Neoplasma Vol.52, p.175-181, 2005
|
| Title: The influence of thalidomide therapy on cytokine secretion,
immunophenotype, BCL-2 expression and microvessel density in
patients with resistant or relapsed multiple myeloma
|
| Author: A., DMOSZYNSKA
; M., PODHORECKA
; J., MANKO
; A., BOJARSKA-JUNAK
; J., ROLINSKI
; D., SKOMRA
; |
|
Abstract: Thalidomide (THAL) is currently used as a novel drug in patients
with chemotherapy resistant or relapsed multiple myeloma. THAL
antitumor activity seems to be very complex, however the precise
mechanisms of its action are still not fully understood.
The aim of this study was to assess some of possible mechanisms of
THAL action both in in vivo analysis of immune cells phenotype and
in in vitro cultures with THAL. The study involved 30 patients
with relapsed or chemotherapy refractory multiple myeloma who were
qualified to THAL treatment. We assessed immunothenotype of
malignant plasma cells and T lymphocytes in both peripheral blood
(PB) and bone marrow (BM) samples taken before and after 4 and 8
weeks of THAL treatment. Before therapy cytokine secretion (VEGF,
HGF, bFGF, TNF, IL-6 an sIL-6R) and Bcl-2 expression in PB and BM
cell cultures with THAL were analyzed. We used flow cytometry
technique and ELISA method. The clinical response to therapy was
assessed after 4 and 8 weeks of treatment. We also investigated
microvessel density (MVD) in bone marrow samples before the THAL
treatment and after 6 months of therapy in the group of responding
patients.
In cell cultures with THAL we detected statistically significant
lowering of analyzed cytokines concentration and the decrease in
Bcl-2 expression by malignant plasma cells in BM and CD8+ T
lymphocytes in BM and PB. In the group of patients responding to
therapy we observed the decrease in the number of myeloma cells
and significant increase of CD4+ and CD8+ cells in both PB and BM
samples. There was statistically significant increase of
CD3+/CD69+ cells in the course of therapy, while the percentage of
CD3+/HLA-DR+ cells was significantly lower after 8 weeks of
therapy. We also detected lowering of MVD after THAL therapy in
responders group.
The obtained results demonstrate that THAL efficacy in MM is
multidirected and included such mechanisms like down-regulation of
proangiogenic cytokines, that could lead to lowering of MVD,
induction of apoptosis and influence on malignant cells and T
lymphocytes immunophenotype.
|
|
| Keywords: apoptosis, cytokines, BCL-2, mmicrovessel density, multiple
myeloma, thalidomide
|
| Year: 2005, Volume: 52, Issue: |
Page From: 175, Page To: 181 |
|
|
|
|
|
 download file |
|
|
|
|
