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Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1β and the ratio of IL1β/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1β, as well as the ratio of IL1β/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.

Mucins and glycoprotein CD10 expression in 55 carcinomas of the stomach has been studied by immunohistochemistry. According to a profile of mucins and CD10 expression, 3 immunophenotypic variants of carcinoma were founded: gastric, intestinal and gastro-intestinal. Gastric and gastro-intestinal variants were more frequently than intestinal one. The correlation between the expression of investigated markers and histological type of carcinoma wasn't revealed The estimation of Ki-67 index has shown that the highest proliferative activity (>20%) in carcinomas with gastric phenotype has been found more often than in gastro-intestinal ones.

The review analyzes telomere lengthening mechanisms in cancer cells of two different tumor types--carcinomas and sarcomas. Basic attention is given to sarcomas which cells lengthen their telomeres through alternative mechanisms for lengthening telomeres (ALT). The features of ALT mechanisms functioning in these cells have been examined in detail. Moreover, the actually existing anti-telomerase drugs and their efficiency in carcinomas treatment were analyzed. The experimental data showing that, contrary to theoretical expectations, activation of ALT was not observed on a background of such anti-telomerase, are presented. This portends a good prognosis in the treatment of the patients with carcinoma. Finally, on the basis of the data analyzed the candidates for a role of targets are proposed for development of anti-ALT antineoplastic therapy. Expected efficiency and toxicity of such drugs are considered in detail.

A transfer factor (TF) specific to antigens of Geren's carcinoma in rat was developed using an original model of intraorganic growth. Intravenous injection (1pg/g body) inhibited primary tumor node growth in the liver by 78% and blocked dissemination to peritoneal viscera. Its effect was due to an immunospecific component promoting antitumor immunological response. The latter presented as generation of cytotoxic effector cells, vascular disorders in tumor parenchyma thus blocking tumor cell proliferation. Possible applications of tumor-specific TF for biotherapy of cancer patients are discussed.

39 cases of transitory cell (15 cases of well differentiated, 12-moderately and 12- poorly differentiated) urothelial bladder carcinoma were studied immunohistochemically. Expression of adhesion molecules, collagen, laminin and tenascsin was investigated. Their role in a decrease of a differentiation degree of urothelial carcinoma was revealed. The possibility of the above markers use for individual prognosis is demonstrated.

Epstein-Barr virus (EBV) is known to be closely associated with the development of anaplastic nasopharyngeal carcinoma (NPC) in some malignancy endemic regions in South-East Asia. LMP1 gene is one of the EBV latent genes, which encodes a latent membrane protein. LMP1 gene is thought to be a classical oncogene since it morphologically transforms cells in vitro and induces tumors in experimental animals in vivo. LMP1 is one of a few genes which is expressed in NPC tissues. It was first shown that C-terminus of LMP1 gene obtained from NPC patients in South-East Asia contained a deletion of 30 base pairs (bp). However, this deleted LMP1 gene was then found in the EBV isolates persisting among healthy virus carriers and patients with other EBV-associated abnormalities from both NPC endemic and non-endemic regions. The aim of this investigation was to accomplish a molecular biological analysis of EBV LMP1 genes obtained from Russian NPC patients. To this end, the authors isolated and sequenced the LMP1 clones amplified from the tumor tissues from 7 NPC patients at the N. N. Blokhin Russian Cancer Research Center and primary blood lymphocytes (PBL) from 6 healthy donors. As a result, the authors could not find the deletion of the above-mentioned 30 bp in NPC LMP1 clones, but could in one healthy donor (PBL-2). A functional analysis revealed no significant differences between LMP1 variants with or without 30 bp deletion in their capacity to activate NF kappa B and jun/AP-1 transcription factors. Nevertheless, Russian NPC-derived LMP1 variants as compared with those from PBLs featured some specific amino acid exchanges. These data indicate that the 30 bp deletion of LMP1 gene is not a factor that predisposes to NPC in Russia.

Parameters of the blood and plasma antioxidant systems were investigated at different stages of specific therapy for T3NxM0 cervical tumors in 23 patients to identify mechanisms of "relative" drug resistance. Treatment included preoperative telegammatherapy (10 Gy), aregional and regional lymphinfusion with low and high doses of cytostatics, respectively, complemented with endolymphatic injection of tocopherol acetate 100 ng. As a result, surgery after Wertheim became feasible in 14 out of 23 patients following external exposure to 30-40 Gy. Morphological examination detected metastases into the regional lymph nodes in 3 patients. The advantages offered by the treatment modality include adequate response to therapy as well as access to control of free-radical processes taking place in membranes of immunocompetent cells which in turn assures good clinical results.

The intensity of infiltration of the primary tumour and its lung metastases with granular leucocytes and lymphocytes was studied in mice with Lewis lung carcinoma. The content of lymphocytes decreases, while that of granular leucocytes increases with the growth of the primary tumour. The relative content of lymphocytes in metastasis tumours is higher than that of granular leucocytes. The primary tumour surgery causes reliable changes in the intensity of tumour infiltration with these cells, as compared with non-operated animals.

11 cases of different types of lymphosarcoma of T- and B-nature are studied immunohistochemically by means of antibodies against epithelial membrane antigen (EMA), including new Soviet monoclonal antibodies ICO-25 to this antigen, common leucocytic antigen, vimentin and cytokeratin. The phenomenon of the EMA including ICO-25 binding to the cells of some lymphosarcomas is confirmed. This indicates that the use of only this "epithelial differentiation marker" in not sufficient for the differentiation between lymphosarcoma and poorly differentiated carcinoma. Variability of lymphosarcoma cells staining by vimentin antibodies is shown, other limitations of the immunohistochemical examination of lymphoma are discussed. The conclusion is made of the necessity to use the spectrum of the above antibodies when differentiating between lymphosarcoma and poorly differentiated carcinoma.

Monoclonal antibodies (Ortho type) were used for immunocytochemical evaluation of cell-mediated immunity in peripheral blood from 29 patients with in situ (TisNoMo) and microinvasive (T1aNoMo) cervical carcinoma. The total number of T cells (OKT3+) was decreased in both patient groups compared to healthy volunteers. Marked difference between OKT4+ (helper/inducer) and OKT8+ (suppressor/cytotoxic) cells was observed OKT8+ level rose with advancement of disease, resulting in inverted OKT4+/OKT8+ ratio in T1aNoMo cancer patients. Antitumor immune resistance proved inhibited in both study groups manifesting itself in suppression of cell-mediated immunity.

The phase changes of biochemical characteristics of hypothalamic mediator systems have been demonstrated in C57Bl mice with Lewis carcinoma. Phase I generated due to implantation of tumour cells was characterized by predominant exciting processes, which can increase the dissemination and sedimentation of tumour cells. During phases II--a period of metastatic formation--the normalization was found in hypothalamic mediator systems, which along with the activation of serotoninergic mechanisms promotes the inhibition of antitumour resistance. Phase III was related to the acute activation of mediator exciting processes and weakening of inhibition processes. Stress reactions arising under these conditions can stimulate tumour cell extravasation and development, and active growth of early metastatic nodules. The depletion of exciting mediator systems of the hypothalamus followed by general exhaustion of the organism was observed in phase IV.

Sera from 24 patients with nasopharyngeal carcinoma (NPC) and from 60 normal subjects were examined for the presence of IgG and IgA antibody to various antigens associated with Epstein-Barr virus (EBV). The results indicate that NPC in Cuba, like in other countries, was accompanied by high titers of EBV-specific IgG antibody the levels of which differed markedly from those in normal subjects. Serological activity of the patients differed depending on the stage of the illness and its duration. Geometric mean antibody titers to the capsid antigen (VCA), D and R components of early antigen (EA) of EBV complex were higher in patients with extensive tumour process (III--IV stages) and in patients with the duration of the disease since the onset less than 3 years. Sera of the most patients contained EBV-specific IgA antibody which were practically completely absent in sera of the control subjects. Alongside with characteristic manifestations of responsiveness to EBV observed by other workers, patients with NPC in Cuba had specific features: higher antibody titers to VCA than in Caucasian subjects in the countries where this disease occurred sporadically, like in Cuba; high levels of antibody to EA, frequently exceeding those in patients with NPC from endemic zones (for instance in Chinese patients); prevalence of EBV-specific antibody to the R component of EA complex.

Immunohistochemical studies (detection of immunoglobulins of G, A, and M classes, and C3-fraction of complement) of tumor tissue from 26 patients with mammary gland carcinoma (MGC) were carried out. In 37 patients, circulating immune complexes (IC) in the blood were determined. Conventional histological methods were also used. The level of circulating IC in patients reached 130 +/- 12.6 units, in donors 55 +/- 2.1 units. IC were detected immunohistochemically in 15 cases (57.7%) only. They were predominantly located in the stroma in the form of small and large clumps. As a rule, IC contained one class of immunoglobulins, mostly IgG. In some cases (5 observations) IC were deposited on the surface of carcinoma cells and whole epithelial complexes. In 3 cases, only C3-fraction of complement was found on the carcinoma cell surface which suggested the existence of receptors against complement on the surface of epithelial cells of MGC.

A highly sensitive method of electroimmunodiffusion in acetate cellulose films developed by G.I. Abelev on the principle of isotachophoresis was used for the detection in human mammary gland carcinoma (HMGC) of an antigen related to envelope antigens of mouse mammary gland cancer (MMGC) virus. In 4 out of 10 HMGC cases, fractions of proteins with molecular weight about 50,000 d previously isolated in PAAG with sodium dodecyl sulphate were found to contain an antigen reacting with the antiserum to p52 MMGCV precipitation band which proved immunological identity of both antigens.

The levels of carcinoembryonic antigen (CEA), embryonic prealbumin 1 and 2 (EPA-1 and EPA-2), thermostable alkaline phosphatase of placental type (TSAP), alpha-fetoproteins (AFP), trophoblastic beta-globulin (TBG), chorionic globulins 1 and 2 (CAG-1 and CAG-2) were determined in 36 fetal, 78 definitive, 31 hyperplastic, 38 adenomatous and 49 malignant tissues of the thyroid (control: 100 donor blood sera) using the immunodiffusion method after O. Ouchterlony modified by N. I. Khramkova and G. I. Abelev and the method of counter immunoelectrophoresis after K. Wilms. Oncofetal antigens TSAP, EPA-1, EPA-2 and CEA characteristic for antigenic reversion of thyroid tumors were identified in thyroid tissues. Antigenic reversion was most noticeable in tissues of papillary thyroid cancer. CEA and EPA-1 identification in the patients' blood sera could be applied to serological diagnosis of thyroid cancer.

The immune competence of C57Bl/6 mice implanted with EL-4 lymphoma of Lewis Lung carcinoma 3LL was investigated during 3 weeks after implantation. Splenic lymphocyte responses to mitogens (Con A, PHA, LPS, PWM) cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2) production were assessed. A dramatic reduction in mitogenic responses to Con A and PHA was observed during tumour progression. LPS and PWM responses were less depressed. Con A-induced IL-2 production correlated with Con A and PHA responses. Allospecific CTL response to mastocytoma P 815 was not decreased in syngeneic tumour-bearing mice.

The reactivity of the lymphocytes from 40 carcinoma patients and 19 patients without detectable malignancies was tested by means of the macrophage-electrophoresis-mobility (MEM) test exposing lymphocytes from one individual to a large spectrum of antigenic preparations. Besides the encephalitogenic protein (EP) and the carcino-embryonic antigen (CEA) hypertonic KCl-extracts from human cancer and normal tissues were used as antigens to be tested. When performed in such a complex manner, the MEM-test resulted in characteristic reaction patterns allowing one not only to discriminate between cancer and noncancer, but also to draw a conclusion in which organ a carcinoma has arisen. The characteristic "immunological tumor profiles", thus obtained, are obviously due to the existance of common antigens in carcinomas of the same tissue origin. The CEA seems to be another antigen of high diagnostic value in that system, since the lymphocyte response to CEA was restricted to patients with tumors of the colon, rectum and stomach. The results show for the first time that lymphocytes of the tumor patients mentioned are able to react to CEA. The human lymphocyte response to CEA seems to be far more cancer- and (or embryo-specific than the reactions obtained with xenogenic hyperimmune sera) which areused for the detection of CEA in human sera or plasma samples. The "immunological tumor profile" opens a new step of quality among the attempts to develop immunological tumor tests.

The study was concerned with the effect of human ceruloplasmin on blastogenic reaction of lymphocytes (BRL) and cyclic nucleotide level in murine organs in the course of Lewis lung carcinoma development. Both ceruloplasmin and an immunomodulator--zymosan--were found to raise the level of cAMP and to lower that of cGMP in the immunocompetent organs (thymus and spleen) of tumor-bearing mice at all stages of the investigation. The results point to an immunomodulating action of human ceruloplasmin involved in tumor growth and the role played by cyclic nucleotides in the process.

Using the analytic microscope "Parmoquant-2" (GDR), histograms were obtained demonstrating electrophoretic mobility (EPM) of lymphoid cells of C57BL/6 mice in the course of growth of the Lewis carcinoma (3LL) and melanoma B16 administered under the skin of the femur. Changes in the average values of EPM of thymic, splenic and lymph nodal cells in the process of tumor growth appeared similar. It is shown that the medium thymocyte EMP is growing towards the terminal stage of tumor growth, at the expense of the decrease in the share of PNA+ cells. Splenic cell bimodal distribution according to EPM became, in the course of tumor growth in intact mice, unimodal with some insignificant decrease in the median EPM values. The median EPM of regional and distant lymph nodes in the process of tumor growth is of phase character. It is supposed that investigation of lymph node EPM could be used for studying tumor growth kinetics.

Functional activity of B- and T-cells was studied in mice during the growth of the inoculated tumours; it appeared that in the course of the tumour growth the capacity of B- and T-cells to the interaction in the immunization with sheep erythrocytes was disturbed. B-cells were affected earlier than T-cells.

Cells of KMPG-1 and SPG-2 cultures obtained from the bone marrow and spleen of baboon hamadryads with hemoblastosis produce herpes-like virus (HLV) having the density of 1.21 and 1.27 g/cm3 in sucrose and cesium chloride density gradients. The density of nucleocapsids is 1.26 and 1.30 g/cm3 correspondingly. The HLV DNA sedimentation constant- 54 +/- 3S, and its density 1.717 g/cm3. The sera of patients with Burkitt's lymphoma and nasopharyngeal carcinoma can bind H3-thymidine labelled HLV that evidences a close antigenic relationship between HLV and NV virus.

The effect of the interaction between lymphocytes from tumor-bearing mice and stem cells was studied. It was found that in the process of tumor growth the property of lymphocytes to inactivate nonsyngeneic stem cells was not impaired. At the same time, during the process of tumor growth the property of lymphocytes to induce redifferentiation of syngeneic hemopoietic stem cells and to render a stimulating effect on the colony-forming activity of stem cells of the bone marrow is impaired under conditions of a manifested allogenic inhibition.

Injection of 2 mg of methylcholanthrene renders a sensitizing effect on separate tissues and enhances the development of skin papillomas and cancer in skin application of methylcholanthrene. To the time of papillomas appearance sensitized animals showed immunosuppression being more significant than in nonsensitized mice. Animals with cancerous tumors, both sensitized and non-sensitized, showed paralysis of immunological mechanisms of the organism protection.

Sinusal histiocytosis (SH) of regional lymph nodes was examined in 100 patients with mammary gland carcinoma in relation to the clinico-morphological characteristics of the tumor and values of the immunity system of the patients. Among patients with SH (43.4%) 84.8% had tumors of the I and II degree of malignancy; moderately and highly differentiated carcinoma (57.4% and 36.0%, respectively), non-metastasizing tumors (63.4%) with marked stromal reaction (51.5%), moderate mitotic activity of tumor cells (5.5 +/- 0.73%) prevailed in the I stage of the process (42.4%). In 64.3% patients of this group the content of T- and B-lymphocytes in the blood was within normal range, in 56.6% the reaction of the delayed type hypersensitivity was positive. Weakening and lack of histiocytic reaction was accompanied by progression of the tumor, increase of cytomorphological and clinical criteria of malignancy, inhibition of the functional activity of lymph nodes, decreased immunological responsiveness. A possible role of SH in the anti-tumor defence and the prognostic importance of this morphological test are noted.

Antigens of milk from normal women and from patients with mammary gland carcinoma and antigens of D type virus from HEp-2 cells were studied by means of microprecipitation in the gel and indirect immunofluorecence tests. An antiserum to HEp2 virus precipitated antigens of some milk specimens from cancer patients. However their virus precipitated antigens of some milk specimens from cancer patients. However their precipitation line was not identical to that of the test-system for group-specific antigens and the antiserum to HE-2 virus detected an antigen localized in the cytoplasm in the following cells: HEp-2, continuous cell lines and imprints of human mammary gland cancer, and epithelial cells from milk of patients with mammary gland carcinoma and from milk of normal women. The antiserum for the antigen of milk from cancer patients absorbed with HEp-2 cell homogenate lost its activity in the IF test. The nature of the detected antigens is discussed.

Suppressor status of immunity in 34 patients with gastric cancer of the III-IV stages was studied before and after (15 days and 3 months) gastrectomy and gastrosplenectomy. The control group consisted of 42 healthy donors. It was shown that gastrectomy caused inhibition of the endogenous activity, but stimulated the function of the prostaglandin-producing suppressor cells while combined gastrosplenectomy induced inhibition of the function of both endogenous and prostaglandin-producing suppressor cells.

The effect of intact mouse spleen cells sensitized in vitro with staphylococcus aureus enterotoxin A (SEA) on spreading of mouse Lewis carcinoma was studied. A significant decrease in a number of metastases in the lungs and in the weight of the lungs was observed after multiple intrapulmonary inoculation of spleen cells treated with SEA for 6 hours. The effect was less marked after inoculation of the sensitized cells intraperitoneally or into the femoral muscle of the leg affected with the tumour. After multiple inoculations of the sensitized cells, the spleen cells of the treated animals develop the state of interferon hyporeactivity to SEA but not to PHA or NDV.