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Biomedical subjects

E A Zhavrid

Publications and source records attributed to E A Zhavrid.

At least 19 recordsLinked to original sources

The effect of hypoxia on photocytotoxicity of TICS tricarbocyanine dye in vitro.

AIM: To evaluate the effect of cell oxygenation on photocytotoxicity of a novel tricarbocyanine indolenine dye covalently bound to glucose (TICS). METHODS: HeLa cells were incubated with 5 microM TICS, 2 h later irradiated by laser at 740 nm with a light dose of 10 J/cm(2), delivered at a power density of 10, 20, 25 or 30 mW/cm(2), in air or in argon atmosphere, and then scored for viability. RESULTS: The photocytotoxicity of TICS increased dramatically as the power density was reduced. Under hypoxia TICS-photosensitized cell death was determined but its value was lowered, compared to photoirradiation in the air. CONCLUSION: Photosensitizing effect of TICS is only partially dependent on the oxygenation of tumor cells.

Cell Hypoxia↗

Oxidative metabolism of rat blood in the course of alveolar hepatic carcinoma PC-1 growth.

AIM: To evaluate oxidative metabolism of rat blood in the course of alveolar hepatic cancer growth in vivo. METHODS: The oxidation imbalance was assessed by the rise in the values of the integral index of oxidation stress. The structural and functional state of erythrocyte membranes was investigated by spin electron paramagnetic resonance spectroscopy. RESULTS: The growth of alveolar carcinoma was found to be associated with intensification of lipid peroxidation processes with increased blood content of conjugated dienes, malonic dialdehyde against the background of decreased concentration of endogenous antioxidants tocopherol and retinol. Destabilization of the structural state of erythrocyte membranes of rat tumor hosts at the development of oxidation stress was studied, which was characterized by nonspecific structural changes of membrane sorption centres, reduction in specific capacity in the protein-lipid contact area and its increase in the phospholipid bilayer, rise in the degree of order and polarity. CONCLUSION: Alveolar carcinoma growth in rats resulted in intensification of free radical lipid peroxidation processes with a shift of the prooxidant-antioxidant balance to the left and development of oxidation stress.

Animals↗

[Salvage thermochemotherapy in advanced refractory malignant tumors in children].

The data are presented on polychemotherapy given to 17 children with advanced refractory malignant tumors using whole body hyperthermia and hyperglycemia. All patients suffered tumor progression throughout treatment and afterwards. Adjuvant Roncoleukin (interleukin-2) was administered in 5. Such salvage therapy was followed by overall tumor regression in 29.3%. Overall 4-year survival in such cases was 19%. Immunological monitoring of adjuvant whole body hyperthermia and interleukin-2 was carried out.

Adolescent↗

[Role of high-dose BEAM-chemotherapy and autologous hemopoietic stem cell transplantation in the treatment of drug-resistant Hodgkin disease].

In 1995-1999, 67 patients with relapsed Hodgkin's disease or refractory to chemotherapy (group A--first relapse, B--primary refractory disease, and C--repeated relapse) received cytoreductive (dexaBEAM, DHAP) therapy followed by high-dose BEAM chemotherapy and autologous bone marrow or blood cell transplantation. Early postoperative transplant-related mortality rate was 4.5%. At day 100, complete remission rates were: group A--95.6%; B--74.1%; and C--76.5%. Survival for all patients was: overall--61.9%; event-free--43.9%; disease-free--46%; and relapse-free survival--49.5%. Such factors as primary refractory disease, age over 30 years and response to cytoreductive therapy had significant influence on overall survival prognosis.

Adult↗

[Effect of chemoradiotherapy on the pituitary-thyroid system in children with Hodgkin's disease].

The functional status of the thyroid gland was evaluated in 63 children with Hodgkin's disease, aged 4-15 years, before, in the course of and 5 years after chemoradiation therapy. Thyroxin (T4), triiodothyronine (T3) and thyroid-stimulating hormone (TSH) in the blood were assayed. The disease was shown to disrupt the pituitary-thyroid system leading to hypothyroidism development which progressed as the disease advanced. While chemotherapy brought the balance between the peripheral thyroid hormone levels and TSH back to normal, thyroid function decreased again following radiotherapy of the neck. The most pronounced and persistent failure of the pituitary-thyroid system was registered with the total target dose of 30 Gy and higher. Irradiation in a dose of 20 Gy caused less disruption and the function was spontaneously restored within 12 months after the treatment.

Adolescent↗

Experimental grounds for using chlorin e6 in the photodynamic therapy of malignant tumors.

The toxicity, pharmacokinetics and antitumour effect of chlorin e6 after light irradiation were studied. The LD50 value of chlorin e6 in C3H mice is 189 +/- 9 mg kg-1 and in Wistar white rats is 113 +/- 18 mg kg-1 14 days after intraperitoneal injection. The concentration of chlorin e6 in blood, liver, kidney, spleen and tumors (sarcoma M-1 and sarcoma 45) of the rats was determined by a fluorescence method, 3, 6, 12, 18, 24, 48 and 72 h after administration at a dose of 10 mg kg-1. For this purpose, chlorin e6 was extracted from tissues by the detergent Triton X-100. The depth of necrosis in sarcoma 45, the regression rate of sarcoma M-1 and the animal cure rate were evaluated after chlorin e6 administration at doses of 1-10 mg kg-1 and subsequent irradiation with krypton laser light. Depending on the dose and the time interval between chlorin e6 injection and irradiation, the depth of necrosis in sarcoma 45 varied from 5.0 to 15.0 mm. The cure rate of the animals with sarcoma M-1 varied from 10% to 60%. The antitumor effect was directly proportional to the chlorin e6 dose and light energy exposure and inversely proportional to the time interval between photosensitizer injection and irradiation.

Animals↗

Sensitivity of different rat tumour strains to photodynamic treatment with chlorin e6.

Transplantable rat tumours (sarcoma M-1, sarcoma 45, alveolar liver cancer PC-1 and Pliss' lymphosarcoma) were used to study chlorin e6 accumulation in tumours and its photodynamic effect. Tumours were irradiated by krypton ion laser light (647 and 676 nm; 90 J cm-2) 15 min and 24 h after chlorin e6 injection at doses of 5 and 10 mg kg-1. The relationship between some morphological peculiarities of these tumour strains, photosensitizer accumulation in tumours and their response to the photodynamic treatment is discussed.

Animals↗

Photodynamic therapy with chlorin e6. A morphologic study of tumor damage efficiency in experiment.

Morphological changes in rat sarcoma M-1 after photodynamic treatment with chlorin e6 were studied. The frequency of necrosis appearance and the depth of its spreading in tumor tissue were evaluated after intraperitoneal injection of chlorin e6 in doses of 1-10 mg kg-1 and subsequent irradiation by a krypton laser with light energy density 22.5-135 J cm-2, using the method of vital staining with Evans blue. It was found that the antitumoral effect of photodynamic treatment was strengthened by increasing the dose of the agent and light and reduced by increasing the time interval between chlorin e6 injection and light irradiation. The treatment being given in the parameters mentioned produced a depth of tumor necrosis which varied from 4.0 mm to 16.6 mm. The mechanisms of tumor tissue damage after photodynamic treatment in vivo are discussed.

Animals↗

[General hyperthermia in the chemoradiotherapy of small-cell lung cancer].

Treatment results were compared in 2 groups of patients with advanced small-cell lung cancer. Group 1 (52 cases) received chemoradiation treatment alone whereas in group 2 (41 patients) it was combined with general hyperthermia (temperature 40-41.8 degrees C during 3-4 hours). Response was observed in 63.5% of patients of group 1 and 79.5% of those in group 2. Complete response rates did not differ significantly (23.1 and 28.2%, respectively). 40.6 +/- 8.2% of patients receiving chemoradiation treatment plus general hyperthermia survived over 1 year, 20.5 +/- 7.1%--over 1.5 years and 15.9 +/- 6.7%--over 2 years. In the control group, the respective rates were 22.2 +/- 5.8%, 5.1 +/- 3.4% and 5.1 +/- 3.4%.

Adult↗

[The effect of whole-body controlled hyperthermia on the energy resources of cancer patients].

The results of examination of 120 patients with advanced malignant melanoma, soft tissue sarcomas and lung and renal cancer suggest disturbance in mechanisms of energy supply during whole-body guided hyperthermia. Cell glucose uptake was inhibited in hyperglycemic patients. High energy loss in due to utilization of such alternative substrates as lipids and proteins which, in turn, potentiates peroxidation of lipids toxic to cell membranes. These data provide biochemical rationale for developing procedures aimed at managing biochemical dysbalance, increase in carbohydrate utilization included.

Antioxidants↗

[Complex treatment of locally advanced soft tissue sarcoma of the limbs].

The experience of treatment of 40 patients with locally-advanced soft tissue sarcoma of the limbs. Treatment included preoperative chemoradiotherapy in combination with electromagnetic hyperthermia. As a result, 38 (95%) patients showed marked response which allowed radical limb-saving surgery whereas in 2 (5%) amputation was performed. Adjuvant chemotherapy was used for anaplastic tumors. Five-year survival rate was 64.7 +/- 6.7%.

Adolescent↗

[Radionuclide studies on the hormonal manifestations of heat stress in cancer patients under controlled total hyperthermia].

The results of the investigations of ACTH, HGH, hydrocortisone, glucagon, C-peptide, insulin in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole-body guided hyperthermia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia treatment, aimed at increasing the range of indications for its use in clinical oncology.

Combined Modality Therapy↗

[The prevention of the hypercoagulation syndrome during the combined treatment of lung cancer patients using artificial hyperglycemia].

Status of hemostasis system and occurrence of postoperative thromboembolic complications were assessed in 246 lung cancer patients in whom combined treatment included artificial hyperglycemia. The latter condition contributed to higher blood coagulability resulting in lung artery thromboembolism in some cases. Administration of a combination of heparin, curantil and nicotinic acid was followed by a decrease in blood coagulability, increase in anticoagulation function, decrease in platelet aggregability, activation of fibrinolysis and regression of biochemical signs of DIC syndrome thereby assuring a drop in the occurrence of thromboembolic complications.

Adult↗

[Effects of induced hyperglycemia on the activity of pancreatic and gastrointestinal secretion of hormones in oncologic patients].

Artificial hyperglycemia (AHG) used in the cancer treatment considerably increases the insulin and S-peptide content in blood, decreases the glucagon concentration and tissue glucose tolerance. The changes are reversible, have a functional character, that indicates the absence of a disbalance in hormonal mechanisms of carbohydrate metabolism control as well as marked disorders of the pancreas function. In order to achieve a wider range of indications for using AHG in complex schemes of the cancer treatment, it is necessary to take measures on optimization of the carbohydrate metabolism state which should be controlled by the suggested complex of laboratory tests.

Antineoplastic Agents↗

[Diagnosis and treatment of mesenchymal chondrosarcoma].

Eight cases of mesenchymal chondrosarcoma (3 males and 5 females aged 15-65) are described. Morphological examination revealed in all cases biphasal tumor consisting of the chondroid tissue of varying maturity and undifferentiated tissue. Combination and complex treatment was given to 6 patients. In 4 cases, radiotherapy was carried out in combination with chemotherapy and local electromagnetic hyperthermia. Out of 8 patients, seven are still alive and are examined at 4 month - 11 year intervals (average of 39.7 months). One female patient died 12 months after the beginning of treatment. Combined and complex procedures should be recommended for treatment of such patients.

Adolescent↗

[Pathomorphosis of cancer of the breast during thermoradiotherapy].

Local UHF-hyperthermia in combined therapy of breast cancer patients as compared to preoperative radiotherapy used alone, resulted in more noticeable therapeutic changes in a tumor. This fact was established during a study of tumor pathomorphosis in 206 patients with stage II breast cancer. A degree of therapeutic tumor pathomorphosis showed good correlation with the frequency and duration of a recurrence-free period of disease. In III-IV degree of tumor pathomorphosis the use of thermoradiotherapy brought about a higher efficacy of radical therapy of breast cancer patients.

Breast Neoplasms↗

[Induced hyperglycemia as a factor of modification of sarcoma 45 sensitivity to chemotherapy].

The injection of sarcolysine, methotrexate, thiophosphamide, cyclophosphamide, adryamycin and platidinum during glucose infusion is shown to increase their antitumour activity. The antitumour effectiveness of 5-FU did not increase under conditions of artificial hyperglycemia, while that of vincristine decreased. Intensification of the activity of some chemotherapeutic drugs in combination with hyperglycemia was observed against the background of their increased general toxic effects.

Animals↗

[Possibility of using high-frequency electromagnetic fields for modeling local controlled hyperthermia].

The possibility to use high-frequency electromagnetic fields (13.56 MHz) as a means of controlled local heating of deep and massive tissue areas was shown in 196 experiments on tissue equivalent phantoms and 20 healthy dogs. The advantages of each type of high-frequency emitters were determined. The thermometric evaluation of heat distribution in local high-frequency heating used in complex treatment of 12 patients with sarcomas of the locomotor system confirmed the experimental results.

Animals↗