losartan-potassium and Hemangiosarcoma

The modern views on the coexistence of secondary polycythaemia with benign and malignant tumours of varying origin are reviewed describing certain mechanisms determining this association. The diagnostic management of secondary polycythaemia is outlined calling attention to the necessity of ruling out coexistence of a neoplasm.

Topics: Adenocarcinoma; Cerebellar Neoplasms; Erythrocyte Count; Erythropoietin; Hemangiosarcoma; Humans; Kidney Neoplasms; Liver Neoplasms; Paraneoplastic Syndromes; Polycythemia

Topics: Brain Neoplasms; Diagnosis, Differential; Erythropoietin; Female; Glioma; Hemangiosarcoma; Humans; Immunohistochemistry; Lectins; Male; Meningioma; Plant Lectins; Receptors, Cell Surface; Receptors, Thrombin; von Willebrand Factor

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Brain Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Cerebellar Neoplasms; Child; Child, Preschool; Choriocarcinoma; Cushing Syndrome; Diagnosis, Differential; Erythropoietin; Female; Gonadotropins; Hemangiosarcoma; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Infant; Infant, Newborn; Insulin; Insulin Secretion; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms; Parathyroid Hormone; Pheochromocytoma; Polycythemia; Pregnancy; Teratoma; Testicular Neoplasms; Thymus Neoplasms

A 20-month-old castrated male Korean shorthair cat was presented with a 3-week history of intermittent vomiting and anorexia, absolute erythrocytosis, and elevated erythropoietin levels. A diagnosis of splenic hemangiosarcoma was made by histopathology and immunohistochemical identification of factor VIII. Paraneoplastic erythrocytosis caused by a splenic hemangiosarcoma in a cat is described.

Topics: Animals; Cat Diseases; Cats; Erythropoietin; Factor VIII; Hemangiosarcoma; Male; Polycythemia; Splenic Neoplasms

To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma. Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma. The resulting mechanistic model confirms previous work proposing that 2-BE induces macrophage activation and inflammation in the liver. In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation. Finally, an immunohistochemistry method (Hypoxyprobe) demonstrated that tissue hypoxia was present in the spleen and BM. Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE-induced hemangiosarcoma in mice.

Topics: Animals; Bone Marrow; Cell Cycle; Cell Differentiation; Cell Hypoxia; Cell Proliferation; Cell Transformation, Neoplastic; Disease Models, Animal; Endothelial Cells; Erythropoiesis; Erythropoietin; Ethylene Glycols; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genomic Instability; Hemangiosarcoma; Hematopoietic Stem Cells; Hemolysis; Hepatitis; Immunohistochemistry; Liver; Macrophage Activation; Male; Mice; Models, Biological; Signal Transduction; Spleen; Systems Biology; Time Factors

We report a 39-year-old female patient with a hepatic hemangioblastoma, polycythemia and elevated plasma erythropoietin (Epo) levels. Following orthotopic liver transplantation (OLTx), her plasma Epo levels and hematocrit normalized but began to rise several months later. This rise correlated with the appearance of multiple lung metastases. The tumor was implicated as the source of excess Epo production using Northern analysis of a resected metastatic lung nodule. Based on our results, the measurement of plasma Epo levels in patients with Epo secreting tumors could be of general utility in assessing tumor burden.

Topics: Adult; Biomarkers, Tumor; Erythropoietin; Female; Hemangiosarcoma; Humans; Liver Neoplasms

Cerebellar hemangioblastoma is a rare cause of secondary erythrocytosis. Although the erythrocytosis is a result of erythropoietin (Ep) stimulation, direct evidence of Ep synthesis by the tumor has been lacking. In an erythrocytotic patient with a cerebellar hemangioblastoma we found elevated levels of Ep in the tumor cyst fluid and for the first time demonstrated Ep mRNA in the tumor by Northern blotting. This finding confirms cerebellar hemangioblastoma as a site of ectopic Ep production.

Topics: Adult; Blotting, Northern; Cerebellar Neoplasms; Erythropoietin; Hemangiosarcoma; Humans; Male; Polycythemia; RNA, Messenger

Although cerebellar hemangioblastomas are known to be associated with secondary polycythemia, the cellular derivation of erythropoietin (EPO) in hemangioblastomas still remains obscure. Specimens from 18 patients with cerebellar hemangioblastomas were immunohistochemically studied using anti-EPO monoclonal antibody. Eight cases of brain tumors, including 2 meningiomas, 2 medulloblastomas, 2 glioblastomas, and 2 metastatic brain tumors were studied as controls. In 9 of 18 cases, EPO-positive cells were scattered around the capillaries and were ultrastructurally shown to be mast cells. These cases were not, however, associated with secondary polycythemia. In contrast, the stromal cells were positive for EPO in 3 cases. Among them, one was associated with secondary polycythemia. Furthermore, one-half of the control cases of brain tumor contained EPO-positive mast cells. Accordingly, it was suggested that mast cells (or small granulocytes) have little relationship to the release of EPO; however, some stromal cells might release EPO with a resultant polycythemia.

Topics: Adolescent; Adult; Cerebellar Neoplasms; Erythropoietin; Female; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Male; Mast Cells; Microscopy, Electron; Middle Aged; Polycythemia

A 59-year-old woman with von Hippel-Lindau disease developed erythrocytosis and a recurrent intracranial hemangioblastoma. Radioimmunoassay showed an elevated level of erythropoietin in her serum. Cyst fluid from the tumor also contained erythropoietin, concentrated a thousandfold relative to the serum level. Production of erythropoietin by hemangioblastomas may explain the erythrocytosis present in some patients with von Hippel-Lindau disease.

Topics: Brain Neoplasms; Brain Stem; Erythropoietin; Female; Hemangiosarcoma; Humans; Magnetic Resonance Imaging; Middle Aged; Polycythemia; Radioimmunoassay; von Hippel-Lindau Disease

We used a battery of antigens to determine whether immunohistochemistry can (a) contribute to resolving the histogenesis of the stromal component of the capillary hemangioblastoma, and (b) answer cases of difficult pathologic differential diagnosis with metastatic clear cell carcinoma. The stromal cells of the capillary hemangioblastoma are antigenically polymorphous and may express immunoreactive erythropoietin, renin, keratin, Leu M1, Leu 7, actin, neuron-specific enolase, S100 protein, and glial fibrillary acidic protein. However, the use of epithelial membrane antigen allows certain histopathologic distinction between capillary hemangioblastoma and metastatic clear cell carcinoma.

Topics: Adenocarcinoma; Aged; Antigens, Differentiation; Antigens, Neoplasm; Carcinoma, Renal Cell; Cerebellar Neoplasms; Diagnosis, Differential; Erythropoietin; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Male; Membrane Glycoproteins; Mucin-1; Renin

Immunohistochemical studies for erythropoietin were carried out in six capillary haemangioblastomas, three of which were also studied by electron microscopy. The immunohistochemical studies showed that positively stained cells were scattered in the vicinity of capillaries, and that neither endothelial cells nor stromal cells were stained. In their morphology and distribution, the positively stained cells were identical to mast cells as observed by electron microscopy. In one case, erythropoietin was demonstrated in the cyst fluid of the tumour. These findings suggest that mast cells with abundant secreting granules in haemangioblastomas are capable of producing erythropoietin.

Topics: Adult; Brain Neoplasms; Erythropoietin; Female; Hemangiosarcoma; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Mast Cells; Middle Aged

Capillary hemangioblastoma is a tumor known to be associated with secondary polycythemia. Therefore, specimens from ten hemangioblastomas were studied by immunohistochemistry for the presence of erythropoietin, renin substrate, and for various endothelial, histiocytic and glial markers. In all tumors scattered cells among the stromal cells showed a positive-staining reaction with both anti-erythropoietin and anti-renin substrate. The same cells also stained positively for alpha-1-anti-trypsin. It is concluded that, in addition to the capillary endothelial cells, pericytes and stromal cells, capillary hemangioblastomas harbor cells containing and perhaps producing renin substrate and/or erythropoietin or a substance with similar antigenic determinants.

Topics: Angiotensinogen; Brain Neoplasms; Cerebellar Neoplasms; Erythropoietin; Hemangiosarcoma; Humans; Immunologic Techniques; Medulla Oblongata

Topics: Angiotensinogen; Antibodies; Brain Neoplasms; Cross Reactions; Electrophoresis, Polyacrylamide Gel; Erythropoietin; Female; Fluorescent Antibody Technique; Hemangiosarcoma; Humans; Molecular Weight; Radioimmunoassay

A patient with cerebellar hemangioblastoma and secondary erythrocytosis is presented. Erythropoietin, indirectly determined by measuring 59Fe incorporation in polycythemic mouse bioassay, was not detected in serum and urine, but was found in cerebrospinal fluid. The significance of erythropoietin determination in cerebrospinal fluid in patients with cerebellar hemangioblastoma is stressed.

Topics: Animals; Biological Assay; Cerebellar Neoplasms; Erythropoietin; Female; Hemangiosarcoma; Humans; Male; Mice; Mice, Inbred CBA; Middle Aged; Polycythemia

We examined eight cerebellar haemangioblastoma tumours from eight patients, aged 16-63 years, 5 females and 3 males. Preoperative haemoglobin values exceeded 180 g/l in four patients, and 150 g/l in four. All high Hb values were normalized upon surgical removal of the tumours. All tumours contained scattered cells which stained positively with antisera against pure human urinary erythropoietin and plasma renin substrate. We conclude that cerebellar haemangioblastomas produce immunoreactive erythropoietin, which shares common antigenic determinants with renin substrate.

Topics: Adolescent; Adult; Cerebellar Neoplasms; Epitopes; Erythropoietin; Female; Fluorescent Antibody Technique; Hemangiosarcoma; Hemoglobins; Humans; Immunoenzyme Techniques; Male; Middle Aged; Renin

We suggested a role for renin substrate (RS, angiotensinogen) in the biogenesis of erythropoietin (EP) (Nature 308:649-652, 1984). Purified RS was prepared from pooled plasma of healthy adult subjects, or from plasma of pregnant, healthy females. Antisera against human RS were shown to cross-react with purified human urinary EP, using a haemagglutination technique. On the other hand, antisera generated against highly purified human urinary EP showed strong cross-reaction with purified human plasma RS, by agglutinating erythrocytes covered with glutaraldehyde-coupled human RS. Moreover, using antisera generated against RS or EP, we have demonstrated monocytoid cells staining positive for both EP and RS in cerebellar haemangioblastoma tumors from 8 patients. Taken together, these observations point to a close relation between RS and EP. One interesting explanation is that renin substrate may be a precursor of erythropoietin.

Topics: Adult; Angiotensinogen; Angiotensins; Cerebellar Neoplasms; Cross Reactions; Erythropoietin; Female; Fluorescent Antibody Technique; Hemangiosarcoma; Humans; Immunoenzyme Techniques; Pregnancy

Erythropoietin (Ep) dependent erythrocytosis was discovered in a 77-year old man with angiosarcoma involving the liver and spleen. At autopsy, tissue from tumorous and normal sections of liver was obtained and extracts prepared for Ep assay in exhypoxic polycythemic mice. Neither tumor nor normal extracts had Ep activity; however, when the extracts were incubated with normal plasma prior to assay, significant amounts of Ep were generated. The normal liver tissue had three times the activity of the tumorous portion, 0.21 U/ml. These results suggest that the tissue contained an Ep activator, probably erythrogenin. It is proposed that the greater amount of erythrogenin activity in the normal tissue may reflect an attempt at liver regeneration following damage by an invading tumor, as regenerating liver has been identified as a stimulus for extrarenal EP and erythrogenin production.

Topics: Aged; Bone Marrow; Erythropoietin; Hemangiosarcoma; Humans; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Polycythemia

Using an in vitro bioassay, erythropoiesis stimulating activity has been measured in serum, cyst fluids and tumour homogenates from fourteen patients with cerebellar haemangioblastoma. Only two patients had elevated peripheral blood red cell counts and haemoglobin concentrations. Significantly elevated serum erythropoiesis stimulating activity was found in only one patient. High level, however, were detected in seven out of the fourteen cyst fluids and in the two homogenates tested. The dose response lines from these paralleled those of normal human erythropoietin. It was possible to neutralise the erythropoiesis stimulating activity in the cyst fluids with anti-human erythropoietin serum, indicating its similarity to erythropoietin, the normal erythropoietic regulating hormone. Significant release of the erythropoietic stimulating factor from the cyst fluids into the blood seemed to be an uncommon occurrence.

Topics: Adult; Biological Assay; Cerebellar Neoplasms; Erythropoiesis; Erythropoietin; Female; Hemangiosarcoma; Humans; Male; Middle Aged

Three cerebellar haemangioblastomas were studied by electron microscopy. One of these shows electron-dense granules within the tumour cells, indicative of erythropoietic activity, as previously described in a haemangioblastoma. The biological significance of these granules is discussed. Biological assay of serum erythropoietic activity was performed in one case.

Topics: Cerebellar Neoplasms; Erythropoiesis; Erythropoietin; Hemangiosarcoma; Hematopoiesis; Humans; Microscopy, Electron

A young female patient developed erythrocytosis during the third recurrence of a cerebellar hemangioblastoma. Elevated erythropoietin levels were found in the patient's plasma with normalization after resection of the tumor. High erythropoietin titers were also found in the tumor saline extract. A fourth recurrence of the tumor was heralded by a rising plasma erythropoietin level and gradual erythrocytosis despite the absence of change in the clinical picture or the brain scan. In this case, serial plasma erythropoietin determinations served as a useful early marker of the tumor activity.

Topics: Adult; Animals; Biological Assay; Cerebellar Neoplasms; Erythropoietin; Female; Hemangiosarcoma; Hormones, Ectopic; Humans; Mice; Polycythemia; Recurrence

Topics: Cerebellar Neoplasms; Erythropoietin; Hemangiosarcoma; Humans; Male; Middle Aged; Polycythemia

Topics: Central Nervous System Diseases; Cerebellar Neoplasms; Diencephalon; Erythropoiesis; Erythropoietin; Hemangiosarcoma; Humans; Hypoxia; Polycythemia

Topics: Adult; Blood Vessels; Cerebellar Neoplasms; Cerebral Angiography; Erythropoietin; Hemangiosarcoma; Humans; Male; Neurologic Manifestations; Polycythemia

Topics: Adrenal Gland Neoplasms; Animals; Biological Assay; Cerebellar Neoplasms; Cysts; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hemangiosarcoma; Hematocrit; Humans; Iron Isotopes; Kidney Neoplasms; Male; Mucoproteins; Pheochromocytoma; Polycythemia; Rats

Topics: Adrenal Gland Neoplasms; Animals; Carcinoma; Cerebellar Neoplasms; Erythropoietin; Female; Hemangiosarcoma; Humans; Hypertension, Renal; Kidney; Kidney Diseases; Kidney Neoplasms; Liver Neoplasms; Neoplasms; Pheochromocytoma; Polycythemia; Polythiazide; Rats; Renin; Uterine Neoplasms

Topics: Animals; Cerebellar Neoplasms; Erythropoietin; Hemangiosarcoma; Hematocrit; Humans; Hypoxia; Mice; Polycythemia; Polycythemia Vera

Topics: Adolescent; Adult; Animals; Biological Assay; Central Nervous System Diseases; Cerebellar Neoplasms; Erythropoiesis; Erythropoietin; Female; Hemangiosarcoma; Hematocrit; Humans; Iron Isotopes; Male; Mice; Teratoma

Topics: Cerebellar Neoplasms; Cerebral Ventriculography; Erythropoietin; Gastrointestinal Hemorrhage; Hemangiosarcoma; Humans; Male; Middle Aged; Polycystic Kidney Diseases; Polycythemia; Urography

Topics: Alpha-Globulins; Anemia; Antibodies; Biological Assay; Blood; Cerebellar Neoplasms; Electrophoresis; Epoetin Alfa; Erythropoiesis; Erythropoietin; Exudates and Transudates; Hemangiosarcoma; Humans; Hypoxia; Immune Sera; Kidney; Kidney Diseases, Cystic; Leukemia; Leukemia, Lymphoid; Neuraminidase; Trypsin

Topics: Anemia; Anemia, Aplastic; Cerebellar Neoplasms; Epoetin Alfa; Erythropoietin; Hemangiosarcoma; Kidney; Kidney Diseases, Cystic; Radiation Effects; Radiation, Ionizing