alpha-chymotrypsin and Colorectal-Neoplasms

All tested variables showed a tendency in favor for Wobe-Mugos E therapy as addition to standard therapy. Enzymes improve the quality of life by reducing cancer disease typical symptoms, they reduce side effects of chemo-/radiotherapy and they have a potential of prolonging life (preliminary data only).

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chymotrypsin; Colorectal Neoplasms; Disease-Free Survival; Double-Blind Method; Drug Combinations; Fluorouracil; Humans; Levamisole; Neoplasm Metastasis; Pancreatic Extracts; Papain; Pilot Projects; Quality of Life; Survival Rate; Thymus Extracts; Trypsin

Chymotrypsin-like activity of proteasomes and total calpain activity were studied in patients with stage T2-4N0-3M0 gastric cancer and stage T2-4N0-2M0-1 colorectal cancer. Activities of proteasomes and calpains in gastric and colorectal cancer tissues were higher than in the corresponding normal tissues. Changes in activities of proteasomes and calpains were mutually related. The appearance of lymphogenic metastases in gastric cancer was associated with the increase in calpain activity. The progress of colorectal cancer and development of lymphogenic and hematogenic metastases were associated with elevated chymotrypsin-like activity of proteasomes.

Topics: Calpain; Chymotrypsin; Colorectal Neoplasms; Fluorometry; Humans; Lymphatic Metastasis; Proteasome Endopeptidase Complex; Statistics, Nonparametric; Stomach Neoplasms

Bowman-Birk inhibitors (BBI) from legumes, such as soyabean, pea, lentil and chickpea, are naturally occurring plant protease inhibitors which have potential health-promoting properties within the mammalian gastrointestinal tract. BBI can survive both acidic conditions and the action of proteolytic enzymes within the stomach and small intestine, permitting significant amounts to reach the large intestine in active form to exert their reported anti-carcinogenic and anti-inflammatory properties. In a previous study, we reported the ability of a recombinant form of TI1B (rTI1B), representing a major BBI isoinhibitor from pea, to influence negatively the growth of human colorectal adenocarcinoma HT29 cells in vitro. In the present study, we investigate if this effect is related directly to the intrinsic ability of BBI to inhibit serine proteases. rTI1B and a novel engineered mutant, having amino acid substitutions at the P1 positions in the two inhibitory domains, were expressed in the yeast Pichia pastoris. The rTI1B proved to be active against trypsin and chymotrypsin, showing K i values at nanomolar concentrations, whereas the related mutant protein was inactive against both serine proteases. The proliferation of HT29 colon cancer cells was significantly affected by rTI1B in a dose-dependent manner (IC50 = 31 (sd 7) μm), whereas the inactive mutant did not show any significant effect on colon cancer cell growth. In addition, neither recombinant protein affected the growth of non-malignant colonic fibroblast CCD-18Co cells. These findings suggest that serine proteases should be considered as important targets in investigating the potential chemopreventive role of BBI during the early stages of colorectal carcinogenesis.

Topics: Anticarcinogenic Agents; Cell Proliferation; Chymotrypsin; Cloning, Molecular; Colorectal Neoplasms; Gene Expression; HT29 Cells; Humans; Mutagenesis, Site-Directed; Pichia; Pisum sativum; Plant Proteins; Recombinant Proteins; Seeds; Trypsin; Trypsin Inhibitors

Bowman-Birk inhibitors (BBI) from soybean and related proteins are naturally occurring protease inhibitors with potential health-promoting properties within the gastrointestinal tract. In this work, we have investigated the effects of soybean BBI proteins on HT29 colon adenocarcinoma cells, compared with non-malignant colonic fibroblast CCD-18Co cells. Two major soybean isoinhibitors, IBB1 and IBBD2, showing considerable amino acid sequence divergence within their inhibitory domains, were purified in order to examine their functional properties, including their individual effects on the proliferation of HT29 colon cancer cells. IBB1 inhibited both trypsin and chymotrypsin whereas IBBD2 inhibited trypsin only. Despite showing significant differences in their enzyme inhibitory properties, the median inhibitory concentration values determined for IBB1 and IBBD2 on HT29 cell growth were not significantly different (39.9+/-2.3 and 48.3+/-3.5 microM, respectively). The cell cycle distribution pattern of HT29 colon cancer cells was affected by BBI treatment in a dose-dependent manner, with cells becoming blocked in the G0-G1 phase. Chemically inactive soybean BBI had a weak but non-significant effect on the proliferation of HT29 cells. The anti-proliferative properties of BBI isoinhibitors from soybean reveal that both trypsin- and chymotrypsin-like proteases involved in carcinogenesis should be considered as potential targets of BBI-like proteins.

Topics: Adenocarcinoma; Alkylation; Anticarcinogenic Agents; Cell Proliferation; Cell Survival; Chymotrypsin; Colorectal Neoplasms; Dose-Response Relationship, Drug; HT29 Cells; Humans; Inhibitory Concentration 50; Peptide Mapping; Protein Interaction Domains and Motifs; Protein Isoforms; Resting Phase, Cell Cycle; Sequence Alignment; Serine Proteinase Inhibitors; Time Factors; Trypsin Inhibitor, Bowman-Birk Soybean; Trypsin Inhibitors

To evaluate the impact of postoperative treatment with an oral enzyme (OE) preparation given complementary to an antineoplastic therapy in patients with all stages of colorectal cancer.. The design of this epidemiological study was a retrolective cohort analysis with parallel groups. Design and conduct of the study were performed to current standards for prospective, controlled clinical trials. Of a cohort of 1,242 patients with colorectal cancer (documented in 213 centres), 616 had received complementary treatment with OE (182 OE only, 405 other complementary drugs, 29 protocol violators) and 626 had not received OE (368 control only, 229 other complementary drugs, 29 protocol violators). Of 1,162 patients who had undergone primary surgery, 526 received adjuvant chemotherapy and 218 radiotherapy. The median follow-up time for the OE group was 9.2 months and for the control group 6.1 months. The primary test criterion of efficacy for OE treatment was the multivariate effect size of the changes from baseline of the disease- and therapy-associated signs and symptoms (nausea, vomiting, changes in appetite, stomach pain or stomach disorder, tiredness, depression, memory or concentration disorder, sleep disturbance, dizziness, irritability, dyspnoea at rest, dyspnoea during activity, headache, tumour pain, cachexia, skin disorders and infections). Tumour-related events, e.g. death, were evaluated by the number of events observed and time to event. Safety of treatment with OE was analysed in terms of number and severity of adverse events, their duration, treatment and outcome.. A significant reduction in disease-associated signs and symptoms was observed in patients treated with OE alone, but not in those receiving OE in addition to other complementary treatments. Adverse reactions to chemo- and radiotherapy were diminished in all patients receiving OE. Analysis of survival did not demonstrate a reduced number of deaths in the OE group. However, a trend to prolongation of survival was demonstrated, particularly in the patients with disease stage Dukes' D, in the subgroup receiving OE in addition to other complementary treatments. Similar but less-pronounced trends were observed for disease stages Dukes' B and C. In the OE group, 21 of 616 patients (3.4%) experienced OE-associated adverse reactions, all of them mild to moderate gastrointestinal symptoms.. Complementary treatment of colorectal cancer patients with OE improves their quality of life by reducing both the signs and symptoms of the disease and the adverse reactions associated with adjuvant antineoplastic therapies. This epidemiological retrolective cohort analysis provides evidence that patients may also benefit by a prolongation of survival time. OE were generally well tolerated.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Chymotrypsin; Cohort Studies; Colorectal Neoplasms; Combined Modality Therapy; Drug Combinations; Endopeptidases; Female; Humans; Male; Middle Aged; Multivariate Analysis; Papain; Retrospective Studies; Survival Rate; Trypsin

Topics: Chymotrypsin; Cohort Studies; Colorectal Neoplasms; Combined Modality Therapy; Drug Combinations; Humans; Neoplasm Staging; Pancreatic Extracts; Papain; Reference Values; Retrospective Studies; Survival Rate; Thymus Extracts; Trypsin