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Biomedical subjects

I A Baldueva

Publications and source records attributed to I A Baldueva.

12 recordsLinked to original sources

Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors: miscellaneous tumors.

BACKGROUND: The use of genetically modified autologous tumor cells appears to be a promising approach for cancer therapy. A phase I/II trial was undertaken to define the feasibility, safety and antitumor effects of the autologous vaccine prepared by transferring tag7/PGRP-S gene into malignant melanoma and renal cell carcinoma cells. PATIENTS AND METHODS: Twenty-one patients (17 with disseminated malignant melanoma and four with metastatic renal cell carcinoma) were enrolled in this study. Cytoreduction was performed in all cases prior to therapy. Autologous tumor cells were transfected with the tag7/PGRP-S gene, irradiated and injected intradermally every 3 weeks. RESULTS: Vaccinations were well tolerated by all patients, without clinically significant signs of toxicity. Delayed-type hypersensitivity was observed in 48% of cases. Antitumor immune response was observed in 95% of patients. There were no complete or partial responses; however, a minor response was achieved in one patient with renal cell carcinoma. The stabilization of neoplastic disease was observed in eight patients (seven with malignant melanoma and one with renal cell carcinoma). Median time to tumor progression was 3 months. CONCLUSIONS: The approach suggested here appears to be well tolerated and produces a number of durable clinical effects. Further studies are required to determine whether promising effects on immune activation will result in an actual clinical benefit for patients with malignant melanoma and renal cell carcinoma.

Adult↗

[An improved procedure for autologous gene-modified cancer vaccine preparation for active specific immunotherapy of disseminated solid tumors].

Resected material was used from 108 patients with disseminated skin melanoma and 47 patients suffering metastasized renal tumors to test procedures of tumor cell culture preparation and to search the best parameters. Gene tag 7 transfer, liposome delivery and electroporation were employed to stimulate immunogenic tumor cells. The transfer results were evaluated by expression of beta-galactosidase and EGFP genes whose products were detected microscopically. Transfer efficiency was boosted by 30% due to selecting suitable parameters of tumor cell modification. Maximum effectiveness was attained by individualized choice of the parameters. Yet, undoubtedly, the best way of cell isolation was mechanical fragmentation of tumor. To speed up cell production, DMEM/F12 medium should be recommended. It should contain cattle embryonic serum (20%), conditioned medium of cultured fibroblasts of human embryonic lungs (20%), transferin, insulin and selenium (standard dose).

Cancer Vaccines↗

[Phase I-II trial of gene therapy with tag-7 modified autologous tumor cells in patients with metastatic solid tumors].

A prospective (phase I-II) trial was undertaken to study the efficacy and toxicity of gene therapy with tag 70-modified autologous tumor cells in 32 patients with metastatic renal cell carcinoma (RC) (5) and melanoma (MBL) (27) treated at the Institute's Clinic (2001-2003). Resected material was reduced to cell culture, which was transfected with tag 70 gene and devitalized by irradiation. Immune blotting was used for gene expression. Clinical and immunological effectiveness was evaluated in 22 patients (MBL--17 and RC--5) who received 1-6 injections (3 on the average). Full course of vaccination was given to 8 (MBL--6 and RC--2). No complete or partial response was reported while least regression (50%) was registered in a case of RC metastatic to the lung. According to CT and ultrasound evidence, stabilization was achieved in 5 (23.8%) (MBL--4 and RC--1). Relapse-free period was 6.5+/-3.5 months beginning from the start of treatment. The vaccine was well tolerated while DHT reaction was observed in 47.6% (10 out of 17) of primary immunized patients. A trend of increased content of T- and B-cells in peripheral blood and intensified functional activity was established.

Adult↗

[Levels of anti-inflammatory cytokines interleukin-2, interleukin-8, and soluble interleukin-2 receptor in blood of patients with various forms of ischemic heart disease].

AIM: To quantify interleukin-8 (IL-8), interleukin-2 (IL-2) and soluble receptor of IL-2 (sIL-2r) in blood serum of patients with various forms of ischemic heart disease (IHD). MATERIAL AND METHODS: Levels of IL-8, IL-2 and sIL-2r were measured with enzyme immunoassay (EIA) in the serum of 75 patients with IHD: angina of effort (group 1), progressive angina (group 2) and acute myocardial infarction (group 3). The EIAs were performed at admission and 2 weeks later. RESULTS: Baseline levels of IL-2 in group 1 and 2 patients were close (9.1 +/- 1.6 and 10.1 +/- 3.8 pg/ml) being significantly lower in group 3 (0.81 +/- 0.57 pg/ml, p < 0.01). 14 days of therapy did not change the values noticeably. IL-8 level was the highest in group 1 (94.2 +/- 27.6, 20.03 +/- 7.4, 22.47 +/- 4.8 pg/ml, respectively). sIL-2r in the three groups did not vary greatly (73.95 +/- 12.23, 89.46 +/- 18.17, 89.2 +/- 14.17 pg/ml, respectively). SIL-2r levels rose in 2 weeks in group 3 (to 147.67 +/- 18.17 pg/ml). CONCLUSION: It is confirmed that IL-2, IL-8 and sIL-2r take part in pathogenesis of IHD. IL-2 and IL-8 levels are persistently high in anginal patients while in patients with acute myocardial infarction they are low. Low concentrations of IL-2 in the latter may be attributed to high levels of its soluble receptor.

Aged↗

[Immunologic parameters in breast cancer patients (depending on age, reproductive function, clinical and pathologic pattern and growth rate of the tumor)].

The immunological indices were studied by spontaneous rosette-formation and immunocytochemical procedure in 226 patients with breast cancer. The levels, ratio and phenotypic patterns of peripheral blood T-cells were assessed in patients with primary tumors vis-a-vis biological pattern of tumor, stage, rate of growth, locally-regional extension, pathogenetical type of tumor and such breast cancer-related physiological characteristics as age and menstrual function. It was found that immunodepression in breast cancer patients can be detected by laboratory examination at stage IIb. It may manifest itself in a changed ratio of main subpopulations of T-lymphocytes, decrease in the total level of T-cells and increase in dysfunctional ones. The worst immunological indices were identified in patients younger than 35 and those with rapidly growing tumors.

Adult↗

[The assessment of cellular immunity parameters in patients with breast cancer and lymphogranulomatosis during dynamic treatment].

The paper discusses the value of various immunologic techniques for the assessment of status of T-cells and their main subpopulations in patients with breast cancer and Hodgkin's disease in the course of treatment. The immunologic parameters can be used as additional criteria of relapse and grade of response as well as to roughly monitor treatment effect.

Adult↗