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Azoximer bromide (AZB) was identified as an immunomodulator, and was initially developed and currently successfully indicated as one of several natural polyelectrolytes, a vaccine adjuvant, and an effective agent for the treatment of infectious and inflammatory diseases of viral, bacterial, and fungal origin. AZB has the potential to increase an individual's resistance to local and general infection and is indicated for the treatment of viral infections, and has also demonstrated clinical efficacy in the treatment of a variety of secondary immunodeficiencies. However, AZB may offer long-term promise beyond use against infection. Multiple clinical trials and research studies in cancer patients have reported favourable outcomes with AZB as well as an optimal safety and tolerability profile. The findings raise the possibility of direct antitumor properties. This literature review analyses the novel mechanisms that mediate the AZB direct anticancer effects. Overall, the evidence suggests that AZB has the hallmark of an agent that could be used to support existing cancer treatments at different stages of disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grivtsova, Falaleeva and Tupitsyn.)

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 study of phenotyping features, membrane markers of epidermic keratinocytes, their production of adhesive molecules has established structural basis of favourable effect of deresinated naphthalan on the skin and articular syndromes in patients with psoriatic adtheritis. The immunohistochemical examination of the skin biopsies using monoclonal antibodies in the test of indirect immunofluorescence has found that deresinated naphthalan in patients suppresses immunoinflammatory reactions in the skin. Monitoring of expression of molecules HLA--on keratinocytes may be helpful for prediction of the skin and joint manifestation.

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.

The results are available of clinical, morphological, cytological and immunological investigations of orbital lymphomas and lymphomas of appendages of the eye. Malignant lymphoma was detected in 17 patients and reactive lymphoid hyperplasia in 3 patients. All the malignant lymphomas had B-cell phenotype. By cell composition, MALT-lymphoma is more polymorphic than lymphoma from mantle zone cells and lymphoma from small lymphocytes and centro follicular lymphoma. The conjunctive is affected primarily with lymphoma from marginal zone cells or mantle zone cells. As a rule, this is a primary local lesion. Other variants of orbital lymphoma and lymphoma of the eye appendages develop more often as secondary lesions in systemic disease and are characterized by more aggressive course. The key in differential diagnosis of reactive lymphoid hyperplasia and small cells lymphomas is immunophenotyping, especially at initial stages of the tumor process.

Classic morphological and lymphohistiocytic variant were found in 46 and 2 cases, respectively, of 49 LCAL cases studied pathohistologically. One patient had a variant with a predominance of small tumor cells. Ultrastructurally, cells with feature of histiocytic and lymphoid differentiation and undifferentiated cells in various proportions were observed.

Using histochemical methods, we studied distribution of dipeptidylaminopeptidase-IV (DPP-IV) in tumor cells of 16 patients with non-Hodgkin's malignant lymphomas (NHL) including B-cell NHL (10 cases), pleomorphic T-cell lymphoma (1 case), CD30+ anaplastic large cell lymphoma (ALCL) of T-cell (1 case) and ALCL of null-cell type (4 cases) and of 13 patients with Hodgkin's disease (HD). The results indicate that tumour cells of pleomorphic T-cell NHL and ALCL of T- and null-cell type showed DPP-IV activity. In contrast, no DPP-IV activity was seen in the tumor cells of B-cell NHL (lymphocytic, centroblastic/centrocytic, centroblastic, immunoblastic), in Berezovsky-Reed-Sternberg and Hodgkin's cells of different HD variants. These results demonstrate that difference in DPP-IV activity between tumor cells of ALCL and HD may be diagnostically important for separation of ALCL from HD and moreover may be used in verification of the borderline between HD-like ALCL and ALCL-like HD. It is possible that DPP-IV activity contributes to pathogenesis of ALCL and may determine clinical behaviour of this NHL being involved in autocrine and paracrine regulation of tumor cell growth of ALCL.

The authors have examined 134 children with acute lymphoblast cell leukemia (ALCL) who were treated at the Research Institute of Pediatric Oncology and Hematology, Russian Cancer Research Center, in January 1990 to November 1999, and followed up till March 1, 1999. The mean duration of follow-ups was 57.46 +/- 2.87 months. The minimum follow-up was 4 months. The immunophenotypical features of stem cell immunological subvariant of ALCL identified from the presence of 10% or 15% of CD34+ lymphoblast cells were similar in the leukemia clone. There is evidence for the isolation of the least mature, stem-cell immunological subvariant of ALCL in children. The immunophenotypic features of stem-cell ALCL in children were as follows: the expression of myeloid antigens (linear and different marker leukemias) and the higher rates of involvement of B-cell leukemias. The clinical and hematological features of stem-cell versus CD34-negative ALCL in children were the low levels of leukocytes (p = 0.009) and blast cells (p = 0.018) in the peripheral blood at diagnosis. At the same time, stem-cell ALCL showed a poorer prognosis. Moreover, blast cell CD34 antigen expression deteriorated prognosis for pre-pre-B (common) immunological variant of ALCL (p = 0.035). Intensified ALCL treatment programmes improved relapseless survival of patients with stem-cell ALCL (p = 0.0042).

Thirty eight children with large-cell anaplastic lymphomas have been recently treated at the Pediatric Department of Malignant Lymphomas, Russian Cancer Research Center, Russian Academy of Medical Sciences. Cytoimmunological studies have revealed that 24 patients had 4 types of cellular elements of large-cell anaplastic lymphoma: Kil(+), Kil(+)B, B-cell, and T-cell lymphomas in 11, 2, 8, and 3 children, respectively. Intensive chemotherapy was performed in relation to the immunophenotype.

Differential diagnosis was established by complex morphological examination in 290 pediatric patients with Langerhans cell, sinus or malignant histiocytosis. An immunologic study was performed in one-third of patients. Clinical symptoms and results of therapy are presented.

We describe a patient with acute myeloblastic leukemia (AML-M0) whose cells had a t(2;11)(p21;q23). Fluorescence in situ hybridization analysis with a probe for MLL showed that it was split, hybridizing to both the derivative 2 and 11 chromosomes. Nineteen other patients with 2p;11q translocations have been described; breakpoints in 14 of these are the same as in the case we describe. The phenotype of these patients is quite variable, with 14 patients having myelodysplastic syndrome which evolved to AML in six. Four patients had AML and two had acute lymphoblastic leukemia. MLL status has been studied in two other patients; one had MLL rearranged and one did not.

Aim: Review of literature data and original experience with Richter's syndrome., Materials and Methods: 250 patients suffering from malignant lymphoproliferative diseases with blood and bone marrow lymphocytosis were observed. 8 (3.2%) of them developed diffuse large-cell lymphoma (criteria and classification of REAL)., Results: 5 of the above 8 patients demonstrated spontaneous regression of lymphocytosis. These cases may illustrate transformation (clonal progression) of one morphological variant of malignant non-Hodgkin's lymphoma into another one, more aggressive. For this rare variant of Richter's syndrome running with regression of lymphocytosis the term Richter-Lortolary syndrome is proposed. Lortolary was the first who revealed a decrease of lymphocytosis in Richter's syndrome. The studies of the genome structure, first of all, of immunoglobulin genes show that in Richter-Lortolary syndrome it is easier, to confirm monoclonality of the two tumors (lymphocytic and large-cell) than to reject it. However, the idea of transformation has not been confirmed morphologically yet., Conclusion: Development of diffuse large-cell lymphoma in the course of chronic lymphatic tumor does not always indicate terminal state, later stage of tumor progression and poor prognosis.

26 cases of lymphoproliferative diseases were studied: 8 cases of reactive follicular hyperplasia (RFH), 11 cases of non-Hodgkin's malignant lymphomas (NML), 7 cases of lymphogranulomatosis (LGM). Only gamma-glutamyl transpeptidase (GGT) was found in lymphoid cells of B- and T-dependent areas of lymph nodes with reactive changes as well as in tumor cells of NML and LGM. GGT activity was more pronounced in NML of high-grade malignancy (centroblast and immunoblast) as compared to lymphomas of lower grade of malignancy (lymphocytic, centroblast-centrocytic and in Lennert lymphoma). GGT activity in cells of Hodgkin and Berezovsky-Sterberg in some cases of LGM was high, in others low. Significant differences in GGT activity between RFH and follicular centroblast-centrocytic lymphoma were not found. Activity of aminopeptidase M was observed in histiocytes, fibroblasts, vessels and areas of connective tissue growth. Aminopeptidase A activity was observed in vessels only. Activity of dipeptidyl(amino)peptidase IV was observed in some lymphoid cells in RFH, NML and LGM. Thus, GGT activity may be considered as a differential-diagnostic marker in separating NML of high and low degree of malignancy and this may presume a different sensitivity to the therapy.

Eighteen patients with relapsed or refractory Hodgkin's disease (HD) have been treated with high-dose chemotherapy (BEAM regimen) followed by autologous peripheral stem cells and/or bone marrow rescue. There were no treatment-related deaths. Overall response rate was 82%. With a median follow-up of 10 months (3-24 months) overall survival and freedom from progression were 100 and 94% (95% confidence interval 58-97%), respectively. The use of peripheral stem cells in addition to bone marrow resulted in a significant shortening of the time to engraftment (p < 0.01). The BEAM regimen is an effective conditioning schedule which is well tolerated.