alpha-chymotrypsin and Neoplasms

Noninvasive monitoring of chymotrypsin-like (ChT-L) activity of proteasomes is of great significance for the diagnosis and prognosis of various cancers. However, commercially available proteasome probes usually lack adequate cancer-cell selectivity. To noninvasively monitor ChT-L activity of proteasomes in living cells, we rationally designed a cascade-activated AIEgen-peptide probe (abbreviated as TPE-1p), which self-assembled in aqueous solution to exhibit bright fluorescence in response to sequential treatment of alkaline phosphatase (ALP) and ChT-L. Transmission electron microscopy, enzymatic kinetics, and in vitro fluorescence experiments validated that TPE-1p was efficiently dephosphorylated by ALP to generate TPE-1, which was recognized by ChT-L in the proteasome, and transformed to form nanofibers with strong fluorescence signals. Cell imaging experiments revealed that bright blue fluorescence was observed in TPE-1p-treated HeLa cells, whereas NIH3T3 and HepG2 cells showed less fluorescence at the same condition. The enhanced fluorescence signals in HeLa cells were attributed to the high activities of endogenous ALP and ChT-L. Moreover, TPE-1p was utilized to noninvasively assess the inhibition efficiency of a ChT-L inhibitor (bortezomib, abbreviated as Btz) in HeLa cells. Significant correlation was found between the fluorescence signals of TPE and the viabilities of Btz-treated cells in concentration ranges from 0 to 1 μM, indicating that TPE-1p could be employed to predict the activity of ChT-L inhibitors. The design of the cascade-activated AIEgen-peptide probe provides a viable approach for noninvasively monitoring the ChT-L activity of proteasomes in living cells, which facilitates high-throughput screening of ChT-L inhibitors in cancer therapy.

Topics: Alkaline Phosphatase; Animals; Chymotrypsin; Fluorescent Dyes; HeLa Cells; Humans; Mice; Neoplasms; NIH 3T3 Cells; Peptides; Proteasome Endopeptidase Complex

Topics: Chymotrypsin; Chymotrypsinogen; Humans; Neoplasms; Trypsin; Trypsinogen

Spirulina platensis is an excellent source of proteins (>60%) that can be hydrolyzed into bioactive peptides.. In this study, whole proteins of Spirulina platensis were extracted and hydrolyzed using three gastrointestinal endopeptidases (pepsin, trypsin and chymotrypsin). Subsequently, gel filtration chromatography was employed to separate hydrolysates, and four fractions (Tr1-Tr4) were obtained. Among them, Tr2 showed the strongest anti-proliferation activities on three cancer cells (MCF-7, HepG-2 and SGC-7901), with IC. Taken together, these peptides possessed anti-proliferation activities on cancer cells and low cytotoxicity on normal cells, suggesting that they might serve as a natural anticancer agent for nutraceutical and pharmaceutical industries. © 2016 Society of Chemical Industry.

Topics: Algal Proteins; Amino Acid Sequence; Anticarcinogenic Agents; Bacterial Proteins; Cell Line; Cell Line, Tumor; Cell Proliferation; China; Chymotrypsin; Colonic Neoplasms; Dietary Supplements; Drug Discovery; Hepatocytes; Humans; Molecular Weight; Neoplasms; Oligopeptides; Pepsin A; Peptide Fragments; Protein Hydrolysates; Spirulina; Trypsin

In this study, 22 new betulinic acid (BA) derivatives were synthesized and tested for their inhibition of the chymotrypsin-like activity of 20S proteasome. From the SAR study, we concluded that the C-3 and C-30 positions are the pharmacophores for increasing the proteasome inhibition effects, and larger lipophilic or aromatic side chains are favored at these positions. Among the BA derivatives tested, compounds 13, 20, and 21 showed the best proteasome inhibition activity with IC(50) values of 1.42, 1.56, and 1.80 μM, respectively, which are three to fourfold more potent than the proteasome inhibition controls LLM-F and lactacystin.

Topics: Antineoplastic Agents; Betulinic Acid; Chymotrypsin; Cysteine Proteinase Inhibitors; Drug Design; Inflammation; Molecular Structure; Molecular Targeted Therapy; Neoplasms; Pentacyclic Triterpenes; Proteasome Inhibitors; Signal Transduction; Structure-Activity Relationship; Triterpenes

The ubiquitin-proteasome pathway has an important role in regulating apoptosis and the cell cycle. The function of proteasomes is mediated by three main catalytic activities: (1) chymotrypsin-like (CT-L), (2) trypsin-like (T-L), and (3) peptidylglutamyl peptide hydrolyzing (PGPH). Recently, proteasome inhibitors have been revealed to have an antitumor effect, and have been used to treat cancers such as multiple myeloma. Previous studies have reported that some flavonoids can inhibit proteasome activity in tumor cells. To further investigate the proteasome-inhibitory mechanism of flavonoids, we examined the effects of the plant flavonoids apigenin, chrysin, and luteolin on the three individual catalytic activities in various cancer cell lines. Using fluorogenic substrates specific for proteasome catalytic subunits, we demonstrated the subunit specificity of each flavonoid. Addition of apigenin, chrysin and luteolin inhibited CT-L and T-L catalytic activities in a dose-dependent manner, whereas their effect on PGPH catalytic activity was weak. Our study suggested that these flavonoids have a specific role in inhibition of CT-L and T-L proteasome catalytic activities.

Topics: Antineoplastic Agents, Phytogenic; Apigenin; Cell Line, Tumor; Chymotrypsin; Dose-Response Relationship, Drug; Flavonoids; Humans; Hydrolysis; Luteolin; Neoplasms; Peptides; Plant Extracts; Proteasome Endopeptidase Complex; Trypsin; Ubiquitin

A novel linker system based on 3-aminoxypropionate was designed and evaluated for drug release using proteolysis as an activation trigger followed by intramolecular cyclization. The hydroxylamine moiety present in the linker system enabled faster release of the parent drug from the linker-drug conjugate at lower pH as compared to an aliphatic amine moiety. Introduction of two methyl groups strategically at the alpha position to the carboxylate in the linker further improved the rate of cyclization by nearly 2-fold. The 3-aminoxypropionate linker was successfully applied to a model prodrug for protease activation using alpha-chymotrypsin as the activating enzyme; the activation of the model prodrug bearing the 3-aminoxypropionate linker was 136 times faster than the corresponding model prodrug bearing an amine linker.

Topics: Antineoplastic Agents; Chemistry, Organic; Chemistry, Pharmaceutical; Chymotrypsin; Cyclization; Drug Design; Humans; Hydrogen-Ion Concentration; Hydroxylamine; Kinetics; Models, Chemical; Neoplasms; Prodrugs; Propionates

Numerous proteins controlling cell cycle progression, apoptosis and angiogenesis are degraded by the ubiquitin/proteasome system, which has become the subject for intense investigations for cancer therapeutics. Therefore, we used in silico and experimental approaches to screen compounds from the NCI chemical libraries for inhibitors against the chymotrypsin-like (CT-L) activity of the proteasome and discovered PI-083. Molecular docking indicates that PI-083 interacts with the Thr21, Gly47 and Ala49 residues of the beta5 subunit and Asp114 of the beta6 subunit of the proteasome. PI-083 inhibits CT-L activity and cell proliferation and induces apoptosis selectively in cancer cells (ovarian T80-Hras, pancreatic C7-Kras and breast MCF-7) as compared to their normal/immortalized counterparts (T80, C7 and MCF-10A, respectively). In contrast, Bortezomib, the only proteasome inhibitor approved by the Food and Drug Administration (FDA), did not exhibit this selectivity for cancer over non-transformed cells. In addition, in all cancer cells tested, including Multiple Myeloma (MM), breast, pancreatic, ovarian, lung, prostate cancer cell lines as well as fresh MM cells from patients, PI-083 required less time than Bortezomib to induce its antitumor effects. Furthermore, in nude mouse xenografts in vivo, PI-083, but not Bortezomib, suppressed the growth of human breast and lung tumors. Finally, following in vivo treatment of mice, PI-083 inhibited tumor, but not hepatic liver CT-L activity, whereas Bortezomib inhibited both tumor and liver CT-L activities. These results suggest that PI-083 is more selective for cancer cells and may have broader antitumor activity and therefore warrants further advanced preclinical studies.

Topics: Animals; Anthracyclines; Antineoplastic Agents; Boronic Acids; Bortezomib; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chymotrypsin; Cyclin-Dependent Kinase Inhibitor p27; Drug Discovery; Humans; Inhibitory Concentration 50; Intracellular Signaling Peptides and Proteins; Mice; Mice, Nude; Neoplasms; Proteasome Inhibitors; Protein Conformation; Pyrazines; Serine Proteinase Inhibitors; Small Molecule Libraries; Xenograft Model Antitumor Assays

In the early 20th century, advocacy of the enzyme therapy of cancer was primarily the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a determined effort to establish this mode of therapy, especially in the years 1905 to 1911. Despite a brief flowering of international interest, Beard's efforts came to naught. During the 20th century, there was a succession of American researchers who continued to investigate this topic. This included Marshall William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central Europe, India, and other parts of the globe, the use of pancreatic enzymes as an adjuvant treatment for cancer has become a fairly routine practice, at least among those doctors who utilize complementary and alternative medicine (CAM). It is also a well-established method for reducing inflammation and mitigating the adverse effects of cytotoxic treatment.

Topics: Chymotrypsin; Complementary Therapies; Drug Combinations; Enzyme Therapy; Enzymes; Europe; History, 20th Century; History, 21st Century; Humans; Hydrolases; India; Neoplasms; Papain; Rutin; Tissue Extracts; Trophoblasts; Trypsin; United States

The supporting role of proteases in tumor progression and invasion is well known; however, the use of proteases as therapeutic agents has also been demonstrated. In this article, the authors report on the differential effects of exogenous serine proteases on the motility of tumor and normal cells. The treatment of normal and tumor cells with a single dose of pancreatic serine proteases, trypsin (TR) and chymotrypsin (CH), leads to a concentration-dependent response by cells, first accelerating and then slowing mobility. Tumor cells are 10 to 20 times more sensitive to exogenous TR/CH, suggesting that a single dose of proteases may cause discordant movements of normal and tumor cells within the tumor environment. The inhibitory effects of TR on cell motility are contradicted by thrombin (TH), particularly in the regulation of normal cells' migration. The purpose of this investigation was to ascertain the role of protease-activated receptors (PARs) in terms of normal and tumor cell motility. Duplicate treatments with proteases resulted in diminished mobility of both normal and tumor cells. Repeated application of TR and TH in 1-hour treatment intervals initially desensitizes cell surface PARs. However, cell surface PARs reappear regardless of subsequent protease treatments in both normal and tumor cells. The resensitization process is retarded in tumor cells when compared with normal cells. This is evidenced by lower expression of PARs as well as by their relocalization at the tumor cell surfaces. Under these conditions, normal cells remain responsive to exogenous proteases in terms of cell motility. Exogenous proteases do not modulate motility of repeatedly stimulated tumor cells, and consequently, the migration of tumor cells appears disconnected from the PAR signaling pathways. The use of activating peptides in lieu of the cognate proteases for a given PAR system indicated that proteases may act through additional targets not regulated by PAR signaling. We hypothesize that the divergent migration patterns of normal and tumor cells due to exposure to proteases is in part mediated by PARs. Thus, treatment with exogenous proteases may cause rearrangement of the tumor and stromal cells within the tumor microenvironment. Such topographical effects may lead to the inhibition of tumor progression and metastasis development.

Topics: Animals; Cattle; Cell Line; Cell Line, Tumor; Cell Movement; Chymotrypsin; Dogs; Enzyme Precursors; Gene Expression; Humans; Neoplasms; Oligopeptides; Peptide Fragments; Rats; Receptor, PAR-1; Receptor, PAR-2; Serine Endopeptidases; Thrombin; Trypsin

Withaferin A (WA) is a steroidal lactone purified from medicinal plant "Indian Winter Cherry" that is widely researched for its variety of properties, including antitumor effects. However, the primary molecular target of WA is unknown. By chemical structure analysis, we hypothesized that Withaferin A might be a natural proteasome inhibitor. Computational modeling studies consistently predict that C1 and C24 of WA are highly susceptible toward a nucleophilic attack by the hydroxyl group of N-terminal threonine of the proteasomal chymotrypsin subunit beta5. Furthermore, WA potently inhibits the chymotrypsin-like activity of a purified rabbit 20S proteasome (IC50=4.5 microM) and 26S proteasome in human prostate cancer cultures (at 5-10 microM) and xenografts (4-8 mg/kg/day). Inhibition of prostate tumor cellular proteasome activity in cultures and in vivo by WA results in accumulation of ubiquitinated proteins and three proteasome target proteins (Bax, p27, and IkappaB-alpha) accompanied by androgen receptor protein suppression (in androgen-dependent LNCaP cells) and apoptosis induction. Treatment of WA under conditions of the aromatic ketone reduction, or reduced form of Celastrol, had significantly decreased the proteasome-inhibitory and apoptosis-inducing activities. Treatment of human prostate PC-3 xenografts with WA for 24 days resulted in 70% inhibition of tumor growth in nude mice, associated with 56% inhibition of the tumor tissue proteasomal chymotrypsinlike activity. Our results demonstrate that the tumor proteasome beta5 subunit is the primary target of WA, and inhibition of the proteasomal chymotrypsin-like activity by WA in vivo is responsible for, or contributes to, the antitumor effect of this ancient medicinal compound.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Chymotrypsin; Ergosterol; Humans; Male; Mice; Mice, Nude; Models, Molecular; Neoplasms; Plants, Medicinal; Prostatic Neoplasms; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Rabbits; Structure-Activity Relationship; Transplantation, Heterologous; Withanolides

A growth-inhibiting activity was identified in supernatants of the neoplastic V79 Chinese hamster cell line based on its ability to inhibit the proliferation of the same cell line. The partially purified activity, provisionally termed "growth inhibiting factor" (GIF) activity, inhibited the growth of a wide variety of human tumor cells, but not various normal human fibroblasts. This species-nonspecific activity was reversible, saturable, and highly potent in tumorigenic cell lines, and was noted in both monolayer culture and in soft agar. The inhibitory activity of GIF was also exhibited in a chemically defined serum-free medium supplemented with insulin and transferrin. GIF activity was stable to acid, heat, trypsin, and dithiothreitol but sensitive to alpha-chymotrypsin. The pattern of growth modulation by GIF on V79 cells was apparently different from those exhibited by bifunctional peptides such as transforming growth factor-beta, tumor necrosis factor-alpha, and interleukin-1-alpha. In addition, GIF activity cannot be ascribed to these cytokines based on the physicochemical and immunologic properties. Although GIF has yet to be purified to homogeneity, these data suggest that GIF might be a novel growth regulator which has a critical role in regulating growth of V79 cells. The growth modulation of tumor cells by this tumor-derived growth inhibiting activity suggested the presence of an autocrine growth regulatory mechanism even in tumor cells.

Topics: Animals; Cell Division; Cell Line; Chymotrypsin; Cricetinae; Cricetulus; Culture Media; Dose-Response Relationship, Drug; Fibroblasts; Growth Inhibitors; Hot Temperature; Humans; Interleukin-1; Neoplasms; Transforming Growth Factor beta; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Serine proteases cause aggregation of the rat ascites tumor cell lines AH-130, AH-109A and YS in vitro, and the tumor cell aggregates are dissolved by treatment with DNase I. We previously demonstrated that these events played a critical role in the augmentation or reduction of experimental blood-borne metastasis of these cell lines. In the present study, the ultrastructural features of this protease-dependent aggregation were analysed. Transmission and scanning electron microscopy revealed that after the protease treatment each tumor cell was surrounded by a thin membranous (sleeve-like) structure. This sleeve-like structure was stained with ruthenium red to an intensity similar to the cell surface of the control. Adjacent cells became attached to each other with microvilli via this fine structure. Immuno-electron microscopy revealed DNA antigen as dense patches on the sleeve-like structure or as faint and diffuse deposits on the outer surface of the cells by indirect immunoperoxidase staining using an anti-DNA monoclonal antibody. Both the sleeve-like structure and immunopositive deposits disappeared after treatment with DNase I. Neither cell viability nor the normal ultrastructure of their organelles was influenced by the enzyme treatment. These results indicate that serine protease-induced tumor cell aggregation is due to cellular contact via the sleeve-like structure, which probably originates from the cell surface glycocalyx in association with DNA molecules of unknown origin.

Topics: Animals; Cell Aggregation; Chymotrypsin; Deoxyribonuclease I; DNA; Female; Glycoproteins; Hyaluronoglucosaminidase; Microscopy, Electron; Microscopy, Electron, Scanning; Microscopy, Immunoelectron; Neoplasms; Pancreatic Elastase; Polysaccharides; Rats; Serine Endopeptidases; Tumor Cells, Cultured

A large body of experimental work has revealed that protease inhibitors (PI) are highly effective suppressors of carcinogenesis. Little is known about the level of PI activity in the diet of the US population. In the present study, we assayed the levels of PI activity in dietary samples from 31 free-living subjects who saved duplicate portions of all foods consumed over two 24-hour periods, six months apart. The majority of samples (90%) contained detectable PI activity; 82% contained trypsin inhibitory activity; 61% contained chymotrypsin inhibitory activity. Of those samples containing chymotrypsin inhibitory activity, 87% also contained trypsin inhibitory activity. The median concentration of soluble chymotrypsin inhibitory activity present in these samples was 6.5 micrograms/g food (range 0-150 micrograms/g food), whereas the median concentration of soluble trypsin inhibitory activity was 14.5 micrograms/g food (range 0-465 micrograms/g food). We conclude that a) human diet samples contain both chymotrypsin and trypsin inhibitory activity, b) the levels of PI in some of these samples was similar to that found to be anticarcinogenic in animal studies, and c) due to the large within-subject variation in PI intake, assessment of long-term dietary intake in epidemiological studies will be necessary to accurately classify subjects according to PI intake.

Topics: Chymotrypsin; Food Analysis; Humans; Neoplasms; Protease Inhibitors; Risk Factors; Trypsin Inhibitors

Topics: Animals; Chymotrypsin; Drug and Narcotic Control; Drug Combinations; Humans; Neoplasms; Neoplasms, Experimental; Pancreatic Extracts; Papain; Peptide Hydrolases; Switzerland; Thymus Extracts; Tissue Extracts; Trypsin

The method described below combines an immunoreaction with Papanicolaou's stain on cytological smears. For the immunoreaction, the avidin-biotin-complex (ABC) method was used. The method was tested on various cytological material with the monoclonal antibody lu-5 and two polyclonal antibodies (anti-keratin and anti-chymotrypsin). Wet fixation of the smears with a modified Delaunay's solution is recommended. Drying of the material impairs immunoreactivity. The main advantages of the technique are the clear-cut permanent immunostaining and the preservation of the nuclear structure, permitting a combined immuncytological characterization of cellular products and conventional cyto-diagnosis.

Topics: Antibodies, Monoclonal; Avidin; Biotin; Chymotrypsin; Cytodiagnosis; Cytological Techniques; Epithelium; Histocytochemistry; Humans; Immunologic Techniques; Keratins; Neoplasms; Pleural Effusion; Staining and Labeling

The Baumgartner perfusion apparatus has been used for quantitative comparison of the interaction of platelets with subendothelium in the presence of microvesicles derived from SKNMC (human neuroblastoma) cells, which aggregate platelets by an adenosine diphosphate (ADP)-dependent mechanism, and U87MG (human glioblastoma) cells, which function by a thrombin-dependent mechanism. The derived microvesicles from each line were as effective as the intact cells in inducing thrombogenesis on both undigested and alpha-chymotrypsin-digested subendothelium. Thrombus size on digested vessels was greater than on undigested vessels by fivefold for SKNMC cells and microvesicles and by 20-fold for U87MG cells and sevenfold for U87MG microvesicles. The results show that microvesicles from both cell lines initiate interactions between platelets and subendothelium identical to those caused by intact tumor cells. The results also demonstrate that intact tumor cells in the circulation may not be necessary for the thromboembolic complications of malignancy.

Topics: Adenosine Diphosphate; Blood Platelets; Cell Line; Chymotrypsin; Humans; Microcirculation; Neoplasms; Perfusion; Platelet Aggregation; Thrombin; Time Factors

We submitted 83 consecutive patients with pleural effusion to routine clinical investigation; 57 were diagnosed as malignant, 18 as benign, and 8 were not diagnosed. Pleural fluid and serum were analysed for carcinoembryonic antigen (CEA), acid glycoprotein (AGP), antichymotrypsin (ACT), C-reactive protein (CRP), alpha 2-pregnancy associated glycoprotein (alpha 2-PAG) and ferritin. Multivariate discriminant analysis was performed on the results of the protein measurements. CEA and ACT values in serum and fluid were found to give a good discriminating function between the benign and malignant groups. The use of such an analysis, in a clinical context, is discussed.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; Analysis of Variance; C-Reactive Protein; Carcinoembryonic Antigen; Chymotrypsin; Evaluation Studies as Topic; Female; Ferritins; Humans; Immunodiffusion; Male; Middle Aged; Neoplasms; Orosomucoid; Pleural Effusion; Pregnancy-Associated Plasma Protein-A; Probability; Prospective Studies

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Carcinoembryonic Antigen; Chymotrypsin; Colonic Neoplasms; Female; Humans; Immunoenzyme Techniques; Male; Neoplasms; Rectal Neoplasms; Trypsin Inhibitors

Lysozyme and alpha 1-antichymotrypsin are useful in differentiation of histiocytic tumours. Both enzymes, however, also can be expressed in epithelial tissues. In contrast to lysozyme, alpha 1-antichymotrypsin is more often found to be positive in non-histiocytic neoplasias. In general, the activity of parent tissue is retained in tumour cells. In malignant melanoma and in single cases of other epithelial tumours an activity of alpha 1-antichymotrypsin was found which could not be demonstrated in normal parent tissue and which may find its explanation in a dedifferentiation of tumour cells.

Topics: alpha 1-Antichymotrypsin; Chymotrypsin; Epithelium; Histiocytes; Humans; Muramidase; Neoplasms

Topics: alpha 1-Antichymotrypsin; Chymotrypsin; Concanavalin A; Humans; Immunoelectrophoresis; Neoplasms

An alpha-macroglobulin (AMG) of similar size and proteinase-binding activity as those of human, alpha 2-macroglobulin was purified to homogeneity from mouse plasma. Even after additional purification steps, AMG still retains a growth-inhibitory activity and a more complex subunit structure than does human alpha 2-macroglobulin. AMG can inhibit the DNA synthesis of all types of murine tumor cells tested in vitro. This activity is cytostatic, dose dependent, and unaffected by the serum concentration in culture. Because this inhibitory activity is resistant to heat, pH 3, and methylamine, it is apparently unrelated to the proteinase-binding activity which is labile to all these treatments. Furthermore, in contrast to the proteinase-binding activity, the inhibitory activity can be partially removed from AMG by acid dialysis. Gel filtration of the dialysate yields two fractions (Mr 12,000 and 1,000 to 5,000) which potently inhibit murine tumor cells but stimulate both the B- and T-lymphocyte reactivities to mitogens in vitro. The growth-inhibitory activities in these fractions are resistant to digestions by chymotrypsin, RNase, and DNase. We conclude from this study that AMG does not inhibit tumor growth by virtue of its proteinase-binding activity; it may inhibit tumor cells via the small biomediators it carries.

Topics: alpha-Macroglobulins; Animals; Cell Line; Chromatography, Gel; Chymotrypsin; Deoxyribonucleases; Dialysis; DNA; Female; Growth Inhibitors; Humans; Lymphocyte Activation; Mice; Mice, Inbred Strains; Neoplasms; Protein Binding; Ribonucleases; Trypsin

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

Cancer-related urinary glycoprotein EDC1 inhibits the action of trypsin and chymotrypsin on casein and synthetic substrates. The amino acid and carbohydrate compositions of EDC1 are different from those reported for pregnancy-related urinary trypsin inhibitors.

Topics: Carboxypeptidases; Caseins; Chymotrypsin; Fibrinolysin; Glycoproteins; Humans; Leucyl Aminopeptidase; Neoplasms; Pancreatic Elastase; Pepsin A; Protein Binding; Tosyl Compounds; Trypsin Inhibitors; Tyrosine

BALB/c mouse 3T3 cells transformed by simian virus 40 (SV3T3), baby hamster kidney cells transformed by polyoma virus or Rous sarcoma virus, and a range of neoplastic human cell lines release material that inhibits the migration of macrophages and lymphocytes. Similar migration-inhibitory factor (MIF) activity was not detected in supernatants from cultures of untransformed 3T3 or baby hamster kidney cells and a variety of human diploid cell strains. Physico-chemical characterization of the MIF produced by SV3T3 and HeLa cells revealed substantial similarities with the MIF produced by mitogen-activated human peripheral lymphocytes. MIF released by tumor cells is inhibited by pancreatic and soybean trypsin inhibitors and by diisopropylfluorophosphate, indicating that it is a serine-protease. Comparison of MIF produced by SV3T3 cells with a serine-protease plasminogen activator released by the same cells indicated that the latter is more heat labile and has a more heterogenous elution profile after chromatography on Sephadex G-75. The possible role of MIF in causing proteolytic modification of the surface properties of tumor cells and in altering cell-mediated immune responses to neoplastic cells is discussed.

Topics: Animals; Avian Sarcoma Viruses; Cell Line; Cell Migration Inhibition; Cell Transformation, Neoplastic; Cell-Free System; Chymotrypsin; Cricetinae; Endopeptidases; HeLa Cells; Hot Temperature; Humans; Isoflurophate; Lymphocytes; Macrophage Migration-Inhibitory Factors; Macrophages; Mice; Mice, Inbred BALB C; Neoplasms; Polyomavirus; Serine; Simian virus 40; Trypsin Inhibitors

Topics: Animals; Antineoplastic Agents; Azirines; Carbamates; Chemotherapy, Cancer, Regional Perfusion; Chymotrypsin; Fibrinolytic Agents; Injections, Intramuscular; Injections, Intravenous; Neoplasm Metastasis; Neoplasms; Quinones; Rabbits

Topics: Ascitic Fluid; Chymotrypsin; Heart Failure; Humans; Liver Cirrhosis; Neoplasms; Pancreatitis; Pleural Effusion; Protease Inhibitors; Trypsin Inhibitors

Topics: Chymotrypsin; Cyclophosphamide; Humans; Neoplasms; Prognosis; Skin Tests

Topics: Animals; Bone Marrow; Cattle; Cell Line; Chymotrypsin; Clone Cells; Culture Techniques; Erythrocytes; HeLa Cells; Neoplasms; Neuraminic Acids; Neuraminidase; Papain; Peptide Hydrolases; Sternum; Trypsin

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Chymotrypsin; Dermatologic Agents; Female; Humans; Neoplasms; Pelvic Inflammatory Disease; Surgical Procedures, Operative; Trypsin

Topics: Chymotrypsin; Dermatologic Agents; Diuretics; Drug Therapy; Edema; Extremities; Humans; Neoplasms; Peptide Hydrolases

Topics: Chymotrypsin; Edema; Facial Neoplasms; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Laryngectomy; Lymph Node Excision; Neoplasms; Postoperative Complications; Radiosurgery

Topics: Acetone; Chloroform; Chymotrypsin; Enterovirus; Enterovirus B, Human; Ethers; Formaldehyde; Hemagglutination; Hemagglutination Inhibition Tests; Hemagglutination Tests; Neoplasms; Neoplasms, Experimental; Papain; Pharmacology; Phenols; Reoviridae; Tissue Culture Techniques; Trypsin

Topics: Animals; Chymotrypsin; Esterases; Lipase; Neoplasm Proteins; Neoplasms; Neoplasms, Experimental; Research; Tissue Culture Techniques

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

Topics: Chymotrypsin; Humans; Neoplasms; Protease Inhibitors; Serum

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

Topics: Chymotrypsin; Humans; Neoplasms; Protease Inhibitors; Trypsin

Topics: Chymotrypsin; Health; Humans; Neoplasms; Serologic Tests; Serum

Topics: Chymotrypsin; Humans; Neoplasms

Topics: Chymotrypsin; Hematologic Tests; Neoplasms

Topics: Biological Phenomena; Chymotrypsin; Hematologic Tests; Neoplasms; Physiological Phenomena