Biomedical subjects

B Rihova

Publications and source records attributed to B Rihova.

6 recordsLinked to original sources

PubMed2005

Induction of systemic antitumour resistance with targeted polymers.

Conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) represent a new generation of antibody-targeted polymeric anticancer drugs with both cytotoxic and immunoprotecting/immunomobilizing activity. 20-90% of mice that are cured of EL4 mouse T-cell lymphoma, BCL1 mouse B-cell leukaemia and 38C13 mouse B-cell lymphoma by injection of doxorubicin-HPMA conjugate develop a long-lasting memory and systemic antitumour resistance. It is suggested that the main activity of the polymeric drug, directly after application is - due to the high level of the drug - of cytotoxic and cytostatic nature. Thereafter, long-term conjugates persist at low concentration in the circulation, which are capable of mobilizing the defence mechanisms of the host. Until now, seven patients with generalized carcinoma were treated with doxorubicin-HPMA-human-Ig conjugate. Disease stabilization, lasting from 6 to more than 18 months, was recorded.

Animals↗

PubMed2004

Polymeric anticancer drugs with pH-controlled activation.

The paper is dealing with the synthesis and properties of new, nontargeted or antibody-targeted pH-sensitive polymer-doxorubicin (DOX) conjugates designed as anticancer drugs facilitating site-specific therapy. These conjugates are stable and inactive during transport in the body but activate inside target cells as a result of pH changes outside and inside the cells. Cytotoxicity of the conjugates depends on the detailed structure of the polymer and of the spacer between the drug and polymer carrier. In both protective and therapeutic regimes of drug administration, the in vivo antitumor activity of the pH-sensitive conjugates containing DOX was significantly enhanced (T-cell lymphoma EL 4, C57BL/16 mice) in comparison with the free DOX or classic PK1, the PHPMA-DOX conjugate clinically tested at present.

Animals↗

PubMed1993

Effect of age on antibody responses in low responder C57BL/10ScSn and high responder A/J strains of mice.

The IgM antibody response to sheep red blood cells (SRBC) appeared significantly earlier in A/J strain mice (already in 10-day-old animals), but after 21 days responses were higher in B10 mice. These differences disappeared after reaching adulthood and IgM responses after either primary or secondary immunization were thereafter comparable in these strains. High-responder A/J mice made significantly more IgG antibodies than low-responder B10 mice from 21 days of age and strong differences lasted until the age of 19 months, when IgG antibody production was again similar. Potentiation of IgM formation by simultaneous application of 10 micrograms of LPS was higher in B10 mice until 19 months of age. On the other hand, potentiation of the IgG response was markedly high in B10 mice only in adult animals (3 months). Thereafter the potentiation was higher in A/J mice. The onset of Ig secretion in A/J mice was at 15 days and markedly increased at the age of 30 days. Levels of immunoglobulin synthesis remained extremely low in B10 mice. Age-related changes in IgG antibody production generally correlated with the decline of MHC class II antigen expression on peritoneal macrophages in these strains.

Aging↗

PubMed1989

Biocompatibility of N-(2-hydroxypropyl) methacrylamide copolymers containing adriamycin. Immunogenicity, and effect on haematopoietic stem cells in bone marrow in vivo and mouse splenocytes and human peripheral blood lymphocytes in vitro.

N-(2-hydroxypropyl)methacrylamide polymeric prodrugs containing adriamycin bound to polymers via glycylphenylalanylleucylglycine side chains and, in one case, galactosamine bound via the same sequence, were tested for immunogenicity after intravenous, subcutaneous and oral application in two inbred strains of mice. The serum antibody level was determined by enzyme-linked immunoassay on the 3rd and 6th day after the last treatment. It was found that antibodies were only produced in very small amounts. In some experimental groups, the antibody titres measured following administration of copolymer conjugate were comparable with those present in non-treated controls. Attachment of adriamycin to N-(2-hydroxypropyl)methacrylamide copolymer considerably decreased its toxicity against haematopoietic precursors in bone marrow as measured by the in vivo colony-forming unit-spleen assay and its ability to inhibit [3H] thymidine incorporation by mouse splenocytes and human peripheral blood lymphocytes measured in vitro.

Animals↗

PubMed1985

Immunological problems of polymer-bound drugs.

For the application of polymer-bound drugs (especially in combination with the targeting antibodies), it is essential to know more about the immunogenicity and possible hazards from immune reactions induced by their repeated application. The immune reaction depends on many factors (including structure of antigen, dose of antigen, schedule and way of the application, genetic background of the immunized, i.e., receiving organism) and could be weakened or eliminated by a choice of suitable factors. Problems connected with the immune reaction of the humoral and cellular type (B and T cell involvement) against different polymers and polymer-bound drugs and possible consequences for their clinical use will be discussed.

Amino Acids↗

PubMedDate not supplied

The effects of 5-fluorouracil on immunocompetent cells depend on the genotype of experimental animals used.

A detailed study was made of the effects of 5-fluorouracil (5-FU) on primary and secondary immune responses to a T-dependent antigen in mice. Subcutaneous, intraperitoneal and intravenous applications gave similar results, oral administration was less effective. The minimal effective dose was found to be 40 mg/kg. Inbred strains known to differ in terms of IgG immune responses were compared and found to respond quite differently to the drug. For example, when 5-FU was injected 24 h before or simultaneously with antigen, IgM plaque-forming cell (PFC) responses of C57BL/10 mice were not substantially affected. In contrast, responses of A/J and Balb/c mice were suppressed 50-90% under the same conditions. If injected 24 h after the antigen, 5-FU inhibited PFC responses completely in all three strains. IgM PFC recovery was fastest in the C57BL/10 strain and started on day 7. In secondary responses, IgM overstimulation was seen in C57BL/10 and Balb/c mice if 5-FU was injected once, i.e. 24 h after primary immunization. IgG PFC were completely suppressed in primary responses in all strains. In secondary responses, the decrease was influenced by the time of drug injection and by the genotype of the treated animal. Inhibition of isotype switching was greatest in low-IgG-responding C57BL/10 mice. These results demonstrate that genotypic variation can be substantial with respect to effects of 5-FU on the immune system.

Animals↗