[Use of cyto-differentiating agents in oncology].
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Antineoplastic Agents↗
Biomedical subjects
A Iu Baryshnikov
Publications and source records attributed to A Iu Baryshnikov.
[Linear and adhesive phenotype of tumor lymphocytes and clinical course of chronic leucosis].
Determination of chronic lymphatic leukemia immunological phenotype, performed by the authors, was based upon the study of quantitative expression of membrane differentiation antigens on peripheral blood lymphocytes. The research included study of co-expression of adhesion molecules, belonging to the following families: beta 2 integrins (CD 11 beta, CD 18), immunoglobulins (CD 50), and CD 38 on tumor blood B-lymphocytes of various CD-types and T-lymphocytes in chronic leucosis. The authors developed a functional model of trans-endothelial migration of peripheral blood lymphocytes in chronic chronic lymphatic leukemia, taking into account their membrane adhesive characteristics and serum level of CD 50. The researchers determined clinical importance of the expression of linear and adhesive antigens on peripheral blood lymphocytes, and soluble HLA-1 (sHLA-1) serum levels in patients with chronic lymphatic leukemia.
Antigens, CD↗
[Melanoma cell lines as the basis for antitumor vaccine preparation].
The aim of the study was to obtain cell lines from tumor samples, and to determine phenotypic cell characteristics in order to choose the optimal line for vaccine preparation. 15 cell lines with stable growth, varying in cultural growth character and cytomorphology, were obtained from samples taken from patients with metastatic skin melanoma. Immunofluorescense method was used to determine the expression of T- and B-lymphocyte markers, antigens of major histocompatibility complex (MHC) class I and II, and CD86 co-stimulating molecule in the cell lines. The expression of melanocyte differentiation antigens and cancer/testicular antigens was evaluated using immunocytochemical assay. The results allowed the authors to distinguish three types of melanoma cell lines according to the expression of MHC molecules: MHC-negative; MHC class I positive; MHC classes I and II positive.
Antigens, Neoplasm↗
[Study of optical absorption of sensitizers in vivo].
The subject of the paper is study of optical absorption of sensitizers in biological tissue. The study shows that absorbance can be used as a tool that allows studying biodistribution of sensitizers and their interaction with tissue in vivo. The article presents a simple technique of determining biological tissue absorption in vivo, and discusses the results of experimental animal studies of some sensitizers.
Equipment Design↗
[Expression of epidermal growth factor receptor (EGFR) in ovarian carcinoma stage III-IV].
Hyperexpression of epidermal growth factor receptor (EGFR) is often identified as unfavorable prognosis for different epithelial cancers. The study was concerned with an attempt of establishing a relationship between EGFR expression, on the one hand, and patient's clinico-morphological status, prognosis and efficacy of chemotherapy for stage III-IV serous ovarian carcinoma, on the other. EGFR hyperexpression predominated in advanced aggressive tumors and involved a significantly shorter period preceding tumor progression. Similarly, overall survival median in patients with EGFR hyperexpression (21+/-4 months) appeared lower than without it (42+/-8 months). In serous ovarian carcinoma stage III-IV, EGFR hyperexpression should be considered sufficient for prognosis of chemotherapy efficacy, pre-progression time and survival.
Adult↗
[Dynamics of the soluble CD50-antigen level in patients with breast cancer in the course of combined therapy].
Immune enzyme assay with polyclonal and monoclonal antibodies was made use of to investigate the dynamic changes of soluble CD50-antigen in patients with breast cancer during chemotherapy and surgical treatment. A dependence of the content of the above antibody on a variety of parameters characterizing the tumor process and patients age was detected. The determination of a dynamic level of this protein provides for evaluating the efficiency of a treatment scheme.
Adult↗
[Cell technologies in the therapy of malignant neoplasms].
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Biomedical Technology↗
[Principles and practice of vaccinotherapy for cancer].
Active specific immunotherapy with cancer vaccines is a new approach to treating cancer. After surgical tumor removal, vaccinotherapy has been ascertained to cause an increase in the duration of an asymptomatic period and to postpone the onset of recurrences. Moreover, vaccinotherapy leads to the regression or stabilization of growth of some types of tumors in patients with clinically determined metastases. The review outlines the principles of designing antitumor vaccines, the role of the immune system in the elimination of tumor cells, as well as tumor-associated antigens and presents the types of antitumor vaccines used in clinical practice.
Antigens, Neoplasm↗
[Monoclonal antibody-based design of antitumor drugs: prerequisites and progress].
To obtain monoclonal antibodies (MAb) to tumor-specific antigens is a promising line in the design of antitumor drugs since this makes it possible to provide a strictly selective effect on tumor cells. As of now, thousands of MAbs to different human and animal antigens have been obtained; hundreds of them have shown their promising properties in experimental studies, tens have been tested in clinical trials and about 10 MAb have been already permitted for clinical use in oncological care. The N. N. Blokhin Russian Cancer Research Center (RCRC), Russian Academy of Medical Sciences (RAMS), is one of few Russian research organizations where the technology of MAb production has been successfully introduced and is applied now. By using this technology, RCRC, RAMS, has designed the drugs Imyteran and ATEMA that may be used to treat tumor and other diseases and at present they are under clinical trials. A great variety of MAbs that can potentially replace expensive imported analogues are pre-clinically designed.
Alemtuzumab↗
[Pharmacological aspects in the development of liposomal medicinal preparations for the internal injection of hydrophobic cytostatics].
To improve the action and selectivity of new drugs on tumor cells and the use of currently available pharmaceutical technologies to develop the systems of controlled transport of well-known antitumor compounds is one of the ways of enhancing the efficiency of drug therapy for tumors. The tropicity of steroid hormones to definite organs and tissues makes it possible to use them as specific messengers of alkylating groups to target tissues and tumors. Hormone cytostatics synthesized by this principle have a double mechanism of hormonal and cytotoxic actions. The original Russian water-insoluble hormone cytostatistics testifenon, kortifen, and cytestrol acetate demonstrated local tissue irritation together with high antitumor activity. No rational dosage forms make it possible to conduct clinical trials by parenteral administration. The aim of this paper is to summarize the authors' results of designing hydrophobic antitumor hormone cytostatics. The advantages and disadvantages of different approaches to designing traditional dosage forms and to applying colloid liposomal systems for intravenous administration of water-insoluble agents are shown.
Antineoplastic Agents, Alkylating↗
[The role of adhesion molecules (ICAM-1 and E-selectin) in development of diabetic microangiopathies].
AIM: To examine the expression of the intercellular adhesion molecule-1 (ICAM-1, CD54) on the surface of leukocytes and a soluble E-selectin (CD62) level in patients with diabetes mellitus type 1 (DM1) at various stages of diabetic nephropathy and retinopathy. MATERIAL AND METHODS: 42 patients with newly diagnosed and long-standing DM1 with presence or absence of microangiopathy (diabetic nephropathy and retinopathy) were examined. Routine laboratory, ophthalmologic tests, a special immunological test with ICAM-1 expression and soluble E-selectin (sES) examination were performed. RESULTS: The tests show increased ICAM-1 expression and sES level in all the patients vs controls. In newly diagnosed DM1 a high sES level was observed. In long-standing DM1 and absence of microangiopathy a sES level was also high. In patients with neovascularisation and proteinuria the sES level was two times higher than that in other subgroups. We also found an increased percentage of ICAM-1, CD54-positive lymphocytes and granulocytes in patients with microalbuminuria and especially with proteinuria and neovascularization. There were no correlations of ICAM-1 and sES levels with sex, DM duration, cholesterol and triglycerides. CONCLUSION: The findings show endothelium and leukocytes activation at early disease stages. Enhanced endothelium and leukocytes activation is associated with late complications.
Adult↗
[Comparison of immunocytochemical and immunohistochemical methods for biomarker detection in breast cancer].
The detection of the biological parameters of the tumor before the treatment beginning becomes of more importance. The present study aimed to carry out the comparative analysis of the molecular markers expression (P53, Ki-67, Her-2/neu, Bcl-2, Bax, ER, FasL and CD95) at the cytologic and the correspondent histologic samples. The 18 tissue samples of the breast cancer were investigated. The immunocytochemical and the immunohistochemical methods of the molecular markers determination were used. Our study showed the correlation between two methods and the possibility of the use of the immunocytochemical staining as routine method of the molecular markers expression determination.
Biomarkers, Tumor↗
[Functional activity of ABC transporters (markers of multidrug resistance) in human colon adenocarcinoma and normal colonic mucosa].
Functional activity of multidrug resistance (MDR) markers (total activity of ABC-transporters, P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) activities) in human colon adenocarcinoma and normal mucosa was examined. Functional activity of ABC-transporters was revealed in all colon tumors and in 70% of normal mucosa samples investigated. Expression of Pgp and MRP functional activity was determined in about 50% and 70% of colon tumors respectively. Pgp+MRP+ phenotype was determined in 36% of normal mucosa and adenocarcinoma samples. Expression of Pgp+MRP- phenotype was practically the same in normal mucosa and tumors (in 10 and 18% of samples respectively). Pgp-MRP+ phenotype was revealed two times more often in tumors than in mucosa--in 36 and 18% respectively. On the contrary, Pgp-MRP- phenotype was detected more rarely in tumors than in mucosa (in 10 and 36% of samples respectively). Transporters different from Pgp and MRP were also determined in some tumors and normal mucosa. At the patients with expression of Pgp function in normal mucosa the activity of the transporter was revealed in 25% of tumor samples only. On the contrary, at the patients with expression of MRP function in normal mucosa the activity of the transporter was revealed in 70% of tumor samples. At the patients with no expression of Pgp or MRP activity in normal mucosa the function of the transporters in tumors was determined in 60% and 70% of samples respectively. It is concluded that functional activity of various ABC-transporters (Pgp, MRP and other different from Pgp and MRP) is expressed in human colon adenocarcinoma; expression of ABC-transporters functional activity in normal mucosa does not predict MDR phenotype of the tumor.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Functional activity and expression of P-glycoprotein in chronic myeloid leukemia].
AIM: To evaluate the prognostic significance of P-glycoprotein (Pgp) in chronic myeloid leukemia (CML). MATERIALS AND METHODS: Functional activity (rhodamine 123 test) and expression of Pgp (binding of UIC2 monoclonal antibodies by cells) were evaluated by flow cytofluorometry. A total of 141 samples of peripheral blood from 121 patients with various stages of CML were examined. RESULTS: The number of patients whose cells express functionally active Pgp increases during the blast crisis (BC) in comparison with the chronic phase (CP). Repeated testing of patients with BC and CP showed that Pgp-expressing cells can disappear from the peripheral blood of patients despite the treatment by Pgp preparations and substrates. However the number of cases with expression and functional activity of Pgp increases in the course of BC. Several patients in whom functionally active Pgp was not detected during diagnosis of BC had longer BC phase than patients with the active protein. CONCLUSION: These data suggest that active Pgp contributes to CML BC (presumably to patient's response to therapy) but this contribution is not decisive.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Apoptosis and proliferative activity of bone marrow cells in patients with aplastic syndromes as evidenced by trephine biopsy].
AIM: To clarify the effect of cyclosporin A (CSA) on the apoptosis and proliferative activity of bone marrow cells in patients with aplastic syndromes by trepanobiopsy evidence. MATERIALS AND METHODS: The TUNEL immunohistochemical assay was used to study apoptosis of bone marrow cells in the histological specimens from 24 patients: 8 with refractory anemia (RA), 8 with acute small-proportion leukemias [RA with excessive blasts (RAEB) + RAEB in transformation (RAEBt)], 3 with acute non-lymphoblastic leukemia (ANLL), 5 with lymphogranulomatosis (LGM). Control apoptosis examination was made in 10 patients treated with CSA. The proliferative activity of bone marrow cell was evaluated by bone marrow histological specimens from 10 patients (8 patients with RA and 2 with RAEB + RAEBt) at the onset of disease and during CSA therapy in the immunohistochemical test with primary nuclear antigen Ki-67 antigen antibodies. Changes in the proliferative activity and degree of apoptosis of bone marrow cells were assessed in relation to the cellularity detectable by the histological specimens. RESULTS: Patients with RA showed an increase in bone marrow cell apoptosis to 25.375 +/- 6.874 (-10.8 +/- 5.122 and 8.333 +/- 5.84 in controls and ANLL patients, respectively). The cells of hemopoiesis and stromal microenvironment are in the process of cell death. Higher bone marrow cellularity is observed in CSA-treated patients at clinical and hematological remission, which is followed by rises in the index of proliferation and the degree of apoptosis. CONCLUSION: The clinical effect of CSA in patients with aplastic syndromes is induced by its direct or mediated stimulating effect on pluripotent stem cells of hemopoiesis, by increasing bone marrow cellularity at the expense of clonal and/or normal hemopoiesis.
Acute Disease↗
[Endothelial dysfunction in the development of vascular complications in diabetes mellitus].
Patients with type 1 diabetes, aged 18 to 42 years, were compared to those aged 11 to 22 years. Activities of endothelial vasoactive factors and endothelial and leukocyte adhesion molecules were studied at different stages of development diabetes complications: nephropathy and retinopathy. The findings reveal role of the vasoactive factors in microangiopathy course.
Adolescent↗
[Monoclonal antibodies in oncology].
A start was made on explorations into hybridoma technologies at the N. N. Blokhin Russian Cancer Research Center in the late 1970s. ICO series monoclonal antibodies (MAb) against different human differentiation leukocyte antigens have been designed in a short period of time. MAb to antigens CD25, CD8, CDw50, CD5, CD4, CD7, CD3, CD71, CD34, CD45, CD38, CD11b, CD16, and CD95 have gained worldwide recognition at International HDLA Workshop Conferences. Today, the collection of hybridomas at the Center includes more than 200 samples. MAb are used for immunophenotypic assays of blood and bone marrow cells, for classification of lymphomas and leukemias, for assessment of human immunity for immunophenotypic diagnosis of minimal residual tumor in multiple myeloma. New prognostic markers in various nosological entities and MAb biological activity are under study. MAb have been used to develop ELISA diagnostic kits. They are employed as vectors for immunotoxin design, for immunomagnetic separation, many MAb-based drugs have been designed. A start has been made on the promising development of a new line of biopharmacy, namely design of new immunoliposomal dosage forms of doxorubicin and betulinic acids.
Antibodies, Monoclonal↗
[Characteristics of drug resistance of tumor plasmocytes in vitro in patients with multiple myeloma differently responsive to chemotherapy].
AIM: To determine sensitivity of tumor plasmocytes in vitro to cytostatic drugs (prednisolone, alkeran belustin, vincristine, rubomycin, doxorubicin, cytarabin, methotrexate, cysplatin, etoposide). MATERIAL AND METHODS: The sensitivity was measured with DISC method in 12 patients with multiple myeloma (MM) in two groups: resistant and responsive to induction polychemotherapy (PCT). RESULTS: The groups appeared significantly different by lowering of pathological paraprotein concentration (PIg): by 7.4 +/- 2.5% and 32.5 +/- 3.7%, respectively (p < 0.05). The resistance to the drugs was higher in the resistant patients than in the responders (0.7 +/- 0.28 versus 0.4 +/- 0.02, p < 0.05). PCT schemes of resistant patients contained 65.0 +/- 2.3% of ineffective drugs. In the responders the percentage was 35.7 +/- 5.3% (p < 0.05). CONCLUSION: The relationship exists between resistance of tumor plasmocytes to drugs in vitro and clinical findings.
Adult↗