[Current state of the problem of treatment and prognosis of colorectal cancer].

The article presents an overview of the current state of the problem of colorectal cancer based on the features of its various clinical forms. It was shown that despite the fact that the surgical method was the leading cancer treatment for colon and rectum cancer the preference should be given to the combined and complex methods and in the treatment of squamous cell carcinoma of the anal canal, the emphasis was on conservative treatment with chemoradiation, leading to stable remission that avoided traumatic surgery in most cases. Also current data are presented on the necessity to identify circulating and disseminated tumor cells to refine prognosis and further explore ways to improve long-term results.

Expression of vascular endothelial growth factor receptors VEGFR1 in cultured multiple myeloma cells: correlation with immunophenotype and drug resistance.

We studied the expression of genes encoding vascular endothelial growth factors VEGF-A, VEGF-C, VEGF-D and their receptors in cell cultures of human multiple myeloma IM9, RPMI 1640, RPMI 8226. The studied cells did not differ by the expression of growth factors. Expression of VEGFR1 receptor was detected only in IM9 cells and VEGFR2 and VEGFR3 receptors were not expressed in multiple myeloma cells. A dependence between the aberrant CD45/CD56 phenotype of human multiple myeloma cells and VEGFR1 expression in them was revealed. The only VEGFR1-positive IM9 cell culture was most resistant to Velcade (bortezomib).

[The dysplasia of myelopoiesis in patients with acute lymphoblastic leucosis].

Nowadays, the analysis of hematopoiesis in patients with acute lymphoblastic leucosis includes only quantitative characteristics of residue myeloid process of bone marrow. The evaluation of myelodysplasia is unexplored still. The analysis of myelopoiesis was carried on sampling of 108 patients with primary acute lymphoblastic leucosis (27 - T-acute lymphohlastic leucosis, 81 - B-acute Iymphoblastic leucosis). The characteristics of dysplasia of granulocytes, erythroid cells and megakaryocytes were based on the parameters of WHO classification of acute myeloid leucosis (2001). The monolinear dysplasia was established in 35 patients (32.4%). multilinear dysplasia--in 9 patients (8.3%). Under T- acute lymphoblastic leucosis the bilinear dysplasia was detected reliably more often and absence of dysplasia more rare than under B-acute lymphoblastic leucosis. The signs of dysplasia of various myeloid lines had no inter-correlation and had no dependencies from indicators of expression of early antigens (CCD34 and TdT) and myeloid antigens (CD13, CD33). The comparison of factual data with indicators of dysplasia under acute mteloid leucosis (181 patients) demonstrated that rates of uni- and multilinear dysplasia under T-acute Iymphoblastic leucosis and acute myeloid leucosis have no significant difference. The myelodysplasia is detected reliably (more often under B-acute lymphoblastic leucosis as compared with acute myeloid leucosis.

[The prognostic value of tumor cells blood circulation after liver surgery for cancer lesions].

The study aimed to prove the prognostic meaning of micrometastases blood circulation during liver resections for cancer lesions. 33 patients took part in the study. Circulating micrometastases were detected in blood using immunocytological method with pancytoceratine antibodies KL-1 and CAM 5.2. The majority of patients had colon cancer liver metastases (72,7%). Blood was sampled once in 8 patients, the rest 25 patients had double sampling: before and after liver mobilization. Patients with multiple liver metastases demonstrated tumor cells circulation more often. Of 58 tests, 25 were positive for tumor cells. 3-year survival in those patients was 45,7 ± 13,1%, 5-year survival was 24,4 ± 13,3%. Survival rates for patients with no circulating tumor cells detected were significantly higher.

Functional properties of extracellular domains of transducer receptor gp130.

Cytokine receptor molecules have been shown to have extracellular domains of complex structure and a multi-step activation system. Glycoprotein gp130 is a typical transducer of cytokine signal; it functions by forming multicomponent receptor complexes and transferring signals of tens of cytokines from the IL-6 family. Structural organization and basic functioning principles of gp130 are well known, as well as related signal pathways, which function during normal differentiation and are involved in pathogenesis of many tumors. The role of gp130 in IL-6-dependent tumors is best studied. In this review, based on extensive accumulated data, we examine the functional significance of certain parts of gp130 extracellular domains. Potentials of a recently developed method for estimation of receptor activation at the level of epitope structure are discussed.

Immunological peculiarities of CD-56-positive serous ovarian adenocarcinoma.

Here we present the results of evaluation of the expression of neural cell adhesion molecules CD56 (NCAM) in serous ovarian adenocarcinoma. The expression was detected in 48.5% cases. Infiltration of tumor stroma and parenchyma with CD8+ and CD4+ lymphocytes was significantly less pronounced in tumors expressing neural cell adhesion molecules; CD3+CD4+CD25+ predominate among CD4+ lymphocytes in CD56+ tumors. CD56+ tumors were lower in size (5.2±0.6, 7.9±0.8 and 10.3±1.5 cm in monomorphic, mosaic, and negative phenotypes, respectively (p=0.05) and were characterized by the absence of cystic component (p=0.012), larger disseminations in the peritoneum (4.2±1.1 and 2.7±0.5 cm; p=0.05), and larger volume of the residual tumor (p=0.018) after surgical treatment. NCAM phenotype of the tumor does not correlate with the stage and differentiation degree of serous ovarian adenocarcinoma.

Preparation of functionally active recombinant human interleukin-6.

The gene of human interleukin-6 (hIL-6) with an additional 20 amino acids on the N-end, including six histidine residues, was cloned into the expression plasmid pET28b(+). The conditions were elaborated for preparing highly active protein both using denaturing agents and without them. Application of a dialysis cascade allowed us to prepare a functionally active hIL-6 of 90-95% purity with the yield of 3 mg from liter of the cell culture. The highest activity was detected by ELISA in the preparation obtained without denaturing agents. The functional activity of hIL-6 was studied by flow cytofluorimetry. Addition of hIL-6 to the cells of immortal lines of human multiple myeloma resulted in dimerization of the gp130 receptor molecule.

Immunophenotypic peculiarities of mobilized stem (CD34+) cells in blood from patients with severe spinal cord injury.

Immunophenotype of mobilized stem blood cells (CD34+) was studied in 29 patients with late post-traumatic spinal lesions. The CD34+ cells demonstrated different levels of expression of CD45, CD38, monomorphic determinants HLA-DR and gp130 epitopes. Most patients presented with a CD34+ cell fraction with no or low expression of common leukocytic antigen CD45. Only 2 patients had greater than 15 percent of HLA-DR-CD38- cells in the CD34+ fraction. A common transducer molecule of interleukin-6 family cytokines gp130 was expressed on stem (CD34+) cells in all the cases, 26 percent of the patients had an activated gp130 phenotype, i.e. a combination of C7+ and A1- epitopes.

[Immunomorphological characteristics of lichen planus of oral mucosa]. / Immunomorfologicheskaia kharakteristika ploskogo lishaia slizistoi obolochki rta.

Immunomorphological studies of lichen planus of the oral mucosa were carried out using a wide spectrum of monoclonal antibodies. Antigenic composition of epithelial cells, lymphocyte subpopulations maintaining destructive processes in the epithelium in various clinical forms of this disease were studied. The study confirmed immunologically-mediated mechanisms of pathogenesis, leading to destructive processes in the epithelium in lichen planus of the oral mucosa, which should be taken into consideration in combined therapy of this disease.

[Hodgkin lymphoma with lymphoid predominance: differential diagnosis of nodular lymphoid predominance and classical variant]. / Limfoma Hodzhkina s limfoidnym preobladaniem: differentsial'naia diagnostika noduliarnogo limfoidnogo preobladaniia i klassicheskogo varianta.

A topical problem of differential diagnosis of nodular lymphoid predominance of Hodgkin's lymphoma and classical variant rich in lymphocytes is discussed. Main morphological diagnostic criteria are considered on the basis of the authors' observations and literature data. Immunological characteristics of two variants of Hodgkin's lymphoma with lymphoid predominance are reviewed.

[Use of Mabtera (rituximab) in treating patients with refractory courses of B-cell lymphoma, along with high-dose chemotherapy and autologous transplantation of hematopoietic stem cells]. / Primenenie mabtery (rituksimab) u bol'nykh refrakternym techeniem B-kletochnym limfom, poluchaiushchikh vysokodoznuiu khimoterapiiu s autologichenoi transplanttatsiei kletok-predshestvennits gemopoéza.

AIM: To study efficacy of rituximab in patients with resistant B-cell lymphoma on high-dose chemotherapy. MATERIAL AND METHODS: From September 2000 to April 2002 we studied efficacy and tolerance of rituximab at different stages of high-dose chemotherapy. The treatment was given to 10 patients with histologically verified CD20+ non-Hodgkin's lymphoma: diffuse large-cell (n = 4), Berkitt's (n = 2), follicular (n = 3), mantle-cell (n = 1). Five patients with diffuse large-cell lymphoma and Berkitt's lymphoma had a primary resistant course of the disease, one patient with diffuse large-cell lymphoma had a refractory recurrence. Follicular and mantle-cell lymphomas were characterized by a resistant course and large tumor masses. The patients received 1-2 courses of induction chemotherapy with dexa-BEAM with collection of peripheral stem cells followed by high-dose chemotherapy (BEAM-9, CBV + mitoxantron-1) with transplantation of autologous stem blood cells. Rituximab infusion (375 mg/m2) was conducted before the collection of the stem cells, prior to high-dose chemotherapy and in posttransplantation period after recovery of hemopoiesis. RESULTS: 4 patients achieved complete remission, 3-partial remission, 2 had progression and 1-stabilization. In mean follow-up 11 (2-20) months 7 of 10 patients were alive, overall survival being 15 +/- 2.4 months (95% confidence interval 10-19.7), median was not reached. 5 patients are in complete remission: 2 of them without further treatment, 3-after progression and repeat therapy including rituximab and interferon-alpha or rotuximab and CHOP chemotherapy. CONCLUSION: The addition of rituximab can improve the results of high-dose chemotherapy of patients with non-Hodgkin's lymphoma resistant to standard doses of cytostatics. Repeat use of this drug can be effective in some patients with progression after high-dose chemotherapy with rituximab.

[Mantle cell lymphoma]. / Limfoma iz kletok mantii.

Two morphological variants of mantle cell lymphoma are described: classic and blastoid. The former consists of small and medium-size cells, the latter is represented by cells with lympho- and centroblast morphology. An immunohistochemical examination has established a high degree of cyclic D1 expression by these lymphomas.

[Clinico-immunological characteristics of lymphoid tumors in children]. / Kliniko-immunomorfologicheskaia kharakteristika limfoidnykh opukholei u detei.

The clinical and immunological characteristics of lymphoid tumors were compared in 591 children with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Comprehensive investigation of a tumor cell by using cytological, morphological, and immunological studies revealed the most significant criteria for differential diagnosis of ALL and NHL in children and showed the specific features of the site of a tumor and the extent of its growth in ALL and NHL in relation to the immunological affiliation of a tumor cell. The predominance of immature forms, such as stem-cell CD34+, pre-pre-B, pre-B and less commonly T-cell forms with almost none peripheral B- and T-cell markers could be immunophenotypically detected in ALL. NHL was, on the contrary, characterized by the prevalence of mature immunological subtypes with peripheral B- and T-cell markers and much less frequently pre-B and pre-T cells and at the same time there was no CD34 antigen in the tumor cells. Anaplastic giant lymphoma was a peculiar type of NHL characterized by the presence of large cells having marked anaplasia and expression on the surface of CD30 antigen. A comprehensive study of lymphoid tumors in children showed that immunophenotyping was of great value, whose results were associated with the specific feature of tumor growth and prognosis, which should be borne in mind while planning antitumor therapy programmes.

[Contemporary possibilities of clinical immunology in oncology]. / Sovremennye vozmozhnosti klinicheskoi immunologii v onkologii.

Clinical immunology involves studies of immunological diagnosis and monitoring of cancer patients, their immunity and treatment-induced changes, including those associated with immunotherapeutical exposures, immunodiagnosis of leukemias, estimation of solid tumor markers. Immunophenotyping of peripheral blood cells from patients with solid tumors treated with chemo- and immunotherapy has elucidated some relationships to evaluate the efficiency of treatment. Detailed characterization of the structure of leukemic clone has promoted development of individual treatment regimens. The authors' experimental studies will evaluate the effects of cytokines on the mechanisms of multidrug resistance caused by mdr-1 gene hyperexpression and on apoptosis processes diminished by bcl-2 gene hyperexpression.

[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.

[Diagnosis of chronic lymphoid leukemia (an immunomorphological study)]. / K diagnostike khronicheskogo limfoleikoza (immunomorfologicheskoe issledovanie).

31 cases of chronic lymphoid leukemia (CLL)/lymphoma from small lymphocytes (LSL) was studied immunomorphologically. All cases had B-phenotype and positive expression of markers CD 5, CD 23. Most characteristic for CLL/LSL was pseudofollicular character of tumour growth. Two morphological variants of CLL/LSL having similar phenotype were distinguished: typical variant with roundish conturs of tumour cells and atypical with centrocytoid morphology of tumour cell nuclei.

[Phenotype characteristics of skin dendritic cells in patients with psoriatic arthritis during the treatment with deresinated naphthalan]. / Fenotipicheskie osobennosti dendriticheskikh kletok kozhi u bol'nykh psoriaticheskim artritom pod vliianiem lecheniia obessmolennym naftalainom.

The study of the phenotype of immunocompetent dendritic cells of the skin in patients with psoriatic arthritis in the course of treatment with deresinated naphthalan (DRN) has revealed some aspects of the mechanism of therapeutic action of DRN. Use of the complex of monoclonal antibodies allowed the authors to determine membrane markers of various cells belonging to the system of mononuclear phagocytes and participating in development of immunoinflammation in the skin. The active stage of the disease is characterized by a fall in the number of CDIa+ cells. HLA-DR+ cells are more resistant. DRN therapy led to prevalence of CDIa+ cells.