Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin (EPO) is the major regulator of erythropoiesis. EPO's actions have been shown to be antiapoptotic and dependent on JAK2 signaling and Akt phosphorylation. These effects serve as link between EPO and heme oxygenase-1 (HO-1). HO-1 is an inducible enzyme with potent antioxidant and antiapoptotic activities which are regulated by Akt signaling. EPO's ability to alter cellular systems that involve apoptosis and oxidants suggests that EPO treatments are likely to have multiple and different effects which may start a good news/bad news story. Recombinant human EPO is the recognized treatment of choice to address anemia and to stimulate erythropoiesis in chronic renal failure patients, through its antiapoptotic action which likely involves HO-1. On the other hand, EPO treatment to address anemia in cancer patients, while providing significant improvements in cancer patients' quality of life, its effects on survival are equivocal, likely due to its linkage with HO-1. Two clinical trials of EPO in patients with solid tumors have, in fact, shown specific negative effects on survival. However, EPO's effect on tumor growth and survival is not uniformily pro growth and pro survival, as EPO may act synergistically with chemotherapy to induce apoptosis. Finally, compounds have been synthesized that do not trigger EPO receptor and thus may allow experimental distinction and, therefore, at least potentially affect at the clinical level the tissue-protective effects of EPO (e.g., antiapoptosis) without provoking its other potentially detrimental effects.
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PMID:A role for heme oxygenase-1 in the antioxidant and antiapoptotic effects of erythropoietin: the start of a good news/bad news story? 1655 68

Severe neutrophilia caused by renal cell carcinoma secreting granulocyte colony-stimulating factor (G-CSF) is a rare manifestation of renal cancer. A 70-year-old woman presented with a 2-year history of severe anemia, severe neutrophilia and elevated serum G-CSF, which completely resolved after radical nephrectomy. Histologic study revealed a histologically high-grade, stage pT1N0M0 renal cell carcinoma. Serum G-CSF level was elevated preoperatively and returned to normal postoperatively. Immunohistochemical study of the tumor tissue using anti-G-CSF monoclonal antibody revealed positive staining in the cancer cells. Careful follow-up of white blood cell count and physical examination for neck lymph node enlargement led to the timely identification of tumor recurrence 17 months after surgery, which resulted in prompt and successful salvage immunotherapy. In this case, G-CSF appeared to contribute to the leukocytosis, as both serum G-CSF level and white blood cell count closely correlated with the clinical tumor growth. White blood cell count should be closely monitored as an indicator of disease activity in patients with G-CSF-producing renal cell carcinoma.
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PMID:Renal cell carcinoma producing granulocyte colony-stimulating factor. 1663 52

Despite local and systemic therapies, the National Cancer Institute estimates that prostate cancer will cause over 30,000 deaths in 2006. This suggests that additional therapeutic approaches are needed. The chicken anemia viral protein Apoptin causes tumor-selective apoptosis in human tumor lines independent of p53 and Bcl-2 status. Tet-regulated expression of Apoptin from an adenoviral vector showed cytotoxicity in DU145, PC-3, and LNCaP tumor cells regardless of expression of p53, Bcl-2, Bcl-xL, Bax, survivin, FLIP(S), XIAP, or CIAP. Apoptin expression caused an increase in the tumor suppressor lipid ceramide, which regulates the cellular stress response. Interestingly, 10 of 15 primary prostate cancers examined by Western blotting overexpressed acid ceramidase (AC), suggesting that ceramide deacylation might serve to negate elevated levels of ceramide, creating a more antiapoptotic phenotype. This was confirmed in AC-overexpressing cells in which we observed decreased sensitivity to apoptosis following treatment with Apoptin. Addition of the AC inhibitor LCL204, in combination with Apoptin, augmented cell killing. This effect was also demonstrated in vivo in that Apoptin and LCL204 cotreatment significantly reduced tumor growth in DU145 xenografts (P<0.05). Taken together, our data demonstrated that Apoptin is a promising therapeutic agent for prostate cancer and that its function is improved when combined with acid ceramidase inhibitors.
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PMID:Modulation of ceramide metabolism enhances viral protein apoptin's cytotoxicity in prostate cancer. 1716 68

Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. To explore the use of the Apoptin gene in cancer gene therapy, we constructed a recombinant fowlpox virus expressing the Apoptin protein (vFV-Apoptin) and compared the tumor-killing activity of the recombinant virus with that of wild-type fowlpox virus in the human hepatoma cell line HepG2. We found that although cells were somewhat resistant to the basal cytotoxic effect of wild-type fowlpox virus, infection with vFV-Apoptin caused a pronounced, additional cytotoxic effect. Furthermore, cell death and disruption of tumor integrity were apparent in the vFV-Apoptin-infected cells. We also tested whether fowlpox virus-mediated expression of Apoptin in tumor cells could stimulate an antitumor effect by injecting aggressive subcutaneous tumors derived from H22 mouse hepatoma cells in C57BL/6 mice with vFV-Apoptin. We found that fowlpox virus-mediated intratumoral expression of the Apoptin gene can induce protective and therapeutic antitumor effects and significantly increase survival. Taken together, these data indicate that infection of tumors with fowlpox virus expressing Apoptin inhibits tumor growth, induces apoptosis and may be an effective cancer treatment.
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PMID:Antitumor effects of a recombinant fowlpox virus expressing Apoptin in vivo and in vitro. 1703 30

Anemia has an incidence both on the quality of life and the evolution of cancer. Anemia may result in cancer from either a bone marrow infiltration of cancer cells or a cytotoxic effect of chemotherapy and/or radiotherapy, or both. EPO is a glycoprotein which stimulates erythrocyte formation by bone marrow progenitory cells. Recombinant EPO has considerably improved treatment of anemic patients, by increasing hemoglobin serum levels and reducing the need for blood transfusion. The quality of life of cancer patients is thus improved and several studies highlight the beneficial role of EPO on the clinical outcome. A preclinical background and some clinical data suggest however a detrimental role of EPO in cancer by a possible stimulation of tumor growth. There is a need of more clinical trials in order to assess the effects of EPO on tumors and their treatment.
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PMID:EPO in cancer anemia: benefits and potential risks. 1719 90

According to recent data erythropoietin receptor (EPOR) is expressed not only by bone marrow erythroid progenitors but by endothelial- and cancer cells and it was suggested that erythropoietin (EPO) may affect their functions as well. We have analyzed the effects of recombinant human erythropoietin-alpha (rHuEPOalpha) on radiation sensitivity of EPOR+ human epidermoid carcinoma (A431) xenograft model. In vivo rHuEPOalpha treatment was started after tumor cell inoculation into SCID mice. 5 Gy irradiation was performed on day 14, the effect of which was measured on day 22. Hemoglobin level, tumor-associated microvessels and HIF-1alpha expression of the xenograft were monitored during the experiment. rHuEPOalpha administration prevented the development of tumor-induced anemia of SCID mice and reduced the level of HIF-1alpha expression of the xenograft tumor without affecting tumor growth. We have found that rHuEPOalpha treatment significantly increased the efficacy of antitumor effect of irradiation which was partly mediated by complex effects on tumor-associated microvessels. In vitro rHuEPOalpha did not affect proliferation of A431 cells but enhanced the antiproliferative and proapoptotic effects of irradiation. We concluded that rHuEPOalpha administration positively modulated the antitumoral effects of irradiation at least by two pathways, decreasing systemic hypoxia resulting in decreased tumoral HIF-1alpha expression and enhancing direct effects on tumor-associated microvessels.
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PMID:[Human recombinant erythropoietin-alpha increases the efficacy of irradiation in preclinical model]. 1741 76

Erythropoietin (EPO) is a glycoprotein hormone produced by renal tissue in response to hypoxia; EPO functions as a cytokine to precursor cells produced by the bone marrow, stimulating red blood cell production. Erythropoiesis stimulating agents (ESAs) are manufactured molecules designed to mimic the ability of endogenous EPO to bind to EPO receptors and increase red blood cell production. To achieve desired dosing schedules and avoid the need for blood transfusions, oncologists have become increasingly reliant on ESAs to counter the anemia often experienced during chemotherapy. In recent years, significant concerns have been raised about the safety of ESAs, including the possibility of increased cardiovascular events and even increased tumor growth and accelerated mortality in cancer patients. ESAs also contribute significantly to the expense of chemotherapy, rendering them unavailable to some patients and available to others only upon achieving insurance-mandated levels of anemia. A recently discovered "normobaric oxygen paradox" demonstrates that renal tissue can be stimulated to increase EPO production via a simple pattern of oxygen breathing at normal atmospheric pressures. This leads directly to the hypothesis that oxygen breathing may provide chemotherapy patients with a convenient and inexpensive alternative to ESAs. Stimulating endogenous EPO production eliminates the small risk of immune system reaction associated with ESAs. Further, the endogenous physiological EPO doses provided by this method may be safer, in terms of cancer mortality, than the exogenous pharmacological doses inherent in ESA administration. A single patient test case is presented to support the hypothesis that normobaric oxygen breathing can be an effective replacement for ESAs in treating chemotherapy-induced anemia. In this case, a stage III breast cancer patient undergoing dose-dense AC+T chemotherapy obtained a clear response equivalent to ESA treatment by using a pattern of simple oxygen breathing.
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PMID:Oxygen breathing may be a cheaper and safer alternative to exogenous erythropoietin (EPO). 1749 66

Safety concerns surrounding the use of recombinant human erythropoietin (Epo) to treat anemia in cancer patients were raised after 2 recent clinical studies reported a worse survival outcome in patients who received epoetin alpha or epoetin beta compared with patients who received placebo. Although those findings contrasted with previous clinical studies, which demonstrated no difference in survival for cancer patients who received erythropoiesis-stimulating agents (ESAs), some investigators have suggested a potential role for ESAs in promoting tumor growth through 1) stimulation of Epo receptors (EpoR) expressed in tumors, 2) stimulation and formation of tumor vessels, and/or 3) enhanced tumor oxygenation. The first and second hypotheses appeared to be supported by some EpoR expression and ESA in vitro studies. However, these conclusions have been challenged because of poor specificity of EpoR-detection methodologies, conflicting data from different groups, and the lack of correlation between in vitro data and in vivo findings in animal tumor models. For this report, the authors reviewed the biology of EpoR in erythropoiesis and compared and contrasted the reported findings on the role of ESAs and EpoR in tumors.
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PMID:Expression and function of erythropoietin receptors in tumors: implications for the use of erythropoiesis-stimulating agents in cancer patients. 1758 31

An assessment was undertaken of survival and prognosis in 30 patients with primary disseminated breast tumors which disintegrated following palliative mastectomy carried out for sanitary purposes. That resulted in significant improvement in general condition, higher hemoglobulin and lowered intoxication which in turn made medication and radiotherapy possible: chemotherapy (4-6 cycles) followed by hormonal therapy (22-73.3%), hormonal therapy (8-26.7%), and radiotherapy for surgical scar (16-53.3%). All patients were followed up for 18 months (median--3.8 years). Tumor progression at different stages was detected in 12 (40%); local recurrences--8 out of them (26.7%). By the time of investigation, 9 (20%) out of 30, had died of tumor progression while 21 (80%) continued their treatment at the Institute's Clinic. Mean survival was 21.5 +/-2.2 months (median--19 (8-60+)). Our method proved effective due to high survival (median--18 months) and significant improvement in quality of life. However, visceral metastases (p = 0.02) and tumor growth duration (p = 0.05) were of prognostic significance. Such characteristics as presence or absence of estrogen and progesterone receptors of tumor, histological pattern, and anemia appeared insignificant, as far as prognosis was concerned. Function chi2 difference was highly significant (Cox) (p = 0.00013).
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PMID:[Role of palliative surgery in complex treatment for disseminated breast cancer]. 1815 13

During the last decade, anemia, a very common situation in patients with malignant diseases, either associated with chemotherapy or not, is being treated with recombinant erythropoietin (rEPO). Recent experimental findings have elucidated the role of EPO as a strongly anti-apoptotic agent in multiple non-erythroid and neoplastic tissues. The discovery of probably functional EPO receptors (EPOR) on malignant cells, hinting that EPO may act as a tumor growth factor, raised embarrassing thoughts regarding the routine administration of erythropoiesis-stimulating agents (ESAs). In addition, the results of a few clinical trials showing a negative impact on overall survival of rEPO-treated cancer patients, although strongly criticized for several methodological pitfalls, led the FDA to force a "black label" warning concerning the use of rEPO and to recommend that physicians should use the lowest possible dose of ESAs in chemotherapy-treated cancer patients. This recommendation comes in accord with the recent guidelines of European Organisation for Research and Treatment of Cancer (EORTC) which are reviewed in this paper, along with the structure of EPO and EPOR, the role of EPO on normal and malignant cells and the clinical applications of EPO.
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PMID:Erythropoietin in cancer: the new face of an old friend. 1840 80


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