losartan-potassium and Neoplasm-Metastasis

Therapy with erythropoiesis-stimulating agents (ESAs) is associated with well-documented benefits to anemic cancer patients undergoing chemotherapy, most importantly a reduction in the likelihood of needing red cell transfusions. One challenge in supportive cancer care is a relative resistance to ESAs, requiring high doses with a significant rate of nonresponse. Recent advances in our understanding of iron metabolism in patients with chronic illness and the results of clinical trials indicate that parenteral iron improves ESA response in this setting. Another issue is the safety of ESA treatment in cancer patients. There is an increased risk of venous thrombosis that must be considered in clinical decision making. There are also recent data raising concerns that ESAs may enhance tumor progression or decrease patient survival. Although the preponderance of the data suggests that ESAs do not alter survival when used to treat chemotherapy-induced anemia, large well-controlled trials addressing this issue are needed.

Topics: Anemia; Cell Hypoxia; Disease Progression; Drug Resistance; Erythropoietin; Hematinics; Humans; Neoplasm Metastasis; Neoplasms

Oxygen deprivation leading to hypoxia is a common feature of solid tumours. Under these conditions a signalling pathway involving a key oxygen-response regulator termed the hypoxia-inducible factor (HIF) is switched on. HIF is a transcription factor that, in hypoxia, drives the induction or repression of a myriad of genes controlling multiple cell functions such as angiogenesis, metabolism, invasion/metastasis and apoptosis/survival. Thus, the level of oxygen in a cell dictates the molecular response of cells through modulation of gene expression. Here we review the central role of HIF in cancer progression through the tumour response to hypoxia. Within this context the following aspects will be discussed: i) the mechanism by which oxygen deprivation inhibits two oxygen-sensor hydroxylases, thereby releasing the alpha subunit of HIF from programmed destruction by the ubiquitin-proteasome system and from a lock on its transcriptional activity; ii) the way in which the bi-transcriptional activity of HIF-alpha, which is regulated by the interplay between an oxygen-sensor attenuator and co-activators, determines the repertoire of gene expression; and iii) the role that HIF plays in tumour metabolism, in particular in glycolysis, and consequent acidification of the microenvironment, which influences both cell survival and cell death. Finally, the direct link of HIF to tumourigenesis and metastasis will be investigated and approaches for fighting tumour progression through a better understanding of HIF-mediated modulation of tumour metabolism and cell death will be considered.

Topics: Cell Death; Cell Hypoxia; Cell Survival; Enzyme Stability; Erythropoietin; Gene Expression Regulation; Homeostasis; Hydroxylation; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Oxygen; Procollagen-Proline Dioxygenase; Vascular Endothelial Growth Factor A

Patients undergoing cancer surgery frequently require blood, and the transfusion of allogeneic blood in these patients has been controversially linked to an increased risk of tumor recurrence. This patient population may therefore benefit from preoperative autologous blood donation (ABD) with or without epoetin alfa therapy, although the precise impact of autologous blood transfusion has not been fully explored. In some trials, preoperative ABD reduced allogeneic blood exposure by 50% in patients undergoing surgery for cancer resection, while, in another study, perioperative treatment with epoetin alfa significantly increased hematocrit (Hct) levels preoperatively and led to a reduction in postoperative allogeneic blood exposure. A combination of epoetin alfa and preoperative ABD seems a reasonable approach to reducing allogeneic blood exposure in patients undergoing cancer surgery.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Colorectal Neoplasms; Disease-Free Survival; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gastrointestinal Neoplasms; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Premedication; Prospective Studies; Recombinant Proteins; Survival Rate; Transfusion Reaction; Treatment Outcome

Tansplantability, growth, morphology, and function of xenotransplanted human tumors, such as carcinomas of the lung, liver, breast, choriocarcinoma, and blastomas of the liver, lung, kidney, and uterus, are described. From the tumor take rate, it is clear that xenotransplantation cannot be used for the study of every human tumor: slow-growing tumors are difficult to analyze, and functioning adenomas and low-grade malignant carcinomas are at present almost impossible to study by this approach. From the authors' transplantation experience, tumor antigenicity to nude mice with no T-cell function, either tumor specific or species specific, was suspected. Therefore, the growth in nude mice may not equate to that in the human body. The stroma of the transplanted tumor, which is most likely of mouse origin, might also alter the growth rate, as it did the histology of some tumors. Another possible hindrance that has not been described in the text is the mouse endogenous virus. Serially transplanted human tumors are often infected with C particles, which could well influence the tumor growth and character. In spite of the presence of some factors unfavorable for the study of human tumors through xenotransplantation, it has, nevertheless, been clearly shown that the nude mouse/human tumor system is a very useful tool for functional analysis of tumors in relation to growth, differentiation, and morphology, such as eutopic or ectopic production of various hormones, AFP, normal serum proteins, colony-stimulating factor, erythropoietin, and so on. This system can be employed to elucidate the production of many other biologically active and inactive substances by a variety of tumors and their effects on the host in the future and should provide better understanding of human cancers. Attempts to induce differentiation and to change the biologic behavior of xenotransplanted human malignant tumors have failed so far, except for induced dormancy of breast carcinoma under unfavorable hormonal conditions. This line of investigation may have particular import on cancer research, particularly in relation to the biology and treatment of human cancers.

Topics: alpha-Fetoproteins; Animals; Blood Proteins; Breast Neoplasms; Carcinoma; Carcinoma, Adenoid Cystic; Cell Division; Choriocarcinoma; Erythropoietin; Female; Graft Survival; Hormones, Ectopic; Humans; Kidney Neoplasms; Liver Neoplasms; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Mesenchymoma; Mice; Mice, Nude; Middle Aged; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Neoplasms, Hormone-Dependent; Pregnancy; Transplantation, Heterologous

Topics: Adrenocorticotropic Hormone; Bronchial Neoplasms; Calcitonin; Carcinoma, Small Cell; Erythropoietin; Fluorescent Antibody Technique; Gastrointestinal Hormones; Gonadotropins, Pituitary; Growth Hormone; Histocytochemistry; Hormones, Ectopic; Humans; Hypercalcemia; Insulin; Insulin Secretion; Neoplasm Metastasis; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Placental Lactogen; Prolactin; Thyrotropin; Vasopressins

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Animals; Brain Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cells, Cultured; Cricetinae; Cysts; Erythropoietin; Esophageal Neoplasms; Female; Growth Substances; Haplorhini; Humans; In Vitro Techniques; Kidney Neoplasms; Leiomyoma; Leukemia; Leukemia, Experimental; Liver Neoplasms; Lymphoma; Male; Mice; Neoplasm Metastasis; Neoplasm Transplantation; Pheochromocytoma; Polycythemia; Rats; Sarcoma, Experimental; Skin Neoplasms; Time Factors; Wilms Tumor

Topics: Amino Acids; Animals; Blood Cell Count; Bone Marrow; Bone Marrow Cells; Clone Cells; Colchicine; Culture Techniques; DNA Replication; Erythropoiesis; Erythropoietin; Hematopoiesis; Humans; Iron; Mitosis; Neoplasm Metastasis; Rabbits; Reticulocytes; Staining and Labeling; Sulfur; Temperature; Thymidine; Tritium; Trypan Blue

PURPOSE, PATIENTS AND METHODS: This retrospective analysis of the BRAVE study evaluated the impact of baseline risk factors and antithrombotic therapy on the risk of thrombovascular events (TVEs) in patients receiving epoetin compared to patients not receiving epoetin.. Baseline risk factors have a significant impact on TVE risk under epoetin therapy. More than 2 risk factors increased the risk of TVEs in patients receiving epoetin (hazard ratio [HR] 2.89, confidence interval [CI] 1.04-8.02, p value [p]=0.04). In patients on epoetin without antithrombotic therapy, the risk for TVEs was higher (HR 4.11, CI 1.37-12.4, p=0.01) compared to those who received antithrombotics (HR 1.37, CI 0.59-3.18, p=0.45).. Our analysis has identified several risk factors which may impact the risk of TVEs under epoetin therapy. These data suggest that antithrombotic therapy may have the potential to reduce the risk of TVEs under epoetin therapy. These findings are hypothesis-generating and need to be confirmed in a prospective, randomised study.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Epidemiologic Methods; Erythropoietin; Female; Fibrinolytic Agents; Hematinics; Hemoglobins; Humans; Middle Aged; Neoplasm Metastasis; Prognosis; Recombinant Proteins; Thrombophlebitis; Thrombosis

To evaluate the effect on survival and quality of life of maintaining hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in women with metastatic breast cancer (MBC) receiving first-line chemotherapy.. Eligible patients were randomly assigned to receive epoetin alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if baseline Hb was < or = 13 g/dL or when Hb decreased to < or = 13g/dL during the study. The primary end point was 12-month overall survival (OS).. The study drug administration was stopped early in accordance with a recommendation from the Independent Data Monitoring Committee because of higher mortality in the group treated with epoetin alfa. Enrollment had been completed, with 939 patients enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for placebo recipients (P = .01). Optimal tumor response and time to disease progression were similar between groups. The reason for the difference in mortality between groups could not be determined from additional subsequent analyses involving both study data and chart review.. In this trial, the use of epoetin alfa to maintain high Hb targets in women with MBC, most of whom did not have anemia at the start of treatment, was associated with decreased survival. Additional research is required to clarify the potential impact of erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Neoplasm Metastasis; Placebos; Quality of Life; Recombinant Proteins; Survival Analysis

In order to study the relation to the metastatic profile and survival, we evaluated the association between pretreatment serum levels of IL-6, TNF-alpha, and erythropoietin (EPO) and metastatic distribution and survival in 16 patients with metastatic malignant melanoma. IL-6 and TNF-alpha immunoassay (R&D Systems, Inc. Minneapolis, USA) employs the quantitative sandwich enzyme immunoassay technique. The Quantikine IVD EPO ELISA (R&D Systems, Inc.) is based on the double-antibody sandwich method. The baseline serum IL-6 and EPO levels were significantly higher in patients with metastatic malignant melanoma than in the control group (p = 0.009 and p = 0.033, respectively). Serum IL-6 levels were higher in patients with weight loss (p = 0.02), who were anemic (p = 0.026), with elevated serum LDH levels (p = 0.028), and who were chemotherapy nonresponding (p = 0.016). The relationship of serum IL-6 concentration to the tumor burden was not determined. Only serum EPO level was influenced by hemoglobin status (p = 0.001). No difference was shown among these three parameters. Elevated serum IL-6 concentration (p = 0.002) was found to be an adverse prognostic factor in patients with poor performance status, weight loss, low serum hemoglobin, elevated serum LDH, and unresponsive to chemotherapy. On the other hand, both serum TNF-alpha and EPO levels were of no prognostic value. Serum levels of IL-6 were found to be prognostic factors as valuable as serum LDH levels in patients with metastatic malignant melanoma. Their prognostic value should be further evaluated in a larger patient population.

Topics: Adult; Aged; Biomarkers, Tumor; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Follow-Up Studies; Humans; Interleukin-6; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Predictive Value of Tests; Prognosis; Skin Neoplasms; Tumor Necrosis Factor-alpha

Erythropoietin is an effective treatment for anemia in patients with various types of cancers, but few studies have evaluated the benefit of treatment in advanced breast cancer. In this multicenter study, we investigated the influence of two different doses of epoetin-beta on the level of hemoglobin, the need for blood transfusion, quality of life and safety aspects in patients with metastatic breast cancer. A total of 180 patients were randomized to receive either 1000 IE or 5000 IE epoetin-beta subcutaneously three times per week for 24 weeks. An increase of 20 g/L was defined as a positive hemoglobin response. Blood transfusions were given, if clinically indicated. Additional laboratory values and adverse events were recorded. Quality of life was measured with the aid of the EORTC QLQ-C30 questionnaire. Hemoglobin levels increased significantly in both groups. In the high-dose group, the initial mean Hb value was 98 g/L (64-110), which increased to 121 g/L (83-165) by week 24. In the low-dose group, the mean Hb value was 99 g/L (77-110.5) and by week 24 it was 116 g/L (81-144). The majority of patients who responded to treatment did so during the first four weeks. After 4 weeks, 7 patients in the low-dose group and 24 patients in the high-dose group had increased their Hb values by more than 20 g/L. The need for transfusion was low and did not differ between the groups. Quality of life was significantly enhanced in both groups, and there was no difference in the global quality of life between the two study arms. Epoetin-beta is a well-tolerated, safe and effective treatment of anemia in patients with metastatic breast cancer. There were significant improvements in Hb levels and quality of life in both groups.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Breast Neoplasms; Erythropoietin; Female; Hemoglobins; Humans; Middle Aged; Neoplasm Metastasis; Quality of Life; Recombinant Proteins

The role of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) combination in hemopoietic recovery was studied in patients with high-risk breast carcinoma and compared to a control group of previously treated identical patients who were not given EPO plus G-CSF. Eleven consecutive patients admitted to this study had Stage III or IV breast cancer. They received 6 cycles of intensive chemotherapy (epirubicin 150 mg/m2 and cyclophosphamide 1300 mg/m2). The 1st cycle served for mobilization of peripheral blood progenitor cells (PBPC). At its end leukaphereses collections of PBPC were performed to be used as hematologic support (PBPCT) in the 5 remaining cycles. The administration of EPO plus G-CSF was started when leukocyte (WBC) count in peripheral blood dropped below 1 x 10(9)/l and hemoglobin (Hb) level fell below 100 g/l. The treatment was stopped when leukocyte count rose to 5 x 10(9)/l and Hb to 130 g/l. EPO plus G-CSF combination after PBPCT produced significant effects in terms of hemopoietic recovery, clinical benefit and supportive care requirements when compared with 12 historic control patients: Periods of leukopenia were shorter which resulted in reduced risk of infectious complications. The grades of leukopenia in the study and control groups were as follows: grade 4 (36 vs. 18%), grade 3 (57 vs. 30%), grade 2 (7 vs. 13%) respectively. Significantly shorter was the time of PLT recovery < 50 x 10(9)/l (p < 0.001). The grades of thrombocytopenia were: grade 4 (29 vs. 11%), grade 3 (21 vs. 12%), grade 2 (25 vs. 36%) respectively. The number of necessary transfusions was significantly reduced as well as the length of hospital stay (p < 0.001). In conclusion, our results obtained in this study confirm that combination of EPO plus G-CSF not only increases the rate of hemopoietic recovery, reduces the number of necessary red blood cell and platelet transfusions but, at the same time, simplifies the clinical management and is more tolerable for the patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Cyclophosphamide; Drug Therapy, Combination; Epirubicin; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Leukapheresis; Leukocyte Count; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Patient Selection; Recombinant Proteins

Patients undergoing cancer surgery frequently require blood, and the transfusion of allogeneic blood in these patients has been controversially linked to an increased risk of tumor recurrence. This patient population may therefore benefit from preoperative autologous blood donation (ABD) with or without epoetin alfa therapy, although the precise impact of autologous blood transfusion has not been fully explored. In some trials, preoperative ABD reduced allogeneic blood exposure by 50% in patients undergoing surgery for cancer resection, while, in another study, perioperative treatment with epoetin alfa significantly increased hematocrit (Hct) levels preoperatively and led to a reduction in postoperative allogeneic blood exposure. A combination of epoetin alfa and preoperative ABD seems a reasonable approach to reducing allogeneic blood exposure in patients undergoing cancer surgery.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Colorectal Neoplasms; Disease-Free Survival; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gastrointestinal Neoplasms; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Premedication; Prospective Studies; Recombinant Proteins; Survival Rate; Transfusion Reaction; Treatment Outcome

Prostate cancer (PCa) is the most prevalent cancer in U.S. men and many other countries. Although primary PCa can be controlled with surgery or radiation, treatment options of preventing metastatic PCa are still limited. To develop a new treatment of eradicating metastatic PCa, we have created an injectable cancer trap that can actively recruit cancer cells in bloodstream. The cancer trap is composed of hyaluronic acid microparticles that have good cell and tissue compatibility and can extend the release of chemokines to 4 days in vitro. We find that erythropoietin (EPO) and stromal derived factor-1α can attract PCa in vitro. Animal results show that EPO-releasing cancer trap attracted large number of circulating PCa and significantly reduced cancer spreading to other organs compared with controls. These results support that cancer trap may serve as a unique device to sequester circulating PCa cells and subsequently reduce distant metastasis.

Topics: Chemokine CXCL12; Chemokines; Erythropoietin; Humans; Hyaluronic Acid; Male; Neoplasm Metastasis; Neoplastic Cells, Circulating; Prostatic Neoplasms

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA. This resulted in reduced transcriptional activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which consequently inhibited the growth of metastatic PHEO. Additionally, IDA downregulated hypoxia signaling by interfering with the transcriptional activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our results indicate that anthracyclines are prospective candidates for inclusion in metastatic PHEO/PGL therapy, especially in patients with gene mutations involved in the hypoxia signaling pathway.

Topics: Adrenal Gland Neoplasms; Animals; Antineoplastic Agents; Basic Helix-Loop-Helix Transcription Factors; Cell Growth Processes; Cell Line, Tumor; Endothelin-1; Erythropoietin; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Idarubicin; Mice; Mice, Nude; Neoplasm Metastasis; Pheochromocytoma; Phosphoglycerate Kinase; Protein Binding; Signal Transduction; Xenograft Model Antitumor Assays

Erythropoietin (Epo) is glycoprotein hormone which binds on erythropoietin receptors (EpoR) promoting proliferation and differentiation. Studies have shown that EpoR, apart from erythrocyte precursors, is expressed on no hematopoietic tissue and various tumor cells. Despite the progress in modern medicine, colorectal carcinoma (CRC) is still the leading cause of increased morbidity and mortality between oncology patients worldwide. Its precursors are benign villous adenomas, which in certain percentage progress to cancer. Anemia of chronic disease is common finding in CRC patients. Some of them are treated with Epo. Epo/EpoR seems to correlate with tumor progression and metastasizing. Therefore, the identification of at-risk group remains a clinical challenge. Vascular endothelial growth factor (VEGF) is a signal protein that stimulates angiogenesis and concentration of VEGF is positive correlated with tumor growth in numerous tumors. The importance of Epo in tumor pathogenesis has led to a growing interest in the potential prognostic value. By our point of view there are many open questions about role of Epo/EpoR in CRC.

Topics: Adenoma; Animals; Biomarkers, Tumor; Colorectal Neoplasms; Erythropoietin; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematopoiesis; Humans; Immunohistochemistry; Models, Theoretical; Neoplasm Metastasis; Neovascularization, Pathologic; Receptors, Erythropoietin; Recombinant Proteins; Vascular Endothelial Growth Factor A

Erythropoietin and its analogue darbepoetin (DPO)-α have been shown to improve liver function and regeneration after partial hepatectomy (Phx). However, previous experimental studies have also shown that DPO significantly enhances Phx-induced engraftment of colorectal liver metastases by increasing neovascularization and tumor cell proliferation. Therefore, the present study analyzed whether DPO affects engraftment and neovascularization of extrahepatic colorectal metastases after major hepatectomy.. Green fluorescent protein-transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Animals received a single dose of DPO (10 µg/kg body weight) at the day of tumor cell implantation (day 0). Phosphate-buffered saline-treated animals served as controls. To study whether the effect of DPO is influenced by Phx, additional animals with and without DPO treatment underwent 70% Phx at day 0. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied repetitively over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry.. In nonhepatectomized animals, DPO significantly accelerated tumor cell engraftment and slightly enhanced tumor neovascularization. Tumor cell migration and host tissue infiltration were not affected by DPO. In hepatectomized animals, DPO slightly enhanced tumor growth and significantly accelerated tumor neovascularization, but did not affect tumor cell migration and infiltration.. The present study indicates that DPO accelerates extrahepatic engraftment of colorectal cancer cells, most probably by stimulating the process of neovascularization.

Topics: Animals; Apoptosis; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Mice, Inbred BALB C; Neoplasm Metastasis; Neovascularization, Pathologic; Random Allocation

Erythropoietin (Epo) is used in clinical settings to enhance hematopoietic function and to improve the quality of life for patients undergoing chemotherapy by reducing fatigue and the need for transfusions. However, several meta-analyses have revealed that Epo treatments are associated with an increased risk of mortality in cancer patients. In this study, we examined the role of Epo in prostate cancer (PCa) progression, using in vitro cell culture systems and in vivo bone metastatic assays. We found that Epo did not stimulate the proliferation of PCa cell lines, but did protect PCa cells from apoptosis. In animal models of PCa metastasis, no evidence was found to support the hypothesis that Epo enhances metastasis. Together, these findings suggest that Epo may be useful for treating severe anemia in PCa patients without increasing metastatic risk.

Topics: Animals; Apoptosis; Blotting, Western; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Erythropoietin; Flow Cytometry; Humans; Male; Mice; Mice, SCID; Neoplasm Metastasis; Prostatic Neoplasms

The microRNA 125b is a double-faced gene expression regulator described both as a tumor suppressor gene (in solid tumors) and an oncogene (in hematologic malignancies). In human breast cancer, it is one of the most down-regulated miRNAs and is able to modulate ERBB2/3 expression. Here, we investigated its targets in breast cancer cell lines after miRNA-mimic transfection. We examined the interactions of the validated targets with ERBB2 oncogene and the correlation of miR-125b expression with clinical variables.. MiR-125b possible targets were identified after transfecting a miRNA-mimic in MCF7 cell line and analyzing gene expression modifications with Agilent microarrays and Sylamer bioinformatic tool. Erythropoietin (EPO) and its receptor (EPOR) were validated as targets of miR-125b by luciferase assay and their expression was assessed by RT-qPCR in 42 breast cancers and 13 normal samples. The molecular talk between EPOR and ERBB2 transcripts, through miR-125b, was explored transfecting MDA-MD-453 and MDA-MB-157 with ERBB2 RNA and using RT-qPCR.. We identified a panel of genes down-regulated after miR-125b transfection and putative targets of miR-125b. Among them, we validated erythropoietin (EPO) and its receptor (EPOR) - frequently overexpressed in breast cancer--as true targets of miR-125b. Moreover, we explored possible correlations with clinical variables and we found a down-regulation of miR-125b in metastatic breast cancers and a significant positive correlation between EPOR and ERBB2/HER2 levels, that are both targets of miR-125b and function as competing endogenous RNAs (ceRNAs).. Taken together our results show a mechanism for EPO/EPOR and ERBB2 co-regulation in breast cancer and confirm the importance of miR-125b in controlling clinically-relevant cancer features.

Topics: 3' Untranslated Regions; Binding Sites; Breast Neoplasms; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; HEK293 Cells; Humans; MCF-7 Cells; MicroRNAs; Molecular Sequence Annotation; Neoplasm Metastasis; Receptor, ErbB-2; Receptors, Erythropoietin; RNA Interference

The authors evaluated the patterns of use and the risk of thromboembolic events (TEE) associated with erythropoietin-stimulating agents (ESAs) in older patients with metastatic breast cancer who were receiving chemotherapy.. The study was retrospective and used the SEER-Medicare linked database. Stage IV breast cancer patients diagnosed from 1995-2005, treated with chemotherapy, ≥66 years old, with full coverage of Medicare A and B were included. The World Health Organization's International Classification of Diseases (ICD-9) and the Healthcare Common Procedure Coding System (HCPCS) were used to identify the use of ESAs, chemotherapy, and complications of therapy. Analyses included descriptive statistics and logistic regression.. Of 2266 women, 980 (43.3%) received ESAs, and 1286 (56.7%) did not. Patients diagnosed after 1999 or who received treatment with taxanes, anthracyclines, or vinorelbine were more likely to receive ESAs. Patients receiving ESAs had higher rates of stroke (18.5% vs 15.1%, P = .031); deep-vein thrombosis (DVT; 21.3% vs 14.4%, P<.001), other/unspecified thromboembolic event (TEE; 19.8% vs 14.7%, P = .001), and any clot (31.3% vs 23.4%, P<.0001). In multivariate analysis, patients receiving ESAs had increased risk for DVT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.75), and any clot (OR, 1.26; 95% CI, 1.02-1.57). A dose-dependent effect was evident for stroke, DVT, other TEE, and any clot.. In this cohort of patients, the use of ESAs increased the risk of TEEs, with a dose-dependent effect for stroke, DVT, other TEE, and any clot. The data show that among patients treated with chemotherapy and ESAs for metastatic breast cancer, TEEs are a common event. Therefore, caution is recommended when using these agents.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Erythropoietin; Female; Humans; Medicare; Neoplasm Metastasis; Retrospective Studies; SEER Program; Stroke; Thrombosis; United States; Venous Thrombosis

Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia. Recent clinical trials have reported increased adverse events and reduced survival in ESA-treated breast cancer patients receiving chemotherapy, potentially related to erythropoietin (EPO)-induced cancer progression. However, minimal preclinical data are available about the impact of EPO on metastatic cell behavior and/or the metastatic process, and this was the goal of our study.. Breast cancer cell lines were treated with recombinant human EPO (rHuEPO) and screened for expression of EPO receptors (EPOR). MDA-MB-231 and MDA-MB-435 cell lines were used for functional assays in vitro (two-dimensional/three-dimensional growth and survival) and in vivo (tumorigenicity and metastasis), in the presence or absence of EPO and/or cytotoxic agents.. A large variation in EPOR expression across cell lines was observed. In vitro, rHuEPO had a protective effect on radiation-treated MDA-MB-435 cells (P < 0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not influence cell survival. In vivo, rHuEPO increased lung metastases in immunocompromised mice injected with MDA-MB-231 or MDA-MB-435 cells and treated with chemotherapy relative to mice treated with chemotherapy alone (P < 0.05).. The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. These studies may begin to uncover the underlying functional explanation for the observed EPO-related adverse events and decreased survival in ESA-treated metastatic breast cancer patients undergoing chemotherapy.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Drug Evaluation, Preclinical; Erythropoietin; Female; Humans; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Transplantation; Recombinant Proteins

This prospective, observational study investigated the haematological response to darbepoetin alfa (DA) administered every three weeks for the treatment of anaemia. Response was also assessed according to baseline characteristics including iron, folate and vitamin B12 status.. Anaemic adult patients with malignant non-myeloid cancer, starting or having already undergone chemotherapy received DA on day of inclusionand were followed up for up to 24 weeks. Concentration of haemoglobin (Hb), as well as iron, vitamin B12 and folate status where available, were recorded at inclusion, after a treatment period of 9 weeks and up to a maximum of 24 weeks or cessation of DA treatment, whichever was sooner.. The main outcome measure assessed in this study was the percentage of patients reaching a Hb concentration of at least 11 g/dL at least once at any time during the study.. A total of 2912 patients were included. The mean Hb concentration increased from 10.0 g/dL at inclusion to 11.4 g/dL at 9 weeks and 11.8 g/dL at 24 weeks. In 74.6% of patients the target Hb level of 11.0 g/dL or above was reached. After initiation of DA treatment, 9.5% of patients required a blood transfusion by week 9, and 5.6% thereafter. Vitamin B12 and folate status were unknown for 80.3% of patients and the iron status for 73.2% of patients. Compared with patients who remained untreated for vitamin B12 or folate deficiency, a higher percentage of patients with vitamin status within normal limits achieved the target Hb concentration. However, achievement of target Hb level appeared not to be affected by iron status.. In this study, the mean Hb level increased in anaemic cancer patients treated with DA and the majority of patients achieved the target Hb level. In contrast to the recommendations of guidelines (EORTC) encouraging the measurement of iron and vitamin levels, the present study demonstrated that data were not routinely collected for these factors.

Topics: Aged; Anemia; Antineoplastic Agents; Cohort Studies; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Female; Folic Acid; France; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Prospective Studies; Vitamin B 12

Erythropoietin (EPO) has been used to correct cancer-related anemia and to improve tumor hypoxia, which both adversely affect the clinical condition of cancer patients and response to radiotherapy. Data available on the effects of EPO treatment in cancer are, however, conflicting. Several clinical studies investigating the influence of EPO treatment have given contradictory results as to whether or not this treatment positively influences survival. In light of these conflicting results, we studied the effects of EPO treatment either alone or in combination with radiotherapy on tumor oxygenation and on the expression pattern of several proteins related to tumor metabolism, survival, and spread in a rat colorectal cancer model. We found a statistically significant upregulation of hexokinase I, N-cadherin, and glucose transporter 3 when EPO treatment was combined with radiotherapy. Because these three proteins have distinct functions in protecting the cell in compromised conditions, these results indicate a detrimental role for the combination of EPO treatment and radiotherapy through the stimulation of tumor-cell metabolism, inhibition of apoptosis, and stimulation of tumor spread and seem to indicate that recombinant human EPO treatment negatively modulates radiotherapy efficacy.

Topics: Animals; Cell Line, Tumor; Cell Nucleus; Combined Modality Therapy; Erythropoietin; Gene Expression Regulation, Neoplastic; Hematocrit; Immunohistochemistry; Male; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Oxygen; Radiotherapy; Rats; Treatment Outcome

Topics: Animals; Cell Differentiation; Erythropoietin; Genomic Instability; Humans; Hydroxylation; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mitochondria; Models, Biological; Neoplasm Metastasis

In this study, we assessed the ability of erythropoietin (EPO) to synergize with various chemotherapeutic agents and suppress the growth and metastasis of solid tumors. Animals were inoculated with Lewis lung carcinoma (LLC) cells and treated with EPO alone, the designated chemotherapeutic drug (cisplatin, mitomycin C or cyclophoshamide) alone, or EPO and the drug. Tumor volume was monitored daily. Thirteen days following cell injection, tumor mass was determined. In addition, the number of the metastatic foci in the lungs was determined. Cisplatin alone was capable of inducing a 7-fold decrease in final tumor volume compared to tumor-bearing animals injected with saline. However, when EPO was combined with cisplatin, the animals experienced an 11-fold reduction in final tumor volume compared to saline-injected animals (P<0.001). A 2.5-fold reduction in tumor mass was observed in animals treated with cisplatin, compared to the saline-injected groups. Furthermore, injections of EPO and cisplatin induced a 4-fold reduction in tumor mass (P<0.001). Blood analysis indicated that a significant increase of more than 30% in WBC was found in animals injected concurrently with cisplatin and EPO, as compared to saline-injected mice (P<0.03). When EPO and mitomycin C were injected together, tumor mass was further reduced by 14% compared to that seen in mice treated with mitomycin C alone. However, this difference was not statistically significant. We conclude from this study that EPO can synergize with chemotherapeutic agents to further suppress the growth of tumors. The level of synergism is drug related.

Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Lewis Lung; Cisplatin; Cyclophosphamide; Disease Models, Animal; Drug Interactions; Erythropoietin; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred C57BL; Mitomycin; Neoplasm Metastasis

Malignant cell contamination in autologous transplants is a potential origin of tumor relapse. Ex vivo expansion of CD34(+) blood progenitor cells (BPC) has been proposed as a tool to eliminate tumor cells from autografts. To characterize the influence of culture conditions on survival, growth, and clonogenicity of malignant cells, we isolated primary mammary carcinoma cells from pleural effusions and ascites of patients with metastatic breast cancer and cultured them in the presence of stem cell factor (SCF), interleukin-1beta (IL-1beta), IL-3, IL-6, and erythropoietin (EPO), ie, conditions previously shown to allow efficient ex vivo expansion of CD34(+) BPC. In the presence of serum, tumor cells proliferated during a 7-day culture period and no significant growth-modulatory effect was attributable to the presence of hematopoietic growth factors. When transforming growth factor-beta1 (TGF-beta1) was added to these cultures, proliferation of breast cancer cells was reduced. Expansion of clonogenic tumor cells was seen in the presence of SCF + IL-1beta + IL-3 + IL-6 + EPO, but was suppressed by TGF-beta1. Cocultures of tumor cells in direct cellular contact with hematopoietic cells showed that tumor cell growth could be stimulated by ex vivo expanded hematopoietic cells at high cell densities (5 x 10(5)/mL). In contrast, culture under serum-free conditions resulted in death of greater than 90% of breast cancer cells within 7 days and a further decrease in tumor cell numbers thereafter. In the serum-free cultures, hematopoietic cytokines and cellular contact with CD34(+) BPC could not protect the tumor cells from death. Therefore, ex vivo expansion of CD34(+) BPC in serum-free medium provides an environment for efficient purging of contaminating mammary carcinoma cells. These results have clinical significance for future protocols in autologous progenitor cell transplantation in cancer patients.

Topics: Antigens, CD34; Ascites; Breast Neoplasms; Cell Division; Cell Survival; Coculture Techniques; Culture Media; Culture Media, Serum-Free; Erythropoietin; Hematopoietic Stem Cells; Humans; Interleukin-1; Interleukin-3; Interleukin-6; Neoplasm Metastasis; Pleural Effusion; Stem Cell Factor; Transforming Growth Factor beta; Tumor Cells, Cultured

Topics: Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Diphosphonates; Erythropoietin; Female; Humans; Male; Neoplasm Metastasis; Neoplasms; Pilot Projects; Radiotherapy

Serum erythropoietin (EPO) concentrations reportedly are depressed in patients with chronic disorders such as cancer, rheumatoid arthritis, and acquired immunodeficiency syndrome. We evaluated serum EPO levels in mice with tumors and found that the EPO response was appropriate for the associated anemia during the major part of the disease process. The levels of the hormone increased as the anemia worsened in association with progression of the disease. The increased EPO levels were comparable to those of controls with a similar degree of experimentally induced anemia. Only during the terminal stages of cancer, when the animals were severely cachectic, were serum EPO concentrations lower than in controls with a similar degree of anemia. These findings suggest that a blunted EPO response in experimental cancer occurs only in association with advanced disease.

Topics: Anemia, Hemolytic; Animals; Erythropoietin; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Tumor Necrosis Factor-alpha

Treatment of metastatic melanoma with biochemotherapy results in the rapid onset of anemia, requiring blood transfusion in 9 of 13 (69%) patients. Prophylactic use of weekly subcutaneous recombinant epoetin alfa eliminated the need for transfusion in all but 1 of 21 (5%) patients.

Topics: Anemia; Blood Transfusion; Cost-Benefit Analysis; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Melanoma; Neoplasm Metastasis; Quality of Life; Recombinant Proteins

Immunoreactive erythropoietin levels were measured in 42 patients with lymphoid malignancies with anaemia and bone marrow involvement. Results were compared to a control group of 16 patients suffering from anaemia due to other causes. Significant inverse correlations between serum erythropoietin level and haemoglobin concentration were shown for the patients with lymphoid malignancies and also for the control subjects. Overall, the erythropoietin levels of patients with lymphoid malignancies with bone marrow infiltration and with normal renal function did not differ significantly from erythropoietin levels of the anaemic controls. We conclude that anaemia in patients with lymphoproliferative disorders with bone marrow infiltration and normal renal function is caused primarily by a diminished/inadequate response to erythropoietin at the level of the target cell.

Topics: Anemia; Bone Marrow Diseases; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Lymphoma; Lymphoproliferative Disorders; Male; Multiple Myeloma; Neoplasm Metastasis

The relationships between prognostic factors and duration of survival in small cell lung cancer were investigated in a consecutive series of 874 patients treated with combination chemotherapy with or without irradiation. The series included 443 patients with limited and 431 patients with extensive stage disease based on staging including bone marrow examination and peritoneoscopy with liver biopsy but no routine scans. The median durations of survival for the two disease categories were 48 and 30 weeks, respectively. The influence on survival of various pretreatment factors was investigated by use of univariate methods and Cox's multivariate regression model. Patients in each stage were treated according to one of three controlled trials. Variations among the applied treatment regimens did not result in significant differences in duration of survival among patients with limited disease. An alternating regimen was superior to continuous therapy in patients with extensive disease and raised serum lactate dehydrogenase. Prognosis was correlated with disease extent. Surgical resection as well as limited stage disease thus both contributed to survival. Poor performance status, reduced hemoglobin concentration, and raised values for serum lactate dehydrogenase were significantly associated with a reduced duration of survival in both stages. Females with limited disease lived significantly longer than males while advanced age was a negative prognostic factor in extensive disease. Plasma sodium and serum urate were both predictive of survival in limited disease. Proved metastatic disease affecting specific sites or total number of metastatic sites did not carry significant prognostic information in a model including a general variable characterizing stage of disease. Fifty of the 778 patients, on whom the multiple regression model was based, were alive and disease free 2 years after the start of the treatment. Two-year survival rates were strongly correlated to groupings based on prognostic factors, and information about disease extent was not mandatory for predicting the probability of long term disease-free survival.

Topics: Adult; Aged; Alkaline Phosphatase; Carcinoma, Small Cell; Combined Modality Therapy; Erythropoietin; Female; Hormones, Ectopic; Humans; L-Lactate Dehydrogenase; Lung Neoplasms; Male; Middle Aged; Models, Biological; Neoplasm Metastasis; Prognosis; Regression Analysis; Risk; Vasopressins

Paraneoplastic erythrocytosis associated with production of erythropoietin and testosterone by a malignant lipid cell tumor is demonstrated in this case report. Several chemotherapeutic regimens failed to halt the progression of this aggressive metastatic lipid cell tumor. The scant literature on malignant lipid cell tumors is reviewed. Possible mechanisms for paraneoplastic erythrocytosis are presented. Adequate control of polycythemia preoperatively will reduce thromboembolic and hemorrhagic complications.

Topics: Combined Modality Therapy; Erythropoietin; Female; Humans; Hysterectomy; Laparotomy; Leydig Cell Tumor; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Paraneoplastic Endocrine Syndromes; Polycythemia; Progesterone; Sex Characteristics; Testosterone; Virilism

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

Erythropoietin was measured by exhypoxic polycythemic mouse method in the course of a 64-yr-old male with renal cell carcinoma associated with erythrocytosis. Serum erythropoietin fluctuated with progression of the disease. Preoperative elevated erythropoietin (0.11 U/ml, p greater than 0.05) subsided after nephrectomy and again increased with developing lung metastasis (0.1 U/ml, p greater than 0.02). Erythropoietin was markedly increased in the tumorous extracts from primary renal cell carcinoma in the kidney (0.2 U/g, p greater than 0.01) and lung metastasis (0.8 U/g, p greater than 0.01). Renal cell carcinoma from the lung metastasis was transplanted into nude mice, resulting in erythrocytosis in some of these mic. In the erythrocytotic mice, erythropoietin was elevated to levels of 0.25--0.9 U/g (p greater than 0.01) in the tumorous extracts and increased (0.67 U/ml, p greater than 0.02) in the serum. These results indicate that this renal cell carcinoma is an erythropoietin-producing tumor, and this tumor has been successfully transplanted in nude mice for the first time.

Topics: Adenocarcinoma; Animals; Erythropoietin; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Mice; Mice, Nude; Middle Aged; Neoplasm Metastasis; Neoplasm Transplantation

A case study is presented of a 55-year-old man who had clear cell renal carcinoma with pulmonary metastases and erythrocytosis. The increase in red blood cell mass was associated with an elevation in erythropoietic stimulatory activity in serum, pleural fluid, and tumor-cyst fluid as determined by the exhypoxic polycythemic mouse assay. It is postulated that the increased erythropoietic stimulatory activity represents autonomous tumor secretion of erythropoietin or an erythropoietin-like material. Electron microscopic studies confirmed the proximal tubular origin of this tumor.

Topics: Adenocarcinoma; Erythropoiesis; Erythropoietin; Humans; Hypoxia; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Polycythemia; Renal Veins; Vascular Diseases

Plasma renin, erythropoietin and chorionic gonadotropin levels were evaluated in 57 patients with renal adenocarcinoma. Renin elevation, found in 37 per cent, was unrelated to blood pressure levels but was associated with high grade, high stage lesions of mixed histologic cell type and predicted a poor prognosis. Erythropoietin was raised in 63 per cent of patients and was more sensitive than renin in indicating the presence of renal adenocarcinoma. However, it was less specific and did not correlate directly with tumor grade, stage, histologic type, prognosis or hematocrit and hemoglobin levels. None of the patients had elevated chorionic gonadotropin levels. Therefore, we believe that renin and erythropoietin determinations may be of value as biochemical tumor markers in renal adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Chorionic Gonadotropin; Erythropoietin; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Nephrectomy; Potassium; Prognosis; Renin

Erythropoietin (ESF) levels were assayed in rats bearing the Wistar-Furth Wilms' transplantable tumor. Sites of tumor inoculation varied from subcutaneous, intramuscular, intrarenal (subcapsular), to intraperitoneal. Two-thirds of the animals exhibited ESF elevations without polycythemia, or severe anemia (HCT less than 30.0 vol%). The elevations of ESF were not detectably related to the time of sacrifice (age of the animal), size of the primary tumor, or number of gross metastatic foci. The diminished ESF response noted to animals given intramuscular tumor implantations is believed to reflect differences in tumor blood and lymphatic supply at the various sites of inoculation. The pattern of ESF responses in the Wistar-Furth Wilms' tumor model is thus quite similar to that which we have observed in man, and appears to represent an animal model for tumor-related ectopic hormone release. The nature of the hormone is believed to differ from that seen in normal physiological states.

Topics: Animals; Erythropoietin; Hematocrit; Male; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Rats, Inbred WF; Wilms Tumor

Topics: Adrenal Gland Neoplasms; Adult; alpha-Fetoproteins; Carcinoma, Hepatocellular; Erythropoietin; Heart Neoplasms; Hemochromatosis; Humans; Hypoglycemia; Iron; Liver; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Metastasis; Polycythemia; Precancerous Conditions

Topics: 5-Hydroxytryptophan; Adrenocorticotropic Hormone; Breast Neoplasms; Calcitonin; Chorionic Gonadotropin; Erythropoietin; Estradiol; Female; Gastrins; Hormones, Ectopic; Humans; Hyperkalemia; Middle Aged; Neoplasm Metastasis; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Progesterone

Topics: Adenocarcinoma; Animals; Antibody Formation; Cell Division; Cell-Free System; Diethylstilbestrol; Disease Models, Animal; Erythropoietin; Female; Hematocrit; Kidney Neoplasms; Male; Medroxyprogesterone; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Sex Factors; Species Specificity; Testosterone; Transplantation, Homologous

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Disease Models, Animal; Erythropoietin; Hematocrit; Hormones; Inclusion Bodies, Viral; Kidney Neoplasms; Kinetics; Mice; Microscopy, Electron; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental

Topics: Adenocarcinoma; Animals; Disease Models, Animal; Erythropoietin; Hematocrit; Kidney; Kidney Neoplasms; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Nephrectomy; Organ Size; Splenic Neoplasms; Time Factors

Topics: Adult; Child; Erythropoietin; Humans; Iron Isotopes; Kidney; Kidney Neoplasms; Neoplasm Metastasis; Nephrectomy; Wilms Tumor

Topics: Adenocarcinoma; Adult; Androgens; Erythropoietin; Female; Humans; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Neoplasm Metastasis; Polycythemia

Topics: Adolescent; Animals; Biological Assay; Blood Urea Nitrogen; Child; Child, Preschool; Erythropoietin; Female; Humans; Infant; Iron Isotopes; Male; Mice; Neoplasm Metastasis; Prognosis; Wilms Tumor

Topics: Adenocarcinoma; Blood Cell Count; Carcinoma, Renal Cell; Epoetin Alfa; Erythropoietin; Geriatrics; Humans; Kidney Neoplasms; Lung Neoplasms; Mercaptopurine; Neoplasm Metastasis; Neoplasms; Neoplasms, Second Primary; Nephrectomy

Topics: Adenocarcinoma; Blood; Body Fluids; Carcinoma, Renal Cell; Epoetin Alfa; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Kidney Neoplasms; Neoplasm Metastasis; Nephrectomy; Pathology; Polycythemia; Urine