Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The usefulness of optimized and newly elaborated histochemical methods for proteinases is illustrated on two selected substances. DAP IV (Gly-Pro-MNA,FBB,pH 7.2) was discovered in 39% and DAP II (Lys-Ala-MNA,FBB,pH 5.5) in 60% of the lymphocytes of human peripheral blood (ly). The reaction product of such ly differs in quality and quantity. On the ultrastructural level, the reaction product of DAP IV (Gly-Pro-MNA,HNF) was found in cell membranes and lysosomes. Enzyme activity in other areas was probably suppressed during the preparation procedure. Although the number of ly revealed with Lys-Pro-MNA and Phe-Pro-MNA at pH 5.5 and with Lys-Pro-MNA at pH 7.2 is high, these substrates do not distinctly discriminate DAP IV and DAP II. DAP IV occurs exclusively in T lymphocytes. The number of DAP IV-positive ly was not decreased in patients with myelofibrosis, plasmacytoma, chronic granulocytic leukemia, or tricholeukemia. It was, however, greatly reduced in chronic lymphatic leukemia (CLL). In patients with malignant lymphomas other than CLL, ly presence is related to the stage of the disease. Decreased values indicate a more severe stage or a relapse. In the majority of patients with gastric cancer DAP IV-positive ly were decreased. They were normal or increased in patients with peptic ulcer. The assessment of the number of DAP IV-positive ly is a simple method that provides information regarding the condition of patients with malignant lymphomas and gastric carcinoma. Neutrophilic leukocytes and their precursors, and to a lesser extent monocytes, are revealed when N-acetyl-Met-I-naphthyl ester (Ac-Met-N) is used as substrate. Membrane-bound lysosomal and cytosol proteinases were investigated together with disaccharidases in jejunal biopsies of patients with malabsorption syndrome. Activities of all enzymes were affected in patients with celiac disease. According to their impairment enzymes could be arranged: Lactase(L). trehalase (T), brush border endopeptidase (BBEP), gamma-glutamyl transferase (GGT), DAP IV, enzyme(s) cleaving Ac-Mer-N, aminopeptidase A, cytosol peptidases and aminopeptidase M. In the propria, DAP IV is decreased or absent, while GGT and, particularly, DAP II are increased. After a gluten-free diet, activities are restored in a reverse order. BBEP and GGT are useful as auxiliary parameters in the assessment of the damage or differentiation degree of enterocytes. DAP IV is a sensitive indicator of the involvement of the propria.
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PMID:Proteinases in pathology. Usefulness of histochemical methods. 701 84

To clarify the role of cathepsin B in tumor invasion, the enzyme was visualized in tissue frozen sections of the subcutaneously growing rabbit V2 carcinoma. Localization of cathepsin B was achieved by immunofluorescent staining and by enzyme histochemistry. For the former approach, a sheep antiserum was raised against purified cathepsin B from rabbit liver. The antibodies, isolated by immunoadsorption, reacted monospecifically with rabbit liver cathepsin B in Ouchterlony double diffusion and in immunoelectrophoresis. In the enzyme histochemical assay, Z-Ala-Arg-Arg-methoxynaphtylamide was used as fluorogenic substrate and nitrosalicylaldehyde as coupling agent. With both methods, cathepsin B was found to be localized within fibroblasts and leukocytes assembled at the tumor invasion front. In addition, immunofluorescent staining demonstrated the occurrence of the enzyme in the extracellular matrix surrounding tumor cell clusters. Carcinoma cells always remained unstained. The conclusion is drawn that cathepsin B is chiefly produced by host cells which are stimulated to increase synthesis and to release the enzyme under the influence of the tumor. A dual function can be ascribed to cathepsin B concentrated in the vicinity of the tumor: it operates intracellularly (in host cells) through degradation of endocytosed protein and extracellularly through activation of collagenase. The resulting lytic action on host structures appears to be a prerequisite for local spread of the V2 carcinoma.
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PMID:Histochemical localization of cathepsin B at the invasion front of the rabbit V2 carcinoma. 703 59

Diazomethyl ketone and chloromethyl ketone analogues prepared from N-tosyl amino acids have been synthesized and tested for antitumor activity in Ehrlich ascites carcinoma and P-388 lymphocytic leukemia screens in mice. The N-tosyl chloromethyl ketone analogues prepared from glycine, L-alanine, beta-alanine, L-valine, and 6-(N-tosyl-amino)caproic acid were the most potent antineoplastic agents in the Ehrlich ascites carcinoma screen. The N-tosyl diazomethyl ketone analogues synthesized from glycine, L-leucine, and L-proline were the most active of this series in the Ehrlich ascites screen, along with 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine and the diazomethyl ketone analogues prepared from 6-(N-tosylamino)caproic acid. In the P-388 lymphocytic leukemia screen, the N-tosyl chloromethyl ketone prepared from glycine and the compound 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine were the most active.
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PMID:Antitumor agents: diazomethyl ketone and chloromethyl ketone analogues prepared from N-tosyl amino acids. 736 42

One hundred ten primary hepatic neoplasms, excluding hematopoietic and vascular tumors, were diagnosed in 12,245 canine necropsies. Included were 55 hepatocellular carcinomas, 24 bile duct carcinomas, 2 combined hepatocellular and cholangiocarcinomas, 15 carcinoids and 14 sarcomas. A majority of the dogs with hepatocellular carcinoma (80%), bile duct carcinoma (65%) and sarcoma (61%) were 10 years old or older; 71% of the dogs with carcinoid were under 10 years old. Hepatocellular carcinoma and sarcoma occurred more often in males, bile duct carcinoma in females, and no sex predisposition was found in dogs with carcinoid. All dogs had hematologic and biochemical abnormalities relating to liver function. The aspartate amino transferase/alanine amino transferase ratio was less than one in cases of hepatocellular carcinoma and bile duct carcinoma, and more than one in cases of carcinoid and sarcoma. A massive lesion in one of the liver lobes was the most common gross morphologic feature in cases of hepatocellular carcinomoa and bile duct carcinoma, with the left lateral lobe affected most often. In cases of carcinoid, most of the lesions were diffuse. The most common sites of metastases were lymph nodes and lungs for hepatocellular carcinoma and bile duct carcinoma, lymph nodes and peritoneum for carcinoid, and spleen for sarcoma.
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PMID:Canine hepatic neoplasms: a clinicopathologic study. 740 66

Inhibition studies were carried out to study possible cross-reactivity between a peptide fragment of the Epstein-Barr virus nuclear antigen, EBNA-1, and keratin/collagen. The 20-amino acid peptide (pAG), derived from a glycine-alanine repeat region of EBNA-1, uniquely makes up about one-third of the viral protein and is a dominant IgA antigenic epitope in patients with nasopharyngeal carcinoma (NPC). A small percentage of normal human sera (NHS) also binds pAG and this reactivity is examined in this study. Ten percent (2/20) and 13.4% (2/15) of IgA-pAG-positive NPC sera and NHS, respectively, were significantly inhibited by keratin in a competitive ELISA system. Conversely, 31.6% (6/19) and 30.8% (4/13) of IgA-keratin-positive NPC sera and NHS, respectively, were significantly inhibited by pAG. This indicated minimum cross-reactivity between IgA serum antibodies to EBNA-1 and keratin. Using collagen as inhibitor, none of 18 and only 2/13 IgA-pAG-positive NPC sera and NHS, respectively, were inhibited. In the collagen ELISA system, only 2/19 (10.5%) and 4/25 (16%) of IgA-collagen-positive NPC sera and NHS, respectively, were inhibited with pAG. Therefore, cross-reactivity with collagen was also low. IgA-pAG-positive NHS may therefore not be a false positive phenomenon, but whether it may represent an early serological profile related to NPC carcinogenesis remains to be determined.
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PMID:Serum IgA cross-reactivity between glycine-alanine repeat sequence of EBNA-1 and keratin or collagen in nasopharyngeal carcinoma. 751 12

By moving chloride into epithelial cells, the Na-K-Cl cotransporter aids transcellular movement of chloride across both secretory and absorptive epithelia. Using cDNA probes from the recently identified elasmobranch secretory Na-K-Cl cotransporter (sNKCC1) (Xu, J. C., Lytle, C. Zhu, T. T., Payne, J. A., Benz, E., and Forbush, B., III (1994) Proc. Natl. Acad. Sci. 91, 2201-2205), we have identified the human homologue. By screening cDNA libraries of a human colonic carcinoma line, T84 cell, we identified a sequence of 4115 bases from overlapping clones. The deduced protein is 1212 amino acids in length, and analysis of the primary structure indicates 12 transmembrane segments. The primary structure is 74% identical to sNKCC1, 91% identical to a mouse Na-K-Cl cotransporter (mNKCC1), 58% identical to rabbit and rat renal Na-K-Cl cotransporters (NKCC2), and 43% identical to the thiazide-sensitive Na-Cl cotransporters from flounder urinary bladder and rat kidney. Similar to sNKCC1 and mNKCC1, the 5'-end of the human colonic cotransporter is rich in G + C content. Interestingly, a triple repeat (GCG)7 occurs within the 5'-coding region and contributes to a large alanine repeat (Ala15). Two sites for N-linked glycosylation are predicted on an extracellular loop between putative transmembrane segments 7 and 8. A single potential site for phosphorylation by protein kinase A is present in the predicted cytoplasmic C-terminal domain. Northern blot analysis revealed a 7.4-7.5-kilobase transcript in T84 cells and shark rectal gland and a approximately 7.2-kilobase transcript in mammalian colon, kidney, lung, and stomach. Metaphase spreads from lymphocytes were probed with biotin-labeled cDNA and avidin fluorescein (the cotransporter gene was localized to human chromosome 5 at position 5q23.3). Human embryonic kidney cells stably transfected with the full-length cDNA expressed a approximately 170-kDa protein recognized by anti-cotransporter antibodies. Following treatment with N-glycosidase F, the molecular mass of the expressed protein was similar to that predicted for the core protein from the cDNA sequence (132-kDa) and identical to that of deglycosylated T84 cotransporter (approximately 135-kDa). The stably transfected cells exhibited a approximately 15-fold greater bumetanide-sensitive 86Rb influx than control cells, and this flux required external sodium and chloride. Flux kinetics were consistent with an electroneutral cotransport of 1Na:1K:2Cl. Preincubation in chloride-free media was necessary to activate fully the expressed cotransporter, suggesting a [Cl]-dependent regulatory mechanism.
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PMID:Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon. 762 5

We have increased up to 65-fold the avidity of BR96, a mAb recognizing Lewis Y (Le(y))-related Ags expressed on the surface of many human carcinomas. Libraries of mutations in the complementarity-determining regions (CDRs) of BR96 were constructed in an M13 phage Fab expression vector by codon-based mutagenesis, a method that efficiently introduces large numbers and potentially all combinations of amino acid substitutions. Two mutants that improved the affinity of BR96 to tumor Ag were identified by screening the libraries on carcinoma cell lines. One mutant, M1, at position 97 (Asp to Ala) in CDR3 of the heavy chain, resulted in an 8- to 10-fold improvement in Ag binding, as assessed by ELISA. A second mutant, M2, at position 53 (Gly to Asp) in CDR2 of VH increased binding three- to fivefold. When these mutations were combined, the resulting Fab M3 was improved approximately 30-fold. An additional library was constructed in CDR1 of M1. M4, a mutation with three amino acid substitutions in CDR1, was isolated by screening the library with an enzyme conjugate of synthetic Le(y) tetrasaccharide (sLe(y)). This mutant improved BR96 Fab affinity to sLe(y) an estimated 15- to 20-fold by ELISA, and 14-fold as measured by surface plasmon resonance. The M4 IgG had 65-fold improved avidity to sLe(y) relative to the BR96 IgG. The mutants will be useful for comparison of the efficacy of Abs with different affinities for delivery of cytotoxic agents to tumor cells.
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PMID:Affinity maturation of the BR96 anti-carcinoma antibody by codon-based mutagenesis. 763 50

Mitochondrial-inner-membrane vesicles, isolated from Ehrlich ascites carcinoma cells by titration with detergents, accumulated L-glutamine by a very efficient transport system. The vesicles lack any phosphate-activated glutaminase activity, allowing measurement of transport rates without interference by L-glutamine metabolism. The time course of the transport was linear for the first 60 s, reaching a steady state after 120 min. L-Glutamine transport showed co-operativity, with a Hill coefficient of 2.2; the kinetic parameters S0.5 and Vmax had values of 5 mM and 26 nmol/30 s per mg of protein respectively. The pH-dependence curve showed a bell shape, with a pH optimum about 8.0. The uptake of L-glutamine was not affected by the presence of a 50-fold molar excess of D-glutamine, L-cysteine, L-histidine, L-alanine, L-serine and L-leucine, whereas L-glutamate behaved as a poor inhibitor. The structural analogue L-glutamate gamma-hydroxamate (5mM) inhibited the net uptake by 68%; interestingly, other analogues (6-diazo-5-oxo-L-norleucine, acivicin and L-glutamate gamma-hydrazide) were ineffective. The impermeant thiol reagent p-chloromercuriphenylsulphonic acid (0.5mM) completely abolished the mitochondrial L-glutamine uptake; in contrast, other thiol reagents (mersalyl and N-ethylmaleimide) did not significantly affect the transport. These data confirm the existence of a specific transport system with high capacity for L-glutamine in the mitochondrial inner membrane, a step preceding the highly operative glutaminolysis in tumour cells.
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PMID:Glutamine transport by vesicles isolated from tumour-cell mitochondrial inner membrane. 777 51

We report the purification of a protease from tumor cells undergoing apoptosis that is involved in activating DNA fragmentation. Initial studies revealed that two inhibitors of serine proteases, N-1-tosylamide-2-phenylethylchloromethyl ketone and carbobenzoxy-Ala-Ala-borophe (DK120), suppressed tumor necrosis factor or ultraviolet (UV) light-induced DNA fragmentation in the U937 histiocytic lymphoma as well as UV light-induced DNA fragmentation in the BT-20 breast carcinoma, HL-60 myelocytic leukemia, and 3T3 fibroblasts. The protease was purified by affinity chromatography with DK120 as ligand and showed high activity on a synthetic substrate preferred by elastase-like enzymes (Ala-Ala-Pro-Val p-nitroanilide), but was inactive on the trypsin substrate, N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester, or the chymotrypsin substrate, Ala-Ala-Pro-Phe p-nitroanilide. The activity of the DK120-binding protease purified from U937 cells undergoing apoptosis was increased approximately 10-fold over that recovered from normal cells. Further purification to homogeneity by heparin-Sepharose affinity chromatography followed by reverse phase high-performance liquid chromatography revealed a single band of 24 kD on a silver-stained sodium dodecyl sulfate gel. In addition to protease activity, the purified enzyme induced DNA fragmentation into multiples of 180 basepairs in isolated U937 nuclei. These findings suggest the 24-kD protease is a novel enzyme that activates DNA fragmentation in U937 cells undergoing apoptosis.
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PMID:Purification of a 24-kD protease from apoptotic tumor cells that activates DNA fragmentation. 796 87

Direct sequencing using Taq enzyme was established for determination of point mutation of K-ras gene at codon 12 in 9 wax samples of pancreatic carcinoma (PC) and 1 of islet cell tumor. Point mutation occurred in 5 of 9 samples of PC and manifested two types of mutation, CCA-->CGA in 4 and CCA-->CAA in 1. The changes of amino acid included changes of glycine to alanine and glycine to valine. The causes of mutation frequency and the content differed from that of foreign reports were analysed in addition to the significance of determining point mutation of K-ras gene at codon 12.
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PMID:[Point mutation of K-ras gene in pancreatic carcinoma]. 806 25


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