Tumor uses various mechanisms to "escape" from immune surveillance including the important role of dysregulation of interaction of signals from corresponding co-stimulatory and co-inhibitory receptors (so-called "control points immunity"-- immune "checkpoints") modulating T-cell activation process. A creation of targeted drugs impacting on immune "checkpoints"" is a new promising trend in modern oncoimmunology. This review is devoted to a brief characterization of some receptors of immune competent cells (such as activation and inhibitor), which play a crucial role in the interaction of the immune system and tumors as well as targeted drugs acting on them for therapeutic purpose.
View Article and Find Full Text PDFVestn Ross Akad Med Nauk
April 2012
The paper contains an overview of the role of certain minor subpopulations of lymphocytes in tumour growth and of the main results obtained in the studies of the phenotype of immunocompetent cells from cancer patients. Special attention is given to selected indicators of immunity as predictors of the disease and efficacy of immunotherapy.
View Article and Find Full Text PDFTo identify C-MYC targets rate-limiting for proliferation of malignant melanoma, we stably inhibited C-MYC in several human metastatic melanoma lines via lentivirus-based shRNAs approximately to the levels detected in normal melanocytes. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2).
View Article and Find Full Text PDFWe studied the effect of Herceptin therapy on the population composition of lymphocytes and percentage of CD4+CD25+ cells (regulatory T cells) in breast cancer patients. Herceptin treatment decreased the number of "professional" T suppressors (CD4+CD25+ cells and regulatory T cells) in the peripheral blood.
View Article and Find Full Text PDFThe ability of synthetic interferon inducer, neovir (sodium 10-methylencarboxylate-9-acridone), was studied dealing with modulation of the sensitivity of HT-29 and K-562 cells, intact and transfected with mdr1 gene, in relation to the cytototoxic action of antitumor drugs. Neovir exerted the direct cytotoxic action on cells of all studied lines. Preliminary incubation of cells with neovir for 24 h efficiently increased the cytotoxic effect of doxorubicin and vincristine.
View Article and Find Full Text PDFClinical 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.
View Article and Find Full Text PDFUsing primary cultures of human smooth muscle intimal cells and mouse peritoneal macrophages it was demonstrated that oral hypoglycemic agents, sulfonylurea derivatives, at concentrations 10(-5)-10(-4) mol/l caused significant (by 25%-60%) intracellular total cholesterol accumulation. This in vitro atherogenic effect was confirmed in an ex vivo model. Sera from Type 2 diabetic patients, taken after sulfonylurea administration, acquired the ability to induce cholesterol accumulation in cultured cells.
View Article and Find Full Text PDFFifty-five serum samples from 99 Type 1 and 71 serum samples from 81 Type 2 diabetic patients (56% and 88%, respectively) brought about a 1.5-3.5-fold increase in total cholesterol content of cultured human intimal aortic cells.
View Article and Find Full Text PDFInvasion Metastasis
March 1994
Interleukin-2 (IL-2) has been reported to induce mononuclear cell-dependent platelet perturbations and to reduce the incidence of metastases in rodent models. In this study, MC-1 leukemic cell-induced platelet aggregation was associated with a significant increase in thromboxane B2 (TXB2) secretion, quantified by RIA, but a decrease in leukotriene B4 (LTB-4) secretion compared to incubations of tumor cells alone. Whereas MC-1 cells also activated platelets as observed by a significant increase in scanning electron-microscopic spheroidal forms distributed throughout the platelet pool, increasing concentrations of IL-2-activated peripheral blood mononuclear cells (PBMC), but not IL-2 or PBMC alone, reversed this effect with a reduction in activated spheroidal forms.
View Article and Find Full Text PDFThe effects of sera and low density lipoproteins (LDL) on cholesterol levels were evaluated in cultured aortic intimal cells from patients with Types 1 and 2 diabetes mellitus. About 80% Type 1 diabetic patients' sera and 90% of Type 2 diabetic patients' sera caused a 1.5-4-fold increase in intracellular cholesterol levels.
View Article and Find Full Text PDFThe results of studies of the accessory functions of various heterologous cells in gamma interferon production by human blood and lymph T-lymphocytes are presented. It was shown that, in addition to autologous and allogeneic monocytes, the role of accessory cells may be played to some extent by xenogeneic (mouse) monocytes as well as human continuous cells of different origin. The degree of the accessory function was different in interaction of the accessory cells with T-lymphocytes from blood and lymph.
View Article and Find Full Text PDFThe cells responsible for production of human alpha and gamma interferons with proper inducers were studied using methods for fractionation of human blood mononuclear cells. The results indicated cooperation and mutual regulation by cells of interferon production. Monocytes were shown to play the leading role in the synthesis of acid-stable alpha interferon, whereas accessory cells were required for gamma interferon synthesis by T lymphocytes.
View Article and Find Full Text PDFThe data on the application of monoclonal antibodies (ICO-10) and rabbit complement for working the conditions of allogeneic bone marrow transplantation are presented in the paper. The treatment with monoclonal antibodies and bone marrow complement from BALB/c mice for 2 times prevented the development of transplant versus host reaction and completely protected lethally irradiated (CBA X X C57B1/6)FI mice-recipients from death. Thymus atrophy and the absence of T-cells in the peripheral blood was observed in these mice.
View Article and Find Full Text PDFA study was made of the mouse life span in relation to the time of tumor cell injection on an hourly basis, while the carcinogenic effect was studied in relation to the time of urethan injection. Changes in both the values were shown to vary with ultradian rhythms. It was found that natural killer cell activity against tumor cells, migration index of normal spleen cells in the presence of tumor cells and the activity of carcinogen-metabolising enzyme system of intact animals also exhibited ultradian oscillations.
View Article and Find Full Text PDFBiull Eksp Biol Med
February 1983
The growth of the syngeneic tumor Acatol in BALB/c mice was retarded if the animals were pretreated with BCG or antilymphocyte serum (ATS). Combined use of BCG and ATS led to a significantly more powerful retardation as compared to the effect produced by each factor alone. Using the adoptive transfer of splenocytes from treated mice it was shown that tumor growth suppression is effected by the cell types other than T lymphocytes and macrophages.
View Article and Find Full Text PDFThe growth of the syngeneic tumor Acatol was retarded and the minimal number of tumor cells necessary for inoculation was increased in BALB/c mice preinjected with cyclophosphamide (100 mg/kg) and/or totally irradiated (5 Gy). Administration of spleen cells from intact mice abolished the antitumor effect of the above factors. The natural killer activity of spleen cells was estimated within 2-9 days after tumor inoculation.
View Article and Find Full Text PDFThe effect of the preparations of human leucocytic interferon (HLI) of various purity levels and of various concentrations was studied with respect to the natural killer activity of human leucocytes. It was shown that the process of purification and concentration of the preparation of HLI with the Kantel method entailed a disproportionally high loss of the activity stimulating the natural killer cells as compared to the antiviral activity.
View Article and Find Full Text PDFThe results of examination of ECG in 44 patients suffering from Itsenko-Cushing's disease at different stages of surgical treatment are presented. The data obtained were compared with the blood potassium and sodium levels, 17-KS, and 17-OCS levels in the urine, arterial pressure and cholesterol content. Various ECG changes before the operation were revealed in 39 patients.
View Article and Find Full Text PDFThe immune antimyeloblast serum (AMS) was obtained from horses immunized with white blood cells from patients suffering from chronic myeloid leukemia (CML) at the blast crisis stage; the serum was completely absorbed with normal red blood cells and white blood cells (WBC). The absorbed antiserum remained cytotoxic to blast cells from 20 of 42 patients with CML at the blast crisis stage. AMS failed to react with the WBC from patients with CML in its chronic phase, and from patients with other types of leukemia Morphological studies indicated a possibility of identification of the antigen associated with myeloblasts from the blood of patients with CML blast crisis, by means to AMS.
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