Use of natural cysteine protease inhibitors in limiting SARS-Co-2 fusion into human respiratory cells.

Specific antibodies that humans acquire as a result of disease or after vaccination are needed to effectively suppress infection with a specific variant of SARS CoV-2 virus. The S protein of the D614G variant of coronavirus is used as an antigen in known vaccines to date. It is known that COVID-19 disease resulting from infection with this coronavirus can often be very dangerous to the health and lives of patients. In contrast, vaccines produce antibodies against an older version of the protein S-D614G (January 2020) and therefore have difficulty recognizing new variants of the virus. In our project we propose to obtain specific and precise antibodies by means of so-called controlled infection against specific infectious variants of the SARS-CoV-2 virus "here and now". Currently, several variants of this pathogen have already emerged that threaten the health and lives of patients. We propose to reduce this threat by partially, but not completely, blocking the fusion mechanism of the SARS-CoV-2 virus into human respiratory cells. According to our plan, this can be achieved by inhibiting cathepsin L activity in respiratory cells, after introducing natural and non-toxic cysteine protease inhibitors into this area. We obtain these inhibitors by our own method from natural, "human body friendly" natural resources. We hypothesize that blocking cathepsin L will reduce the number of infecting viruses in cells to such an extent that COVID-19 developing in infected individuals will not threaten their health and life. At the same time, the number of viruses will be sufficient for the body's own immune system to produce precise antibodies against a specific version of this pathogen.

The effects of chicken egg white cystatin and proteinase inhibitor on cysteine peptidase-like activity in the sera of patients with breast cancer.

BACKGROUND: The activity of autogenic proteolytic enzymes is regulated in vivo by autogenic inhibitors. They play important roles in maintaining a balance in many processes in the human body. In pathological conditions, enzymes are overexpressed and the balance is disturbed. Such uncontrolled changes may lead to the development of local or systemic cancer. OBJECTIVES: To evaluate the effects of specific inhibitors, i.e., chicken egg white cystatin (CEWC) and proteinase inhibitor (E-64) on autogenic cysteine peptidases (CPs) in the sera of patients reporting for subsequent stages of treatment after being diagnosed with breast cancer. Cysteine peptidases play a vital role in the basic processes that are associated with cancer progression. MATERIAL AND METHODS: We selected serum samples from 108 patients with a diagnosis of breast cancer (stages IIA-IIIA) who had received no previous treatment. The blood samples were centrifuged, and the resulting serum was placed in liquid nitrogen and stored at -80°C. The biochemical tests were performed at the laboratory of the Department of Physical Chemistry and Microbiology. RESULTS: For CEWC, we found an inhibitory effect in 37 out of 108 samples; for E-64, 14 out of 22 samples displayed an inhibitory effect. In the remaining blood samples, these inhibitors caused an increase in fluorescence. In a parallel test, we added pure cathepsin B to 9 serum samples, and then used CEWC to inhibit the activity of autogenic CPs. Chicken egg white cystatin completely inhibited the cathepsin B that was added to the serum without changing its effect on the autogenic CPs. CONCLUSIONS: The results suggest that there may be a potential difference between the commercially available cathepsin B and its autogenic analogues found in the serum of cancer patients. The increase in fluorescence induced in the reaction between the inhibitors and autogenic CPs is still unexplained. There was no relationship between the observed inhibition/activation of CPs and any of the available indicators of the health of the patients examined.

Differences in cysteine peptidases-like activity in sera of patients with breast cancer.

BACKGROUND: The key role in carcinogenesis with destruction of the extracellular matrix is played by proteases released by invasive cancer cells. Cysteine peptidases, such as cathepsin B and L, take an important role in cancer progression and metastasis. OBJECTIVES: Cysteine peptidase-like activity (CPA) in sera of patients with breast cancer at different stages of disease and the influence of genetic predisposition associated with BRCA-1 gene mutations were analysed. METHODS: CPA in serum was determined with the spectrofluorometric technique using Z-Phe-Arg-AMC as a substrate. Determination was carried out in 111 breast cancer patients in comparison to a control group of 50 healthy subjects. RESULTS: The highest CPA was found in breast cancer patients with a hereditary predisposition bearing BRCA1 gene mutations, and the lowest activity was found in patients who had a tumour surgically removed and before adjuvant therapy. The differences in the activities between control group and cancer groups were statistically significant (p< 0.05), except from group of cancer patients in complete remission (p< 0.52). CONCLUSIONS: Serum CPA in patients with breast cancer differs depending on the cancer stage and treatment methods. Our study demonstrate the correlation between BRCA-1 gene mutations and the increased level of CPA.

Antipapain activity in the serum of patients with breast cancer.

BACKGROUND: Complement information about the share the role of antipapain activity in serum people with breast cancer. OBJECTIVE: We measured the activity of cysteine peptidase inhibitors in the sera of 150 patients with breast cancer. Patients were divided into four groups depending on the cancer type and treatment method. We also analysed the control group. The activity of cysteine peptidase inhibitors was defined as a 'defensiveness' marker. METHODS: The activity of cysteine peptidase inhibitors was measured against papain using the colorimetric method and the BANA substrate. RESULTS: The highest activity of enzymes was found in the group of patients with BC and hereditary predisposition to it, and the lowest activity was found in patients after surgical treatment. CONCLUSION: The activity of cysteine peptidase inhibitors in serum was measured against papain. We found that the activity levels were correlated with the cancer stage and treatment method. The lowest activity was found in patients after surgical treatment; the highest in women with active cancer and a hereditary predisposition to it.

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.

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.

The imbalance of cathepsin B-like activity in acromegalic patients--preliminary report.

OBJECTIVE: Acromegaly is a rare disease due to growth hormone (GH) excess. Patients must be carefully follow up because of mortality and co-morbidity increased risks. Since routinely used GH and insulin-like growth factor-1(IGF-1) estimations are not always sufficient, patients require assessment of organ- or tissue-specific tests. Cysteine proteases (CP), including cathepsin B, have been tested in a number of pathologies in respect of a role in pathogenesis and potential utility in the disease activity and prognosis assessment. There is lack of data on CP activity in acromegaly. MATERIALS AND METHODS: In present study cathepsin B-like and cysteine peptidase inhibitor (CPI) activities have been tested in 29 acromegaly patients and in 15 healthy controls. Cathepsin B activity was assayed with N-bansoyl-DL-arginine-beta-naphthylamide (BANA) as substrate by the Barrett method. CPI activity was determined by measuring the inhibition of papain. RESULTS: Serum cathepsin B activity (median: 1.38 U/ml) and CPI activity (median: 93.08 U/ml) were higher in acromegaly then in controls (0.93 U/ml and 82.55 U/ml, p=0.000017 and 0.00285, respectively). Neither cathepsin B nor CPI activity was correlated with GH or IGF-1 level. No correlation was recorded between cathepsin B and CPI activity. CONCLUSION: It was shown for the first time that cathepsin B and CPI activities are increased in acromegaly. These findings suggest to study cathepsin system as an adjuvant parameter in the assessment of the overall acromegaly complications. Moreover, CP may be involved in pathomechanism of organ complications in acromegaly and may interfere with IGF-1 action.

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

The work's 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.

[Humoral-circulatory response in the somato-vegetative reflex caused by pain factors]. / Odpowiedz krazeniowo-humoralna w odruchu somatyczno-wegetatywnym wywolanym przez czynniki bólowe.

The somato-vegetative reflex is an organism's answer to physical stress, resulting from the action of miscellaneous stimuli on extero- and proprioreceptors. It is realized in two types of responses of alarm groups: Response to a stressor with superiority of the parasympathetic system. This is not often present and manifests as decrease in pulse, heart stroke volume and pressure. An adrenergic response to a stressor, realized sequntionally in time periods. The neurogenic phase and humoral phase connected with the ejection of amine from the core of the suprarenal gland are separately distingiushed in this type of response. Significant increase in blood pressure, vascular resistance, augmentation of flow of blood in the aorta and tachycardia were observed in these two phases to a considerable extent. An important role in this reflex is performed by the limbic system, whose activation causes a circulation of stimulation in the Papez emotive district, which lies at the basis of the appearance of vegetative symptoms of emotions. Knowledge of the mechanism of this reflex is important, as it may play an important role, without the participation of the consciousness (anesthesia) in diagnosing pain in miscellaneous surgical and dental procedures and sharp pain syndromes, as well as the prevention of the occurrence of this reflex and its hemodynamic repercussion.

Pretreatment of plantar warts with azone enhances the effect of 5-aminolevulinic acid photodynamic therapy.

5-Aminolevulinic acid (5-ALA) is a well characterized precursor in the synthesis of various endogenous porphyrins used in photodynamic therapy (PDT). It is most often administered topically into a tumor which is then irradiated with visible light at established wavelength to sensitize porphyrins accumulated therein. Our main aim in the present study was to increase the penetration of 5-ALA through the altered skin by application of 3% azone (1-dodecyl-azepan-2-one) before the application of 20% 5-ALA in patients with plantar warts: mosaic warts (MW) and myrmecia (MY). We also used 20% 5-ALA only to treat warts in other patients. We compared the therapeutic and cosmetic effects of the two treatment modalities. The lesions treated with modification of 5-ALA-PDT by pretreatment with azone responded with better effectiveness. In 18 patients subjected to 5-ALA-PDT plus 3% azone, we observed 66.7% complete response of MW and 100% of MY following PDT repeated two or three times; whereas in other 18 patients treated with 5-ALA-PDT alone, we observed only 37.5% complete response of MW and 70% of MY. These results provide evidence that the pretreatment with azone should be considered as the step that enhances 5-ALA penetration in tissues and thus increases the effectiveness of applied PDT.

Total and lipid-bound plasma sialic acid as diagnostic markers in colorectal cancer patients: correlation with cathepsin B expression in progression to Dukes stage.

PURPOSE: Serum cathepsin B (CB), Total Sialic acid (TSA), total sialic acid (TSA) and lipid bound sialic acid (TSA) concentrations more useful than the other markers investigated for detecting different malignancies. Our aim was to investigate the possible correlation between serum CB with TSA, LSA in colorectal carcinoma with pathological stages progressed of the disease. METHODS: The study was performed on 177 patients (109 patients with colon and 68 patients with rectal) and 50 healthy individuals comprised the control group. Serum CB activity was determined using fluorogenic substrate. Serum TSA and LSA Concentrations were measured according to the method described by Katopodis. RESULTS: Plasma CB and TSA levels in the tumor group were significantly increased in comparison with the controls group (P < or = 0.0001). No significant differences were observed in LSA level between the tumor group and the controls group. T/N ratios for CB, TSA elevated 2.3-fold, 2.5-fold respectively). LSA 1.8-fold. Serum CB activity, TSA concentrations values in plasma samples of patients were increased significantly with pathological stages progressed (P < or = 0.0001). CB is seen to correlate more strongly with TSA in tumor group (P < or = 0.0001, r= 0.7277) in comparison with controls group. These correlations became more significant as the stage of the disease progressed. CONCLUSION: The present investigations indicate that CB activity, serum TSA, concentrations are sensitive markers for detecting and earliest diagnosis of colorectal cancer. These markers with other clinical and biochemical criteria may play important metabolic roles in cancer progression.

Cysteine peptidase and its inhibitor activity levels and vitamin E concentration in normal human serum and colorectal carcinomas.

AIM: Cysteine peptidase (CP) and its inhibitor (CPI) are a matrix protease that may be associated with colorectal carcinoma invasion and progression, and vitamin E is also a stimulator of the immunological system. Our purpose was to determine the correlation between the expression of cysteine peptidases and their endogenous inhibitors, and the level of vitamin E in sera of patients with colorectal cancer in comparison with healthy individuals. METHODS: The levels of cysteine peptidases and their inhibitors were determined in the sera of patients with primary and metastatic colorectal carcinoma and healthy individuals using fluorogenic substrate, and the level of vitamin E was determined by HPLC. RESULTS: The levels of cysteine peptidases and their inhibitors were significantly higher in the metastatic colorectal cancer patients than that in the healthy controls (P<0.05). The activity of CP increased 2.2-fold, CPI 2.8-fold and vitamin E decreased 3.4-fold in sera of patients with metastasis in comparison with controls. The level of vitamin E in healthy individuals was higher, whereas the activity of cysteine peptidases and their inhibitors associated with complexes was lower than that in patients with cancer of the digestive tract. CONCLUSION: These results suggest that the serum levels of CP and their inhibitors could be an indicator of the prognosis for patients with metastatic colorectal cancer. Vitamin E can be administered prophylactically to prevent digestive tract neoplasmas.

Effect of vitamin E and human placenta cysteine peptidase inhibitor on expression of cathepsins B and L in implanted hepatoma Morris 5123 tumor model in Wistar rats.

AIM: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma. METHODS: Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates. RESULTS: Cathepsins B and L activities were elevated by 16-fold in comparison with negative control tissues, and their endogenous inhibitor activity decreased by 1.2-fold before treatment. In several cases, tumors completely disappeared following vitamin E plus human placental cyteine protease inhibitor (CPI) compared with controls. The number of complete tumor responses was higher when 20 m/kg vitamin E plus 400 microg of CPI was used, i.e. 7/10 rats survived more than two mo. Cathepsins B and L were expressed significantly in tumor, liver, lung tissues and sera in parallel to the increasing of the endogenous inhibitor activity compared with the controls after treatment (P<0.0001). CONCLUSION: The data indicate formation of metastasis significantly reduced in treated rats, which might provide a therapeutic basis for anti-cancer therapy.

[The influence of occupational exposure to arsenic and heavy metals on the activity of catepsins and their inhibitors in blood serum of copper smelters]. / Wplyw zawodowego narazenia na arsen i metale ciezkie na aktywnosc katepsyn i ich inhibitorów w surowicy krwi pracowników huty miedzi.

BACKGROUND: Exposure to arsenic, lead, and cadmium poses the risk of cancer. Cathepsins (CP) and their natural inhibitors (CPI) in blood serum are markers of carcinogensis. The aim of this work was to verify the existence of relationships between the exposure to the airesaid elements and the activity of CP and CPL. MATERIALS AND METHODS: The levels of Pb and Cd in blood, Mn, Cu, Zn, Ca, Mg, Fe, Se CP as well as free and bound CPI in serum, FEP in erythrocytes, and As in urine were measured in 186 production workers of Legnica Copper Smelter (study group) and 56 administrative employees (control group) and then analyzed. RESULTS: CF levels were significantly elevated in both groups and CPI levels were elevated in the study group vs. the control group. There were no statistically significant relationships between CF and CPI levels and the remaining parameters in the study group. whereas they were found for CPI in the control group. The results indicate that occupational and environmental exposures to toxic metals (arsenic, lead, cadmium) may lead to the elevated levels of CF and CPI. CONCLUSIONS: The obtained results support the assumptions of the study.

Cathepsin D expression in human colorectal cancer: relationship with tumour type and tissue differentiation grade.

OBJECTIVE: Cathepsin D (CD) is one of the main proteolytic enzymes contributing to the development of cancer. The aim of this study was to CD activity assay in the homogenates of tissues from the centre of the tumour (0) and tumour free area 2 cm, and 5 cm from the tumour border in human colorectal cancer. Activity in the centre of the tumour was compared with immunohistochemical expression CD. METHODS: CD activity was measured using acid denatured Hb as a substrate. For immunohistochemical staining peroxidase method was used. RESULTS: Activity of CD was significantly higher (15-fold) in tumour tissue homogenates in comparison to normal mucosa adjacent (control) (p < or = 0.0001) and raised parallel to the stage of tumour tissue differentiation grade. CD activity decreased significantly (p < or = 0.0001) with the distance from the tumour border 2 cm (12.7 fold) and 5 cm (5.7 fold) in comparison to the centre of the tumour. In immunohistochemical examinations CD was detected as diffuse cytoplasmic as well as fine granular staining of the cytoplasm, with occasional coarse cytoplasmic granules staining in the same cases that were positive for both. Positive staining was observed in 2 of 3 in well-differentiated (66%), 4 of 10 in moderately-differentiated (40%) and 4 of 5 in poorly-differentiated (80%), tubular adencarcinomas represented: 3 of 7 (42%) and 9 of 13 in invasive adencarcinoma (69%). CONCLUSION: We have observed a wide range of cathepsin D and their antigen expressions patterns in colorectal tumours with the development the disease stage, this finding may be used as a daignostic tumor marker in colorectal cancer.

Actin content and actin polymerization in hepatoma Morris 5123 tumor bearing rats after treatment with cysteine protease inhibitor and vitamin E.

AIM: Actin microfilaments are components of cytoskeleton, the structure involved in many cellular functions, including cell motility, and morphology, its necessary for tumor progression and metastasis. We investigated the effects of vitamin E and human placetal cysteine protease inhibitor (CPI) on actin content and polymerization after implantation the hepatoma Morris 5123 tumor in Buffalo rat. METHODS: We measured the size and survival animals treated with human placental cysteine protease inhibitor (CPI) plus vitamin E and none treated rats. Also measured the actin content and polymerization in the tumor and liver tissues by the inhibition of DNase I from bovine pancreas under standard assay conditions RESULTS: We observed that the combination 10 mg of vitamin E plus 200 microg CPI obtained the best results than authors. In those cases the animals survived for longer than 4 weeks. In numerous cases the 70 % of tumors disappeared following CPI and vitamin E application. The number of complete tumor responses was higher after combination 10 mg of vitamin E plus CPI 200 microg i.e. 5/7 rats than others group. We showed statistically significant decrease of monomeric (G), filamentous (F) and total actin as well as the F:G ratio level in tumor tissues after the rats was treated with CPI plus vitamin E in comparison with control animals. CONCLUSIONS: The new therapy may be the way for therapeutic intervention, aimed at stopping and possibly reversing the process of metastatic growth, with the use of drugs affecting actin polymerization.

Expression of cystatin C in clinical human colorectal cancer tissues.

We studied the relation between the antipapain activity of cysteine proteinase inhibitors (CPI) and immunohistochemical staining for cystatin C, using anti-chicken cystatin antibodies, in the colorectal cancer tissues. In primary tumour tissues immuno-peroxidase reactivity was present in the cytoplasm and on the cell surface membranes. Sections of non malignant tissues showed no staining. The percentages of positive staining were greater for adenocarcinoma than carcinoma,100% and 77% respectively. Antipapain activity which was increased in malignant tissues in comparison to control, rose successively from well differentiated carcinomas through moderately to poor differentiated. Invasive adenocarcinomas had higher antipapain activity than noninvasive ones. The results indicated that immunohistochemical detection of cystatin using anti-chicken cystatin antibodies could be useful in studying the prognostic significance of cystatin C expression in colorectal cancer.

Enhancement of photodynamic therapy by use of aminolevulinic acid/glycolic acid drug mixture.

5-aminolevulinic acid (5-ALA) is a precursor in synthesis of endogenous porphyrins used to sensitize tumor tissues in photodynamic therapy (PDT). It is administered topically into a tumor which after the certain time, required for porphyrins to accumulate, is irradiated with visible light from the proper source at established wavelength. Our main aim in the present study was to increase the penetration of 5-ALA through the skin and other tissues by addition of glycolic acid (GA) to 5-ALA on cell lines in vitro and on animals. We also applied 5-ALA ointment with glycolic acid to patients suffering from squamous cell carcinoma (SCC). In our study, we used 5-ALA, dimethyl sulfoxide (DMSO), ethylenediaminetetraacetic acid, disodium salt (EDTA) and GA together in one formulation (5-ALA-GA) on eucerin support. We compared both therapeutic and cosmetic effects in 5-ALA-GA-PDT and in control group of patients. Our results showed that modification of 5-ALA ointment by addition of 5% GA caused that the treated lesions responded with rapid regression. In 12 patients with single lesions of SCC type subjected to 5-ALA-GA-PDT, we observed 100% regression of tumors following single or repeated two-three times PDT. In vitro and in vivo in animals total porphyrin levels after addition of 5% GA increased significantly (P<0.01). These results provide evidence that addition of glycolic acid should be considered as the agent which enhances 5-ALA penetration in tissues and thus increases the effectiveness of photodynamic therapy.

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

BACKGROUND: Many 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: The 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).

Determination of cysteine peptidases-like activity and their inhibitors in the serum of patients with ovarian cancer treated by conventional chemotherapy and vitamin E.

Enzymatic activity of cysteine peptidases (cathepsins B and L) --associated with carcinogenesis is controlled by their specific inhibitors. The study was objected to the effects enhanced by taxol and cisplatin in patients pretreated with the vitamin E, by determining the levels of cathepsins B and L in sera of patients with ovarian cancer. The activity of cysteine peptidase (CP) and their inhibitors (CPI) in serum from patients with ovarian cancer and noncancerous patients were measured by using fluorogenic substrate before and after the routine anticancer chemotherapy, and a complementary combination of chemotherapy with vitamin E. The cat B and L activities were significantly higher in patient sera with ovarian cancer than non-cancerous patients (0.0001 pounds sterling). The results shows that, inhibitory activity of CPI and complex form were significantly decreased from 4.6 mEU/mg protein in a group of non-cancerous patients to 0.7 mEU/mg protein in a group of patients with ovarian cancer (p < or = 0.0001). Supplementation with vitamin E after a cycle of therapy with toxic drugs caused a decrease of the cysteine peptidases activities, that is 2.8-fold in patients to whom 40 0mg of vitamin E per day was given in comparison with control, and 6-fold after the third course. The CPI and DCPI complex increased 3-fold and 2.3 fold respectively, as compared to a group of patients were vitamin E was not administered. We observed that vitamin E administered to the patients with ovarian cancer in periods between anticancer drugs therapy courses decreases the cysteine peptidases activity and increases the enzyme-inhibitor complexes level