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Drug
Enzyme
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Target Concepts:
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Query: UMLS:C0026986 (
myelodysplastic syndrome
)
14,926
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Interleukin-3
(
IL-3
) is a multipotent
hematopoietic growth factor
produced by activated T-cells, monocytes/macrophages and stroma cells. Human
IL-3
gene is located on chromosome 5 near segment 5q31. The high affinity receptor for human
IL-3
is composed of alpha and beta subunits.
IL-3
shares common beta subunit with GM-CSF and IL-5 which has been mapped to chromosome 22q13.1. The biological effects of
IL-3
have been studied in human and murine hematopoietic cell lines and normal human bone marrow cells. Addition of
IL-3
to the culture medium induces proliferation, maturation and probably self renewal of pluripotent hematopoietic stem cells and cells of myeloid, erythroid and megakaryocytic lineages. Various clinical trials have assessed the in vivo potential of recombinant human interleukin 3 (rhIL-3). Initial results of phase I/II studies of
IL-3
at a dose of 5-10 ug/kg subcutaneous (s/c) daily for 5-10 days in patients with relapsed lymphomas, small cell lung cancer, breast cancer and ovarian cancer have shown that post-chemotherapy application of
IL-3
reduces chemotherapy delays and induces faster regeneration of granulocytes and platelets. However, these results were not confirmed in phase III studies. The role of
IL-3
alone in the treatment of
myelodysplastic syndromes
(
MDS
), aplastic anemia (AA) and other bone marrow failure disorders have also been disappointing. However, preliminary studies of
IL-3
in combination with chemotherapeutic agents and immunosuppression have demonstrated encouraging results in patients with
MDS
and aplastic anemia respectively. The therapeutic potential of
IL-3
in peripheral blood stem cell harvesting and priming of stem cells before harvest is beginning to be identified. Initial results of
IL-3
in combination with granulocyte macrophage colony stimulating factor (GM-CSF) or later acting growth factor like granulocyte colony stimulating factor (G-CSF) have yielded larger amounts of peripheral blood stem cells during PBSC harvesting. This approach and application of
IL-3
with cocktail of other cytokines for ex-vivo expansion of stem cells, dendritic cell development and gene transfer requires further evaluation. The role of
IL-3
in murine models of antiphospholipid syndrome (APLS) for prevention of recurrent abortion remains experimental and warrants careful assessment of adverse effects of
IL-3
therapy on pregnant woman and fetus. The exact therapeutic role of
IL-3
in oncology and nononcology patients is beginning to be identified. It appears that future application of
IL-3
in combination with other cytokines is an attractive way forward in the prevention of treatment related mortality and morbidity in oncology patients. It also holds prospects for development of new therapeutic strategies for dose escalation and immune modulation for relapsed cancer patients.
...
PMID:Interleukin-3: Promises and Perspectives. 2741 83
Human granulocyte colony stimulating factor (hG-CSF) is an expensive
hematopoietic growth factor
that is clinically used in human for the treatment of neutropenia in diseases such as AIDS, aplastic anemia,
myelodysplastic syndrome
and congenital or chemotherapy-induced neutropenia. Here, through a computational biology approach, we show that human stem cell factor (hSCF) could be a better fusion partner than human thyroid peroxidase (hTPO), human erythropoietin (hEPO) and human interleukin-3 (hIL3) for co-expression with hG-CSF. Molecular modeling of hG-CSF-hSCF fusion protein with hG-CSF and hSCF receptors showed that binding of fusion protein with human granulocyte colony stimulating factor receptor (hG-CSFR) did not inhibit its binding to human stem cell factor receptor (hSCFR) and vice versa. To validate the results, coding sequences of hG-CSF and hSCF were cloned and co-expressed as fusion protein and their bioactivity was evaluated on hG-CSF responsive 3T3 cell line. The fused expression vector expressed recombinant hG-CSF-hSCF upon IPTG-induction, as revealed by real-time polymerase chain reaction (RT-PCR), sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. Bioactivity analysis confirmed that rhG-CSF-hSCF protein had higher bioactivity than hG-CSF. Thus, hSCF could be a good fusion partner for hG-CSF and its co-expression as hG-CSF-hSCF may offer an alternative to individual use of two hematopoietic factors in clinics. Future studies should determine the purification strategies, folding status and mechanism of action of the recombinant proteins. Communicated by Ramaswamy H. Sarma.
...
PMID:Molecular modeling and co-expression analysis of human stem cell factor as fusion partner to granulocyte colony stimulating factor for improving their bioactivity. 3272 May 81
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