losartan-potassium and Adenocarcinoma

Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs). In breast cancer, CICs can be identified by phenotypic markers and their fate is controlled by the Notch pathway.. In this study, we investigated the effect of erythropoietin on CICs in breast cancer cell lines. Levels of erythropoietin receptor (EpoR), CD24, CD44, Jagged-1 expression, and activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity of CICs was investigated in sphere formation assays.. EpoR expression was found on the surface of CICs. Recombinant human Epo (rhEpo) increased the numbers of CICs and self-renewing capacity in a Notch-dependent fashion by induction of Jagged-1. Inhibitors of the Notch pathway and PI3-kinase blocked both effects.. Erythropoietin functionally affects CICs directly. Our observation may explain the negative impact of recombinant Epo on local control and survival of cancer patients with EpoR-positive tumors.

Topics: Adenocarcinoma; Amyloid Precursor Protein Secretases; Breast Neoplasms; Cell Adhesion; Cell Division; Chromones; Erythropoietin; Female; Humans; Hyaluronan Receptors; Morpholines; Neoplasm Proteins; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Receptor, Notch1; Receptors, Erythropoietin; Recombinant Fusion Proteins; Recombinant Proteins; Sialic Acid Binding Ig-like Lectin 2; Spheroids, Cellular; Transfection; Tumor Cells, Cultured

This article reviews complementary and alternative therapies for advanced prostate cancer. This is not a comprehensive survey of nontraditional therapies for prostate cancer. Rather, this review focuses on alternative and complementary therapies with published studies to evaluate efficacy and safety. Three areas are addressed: alternative forms of hormonal therapy, management of side effects of hormonal therapy, and management of skeletal complications.

Topics: Acupuncture; Adenocarcinoma; Androgen Antagonists; Androgens; Anemia; Anticarcinogenic Agents; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials, Phase II as Topic; Complementary Therapies; Depression; Diphosphonates; Drugs, Chinese Herbal; Erythropoietin; Female; Flushing; Humans; Hypericum; Male; Multicenter Studies as Topic; Neoplasms, Hormone-Dependent; Osteoporosis; Phytotherapy; Pilot Projects; Plant Extracts; Prospective Studies; Prostatic Hyperplasia; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Serenoa

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

The diverse systemic effects associated with malignant renal tumours are described. It is emphasized that their recognition is essential for the early diagnosis of the tumour and that many of these effects may be overlooked unless the clinician is alert to their significance. Many of these early diagnostic clues also have a prognostic value.Although the basic management of a patient with a renal tumour continues to be a nephrectomy, the importance of tumour staging in relation to radical surgery is emphasized. Adjuvant therapy by radiotherapy, drugs, or immunotherapy is described and evaluated.

Topics: Adenocarcinoma; Alkaline Phosphatase; Alpha-Globulins; Amyloidosis; Anemia; Blood Sedimentation; Cachexia; Erythropoietin; Feeding and Eating Disorders; Fever of Unknown Origin; Hematuria; Hemoglobinometry; Humans; Immunotherapy; Kidney Neoplasms; Liver Function Tests; Medroxyprogesterone; Nephrectomy; Parathyroid Hormone; Prognosis; Renin; Urography

Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Arginine; Biliary Tract Diseases; Bronchial Neoplasms; Carcinoma; Chorionic Gonadotropin; Colonic Neoplasms; Cushing Syndrome; Erythropoietin; Female; Follicle Stimulating Hormone; Growth Hormone; Gynecomastia; Hormones, Ectopic; Humans; Hypercalcemia; Lactation Disorders; Lung Neoplasms; Luteinizing Hormone; Models, Biological; Neoplasms; Paraganglioma; Paraneoplastic Endocrine Syndromes; Polycythemia; Pregnancy; Prolactin; Thyroid Neoplasms; 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

The study aimed to analyse the feasibility and efficacy of administration of a single intravenous iron infusion (IVI) in the preoperative optimization of colorectal cancer patients with anaemia.. Twenty patients were recruited at least 14 days before the planned date of surgery. A single 1000 mg dose of ferric carboxymaltose (Ferinject) was administered as an outpatient procedure. Blood samples were taken at recruitment prior to drug administration (REC), on the day of surgery prior to any intervention (DOS) and on the first postoperative day. Allogeneic red blood cell transfusions (ARBT) and outcomes were recorded from recruitment throughout the study period.. There was a significant median rise in haemoglobin levels (Hb) from REC to DOS of 1.8 g/dl [interquartile range (IQR) 0.75-2.45, P < 0.001] for the entire cohort. Two patients received ARBT preoperatively, and for those not transfused preoperatively (n = 18), this incremental Hb rise remained significant (P < 0.001, median 1.65 g/dl, IQR 0.5-2.3). Of these patients, those who responded to IVI had higher erythropoietin (EPO) levels at recruitment (P < 0.01) and lower recruitment Hb values, transferrin-saturation (TSAT) and C-reactive protein (CRP) levels (P < 0.05). REC Hb (Rs = -0.62, P < 0.01), REC TSAT levels (Rs = -0.67, P < 0.01) and REC EPO (Rs = 0.69, P < 0.01) correlated with the magnitude of treatment change in Hb levels. Five patients received ARBT until the fourth postoperative day, which was significantly fewer than predicted (P < 0.05).. IVI can be administered preoperatively in the outpatient clinic to colorectal cancer patients with anaemia, with associated reduction in ARBT use and increase in Hb levels.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; C-Reactive Protein; Colorectal Neoplasms; Erythrocyte Transfusion; Erythropoietin; Feasibility Studies; Female; Ferric Compounds; Hemoglobins; Humans; Infusions, Intravenous; Length of Stay; Male; Maltose; Middle Aged; Pilot Projects; Postoperative Complications; Preoperative Care; Transferrins

Continuous erythropoietin receptor activator (CERA; methoxy polyethylene glycol-epoetin beta) is a new erythropoiesis-stimulating agent with a prolonged half-life. The objective of this study was to select a starting dose of CERA for the treatment of anemia in non-small-cell lung cancer (NSCLC) patients.. The study was an open-label randomized phase II trial containing four treatment groups of patients with anemia and stage IIIB or IV NSCLC. The fourth treatment group was a reference group of patients treated with darbepoetin alfa administered at either 6.75 μg/kg s.c. every 3 weeks or 2.25 μg/kg weekly. Due to observed imbalances in death across treatment arms, this study was prematurely terminated.. The primary efficacy parameter of the mean hemoglobin (Hb) change from baseline during weeks 5-13 was +0.03 g/dl, +0.50 g/dl, and -0.02 g/dl in the CERA 6.3, 9, and 12 μg/kg dose groups, respectively, and +0.26 g/dl in the darbepoetin alfa dose group (P value not significant for all three study arms). Eight (21%), 12 (32%), 9 (24%), and 4 (10%) patients in the CERA 6.3, 9, and 12 μg/kg and darbepoetin groups, respectively, died.. In this phase II study in patients with stage IIIB or IV NSCLC receiving chemotherapy, none of the four treatment arms showed an adequate increase in mean Hb level.

Topics: Adenocarcinoma; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Erythropoietin; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Survival Rate; Treatment Outcome

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; Castration; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Recombinant Proteins; Venous Thromboembolism

We investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a randomized phase II study without [A] or with [B] a putative chemoprotective agent, BNP7787.. Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 mug day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles. The primary end point was to differentiate between grade >/=2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and /=2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20% of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were 84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and 51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A] and 6.5/14.1 month on [B].. This dose-dense treatment regimen is active, feasible, and tolerable. Its further investigation in the curative setting in non-small cell lung cancer should be considered. BNP7787 did not result in significant protection from neurotoxicity.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Darbepoetin alfa; Docetaxel; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythropoietin; Feasibility Studies; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Mesna; Middle Aged; Neoplasm Staging; Neutropenia; Polyethylene Glycols; Prognosis; Recombinant Proteins; Survival Rate; Taxoids

A phase II trial was performed to determine the efficacy and tolerance of docetaxel plus oxaliplatin with hematopoietic growth factor support in previously untreated patients with advanced gastroesophageal adenocarcinoma. Thirty-five patients were entered in this trial. Treatment consisted of 3-weekly docetaxel 80 mg/m2 and oxaliplatin 100 mg/m2 both infused on day 1. A prophylactic 5-day course of human granulocyte colony-stimulating factor 5 microg/kg/day was given subcutaneously, and erythropoietin (10,000 IU subcutaneously three times per week) was administered if hemoglobin was less than 12.0 mg/dl. The confirmed overall response rate was 34%, including two complete responses (6%) and 10 partial responses (28%). Fifteen patients (43%) had stable disease. The median time to response was 2.5 months (1-3.5), the median time to progression was 8.9 (4-42.5) months and the median overall survival time was 11.6 (2.5-51) months. Hematologic toxicity was common, though World Health Organization grade 3 or 4 neutropenia occurred only in six (17%) patients and anemia in six (17%) patients, respectively. Nonhematologic adverse reactions were usually mild-to-moderate. Our data suggest that the combination of docetaxel and oxaliplatin with granulocyte colony-stimulating factor and erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Erythropoietin; Esophageal Neoplasms; Female; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Stomach Neoplasms; Survival Rate; Taxoids

This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to 14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC).. Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT.. Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09).. The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

Topics: Adenocarcinoma; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Female; Fluorouracil; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Radiotherapy Dosage; Recombinant Proteins

In a previous study we showed that many patients with esophagogastric adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now investigated the role of erythropoietin in managing anemia during neoadjuvant chemotherapy.. Patients with esophagogastric adenocarcinoma who experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were the response to erythropoietin, safety, the need for allogeneic red blood cell transfusion, and the rate of postoperative complications.. Between April 2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin level before patients received erythropoietin was 11.5 g/dL. One year after involvement in the trial, 4 of 17 analyzable patients were still anemic (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and 16 (73%) responded. We could observe a significant increase in hemoglobin concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two patients (8%) received allogeneic transfusions; the rate of postoperative complications was 16%. There were no erythropoietin-related adverse events.. Treatment with erythropoietin is effective and well tolerated in patients with esophagogastric adenocarcinoma who experience anemia during neoadjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Anastomosis, Surgical; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Hemoglobins; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Postoperative Complications; Prospective Studies; Recombinant Proteins; Stomach Neoplasms; Survival Analysis

To assess the pharmacokinetic profile and time-course of trough concentrations and hemoglobin levels associated with subcutaneous weekly administration of epoetin beta in lung cancer patients with chemotherapy-induced anemia.. Epoetin beta was subcutaneously administered to 15 anemic lung cancer patients once weekly for 8 weeks at doses of 9000, 18,000 and 36,000 IU. Pharmacokinetic parameters (C(max), AUC(inf) and T(1/2)) were determined after the first single dose administration on a model-independent basis, and the relationship between the dose and these parameters was examined for linearity.. Weekly administration of epoetin beta at 9000, 18,000 and 36,000 IU produced C(max) values of 308 +/- 117 (mean +/- standard deviation), 678 +/- 86.7 and 1316 +/- 766 mIU/ml, and AUC(inf) values of 15,300 +/- 9524, 54,574 +/- 16,265 and 88,501 +/- 55,687 hr mIU/ml, respectively, showing dose-proportional increases. Trough concentrations tended to increase in the presence of severe bone marrow suppression induced by chemotherapy or other factors. Extremely high values were seen in three patients, but there was no apparent trend toward an increase with repeated doses. After 8 weeks' administration at 9000, 18,000 and 36,000 IU, hemoglobin levels were changed by -0.37 +/- 1.26, 2.15 +/- 1.36 and 2.82 +/- 2.17 g/dl, respectively.. Epoetin beta exhibited linear pharmacokinetics when administered to anemic cancer patients at weekly doses of 9000-36,000 IU and did not cause drug accumulation. Hemoglobin levels increased with weekly doses of 18,000 or 36,000 IU.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Agents; Carcinoma, Large Cell; Carcinoma, Squamous Cell; Drug Administration Schedule; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins

Results of treatment of 39 patients, to whom pancreatoduodenal resection was performed for periampullar zone tumour, were analyzed. Anemia, revealed before the operation, had constituted the factor, which trustworthily increased the postoperative complications occurrence risk. Therapeutic course, using recombinant erythropoietins, was conducted for correction of anemia in 7 patients. This had promoted the hemoglobin level raising, the risk of postoperative complications occurrence lowering, but did not influence the intraoperative blood loss severity and perioperative hemotransfusion volume.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anemia; Bile Duct Neoplasms; Digestive System Neoplasms; Drug Administration Schedule; Duodenal Neoplasms; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Recombinant Proteins; Risk Factors; Treatment Outcome

A phase II trial was performed to determine the antitumour efficacy and tolerance of combined paclitaxel and cisplatin with or without hematopoetic growth factor support in patients with advanced gastric cancer. Forty-five patients with histologically confirmed metastatic gastric cancer were entered in this trial. Treatment consisted of 2-weekly courses of paclitaxel 160 mg per m2 and cisplatin 60 mg per m2 both given on day 1. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1000-2000 per microl), a 5-day course of human granulocyte colony-stimulating factor 5 microg x kg(-1) per day was given subcutaneously; in addition, if haemoglobin was <12.0 mg dl(-1), erythropoietin 10 000 IU was administered subcutaneously three times per week. The confirmed overall response rate (intent-to-treat) was 44%, including five complete (11%) and 15 partial remissions (33%). Twelve patients had stable disease (27%), 11 (24%) progressed while on chemotherapy, and two patients were not evaluable. The median time to response was 3 months, the median time to progression 7.0 months, and the median survival time was 11.2 months with 12 patients currently alive. Haematologic toxicity was common, though WHO grade 4 neutropenia occurred in only five patients (11%). Apart from total alopecia in 16 patients (36%), severe non-haematologic adverse reactions included grade 3 peripheral neuropathy in six (13%) and anaphylaxis in two patients. In addition, there was one patient each who experienced grade 3 emesis, diarrhea, and infection, respectively. Our data suggest that the combination of paclitaxel and cisplatin with or without G-CSF and/or erythropoietin has promising therapeutic activity in patients with advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Humans; Male; Middle Aged; Paclitaxel; Stomach Neoplasms; Survival Rate; Treatment Outcome

The safety and effects on hematocrit of recombinant human erythropoietin (epoetin alfa) were evaluated in men undergoing radical retropubic prostatectomy.. Between February 1, 1997 and November 2, 1998, 305 men with clinically localized adenocarcinoma of the prostate underwent radical retropubic prostatectomy performed by a single surgeon (H. L.). Of these men 283 with a baseline hematocrit of less than 48% received 600 IU/kg. epoetin alfa 14 days (-14) and 7 days (-7) before radical retropubic prostatectomy. Hematocrit was measured at baseline on day -14, on day -7, just before anesthesia induction on day 0, immediately postoperatively and on the day of discharge home. The number of allogeneic units transfused, and all intraoperative and postoperative complications were recorded.. Mean hematocrit at baseline on day -14 and at induction on day 0 was 42.9% and 45.8%, respectively (p = 0.0001). The frequency of hematocrit decreasing, showing no change or increasing 0.1 to 1.9, 2.0 to 3.9 or greater than 4.0 hematocrit points was 16.5%, 0.5%, 23%, 22% and 38%, respectively. Of the men 17% had no increase in hematocrit. A weak correlation existed between baseline hematocrit and the erythropoietic response to epoetin alfa (r2 = 0.06). Mean change in hematocrit after treatment with epoetin alfa in the quartile baseline hematocrit groups 34.2 to 41.4, 41.5 to 43.2, 43.3 to 44.9 and 45.0 to 48.0 hematocrit points was 3.71, 2.45, 3.86 and 1.02 hematocrit points, respectively. Of the surgical candidates 22 (9.1%) achieved an induction hematocrit of greater than 51%. Of the 283 men receiving epoetin alfa 21 (7.4%) also received an allogeneic transfusion. The transfusion rate did not correlate with induction hematocrit. The only adverse cardiovascular event was an uncomplicated postoperative pulmonary embolus.. Our prospective study demonstrates that epoetin alfa given preoperatively in 2 doses of 600 IU/kg. is safe for significantly increasing hematocrit in men before radical retropubic prostatectomy. It is intuitive that the significant increase in hematocrit decreases the requirement for allogeneic blood transfusion.

Topics: Adenocarcinoma; Blood Loss, Surgical; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Male; Middle Aged; Preoperative Care; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins

Preoperative treatment with 600 U/kg of recombinant human erythropoietin (r-HuEPO) effectively increases erythropoiesis in cancer patients. The aim of this study was to evaluate the erythropoietic response after different doses of r-HuEPO in order to find the minimum effective dose.. Twenty anemic sideropenic patients (hemoglobin

Topics: Adenocarcinoma; Aged; Anemia; Colorectal Neoplasms; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Preoperative Care; Prospective Studies; Recombinant Proteins; Stomach Neoplasms

Peripheral blood progenitor cells (PBPC) can be mobilized by chemotherapy, cytokines, or the combination of both. Recently, data from two non-randomized studies were published, showing an advantage for a combination of rhG-CSF plus rhEpo compared to rhG-CSF alone in mobilization of PBPC. To address this question we initiated a prospective, randomized trial in patients with breast cancer. Thirty (28 female, two male) of 32 randomized patients were evaluable. After primary surgery, therapy consisted of two cycles of VIP-E chemotherapy followed by high-dose (HD) chemotherapy with VIC. Mobilization and harvest of PBPC followed cycle 2. Group A received 5 microg rhG-CSF/kg body weight (bw) plus 150 IU rhEpo/kg bw. Group B was treated with 5 microg rhG-CSF/kg bw from dl until end of harvest. In the peripheral blood CD34+ cells as well as colony-forming units (CFU) started to rise on d8 with a peak on d10, followed by a decrease. No significant differences were observed between the groups. Furthermore, there was no significant difference with regard to MNC, CD34+ cells BFU-E and CFU-GM in apheresis products. Transplantation of > 1 x 10(6) CD34+ cells/kg bw after HD chemotherapy resulted in normal hematological recovery of all patients. No differences were observed in time to neutrophil or platelet recovery and need for blood product support. In this study addition of rhEpo to our standard mobilization chemotherapy did not result in improved mobilization of PBPC or in clinical benefits after HD chemotherapy.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cisplatin; Cyclophosphamide; Epirubicin; Erythropoietin; Etoposide; Female; Fluorouracil; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Male; Methotrexate; Middle Aged; Prospective Studies; Recombinant Proteins; Transplantation Conditioning; Transplantation, Autologous

Serum erythropoietin (EPO), hematocrit and hemoglobin levels were determined in 17 female patients with stage II breast cancer before, during and at the conclusion of non-nephrotoxic chemotherapy. Serum EPO levels were determined using the ELISA technique. No irradiation was given to any patient. The hemoglobin and hematocrit levels remained stable. However, a statistically significant increase in EPO was noted (p<0.05). The possible factors involved in this increase are reviewed, however the exact mechanism remains to be elucidated.

Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Fluorouracil; Hematocrit; Hemoglobins; Humans; Methotrexate; Neoplasm Staging; Prognosis; Sensitivity and Specificity

To evaluate the relationship between the hematocrit (HCT), serum erythropoietin (EPO) and insulin-like growth factor-1 (ILGF-1) levels in breast cancer patients receiving non-nephrotoxic chemotherapy.. Seventeen patients with stage II breast cancer were included. All received 6 cycles of non-nephrotoxic chemotherapy (cyclophosphamide, 5-fluorouracil and doxorubicin or methotrexate with or without tamoxifen). Insulin-like growth factor-1 and EPO levels were determined before and at the end of therapy. Serum EPO levels were determined by Enzyme linked- immunosorbant assay (ELISA) while those of ILGF- I by radioimmunoassay (RIA).. A significant drop in mean HCT from 37.41%+/-0.77% to 35.18%+/-0.70%, associated with a significant decline in ILGF-1 levels from 92.1+/-15.48 ng/ml to 52.75+/-10.5 ng/ml at the end of the treatment was noted. This association became significant when patients receiving tamoxifen were excluded (r=0.69, p=0.02). The mean serum EPO levels increased significantly from 13.64+/-0.55 U/l to 19.44+/-3.18 U/l and correlated negatively with ILGF-1 level (r=-0.46, p=0.05). There was no significant relation between the serum EPO levels and HCT (r=-0.26, p=0.32).. The current data show that ILGF-1 may play an important role in erythropoiesis and it correlates better than EPO with HCT in breast cancer patients receiving non-nephrotoxic chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Confidence Intervals; Cyclophosphamide; Doxorubicin; Erythropoietin; Female; Fluorouracil; Hematocrit; Humans; Insulin-Like Growth Factor I; Methotrexate; Middle Aged; Neoplasm Staging; Prognosis; Sensitivity and Specificity

To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy.. This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the "treatment arm" receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale.. Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl.. (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.

Topics: Adenocarcinoma; Anemia; Breast Neoplasms; Combined Modality Therapy; Erythropoietin; Female; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Recombinant Proteins

Topics: Adenocarcinoma; Amidines; Anemia; Antimalarials; Clinical Trials as Topic; Colonic Neoplasms; Erythropoietin; Humans; Levamisole; Malaria; Mefloquine; Pentamidine; Pneumonia, Pneumocystis; Quinolines; Recombinant Proteins

The erythropoietin receptor (EPOR) is a transmembrane type I receptor with an essential role in the proliferation and differentiation of erythroid progenitors. Besides its function during erythropoiesis, EPOR is expressed and has protective effect in various non-hematopoietic tissues, including tumors. Currently, the advantageous aspect of EPOR related to different cellular events is still under scientific investigation. Besides its well-known effect on cell proliferation, apoptosis and differentiation, our integrative functional study revealed its possible associations with metabolic processes, transport of small molecules, signal transduction and tumorigenesis. Comparative transcriptome analysis (RNA-seq) identified 233 differentially expressed genes (DEGs) in EPOR overexpressed RAMA 37-28 cells compared to parental RAMA 37 cells, whereas 145 genes were downregulated and 88 upregulated. Of these, for example,

Topics: Adenocarcinoma; Animals; Cell Proliferation; Erythropoietin; Ligands; Rats; Receptors, Erythropoietin; Signal Transduction

While erythropoietin (EPO) regulates erythropoiesis, the erythropoietin receptor (EPOR) has been identified in many non‑hematopoietic cells, including cancer. Our previous study demonstrated that overexpression of EPOR altered the cell growth and the sensitivity of RAMA 37 breast cancer cells to tamoxifen. Indeed, results of the present study uncovered the role of EPOR in the resistance of EPOR‑overexpressing RAMA 37‑28 cells to paclitaxel chemotherapy. In this regard, EPOR silencing in the presence of paclitaxel therapy decreased RAMA 37‑28 cell proliferation, confirming its role in the sensitivity or resistance of RAMA 37‑28 cells to paclitaxel. Notably, compared to parental RAMA 37 cells, RAMA 37‑28 cells also showed a lower rate of apoptosis induced by paclitaxel, as monitored by caspase 3/7 activation and Annexin V by IncuCyte ZOOM system. Moreover, enhanced activation of signaling pathways mediated by pERK1/2 in RAMA 37‑28 cells as detected by western blot analysis was demonstrated to be essential for paclitaxel resistance.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Proliferation; Drug Resistance, Neoplasm; Erythropoietin; Female; Humans; Mammary Neoplasms, Animal; Paclitaxel; Rats; Tumor Cells, Cultured

With growing use of nivolumab, rare but serious side effects have surfaced in some patients. We present a case of autoimmune haemolytic anaemia that developed after 39 cycles of nivolumab. A 78-year-old man with metastatic lung adenocarcinoma, refractory to multiple lines of chemotherapy was switched to nivolumab. After around 2 years of stable course on nivolumab, he developed transfusion-dependent anaemia with haemoglobin of 8.6 g/dL. Nivolumab was held immediately. Bone marrow biopsy findings were inconclusive of myelodysplastic syndrome. Further testing was suggestive of haemolysis with haptoglobin <10 mg/dL, elevated reticulocyte count and identification of immunoglobulin G antibody. Haemoglobin improved significantly with initiation of 1 mg/kg prednisone in addition to rituximab weekly × four doses. The development of transfusion-dependent anaemia with the exposure to cytotoxic chemotherapy usually raises the question for myelodysplastic syndrome. In contradiction, our patient was diagnosed to have a haematological autoimmune complication related to immunotherapy.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Aged; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Hemoglobin A; Humans; Lung Neoplasms; Male; Nivolumab; Treatment Outcome

Paraneoplastic erythrocytosis can be brought on by ectopic erythropoietin production usually in kidney, brain, and liver tumor with increase of serum erythropoietin level. We report here a paraneoplastic erythrocytosis of colon cancer with serum erythropoietin within the normal reference, which required an immunohistologic test for erythropoietin-antibody to be diagnosed.. Our case report was of a 75-year-old woman with erythrocytosis. Her hemoglobin and serum erythropoietin levels were 191 g/dL and 12.6 IU/L (reference range, 9.1-32.8), respectively. Colonoscopy revealed an advanced sigmoid colon tumor 20 mm in diameter. She underwent colectomy, and immunohistochemical examination showed the colon adenocarcinoma was focally positive for erythropoietin-antibody. One month after the surgery, her hemoglobin level decreased to 117 g/L.. Colon cancer can cause paraneoplastic erythrocytosis, and it is important to consider not simply the absolute serum erythropoietin level but also the serum erythropoietin level relative to simultaneously measured hemoglobin level. We should include paraneoplastic erythrocytosis as a differential diagnosis in cases of high hemoglobin level unexplained by other diseases.

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Erythropoietin; Female; Humans; Paraneoplastic Syndromes; Polycythemia; Reference Values

Anemia is a relatively common symptom coexisting with colorectal carcinoma. Besides having a positive impact on hematological parameters, erythropoietin (Epo) has the serious adverse effect of promoting the neoplastic process. The role of Epo in colon cancer has not been clearly shown. The aim of this study was to assess the effects of Epo therapy on colorectal carcinoma cells both in in vitro and in animal models. Human colon adenocarcinoma cells DLD-1 and Ht-29 were cultured in medium with Epo beta in normoxia. Cell proliferation was measured with an automated cell counter. Expression of erythropoietin receptor (EpoR) mRNA, Akt mRNA, and their proteins were assessed by RT-PCR and confocal microscopy, respectively. Nude mice were inoculated with adenocarcinoma cells and treated with a therapeutic dose of Epo. Expression of EpoR, VEGF, Flt-1 and CD31 was evaluated in xenograft tumors. We identified that Epo through EpoR activates Akt, which promotes colon cancer cell growth and proliferation. Epo, and high levels of phosphorylated EpoR, directly accelerates tumor growth through its proliferative and proangiogenic effects. This study demonstrated that Epo had enhanced carcinogenesis through increase of EpoR and Flt-1 expression, and thereby contributed to tumor development. These results suggest that both EpoR-positive and EpoR-negative cancer cells could be regulated by exogenous Epo. However, an increased response to erythropoietin was observed in the EpoR-positive cells. Thus, erythropoietin increases the risk of tumor progression in colon cancer and should not be used to treat anemia in this type of cancer.

Topics: Adenocarcinoma; Animals; Cell Line, Tumor; Erythropoietin; Heterografts; Humans; Mice; Neoplasm Proteins; Neoplasm Transplantation; Neovascularization, Pathologic; Receptors, Erythropoietin

Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer.. Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation.. Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB2 (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p=0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p=0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies.. Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Erythropoietin; Female; Fluorouracil; Humans; Hydroxyurea; Middle Aged; Multivariate Analysis; Neoplasm Staging; Prognosis; Proportional Hazards Models; Radiotherapy; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Tumor Burden; Uterine Cervical Neoplasms

Erythropoietin (Epo) is a key regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of the recombinant protein, it is widely used to treat various types of anemias, including that associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Our previous studies confirmed the presence of Epo receptors (EpoRs) in ovarian adenocarcinoma cell lines and demonstrated that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling and increased paclitaxel resistance. In the present study, we carried out a series of experiments to analyze the pro-angiogenic potential of Epo-treated A2780 and SKOV-3 cells. Our studies revealed that conditioned media of Epo-treated A2780 cells had a stimulative effect on human umbilical vein endothelial cells (HUVECs). This effect was only seen when A2780 cells were incubated under hypoxic conditions. Furthermore, Epo increased the secretion of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, GM-CSF and interferon-γ by A2780 cells that grew in hypoxic conditions. In this regard, conditioned media of hypoxic and Epo-treated A2780 cells induced a significant phosphorylation of STAT-5 in HUVECs. Our results may have important implications for ovarian cancer patients receiving Epo.

Topics: Adenocarcinoma; Blotting, Western; Cell Proliferation; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia; Neovascularization, Pathologic; Ovarian Neoplasms; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

It has been suggested that preoperative administration of erythropoietin (Epo) in patients with gastrointestinal cancer reduces transfusional needs and is also associated with lower morbidity. On the other hand, experimental and clinical studies show that Epo might enhance tumor growth and angiogenesis. Our aim was to ascertain whether preoperative administration of Epo has any effect on tumor recurrence after curative surgery using an experimental model of colon cancer.. We induced tumors by injecting B51LiM colon cancer cells into the cecal wall of Balb/c mice. We randomized the animals into three groups of treatment with (1) recombinant human Epo, (2) recombinant mouse Epo, or (3) vehicle alone, for 12 d until cecectomy. On postoperative day 12, we killed mice and analyzed tumor recurrence. We measured serum levels of vascular endothelial growth factor and determined vascular endothelial growth factor expression and tumor microvessel density by immunohistochemistry. We also investigated the in vitro effect of Epo on B51LiM cell line proliferation.. All three groups displayed tumor recurrence, but the final tumor load score and total tumoral weight were higher in the two groups that included Epo. The differences were statistically significant when we compared the recombinant mouse Epo group with the control group. We found no evidence of increased angiogenesis or enhanced cell proliferation as possible mechanisms of Epo-induced recurrence.. Preoperative administration of Epo stimulates tumor recurrence in an animal model of colon cancer. Our results point to the need for further research on the mechanisms of tumor growth enhancement by Epo, to better understand the benefits or disadvantages of Epo treatment.

Topics: Adenocarcinoma; Anemia; Animals; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Erythropoietin; Female; Mice; Mice, Inbred BALB C; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Preoperative Care; Vascular Endothelial Growth Factor A

Tumor anemia is very common in patients with cancer. The causes are very diverse and the parameter value depends on several factors. If this however develops to be symptomatic it may adversely impact health related quality of life. Erythropoietin or blood transfusion provides options for treatment. However, these are not always uneventful. There could also be a lack of response to Erythropoietin. This case report describes the complexity of tumor anemia. It also includes a more detailed discussion on the Fatigue Syndrome, which is one of the most common symptoms of patients with cancer. In the context of palliative care there is often the question of alternatives for improving the quality of patients life. Some kinds of treatment may also cause the opposite effect. A multidimensional assessment should help to approach this difficult issue and to find ways for a meaningful treatment of the symptoms of anemia.

Topics: Adenocarcinoma; Aged; Anemia; Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Darbepoetin alfa; Disease Progression; Erythrocyte Transfusion; Erythropoietin; Fatigue; Female; Hematinics; Humans; Medical Futility; Neoplasm Staging; Palliative Care; Quality of Life; Treatment Failure; Treatment Outcome

A 79-year-old man was admitted to the hospital because of a 20-lb weight loss, low back pain, and leg weakness. He had a 1-year history of fibrotic myelodysplasia, possibly therapy related, with a highly complex chromosome karyotype. Radiologic evaluation showed extensive destructive bone lesions, retroperitoneal lymphadenopathy, and evidence for thoracic spinal cord compression. Core biopsies of a retroperitoneal lymph node showed groups of large, immature-appearing mononuclear cells which, on Wright-stained touch preparation, appeared similar to dysplastic erythroid precursors noted on recent marrow aspirate smears. Immunohistochemical staining showed negativity of neoplastic cells to an extensive panel of nonhematopoietic and myeloid markers, and positivity for CD117, glycophorin A, and CD71, consistent with a diagnosis of erythroblastic sarcoma. This lesion is a very unusual variant of myeloid sarcoma and has been described only rarely in the medical literature.

Topics: Abnormal Karyotype; Adenocarcinoma; Aged; Azacitidine; Biopsy, Large-Core Needle; Bone Marrow; Bone Marrow Neoplasms; Bone Neoplasms; Combined Modality Therapy; Disease Progression; Drug Therapy, Combination; Erythroblasts; Erythropoietin; Fatal Outcome; Humans; Lymph Nodes; Male; Myelodysplastic Syndromes; Rare Diseases; Rectal Neoplasms; Sarcoma, Myeloid

To investigate the expression of Erythropoietin (Epo) and its receptor (EpoR) in gastric adenocarcinoma (GAC) and the correlation with angiogenesis and clinicopathological features.. The expressions of Epo, EpoR and vascular endothelial growth factor (VEGF), as well as microvessel density were evaluated in 172 GAC biopsies by immunohistochemical staining. The correlations between these parameters and patient's clinicopathological features were analyzed statistically.. The proportion of Epo and EpoR alterations in GAC was higher than that in adjacent normal mucosa (P = 0.035 and 0.030). Epo high-expression was associated with EpoR high-expression, Lauren type, extensive lymph node metastasis and advanced stage of GAC (P = 0.018, 0.018, 0.004 and 0), while EpoR expression was linked with older age, World Health Organization type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.013, 0.008 and 0.001). VEGF high expression was significantly correlated with EpoR low-expression, Lauren type, extensive lymph node metastasis and advanced stage (P = 0.001, 0.001, 0.001 and 0.007). The expression of Epo or EpoR was associated with microvessel density (P = 0.004 and 0.046). On multivariate analysis, only lymph node metastasis, abnormal Epo expression and tumor nodes metastases stage were independently associated with survival. In addition, a strong association with the immunohistochemical expression of EpoR and the angiogenic protein, VEGF, was noted.. Increased expression of Epo and EpoR may play a significant role in the carcinogenesis, angiogenesis and progression of GAC. Epo may be an independent prognostic factor.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Disease Progression; Erythropoietin; Female; Humans; Male; Middle Aged; Neovascularization, Pathologic; Prognosis; Receptors, Erythropoietin; Stomach Neoplasms; Survival Rate; Vascular Endothelial Growth Factor A; Young Adult

Taxanes, including docetaxel (DOCE), are severely neurotoxic, causing disabling peripheral neuropathy. Co-treatment with neuroprotective agents has been proposed to prevent or reverse this. Besides its hemopoietic effects, erythropoietin (EPO) has neuroprotective and neurotrophic properties and when administered systemically it has a wide range of neuroprotective action in animal models of nervous system damage, including cisplatin-induced peripheral neurotoxicity. The present study investigated the effects of EPO on chemotherapy-induced peripheral neurotoxicity (CINP) by DOCE in vivo and whether it interfered with tumor growth or antitumor activity. Female Fischer rats bearing 13762 mammary carcinoma were randomly divided into four groups: untreated, treated with EPO, DOCE, or DOCE + EPO. DOCE was given once a week (5 mg/kg, i.v.) and EPO three times a week (50 microg/kg i.p.), for 4 weeks. Three other groups of rats without tumors were left untreated or given DOCE or DOCE + EPO. The rats were observed for 4 weeks after treatment. CINP and neuroprotection were evaluated by measuring nociception, electrophysiological, and biochemical parameters. EPO protected against CINP, and tumor growth in EPO-treated rats was the same as in controls. EPO significantly improved the thermal threshold, tail nerve conduction velocity, and intra-epidermal nerve fiber density. These benefits lasted through the follow-up period and EPO speeded-up spontaneous recovery after treatment withdrawal. EPO did not impair DOCE antitumor activity. Since CINP induced by DOCE reproduces the clinical utility of taxane in humans, the findings reported might provide a basis for investigating EPO as a neuroprotective agent in patients receiving therapy with DOCE.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Docetaxel; Drug Interactions; Erythropoietin; Female; Humans; Neuroprotective Agents; Peripheral Nervous System Diseases; Rats; Rats, Inbred F344; Taxoids; Xenograft Model Antitumor Assays

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anemia; Antineoplastic Agents, Hormonal; Erythrocyte Count; Erythropoiesis; Erythropoietin; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Prostatic Neoplasms; Receptor, IGF Type 1; Recombinant Proteins; Testosterone

Topics: Adenocarcinoma; Aged; Biopsy; Erythropoietin; Humans; Lung; Lung Neoplasms; Male; Neovascularization, Pathologic; Tomography, X-Ray Computed

EPO (erythropoietin) counteracts p53-dependent apoptosis. EPO, which acts via its receptor EPOR, protects cells and inhibits apoptosis in normal cells and some cancer tissues by severe down-regulation of Bak. We aimed to investigate the relationship between p53 and Bak expression and EPO and EPOR in human colorectal carcinomas.. The expression of p53 was compared with Bak, EPO and EPOR in 96 colorectal carcinomas by means of immunohistochemistry.. Purely nuclear p53 was significantly higher expressed in the moderately differentiated cancers in comparison with the poorly differentiated ones (p=0.007). P53 expression did not correlate with cytoplasmic markers: Bak, EPO and EPOR, but EPO and EPOR were significantly associated with Bak expression (p<0.001, r=0.524 and p<0.001, r=0.455, respectively). p53 expression was not associated with disease-free survival during the 3 years and 9 months long follow-up.. A complete disruption of association between p53 and Bak could impair of p53-dependent apoptotic pathway that involves Bak. The relationship of Bak with EPO and EPOR is evidence of their co-expression suggesting competition between EPO mediated cell survival and Bak associated apoptosis in colorectal carcinomas.

Topics: Adenocarcinoma; bcl-2 Homologous Antagonist-Killer Protein; Cell Nucleus; Colorectal Neoplasms; Cytoplasm; Disease-Free Survival; Erythropoietin; Female; Humans; Immunohistochemistry; Male; Neoplasm Staging; Receptors, Erythropoietin; Tumor Suppressor Protein p53

Jehovah's Witnesses' religious convictions disallow blood transfusion. Major surgery in these patients is therefore problematic. The objective of this study is to describe our experience with microvascular reconstruction of complex head and neck defects in Jehovah's Witness patients.. This was a retrospective review of all Jehovah's Witnesses' patients undergoing head and neck free-flap reconstruction at a tertiary academic referral center from 1997 to 2006.. Five Jehovah's Witnesses patients underwent a total of 7 free-flap reconstructions (6 radial, 1 rectus). Four flaps were immediate: 1 osteocutaneous radial forearm, 2 fasciocutaneous radial forearm, and 1 rectus abdominus myocutaneous. One fasciocutaneous radial forearm flap was staged. Two patients were planned secondary reconstructions, both facsciocutaneous radial forearm. Iron supplements and/or erythropoietin were administered perioperatively in 6 of the 7 microvascular reconstructions. Selective external carotid embolization was performed preoperatively in 1 patient. Hematocrit levels were 36% to 46% preoperatively and 30% to 41% postoperatively. Immediate postoperative hematocrit decline was 5.2% (3.0% to 6.0%). No transfusions or blood products were administered.. Our case series supports the feasibility of head and neck free-flap reconstruction in these challenging patients.

Topics: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Carotid Artery, External; Embolization, Therapeutic; Erythropoietin; Female; Ferrous Compounds; Head and Neck Neoplasms; Hematocrit; Humans; Jehovah's Witnesses; Male; Microsurgery; Middle Aged; Perioperative Care; Preoperative Care; Retrospective Studies; Surgical Flaps; Treatment Outcome

Topics: Adenocarcinoma; Adult; Antibiotics, Antineoplastic; Antigens, CD34; Biomarkers; Burkitt Lymphoma; Calcineurin; Endothelium, Vascular; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Male; Mitomycin; Renal Dialysis; Stomach Neoplasms

Recent data suggest that recombinant human erythropoietin (rhEPO) modulates tumour growth and therapy response. The purpose of the present study was to examine the modulation of radiotherapy (RT) effects on tumour microvessels by rhEPO in a rat colorectal cancer model. Before and after 5 x 5 Gy of RT, dynamic contrast-enhanced -magnetic resonance imaging was performed and endothelial permeability surface product (PS), plasma flow (F), and blood volume (V) were modelled. Imaging was combined with pO(2) measurements, analysis of microvessel density, microvessel diameter, microvessel fractal dimension, and expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1alpha), Bax, and Bcl-2. We found that RT significantly reduced PS and V in control rats, but not in rhEPO-treated rats, whereas F was unaffected by RT. Oxygenation was significantly better in rhEPO-treated animals, and RT induced a heterogeneous reoxygenation in both groups. Microvessel diameter was significantly larger in rhEPO animals, whereas VEGF expression was significantly lower in the rhEPO group. No differences were observed in HIF-1alpha, Bax, or Bcl-2 expression. We conclude that rhEPO results in spatially heterogeneous modulation of RT effects on tumour microvessels. Direct effects of rhEPO on neoplastic endothelium are likely to explain these findings in addition to indirect effects induced by increased oxygenation.

Topics: Adenocarcinoma; Animals; Colorectal Neoplasms; Erythropoietin; Humans; Magnetic Resonance Imaging; Male; Models, Biological; Neovascularization, Pathologic; Rats; Receptors, Erythropoietin; Recombinant Proteins

Anemia is a common morbidity of advanced prostate cancer, and prostate cancer treatment and has been associated with a worse overall survival and reduced quality of life in patients with prostate cancer. We sought to determine if infrequent dosing of darbepoetin alfa is safe and effective in treating anemia in patients receiving systemic therapy for prostate cancer.. Sixteen patients with histologically confirmed prostate cancer with bone metastases on androgen deprivation therapy with or without chemotherapy; and a baseline hemoglobin (Hb) < or = 12 g/dL (amended to < or = 11 g/dL) were enrolled. The primary endpoints were the proportion of patients who had a baseline Hb > or = 12.5 g/dL and the proportion whose baseline Hb increased by > or = 1 g/dL. Patients were initially treated with 300 microg of darbepoetin alfa every 4 weeks. The dose was increased to 500 microg, 800 microg, and 1000 microg at each subsequent visit if the baseline Hb was not at target and had not increased by > or = 1 g/dL during the previous 4 weeks. Treatment was planned for 6 months.. Treatment was well tolerated with no grade > or = 3 toxicities. Fourteen patients were assessable. The median Hb at study entry was 10.7 g/dL (range, 8.4-12). Serum Hb increased by > or = 1 g/dL in 10 patients (71%; 95% confidence interval, 42%-92%) and 7 patients (50%; 95% confidence interval, 23%-77%) reached an Hb of > or = 12.5 g/dL after treatment with doses that ranged from 300 microg to 1000 microg.. Darbepoetin alfa administration every 4 weeks is feasible and well tolerated. Target Hb increases were achieved in approximately half of the patients and required doses that ranged from 300 microg to 1000 microg.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Bone Neoplasms; Darbepoetin alfa; Erythropoietin; Feasibility Studies; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Prostatic Neoplasms

Although a significant negative prognostic factor, tumor hypoxia can be exploited for gene therapy. To maximize targeting within the tumor mass, we have developed synthetic gene promoters containing hypoxia-responsive elements (HREs) from the erythropoietin (Epo) gene as well as radiation-responsive CArG elements from the early growth response (Egr) 1 gene. Furthermore, to achieve high and sustained expression of the suicide gene herpes simplex virus thymidine kinase (HSVtk), our gene therapy vectors contain an expression amplification system, or 'molecular switch', based on Cre/loxP recombination. In human glioma and breast adenocarcinoma cells exposed to hypoxia and/or radiation, the HRE/CArG promoter rapidly activated Cre recombinase expression leading to selective and sustained HSVtk synthesis. Killing of transfected tumor cells was measured after incubation with the prodrug ganciclovir (GCV; converted by HSVtk into a cytotoxin). In vitro, higher and more selective GCV-mediated toxicity was achieved with the switch vectors, when compared with the same inducible promoters driving HSVtk expression directly. In tumor xenografts implanted in nude mice, the HRE/CArG-switch induced significant growth delay and tumor eradication. In conclusion, hypoxia- and radiation-activated 'molecular switch' vectors represent a promising strategy for both targeted and effective gene therapy of solid tumors.

Topics: Adenocarcinoma; Adenoviridae; Animals; Antiviral Agents; Brain Neoplasms; Breast Neoplasms; Cell Death; Cell Hypoxia; Combined Modality Therapy; Early Growth Response Protein 1; Erythropoietin; Ganciclovir; Gene Expression Regulation, Neoplastic; Genes, Switch; Genes, Transgenic, Suicide; Genetic Engineering; Genetic Therapy; Genetic Vectors; Glioma; Humans; Mice; Mice, Nude; Neoplasms; Oncolytic Virotherapy; Promoter Regions, Genetic; Simplexvirus; Thymidine Kinase; Tumor Cells, Cultured

Activation of the Wnt signaling pathway initiates the transformation of colorectal epithelial cells, although the transition to metastatic cancer requires angiogenesis. We have investigated the expression of the von Hippel-Lindau (VHL) tumor suppressor in the intestines from humans and mice. Here, we show that VHL expression is regulated by TCF4 and is restricted to the proliferative compartment at the bottom of intestinal crypts. Accordingly, VHL is completely absent from the proliferative intestinal pockets of Tcf4(-/-) perinatal mice. We observed complementary staining of the hypoxia-inducible factor (HIF) 1alpha to VHL in normal intestinal epithelium as well as in all stages of colorectal cancer (CRC). To the best of our knowledge, this is the first report demonstrating the presence of nuclear HIF1alpha in normoxic healthy adult tissue. Although we observed upregulated levels of VHL in very early CRC lesions from sporadic and familial adenomatous polyposis patients - presumably due to activated Wnt signaling - a clear reduction of VHL expression is observed in later stages of CRC progression, coinciding with stabilization of HIF1alpha. As loss of VHL in later stages of CRC progression results in stabilization of HIF, these data provide evidence that selection for VHL downregulation provides a proangiogenic impulse for CRC progression.

Topics: Adenocarcinoma; Adenoma; Adenomatous Polyposis Coli; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; beta Catenin; Cell Line; Cell Transformation, Neoplastic; Colon; Colonic Polyps; Colorectal Neoplasms; Disease Progression; Epithelial Cells; Erythropoietin; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intestinal Mucosa; Kidney; L Cells; Mice; Mice, Knockout; Neovascularization, Pathologic; Nerve Tissue Proteins; Precancerous Conditions; Promoter Regions, Genetic; Recombinant Fusion Proteins; Signal Transduction; TCF Transcription Factors; Transcription Factor 4; Transcription Factor 7-Like 2 Protein; Von Hippel-Lindau Tumor Suppressor Protein; Wnt Proteins; Wnt3 Protein

Evidence for erythropoietin signaling has been shown in several nonhematopoietic tissues, including many tumor types. Clinically, recombinant erythropoietin treatment of malignancy-related anemia has yet to be definitively associated with any modulation of chemotherapy or radiotherapy efficacy. Preclinically, recombinant erythropoietin has been shown to increase tumor oxygenation, but the direct effects of recombinant erythropoietin on tumor cells that express erythropoietin receptor are not yet fully characterized. This study examined the effects of exogenous recombinant erythropoietin on rodent mammary adenocarcinoma cells (R3230) in vitro and in vivo, and determined the effects of systemic recombinant erythropoietin on tumor growth delay in Taxol treatment. We showed that systemic recombinant erythropoietin treatment of rats bearing R3230 mammary carcinomas induced an increase in phospho-Akt levels within tumor cells. This was associated with a decrease in the frequency of apoptotic cells in tumors from recombinant erythropoietin-treated animals, but did not noticeably affect tumor growth rate. In vitro studies revealed that not only does recombinant erythropoietin induce Akt phosphorylation, but it also stimulates phosphorylation of p44/42 mitogen-activated protein kinases, Erk1 and Erk2. Activation of erythropoietin-mediated signaling in R3230 cells was associated with dose-dependent inhibition of apoptosis in response to Taxol treatment and serum starvation, an effect that was blocked by the addition of a phosphatidylinositol-3-kinase inhibitor. Despite its cytoprotective effects in vitro, recombinant erythropoietin did not significantly affect tumor growth delay in Taxol treatment. This study shows direct recombinant erythropoietin-mediated activation of specific intracellular signaling pathways in mammary adenocarcinoma cells in vivo and in vitro. Modulation of tumor apoptosis pathways by recombinant erythropoietin may have negative consequences by decreasing the chemosensitivity and radiosensitivity of erythropoietin receptor-positive breast tumors, although it did not have any obvious effects on growth with or without chemotherapy in this model.

Topics: Adenocarcinoma; Animals; Apoptosis; Breast Neoplasms; Drug Resistance, Neoplasm; Erythropoietin; Extracellular Signal-Regulated MAP Kinases; Female; Paclitaxel; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Receptors, Erythropoietin; Recombinant Proteins; Tumor Cells, Cultured

Tumor hypoxia is associated with poor clinical outcome in a variety of tumors, including cervical, head/neck and breast cancer. Administration of erythropoietic factors has been suggested as a means of improving tumor oxygenation (pO2). This study randomized rats to treatment with low-dose or high-dose darbepoetin alfa or a placebo to determine the effect of darbepoetin alfa on the pO2, growth and response to radiation therapy of R3230 mammary adenocarcinoma. Rats received 3 microg/kg (high dose) or 0.2 microg/kg (low dose) darbepoetin alfa or placebo for eight doses prior to either (1) pO2 measurement and pimonidazole staining or (2) irradiation or sham irradiation on post-transplant day 20. In the animals randomized to radiation treatment, placebo or darbepoetin alfa administration at a reduced dose was continued for 9 weeks or until the tumor diameter exceeded 15 mm (defined as failure for survival analysis). Treatment with high-dose and low-dose darbepoetin alfa produced hematocrits of 68 and 56% compared to 44 and 45% in their respective control groups (both P < 10(-5)). At 18 days post-transplant, tumor volume was not different for either darbepoetin alfa group compared to the placebo group. Tumor oxygenation, as measured by the fraction of pO2 measurement <10 mmHg and the intensity of pimonidazole staining, was significantly improved in the high-dose group (P = 0.046 and 0.03, respectively, compared with controls) but not in the low-dose group. Growth delay curves after irradiation did not differ significantly for high- or low-dose darbepoetin alfa compared to placebo. In this nonanemic animal model of mammary adenocarcinoma, darbepoetin alfa does not significantly alter tumor growth or radioresponsiveness, even though it improves oxygenation when administered at high doses.

Topics: Adenocarcinoma; Animals; Cell Proliferation; Chemotherapy, Adjuvant; Darbepoetin alfa; Dose-Response Relationship, Drug; Erythropoietin; Female; Mammary Neoplasms, Animal; Oxygen; Oxygen Consumption; Radiation Dosage; Radiation Tolerance; Radiation-Sensitizing Agents; Random Allocation; Rats; Rats, Inbred F344; Survival Rate; Treatment Outcome

In a large, 16-week, prospective study of 2,964 anemic patients with various cancers undergoing chemotherapy, once-weekly subcutaneous administration of 40,000 U of epoetin alfa,with potential escalation to 60,000 U, increased hemoglobin (Hgb) levels, decreased transfusion requirements, and improved quality of life (QOL) as assessed using the Linear Analog Scale Assessment (LASA) for energy, activity, and overall QOL and the Functional Assessment in Cancer Therapy-Anemia (FACT-An) QOL instrument. A retrospective subset analysis conducted in 244 colorectal cancer patients enrolled in the study showed statistically significant improvements from baseline to final readings in LASA energy, activity, and overall QOL and FACT-An Anemia Symptoms and Fatigue subscale scores (P < 0.02). Moreover, patients who achieved larger improvements in Hgb levels also demonstrated greater percentage improvements in QOL over baseline measurements. Mean Hgb levels increased by 1.2 g/dL after 4 weeks of treatment and by 1.6 g/dL by study end, independent of red blood cell transfusion within 28 days prior to the Hgb assessment. Hematopoietic response (Hgb level > or = 12 g/dL and/or increase in Hgb level > or = 2 g/dL, independent of transfusion) was observed in 61% of patients (139/229). Additionally, the proportion of patients receiving transfusions decreased from 17% at baseline to 4% during the final month of therapy. Epoetin alfa was well tolerated, with no evidence of unexpected adverse events. Except for significantly higher QOL scores at baseline, results for the cohort of colorectal cancer patients were similar to those for patients with other cancer types in the main study population.

Topics: Adenocarcinoma; Adult; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Colorectal Neoplasms; Epoetin Alfa; Erythropoietin; Fatigue; Hemoglobins; Humans; Quality of Life; Recombinant Proteins; Retrospective Studies

Jehovah's Witnesses refuse transfusions of the main blood components. This challenges the safety of performing major surgical procedures. At the Norwegian Radium Hospital, we have taken the views of Jehovah's Witnesses regarding blood transfusions into account when planning major surgical procedures and perform these without such transfusions. We present a case and our experiences and routines when performing major cancer surgery on Jehovah's Witness patients.. The medical records of Jehovah's Witnesses, who underwent major surgery at the Norwegian Radium Hospital from April 1992 to February 2006, were surveyed retrospectively. Based on relevant literature, our routines and methods are discussed along with some legal and ethical aspects.. Major transfusion-free surgery can be performed successfully on Jehovah's Witnesses. This requires advanced planning, good routines and close collaborative team efforts. The most relevant techniques to make major surgery feasible are preoperative optimalisation of the haemoglobin levels and acute normovolemic haemodilution and the use of cell saver under surgery.

Topics: Adenocarcinoma; Aged; Blood Transfusion; Erythropoietin; Female; Hemodilution; Humans; Jehovah's Witnesses; Male; Neoplasms; Patient Care Planning; Rectal Neoplasms; Religion and Medicine; Retrospective Studies

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Carcinoma, Signet Ring Cell; Erythropoietin; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Lymphatic Metastasis; Microvessels; Middle Aged; Stomach; Stomach Neoplasms; Tissue Array Analysis

It has been suggested that hemoglobin levels of 12-14 g/dL are optimal for tumor oxygenation, radiosensitivity, and prognosis. In this prospective study, the authors evaluated the effectiveness of epoetin-alpha to maintain hemoglobin levels at 12-14 g/dL during radiotherapy (RT) for patients with UICC Stage III esophageal carcinoma, and they examined the impact of erythropoetin on overall survival (OS), metastatic-free survival (MFS), and local control (LC).. Sixty patients who received RT between March, 2001 and September, 2004, were included in this prospective, nonrandomized study. Thirty patients received epoetin-alpha (150 IU/kg 3 times per week) during RT (Group A), and 30 patients did not receive epoetin-alpha (Group B). Epoetin-alpha was started at hemoglobin levels < 13 g/dL and was stopped at hemoglobin levels > or = 14 g/dL. Hemoglobin was measured before RT and once weekly during RT.. Both patient groups were balanced for age, gender, performance status, tumor location/length, histology, grading, tumor classification, lymph node status, chemotherapy, treatment (45-50.4 grays [Gy] plus resection vs. 45.0-50.4 Gy vs. 59.4-66.0 Gy), and hemoglobin level before RT. In 20 of 30 patients (67%) from Group A and in 3 of 30 patients (10%) from Group B, > or = 60% of hemoglobin levels during RT were 12-14 g/dL (P = 0.003). The median change in hemoglobin was + 0.4 g/dL per week in Group A and - 0.4 g/dL per week in Group B. LC was significantly better in Group A (66% vs. 38% at 1 year, respectively; P = 0.012), a trend was observed for OS (59% vs. 33%, respectively; P = 0.08), and MFS did not differ significantly (43% vs. 38%, respectively; P = 0.34). No epoetin-alpha-related toxicity was observed.. Epoetin-alpha was effective in maintaining the hemoglobin levels at 12-14 g/dL during RT. The application of epoetin-alpha significantly improved LC, and a trend was observed for OS.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Female; Gamma Rays; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Survival Rate

In cancer cachexia, erythropoietin often yields beneficial therapeutic effects by improving patient's metabolic and exercise capacity via an increased erythrocyte count. However, erythropoietin also has counter-regulatory effects against pro-inflammatory cytokines, which are postulated to be mediators of cancer cachexia. We investigated the mechanisms by which erythropoietin improves the cachectic condition. In this study, 100 Units/day of erythropoietin were administered intraperitoneally to BALB/c male mice, carrying a subclone of colon 26 adenocarcinoma, beginning on the day after tumor inoculation and continuing until they died. Erythropoietin administration attenuated the decline in body weight, as well as the decline in fat and muscle weights, of tumor-bearing mice, but improved the survival of cachectic mice. Mice receiving erythropoietin had increased erythrocyte and platelet counts, but significantly decreased white blood cell count. In addition, erythropoietin administration significantly decreased interleukin-6 levels, not only in serum but also in the inoculated tumor. These results indicate that the positive therapeutic effects of erythropoietin on cancer cachexia are due, not only to improving metabolic and exercise capacity via an increased erythrocyte count, but also to attenuation of cachectic manifestations by decreased production of the cachexia-inducing cytokine, interleukin-6.

Topics: Adenocarcinoma; Animals; Cachexia; Colonic Neoplasms; Cytokines; Disease Models, Animal; Down-Regulation; Eating; Erythropoietin; Interleukin-6; Liver; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Spleen; Survival Rate

Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.. Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.. Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.. Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

Topics: Adenocarcinoma; Animals; Cachexia; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Glycolysis; Hematocrit; Hemoglobins; Inhalation; Mice; Mice, Inbred BALB C; Oxygen; Recombinant Proteins; Weight Loss

Gene therapy is a modality for the treatment of solid tumors that involves the introduction of a suicide gene into the tumor cells. Genetic radiotherapy involves the placement of a radiation-sensitive promoter upstream from a suicide gene. Because of their irregular vasculature some solid tumors are chronically hypoxic and hence are resistant to conventional treatment with chemotherapy and ionizing radiation (IR). The purpose of this study was to demonstrate that regional tumor hypoxia could be exploited to improve local tumor control. The cDNA coding the erythropoietin hypoxia-responsive element (EPO) was placed upstream from the Egr-TNF-alpha construct. WIDR human colon adenocarcinoma cells were injected into the right hind limb of nude mice and treated with Epo-Egr-TNF-alpha plasmid with or without IR. Tumor volumes were measured by calipers and tumor necrosis factor (TNF)-alpha content of the tumor was determined by enzyme-linked immunosorbent assay. Treatment with the combined regimen of Epo-Egr-TNF-alpha plasmid + IR resulted in significant tumor growth delay. Tumor TNF-alpha content was increased by 30 per cent in the combined treatment group compared with each treatment alone. Regional tumor hypoxia can be exploited successfully to induce tumor growth delay, enhance local control, and enhance the therapeutic ratio.

Topics: Adenocarcinoma; Animals; Cell Hypoxia; Colonic Neoplasms; Combined Modality Therapy; DNA-Binding Proteins; Early Growth Response Protein 1; Erythropoietin; Female; Gene Expression; Genetic Therapy; Genetic Vectors; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Immediate-Early Proteins; Mice; Mice, Nude; Neoplasm Transplantation; Nuclear Proteins; Oxygen; Plasmids; Transcription Factors; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of erythropoietin (Epo) in angiogenesis has not been completely clarified, although its involvement has been reported. In this study we correlated microvascular density and Epo receptor (Epo-R) expression in endothelial and tumour cells with histopathological type in gastric cancer.. Specimens of primary gastric adenocarcinomas obtained from 40 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti-CD31 and anti-Epo-R antibodies. Stage IV gastric carcinoma had a higher degree of vascularization than other stages, and Epo-R expression in both endothelial and tumour cells increased in parallel with malignancy grade and was highly correlated with the extent of angiogenesis.. Epo-R level correlates with angiogenesis and progression of patients with gastric carcinoma and we suggest that Epo might have a trophic effect on the vasculature of the gastrointestinal tract. Understanding mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an anti-angiogenic therapy in patients with gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Endothelium, Vascular; Erythropoietin; Female; Humans; Immunohistochemistry; Male; Microcirculation; Middle Aged; Neoplasm Staging; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Erythropoietin; Stomach Neoplasms

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.

Topics: Adenocarcinoma; Aged; Diabetic Nephropathies; Erythropoietin; Gastrectomy; Gastrointestinal Hemorrhage; Hormones, Ectopic; Humans; Male; Paraneoplastic Endocrine Syndromes; Polycythemia; Renal Dialysis; Stomach Neoplasms

Tumor oxygenation is known to be an important predictive/prognostic marker in a variety of tumors, including cervix, head/neck, sarcoma, non-small cell of the lung, and breast. Tumor oxygenation is influenced by many interactions, including oxygen delivery (angiogenesis, permeability, and HgB) and consumption (metabolic and growth rates). This study randomized 30 nonanemic, female Fischer 344 rats into three treatment arms to examine the effects of recombinant human erythropoietin (EPO) on R3230 rodent mammary carcinoma oxygenation. The three treatment arms were: (a) placebo; (b) EPO after tumor implantation (2000 units/kg/SQdose, M/W/F for six doses); and (c) EPO before tumor implantation (2000 units/kg/SQdose, M/W/F for six doses). Tumors were implanted in the hindflank, and in vivo oxygenation was measured at day 22 after implantation using the Oxylite system (Oxford Optronix, Oxford, England). An average of 180 measurements/animal were performed. On day 22, median tumor volume was 399 mm(3) (range: 65-950 mm(3)), and no differences in tumor volume were seen between treatment arms. Mean hematocrit was equal between arms at therapy initiation but were significantly higher for both arms receiving EPO at day 22 (placebo versus Arm B versus Arm C; Wilcoxon P = 0.052). EPO-treated tumors had significantly less hypoxic measurements when compared with either the placebo or those receiving EPO before implantation. These data confirm that tumor oxygenation in nonanemic individuals may be improved through the administration of EPO, and this improvement appears to be independent of HgB effects.

Topics: Adenocarcinoma; Animals; Erythropoietin; Female; Hemoglobins; Humans; Mammary Neoplasms, Experimental; Neoplasm Transplantation; Oxygen; Partial Pressure; Random Allocation; Rats; Rats, Inbred F344; Recombinant Proteins

The goal of this study was to evaluate serum level of EPO in 32 men with lung cancer (Squamous cell lung cancer N = 11, Adenocarcinoma N = 10, Small cell lung cancer N = 11) in relation to the degree of anemia, stage of disease and the regimen of anticancer therapy. The control group consisted of 29 men, among whom were 15 patients with posthemorrhagic anemia. Blood samples were withdrawn for assessment of blood count, serum concentration of EPO, iron, total iron binding capacity (TIBC) and ferritin. The assessment of all parameters was repeated after 3 months of therapy:. Patients suffering from lung cancer were characterized by a lower hemoglobin level and higher level of EPO as compared with the control group. A significant negative correlation was found between hemoglobin level and EPO serum concentration in all groups of patients and in the control group. The strongest correlation was observed in the control group t = -0.812. In each group of patients the serum level of EPO increased after treatment; although a significant increase was found only in surgically treated patients and patients after chemotherapy. After treatment the correlation between hemoglobin and EPO became stronger especially in the group of patients with small cell lung cancer.. 1. Patients with lung cancer are characterized by inappropriately low serum EPO levels when related to the degree of anemia, 2. The suppressive effect of lung cancer on EPO secretion depends on the histological type of the cancer (with the exception of small cell lung cancer). 3. The increase of EPO level after treatment seems to be caused not only by a decrease of hemoglobin concentration, but also by reduction of the tumor mass.

Topics: Adenocarcinoma; Anemia; Biomarkers; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Case-Control Studies; Erythropoietin; Ferritins; Hemoglobin A; Humans; Iron; Lung Neoplasms; Male; Middle Aged; Time Factors

To better understand the control of apoptosis during erythropoiesis, this study investigated the role of a novel tumor-associated antigen, RCAS1 (receptor binding cancer antigen expressed on SiSo cells), with regard to the regulation of apoptosis of erythroid progenitor cells. Erythroid colony-forming cells (ECFCs) purified from human peripheral blood were used. Binding experiments of RCAS1 showed that ECFCs abundantly expressed receptors (RCAS1R) for RCAS1 and that the degree of binding of RCAS1 to the receptors diminished rapidly during erythroid maturation in vitro. When the soluble form of RCAS1 was added to the cultures, ECFCs underwent apoptosis, including collapse of the mitochondrial transmembrane potential, and activation of caspases 8 and 3. The addition of an anti-Fas blocking antibody or Fas-Fc failed to reduce the apoptosis induced by RCAS1, thereby indicating that effects of RCAS1 are independent of Fas activation. When binding of RCAS1 to normal bone marrow cells was analyzed, RCAS1R was evident on cells with an immature erythroid phenotype (transferrin receptor(+)/glycophorin A(-)) but not with a mature phenotype (transferrin receptor(-)/glycophorin A(+)). Histochemical staining revealed the expression of RCAS1 in the cytoplasm of bone marrow macrophages. These findings indicate that RCAS1, which is mainly produced by macrophages in hematopoietic tissue, may have a crucial role in controlling erythropoiesis by modulating apoptosis of erythroid progenitor cells via a Fas-independent mechanism.

Topics: Adenocarcinoma; Antigens, Neoplasm; Antigens, Surface; Apoptosis; Bone Marrow Cells; Caspase 3; Caspase 8; Caspase 9; Caspases; Cell Division; Colony-Forming Units Assay; Cytoplasm; Enzyme Activation; Erythroid Precursor Cells; Erythropoietin; fas Receptor; Female; Glycophorins; Granulocytes; Histocytochemistry; Humans; Macrophages; Membrane Potentials; Receptors, Cell Surface; Receptors, Transferrin; Recombinant Proteins; Tumor Cells, Cultured; Uterine Neoplasms

Topics: Adenocarcinoma; Carcinoma, Pancreatic Ductal; DNA, Complementary; Erythropoietin; Humans; Immunohistochemistry; Male; Middle Aged; Pancreatic Neoplasms; RNA, Messenger

Nine patients with hormone-refractory metastatic prostatic adenocarcinoma and anemia were treated with recombinant human erythropoietin (rHuEpo) at a median dose of 150 U/kg BW 3 times a week subcutaneously. Baseline hemoglobin (Hb) ranged from 70 to 116 g/L, and the study duration was 12 weeks (median patient participation period was 8 weeks).. Four patients demonstrated a median Hb increase of 20 g/L and were considered responders. Three patients showed a median increase of 17 g/L but required blood transfusion once, and were therefore considered as partial responders. Baseline erythropoietic status showed a significant correlation between serum Epo and Hb. Inadequate Epo production, evaluated by the observed/predicted log Epo ratio, was found in two patients. Defective bone marrow activity, demonstrated by low transferrin receptor (TfR), and hypoferremia in spite of abundant iron stores were also shown. Hemorheological investigations showed elevated plasma viscosity.. Our results indicate that suppression of erythropoiesis can be mainly explained by the depressed marrow activity. The altered hemorheology might contribute to the anemia. This anemia could possibly be corrected with rHuEpo.

Topics: Adenocarcinoma; Aged; Anemia; Blood Transfusion; Blood Viscosity; Bone Marrow; Erythropoietin; Hemoglobins; Humans; Iron; Male; Middle Aged; Prostatic Neoplasms; Receptors, Transferrin; Recombinant Proteins; Transferrin

Topics: Adenocarcinoma; Ascitic Fluid; CA-125 Antigen; Endometrial Neoplasms; Erythrocyte Count; Erythropoietin; Female; Humans; Middle Aged

A Jehovah's Witness presented with colon cancer and profound anemia. On admission, her hemoglobin level was 30 g/L (3.0 g/dL). She refused all transfusions and failed to respond to oral iron therapy. She was ultimately prepared for surgery using recombinant human erythropoietin, iron dextran, and total parenteral nutrition. It took nearly 1 month to increase her hemoglobin level to an acceptable preoperative level of 110 g/L (11.0 g/dL). During the postoperative period, erythropoietin and parenteral iron therapy were briefly continued and a follow-up hemoglobin level of greater than 120 g/L (12.0 g/dL) was observed. Recombinant human erythropoietin, along with parenteral iron and adequate nutrition, may be useful in patients who refuse transfusion or cannot be transfused because of difficult cross-reacting antibodies.

Topics: Adenocarcinoma; Anemia; Christianity; Erythropoietin; Female; Humans; Iron-Dextran Complex; Middle Aged; Parenteral Nutrition, Total; Patient Compliance; Postoperative Care; Preoperative Care; Recombinant Proteins; Severity of Illness Index; Sigmoid Neoplasms

One to five percent of human renal cell carcinomas are associated with polycythemia. It is generally assumed that polycythemia results from the secretion of erythropoietin (Epo) by the malignant cells. However, there is no direct proof supporting this hypothesis. Three patients with typical renal adenocarcinoma and polycythemia were studied. All three exhibited high Epo serum levels as measured by radioimmunoassay (RIA). A strong Epo signal was observed on Northern blot analysis of total RNA extracted from the renal tumors. The Epo message seemed to be of normal size and no Epo gene rearrangement was observed with the restriction enzymes tested. Using the in situ hybridization technique, a significant labeling was constantly observed on the tumor cells. Immunohistochemical studies showed that these tumor cells, known to be of tubular origin, were labeled by an anti-cytokeratin antibody and therefore were of epithelial nature. Thus, this study demonstrated that malignant cells of tubular origin were able to produce Epo constitutively, whereas in the mouse hypoxic kidney, peritubular cells (probably capillary endothelial cells) were the major site of Epo synthesis.

Topics: Adenocarcinoma; Blotting, Southern; Carcinoma, Renal Cell; DNA Probes; DNA, Neoplasm; Epithelium; Erythropoietin; Gene Rearrangement; Hormones, Ectopic; Humans; Kidney Neoplasms; Nucleic Acid Hybridization; Polycythemia; RNA, Messenger; RNA, Neoplasm

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

The renal tumor RCC-3-JCK, when transplanted into immunodeficient mice, caused an erythrocytic polycythemia. When grown in culture, the tumor cells secreted a substance into the culture medium that chromatographed by size-exclusion high-performance liquid chromatography similarly to purified human erythropoietin (Ep) and was positive when assayed for Ep by its ability to stimulate erythropoiesis in fetal mouse liver cells (the FMLC assay). The poly(A) + RNA was extracted from the tumor cells and injected into Xenopus oocytes, inducing the appearance of Ep(FMLC) in the oocyte culture medium. Both the tumor cells and oocyte culture media were fractionated by size-exclusion high-performance liquid chromatography, and two fractions with Ep(FMLC) activity were found in the tumor-cell culture medium. Three active fractions were found in the medium from the mRNA-injected oocytes. The largest component from both culture media had the same elution time as a human standard (Ep). The poly(A) + RNA was fractionated by sucrose density-gradient centrifugation and the 8S and 10S fractions were found to induce Ep(FMLC) synthesis when they were injected into the oocytes. We conclude that poly(A) + RNA isolated from the Ep-producing tumor RCC-3-JCK included mRNA for Ep and that the Ep was a translational product of Xenopus oocytes injected with this mRNA.

Topics: Adenocarcinoma; Animals; Cells, Cultured; Erythropoietin; Female; Fetus; Humans; Kidney Neoplasms; Liver; Mice; Mice, Nude; Neoplasm Transplantation; Oocytes; Poly A; Polycythemia; Protein Biosynthesis; RNA, Messenger; Xenopus laevis

Topics: Adenocarcinoma; Erythropoietin; Humans; Hypertension; Kidney Neoplasms; Nephrectomy; Polycythemia; Renin

Topics: Adenocarcinoma; Animals; Dog Diseases; Dogs; Erythropoietin; Kidney Neoplasms; 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

Topics: Adenocarcinoma; Erythropoietin; Hormones; Hormones, Ectopic; Humans; Kidney Neoplasms; Parathyroid Hormone; Renin

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; Humans; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Renin

Topics: Adenocarcinoma; Aged; Erythropoietin; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Neoplasms; Kidney Transplantation; Male; Middle Aged; Polycystic Kidney Diseases

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; Erythrocytes; Erythropoietin; Hematocrit; Hemoglobins; Humans; Iron Radioisotopes; Kidney Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Nephrectomy; Polycythemia; Time Factors

Topics: Adenocarcinoma; Aged; Erythropoietin; Female; Humans; Kidney Diseases; Kidney Diseases, Cystic; Kidney Neoplasms; Male; Middle Aged; Polycythemia; Radionuclide Imaging

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: 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: Adenocarcinoma; Erythropoietin; Hormones, Ectopic; Humans; Hydronephrosis; Hypercalcemia; Kidney Neoplasms; Male; Middle Aged; Parathyroid Hormone; Polycythemia

Topics: Adenocarcinoma; Alkaline Phosphatase; Erythropoietin; Female; Fever; Haptoglobins; Hepatomegaly; Humans; Infant; Kidney Neoplasms; Leukemoid Reaction; Renin; Splenomegaly; Urography

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

Topics: Adenocarcinoma; Blood Cell Count; Blood Platelets; Erythrocyte Count; Erythropoietin; Female; Humans; Polycythemia; Urography

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Animals; Brain Neoplasms; Child; Child, Preschool; Dogs; Electric Stimulation; Erythropoiesis; Erythropoietin; Ethacrynic Acid; Haplorhini; Humans; Hydronephrosis; Hypertension; Hypothalamus; Infant; Iron Isotopes; Kidney Diseases; Kidney Neoplasms; Lung Neoplasms; Male; Mice; Middle Aged; Polycythemia Vera; Rats; Testicular Neoplasms; Testosterone; Urinary Calculi; Urologic Diseases; Wilms Tumor; Wounds and Injuries

Topics: Adenocarcinoma; Animals; Biological Assay; Blood; Erythropoietin; In Vitro Techniques; Kidney; Kidney Neoplasms; L-Lactate Dehydrogenase; Mercury; Neoplasms, Experimental; Nitrosamines; Organ Size; Pyelonephritis; Radioisotopes; Rats; Urine

Topics: Adenocarcinoma; Animals; Erythropoietin; Hypertension, Renal; Ischemia; Kidney Diseases; Kidney Neoplasms; Male; Mercury; Nitrosamines; Radioisotopes; Rats

Topics: Adenocarcinoma; Animals; Blood; Carcinoma; Carcinoma, Hepatocellular; Epoetin Alfa; Erythropoietin; Growth Substances; Humans; Iron; Iron Isotopes; Liver Extracts; Liver Neoplasms; Liver Neoplasms, Experimental; Lymphoma; Neoplasms; Neoplasms, Experimental; Radiometry; Rats

Topics: Adenocarcinoma; Animals; Erythropoietin; Humans; In Vitro Techniques; Mammary Neoplasms, Experimental; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Plasmacytoma; Rabbits

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

Topics: Adenocarcinoma; Bone Marrow Examination; Carcinoma, Renal Cell; Epoetin Alfa; Erythrocytes; Erythropoiesis; Erythropoietin; Hematocrit; Kidney Neoplasms; Polycythemia; Rats; Research; Tissue Extracts