Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell proliferation is required for transduction by standard retrovirus vectors derived from viruses in the murine leukemia virus (MuLV) group. Since proliferation rates are low in the mature pulmonary epithelium, we tested the hypothesis that the efficiency of retrovirus-mediated transduction of respiratory epithelial cells can be enhanced by stimulation of cell proliferation with recombinant human keratinocyte growth factor (rhKGF). A marked increase in proliferation of bronchiolar and alveolar epithelial cells was observed after intratracheal administration of rhKGF (30 mg/kg) to adult FVB/N mice. Two days after rhKGF or saline treatment, 10(7) AP+ FFU of LAPSN, a recombinant amphotropic retrovirus that expresses human placental alkaline phosphatase (AP), was instilled intratracheally into the mice. Transduction efficiency, measured 2 days after infection, was increased approximately 70-fold by rhKGF pretreatment. However, even after KGF treatment the total numbers of AP-expressing cells were few. Transduction efficiency was similar using either LAPSN packaged by amphotropic host range packaging cells or LAPSN pseudotyped with 10A1 MuLV envelope protein (0.091 +/- 0.006 versus 0.094 +/- 0.028 transduction events/mm2, respectively). Amphotropic vectors use Pit-2 for cell entry, while 10A1 MuLV vectors can use Pit-1 or Pit-2 for cell entry. By in situ hybridization the retroviral receptor Pit-2 (Ram-1) mRNA was expressed only in the pulmonary vasculature, and Pit-1 (Glvr-1) mRNA was expressed at low levels throughout the lung. In vitro studies demonstrated that retrovirus was inactivated by pulmonary surfactant. Stimulating proliferation of the respiratory epithelium increased retroviral transduction in vivo, but the paucity of retroviral receptors and inactivation by surfactant are additional barriers to high-level retroviral gene transfer in the lung.
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PMID:Keratinocyte growth factor stimulates transduction of the respiratory epithelium by retroviral vectors. 1004 87

Acute graft-versus-host disease (aGVHD) is the major complication of allogeneic stem cell transplantation (allo-HSCT), significantly limits the application of the therapy. Current evidence suggests that dysregulated cytokine production is responsible for many manifestations of aGVHD. The mechanisms have been most clearly delineated in mouse models, detailed analysis of human tissue is required. Monitoring serum levels of cytokine sIL-2R, TNF-alpha and IFN-gamma after transplantation or cytokine gene expression before transplantation can predict prognossis of aGVHD. GVHD have graft-versus-leukemia (GVL) effect, and GVL can be seperated from GVHD. IL-2, IL-12, IL-11, KGF and G-CSF could possess the roles of reducing GVHD while preserving GVL.
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PMID:[Roles of Cytokines in Acute Graft-Versus-Host Disease] 1257 74

RhKGF is developed for prevention and treatment of chemotherapy- and radiation-induced epithelial damage in cancer patients. Little information exists on growth modulation of malignant cells by KGF. We have tested the anchorage-independent clonal growth of 35 human tumor and 22 lymphoma and leukemia cell lines in semisolid media with or without rhKGF. Growth of the majority of cell lines was not significantly influenced by rhKGF. Growth of 5 cell lines (2 lung, 1 stomach, 1 colorectal, 1 breast) was significantly stimulated by rhKGF. The effect was dose-dependent with significant stimulation at concentrations >1-10 ng/ml. Growth modulation was amplified by serum reduction and abolished by anti-hKGF antibodies. Responding cell lines expressed KGF receptor RNA and showed specific KGF-binding. To determine whether KGF-induced higher colony numbers represented cell divisions with resulting differentiation and growth arrest or self-renewal we performed experiments on serial plating efficacy of colony-derived tumor cells with or without continued presence of rhKGF. Results revealed KGF stimulation of colony formation as representing increase of cellular self-renewal. To test possible interaction of rhKGF with activity of cytotoxic drugs in clinical protocols, we have used combination protocols with 5-fluorouracil (5-FU). Results showed that rhKGF incubation before, after (or both) addition of 5-FU did not diminish the sensitivity of tumor cells to 5-FU cytotoxicity under serum concentrations relevant for the clinical situation. In conclusion, some epithelial tumor cells have receptors for KGF signaling for clonal growth. When considered in the planning of treatment protocols, this effect is unlikely to compromise chemotherapy sensitivity.
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PMID:Influence of keratinocyte growth factor on clonal growth of epithelial tumor cells, lymphoma and leukemia cells and on sensitivity of tumor cells towards 5-fluorouracil in vitro. 1537 50

In this multicenter study, 30 patients undergoing matched related or unrelated allogeneic stem-cell transplantation for leukemia were treated with palifermin, and retrospectively compared to a matched control group. Palifermin recipients transplanted with an unrelated donor showed a significant reduction of severity, incidence and duration of oral mucositis WHO grades 2-4. In addition, in the palifermin group the use of opioid analgesics and the duration of total parenteral nutrition decreased, whether stem cells were used from matched related or unrelated donors. No beneficial influence of palifermin on the incidence and severity of acute GVHD (aGVHD) was apparent. The incidence and duration of febrile neutropenia, documented infections, hematopoietic recovery or overall survival remained unchanged. The most common adverse effects included rash or erythema, generally mild and transient in appearance. Thus, the administration of palifermin was generally well tolerated and safe, and significantly reduced oral mucositis whereas--regardless of donor status--no effect on the incidence and severity of aGVHD was seen.
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PMID:Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients. 1850 Mar 68

Palifermin and pegaspargase are Escherichia coli-derived drug products. Hypersensitivity reactions, including anaphylaxis, are frequently reported with pegaspargase. In high-risk acute lymphoblasic leukemia (ALL), patients undergoing allogeneic hematopoietic stem cell transplant may be treated with palifermin as a supportive care measure for mucositis prophylaxis. However, no literature exists documenting the cross-reactivity between palifermin and pegaspargase. We report a case in which a child with very high-risk ALL having experienced severe anaphylaxis with pegaspargase was later successfully treated with palifermin during stem cell transplant conditioning.
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PMID:Successful use of palifermin following severe anaphylaxis to pegaspargase in a pediatric patient with acute lymphoblastic leukemia. 2556 19