alpha-chymotrypsin and Lung-Neoplasms

Lung cancer is the most common cancer in the world accounting for 17.6% cancers worldwide. The AAR i n I ndian population varies f r om 0.98-15.55. The aim of t he present study was to analyze areduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and III B) using Wobe Mugos E and its evaluation using micronuclei as a cytogenetic marker. Micronuclei, which are cytoplasmic fragments of DNA, have been used as a biological dosimeter to assess DNA damage.. Fourty patients of locally advanced NSCLC were randomized into two study groups between 2001-2003. One group received neoadjuvant chemotherapy using Cisplatin and Etoposide. The other group received neoadjuvant chemotherapy using Cisplatin and Etoposide along with Wobe Mugos E which is a proteolytic enzyme preparation. A study of micronuclei frequency was done pre and post chemotherapy in both groups.. Thirty eight patients were available for final evaluation. Anemia was the most common hematological toxicity observed. Nausea and vomiting were the most common non -hematological toxicity seen. Wobe Mugos E was found to reduce the incidence of leucopenia (p = 0.005), nausea (p=0.004), vomiting (p= 0.003), sensory neuropathy (p = 0.032) and treatment related depression (p= 0.005). A reduction in micronuclei was seen in patients in patients on Wobe Mugos E. (p =0.01).. Neo-adjuvant chemotherapy related acute toxicity is a major problem in patients with advanced lung cancer. A reduction in micronuclei frequency shows Wobe Mugos E to be effective in reducing chemotherapy related acute toxicity.

Topics: Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Chymotrypsin; Drug Combinations; Female; Humans; India; Lung Neoplasms; Male; Micronuclei, Chromosome-Defective; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Papain; Trypsin

We analyzed the content of β-catenin fractions and activity and content of proteasomes in the tissues of patients with non-small cells lung cancer. The content of β-catenin fractions was elevated and proteasome-dependent proteolysis in the tumor tissue was enhanced in comparison with the corresponding unchanged lung tissue. A negative regression relationship of caspase-like activity of proteasomes and a positive correlation between the content of proteasomes and both fractions of β-catenin were found. We hypothesize that proteasomes are involved in the degradation of β-catenin due to caspase-like activity.

Topics: beta Catenin; Carcinoma, Non-Small-Cell Lung; Caspases; Chymotrypsin; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Proteasome Endopeptidase Complex; Wnt Signaling Pathway

Topics: Amino Acid Motifs; Animals; Anti-Infective Agents; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Chymotrypsin; Drug Screening Assays, Antitumor; Hemolytic Agents; Humans; Lung Neoplasms; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Ranidae; Trypsin Inhibitors

The first amphibian skin secretion-derived Bowman-Birk type chymotrypsin inhibitor is described here from the Asian green frog, Hylarana erythraea, and was identified by use of molecular cloning and tandem mass spectrometric amino acid sequencing. It was named Hylarana erythraea chymotrypsin inhibitor (HECI) and in addition to inhibition of chymotrypsin (Ki = 3.92 ± 0.35 μM), the peptide also inhibited the 20 S proteasome (Ki = 8.55 ± 1.84  μM). Additionally, an analogue of HECI, named K

Topics: Amino Acid Sequence; Animals; Biological Products; Cell Line, Tumor; Cell Proliferation; Chymotrypsin; Cloning, Molecular; Drug Screening Assays, Antitumor; Enzyme Assays; Erythrocytes; Hemolysis; Horses; Humans; Lung Neoplasms; Peptides; Proteasome Endopeptidase Complex; Ranidae; Sequence Analysis, Protein; Skin; Tandem Mass Spectrometry; Toxicity Tests; Trypsin Inhibitors

The aim of the present study was to investigate the effect of a mixture of proteolytic enzymes (comprising trypsin, chymotrypsin and papain) on the metastatic model of syngeneic melanoma B16.. 140 C57B16 mice were divided into two control and two "treated" groups. Control groups received saline rectally, twice a day starting 24 h after intracutaneous transplantation (C1) or from the time point of the primary B16 melanoma extirpation (C2), respectively. "Treated" groups were rectally administered a mixture of 0.2 mg trypsin, 0.5 mg papain, and 0.2 mg chymotrypsin twice daily starting 24 h after transplantation (E1) or after extirpation of the tumor (E2), respectively. Survival of mice and B16 melanoma generalization were observed for a period of 100 days. Immunological evaluation of B16 melanoma cells in the ascites was accomplished. CD44, CD54 and CD106 cells were measured by flow cytometry.. Administration of proteolytic enzymes to mice inhibited the growth of primary tumors, and tumor recurrences were less numerous. Importantly, metastasis was considerably curtailed both in the vicinity of the primary tumor and at distant locales. These findings correlated with a decreased expression of CD44 and CD54 molecules in tumors exposed to proteolytic enzymes in vivo.. Our data suggest that serine and cysteine proteinases suppress B16 melanoma, and restrict its metastatic dissemination in C57B16 mice.

Topics: Administration, Rectal; Animals; Antigens, Surface; Antineoplastic Agents; Cell Division; Chymotrypsin; Drug Combinations; Endopeptidases; Female; Hyaluronan Receptors; Immunoglobulins; Intercellular Adhesion Molecule-1; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Papain; Trypsin

The systemic enzymotherapy using Wobe-Mugos E in the combined treatment of 32 patients with pulmonary cancer and of 21 patients with malignant thymoma was applied. After the chemotherapy and radiotherapy conduction the reduction of the postoperative septic-purulent complications, the pneumofibrosis occurrence prophylaxis was noted.

Topics: Adjuvants, Immunologic; Chymotrypsin; Combined Modality Therapy; Drug Combinations; Humans; Lung Neoplasms; Pancreatic Extracts; Papain; Thymoma; Thymus Extracts; Thymus Neoplasms; Trypsin

Long-term rectal administration of enzyme mixture containing papain, trypsin and chymotrypsin in the same ratio as the preparation Wobe-Mugos E (Mucos Pharma, Germany) was evaluated for their antitumor effects in C57Bl6 inbred mice inoculated with Bl6 melanoma cells. 30% of animals in the test group (3 pcs) have been cured of cancer. In the rest of animals (70%) the survival time was prolonged by 58.3% compared to the control group (from average survival time of 24 days in control group to 38 days in the test group). Based on histological and immunohistochemical evaluation a faster process of metastasizing was found in control group than in the group treated with the polyenzyme preparation. In the case of melanoma Bl6 an antimetastatic effect of the preparation was thus proved.

Topics: Animals; Cell Division; Chymotrypsin; Drug Combinations; Immunohistochemistry; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Pancreatic Extracts; Papain; Thymus Extracts; Trypsin

This study examines the roles of peptides and nitric oxide (NO) as mediators of inhibitory nonadrenergic, noncholinergic (NANCi) neurons in human and guinea pig airways in vitro. Tissues were contracted with 0.3 microM methacholine (MCh) and relaxation studied before and after the addition of the peptidase alpha-chymotrypsin (alpha-CT) (2 U/ml) and NG-nitro-L-arginine methyl ester (L-NAME 0.1-1.1 mM), an inhibitor of NO synthase, the enzyme catalyzing the formation of NO. alpha-CT alone, in comparison to parallel time controls, inhibited control relaxation to electrical field stimulation (EFS) by 29.2 +/- 8.6% in guinea pig tracheae (n = 9), whereas a small augmentation of relaxation was observed in human bronchi (n = 7). L-NAME inhibited the NANCi response in both guinea pig tracheae and human bronchi: in guinea pig tracheae, maximal inhibition of the alpha-CT-insensitive relaxation was 59.3 +/- 11.5% (SE, P = 0.003) at low frequencies (4-16 Hz) and 28.6 +/- 8.9% (P = 0.08) at 32 Hz; in human bronchi, the maximal inhibition was 37.7 +/- 9.3% (P = 0.008) at 8 or 16 Hz, and 37.9 +/- 5.9% (P = 0.005) at 32 Hz. Inhibition was greater after repeated baseline EFS for 90 min before initiation of contraction with MCh and addition of L-NAME (59.8 +/- 13.9% after repeated baseline EFS, n = 4; vs. 34.9 +/- 6.2% without repeated baseline EFS, n = 9, P = 0.025). Relaxant responses to sodium nitroprusside, vasoactive intestinal peptide, and isoproterenol were not affected by L-NAME. L-Arginine (10 mM), a precursor of NO, partially reversed the effect of L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Bronchi; Chymotrypsin; Dose-Response Relationship, Drug; Electric Stimulation; Female; Guinea Pigs; Humans; In Vitro Techniques; Isoproterenol; Lung Neoplasms; Male; Methacholine Chloride; Middle Aged; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Neurons; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; Trachea; Vasoactive Intestinal Peptide

The conjugate of the Bowman-Birk inhibitor (BBI) with poly(D-lysine) (PDL-ss-BBI) has been suggested as a lung-targeted anti-carcinogenic agent. The authors demonstrate that PDL-ss-BBI, given i.p., reduces the tumor number in the lungs of 3-methylcholanthrene treated mice (61-71% compared to control group) in a dose-dependent manner, but is toxic to the treated animals at a high dosage. In order to develop a better lung-targeted anti-carcinogenic agent, spermine-conjugated BBI (spermine-BBI) was synthesized by coupling BBI to spermine through amide bonds using a carbodiimide-mediated reaction. Results from in vitro transformation assays demonstrated that spermine-BBI was at least as effective as BBI in reducing the transformation yield in C3H10T1/2 cells. When injected intravenously into mice [125I]spermine-BBI accumulated to a greater extent in the lungs and the liver compared to BBI. The in vitro cytotoxicity of spermine-BBI in C3H10T1/2 cells was 30-fold less than that of PDL-ss-BBI. These results suggest that spermine-BBI is likely to be an improved cancer chemopreventive agent compared to BBI or PDL-ss-BBI.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Cell Survival; Chromatography, Gel; Chymotrypsin; Injections, Intravenous; Lung Neoplasms; Male; Methylcholanthrene; Mice; Mice, Inbred A; Mice, Inbred BALB C; Polylysine; Spermine; Tissue Distribution; Trypsin Inhibitor, Bowman-Birk Soybean; Tumor Cells, Cultured

The ability of tumor cells to express elevated levels of proteinases capable of degrading tissue matrix and basement membrane components in vitro has been correlated to their invasive and metastatic potential. Many in vitro invasion assays have been performed either in the presence of serum or with tumor cells that had been previously grown in serum. Since serum contains large amounts of active proteinase inhibitors, their presence could complicate interpretations. We have, therefore, attempted to measure the amounts of serine proteinase inhibitors released into culture medium by two rat mammary adenocarcinoma metastatic variants selected in vitro for serum-independent growth and differing in their in vivo metastatic behavior. Concentrated spent media (CSM) derived from cultures of poorly metastatic MTLn2(T42D) and highly metastatic MTLn3(T17D) tumor cells, grown in the presence and absence of fetal bovine serum (FBS) for 20-24 h, were compared for the presence of serine proteinase inhibitors capable of inactivating alpha-chymotrypsin. Our results show that when MTLn2(T42D) and MTLn3(T17D) tumor cells were exposed to FBS, the CSM of MTLn2(T42D) exhibited nearly 5-fold greater amounts of active proteinase inhibitors than that of MTLn3(T17D). The amount of proteinase inhibitory activity detected in the CSM of tumor cells not exposed to FBS was not eliminated but declined by 82% and 37% for MTLn2(T42D) and MTLn3(T17D), respectively. Analysis for enzyme-inhibitor (E-I) complex formation by nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography confirmed the kinetic results and revealed that the major inhibitor present in CSM/FBS of both variants forms a heat- and sodium dodecyl sulfate-stable E-I complex with an apparent molecular weight of approximately 79,000, identical to that formed when FBS or purified alpha 1-proteinase inhibitor is incubated with [alpha-125I]chymotrypsin. E-I complexes with apparent molecular weights of 44,000 and 50,000 were formed from CSM/bovine serum albumin of MTLn3(T17D) and MTLn2(T42D), respectively, that were not detected when [alpha-125I]chymotrypsin was incubated with bovine serum albumin. We infer from these observations that, in culture, poorly metastatic MTLn2(T42D) tumor cells, as compared to their highly metastatic MTLn3(T17D) counterparts, exhibit an increased capacity to retain and subsequently release significantly greater amounts of serum-derived active proteinase inhibitors

Topics: Adenocarcinoma; Animals; Chymotrypsin; Electrophoresis, Polyacrylamide Gel; Female; Lung Neoplasms; Mammary Neoplasms, Experimental; Neoplasm Invasiveness; Neoplasm Metastasis; Rats; Rats, Inbred F344; Serine Proteinase Inhibitors

Two human tumor cell lines were analyzed for the production of human antileucoprotease (ALP). One of them, a human squamous lung carcinoma cell line (HS-24) synthesized, as confirmed by Western blot analysis, high amounts of ALP in serum-free medium. The supernatant inhibited elastase, chymotrypsin and trypsin. Northern blot analysis with an 18-mer radiolabelled oligonucleotide, derived from an ALP specific cDNA clone, revealed a specific mRNA of about 700-800 nucleotides in HS-24 tumor cells. In contrast, a secondary human lung tumor cell line (SB-3), derived from the adrenal cortex, did not synthesize ALP when assayed under identical conditions. The supernatant inhibited only trypsin and chymotrypsin.

Topics: Carcinoma, Squamous Cell; Chymotrypsin; Culture Media; Humans; Lung Neoplasms; Neoplasm Proteins; Pancreatic Elastase; Protease Inhibitors; Proteinase Inhibitory Proteins, Secretory; Proteins; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

Antigenic reactivity of 35 perchloric acid (PCA) extracts of different histologic human lung cancer tissues was studied--in comparison with the reactivity of the carcinoembryonic antigen (CEA), the nonspecific cross-reacting antigen (NCA), and alpha-1-antichymotrypsin--with the use of specific immune sera against PCA extracts of lung squamous cell carcinoma, and anti-CEA, anti-NCA, and anti-alpha-1-antichymotrypsin sera. The following antigenic systems were found in lung cancers: a) antigens specific for most squamous cell cancers and adenocarcinomas, which are undetectable in small cell cancers; b) NCA-type antigens; c) CEA-like antigens; and d) the antigen responsible for alpha-1-antichymotrypsin reactivity. A considerable antigenic heterogeneity among lung cancers indicates the necessity for precise histopathologic verification of individual lung cancer cases before commencement of immunologic studies and purification of antigens specific for lung cancers.

Topics: Adenocarcinoma; alpha 1-Antichymotrypsin; Antibody Specificity; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chymotrypsin; Cross Reactions; Humans; Immunodiffusion; Lung Neoplasms

Topics: Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Chymotrypsin; Diagnosis, Differential; Histiocytoma, Benign Fibrous; Humans; Lung; Lung Neoplasms; Male; Neoplasm Metastasis; Protease Inhibitors

Media conditioned by tumor cells were studied for the presence of factor(s) that increase the rate of random migration (chemokinesis) of Corynebacterium parvum-activated macrophages. A capillary tube assay was developed and utilized to expediently monitor the chemokinetic activity of macrophages incubated in whole and fractionated media. Media conditioned by six different syngeneic and allogeneic mouse tumor cell lines demonstrated significantly higher chemokinetic activity than unconditioned or normal fibroblast conditioned media. The chemokinetically active component of the Lewis Lung conditioned media was found to be a trypsin sensitive, heat stable, high molecular weight (300,000-480,000 dalton range) factor that had no chemotactic (directional migration) activity. Pyran-activated macrophages also responded chemokinetically to the Lewis Lung factor while oyster glycogen and thioglycolate-elicited macrophages did not. The similarity and differences between the physical properties of the chemokinetic factor, other migration stimulating factors, and tumor-associated proteins are discussed.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Line; Cell Movement; Chemotactic Factors; Chemotaxis; Chymotrypsin; Fibrosarcoma; Lung Neoplasms; Macrophages; Male; Mammary Neoplasms, Experimental; Melanoma; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Trypsin

Topics: alpha 1-Antichymotrypsin; Antigens, Neoplasm; Chymotrypsin; Cross Reactions; Electrophoresis, Polyacrylamide Gel; Humans; Immune Sera; Immunoassay; Immunodiffusion; Kinetics; Lung Neoplasms; Trypsin Inhibitors

Topics: Antineoplastic Agents; Bronchial Neoplasms; Chloroquine; Chymotrypsin; Cyclophosphamide; Female; Fibrinolysin; Fibrinolytic Agents; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycins; Phenobarbital; Serotonin; Trypsin

Topics: Chymotrypsin; Cytodiagnosis; Lung Neoplasms; Stomach Neoplasms

Topics: Chymotrypsin; Humans; Lung Neoplasms; Sputum