[Discordance of estrogen receptor status between primary and metastatic breast cancer--possible reasons and prognostic value].

The aim of the review was systematization of the data on discordance in expression of estrogen receptors between primary and metastatic breast cancer, different metastases and repeated analyses of the same tissue. The possible reasons for the phenomenon are discussed. The authors emphasize the need to analyze estrogen receptors in breast cancer metastases, regardless of the receptor status of the primary tumor, for predicting the course of the metastatic disease and providing an adequate treatment of the metastatic tumor in strict accordance with its receptor status during drug therapy. The works cited in the search engine Pub Med to May 2013 were analyzed.

[Radical removal of a malignant mediastinum hemangioendothelioma with restoration of the main blood supply to the brain].

46 year old man appealed to the Cancer Research Center of RAMS in October 2012 with unverified anterior superior mediastinal tumor, which was diagnosed in 2010. Progressive compartment syndrome of the superior vena cava was observed. On examination: CT, MRI, angiography, histological and cytological examination of biopsy material did not allow to confirm the morphological structure of the tumor. Removal of the tumor with bifurcation of the brachiocephalic trunk prosthetics was performed. Immunohistochemical (IHC) study verified malignant hemangioendothelioma.

[Estrogen receptors beta--new target in cellular lung cancer treatment].

Literature review upon various types of estrogen receptors expression (type alpha and beta) in the cells of cellular lung cancer, their participation in estrogen and antiestrogen effects implementation, influence of estrogens and antiestrogens on occurrence and progression of malignant lung tumors in animals and humans. Were analyzed reasons of data ambiguity on type beta estrogen receptors (ERbeta) expression frequency. The results of authors own research in quantitative assessment of ERbeta expression in tumor tissue of patients with cellular lung cancer (79 male and 22 female patients are presented in this article. An increase in expression rate and incidence of tumors with high ERbeta level has been shown in patients with lung adenocarcinoma regardless of smoking status or gender. A new strategy of antiestrogen use, especially tamoxifen, has been formulated for cellular lung cancer treatment. Authors believe in a positive effect of adjuvant treatment with tamoxifen in patients with ERbeta-positive cellular lung cancer used independently or during and after the chemotherapy, by analogy with breast cancer patients.

[Heterotopic transplantation of non-immunogenic trachea populated with recipient bone marrow stromal cells].

Morphological changes in decellularized allogenic trachea populated with recipient bone marrow stromal (mesenchymal) stem cells and transplanted heterotopically, were examined in 30 C57Bl/6 and Balb/c mice of 22-25 g body mass. The research results have shown the insufficient efficacy of a transplant preparation mode by freezing and thawing method as in this case inflammatory reaction developed in the transplant area and its rejection took place. It was established that the mode of obtaining decellularized tracheal transplant by means of sodium perchlorate (NaClO4) treatment, proposed by the authors, unlike a freezing-thawing mode, allowed to efficiently remove immunocompetent cells that expressed MHC I and II markers. NaClO4 effect did not result in either chondrocyte damage or significant disturbance of tracheal cartilaginous and connective tissue structure in heterotopic transplants. Since transplant population with bone marrow stromal stem cells promoted connective tissue restoration, reduced the formation of granulations in anastomosis area and favored faster transplant epithelization, most promising method of trachea preparation for transplantation apparently seems to be the combination of immune cell removal from this organ by NaClO4 treatment with subsequent bone marrow stromal stem cell population of transplant obtained.

[Tamoxifen molecular targets different from estrogen receptors].

Experimental studies showing ever new biological effects of tamoxifen on tumor cells, both expressing and nonexpressing estrogen receptors, are providing a novel conception of the drug, likely well known at present. The review describes tamoxifen targets, whose blocking induces inhibition of tumor cell growth and angiogenesis, stimulation of the programmed cell death (apoptosis, autophagia and necrosis), inhibition of multiple drug resistance mechanism and inhibition of invasion and metastasizing. In all the events, the results of the tamoxifen interaction with the cells are prognostically favourable from the viewpoint of both the inhibition of the tumor growth and metastasizing and the susceptibility to the medicinal therapy, that is considered by some authors as an extremely important addition to the tamoxifen antiestrogenic effect. The strategy of long-term tamoxifen adjuvant therapy of breast cancer with positive status of the estrogen reseptors was developed by Craig V. Jordan as far back as in the seventies of the XXth century, however there are arguments allowing to consider it also useful for the treatment of other tumors. First of all it is the fact described lately in regard to expression of estrogen beta-reseptors in solid tumors of practically all known localization and histological types, that are also the targets of tamoxifen. Apart from estimation of estrogen receptors, it is believed by some authors that molecular and biological choice of patients is necessary with an account of expression of other cell targets of antiestrogen for complete realization of all the aspects of tamoxifen biological activity in long-term adjuvant therapy of malignant tumors of various localization.

Optimization of a method for preparation and repopulation of the tracheal matrix for allogenic transplantation.

A method for decellularization of the trachea for subsequent repopulation with allogenic MSC was optimized. Tracheas from C57BL/6 mice were devitalized and repopulated with MSC from BALB/c mice. The tracheal matrix with devitalized mucosa and intact cartilaginous structure, fit for repopulation with allogenic MSC, was obtained by chemical treatment with NaClO4. This approach seemed to be promising for transplantation of allogenic trachea.

[Treatment of relapsed osteosarcoma. Role of chemotherapy using ifosamide and carboplatin].

Our investigation involved 27 patients with osteosarcoma and 2--malignant fibrous histiocytoma of long tubular bones treated at the Center's Clinics (2001-2008). Two regimes were used for relapsed tumor: ifosamide up to 5-10 g/m2 (median 7.5) + carboplatin 300-750 mg/m2 (median 350) + etoposide 300-500 mg/m2 (median 450) (ICE), or doxorubicin 50-80 mg/m2 (median 60) (ICA). Surgical treatment used atypical resection of the lung or precision excision of metastasis. Median post-relapse follow-up was 18 months. When ICE was used, partial effect was reported in 3 (17.6%), stabilization--10 (58.8%), and tumor progression--4 (23.5%); ICA: partial effect--3 (25%), stabilization--6 (50%), tumor progression--3 (25%). Metastases were removed after a course of chemotherapy in 16 cases. Overall 3- and 5-year survival was 51.6 +/- 11% and 34.4 +/- 16%, respectively. Relatively more aggressive was the course of the disease in cases of early relapse (< or = 12 months), combination of local recurrence and distant metastasis and those who had not survived until a second surgical remission. Hence, timely combination therapy of relapsed high-grade osteosarcoma may secure relatively long remission in 35-40.3%.

[Estrogen receptor expression in tumors different from breast cancer].

A review of the literature data on expression of estrogen receptor alpha and beta (ERalpha and ERbeta) in tumors different from breast cancer. The results regarding the ERalpha and ERbeta expression frequency in non-small cell and small cell lung cancer, colorectal cancer, esophageal, ovarian, prostate and brain tumors are presented. High frequency of estrogen receptor expression (in up to 50 and more per cent of cases) in various types of tumors, differences between ERalpha and ERbeta in expression frequency, prognostic significance and prediction of the neoplastic process aggressiveness as well as in biological implications of interaction with antiestrogens (antagonistic and/or agonistic effect) are shown. The data on comparative evaluation of ERalpha and ERbeta expression in lung, ovarian, prostate tumor cells and corresponding nonneoplastic tissues are reported. Authors consider necessary to include the ERalpha and ERbeta detection into the routine clinical practice not only in breast cancer but in other tumors as well. Prospects of the clinical application of antiestrogens, in particular tamoxifen, in adjuvant therapy of different tumors with positive ER status are discussed.

[Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer].

Chromosomal and genome abnormalities of 3p are frequent events in many epithelial tumours, including lung cancer. Several critical regions with high frequency of hemi--and homozygous deletions in tumours were detected on 3p and more then 20 different cancer-related genes were identified in 3p21.3 locus. Real-time PCR was used to measure mRNA level of tumour-suppressor genes and candidates in 3p21.3 (RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 in basic types of non-small cell lung cancer (NSCLC)--squamous cell lung cancer (SCC) and lung adenocarcinoma (AC). Significant (from 2 to 100 times) and frequent (from 44 to 100%) mRNA level decrease was shown in NSCLC. Level and frequency of mRNA decrease for all genes depended on histological type of NSCLC. Down-regulation of RASSF1A and ITGA9 was associated significantly with AC progression, the same tendency was found for genes RBSP3/CTDSPL, NPRL2/G21, HYAL1 and HYAL2. On the contrary, down-regulation of all genes in SCC was not associated with clinical stages, tumor cells differentiation and metastases in lymph nodes. Significant decrease of RBSP3/CTDSPL, NPRL2/G21, ITGA9, HYAL1 and HYAL2 mRNA levels (on average, 5-13 times) with high frequency (83-100%) was already shown at the first stage of SCC. Simultaneous decrease of all six genes mRNA level was found in the same tumor samples and was not depended on their localization on 3p21.3 and functions of the proteins. Spearman's correlation coefficient r(s) was from 0.63 to 0.91, P < 0.001. Co-regulation of gene pairs ITGA9 and HYAL2, HYAL1 and HYAL2, which mediate cell-cell adhesion and cell-matrix interaction, was suggested based on the obtained data. It was shown that genetic and epigenetic mechanisms were important for down-regulation of RBSP3/CTDSPL and ITGA9 genes. These results supported the hypothesis on simultaneous inactivation of cluster cancer-related genes in extended 3p21.3 locus during development and progression of lung cancer and other epithelial tumors. Significant and frequent decrease of mRNA level of six genes in SCC could be important for development of specific biomarker sets for early SCC diagnosis and new therapeutic approaches/strategies for NSCLC.

[Significance of the expression of nucleolar argyrophilic proteins and antigen Ki-67 in the evaluation of cell proliferative activity and in the prediction of minimal (T1) lung cancer].

S u m m a ry. - The subject of the study was 20 cases of non-small-cell lung carcinomas, up to 3 cm in diameter, conventionally designed as minimal lung cancers removed in patients operated on at the N. N. Blokhin Cancer Research Centre, Russian Academy of Medical Sciences in 1986 to 2001. According to survival rates after surgery, the patients were divided into two groups: 1) those who died within the first two years; 2) those who were followed up for 3-5 years. Histological, histochemical, and immunohistochemical studies were performed. The expression of argyrophylic nucleolar organizer site proteins (Ag-NOS-proteins) that characterized the rate of cell proliferation (the duration of a cellular cycle) and the expression of Ki-67 antigen, which reflected the fraction of growth (the number of proliferating cells), were revealed in the tumor cells. Minimal lung cancers were found to be a heterogeneous group of neoplasms showing differences in both the rate of cell proliferation and the count of proliferating cells. The cell proliferation rate is a determinant of the clinical course of minimal lung cancers. Group 1 tumors characterized by the superexpression of Ag-NOS-proteins and, accordingly, the higher cell proliferation rate and the moderate count of proliferating cells had a poor prognosis even in the presence of Stage IA whereas Group 2 tumors with a large quantity of proliferating cells, but with the less rate of cell proliferation were characterized by a much better prognosis. The rate of cell proliferation (expression of Ag-NOS-proteins) and the count of proliferating cells (the expression of Ki-67 antigen) should be simultaneously studied to have more complete information on the proliferative potential of tumor cells and on the prediction of the course of neoplasms.

[Surgery for mesenchymal tumours of the mediastinum].

Results of treatment of 52 patients with mesenchymal tumours of the mediastinum. Clinical finding is various and nonspecific. Computer tomography and MRT are the most informative diagnostic techniques. Among 52 patients with mesenchymal tumours of the mediastinum, 40 patients were treated surgically and 12 patients got conservative treatment. Chemotherapy and radiotherapy were carried out in 7 patients in pre- and postoperative periods. Radical surgical treatment was carried out in 21 patients with benign tumors. Among 19 patients with malignant tumors, 42% of patients got radical surgical treatment, and 58 % of patients got palliative therapy in combination with chemotherapy. Benign tumors have a favorable prognosis after surgical treatment. Major factors of the prognosis of surgical treatment are dissemination and the histologic form of a tumor as well as type of surgical intervention. Re-operation is necessary in case of relapse.

[The pharmacological strategy of overcoming the phenotype of the multiple pharmacoresistance of non-small-cell lung cancer].

The authors discuss literature data and the results of their own many-year research into molecular markers of multiple pharmacoresistance associated with the function of ABC-transporters (MDRABC) from the point of view of their clinical significance. They consider the evolution of views on the mechanism of functioning and intracellular localization of ABC-transporters in normal and tumoral cells, in particular, the role of these transport proteins in the protection of nuclear targets from toxic agents, including antitumoral preparations. By the example of non-small-cell lung cancer (NSCLC) the authors critically analyze the reasons why data on the frequency of ABC-transporters expression in human solid tumors and on their prognostic value are inconsistent. The article contains a detailed analysis of the results of the authors' own research into the activity of ABC-transporters in NSCLC, in which the frequency of expression and co-expression of different transport proteins (including Pgp and MRP) is defined and new characteristics and mechanisms of the regulation of the functioning of MDRABC molecular markers are revealed. A methodical approach to routine characterization of MDRABC phenotype in NSCLC is offered. The main directions of pharmacological strategy of overcoming the multiple pharmacoresistance of NSCLC are formulated.

[Epidermal growth factor receptors and their ligands in non-small-cell lung carcinoma]. / Retseptory épidermal'nogo faktora rosta i ikh ligandy pri nemelkokletochnom rake legkogo.

Investigators and clinicians have recently called attention not only to the clinical and morphological parameters, but to the parameters characterizing the biological activity of nonsmall-cell carcinoma of the lung (NSCCL) from biochemical and molecular biological points of view. These include production of epidermal growth factor (EGF) receptors (EGFR) and their ligands which are important auto/paracrine regulation of lung tissue formation in health and tumor growth. Active studies of EGFR and EGF-like peptides (mainly, EGF and alpha-TGF) have failed to gain an insight into their role in the pathogenesis of NSCCL. Most authors suppose that tumor EGFR production increases as cell atypical features enhance and tumors show EGFR hyperexpression as compared with intact lung tissue. The expression of EGF and alpha-TGF is associated with poor prognosis in NSCCL. Attempts at designing and clinically testing the agents that block the transmission of EGFR ligands within the tumor cell are well-known, which open up new possibilities for antitumor therapy of patients with NSCCL.

[Germ cell tumors of the testis: current status and future progress]. / Germinogennye opukholi iaichka: sostoianie problemy i nauchnyi progress.

The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and widespread recognition of its curative potentials at any stages of disease. This article provides an overview on statistical and epidemiological information, the latest developments in testicular cancer biology. Also, the results of treating 360 patients with nonseminomatous and 97 patients with seminomatous germ cell tumors are presented. A combined chemotherapy with cisplatin, etoposide and bleomycin demonstrates the highest rate of activity in nonseminomatous germ cell tumor patients. Surgical resection of residual masses after chemotherapy continues to be an important component of combined modality therapy in nonseminomatous testicular tumors. The needs for regular clinical examination during a follow-up have been underlined.

[Large cell carcinoma of the lung: ultrastructural classification, diagnosis, prognosis]. / Krupnokletochnyi rak legkogo: ul'trastrukturnaia klassifikatsiia, diagnostika, prognoz.

16 lung large cell carcinomas (13 of them were followed for a long time) were studied. It is established that these tumours are a heterogeneous group of neoplasms which may be undifferentiated or with squamous, glandular, oncocytic and endocrine differentiation. Ultrastructural classification is presented reflecting diagnostic and prognostic aspects of these tumours. Tumours with pneumocytes type II, oncocytic differentiation and many lipid inclusions have more favourable prognosis. Unfavourable prognosis is typical for large cell carcinoma formed of undifferentiated cells only or with differentiation in the direction of goblet cells.

[Ultrastructure of pulmonary squamous cell carcinoma as a prognostic factor in surgical treatment]. / Ul'trastruktura ploskokletochnogo raka legkogo kak faktor prognoza pri khirurgicheskom lechenii.

163 operated on patients were divided into 2 groups: the 1st group--those surviving 5 years without recurrence (44.2%) and the 2nd group--those dying earlier from the tumour progression (55.8%). Central carcinoma was in 104, peripheral one in 59 cases. The number of dark cells (DC) and the degree of desmosome development revealed ultrastructurally have the greatest practical importance as the favourable course in the 1st group was associated with the absence or low number of DC (7%) and the high number of desmosomes (89%). These indices were found in the 2nd group in 86 and 41%, respectively. Both indices are of independent importance and are not associated with the spread of the carcinoma. The level of DC is of greater importance. Prognosis of the squamous cell carcinoma is the worse the higher is DC number in the tumour and the lower the desmosome number.

[The ultrastructural characteristics of human lung adenocarcinomas as a factor in the prognosis in surgical treatment]. / Ul'trastrukturnye osobennosti stroeniia adenokartsinom legkogo cheloveka kak faktor prognoza pri khirurgicheskom lechenii.

The material of 70 patients with lung adenocarcinomas radically operated at the All-Union Cancer Research Centre is analyzed. The spread of tumour expressed in terms of TNM system (I group--T1-3 N0M0--37 patients, II group--T1-3 N1M0--18 patients, III group--T1-3 N2M0--11 patients, IV group--T1-3 N1M1--4 patients) and its ultrastructure served as criteria. The correlation is found between the life-span, degree and type of the tumour cell ultrastructural differentiation. The most favourable prognosis at comparable tumour spread is found when the tumour cell ultrastructural differentiation corresponded to that of Clara type, pneumocytes of II order and ciliary type. Less favourable ultrastructural features were the domination of undifferentiated cells and the presence of goblet cells and those having the signs of differentiation into the various directions. The lack of correlation of the differentiation at the light microscopic and ultrastructural levels is found in some cases this being reflected in delayed results.

[Electron microscope study of lung carcinoid]. / Elektronno-mikroskopicheskoe issledovanie kartsinoidov legkogo.

123 lung carcinoids were studied, 32 of them electron-microscopically. Ultrastructural features were evaluated with the use of multivariate analysis. The most informative ultrastructural features were the following: correlation between differentiated and undifferentiated cells, the number of cytoplasm organoids including endocrine granules, degree of nuclei polymorphism and their size, specialized contacts, mitoses. Up to 18% of carcinoids, on the average, need ultrastructural verification of the anaplasia degree, this percentage increasing to 27.2% in atypical carcinoids. The above ultrastructural criteria allow to specify malignant potential of carcinoids, facilitate differential diagnosis and make their prognosis.

[Clinical evaluation of the small-cell and poorly differentiated forms of squamous-cell and glandular lung cancers]. / Klinicheskaia otsenka melkokletochnogo i malodifferentsirovannykh form ploskokletochnogo i zhelezistogo raka legkogo.

The paper deals with the results of analysis of the data on 263 cases of lung cancer (small-cell--145, poorly differentiated--63 and glandular--55). Clinical manifestations and treatment procedures are discussed. The advantages offered by radical surgery used as a component of combined treatment for small-cell cancer are presented. No gain in survival was obtained by application of extended or combined surgery as compared with conservative treatment. In poorly differentiated carcinoma, radical surgery was shown to improve the end results in cases of limited expansion of tumor without involvement of the lung root or mediastinal lymph nodes.

[Steroid hormone receptors in lung cancer tissue]. / Retseptory steroidnykh gormonov v tkani raka legkogo.

Receptors to estrogens (ER), progesterone (PR), glucocorticoids (GR) and androgens (AR) were assayed in 44 lung cancer patients to evaluate hormonal sensitivity of tumor. In 30 cases, active forms of GR were additionally measured by DNA-cellulose adsorption method. GR appeared to be most frequent (65%). Tumors contained PR and ER in 22% and 16% respectively, but failed to reveal AR. A correlation was established between stage and GR positivity, with 83 +/- 8% of GR-positive tumors observed at stage T1-3N0M0 as compared to 50 +/- 12% at stage T1-3N 1-2M0 (P less than or equal to 0.05). As few as 55% (11 out of 20) of GR-positive tumors revealed receptors capable of activation and interaction with DNA-cellulose. These tumors alone, one third of tumors studied, are likely to respond to glucocorticoid treatment.