alpha-chymotrypsin and Carcinoma

Topics: Amylases; Animals; Arginase; Benz(a)Anthracenes; Carcinoma; Carcinoma 256, Walker; Carcinoma, Brown-Pearce; Carcinoma, Ehrlich Tumor; Catalase; Chymotrypsin; Deoxyribonucleases; Enzyme Therapy; Humans; Hyaluronoglucosaminidase; Mammary Neoplasms, Experimental; Mice; Neoplasms, Experimental; Osteosarcoma; Peroxidases; Rats; Ribonucleases; Sarcoma; Sarcoma 180; Sarcoma, Experimental; Trypsin

Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of the tumor peptidome has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the tumors peptidome information in cancer research have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. To address this need, we have recently developed an effective and robust analytical platform as well as a novel informatics approach for comprehensive analyses of tissue peptidomes. The ability of this new peptidomics pipeline for high-throughput, comprehensive, and quantitative peptidomics analysis, as well as the suitability of clinical ovarian tumor samples with postexcision delay limited to less than 60min before freezing for peptidomics analysis, has been demonstrated. These initial analyses set a stage for further determination of molecular details and functional significance of the peptidomic activities in ovarian cancer.

Topics: Carcinoma; Chromatography, High Pressure Liquid; Chymotrypsin; Cluster Analysis; Databases, Protein; Double Effect Principle; Female; Humans; Molecular Weight; Neoplasm Grading; Neoplasm Proteins; Neoplasm Staging; Ovarian Neoplasms; Ovary; Peptide Fragments; Protein Stability; Proteolysis; Proteomics; Regression Analysis; Tandem Mass Spectrometry

Topics: Carcinoma; Chymotrypsin; DNA-Binding Proteins; Gene Fusion; Genes, myb; HMGA2 Protein; Humans; NFI Transcription Factors; Nuclear Proteins; Protein-Tyrosine Kinases; Salivary Gland Neoplasms; Trans-Activators; Transcription Factors

Protease inhibitors have been known to exhibit anticarcinogenic activity in a variety of model systems, although the biological target(s) and mechanism remain enigmatic. Human papillomavirus (HPV) is the primary etiological agent of cervical cancer. Here we show that a nuclear chymotrypsin-like protease activity (NCLPA), which appears to be involved in transformation in several different experimental models, is significantly elevated in keratinocytes infected with high-risk HPV. Further, we demonstrate a marked growth inhibition of organotypic raft cultures, which is specific for cells infected with high-risk HPV types, using a chloromethyl ketone inhibitor previously shown to be relatively selective for the NCLPA. Surprisingly, this HPV-dependent inhibitory effect is independent of any alterations in the NCLPA. This finding has clear implications for the development of novel therapeutics specifically targeted to cervical dysplasias with HPV-infected cells.

Topics: Amino Acid Chloromethyl Ketones; Carcinoma; Cell Culture Techniques; Cell Nucleus; Cell Proliferation; Cells, Cultured; Chymotrypsin; Dimethyl Sulfoxide; Dose-Response Relationship, Drug; Female; Genome, Viral; Humans; Keratinocytes; Male; Oligopeptides; Papillomaviridae; Papillomavirus Infections; Peptide Hydrolases; Protease Inhibitors; Uterine Cervical Neoplasms

We have examined the microscopic appearance, immunohistochemical staining properties, and clinical behavior of 28 cases of acinar cell carcinoma of the pancreas. Two of the tumors occurred in children. The adult patients ranged in age from 40 to 81 years (mean, 62 years). Males greatly outnumbered females, and most of the patients were white. Presenting symptoms were nonspecific, and jaundice was infrequent. The frequently reported complications from increased serum lipase levels (i.e., arthralgias and subcutaneous fat necrosis) were present in only 16% of the patients. Grossly, the tumors were relatively circumscribed and fleshy, averaging 10.8 cm, with occasionally extensive hemorrhage and necrosis. Microscopically, the tumors were very cellular and characteristically lacked a desmoplastic stroma. Acinar, solid, trabecular, and glandular patterns of growth were identified; individual tumors were usually mixed. Nuclei were round to oval, with minimal pleomorphism and single prominent nucleoli. Mitotic activity was variable. In general the cytoplasm was moderately abundant, eosinophilic, and granular, but many of the solid tumors had cells with scanty cytoplasm. Characteristic periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules were demonstrated in greater than 90% of the cases, and the butyrate esterase histochemical stain for lipase activity was positive in 73%. Immunohistochemically, there was positivity for trypsin in 100% of the cases, for lipase in 77%, for chymotrypsin in 38%, and for amylase in 31%. A minor endocrine component was recognized with antibodies against chromogranin or islet cell hormones in 42% of the tumors. Ultrastructurally, exocrine secretory features were present, with polarized cells showing microvillilined lumina, abundant rough endoplasmic reticulum, and 125-1,000-nm zymogen-like granules. In addition, many cases showed pleomorphic electron-dense granules measuring up to 3,500 nm and containing fibrillary internal structures. Follow-up information was available in 88% of the cases. Half of the patients had metastatic disease at presentation and an additional 23% subsequently developed metastases, which were usually restricted to the regional lymph nodes and liver. The mean survival for all cases was 18 months, with 1- and 3-year survivals of 57 and 26%, respectively. Patients presenting before age 60 years survived nearly twice as long as older patients did. Stage also influenced prognosis, whereas the histo

Topics: Adult; Aged; Aged, 80 and over; alpha-Amylases; Carcinoma; Cell Division; Cell Nucleus; Child; Chymotrypsin; Cytoplasmic Granules; Diagnosis, Differential; Female; Glucagon; Humans; Immunohistochemistry; Insulin; Keratins; Lipase; Male; Microscopy, Electron; Middle Aged; Mitotic Index; Pancreatic Neoplasms; Prognosis; Trypsin

Hepatocellular carcinoma with osteoclast-like giant cells (hepatic giant cell carcinoma [HGCC]) is a rare entity, with only three cases reported. The tumor is histologically similar to giant cell tumor (GCT) of bone, and the origin of the multinucleated giant cells and mononuclear stromal cells has not been determined. The purpose of this report is to present a case of this rare tumor and compare its ultrastructural and immunohistochemical features with those of a conventional GCT of bone. Histologically, the HGCC consists of sheets of osteoclast-like giant cells with a background of mononuclear cells. The giant cells lack the pleomorphism seen in hepatocellular carcinomas with anaplastic giant cells. At the light microscopic level, most of this tumor was nearly identical to a GCT of bone, but several microscopic fields (less than 5% of the tumor) had the histologic appearance of a "usual" hepatocellular carcinoma. The hepatic tumor was negative for HAM 56, epithelial cytokeratins, muramidase, and alpha-1-antitrypsin, with only focal positivity for chymotrypsin in mononuclear and giant cells. The GCT was strongly positive for alpha-1-antitrypsin and chymotrypsin in both the mononuclear and giant cells and showed focal, weak staining for AE1 and AE3 in the mononuclear stromal cells. Ultrastructurally, both mononuclear and giant cells of the HGCC showed features typical of hepatocellular carcinoma. Although the patient presented in this report died, the pattern of growth was different from most hepatocellular carcinomas. The overall histologic features of this tumor are distinctive and appear to justify separating this variant from other types of hepatocellular carcinoma.

Topics: Adult; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Cell Nucleus; Chymotrypsin; Cytoplasm; Female; Humans; Immunohistochemistry; Liver Neoplasms; Microscopy, Electron; Osteoclasts; Protease Inhibitors

The interaction of cells with laminin and laminin fragments was studied in short-term cell attachment assays. Neurite-promoting chymotrypsin fragments of laminin were isolated using a monoclonal antibody which blocks neurite outgrowth on laminin. The fragments were shown, by electron microscopy after rotary shadowing and by immunological reactivity with different monoclonal antibodies, to contain only the distal end of the long arm. These fragments promoted the attachment and spreading of glioma, sarcoma, carcinoma, muscle, and endodermal cells to the same extent as intact laminin. The attachment was unaffected by peptides containing the RGD sequence. The morphology of the cells on the chymotrypsin fragments was indistinguishable from that on intact laminin but different from the morphology of the same cells on fibronectin. Light microscopy and scanning electron microscopy showed extensive process formation on laminin but not on fibronectin suggestive of increased cell motility in response to laminin. We conclude that the neurite-promoting domain of laminin contains a major site of interaction for non-neuronal cells and that this site induces a cellular response in certain non-neuronal cells that is unique to laminin.

Topics: Animals; Antibodies, Monoclonal; Axons; Carcinoma; Cell Adhesion; Cell Movement; Chymotrypsin; Endoderm; Glioma; Humans; Immunohistochemistry; Laminin; Microscopy, Electron; Microscopy, Electron, Scanning; Muscles; Osteosarcoma; Peptide Fragments; Rats; Tumor Cells, Cultured

Using an avidin-biotin immunoperoxidase technic, the authors studied 29 anaplastic thyroid tumors (ATTs) to determine the frequency of hormonal (thyroglobulin--TG; calcitonin--CT), epithelial (epithelial membrane antigen, monoclonal keratin), or sarcoma (desmin; alpha-1-antichymotrypsin--ACT; vimentin) markers. Their results indicate that 27% of ATTs stain for TG and none for CT. Fifty-five percent showed epithelial markers, 48% marked for ACT, and 47% for vimentin. Coexpression of keratin and vimentin was found in 39% of cases tested. The expression of the tested antigens did not correlate significantly with histologic pattern (epithelial vs. "sarcomatous"). Of note is the fact that 30% of the ATTs the authors tested expressed none of the markers they examined, indicating total lack of differentiation.

Topics: Adult; Aged; Aged, 80 and over; Anaplasia; Calcitonin; Carcinoma; Chymotrypsin; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Mucin-1; Sarcoma; Thyroglobulin; Thyroid Neoplasms; Vimentin

The murine monoclonal antibody 791T/36 cross-reacts with cells other than the immunizing osteogenic sarcoma cell line 791T, upon which the 791T/36-defined epitope is expressed on a protein of apparent molecular weight 72,000. An investigation was performed to determine whether the epitope occurred on similar molecules on other cell lines. Radiolabelled immunoprecipitates, prepared with the 791T/36 antibody, from three osteogenic sarcoma cell lines (2 OS, 788T and 278T), the prostate carcinoma EB33 and the colon carcinoma HcLo each contained a protein with a molecular weight of 72,000 as the major constituent, together with, in some cases, material of lower molecular weight. This heterogeneity was shown by neuraminidase treatment of the immune precipitates to be due to variations in sialic acid content of the antigens since, in five of the six cell lines tested, such treatment produced homogeneous material of apparent molecular weight 55,000. Chymotrypsin treatment of the immune precipitates produced in each instance a major polypeptide of molecular weight 47,000 which displayed no microheterogeneity. Immunoadsorbent-purified antigen from 791T cells was shown to bind strongly to Sepharose-wheat-germ agglutinin and less to Sepharose-concanavalin A, confirming the glycoprotein nature of this antigen. These studies demonstrate that molecules expressing the 791T/36-defined epitopes on different tumour cell lines are glycoproteins which display heterogeneity with respect to apparent molecular weight that is attributable to varying degrees of sialylation. No apparent differences were detected in the polypeptide "backbone" of these antigenic molecules.

Topics: Antigens, Neoplasm; Antigens, Surface; Carcinoma; Cell Line; Chymotrypsin; Humans; Lectins; Melanoma; Molecular Weight; Osteosarcoma; Papain

The light microscopic, electron microscopic and histochemical features of a highly malignant colonic tumor resected from a 39 year old man are presented. The tumor was composed predominantly of undifferentiated cells with focally admixed neuroendocrine, exocrine and squamous cells, occasionally arranged in an organoid manner. Histochemically the tumor contained argyrophilic cells as well as cells that reacted positively with the antibodies to alpha-1-antitrypsin, alpha-1-antichymotrypsin, carcinoembryonic antigen and lysozyme. The term "stem cell carcinoma of the intestine" is proposed for this highly malignant tumor composed of undifferentiated cells exhibiting only focally their multidirectional developmental capacity.

Topics: Adult; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Carcinoembryonic Antigen; Carcinoma; Chymotrypsin; Colonic Neoplasms; Histocytochemistry; Humans; Immunologic Techniques; Keratins; Male; Microscopy, Electron; Muramidase; Staining and Labeling

Breast carcinoma with multinucleated reactive stromal giant cells is a rare histological type. The number of published cases, to which we add two new cases, is too small for it to be possible to reach a conclusion as to whether this type of complaint, for which the authors put forward morphological criteria, should or should not be considered as an anatomoclinical entity. The diagnosis can be made as soon as cytological examination has shown a large number of multinucleated giant cells associated with carcinomatous cells. Ultrastructural study confirms the macrophagic origin of the giant cells but does not show any macrophagic activity.

Topics: alpha 1-Antichymotrypsin; Breast Neoplasms; Carcinoma; Chymotrypsin; Female; Humans; Immunoenzyme Techniques; Middle Aged; Muramidase

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

The levels of serum acute phase reactant proteins (APRPs) have been examined in untreated kidney carcinoma and during the evolution of metastases. These proteins can provide a warning of the likelihood of extensive local or metastatic spread at first presentation. The levels of APRPs rise with increasing tumour burden but the system is insensitive to small tumour burdens. beta 2-Microglobulin levels do not contribute additional information. Serum phosphohexose isomerase tends to be elevated when there is a large tumour burden but its change does not accurately mirror the rate of expansion of the tumour. The APRPs and phosphohexose isomerase are useful in alerting the clinician to the probability of metastases or large local masses in kidney cancer, but have a limited use in monitoring.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; beta 2-Microglobulin; Blood Proteins; C-Reactive Protein; Carcinoma; Chymotrypsin; Female; Glucose-6-Phosphate Isomerase; Haptoglobins; Humans; Kidney Neoplasms; Male; Orosomucoid; Protease Inhibitors

The diagnostic aids of acute pancreatitis include the clinical presentation, laboratory investigations and abdominal sonography. The assessment of amylase creatinin clearance ratio is not superior to simple amylase estimations in identifying unspecific hyperamylasemias apart from acute pancreatitis. The management of acute pancreatitis consists of a standardized basic treatment which does not depend on the degree of the severity of the disease and supplementary measures which are adjusted to the degree of severity and complications. In case of chronic pancreatitis a variety of indirect and direct morphological and functional examinations are available. The diagnostic safety of all procedures--each taken by its own--is below 90%; however, the combined use has to be adjusted to the severity of the symptoms suspicious of pancreatis disease. The therapeutic goal includes the conservative management of the painful recurrences to achieve transmission into the final stage of the disease which presents only minor symptoms. Operation has to be considered in case of untreatable pain and local complications. The obstruction of the pancreatic duct by means of synthetic glue instillations is a hopeful approach.

Topics: Acute Disease; Calcitonin; Carcinoma; Chronic Disease; Chymotrypsin; Humans; Hypocalcemia; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancreatitis; Tomography, X-Ray Computed; Ultrasonography

Topics: Adult; Amino Acid Sequence; Animals; Antibody Specificity; Calcitonin; Carcinoma; Cattle; Chymotrypsin; Dose-Response Relationship, Immunologic; Humans; Immune Sera; Isoelectric Focusing; Oxidation-Reduction; Peptide Fragments; Rabbits; Radioimmunoassay; Rats; Species Specificity; Swine; Thyroid Gland; Thyroid Neoplasms; Time Factors; Trypsin

Topics: Carbon Radioisotopes; Carcinoma; Cell Line; Cell Survival; Chymotrypsin; Diphtheria Antitoxin; Diphtheria Toxin; Kinetics; Mouth Neoplasms; Neoplasm Proteins; Phospholipases; Pronase; Protein Biosynthesis; Time Factors; Trypsin; Valine

Topics: Blood Proteins; Breast Neoplasms; Carcinoma; Chymotrypsin; Cyclophosphamide; Female; Hematocrit; Hemoglobins; Humans; Kininogens; Kinins; Leukocyte Count; Leukocytes; Time Factors

Topics: Acrylates; Adenoviridae; Amino Acids; Anhydrides; Antigens; Autoanalysis; Carcinoma; Cell Line; Centrifugation, Density Gradient; Centrifugation, Zonal; Chromatography; Chromatography, DEAE-Cellulose; Chymotrypsin; Complement Fixation Tests

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Cholecystitis; Chymotrypsin; Colorimetry; Duodenal Ulcer; Female; Hepatitis; Humans; Intestinal Diseases; Liver Cirrhosis; Lung Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Neoplasm Metastasis; Pancreatitis; Pregnancy; Respiratory Tract Infections; Trypsin Inhibitors

Topics: Adenoviridae; Animals; Arginine; Carcinoma; Cell Line; Chymotrypsin; Culture Techniques; Cytopathogenic Effect, Viral; Humans; Hydrocarbons, Halogenated; Keratoconjunctivitis; Mouth Neoplasms; Mycoplasma; Rabbits; Ultracentrifugation; Virus Cultivation; Virus Replication

Topics: Amides; Amino Acid Sequence; Amino Acids; Ascitic Fluid; Buffers; Carcinoma; Chemical Phenomena; Chemistry; Chromatography, Gel; Chromatography, Ion Exchange; Chromatography, Paper; Chromatography, Thin Layer; Chymotrypsin; Electrophoresis; Female; Fluoroacetates; Genetics, Medical; Haptoglobins; Heterozygote; Humans; Macromolecular Substances; Methods; Naphthalenes; Ovarian Neoplasms; Peptides; Sulfonic Acids; Trypsin

Topics: Blood Proteins; Carcinoma; Chymotrypsin; Fructose; Hematologic Diseases; Humans; Neoplasms; Protease Inhibitors

Topics: Breast; Breast Neoplasms; Carcinoma; Chymotrypsin; Humans