[Influence of neoadjuvant therapy on VEGFR-2 levels in tumor and blood serum from breast cancer patients].

Degree and trends of changes taking place in the angiogenic factors VEGF and VEGFR-2 were studied in cytosols and blood serum sampled from breast cancer patients in the course of neoadjuvant therapy. Such evidence was evaluated vis-alpha-vis basic indices for clinic-morphological features of the disease. The study included 30 cases of locally-advanced tumors. Our results pointed to an influence produced by preoperative therapy on the levels of angiogenic factors both in tumor and serum. However, trends of development of such parameters are different and independent of therapeutic modality. Correlation was established between VEGF and VEGFR-2 levels in residual tumor, on the one hand, and degree of therapeutic pathomorphosis, on the other.

[The use of 1H-NMR spectroscopy for the prognosis of overall survival of breast cancer patients].

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 specificity of expression of molecular biological markers in tumors of the mammary gland]. / Osobennosti ékspressii molekuliarno-biologicheskikh markerov v opukholiakh molochnoi zhelezy.

Data are described on a retrospective immunohistochemical study of the Ki-67, PCNA, Bcl-2, BAX, BclX and VEGF expression in tumors of two groups of patients with breast cancer (BC) and with the favorable and unfavorable clinical courses. A reliably high level of VEGF expression was detected in tumors of patients with an early BC relapse. Apart from VEGF, higher levels of the Ki-67 and PCNA expression were registered in tumors of the discussed patient's category. It can be suggested that the expression parameters of VEGF, Ki-67 and PCNA in the primary tumor can be made use of in evaluating the BD prognostications or describing the features of high-risk groups with a high probability of early disease relapses.

[Experience with turbulent magnetic field as a component of breast cancer therapy]. / Opyt primeneniia vikhrevogo magnitnogo polia v lechenii raka molochnoi zhelezy.

No adverse side-effects were reported in an investigation of the antitumor effect of turbulent magnetic field (TMF) carried out as a component of preoperative chemoradiotherapy for breast cancer at the Center's Clinic. The study group included 114 patients with locally advanced tumors(T3, N1-N3, M0). According to the clinical, roentgenological and histological evidence on the end-results, the procedure was highly effective. Also, it was followed by shorter and less extensive postoperative lymphorrhea.

[The experience in the use of DNA flow cytometry to predict the natural history of malignant neoplasms]. / Opyt primeneniia protochnoi DNK-tsitometrii dlia prognozirovaniia techeniia zlokachestvennykh novoobrazovanii.

The aim is to study the pattern of a cell population (ploidy) and to evaluate the latter's significance in the prognosis of different carcinomas. A total of 467 patients with primary carcinomas of the breast (n = 177), lung (n = 88), head and neck (n = 140), and colon and rectum (n = 62) were examined. All the patients underwent surgery alone or in combination with radiotherapy (X-ray)/chemotherapy. A follow-up lasted 6 to 120 months. DNA was measured in the operative tumor tissue specimens by using an ICP-22 flow cytometer. Diploid and aneuploid cancers occurred in 20.4-53.6 and 43.6-79.6% of cases, respectively. The frequency of recurrences was mainly associated with aneuploidy and it was more than thrice higher than that with diploidy (21.0-43.2 versus 4.5-14.4%). Five-year survival was twice worse in patients with aneuploid tumors than in those with diploid ones. The survival rates after one operation, preoperative, and postoperative radiation therapy was greater in patients with diploid tumors than in patients with aneuploid ones. Thus, DNA-ploidy of the study neoplasms is of high informative value in predicting the course of a tumorous process and in choosing treatment policy on an individual basis.

[Contemporary treatment methods in primary breast carcinoma]. / Sovremennye printsipy lecheniia pervichnogo raka molochnoi zhelezy.

Surgery for primary breast carcinoma is the method of choice. The use of the so-called conservative (sparing) techniques greatly improves late outcomes. Thus, five-year survival in patients with early cancer stages after radical resections followed by radiation therapy was 87.6% and relapse-free survival was 80.4%. Six courses of adjuvant chemotherapy in 400 patients with Stage IIb provided 5-year overall survival in 81.3% of cases and relapse-free survival in 73.7%. Neoadjuvant chemo- and radiation therapy followed by radical mastectomy preserving both breasts and adjuvant chemo- and hormone therapy increases five-year overall and relapse-free survival up to 71.6 and 41.6%, respectively. The promises of improving therapeutical outcomes are associated with early and, in some cases, preclinical diagnosis.

[The role of epithelial antigens in diagnosis and staging of breast cancer]. / Rol' épitelial'nykh antigenov v diagnostike i stadirovanii raka molochnoi zhelezy.

The study of different epithelial antigen expression has been performed in 183 breast cancers. In 73 patients regional lymph nodes were studied as well. Panepithelial antigen Egp-34 (Mab HEA-125) was expressed in 100% of primary tumors and metastases. Antigen MUC-1 (Mab ICO-25) was identified in 93% of breast cancers. Monomorphic type of expression in tumor cells was typical for Egp-34, MUC-1 being in certain cases expressed as a proportion of cells. Additional immunohistochemical study of regional lymph nodes with Mab to Egp34 and MUC-1 provides a 10% increase in the rate of breast cancer metastases detection compared to histological examination alone. The carcinoembryonic antigen (CEA) was useful in identification of metastases only in CEA-positive breast cancers.

[Prognostic significance of epidermal growth factor receptors in stage I-II breast cancer: results of a six-year follow-up]. / Prognosticheskoe znachenie opredeleniia retseptorov èpidermal'nogo faktora rosta u bol'nykh rakom molochnoi zhelezy I-II stadii: rezul'taty shestiletnego nabliudeniia.

The disease-free (DFS) and overall (OS) survival was retrospectively assessed using mono- and multiparametrical methods in 197 patients with T1-2N0-1M0 tumors of the breast during a 3-73 month follow-up. No significant differences in DFS or OS were observed between epidermal growth factor receptor(EGFR)-positive or negative patients, either in the general study group or in those without metastases in the lymph nodes. However, DFS was much and significantly higher in patients with an "endocrine" receptor phenotype of tumor (EGFR-ER+PR+) than with an "auto/paracrine" one (EGFR+ER-PR). The DFS difference was particularly pronounced within the first 48 months (up to 30%) and subsequently smoothed down. In early-stage breast cancers, ER and PR status-related studies alone failed to reliably identify the group with unfavorable prognosis. The study also failed to establish any correlation between either of the phenotypes and the relative hazard rate for DFS in cases of no post-surgical treatment or treatment lacking the endocrine component. Conversely, the risk of relapse and/or metastasis was markedly higher in tumor with EGFR, after adjuvant hormone or chemohormonal therapy. The correlation between the ER or PR-positive and negative patterns and risk of relapse were significantly lower.

[Expression of epidermal growth factor receptors and their ligands in malignant tumors of the breast]. / Ekspressiia retseptorov épidermal'nogo faktora rosta i ikh ligandov v zlokachestvennykh opukholiakh molochnoi zhelezy.

Epidermal growth factor receptors (EGFR) have been investigated in the tumors of 166 breast cancer patients and concentrations of their ligands (alpha-TGF and EGF) were measured in 104 tumors by radioimmunoassay. EGFR and both growth factors were simultaneously detected in 18% and EGFR and one of the ligands were found in 11%. There were trends to higher frequency of EGFR expression in advanced tumors, in ductal and lobular infiltrative cancers with high grade of malignancy and in estrogen receptor negative breast cancers. A possible role of the parameters studied in the prediction of breast cancer and in the choice of therapy is discussed.

[Tumor markers CEA, CA 15-3, MCA, TPA, ferritin and PTH in the diagnosis and monitoring of primary breast cancer]. / Opukholevye markery REA, CA 15-3. MCA, TPA, ferritin i PTG v diagnostike i monitoringe pervichnogo raka molochnoi zhelezy.

Sera from 254 females were assayed for markers of tumor growth, such as cancer embryonal antigen (CEA), breast cancer-associated antigen (CA 15-3), mucinoid cancer antigen (MCA), ferritin, tissue polypeptide antigen (TPA), parathyroid hormone (PTH) by means of monoclonal antibody kits by using radioimmunoassay and enzyme immunoassay. Forty nine patients were diagnosed as having benign breast neoplasms, 171 patients were admitted to the clinic for primary breast cancer of varying severities, 34 patients without any breast abnormalities and somatic diseases comprised a control group. There was a close correlation between the higher levels of markers and the stage of a tumorous process. Various therapies-induced decreases in the levels of the markers serve as an objective criterion for the efficiency of the latter. Steady increases in the mean concentrations of tumor markers in the intra- and post-therapeutical periods are indicative of an extremely poor prognosis in this group of patients.

[Evaluation of the effectiveness of tamoxifen in malignant breast tumors: new approaches]. / Opredelenie éffektivnosti deistviia tamoksifena na zlokachestvennye opukholi molochnoi zhelezy: novye podkhody.

It has been shown that 17 beta-estradiol stimulates the cycle of phospholipid conversion in the breast tumor cells. The action of tamoxifen on antiestrogen cells is not limited by weakening the stimulating effect of 17 beta-estradiol on the exchange of intracellular phospholipids, but gives rise to a more complicated pattern of changes: inhibited incorporation of 32-P-phosphatidylcholine (PC) and activated exchange of phosphoinositides (PI). The experimental findings of 53 breast tumors have indicated that in 47.2% of cases Tamoxifen alters the PC/PI ratio and causes its 2-fold increase. Such alterations have been found to be induced by the ability of Tamoxifen to suppress the activity of protein kinase C that regulates the synthesis of PC and PI. It is suggested that the revealed capacity of Tamoxifen to change the rate of intracellular phospholipid conversion might be used for evaluating the efficiency of this agent on malignant tumors.

[DNA ploidy of tumor cells in prognostication of the course of malignant neoformations]. / Ploidnost' DNK opukholevykh kletok v prognozirovanii techeniia zlokachestvennykh novoobrazovanii.

DNA flow cytometry (FCM) was used for the clinical prognosis in patients undergone surgical removal of a tumor. The relationship between the structure of the tumor cell population (ploidy) and the frequency, time of a relapse onset (recurrence, metastasis), and the survival length were analyzed. All the patients had presurgical treatment (chemo- and/or radiotherapy). The patients were followed up for 5 to 9 years after surgery. The groups under study included 177 cases of breast cancer, 81 cases of larynx cancer, and 62 cases of colon cancer. Among the patients, the onset of a relapse was earlier and occurred more frequently in cases of aneuploid tumors among the patients regardless of the tumor type. In patients with aneuploid tumors, the most unfavorable prognosis was inherent in the hyperdiploid and multiclonal ones. The probability of 5-year survival for patients with aneuploid tumors appeared to be 20-30% lower than that in cases of diploid ones.

[The effect of steroid hormones and tamoxifen on the rate of phospholipid turnover in the cells of uterine and breast tumors]. / Vliianie steroidnykh gormonov i tamoksifena na skorost' obrashcheniia fosfolipidov v kletkakh opukholei matki i molochnoi zhelezy.

The cycle of phospholipid turnover has been found to be under the negative control of hormonal cytostatics (progesterone) and under the positive control of proliferation stimulants (17 beta-estradiol, epidermal growth factor). Specific changes in the synthesis of phospholipids are shown when tamoxiphen, an antiestrogen and an inhibitor of protein kinase C, was used. The findings suggest that changes in the turnover rate of phospholipids are one of the key stages of steroid action on target cells and may be regarded as an additional criterion of tumor genetic sensibility.

[Chromosome fragile sites in patients with multiple primary tumors and familial forms of breast cancer]. / Izuchenie khromosomnoi sait-lomkosti u bol'ynkh s pervichno-mnozhestvennymi opukholiami i semeinymi formami raka molochnoi zhelezy.

An analysis was carried out of chromosomal site-fragility in patients with primary multiple tumors and familial breast cancer. A possible correlation is discussed between fragile sites, breakpoints in chromosome rearrangements in cancer patients and the localization of oncogenes mapped in chromosomal regions involved in said rearrangements.

[The lymphocyte immunological phenotype of young and middle-aged breast cancer patients]. / Immunologicheskii fenotip limfotsitov u bol'nykh rakom molochnoi zhelezy molodogo i srednego vozrasta.

The immunologic phenotype of lymphocytes of young and middle-aged patients with breast cancer was identified using ICO monoclonal antibodies. The parameters were compared to that of healthy subjects of the corresponding age groups. Breast cancer patients of both age groups were shown to have lower T-cell level as compared to donors. Parameters of T-cell-mediated immunity did not differ significantly between the young and middle-aged patients, although the former group tended to have lower level of mature T-lymphocytes. A significant decrease in parameters of B-cell-mediated immunity was observed in young patients as compared to donors whereas in middle-aged patients B-lymphocyte and monocyte levels were 4 times those in donors. B-lymphocyte level in young patients tended to be lower than in middle-aged ones.