losartan-potassium and Central-Nervous-System-Neoplasms

Hemangioblastomas express erythropoietin and the patients often present with polycythemia.. Serum erythropoietin was measured using a commercial immunoassay, a functional erythropoietin assay and iso-electric focusing.. Despite the polycythemia, serum erythropoietin remained low, while a functional erythropoietin-assay showed a 4-5 higher activity in serum compared to the immunoassay. Iso-electric focusing of serum erythropoietin indicated overrepresentation of highly sialylated erythropoietin isoforms produced by the tumor. As a result, altered affinity of the monoclonal antibody used in the immunoassay for the hypersialylated isoforms was suggested.. Analysis of erythropoietin isoforms may be helpful in distinguishing the ectopic erythropoietin isoforms from normally glycosylated erythropoietin.

Topics: Antibodies, Monoclonal; Artifacts; Central Nervous System Neoplasms; Erythropoietin; Glycosylation; Hemangioblastoma; Humans; Immunoassay; Isoelectric Focusing; Male; Middle Aged; Polycythemia; Protein Isoforms

Multiple hemangioblastomas (HBs) of the central nervous system (CNS) and retina are associated with von Hippel-Lindau disease (VHL) and also predispose individuals to renal cell carcinomas and visceral cysts. In VHL, microsurgery or radiosurgery cannot prevent new HBs from arising in the CNS or coagulation of retinal HBs. Multiple but thus far asymptomatic HBs pose a therapeutic problem. IFN-alpha-2a has antiangiogenic activity with an especially favorable effect on life-threatening hemangiomas of the liver in children. This is the first study to assess the efficacy of IFN-alpha-2a in treatment of asymptomatic HBs of the CNS and retina. Four patients (three with VHL) with a combined total of 15 HBs of the CNS, 3 HBs of the retina, and 14 renal and 2 pancreatic cysts were treated with s.c. IFN-alpha-2a for 12 months at 3 x 10(6) IU, 3 times/week. Baseline workup consisted of detailed neurological, ophthalmological, and radiological examinations. Follow-up studies at 3, 13, and 21 months were used to monitor the response. No de novo HBs were detected during the therapy, but one appeared 9 months after cessation of IFN-alpha-2a therapy. HBs of the CNS did not shrink markedly during the therapy. IFN-alpha-2a may decrease blood flow in HBs as suggested by shrinkage and diminished leakage of two retinal HBs. However, the therapy did not prevent visceral cysts from growing. The systemic response was also monitored by measurement of serum levels of vascular endothelial growth factor and erythropoietin, which remained essentially unchanged during the treatment. No serious side effects were recorded.

Topics: Adult; Aged; Antineoplastic Agents; Central Nervous System Neoplasms; Dose-Response Relationship, Drug; Endothelial Growth Factors; Erythropoietin; Female; Hemangioblastoma; Humans; Interferon alpha-2; Interferon-alpha; Lymphokines; Male; Middle Aged; Recombinant Proteins; Retinal Neoplasms; Time Factors; Treatment Outcome; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Hemangioblastomas are highly vascular tumors of the central nervous system that overexpress the hypoxia-inducible gene, vascular endothelial growth factor (VEGF), as a consequence of mutational inactivation of the von Hippel-Lindau tumor suppressor gene (VHL). Previous reports showed that hemangioblastomas can also express erythropoietin (Epo), which is also hypoxia-inducible. However, Epo expression in hemangioblastomas was observed only in individual cases, and the analyses were mainly based on indirect determination of erythropoiesis-stimulating activity. Therefore, we analyzed a series of 11 hemangioblastomas for Epo, VEGF, and VHL expression by Northern blot analysis and compared the results with normal brain and glioblastomas. Surprisingly, we observed Epo mRNA expression in all hemangioblastoma specimens analyzed, but in none of four glioblastomas. In contrast, VEGF mRNA was expressed in all hemangioblastomas and all glioblastomas. In situ hybridization revealed neoplastic stromal cells as Epo- and VEGF-producing cells in hemangioblastomas. These results suggest that in the nonhypoxic microenvironment of hemangioblastoma, Epo, similar to VEGF, might be negatively regulated by the VHL gene product.

Topics: Adult; Aged; Brain; Brain Neoplasms; Cell Hypoxia; Central Nervous System Neoplasms; Endothelial Growth Factors; Erythropoiesis; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Glioblastoma; Hemangioblastoma; Hormones, Ectopic; Humans; In Situ Hybridization; Ligases; Lymphokines; Male; Middle Aged; Neoplasm Proteins; Nerve Tissue Proteins; Protein Biosynthesis; Proteins; RNA, Messenger; Stromal Cells; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; von Hippel-Lindau Disease; Von Hippel-Lindau Tumor Suppressor Protein