losartan-potassium and Sarcoma

Hypoxia is a common feature of solid tumors that occurs across a wide variety of malignancies. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. These effects, in turn, can lead to increased invasiveness and metastatic potential, loss of apoptosis, and chaotic angiogenesis, thereby further increasing treatment resistance. Investigations of the prognostic significance of pretreatment tumor oxygenation status have shown that hypoxia (oxygen tension [pO(2)] value < or =10 mmHg) is associated with lower overall and disease-free survival, greater recurrence, and less locoregional control in head and neck carcinoma, cervical carcinoma, and soft-tissue sarcoma. In view of the deleterious effect of hypoxia on standard cancer treatment, a variety of hypoxia- and anemia-targeted therapies have been studied in an effort to improve therapeutic effectiveness and patient outcomes. Early evidence from experimental and clinical studies suggests the administration of recombinant human erythropoietin (rHuEPO) may enhance the effectiveness of radiation therapy and chemotherapy by increasing hemoglobin levels and ameliorating anemia in patients with disease- or treatment-related anemia. However, further research is needed in the area of hypoxia-related treatment resistance and its reversal.

Topics: Anemia; Cell Hypoxia; Combined Modality Therapy; Drug Resistance, Neoplasm; Erythropoietin; Female; Head and Neck Neoplasms; Hemoglobins; Humans; Radiation Tolerance; Sarcoma; Uterine Cervical Neoplasms

To evaluate the effect of recombinant human erythropoietin (EPO) and iron supplementation on transfusion requirements in pediatric patients with sarcoma who were receiving chemotherapy, we performed a double-blind, placebo-controlled, randomized trial.. Twenty-four pediatric patients with malignant solid tumors were randomly assigned to receive either placebo (saline solution) or EPO for a 16-week study period. The starting dose was 150 IU/kg per dose three times a week and was escalated by 50 IU/kg per dose increments monthly until packed red blood cell (PRBC) transfusion independence was achieved or a dosage of 300 IU/kg per dose was reached. Iron supplementation was prescribed at a dose of 6 mg of elemental iron per kilogram daily. The primary study end point was the comparison of PRBC transfusion requirements in the two groups.. Of 24 patients, 20 were evaluable for response. The median PRBC transfusion requirement during the 16-week period was 23 ml/kg in EPO-treated patients versus 80 ml/kg in placebo patients (p = 0.02). The median number of single-donor platelet units transfused was zero in the EPO-treated patients compared with four in the placebo group (p = 0.005). No statistical difference in the intensity of bone marrow suppression was seen, as measured by the median number of complete blood cell counts with an absolute neutrophil count of < 1000 cells/microliter.. Treatment with EPO and iron significantly reduces PRBC transfusions in pediatric patients receiving concomitant chemotherapy for malignant sarcomas. A decrease in the number of platelet transfusions was also seen and deserves further study.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Double-Blind Method; Erythrocyte Transfusion; Erythropoietin; Female; Humans; Male; Platelet Transfusion; Recombinant Proteins; Sarcoma; Treatment Outcome

A 7-year-old mixed breed dog was evaluated for erythrocytosis with an initial hematocrit of 82.3%. Abdominal ultrasound revealed a 6 cm mass on the cranial pole of the right kidney. Daily therapeutic phlebotomies were performed, reducing the hematocrit to 54%. The dog underwent a right nephroureterectomy, recovered without complications, and was discharged 3 days after surgery. Histopathologic evaluation revealed a completely excised grade II soft tissue sarcoma. The preoperative erythropoietin level was 7.00 mU/mL (RI 1.90-22.90 mU/mL) and the 3-day postoperative erythropoietin level was 0.99 mU/mL, supporting a diagnosis of inappropriate secondary erythrocytosis due to the renal tumor. Secondary erythrocytosis resulting from renal soft tissue sarcoma is rare. Confirmatory testing with erythropoietin levels can assist in the diagnosis of secondary erythrocytosis. Erythropoietin levels that are normal or increased in the face of erythrocytosis indicate a source of inappropriate erythropoietin production.

Topics: Animals; Dog Diseases; Dogs; Erythropoietin; Female; Kidney Neoplasms; Polycythemia; Sarcoma

Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic tumor usually found in children, with rare cases reported in adults. We present a case of a 53-year-old woman with an undifferentiated sarcoma of the liver (USL), which resembles UESL, who initially presented with a markedly elevated hematocrit (61.2%). Cytogenetic studies for polycythemia vera were negative, but the patient's erythropoietin (EPO) was elevated. A computed tomography scan and subsequent partial hepatectomy revealed a well-circumscribed, partially cystic mass in the right lobe of the liver measuring 34 cm. Following surgery, the patient's EPO level and hematocrit dropped to within normal range and remained so for 1 year, at which point it rose again. A subsequent magnetic resonance imaging scan showed a liver mass at the previous resection margin, consistent with a recurrence. In this case study, we describe the first reported USL resembling an UESL that secretes EPO, which was a useful marker of tumor recurrence.

Topics: Erythropoietin; Female; Humans; Liver Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Sarcoma

The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied.. Anemia was induced by total body irradiation ([TBI], 2 x 4 Gy) of mice before tumor implantation into the subcutis of the hind leg. The development of anemia was prevented by rhEPO (750 U/kg s.c.) given 3 times weekly starting 2 weeks before TBI. Fourteen days after fractionated TBI (tumor volume of approx. 40 mm(3)), single-dose irradiation of the tumor with varying doses was performed so that in full dose-response relationship for the probability of tumor cure was obtained.. Radiation-induced anemia (hemoglobin concentration [cHb] = 9.9 g/dl) led to a reduced radiosensitivity compared to controls [49.4 vs. 40.1 Gy radiation dose to control 50% of the tumors (TCD50)]. Upon rhEPO treatment for anemia prevention (cHb = 13.3 g/dl), the TCD50 was 39.8 Gy, illustrating restored radiosensitivity compared to anemic mice.. These data provide further experimental evidence for restored radiosensitivity upon prevention of anemia with rhEPO.

Topics: Anemia; Animals; Cell Hypoxia; Dose Fractionation, Radiation; Drug Evaluation, Preclinical; Erythropoietin; Hemoglobins; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Radiation Injuries, Experimental; Radiation Tolerance; Recombinant Proteins; Sarcoma; Transplantation, Heterologous; Whole-Body Irradiation

Topics: Abdominal Neoplasms; Adenocarcinoma; Adenoma; Animals; Carcinogens; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Erythropoietin; Esters; Female; Injections, Intraperitoneal; Lung Neoplasms; Male; Mediastinal Neoplasms; Methane; Neoplasms, Experimental; Nephrectomy; Pituitary Neoplasms; Rats; Sarcoma; Sex Factors; Sulfonic Acids; Thyroid Neoplasms; Time Factors

Topics: Carcinoma; Cells, Cultured; Erythropoietin; Humans; Iron; Iron Isotopes; Kidney Neoplasms; Sarcoma