Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the ability of a soybean extract containing the Bowman-Birk protease inhibitor (BBI), referred to as BBI concentrate (BBIC), purified BBI (PBBI), and the chymotrypsin inhibitor from potatoes to suppress oral carcinogenesis in hamsters induced by 7,12-dimethyl-benz[a]anthracene (DMBA). Application of 1% solutions of BBIC and PBBI five times per week to DMBA-treated hamster cheek pouches were highly effective in suppressing oral carcinogenesis, whereas a 1% solution of the chymotrypsin inhibitor from potatoes did not lead to a significant suppression of carcinogenesis. BBIC and PBBI suppressed carcinogenesis at concentrations ranging from 1% to 0.01% and were equally effective when given as a 1% solution five times per week, three times per week, or once per week. A 1% solution of BBIC suppressed oral carcinogenesis when given at the following times during the assay period: 0-180, 0-90, 14-90, and 45-135 days. Thus, protease inhibitor treatment could be started as late as 45 days after the beginning of the carcinogen exposure and have an irreversible suppressive effect on the carcinogenic process.
Nutr Cancer 1993
PMID:Effects of various preparations of dietary protease inhibitors on oral carcinogenesis in hamsters induced by DMBA. 850 89

This study was initiated to clarify whether the main hydrolytic enzymes of the pancreas are activated or inactivated when secreted into the stomach of patients who had undergone a pylorus-preserving pancreaticoduodenectomy (PPPD) and were given a pancreaticogastrostomy (PG) for the reconstruction. Seventeen such patients, 15 cancer patients and two pancreatic patients, who underwent PPPD-PG reconstruction were postoperatively followed up for 3 or more years to investigate the influence of the gastric acid on the p-type amylase and lipase activity. Results revealed that when the pH was < 3.0, both the p-type amylase and the lipase secretion remained inactivated, but when the pH was > 3.1, the activity of both enzymes increased proportionately. The pancreatic enzyme activity in the small intestine was also investigated in seven patients, six cancer cases and one case of pancreatitis, given a PPPD-PG reconstruction, and it was found that the pancreatic enzyme activity in the small intestine increased after milk loading. Further, the fecal pancreatic enzyme activity was investigated in 17 patients given a PPPD-PG reconstruction. Results reveal that the fecal p-type amylase, lipase, and chymotrypsin activity amounted to 21, 27, and 31% of the respective values seen in 10 healthy volunteers. However, the fecal pancreatic enzyme activity levels did not differ significantly from the levels seen in 20 pancreaticoduodenectomy patients given a pancreaticojejunostomy reconstruction. In conclusion, it was found that the main hydrolytic enzymes of the pancreas are activated when the gastric acidity is over pH 3.1, which normally occurs after ingestion of a meal.
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PMID:Pancreatic enzyme activity after a pylorus-preserving pancreaticoduodenectomy reconstructed with pancreaticogastrostomy. 857 82

The mechanism of human bladder cancer cell invasion is not clear, but it appears that extracellular matrix components, such as fibronectin, may be involved. To investigate the role of fibronectin in tumor cell invasion and progression, we used an in vitro invasion assay to define the motility stimulating fragment of fibronectin for invasive human bladder cancer T24 cells. Using a modified Boyden chamber assay and purified fragments of fibronectin, we demonstrated that both the 120 kDa chymotrypsin generated fragment of fibronectin (containing the cell attachment RGD motif and additional sequences towards the carboxyl-terminal heparin binding domain), as well as the trypsin generated 60 kDa fragment of fibronectin (containing the carboxyl-terminal heparin binding domain and additional sequences towards the cell attachment RGD motif), were able to stimulate the migration of invasive human bladder cancer T24 cells. Control fragments containing only the amino-terminal gelatin binding region of fibronectin did not stimulate the motility of the human bladder cancer T24 cells. To determine the molecular mechanism in which these fragments may stimulate the migration of the T24 cells, we assayed for intracellular signal transduction pathway protein kinase C (PKC). We demonstrated that both the 120 kDa and the 60 kDa fragments were able to stimulate the activation of protein kinase C. Non-motility stimulating fragments of fibronectin were not able to activate protein kinase C. We conclude that the PKC signal transduction pathway may be involved in matrix mediated motility, and suggest that the inhibition of such pathway(s) may alter the malignant phenotype of human bladder cancer.
Cancer Lett 1996 Feb 27
PMID:Specific sequences of fibronectin activate the protein kinase C signal transduction pathway in invasive bladder cancer. 862 Apr 37

The tumour-associated epitope recognised by monoclonal antibody (MAb) 4D3 is expressed on a high m.w. mucin glycoprotein preparation known as small intestinal mucin antigen (SIMA). This epitope is detected in tissue from a high proportion of patients with colorectal cancer, and elevated levels occur in serum from a significant number of such patients, highlighting the potential clinical utility of MAb 4D3. In the present study, insight into the composition and structure of the carbohydrate epitope recognised by MAb 4D3 was gained following characterisation of 2 glycopeptides that co-purified with SIMA. Sequence analysis of 1 of these glycopeptides revealed that it was identical to the glycoprotein alpha-1-anti-chymotrypsin. This glycoprotein was subsequently deglycosylated to yield 5 forms corresponding to alpha-1-anti-chymotrypsin substituted with 4, 3, 2, 1 or no branched glycans. MAb 4D3 was reactive with each of the glycosylated forms, including the form carrying only 1 branched glycan, but did not react with fully deglycosylated alpha-1-anti-chymotrypsin. MAb 4D3 also reacted to different extents with ovine, bovine or porcine submaxillary mucins, each of which has a different amount of the O-linked sialylated disaccharide known as sialosyl Tn. Of these mucins, MAb 4D3 was most reactive with ovine submaxillary mucin, in which almost all of the carbohydrate chains are sialosyl Tn. Reactivity of MAb 4D3 towards isolated glycans, sialosyl Tn and related structures led to the conclusion that the preferred MAb 4D3 epitope involves the sialylated N-acetyl galactosamine disaccharide as well as an additional monosaccharide present on a neighbouring carbohydrate chain. Although the preferred epitope recognised by MAb 4D3 involves this sialylated disaccharide, the specificity of MAb 4D3 was different from that of other MAbs with a reported specificity for sialosyl Tn.
Int J Cancer 1996 May 29
PMID:Characterisation of the tumour-associated carbohydrate epitope recognised by monoclonal antibody 4D3. 864 26

Squamous cell carcinoma antigen (SCCA) has been used as a promising aid for the management of squamous cell carcinoma of various sites. Recently, SCCA gene has been demonstrated at the 18q21.3 locus, and the exon sequence of SCCA gene shows a close homology with inhibitory-type serpins. Actually, SCCA inhibits human chymotrypsin, papain, calpain 1, or cathepsin L. Since serpins are involved in the intercellular adhesion events, it is likely that SCCA takes some part in the malignant behavious of squamous cancer, e.g. invasion or metastasis. SCCA is also present in the spinous and granular compartments of the mature squamous epithelium. Southern blot analysis of the SCCA gene in several vertebrates reveals that it is present in most of the eutherian species, but not in the metatheria, bird, reptile, amphibian or teleost. Thus, SCCA appears to play important roles in the stratification or differentiation of the integument. The present paper describes the expression and function of SCCA, and discusses its possible role in the biological behavious of malignant and nonmalignant squamous cells.
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PMID:Expression and function of squamous cell carcinoma antigen. 869 35

The prostate specific antigen (PSA) level represents all of the immunoreactive serum PSA, either free or bound to alpha-1-anti-chymotrypsin. Isolated assay of free PSA has demonstrated a higher free PSA/total PSA ratio in cases of benign prostatic hyperplasia (BPH) than in cases of cancer, suggesting the possible use of this ratio in the detection of prostatic cancer when the PSA level is between 4 and 10 ng/mL. We retrospectively assayed free PSA in 64 cases of localized prostate cancer, 90 cases of BPH before transurethral resection and 59 healthy controls. By comparing the mean values of the 3 populations and the ROC curves, we confirmed the superiority of the free PSA/total PSA ratio over total PSA in the detection of prostatic cancer, but these results, established in a retrospectively constituted population, need to be confirmed by prospective epidemiological studies. Nevertheless, in routine urological practice, we propose that free PSA assay be performed in all men with a PSA level between 4 and 10 ng/mL and a normal prostate on digital rectal examination.
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PMID:[Clinical assessment of free serum prostate specific antigen (PSA)]. 876 91

Cryptophycin 1 is a new cytotoxic antimicrotubule agent with excellent antitumor activity. The methods of Sackett (Biochemistry, 34, 7010-7019, 1995), utilizing the selective and specific proteolysis of alpha- and beta-tubulin by trypsin and chymotrypsin, was used to identify the cryptophycin 1 binding site on tubulin. Occupancy of the colchicine or vinca binding sites causes changes in the structure of tubulin that can be detected by proteolysis with trypsin and chymotrypsin. The addition of cryptophycin 1 to tubulin causes changes in both the tryptic and chymotryptic cleavage of tubulin consistent with occupation of the vinca binding site and distinct from occupation of the colchicine binding site. The effects of cryptophycin 1 on the tryptic digests are identical to the effects seen with vinblastine and differ saliently from the effects of maytansine and rhizoxin, other agents known to bind to the vinca site. The data suggest that the binding site of cryptophycin 1 may overlap the vinca binding site on tubulin.
Cancer Lett 1996 Oct 01
PMID:Cryptophycin 1 binds to tubulin at a site distinct from the colchicine binding site and at a site that may overlap the vinca binding site. 891 66

Monoclonal antibodies were raised against prostate-specific antigen (PSA) by immunization with purified free PSA, i.e. not in complex with any protease inhibitor (F-PSA) and PSA in complex with alpha1-anti-chymotrypsin (PSA-ACT). Epitope mapping of PSA using the established monoclonal antibody revealed a complex pattern of independent and partly overlapping antigenic domains in the PSA molecule. Four independent antigenic domains and at least three partly overlapping domains were exposed both in F-PSA and in the PSA-ACT complex, while one antigenic domain was specific for F-PSA. The different domains contained both continuous and discontinuous epitopes. The combination of antibodies recognizing antigenic domains exposed both in F-PSA and PSA-ACT made it possible to develop several highly sensitive sandwich immunoassays for determination of total PSA, i.e. F-PSA + PSA-ACT, with the same molar response for F-PSA and PSA-ACT. Assays specific for F-PSA (cross-reactivity between F-PSA and PSA-ACT < 1%) were developed by the combination of antibodies recognizing epitopes exposed only in F-PSA and antibodies recognizing epitopes exposed both in F-PSA and PSA-ACT.
Br J Cancer 1997
PMID:Antigenic determinants of prostate-specific antigen (PSA) and development of assays specific for different forms of PSA. 906 97

Antibodies have been investigated as specific targeting agents for cancer diagnosis and therapy, to inactivate toxic substances including drugs and also as passive immunotherapy for neoplastic or infectious diseases. In most cases the antibodies were administered systemically by the intravenous route. More recently, however, there has been increasing interest in the oral administration of antibodies for localised treatment of infections or other conditions in the gastrointestinal tract. The normal physiological handling of ingested proteins is degradation by proteases in the stomach and intestine into small peptides or amino acids which are subsequently absorbed. Proteolytic enzymes involved in the degradation of orally administered immunoglobulins include pepsin, trypsin, chymotrypsin, carboxypeptidase and elastase. These enzymes initially degrade the antibodies to F(ab')2. Fab and Fc fragments. The F(ab')2 and Fab fragments, however, retain some of their neutralising activity locally in the gastrointestinal tract. Various approaches are possible to increase the stability of orally administered antibodies against proteolysis, including formulation in liposomes, coating with polymers and genetic engineering of resistant forms. The clinical application of orally administered antibodies includes the treatment and prevention of gastrointestinal infections caused by enteric pathogens such as rotavirus, Escherichia coli or Vibrio cholerae in susceptible individuals including those with immunodeficiency diseases and patients with bone marrow transplants. There is also a suggestion that such agents may be useful in preventing chemotherapy-induced gastrointestinal mucositis. Future opportunities for research include the design of oral dosage forms of antibodies which resist proteolysis and can deliver a greater fraction of immunoreactive antibody locally in the gastrointestinal tract for the treatment of infections or perhaps even to allow the absorption of antibodies for the treatment or prevention of systemic conditions.
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PMID:Oral delivery of antibodies. Future pharmacokinetic trends. 911 39

Sera from patients with a variety of cancers, including solid carcinomas, leukemias, and lymphomas, contain a ca. 33.5-kDa protein absent from sera of healthy volunteers or patients not diagnosed as having cancer. The protein exhibits an NADH oxidase activity inhibited by 8-methyl-N-vanillyl-6-noneamide (capsaicin). The activity and the protein are resistant to digestion by proteases (trypsin, chymotrypsin, proteinase K, subtilisin) and to heat. Following protease digestion to reduce the content of major serum proteins, the 33.5-kDa protein could be detected on Western blots of SDS-PAGE transferred to nitrocellulose membranes using polyclonal antisera to a corresponding partially purified 33.5-kDa protein shed into culture media conditioned by growth of HeLa cells. No corresponding protein was seen with control sera. The findings confirm the capsaicin-inhibited NADH oxidase activity of cancer sera as a circulating marker potentially specific to sera of cancer patients and identify a ca. 33.5-kDa protein resistant to proteases and heat as the source of the circulating capsaicin-inhibited NADH oxidase activity.
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PMID:A 33.5-kDa heat- and protease-resistant NADH oxidase inhibited by capsaicin from sera of cancer patients. 918 12


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