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IGF-1, IGF-2, and IGFBP-1,2,3 were assayed in blood serum of patients with malignant ovarian tumors (n=44), borderline ovarian tumors (n=11), and benign ovarian tumors (n=12) as well as in healthy women (n=33). In blood serum of patients with malignant ovarian tumors, the level of IGF-1 was lower and IGFBP-1 was higher than in other groups. In patients with malignant and borderline ovarian tumors, the level of IGFBP-2 was higher than in healthy women and in patients with benign ovarian tumors. There was no correlation between most examined parameters and the clinical and morphological peculiarities of ovarian tumors. The study revealed IGF/IGFBP imbalance in patients with malignant ovarian tumor and showed that IGFBP-2 proved to be a potential diagnostic serological marker w with 90% sensitivity and 90% specificity.

46 cases of nonendometrial carcinoma of the corpus uteri have been studied. The expressions of E-cadherin, alpha and beta-catenins were detected by immunohistochemical method. The high level of studied markers expression was founded out in clear cell carcinoma, whereas the less expression was detected in the corpus uteri of patients with serous, papillary, undifferentiated and mixed cancer. The absence of E-cadherin, alpha and beta-catenins complex expression correlated with unfavorable clinic-morphological features of carcinoma.

The content of vascular endothelium growth factor is significantly increased, while the level of matrix metalloproteinase-2 is 2-fold reduced in ovarian cancer tissue compared to benign tumors. A trend to an increase in the levels of matrix metalloproteinases 7 and 9 and reduction of vascular endothelial growth factor type 2 receptors in tumor tissue was also detected. A highly significant negative correlation between the levels of vascular endothelial growth factor and matrix metalloproteinase 2 and positive correlations between vascular endothelial growth factor and matrix metalloproteinase 7, vascular endothelial growth factor and matrix metalloproteinase 9, matrix metalloproteinase 2 and vascular endothelial growth factor type 2 receptors were revealed. In the tumors assayed after preoperative therapy, relative normalization of the studied parameters was observed: the level of vascular endothelial growth factor decreased significantly, while the levels of matrix metalloproteinase 2 and vascular endothelial growth factor type 2 receptors increased. The levels of the markers differed significantly in ovarian tumors of different histological types, and the levels of vascular endothelial growth factor type 2 receptors were higher in patients with stage III compared to stage I and the content of matrix metalloproteinase 7 was higher in stage III compared to stage II cancer.

The content of matrix metalloproteinases 7 and 9 was significantly increased, while the content of metalloproteinase 2 was reduced in ovarian cancer tissue compared to benign tumors. In blood serum from patients with ovarian cancer, the concentrations of matrix metalloproteinases 7 and 9 and their type 1 tissue inhibitor were significantly elevated, while the concentration of matrix metalloproteinase 2 was reduced compared to the corresponding parameters in healthy women. After chemotherapy, tissue and serum concentrations of metalloproteinases and their inhibitor in patients practically returned to normal. A significant positive correlation between serum levels of matrix metalloproteinases 7 and 9 and tissue inhibitor of metalloproteinases-1 in patients with ovarian cancer and the size of primary tumor (ultrasound examination) and a positive correlation between these parameters and the concentration of classical ovarian cancer marker CA-125 were demonstrated.

The initial levels of soluble Fas antigen (sFas), leptin, and vascular endothelium growth factor (VEGF) were measured in the sera of 100 patients with ovarian cancer and benign tumors and in 60 healthy women aged 28-65 years. Serum levels of sFas and VEGF were elevated in the total group of patients with ovarian tumors, while leptin levels were the same as in healthy women. The studied parameters did not depend on the age of patients and healthy women. The levels of sFas and leptin were virtually the same in benign and malignant ovarian tumors, while VEGF concentration was higher in patients with ovarian cancer. The mean serum levels of sFas, VEGF, and leptin in patients with poorly and moderately differentiated serous ovarian cancer were 2-fold higher than in well-differentiated tumors (p<0.05), while serum concentrations of sFas and leptin increased with the disease stage progress in patients with ovarian cancer (p<0.05). According to the data of unifactorial analysis, the increase in serum levels of sFas and VEGF in ovarian cancer patients correlated with short duration of the relapse-free period. Multifactorial analysis showed that the disease stage (p=0.006), presence of ascites (p=0.03), VEGF concentration (p=0.02), and the sFas/leptin coefficient (p=0.045) are highly significant independent factors for predicting the relapse-free survival of patients with serous ovarian cancer.

The report deals with retrospective research in possible induction of relapse by breast reconstruction carried out simultaneously with surgery for breast cancer. The end results were compared between cases of modification of radical mastectomy combined with reconstruction (n=124) and controls who underwent surgery for cancer alone (n=379). Standard radio- and systemic therapy was used. Median follow-up was 64 months. Local and general recurrence as well as relapse-free and overall survival rates were identical. Multivariate analysis failed to establish any correlation between primary breast reconstruction and relapse. Nor did it increase the risk of the development of the latter.

The investigation was concerned with use of 99mTc-methoxyisobutyl isonitrile (99m Tc-MIBI)-assisted prognosis for chemotherapy of locally-advanced breast cancer based on the assessment of 99m Tc retrieval from primary tumor in 26 patients. 99mTc was administered in the course of two-phase scintigraphy of the breast prior to chemotherapy. The dynamics of accumulation and withdrawal from tumor was identified. In view of the absence of any correlation between accumulation and chemotherapy efficacy, one was established between high rates of label withdrawal, on the one hand, and lack of pathomorphosis, on the other, while medium and low rates were associated with marked pathomorphosis in 44 and 50%, respectively (p < 0.05).

The pool of low-molecular metabolites in untreated breast cancer patients was investigated by high-resolution 1H-NMR spectrometry. It was found that the delta = 1.75 m.d signal can serve as a prognostically significant negative factor. Beside other markers, its absence in tumor sample extracts may indicate favorable prognosis.

The activities of lipid peroxidation and of platelets' antioxidant protection were investigated in 30 healthy women and in 44 patients with primarily diagnosed different-stage ovary cancer (OC). An essentially higher activity of superoxide dimutase (SOD, by 2.5 times) and of catalase (by 1.5 times) was detected in platelets of OC patients versus the norm. A simultaneous increase of malonic dialdehyde (MDA) by 2.5 times denotes a free-radical activation. There was also an insignificant growth of the glutathione level, whereas the activity of glutathione-S-transferase (GST) did not virtually change. A comparative analysis of the biochemical indices of patients with different stages of the disease revealed valuable distinctions related with a higher activity of SOD and catalase in stages 3-4 versus the initial stages. Notworthility, the MDA level was decreasing. Minor changes in the system of glutathione are not obviously decisive in impairing the regulatory mechanism of antioxidant protection in platelets unlike in malignant cells. The results provide a solid basis for assuming that the impact made by deranged regulations of free radicals on the platelet chain in the hemostasis system causes changes in the blood rheological properties entailing a higher aggregation of platelets, thus, triggering the onset of platelet-embolic complications in the discussed patient category. The impaired regulation mechanism of antioxidant protection in platelets is a major manifestation of the oxidant stress evolving due to a growing tumor; the mechanism is important for evaluating the structural-and-functional platelets' condition.

Enzyme immunoassay showed that the content of free vascular endothelial growth factor increases in tumor cytosols and blood serum from patients with breast cancer. A positive correlation was found between the contents of vascular endothelial growth factor in tumor cytosols and blood serum. After removal of the tumor the content of vascular endothelial growth factor decreased only in 49% patients. It should be emphasized that changes in these parameters did not depend on their initial values.

Glutathione content, the activity of glutathione-dependent enzymes (glutathione reductase, glutathione peroxidase, and glutathione S-transferase), and also SOD (superoxide dismutase) and catalase were studied in human malignant tumors (uterus, breast, and ovaries) and normal tissues. Glutathione level and the activity of glutathione-dependent enzymes were 2-3 times higher in the malignant tumors than in normal tissues. A negative correlation between the level of glutathione and glutathione-dependent enzymes (glutathione peroxidase and glutathione S-transferase) in tumors and the efficacy of postoperative chemotherapy may characterize the degree of tumor resistance to chemotherapy and therefore may have prognostic value. Low SOD and catalase activity and high activity of glutathione-dependent enzymes in tumors suggest that glutathione peroxidase and glutathione S-transferase play a major role in peroxide utilization in malignant tumors.

Expression of DNA sequences homologous to sequences of env gene of mouse mammary tumor virus (MMTV) in the lymphocytes of patients with breast cancer and in subjects at a high risk of breast cancer has been reported. Antigen analogous to envelope protein gp52, product of MMTV env gene, is detected in T lymphocytes of virtually all patients with breast cancer and extremely rarely in T cells of controls, where its expression is confined to B cells. For explaining such unexpected results, we studied the molecular basis of this antigen synthesis. Specific PCR products were obtained using primers to gp52-coding region of MMTV env gene. One of them (957 nucleotides) was used as a probe for hybridization of DNA and RNA from lymphocytes of patients with breast cancer and controls. This sequence was hybridized with 90% frequency with genome DNA of breast cancer patients and with 85% frequency with genome RNA of such patients, which is almost 4-fold more than in the controls (patients with gynecological tumors or donors). These results correlate with the frequency of detection of the studied antigen in patients with breast cancer and control group patients.

Experiments on male hybrid mice demonstrated that specific immunotherapy with preparations based on carcinoembryonal antigen and mucin containing CA 125 antigen was not associated with general toxicity, local irritating effect, and hepatorenal dysfunction. The absence of toxicity is apparently due to the fact that antigens injected intramuscularly or subcutaneously virtually do not enter the blood. Injections of preparations based on carcinoembryonal antigen and mucin containing CA 125 antigen to mice induced a standard immune response with predominance of class M immunoglobulins during the early terms and class G immunoglobulins at later terms.

Epidermal growth factor receptors (EGFR) were identified in the membrane fraction of tumor in 21 out of 58 (36%) endometrial cancer patients. EGFR ligands--EGF-like peptides--were found in tumor cytosols in 36% of patients. However, EGFR and EGF-like peptides were observed in 7% of tumors only; there were no receptors or ligands in 39% of patients. Both EGFR and steroid receptors were expressed in 20 tumor patients. The frequency of EGFR expression in endometrial carcinomas was practically identical to that of normal endometrium at the proliferative stage of menstrual cycle and half that of hyperplastic endometrium. Postmenopausal patients tended to show a decrease in hormonal sensitivity of carcinoma and EGFR expression frequency rate and a lower degree of endometrial carcinoma cell differentiation. Also, a significant rise in the EGFR expression frequency and mean concentration was found in conjunction with a deeper invasion of tumor into the myometrium.

A retrospective analysis of data on 27 patients with uterine choriocarcinoma metastatic to the brain and other distant sites treated at the Center's Clinic (1980-1996) has been undertaken. Advantages offered by combined treatment (irradiation of the brain + combination chemotherapy) of 15 patients are discussed and practical advice is given.

High-dose chemotherapy using transplantation of hemopoietic precursor cells offers much advantage for treatment of prognostically unfavorable cancers of the breast. Both experimental and clinical evidence points to a potential of raising antitumor effect by increased dosage of chemical drugs. Clinical studies using high-dose chemotherapy for treating patients with stage II-III tumors or with greater than or equal to 10 positive axillary lymph nodes, and locally-advanced and disseminated tumor established a relative rise in overall and recurrence-free survival, as compared with standard treatment. Hazardous cytopenia and related complications can be significantly reduced when hemopoietic precursor cells are transplanted from peripheral blood.

Different procedures of breast reconstruction were employed in the treatment of 223 breast cancer patients (primary reconstruction-97; delayed reconstruction-136). No major complications were recorded, including total necrosis of transverse abdominal island flap. The advantage offered by the latter is due to its resistance to chemoradiotherapy: complications such as boundary necrosis do not destroy cosmetic effect as in the case of expander application.

A method of autolymphochemotherapy was developed based on administration of a "therapeutic" course of chemotherapy following cytotoxic treatment of a large amount (1.5-2 l) of central lymph obtained by external drainage of the thoracic duct. Immediate results of treatment of 15 patients with advanced breast, lung (non-small-cell) and ovarian cancer with various degree of chemoresistance are presented. Marked response was observed in 14 cases. It seems justified to use the method for the treatment of locally advanced cancer.

An electron microscopic study of 30 cases of squamous cell carcinoma of the lung of varying degree of cell differentiation was aimed at evaluating prognostic significance of ultrastructural features of tumor. A high level of dark cells was found to be associated with poor prognosis whereas the presence of well-formed and multiple cellular contacts (desmosomes) was in direct correlation with survival.

The twenty-year experience gained in the surgical treatment of 1,100 cases of lung cancer at the Clinic of Thoracic Oncology and Reanimation Department of the Center is summarized. Surgical and anesthetic procedures, premedication and methods of postoperative intensive care following resection or removal of the lung are discussed. The paper contains a detailed description of age-associated and concommitant diseases. Factors contributing to extension of indications for surgical treatment of lung cancer are analysed. Prevention and treatment of postoperative complications are considered.

The report discusses a 20 year-old experience with surgical treatment for lung cancer. In 1961-1980, the following surgical procedures were carried out in 1,100 cases of lung cancer: pneumonectomy--417 (38%), lobe- and bilobectomy--506 (46%), and exploratory thoracotomy--117 (16%). The range of indications for surgical treatment has been extended within the last 10 years; the percentage of surgical cases older than 60 years has grown from 17 to 35%, with patients older than 70 amounting to 12%. Risk of surgery for lung cancer has been reduced thanks to complex and pathogenetically-grounded therapy given before and immediately after operation as well as application of improved surgical and anesthesiologic support procedures. Among the most frequent death-causing post-operative complications were thromboembolism of the pulmonary artery, bronchial fistula, empyema of the chest and cardiopulmonary failure.

The results of radiation therapy of 117 patients with squamous cell lung carcinoma taking into account yearly survival were analyzed. Clinico-laboratory and roentgenological factors of prognosis were identified. The use of methods of mathematical statistics and a method of structural risk minimization made it possible to work out a decision rule permitting prognosis of yearly outcome of disease with the minimal probability of 72% even before the start of radiation therapy.