The activities of Ca+2-PL dependent protein Kinase (PKC) and independent protein kinase(RKM) were measured in human stomach and breast tumors and in the respective counterparts of normal tissue. Expression of c-fos and c-myc of the tissues were also measured. RNAs of c-fos and c-myc were unexpectedly high in the tissue from normal stomach and breast as well as in all cancer tissue. On the other hand, cytosolic and particulate PKC activities were higher in the tumors as compared to those of normal controls. Notably, some cases exhibited. altered activities of PKC i.e. increased RKM activities as high as RKC, which might be related to the autocrine control of growth in the tumor mass.
Adenocarcinoma/enzymology* ; Breast Neoplasms/enzymology* ; Carcinoma, Intraductal, Noninfiltrating/enzymology* ; Human ; Protein Kinase C/metabolism* ; Stomach Neoplasms/enzymology*

BACKGROUND: Helicobacter pylori (H. pylori) has been considered a definitive carcinogen in gastric cancer. Telomerase is activated in gastric cancer and some premalignant gastric lesions, including intestinal metaplasia (IM). In this study, we evaluated the relationships of both H. pylori infection and telomerase activity with endoscopic and histologic features in IM. The effects of H. pylori eradication on endoscopic, histologic and biochemical changes were evaluated. METHODS: Endoscopic biopsies were obtained from 43 patients with IM for rapid urease, histologic and telomerase tests. The endoscopic and histologic features, H. pylori infection and telomerase were assessed. After H. pylori eradication, 15 patients were re-evaluated and compared after 4 months. RESULTS: Thirty-four (79.1%) patients were infected with H. pylori. The incidence of H. pylori infection was borderline correlated to the severity of IM (p=0.076). Telomerase was elevated in eight (18.6%) patients. Telomerase tends to be high in subtype III and endoscopic grade III of IM. After H. pylori eradication, endoscopic extent (p=0.039) and histologic severity (p=0.074) showed improvements, and telomerase decreased significantly (p=0.0001). CONCLUSION: Our data suggest that telomerase is associated with the severity and extent of IM and that H. pylori eradication improves the endoscopic and histologic features in IM, and decreases telomerase activity. H. pylori eradication can be considered one of the methods to prevent gastric cancer in patients with H. pylori-infected IM. Further long-term and large-scaled study will be needed.
Female ; Helicobacter Infections/*enzymology ; *Helicobacter pylori ; Human ; Intestinal Mucosa/enzymology/microbiology/*pathology ; Male ; Metaplasia/enzymology/microbiology ; Middle Aged ; Precancerous Conditions/enzymology/microbiology ; Stomach Neoplasms/*enzymology/microbiology ; Telomerase/*metabolism

OBJECTIVETo study the role of arginase-1 (Arg-1) expression in differential diagnosis of hepatocellular carcinoma (HCC), Arg-1 staining pattern in clear cell neoplasm (HCC and non-HCC) and Arg-1 expression in non-hepatocellular tumors.

METHODSSeventy-eight cases of HCC (including 8 cases of clear cell type and 70 cases of non- clear cell type) and 246 cases of non-hepatocellular neoplasms (including 29 cases of metastatic tumors such as breast cancer, nasopharyngeal carcinoma and neuroendocrine carcinoma, 77 cases of tumors with clear cell changes such as malignant melanoma, clear cell renal cell carcinoma and alveolar soft part sarcoma, and 140 cases of other types of tumors such as ovarian endometrioid adenocarcinoma, pituitary tumor and thyroid papillary carcinoma) were studied.Immunohistochemical study for Arg-1 was performed on the paraffin-embedded tumor tissue.

RESULTSIn HCC, Arg-1 demonstrated both cytoplasmic and nuclear staining, with an overall sensitivity of 96.2% (75/78).In well, moderately and poorly differentiated HCC, the sensitivity was 15/15, 100% (41/41) and 86.4% (19/22), respectively. That was in contrast to negative staining for Arg-1 in all the 29 cases of metastatic tumors studied. The sensitivity, specificity, positive predictive value and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors was 96.2%, 100%, 100% and 90.6%, respectively. Cytoplasmic and membranous staining was observed in clear cell type of HCC. The overall sensitivity of Arg-1 expression in the 77 cases of tumors with clear cell changes was 14.3% (11/77), including 8/15 for malignant melanoma, 2/4 for ovarian clear cell carcinoma and 1/1 gall bladder adenocarcinoma with clear cell component.In malignant melanoma and ovarian clear cell carcinoma, only cytoplasmic staining was demonstrated. There was no expression of Arg-1 in the 140 cases of other tumor types studied.

CONCLUSIONSArg-1 is a sensitive and specific marker for HCC.It is a potentially useful immunohistochemical marker in distinguishing HCC from metastatic tumors. Though also expressed in malignant melanoma and ovarian clear cell carcinoma, Arg-1 shows a different staining pattern as compared with that in HCC.

Adenocarcinoma ; enzymology ; Adult ; Aged ; Arginase ; metabolism ; Carcinoma, Hepatocellular ; enzymology ; pathology ; secondary ; Cell Differentiation ; Diagnosis, Differential ; Female ; Gallbladder Neoplasms ; enzymology ; Humans ; Liver Neoplasms ; enzymology ; pathology ; secondary ; Male ; Melanoma ; enzymology ; Middle Aged ; Ovarian Neoplasms ; enzymology ; Stomach Neoplasms ; enzymology ; pathology

BACKGROUND/AIMS: Telomerase activity and telomerase reverse transcriptase (TERT) expression have been proposed as a marker for malignancy. However, little is known about those markers in intestinal metaplasia (IM). This study was performed to evaluate the usefulness of telomerase activity in gastric washing fluid and TERT expression in tissue as a marker for early diagnosis of stomach cancer. METHODS: Gastric washing fluid and biopsies were taken endoscopically. We examined the telomerase activity by telomeric repeat amplification protocol (TRAP) and the TERT expression by semiquantitative reverse transcription-polymerase chain reaction in 26, 21 and 15 cases of cancer, IM, and normal mucosa respectively. RESULTS: The telomerase activity was positive in 65% of cancer, 44% of incomplete IM, and 33% of complete IM. The TERT was expressed in 89% of cancer, 81% of IM, but not in normal mucosa. The TERT expression level was higher in cancer and incomplete IM than in complete IM and normal mucosa (p<0.05). CONCLUSIONS: Telomerase activity in gastric washing fluid and TERT expression in tissue may have limited usefulness as a marker for the early diagnosis of stomach cancer. However, the increased levels of TERT expression in IM and cancer suggest that TERT expression may be associated with carcinogenesis in stomach cancer.
DNA-Binding Proteins ; Gastric Lavage ; Gastric Mucosa/enzymology ; Humans ; Metaplasia ; Precancerous Conditions/diagnosis ; Stomach/enzymology ; Stomach Neoplasms/*diagnosis/enzymology ; Telomerase/*analysis ; Tumor Markers, Biological/*analysis

The effects of thyroid hormone on hepatic and gastric alcohol dehydrogenase (ADH) activities (nM of NADH/min/mg of cytosolic protein) have been investigated in male Sprague Dawley rats treated with thyroxine (1 mg/kg, po) for 14 days. Whereas hepatic ADH activity in thyroxine-treated rats decreased by 61.3% of control rats (26.4 vs 43.2, p<0.001), gastric ADH activity increased by 262.9% of control rats (4.9 vs 1.9, p<0.001). As for the activities of the lung and kidney, thyroxine treatment did not produce any statistically significant changes. These data suggest that thyrotoxicosis causes a decrease of hepatic alcohol metabolism, and that the increase of gastric ADH activity in thyrotoxic rats can partly restore the first-pass metabolism of ethanol.
Alcohol Dehydrogenase/*metabolism ; Animal ; Gastric Mucosa/enzymology ; Kidney/enzymology ; Liver/drug effects/*enzymology ; Lung/enzymology ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach/drug effects/*enzymology ; Thyrotoxicosis/chemically induced/metabolism ; Thyroxine/administration & dosage/*metabolism/pharmacology

BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be involved in the process of invasion, growth and apoptosis in colorectal carcinoma and in the growth and tumorigenesis in familial adenomatous polyposis. This study was conducted to determine the significance of the expression of COX-2 in gastric and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty-seven samples of colorectal adenoma were obtained by endoscopic mucosal resection or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression was determined by immunohistochemistry. Correlation between COX-2 expression and several clinical factors were compared in each gastric and colorectal adenomas. RESULTS: The expression of COX-2 in epithelial cells was significantly higher in the group with large adenoma (>1 cm) compared with the group with small adenoma ( Adenoma/enzymology/*pathology ; Aged ; Colorectal Neoplasms/enzymology/*pathology ; English Abstract ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prostaglandin-Endoperoxide Synthase/*analysis ; Stomach Neoplasms/enzymology/*pathology

Cytoplasmic Cu/Zn superoxide dismutase (SOD1) is an antioxidant enzyme that converts superoxide to hydrogen peroxide in cells. Its spatial distribution matches that of superoxide production, allowing it to protect cells from oxidative stress. SOD1 deficiencies result in embryonic lethality and a wide range of pathologies in mice, but little is known about normal SOD1 protein expression in developing embryos. In this study, the expression pattern of SOD1 was investigated in post-implantation mouse embryos and extraembryonic tissues, including placenta, using Western blotting and immunohistochemical analyses. SOD1 was detected in embryos and extraembryonic tissues from embryonic day (ED) 8.5 to 18.5. The signal in embryos was observed at the lowest level on ED 9.5-11.5, and the highest level on ED 17.5-18.5, while levels remained constant in the surrounding extraembryonic tissues during all developmental stages examined. Immunohistochemical analysis of SOD1 expression on ED 13.5-18.5 revealed its ubiquitous distribution throughout developing organs. In particular, high levels of SOD1 expression were observed in the ependymal epithelium of the choroid plexus, ganglia, sensory cells of the olfactory and vestibulocochlear epithelia, blood cells and vessels, hepatocytes and hematopoietic cells of the liver, lymph nodes, osteogenic tissues, and skin. Thus, SOD1 is highly expressed at late stages of embryonic development in a cell- and tissue-specific manner, and can function as an important antioxidant enzyme during organogenesis in mouse embryos.
Animals ; Cerebral Cortex/embryology/enzymology ; Copulation ; Cytoplasm/*enzymology ; Embryonic Development/*physiology ; Female ; Immunohistochemistry ; Lung/embryology/enzymology ; Male ; Mice ; Mice, Inbred ICR ; Organogenesis/*physiology ; Pregnancy ; Stomach/embryology/enzymology ; Superoxide Dismutase/deficiency/genetics/*metabolism

OBJECTIVETo study the level of expression of Caspase-3 protein in precancerous lesions of stomach and its relation to gastric carcinogenesis.

METHODSFormalin-fixed paraffin embedded tissues from 184 cases of gastric mucosa biopsy and surgically removed specimens, including gastric cancer (GC, N = 20), chronic atrophic gastritis (CAG, N = 6), atrophic gastritis with intestinal metaplasia (IM, N = 31), atrophic gastritis with dysplasia (DYS, N = 114) and normal controls (N = 13) were examined for expression of Caspase-3 protein and Ki-67 index by SABC immunohistochemistry, and for apoptosis by TdT-mediated dUTP biotin nick end labeling (TUNEL) method. Caspase-3, Ki-67 and TUNEL index were compared in different stages of gastric precancerous lesions and their correlation was analyzed.

RESULTSThe positive index of Caspase-3 protein in severe DYS (29.8% +/- 3.9%) showed no significant difference compared with that in GC (26.9% +/- 3.0%, P > 0.05), but was significantly lower than that in low (58.3% +/- 4.2%) and moderate grade DYS (50.4% +/- 4.8%), CAG (68.3% +/- 3.3%) and IM (70.9% +/- 4.3%, P < 0.05). Caspase-3 positive index was significantly correlated with that of apoptosis detected by TUNEL (r = 0.94, P < 0.05). Ki-67 index in Caspase-3 protein positive group (18.3% +/- 2.2%) was significantly lower than that in Caspase-3 negative group (48.9% +/- 3.1%, P < 0.05).

CONCLUSIONCaspase-3 protein expression was upregulated in CAG with or without IM and low or moderately low in DYS, while down-regulated in severe DYS and gastric carcinoma, and significantly positively correlated with cell apoptosis. It is suggested that down-regulated expression of Caspase-3 protein somehow contributes to gastric carcinogenesis through an imbalance between cell apoptosis and proliferation.

Adult ; Aged ; Apoptosis ; Caspase 3 ; metabolism ; Down-Regulation ; Female ; Gastric Mucosa ; enzymology ; metabolism ; pathology ; Gastritis, Atrophic ; enzymology ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Metaplasia ; Middle Aged ; Precancerous Conditions ; enzymology ; metabolism ; Stomach Neoplasms ; enzymology ; metabolism

OBJECTIVETo study the thymidine phosphorylase (TP) expression in different types of cancer and its correlation with tumor microvessel density (MVD).

METHODSThe expression of TP and MVD was detected by immunohistochemistry method. In a series of 251 cancer patients there were 48 patients with gastric cancer, 53 with colorectal cancer, 47 with breast cancer, 56 with cervical cancer, 47 with lung cancer. Normal gastric (n = 25), colorectal (n = 25), cervical (n = 17) and lung (n = 25) tissues around the cancer were also examined.

RESULTSThe TP expression rate was 64.6% in gastric cancer, 67.9% in colorectal cancer, 80.9% in breast cancer, 82.1% in cervical cancer, and 63.8% in lung cancer, which was significantly higher than that in normal tissues (P = 0.0000). TP expression was positively correlated with MVD in gastric, colorectal, breast, and cervical cancers. The correlation was not statistically significant in lung cancer.

CONCLUSIONThis study indicates that TP overexpression in cancer may be associated with tumor angiogenesis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; blood supply ; enzymology ; Colorectal Neoplasms ; blood supply ; enzymology ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Stomach Neoplasms ; blood supply ; enzymology ; Thymidine Phosphorylase ; metabolism ; Uterine Cervical Neoplasms ; blood supply ; enzymology

Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8 x 4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.
Antigens, CD30/*metabolism ; Female ; Humans ; Immunohistochemistry ; Korea ; Lymphoma, Large-Cell/enzymology/*immunology/*pathology ; Middle Aged ; Protein-Tyrosine Kinase/metabolism ; Stomach Neoplasms/enzymology/*immunology/*pathology