Maciej Siewinski

Evaluation of changes in the activity of proteolytic enzymes and their inhibitors in the processes that accompany the growth of gastric cancer

BackgroundMany investigators have observed a correlation between the aggressiveness of malignant tumor growth and the levels of cysteine peptidases and their autogenous inhibitors. Cathepsins B and L are activated by pepsin in an acidic pH. This fact encouraged us to measure the activity of these enzymes in tissue samples of gastric cancer.MethodsWe measured the activities of cathepsins B and L, and their precursors and inhibitors, in homogenates of tissue samples obtained from operations for gastric cancer. We compared the results for the homogenates of tissues from three different sites: the tumor center, the zone of cancer invasion (border of the tumor), and healthy tissue.ResultsThe highest activities of free cysteine peptidases and those in complexes with their inhibitors, as well as their precursors, were observed in the border of the tumor, while the activities in healthy tissue were significantly lower.ConclusionThe local activities of cysteine peptidases and their inhibitors reflect the topographical differences between the center of the tumor, the zone of invasion, and healthy tissues in gastric cancer patients. In addition, the results for the pattern of changes in the activity of cysteine peptidases according to the degree of tissue infiltration were not dependent on the method of measurement (colorimetry vs spectrofluorometry).

Cysteine peptidase inhibitors and activator(s) in urine of patients with colorectal cancer.

The total activity of cysteine peptidase inhibitors and activator(s) was determined in the samples of urine received from colorectal cancer patients. Patients with peptic ulcer and healthy volunteers agreed to be a control group. The studies revealed a marked difference between the values of the determined parameters for the patients with colorectal cancer and those for the control group. Determination of cysteine peptidase inhibitors in patients urine is proposed as a new diagnostic procedure.

Cysteine peptidases and their inhibitors in breast and genital cancer.

Cysteine proteinases and their inhibitors probably play the main role in carcinogenesis and metastasis. The metastasis process need external proteolytic activities that pass several barriers which are membranous structures of the connective tissue which includes, the basement membrane of blood vessels. Activities of the proteinases are regulated by endogenous inhibitors and activators. The imbalance between cysteine proteinases and cystatins seems to be associated with an increase in metastatic potential in some tumors. It has also been reported that proteinase inhibitors, specific antibodies for these enzymes and inhibition of the urokinase receptor may prevent cancer cell invasion. Some proteinase inhibitor could serve as agents for cancer treatment.

Control of active B and L cathepsins in tissues of colorectal cancer using cystatins isolated from chicken egg proteins: in vitro studies

The activity of cysteine peptidases (cathepsins B and L) was estimated in homogenates of tissues sampled during surgery from 60 patients operated due to colorectal tumors. The results were compared to those obtained using tissues in which histopathology disclosed no tumorous cells, obtained from 20 patients of the same group, treated as a control. Activity of the enzymes was inhibited using cysteine peptidase inhibitors isolated from chicken egg proteins. Application of the inhibitors was found to inhibit activity of the enzymes which play a key role in tumor development. It is suggested that in future the inhibitors may provide a component of new generation drugs in the so-called inhibitor therapy.

Inhibition of cysteine peptidase activity in ascitic fluid in pancreatic cancer patients.

The works objective is to answer the question whether there is any possibility of activity inhibition of cysteine peptidases inhibitors playing an important role in key processes accompanying cancer formation, including pancreas. There is a justified speculation that specific inhibitors of these enzymes may inhibit development of cancer processes by inhibiting their activity. In vitro studies confirmed that these enzymes in ascitic fluid were inhibited with egg whites inhibitors even to 90% of their original activity.