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Biomedical subjects

I A Vorob'ev

Publications and source records attributed to I A Vorob'ev.

At least 19 recordsLinked to original sources
PubMed2006

[Characteristics of T-cell immunity in patients with acute leukemia].

AIM: To study a cytokine profile of cytotoxic T-cells and T-helpers at diagnosis of acute myeloid and lymphoblastic leukemia (AML and ALL) and at different stages of its treatment. MATERIAL AND METHODS: T-cell population of peripheral blood lymphocytes was studied in 19 AML patients at diagnosis, 13 AML patients in remission, 5 AML patients in developing recurrence and 5 ALL patients at diagnosis. The control group consisted of 10 healthy donors. A mononuclear fraction of peripheral blood cells was stained with monoclonal antibodies. Surface expression of CD3, CD4, CD8 antigens was estimated with the use of flow cytofluorimeter FACS Calibur. Part of the cells were cultured for production of activated lymphocytes. The cytokine profile of T-cells was investigated according to the modified method of Rostaing et al. in the population of CD3+CD8+ and CD3+CD8- T-cells using the flow cytofluorimeter FACS Calibur. The results were processed with the programs CellQuest and WinMDI, Statistica Module Switcher. RESULTS: The percentage of CD3+CD8+ cells producing interferon-gamma (IF-g) was the same in AML patients and donors. The percentage of CD3+CD8- cells (T-helpers) producing IF-g was similar in the patients at diagnosis and in complete remission being higher than in healthy donors. The number of CD3+CD8- cells producing IF-g was reduced in recurrence while the number of CD3+CD8+ and CD3+CD8- cells producing interleukin-4 (IL-4) increased. In the onset of the disease, ALL patients had significantly increased percentage of CD3+CD8- IL-4 cells. CONCLUSION: The results obtained evidence for different polarization of T-cell immunity in AML and ALL patients at the time of diagnosis, remission and recurrence: in the onset of AML there was an increase in the production of Th1--proinflammatory cytokines, in ALL--in percent of Th-2 cytokines. In AML recurrence the balance of cytokines shifted in the direction of Th-2 response.

Acute Disease↗
PubMed2006

[Flow fluorimetry in differential diagnosis of diffuse large B-cell lymphoma].

AIM: To analyse immunophenotype of diffuse large B-cell lymphoma (DLBCL) with flow cytometry. MATERIAL AND METHODS: Combinations of antibodies against the following antigens were used: CD3/ CD19/CD45, CD5/CD19/CD38, CD19/CD10/CD23, CD4/CD8/CD3, kappa/lambda/CD19, CD25/CD20/FMC7; CD43/CD22/CD20; CD79a/Ki-67/CD3; cytoplasmic kappa/lambda. The analysis was made on flow fluorimeter FacsCalibur using computer program CellQuest (Beckton Dickenson, USA). RESULTS: Specific coexpression of markers is not detectable in DLBCL, in the greatest degree the phenotype corresponds to lymphoma from the cells of the marginal zone. The study of cells with maximal direct light diffusion provides more precise assessment of clonality and proliferative potential of tumor cells than the analysis of the whole lymphocytic polygon. The proliferative index in 33 cases of DLBCL varied in the range 10-60%. CONCLUSION: Flow cytometry in most DLBCL cases allows identification of B-cell clonality, more precise assessment of a proliferative potential of the tumor.

Antigens, Neoplasm↗
PubMed2006

[The modified program NHL-BFM-90 in the treatment of patients with diffuse large B-cell lymphosarcoma].

AIM: To investigate efficacy of the modified protocol NHL-BFM-90 in patients with diffuse large B-cell lymphosarcoma (DLBCLS). MATERIAL AND METHODS: A total of 13 DLBCLS patients with stage II-IV of the disease with affection of lymph nodes at the disease onset (nodal lesion) and stage II with tumor size more than 10 cm (bulky disease) received first-line treatment according to the modified program NHL-BFM-90 from 2002 to 2005. The diagnosis was made by WHO criteria. RESULTS: A complete remission was achieved in 76.9% patients. Resistance to therapy was observed in the patients with bone marrow affection. The 2.5-year overall survival was 74%, 2-year event-free survival was 75% (the events were recurrence and resistance). Follow-up continued from 5 to 47 months. CONCLUSION: The efficacy of the modified protocol NHL-BFM-90 in DLBCLS patients with stage III-IV of the "nodal" disease and stage II of the "bulky" disease was high.

Adult↗
PubMed2006

[Microtubules are necessary for lamellae retraction of Vero cells].

Behavior of Vero cells under the 2,3-butaneodione monoxime (BDM) treatment was examined using video-microscopy with contrast enhancement. After addition of BDM to the culture medium the area of cell contact with substratum gradually reduced--within 5 min of treatment cell lamellae became thicker, after 60 min the cell area decreased approximately 70 %, and the cells became nearly rounded. At the same time actin bundles (stress fibers) depolymerized, and microtubule network became denser. Partial depolymerization of microfilaments by treatment with latrunculin B at a concentration of 5 nM resulted in complete loss of stress fibers, yet cells slightly change their form, and microtubule system remained the same as in the control cells. However, after addition of BDM in the presence of latrunculin B cells retracted their lamellae more quickly then under BDM sole treatment. To evaluate the role of microtubules in the process of cell retraction we depolymerized them with nocodazole taken at the concentration of 5 ng/ml. Under nocodazole treatment the cell area decreased approximately 20 %, and stress fibers became more thick and abandon. The cells did not change their form, and stress fibers depolymerized very slowly under BDM treatment in the absence of microtubules. After 1 h of BDM treatment in the presence ofnocodazole stress fibers were still more numerous than in the control cells. Complete depolymerization of stress fibers happened in 90 % of cells only in 24 h after addition of BDM. When nocodazole had been washed out of the culture medium in the presence of BDM, lamellae started shrinking in 6 min. This time corresponds to the time required for the partial restoration of microtubule system. On the bases of the results obtained we conclude that retraction of the lamellae in Vero cells is guided rather mainly by microtubules, than stress-fibers.

Animals↗
PubMed2005

[Acute lymphoblastic leukemias with aberrations of BCR-ABL genes].

AIM: To develop an original therapeutic strategy in Ph-positive acute lymphoblastic leukemia (ALL). MATERIAL AND METHODS: In November 2001 Hematological Research Center (HRC) initiated the study of chimeric BCR-ABL gene. During the first stage of the study (November 2001-July 2004), 18 primary ALL patients were recruited in HRC, from July 2004 to January 2005--16 patients in HRC, N.N. Burdenko Central Military Hospital, regional Samara hospital. The diagnosis of Ph-positive ALL was established in detection of translocation t(9;22) by standard cytogenetic test or fluorescent hibridization in situ with double signal (D-FISH), or by polymerase chain reaction with reverse transcription (RT-PCR). In detection of aberration of BCR-ABL gene the patients received stem hemopoietic cells, from June 2004 imatinib was added to chemotherapy in the period of induction and consolidation. RESULTS: Incidence rate of BCR-ABL-positive ALL by standard cytogenetic test and D-FISH makes up 20%, by RT-PCR--25%. Differences in chimeric transcripts detectability by different methods may be explained by different sensitivity of the methods. Complete hematological remissions were achieved in the majority of the patients (6 of 8) irrespective of imatinib administration. Achievement of molecular remission in BCR-ABL-positive ALL occurs also in standard chemotherapy but molecular remissions begin 2-4 months later than clinicohematological ones. CONCLUSION: In using imatinib combination with chemotherapy, molecular remission can be achieved simultaneously with hematological one. Long-term results will be analysed later.

Adolescent↗
PubMed2005

[Treatment of adult Berkitt-like lymphoma].

AIM: To compare programs of chemotherapy used in adult Berkitt-like lymphoma (ABLL); to assess efficacy and toxicity of the protocol AblL-M-04. MATERIAL AND METHODS: 31 ABLL patients (23 males, 8 females, mean age 27 years) participated in the study performed in Hematological Research Center in 1995-2004. ABLL stage I, II, III and IV was diagnosed in 3, 5, 8 and 15 patients, respectively. 10 patients had diffuse large B-cell lymphoma. 9 patients received 2 to 6 courses of CHOP, 1 patient--6 courses of Pro-Mace-Cytabom, 11 patients with newly diagnosed ABLL and 5 pretreated with CHOP--NHL-BFM-90. The modified protocol ABLL-M-04 of intensive short-term therapy included 10 patients, 2 of them pretreated. RESULTS: Of 10 patients given CHOP or CHOP-like courses 9 were resistant to therapy, 2 died of rapid progression, 7 were converted to the program therapy. 5 patients on the protocol NHL-BFM-90 died after short-term improvement. None of them achieved remission. Of 10 patients with newly diagnosed ABLL treated according to NHL-BFM-90 protocol, remission was achieved in 4 patients, follow-up median--34 months (2-56). Six patients died: 4 of progression, 2 of chemotherapy complications. BLL-M-04 therapy was made in 9 patients: 7 patients persisted on the first remission, 2 patients died of chemotherapy complications. Overall duration of the treatment was 3-3.5 months. CONCLUSION: The protocol ABLL-M-04 seems to be more effective than a classic NHL-BFM-90, but this must be supported by more cases. CHOP therapy cannot be recommended for patients with ABLL because of poor efficacy (all the CHOP patients died).

Adolescent↗
PubMed2005

[A CHOP-21 course efficacy in therapy of diffuse large B-cell lymphosarcoma].

AIM: To examine efficacy of polychemotherapy (PCT) CHOP-21 in patients with diffuse large B-cell lymphosarcoma (DLBCL). MATERIAL AND METHODS: Fifty-five DLBCL patients received first-line therapy according to CHOP-21 program in 1996-2004. The diagnosis was made by WHO criteria. RESULTS: Initially, 37 patients had lymph node lesions, 18--nonlymphatic lesions. Complete remissions were achieved in 49% (56.7% in nodal lesions, 33.3% in extranodal ones). Overall 5-year survival was 35%, event-free--25%, for patients with nodal lesions--36 and 32%, respectively, extranodal lesions--35 and 22%, respectively. Overall 5-year and event-free survival in patients with local lesions was 85 and 75%, generalized--25 and 20%, respectively. In patients with involvement of the gastrointestinal tract 3-year overall and event-free survival reached 50 and 45%. Event-free survival was not seen in patients with extranodal lesions of other locations in overall 3-year survival 45%. CONCLUSION: PCT program CHOP-21 was effective in DLBCL patients with local nodular lesions except cases with large-size tumors, invasion in the adjacent organs and tissues and isolated gastric lesion.

Adolescent↗
PubMed2005

[Tumor cell proliferative activity in aggressive human lymphomas: the influence of reactive cell admixture on the assessment of proliferative indices].

Uncontrolled proliferation is one of the main features of tumor cells, and therefore proliferative indices provide prognostic information, which might be valuable for treatment selection. However, in aggressive human lymphoid tumors, an admixture of normal (reactive) cells may be available in all organs infiltrated by neoplastic cells. We have presented data on determining proliferative activity using Ki-67 immunostaining, and demonstrated that an admixture of reactive cells could exert significant influence on the assessments of proliferative indices. We developed an experimental approach, which makes it possible to select neoplastic cells from the overall lymphoid population and to assess their proliferative activity - tumor cell proliferative indices. Tumor cell proferative indices determined in large cell lymphomas might be significantly higher than proliferative indices of overall populations, and the use of tumor cell proliferative indices will result in a more accurate assessment of disease prognosis.

Burkitt Lymphoma↗
PubMed2004

[The dynamics of microtubule repolymerization in a cell: rapid growth from the centrosome and slow recovery of free microtubules].

According to the current view, the microtubule system in animal cells consists of two components: microtubules attached to the centrosome (these microtubules stretch radially towards the cell margin), and free microtubules randomly distributed in the cytoplasm without visible association with any microtubule-organizing centers. The ratio of the two sets of microtubules in the whole microtubule array is under discussion. Addressing this question, we have analysed the recovery of microtubules in cultured Vero nucleated cells and cytoplasts, with and without centrosomes in these. Cells were fixed at different time points, and individual microtubules were traced on serial optical sections. During a slow recovery after cold treatment (4 degrees C, for 4 h; recovery at 30 degrees C) polymerization of microtubules started mainly from the centrosome. At early stages of recovery the share of free microtubules made about 10% of all microtubules, and their total length increased slower than the lenght of centrosome-attached microtubules. During a rapid recovery after nocodazole treatment (10 microg/ml, 2 h; recovery in drug-free medium at 37 degrees C), the share of free microtubules was about 35%, but their total length increased slower than the length of centrosome-attached microtubules. In 6-8 min (rapid recovery) or 12-16 min (slow recovery), tips of centrosomal microtubules reached the cell margin, and their increased density made it impossible to recognize individual microtubules. However, under the same conditions in cytoplasts without centrosomes the normal number of microtubules recovered only in 60 min, which enabled us to suppose that the complete recovery of microtubule system in the whole cells may be also rather long. When the first centrosomal microtubules reached the cell margin, the optical density of microtubules started to decrease from the centrosome region towards the cell margin, according to the exponential curve. Later on, the optical density in the centrosome region and near the cell margin remained at the same level, but microtubule density increased in the middle part of the cell, and in 45-60 min the plot of the optical density vs the distance from the centrosome became linear, as in control cells. Since no significant curling of microtubules occurs near the cell margin, the density of microtubules in the endoplasm may increase due only to polymerization of free microtubules. We suppose that in cultured cells the microtubule network recovery proceeds in two stages. At the initial stage, a rapid growth of centrosomal microtubules takes place in addition to the turnover of free microtubules with unstable minus ends. At the second stage, when microtubule growth from the centrosome becomes limited by the cell margin, a gradual extension of free microtubules occurs in the internal cytoplasm.

Animals↗
PubMed2004

[Prognostic value of a focal bone marrow lesion in diffuse large B-cell lymphosarcoma].

AIM: To study prognostic implications of a focal mature cell lesion of the bone marrow (BM) in patients with diffuse large B cell lymphosarcoma (DBLCL). MATERIAL AND METHODS: 54 patients with histologically confirmed DBLCL were given first-line CHOP and CHOP-like courses from 1996 to 2003. B-cell nature of the tumor was confirmed immunohistochemically, immunophenotypically and with flow fluorimetry. RESULTS: In debute of the disease 16 patients had local involvement of the lymph organs (stage I-II by Enn-Arbor), 21 patients--generalized disease (stage III-IV) and 17 patients--involvement of non-lymphatic organs. Overall 3-year survival in first-line therapy in mature cell lesion of BM was 23%, without it--0%. One-year event-free survival was 34 and 0%, respectively. CONCLUSION: The presence of a focal mature cell lesion of BM in DBLCL patients influences the prognosis. Regarding high frequency of transformation of mature cell lymphoproliferative diseases in DBLCL, focal lesion of BM is an indirect sign of a secondary nature of the disease.

Adult↗
PubMed2004

[Reorganization of microtubule system in pulmonary endothelial cells in response to thrombin treatment].

Thrombin induces rapid and reversible increase of endothelial (EC) barrier permeability associated with actin cytoskeleton remodeling and contraction. The role of microtubules (Mts) in EC barrier regulation compared with actin systems is poorly understood. In this work we studied pathways of Mt and actin regulation in response to thrombin treatment in cultured EC, and the involvement of trimeric G-proteins and in this process. Cells were treated with thrombin, and further analysed using immunofluorescent staining of actin and Mts, digital microscopy and morphometric analysis. In normal cells actin network consists of thin bundles basically located in the cell periphery, Mt density decreases from the cell center to the cell edge. Thrombin (25 nM) induced endothelial dysfunction associated with a rapid (within 5 min) decrease of peripheral Mt network and a slower actin stress fiber formation in the cytoplasm. Pretreatment with Pertussis toxin, which is Gi protein inhibitor, attenuated thrombin-induced stress fiber formation and Mt disassembly. Overexpression of activated G12, G13, Gi and Gq proteins, which are involved in thrombin receptor-mediated signaling, resulted in increasing stress fibers thickness and density and complete Mt disassembly. From the results obtained we suggest that thrombin regulates actin cytoskeleton of EC using local Mt depolymerization at the cell edge.

Actins↗
PubMed2003

[Morphological, morphometrical, and immunophenotypic characteristics of primary mediastinal B-cell lymphosarcoma].

AIM: To define histological, cytological, computer-morphometric and immunophenotypical features of primary mediastinal B-cell lymphosarcoma. MATERIAL AND METHOD: The study enrolled 43 patients with primary mediastinal B-cell lymphosarcoma (PMBCL) treated in Hematological Research Center from 1994 to 2002. The examination included morphological and immunophenotypical tests, computer morphometry of the cells by histological sections. RESULTS: PMBCL is represented by a composite population of cells of a giant, large and small size (nuclear areas 76.24 +/- 19.99, 37.77 +/- 8.0 and 17.12 +/- 4.34 mcm2. Three types were identified: giant-cell, large-cell and small-cell. A giant-cell type is represented by large and giant cells comprising, on the average, 44 and 31% of overall number of lymphoid cells. A large-cell type is primarily represented by large lymphoid cells (62% of the lymphoid population). Small-size type is represented by small cells (72% of cells). Frequent histological signs are diffuse sclerosis and focal necrosis. Tumor cells have B-cell nature. In the giant and large cell type more than 70% cells express PCNA, in the small cell type--less than 30%. Expression of activation marker CD30 is observed in 18% cases in the giant and large cell types. CONCLUSION: PMBCL is a morphologically heterogenous disease represented by combination of giant, large and small cells with immunophenotypically B-cell nature characterized in a giant cell and large cell type by prominent but in a small cell and large cell type by insignificant proliferative activity. CD30 expression is observed only in giant cell and large cell types.

Cytological Techniques↗