losartan-potassium and Peripheral-Nervous-System-Neoplasms

The glycoprotein hormone Erythropoietin (EPO) stimulates red cell production and maturation. EPO is produced by the kidneys and the fetal liver in response to hypoxia (HOX). Recently, EPO expression has also been observed in the central nervous system where it may be neuroprotective. It remained unclear, however, whether EPO is expressed in the peripheral nervous system and, if so, whether a neuronal phenotype is required for its regulation. Herein, we report that EPO expression was induced by HOX and a HOX mimetic in two cell lines derived from neuroblastoma (NB), a tumor of the peripheral nervous system. Both cell lines with inducible EPO expression, SH-SY5Y and Kelly cells, expressed typical neuronal markers like neuropeptide Y (NPY), growth-associated protein-43 (GAP-43), and neuron-specific enolase (ENO). NB cells with a more epithelial phenotype like SH-SHEP and LAN-5 did not show HOX inducible EPO gene regulation. Still, oxygen sensing and up-regulation of hypoxia-inducible factor-1 (HIF-1) were intact in all cell lines. We found that CpG methylation of the HIF binding site (HBS) in the EPO gene 3' enhancer was only present in the SH-SHEP and LAN-5 cells but not in SH-SY5Y and Kelly cells with regulated EPO expression. The addition of recombinant EPO to all NB cells, both under normoxic and hypoxic conditions, had no effect on cell proliferation. We conclude that the ability to respond to HOX with an increase in EPO expression in human NB may depend on CpG methylation and the differentiation status of these embryonic tumor cells but does not affect the proliferative characteristics of the cells.

Topics: Binding Sites; Blotting, Western; Cell Differentiation; CpG Islands; DNA Methylation; DNA-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Gene Expression Regulation; Helix-Loop-Helix Motifs; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Neuroblastoma; Nuclear Proteins; Peripheral Nervous System Neoplasms; Receptors, Erythropoietin; Transcription Factors; Tumor Cells, Cultured

An 11-year-old, spayed female mixed-breed dog showed clinical signs of right forelimb lameness and pain by palpation around the neck. Radiography and computed tomography (CT) revealed an extradural mass at the 6th and 7th cervical vertebrae, which compressed the spinal cord. The mass was surgically removed and histopathologically diagnosed as schwannoma. The dog recovered her normal gait after hemilaminectomy and removal of the mass. Ten months after the surgery, the tumor recurred with absolute erythrocytosis and was surgically removed again. This removal temporarily resolved the erythrocytosis with a decrease in plasma erythropoietin (EPO) concentration. EPO protein was detected immunohistochemically in the tumor cells. Erythrocytosis in this dog may be caused by ectopic EPO produced in the schwannoma tissues.

Topics: Animals; Dog Diseases; Dogs; Erythropoietin; Female; Hematocrit; Immunohistochemistry; Neurilemmoma; Peripheral Nervous System Neoplasms; Polycythemia; Radiography; Spinal Nerve Roots

The care of patients refusing blood transfusion who require major ablative surgery for malignancy is a continuing challenge. The use of recombinant human erythropoietin is clearly efficacious in patients with renal disease and may be useful in anemic patients who refuse transfusion. Herein, we report a successful extended hemipelvectomy in a Jehovah's Witness using recombinant human erythropoietin support.

Topics: Adult; Blood Transfusion; Christianity; Erythropoietin; Hemipelvectomy; Humans; Male; Pelvic Neoplasms; Peripheral Nervous System Neoplasms; Recombinant Proteins; Religion and Medicine; Sciatic Nerve; Surgical Flaps