alpha-chymotrypsin and Stomach-Neoplasms

Although pancreatic acinar metaplasia in the gastric mucosa is well recognized in chronic gastritis, gastric carcinoma with acinar differentiation is very rare. We encountered a case of gastric adenocarcinoma with prominent histologic and immunohistochemical features of pancreatic acinar differentiation in the absence of identifiable heterotopic pancreatic tissue. Distinct glandular and diffuse patterns of adenocarcinoma were also present, and there was focal mucin production. The tumor strongly expressed pancreatic exocrine enzymes trypsin and chymotrypsin, and focal neuroendocrine staining was also present. To investigate the prevalence of acinar differentiation in histologically typical gastric cancers, we performed immunohistochemical staining for trypsin and chymotrypsin on a tissue microarray containing 111 conventional gastric adenocarcinomas (60 intestinal, 28 mixed, 22 diffuse type, and 1 undifferentiated). No obvious morphologic evidence of acinar differentiation was identified in any of the 111 cases. Although some cases showed equivocal staining for at least 1 pancreatic exocrine enzyme on the initial tissue microarray sections, repeat immunohistochemical staining on representative whole-tissue sections failed to reproduce positive staining. Thus, acinar differentiation is rare in gastric adenocarcinomas, other than in histologically unusual cases such as the one we report, and in others from the literature, which are reviewed.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Acinar Cell; Cell Differentiation; Chymotrypsin; Female; Gastrectomy; Humans; Immunohistochemistry; Male; Metaplasia; Middle Aged; Stomach Neoplasms; Tissue Array Analysis; Trypsin

Topics: Aged; alpha 1-Antichymotrypsin; Chymotrypsin; Collagen; Female; Histiocytes; Histiocytoma, Benign Fibrous; Humans; Mitosis; Muramidase; Necrosis; Stomach; Stomach Neoplasms; Vimentin

Chymotrypsin-like activity of proteasomes and total calpain activity were studied in patients with stage T2-4N0-3M0 gastric cancer and stage T2-4N0-2M0-1 colorectal cancer. Activities of proteasomes and calpains in gastric and colorectal cancer tissues were higher than in the corresponding normal tissues. Changes in activities of proteasomes and calpains were mutually related. The appearance of lymphogenic metastases in gastric cancer was associated with the increase in calpain activity. The progress of colorectal cancer and development of lymphogenic and hematogenic metastases were associated with elevated chymotrypsin-like activity of proteasomes.

Topics: Calpain; Chymotrypsin; Colorectal Neoplasms; Fluorometry; Humans; Lymphatic Metastasis; Proteasome Endopeptidase Complex; Statistics, Nonparametric; Stomach Neoplasms

To investigate the state of activation of the ATP-ubiquitin-dependent proteolytic system in the skeletal muscle of gastric cancer patients.. Muscle wasting in experimental cancer cachexia is frequently associated with hyperactivation of the ATP-dependent ubiquitin-proteasome proteolytic system. Increased muscle ubiquitin mRNA levels have been previously shown in gastric cancer patients, suggesting that this proteolytic system might be modulated also in human cancer.. Biopsies of the rectus abdominis muscle were obtained intraoperatively from 23 gastric cancer patients and 14 subjects undergoing surgery for benign abdominal diseases, and muscle ubiquitin mRNA expression and proteasome proteolytic activities were assessed.. Muscle ubiquitin mRNA was hyperexpressed in gastric cancer patients compared to controls. In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls. Advanced tumor stage, poor nutritional status, and age more than 50 years were associated with significantly higher CTL activity but had no influence on TL and PGP activity.. These results confirm the involvement of the ubiquitin-proteasome proteolytic system in the pathogenesis of muscle protein hypercatabolism in cancer cachexia. The observation that perturbations of this pathway in gastric cancer patients occur even before clinical evidence of body wasting supports the thinking that specific pharmacologic and metabolic approaches aimed at counteracting the upregulation of this pathway should be undertaken as early as cancer is diagnosed.

Topics: Biopsy; Chymotrypsin; Cysteine Endopeptidases; Endopeptidases; Female; Gene Expression; Humans; In Vitro Techniques; Male; Middle Aged; Multienzyme Complexes; Nutritional Status; Proteasome Endopeptidase Complex; Rectus Abdominis; RNA, Messenger; Stomach Neoplasms; Trypsin; Ubiquitin; Weight Loss

Hepatoid adenocarcinomas of the stomach are gastric carcinomas with both adenocarcinomatous and hepatocellular differentiations. They usually produce large amounts of alpha-fetoprotein (AFP) with a Concanavalin A-binding property of hepatic type. In this study, these carcinomas occurred in older persons, with the antrum being a common site. Observed grossly, growth of the tumors was nodular and massive. Prognosis was poor because of frequent liver metastases. In the cytoplasms of tumor cells, various serum proteins were identified, including AFP, alpha-1 antitrypsin (AAT), alpha-1 antichymotrypsin (ACT), albumin, and prealbumin. Localizations of ferritin, prothrombin, and transferrin were demonstrated with less frequency. Adenocarcinomatous foci were composed of well-differentiated, intestinal-type epithelial cells and often contained carcinoembryonic antigen. These adenocarcinomatous and hepatoid areas were often intermingled with each other. There were extensive venous involvements by tumor cells. The poor prognosis of the tumors may be attributed to these involvements as well as to production of AFP and presence of AAT/ACT, which have immunosuppressive and protease-inhibitory properties, respectively.

Topics: Adenocarcinoma; Adult; Aged; Albumins; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cell Differentiation; Cell Nucleus; Chymotrypsin; Cytoplasm; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Liver Neoplasms; Male; Middle Aged; Prealbumin; Prognosis; Staining and Labeling; Stomach Neoplasms

Carcinoembryonic antigen (CEA), beta-human chorionic gonadotropin (HCG), alpha-1-antichymotrypsin (ACT), alpha-1-antitrypsin (AAT) and Lysozyme (LYS) were traced by immunoperoxidase staining in gastric carcinomas. The immunohistological results were evaluated in relation to histological types (WHO and Laurén), stage of disease, grade and survival time. CEA was demonstrated in 96% of the tumours, HCG in 34%, ACT in 78%, AAT in 42%, and LYS in 71%. Comparing the staining patterns of the antigens and the intensity of staining some differences were notable. Except for signet-ring cell carcinomas, all of which were intensively positive, CEA expression decreased significantly with loss of differentiation. This observation was not seen with the other marker substances. None of the tested markers was characteristic for one particular histological type, nor could they be correlated with the tumour stage or grade. The marker positivity of CEA, ACT and LYS was not related to survival time. For HCG only, a correlation between tissue expression and a restricted survival time was established. Patients with AAT positive carcinomas had a significantly better survival probability.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chymotrypsin; Humans; Immunoenzyme Techniques; Muramidase; Prognosis; Stomach Neoplasms

Human stomach adenocarcinomas containing alpha-1-antichymotrypsin (ACT) in their cell nuclei were transplanted into nude mice. The presence of ACT was monitored using an immunohistochemical technique with horseradish peroxidase-labeled rabbit anti-ACT Fab' as well as single radial immunodiffusion. Two weeks after transplantation, ACT could be found neither in transplanted carcinoma cells nor in the sera of carcinoma-bearing nude mice. However, if human ACT was injected i.v., it could be detected in the transplanted carcinoma cell nuclei 2 h after injection. The ACT was detected immunohistochemically and was confirmed by biochemical fractionation using 125I-labeled ACT. On the other hand, the amount of ACT production was not sufficient to indicate biosynthesis. These results demonstrated that ACT detected in stomach carcinoma cell nuclei was not synthesized in carcinoma cells but was incorporated from the blood circulation.

Topics: Adenocarcinoma; alpha 1-Antichymotrypsin; Animals; Biological Transport; Cell Nucleus; Chymotrypsin; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Stomach Neoplasms

One hundred twenty-six gastric carcinomas (68 advanced cancers and 58 early cancers) were examined immunohistochemically for alpha 1-antitrypsin (AAT), alpha 1-antichymotrypsin (ACT), and alpha 2-macroglobulin (AMG) within tumor cells. The incidence of these three protease inhibitors was markedly higher in advanced than in early cancers, regardless of the histologic type of gastric carcinoma. In advanced cancers the incidence of both AAT and AMG was significantly higher in well-differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, but no difference was observed in the expression of ACT between these two types of advanced carcinomas. Eighty per cent of the AAT-positive advanced carcinomas had ACT, and 40 per cent of these tumors also contained AMG. The two-year survival rates clearly indicated that well-differentiated adenocarcinomas with AAT have worse prognoses than well-differentiated adenocarcinomas without AAT, but there was no relation between the expression of ACT or AMG and prognosis. These results strongly suggest that the presence of protease inhibitors in gastric carcinomas is related to the invasive growth of the tumors and that AAT is a tissue tumor marker of well-differentiated adenocarcinomas of the stomach. It may also serve as a biologic marker of high malignancy in patients with these gastric cancers.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; alpha-Macroglobulins; Chymotrypsin; Follow-Up Studies; Gastric Mucosa; Histocytochemistry; Humans; Immunochemistry; Prognosis; Retrospective Studies; Stomach Neoplasms; Tissue Distribution

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Alpha-Globulins; alpha-Macroglobulins; Antithrombin III; Chymotrypsin; Complement C1 Inactivator Proteins; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Middle Aged; Plasminogen; Protease Inhibitors; Stomach Neoplasms; Trypsin Inhibitors

A radioimmunoassay for human pancreatic chymotrypsin II has been developed. Serum immunoreactive chymotrypsin II content in healthy individuals ranged from 14.7 ng/ml to 77.5 ng/ml, the average being 37.5 ng/ml (SD = 19.6). Elevated values were observed in patients with acute pancreatitis and renal failure. After total pancreatectomy, serum immunoreactive chymotrypsin II was not detectable. A significant positive correlation was observed between serum immunoreactive chymotrypsin II and cationic trypsin contents.

Topics: Antibody Specificity; Chymotrypsin; Humans; Kidney Failure, Chronic; Pancreas; Pancreatic Diseases; Radioimmunoassay; Stomach Neoplasms

Serum IAP and IS levels were studied in patients with stomach cancer. We found that the serum levels of IAP and IS increased as the disease progressed; their true positive rates as tumor markers were 49.3% and 39.8%, respectively. There was some delicate difference between these glycoproteins and T-cell subpopulation. IAP and IS correlated well with a correlation coefficient of 0.847, their value in clinical oncology are thought to be equivalent. Some difference was found between their substances and ASP, this might indicate the heterogeneous nature of the circulating glycoproteins in varying cancer-bearing status.

Topics: Adenocarcinoma; alpha 1-Antichymotrypsin; Chymotrypsin; Glycoproteins; Humans; Immunity, Cellular; Neoplasm Proteins; Sialic Acids; Stomach Neoplasms

The cellular localization of alpha-1-antichymotrypsin (alpha 1-ACT) was studied immunohistochemically using rabbit HRP-labeled Fab' against human alpha 1-ACT. alpha 1-ACT was found in cell nuclei of carcinomas of the stomach, liver, breast, pancreas and leiomyosarcoma and in cell nuclei of lymphoid cells infiltrated into the stomach carcinoma mass. alpha 1-ACT was not found in carcinoma cells of the colon, uterus, rectum or esophagus, or in lymphoid cells infiltrated into the rectal carcinoma mass or into inflammatory regions such as gastric ulcers or appendicitis. Further, alpha 1-ACT was not found in normal cells around the carcinoma mass or in normal tissues.

Topics: alpha 1-Antichymotrypsin; Breast Neoplasms; Carcinoma; Cell Nucleus; Chymotrypsin; Humans; Immunologic Techniques; Leiomyosarcoma; Liver Neoplasms; Lymphoid Tissue; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Trypsin Inhibitors

Lysozyme, alpha 1-Antichymotrypsin and alpha 1-Antitrypsin were demonstrated by an immunoperoxidase technique (PAP) in malignant cells of adenocarcinomas of the stomach but not of the large intestine. Lymph-node metastases showed identical immunoreactivity to that of the primary tumour. Neoplasms arising from the cardia, the body and the pyloric antrum of the stomach showed different immunostaining reactions. It seems that these differences partly reflect the distribution of lysozyme, alpha 1-Antichymotrypsin and alpha 1-Antitrypsin in the normal gastric mucosa. The usefulness of our findings in the identification of the primary tumour in cases of lymph node metastases of unknown origin, is also discussed.

Topics: Adenocarcinoma; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Cardia; Chymotrypsin; Colonic Neoplasms; Gastric Mucosa; Histocytochemistry; Humans; Immunoenzyme Techniques; Lymphatic Metastasis; Muramidase; Pyloric Antrum; Stomach Neoplasms

In 104 patients with gastric cancer the serum proteins carcinoembryonic antigen (CEA), C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP) (orosomucoid) and alpha 1-antichymotrypsin (ACT) were measured pre-operatively. The estimated median survival of patients with both raised CEA and ACT was only 5 weeks in contrast to 64 weeks for those with both proteins normal. An intermediary group with one of these proteins raised and the other normal had an estimated median survival of 15 weeks. Similar results were obtained by considering a combination of CEA with either AGP or CRP. For these data the results were not explicable in terms of associations between survival time and patient's age, stage, operative procedure, histological classification or site of primary tumour.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; Blood Proteins; C-Reactive Protein; Carcinoembryonic Antigen; Chymotrypsin; Female; Gastrectomy; Humans; Male; Middle Aged; Orosomucoid; Prognosis; Stomach Neoplasms

Topics: alpha 1-Antichymotrypsin; Chymotrypsin; Gastric Juice; Humans; Stomach Neoplasms; Trypsin Inhibitors

Topics: Chymotrypsin; Cytodiagnosis; Gastric Juice; Humans; Stomach Diseases; Stomach Neoplasms

Topics: Chymotrypsin; Cytodiagnosis; Gastric Lavage; Humans; Sodium Chloride; Stomach Neoplasms

Topics: Chymotrypsin; Cytodiagnosis; Gastric Lavage; Humans; Stomach Neoplasms

Topics: Chymotrypsin; Cytodiagnosis; Humans; Radiography; Stomach Neoplasms

Topics: Achlorhydria; Adenocarcinoma; Anemia; Anemia, Pernicious; Chymotrypsin; Cytodiagnosis; Gastric Acidity Determination; Gastroscopy; Geriatrics; Humans; Mass Screening; Neoplasm Metastasis; Radiography; Stomach Neoplasms; Surgical Procedures, Operative

Topics: Chymotrypsin; Cytodiagnosis; Lung Neoplasms; Stomach Neoplasms

Topics: Chymotrypsin; Cytodiagnosis; Gastric Lavage; Gastritis; Humans; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer

Established centers find that cytological study of gastric washings with saline or chymotrypsin, adequately performed, is a valuable diagnostic tool in the detection of early and curable gastric carcinoma.Our experience with a small series of 150 patients, studied by saline gastric washing, has emphasized the difficulties of collection and the particular importance of obtaining, by repeated washings if necessary, an adequate specimen of gastric epithelial cells for diagnosis, before an opinion is given. It seems likely that the cytological method will be of future value in study of the natural history of gastric malignant disease and in detection of its surface lesions in their earliest form in asymptomatic, known-susceptible persons. Further, it should become a complementary part of the "stomach profile" in gastric diagnostic problems, where roentgenologic and gastroscopic studies may be expected to reveal the older, necrotic, or infiltrative lesions; cytological study, the earlier and more superficial stages of disease.

Topics: Cell Count; Chymotrypsin; Epithelial Cells; Gastroscopy; Humans; Necrosis; Sodium Chloride; Stomach Neoplasms

Topics: Chymotrypsin; Gastric Juice; Hematologic Tests; Humans; Stomach Neoplasms

Topics: Chymotrypsin; Cytodiagnosis; Hematologic Tests; Humans; Stomach Neoplasms

Topics: Chymotrypsin; Endopeptidases; Humans; Hydrolases; Peptide Hydrolases; Stomach Neoplasms; Therapeutic Irrigation

Topics: Chymotrypsin; Endopeptidases; Humans; Hydrolases; Neoplasms; Peptide Hydrolases; Stomach Neoplasms; Therapeutic Irrigation