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Biomedical subjects

T Skorski

Publications and source records attributed to T Skorski.

7 recordsLinked to original sources
PubMed1992

Inhibition of proliferation by c-myb antisense RNA and oligodeoxynucleotides in transformed neuroectodermal cell lines.

Transfection of a neuroblastoma cell line with expression vectors containing two different segments of human c-myb complementary DNA in antisense orientation yielded far fewer transfectant clones than did the transfection with the identical segments in sense orientation. In cell clones expressing c-myb antisense RNA, levels of the c-myb protein were down-regulated and the proliferation rate was slower than that of cells transfected with sense constructs or the untransfected parental cell line. Treatment of neuroblastoma and neuroepithelioma cell lines with a c-myb antisense oligodeoxynucleotide strongly inhibited cell growth. These data indicate a definite involvement of c-myb in the proliferation of neuroectodermal tumor cells extending the role of this protooncogene beyond the hematopoietic system. The availability of cell clones that transcribe c-myb antisense RNA provides a useful tool to study the involvement of other genes in the proliferation and differentiation of neuroblastoma cells.

Animals↗
PubMed1992

Growth factor-dependent inhibition of normal hematopoiesis by N-ras antisense oligodeoxynucleotides.

To determine whether N-ras expression is required at specific stages of the process of in vitro normal human hematopoiesis, adherent- and T lymphocyte-depleted mononuclear marrow cells (A-T-MNC) or highly purified progenitors (CD34+ cells) were cultured in semisolid medium, under conditions that favor the growth of specific progenitor cell types, after exposure to N-ras sense and antisense oligodeoxynucleotides. N-ras antisense, but not sense, oligodeoxynucleotide treatment of A-T-MNC and CD34+ cells resulted in a significantly decreased number of granulocyte/macrophage colony-forming units (CFU-GM) induced by interleukin 3 (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and of macrophage colonies (CFU-M) induced by M-CSF, but not of granulocytic colonies induced with G-CSF or IL-5. However, the same treatment significantly inhibited colony formation induced by each of the above factors in combination with IL-3. Megakaryocytic colony (CFU-Meg) formation from A-T-MNC or CD34+ cells in the presence of IL-6 + IL-3 + erythropoietin (Epo) was also markedly decreased after antisense oligodeoxynucleotide treatment. Erythroid colonies derived from A-T-MNC in the presence of Epo (CFU-E) were not inhibited upon antisense treatment, whereas those arising from A-T-MNC or CD34+ cells in the presence of IL-3 + Epo (BFU-E) were markedly affected. These results are consistent with the hypothesis that distinct signal transduction pathways, involving N-ras or not, are activated by different growth factors in different hematopoietic progenitor cells.

Antigens, CD↗
PubMed1992

Antisense oligonucleotides.

Growing evidence indicates that antisense oligodeoxynucleotides can specifically inhibit gene expression thereby providing an essential tool for understanding gene function and the potential to affect abnormal cell proliferation. Because oncogene activation is intimately involved in tumour initiation and progression, down-regulation of oncogene expression is associated with a selective or a preferential inhibition of tumour as compared to normal cell proliferation. Even though numerous studies attest the short-term in vitro efficacy of antisense oligodeoxynucleotides as inhibitors of tumour growth, the use of these compounds as therapeutic agents awaits a more rigorous demonstration of their long term effects and favourable pharmacological properties.

Antineoplastic Agents↗
PubMed1991

Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides.

To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte-macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells were mixed, exposed to the oligodeoxynucleotides, and assayed for residual colony formation, the majority of residual cells were normal. These findings demonstrate the requirement for a functional BCR-ABL gene in maintaining the leukemic phenotype and the feasibility of gene-targeted selective killing of neoplastic cells.

Base Sequence↗
PubMed1990

Early induction of immune resistance against leukemia in lethally total body irradiated mice reconstituted with syngeneic bone marrow cells obtained from previously immunized donor mice.

BALB/c x DBA/2 F1 (CD2F1) mice were lethally irradiated and reconstituted with syngeneic bone marrow cells (SBMC) obtained from normal or previously immunized (against L1210 lymphatic leukemia) donors. These recipient mice are called TBI + SBMT or TBI + Imm-SBMT mice, respectively. TBI + Imm-SBMT, but not TBI + SBMT mice, were able to develop strong immune resistance against L1210 leukemia, but not against MOPC 104E plasmacytoma, if the immunization procedure (four i.p. injections at weekly intervals of immunogenic L1210 cells) was started as early as 7 days posttransplantation. Incubation of Imm-SBMC with mafosfamide (ASTA Z7654) before grafting abrogated the ability of the recipient mice to develop early resistance against the leukemia. Treatment of Imm-SBMC with monoclonal or polyclonal antibodies plus complement showed that two or three subpopulations of Imm-SBMC were necessary for the transfer of immune information against leukemia: T lymphocytes with phenotype Thy 1.2+, Lyt 1+2-, I-Ad-, macrophages with phenotype Mac-1+, I-Ad-, and probably asialo-GM 1+ cells. Recipient mice immunized against L1210 leukemia before TBI + SBMT do not develop early resistance to the leukemia.

Animals↗