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Biomedical subjects

A O Danilov

Publications and source records attributed to A O Danilov.

10 recordsLinked to original sources
PubMed2005

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↗
PubMed2004

[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↗
PubMed2004

[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↗
PubMed2000

[The MDR gene and cellular sensitivity to various effects].

mdr-Transfected K-562 cells revealed a relatively high resistance to cytotoxic monokines and ionizing radiation as compared to parental cells. Taken together with what is known about the resistance of mdr-expressing cells to multiple cytotoxic drugs, our results point to malignant cells having universal mechanisms of chemo-, bio- and radioresistance.

Cell Division↗
PubMed1997

[The effect of activated macrophage products on neurite growth in an organotypic culture of chick embryo sensory ganglia].

Murine peritoneal macrophages, activated by BCG vaccine, and human peripheral blood monocytes, activated by lipopolysaccharides, exerted neurite stimulating or neurite inhibiting effects in various periods of activation. The supernatants of these preparations were active in organotypic culture of chick embryo dorsal root ganglia. The inhibition of neurite growth on the 1st day of cultivation was followed by the neurite-stimulating effect. The fluctuation of neurite-inhibition and neurite-stimulation effect of macrophage supernatants suggest the availability of certain changes in cytokine composition in different periods of macrophage activation.

Animals↗
PubMed1996

[Synthesis and expression of transforming growth factor-beta in activated macrophages].

It has been established that once macrophages become activated, they pass through different stages of functional activity. Mouse macrophages activated by BCG "exerted" pronounced cytotoxic effects for 2-5 days to be followed later by growth-stimulating ones. However, in other experiments, the cytotoxic effect was either absent or occurred at later stages which was probably due to a certain functional state of macrophages before activation. The synthesis of TGF-beta increased 1-2 days after activation with BCG vaccine, lipopolysacharide and gamma radiation. An increase in mRNA TGF-beta i expression was observed only 5 days after activation of macrophages.

Animals↗
PubMed1992

Modulation of KB and A431 cell adhesion by epidermal growth inhibitory pentapeptide.

A pentapaptide, pyroGlu-Glu-Asp-Ser-GlyOH (EPP), isolated from mouse epidermis, inhibits mitoses and enhances differentiation in primary cultures and in transformed mouse epidermal cells in vitro (Elgjo et al. 1986 b). The present work demonstrates that EPP also modulates the adhesiveness of two human tumour cell lines (KB and A431) of epidermal origin to uncoated plastic and to plastic coated with fibrinogen or collagen type 1. The adhesion modulatory effect of EPP was observed over a broad range of concentrations (10(-12)-10(-6) M), and depended on the substrate the cells were growing on. Thus, when cells were seeded on plastic or collagen, the attachment to the substrate was suppressed at the highest concentrations of EPP, and stimulated at the lowest ones. The opposite concentration-response pattern was observed when fibrinogen was used as substrate.

Amino Acid Sequence↗
PubMed1990

[Immunoenzyme analysis of the Willebrand factor using monoclonal antibodies].

A method for measuring Willebrand's factor protein has been developed, based on indirect solid-phase enzyme immunoassay with Soviet monoclonal antibodies to this factor. Normal Willebrand's factor level in the plasma has been found 55-161 percent. The method has been tried in patients with Willebrand's disease and with oncologic diseases.

Antibodies, Monoclonal↗
PubMedDate not supplied

[Immunoenzyme method of determination of Willebrand's platelet factor].

A method for Willebrandt factor antigen measurement in platelets has been developed based on indirect solid-phase enzyme immunoassay with monoclonal antibodies. The mean platelets Willebrandt factor level in 17 normal subjects was 21.5% (S = +/- 8.88; S mean = 2.16%). The method was tried in a group of patients with Willebrandt's disease. A relationship was demonstrated between Willebrandt platelet factor level and the degree of disorders in hemorrhage duration.

Female↗