using a model of H. pylori infection in Mongolian gerbils. The animals were challenged p.o. with H. pylori ATCC-43504 and sacrificed at 6, 12, and 18 months after inoculation for histological examination. All inoculated animals were infected with H. pylori. Severe infiltration of the lamina propria by polymorphonuclear and mononuclear cells appeared in the lesser curvature of the antrum, with an increase in epithelial cell proliferation, and the infiltration extended to the body. Atrophic gastritis and focal intestinal metaplasia also appeared in the lesser curvature of the antral mucosa at 6 months after inoculation. Intestinal metaplasia became severe, with dysplasia, after that. At 18 months after H. pylori inoculation, two of five infected animals showed three well-differentiated gastric cancers. The uninfected control animals showed no abnormal findings throughout the entire observation period. Here, it was confirmed that H. pylori infection alone causes gastric cancer in an animal model.     

Multiple primary colorectal and gastric carcinoma in Japan

We investigated the occurrence of multiple primary colorectal and gastric cancer (MPCGC) in 1277 colorectal cancer patients between 1972 and 1996. MPCGC was found in 65 (5.1%). In the 28 synchronous cases, gastric or colorectal cancer was accidentally detected by pre-, intra-, or postoperative examinations. In 23 of the 37 metachronous cases, colorectal cancer developed on average 83 months after the operation for gastric cancer. In the other 14 cases, gastric cancer developed on average 70 months after the operation for colorectal cancer. Therefore, careful pre-, intra-, or postoperative examinations are strongly called for in order to not overlook the presence of colorectal or gastric lesions in MPCGC cases.