Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue hypoxia is a characteristic property of cervical cancers that makes tumors resistant to chemo- and radiation therapy. Erythropoietin (Epo) is a hypoxia-inducible stimulator of erythropoiesis. Acting via its receptor (EpoR), Epo up-regulates bcl-2 and inhibits apoptosis of erythroid cells and rescues neurons from hypoxic damage. In addition to human papillomavirus infection, increased bcl-2 expression and decreased apoptosis are thought to play a role in the progression of cervical neoplasia. Using reverse transcriptase-polymerase chain reaction and Western blotting we showed that HeLa and SiHa cervical carcinoma cells and human cervical carcinomas express EpoR, and that hypoxia enhances EpoR expression. Exogenous Epo stimulated tyrosine phosphorylation and inhibited the cytotoxic effect of cisplatin in HeLa cervical carcinoma cells. Using immunohistochemistry, we examined the expression of Epo, EpoR, p16, hypoxia-inducible factor (HIF)-1alpha, and bcl-2 in benign and dysplastic cervical squamous epithelia and invasive squamous cell carcinomas (ISCCs). EpoR expression in benign epithelia was confined to the basal cell layers, whereas in dysplasias it increasingly appeared in more superficial cell layers and showed a significant correlation with severity of dysplasia. Diffuse EpoR expression was found in all ISCCs. Expression of Epo and HIF-1alpha was increased in dysplasias compared to benign epithelia. Focal Epo and HIF-1alpha expression was seen near necrotic areas in ISCCs, and showed correlation in their spatial distribution. Significant correlation was found between expression of EpoR, and p16 and bcl-2 in benign and dysplastic squamous epithelia. Our results suggest that increased expression of Epo and EpoR may play a significant role in cervical carcinogenesis and tumor progression. Hypoxia-inducible Epo signaling may play a significant role in the aggressive behavior and treatment resistance of hypoxic cervical cancers.
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PMID:Hypoxia-inducible erythropoietin signaling in squamous dysplasia and squamous cell carcinoma of the uterine cervix and its potential role in cervical carcinogenesis and tumor progression. 1275 37

Anemia is common in patients with cancer. This systematic literature review of reports published in 1966 through February 2003 identified the prevalence of anemia in specific cancers and assessed the impact of anemia on survival and quality of life (QOL). Studies about chemotherapy-induced anemia were excluded. Anemia prevalence varied widely; most studies found that between 30% and 90% of patients with cancer had anemia. Prevalence was affected strongly by the definition of anemia: 7% of patients with Hodgkin disease had anemia when the condition was defined as a hemoglobin level <90.0 g/L; as many as 86% of patients had anemia when it was defined as a hemoglobin value <110.0 g/L. Prevalence varied by cancer type and disease stage: 40% of patients with early-stage colon tumors and nearly 80% of patients with advanced disease had anemia. Patients with anemia had poorer survival and local tumor control than did their nonanemic counterparts in 15 of 18 studies. In 8 of 12 studies, patients without anemia (most treated with epoetin) needed fewer transfusions. QOL was positively correlated with hemoglobin levels in 15 of 16 studies. There was no significant difference in treatment toxicity between patients with and without anemia. Tumor hypoxia, which has been associated with resistance to radiation therapy and chemotherapy, may stimulate angiogenesis, leading to poor local control of tumors and increased morbidity and mortality. Treatment of anemia may have a significant impact on patient survival and QOL. However, a standard definition of anemia is needed, as is research about the effect of anemia on cancer progression.
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PMID:Prevalence and outcomes of anemia in cancer: a systematic review of the literature. 1505 Aug 83

The presence of hypoxic areas is a common feature of solid tumors and has been associated with decreased sensitivity of the tumors to radiation therapy and oxygen-dependent chemotherapeutic agents, as well as worsened outcomes, including survival. Anemia is also common in cancer patients and is believed to contribute to tumor hypoxia. Thus, the rationale exists for administering recombinant human erythropoietin (rHuEPO, epoetin alfa) in an effort to increase hemoglobin levels, correct anemia, and thereby possibly increase the sensitivity of tumors to standard cancer treatment and improve patient outcomes. The results of several preclinical studies that examined the impact of anemia prevention by rHuEPO on tumor sensitivity to radiation therapy in rodent models of cancer showed that induction of anemia increased hypoxia in tumor cells and that correction of anemia with rHuEPO could improve tumor oxygenation. Further studies in rodent models showed significantly delayed tumor growth in both irradiated mice and irradiated rats treated with rHuEPO. In those studies, the increased radiosensitivity observed was believed to be due to improved tumor oxygenation following the correction of anemia. Similarly, enhancements in chemosensitivity were found in rHuEPO-treated rodent models. In the chemosensitivity studies, as in the radiosensitivity studies, the therapeutic benefit obtained was believed to reflect improved tumor oxygenation subsequent to an rHuEPO-related increase in oxygen availability. One study evaluated the potential biologic effects of epoetin alfa on tumor progression using murine myeloma models (MOPC-315 and 5T33 MM). Treatment of MOPC-315 tumor-bearing mice with epoetin alfa induced complete tumor regression in 30%-60% of mice. Regression was found to be tumor specific, and the effect of epoetin alfa was shown to be T-cell mediated. Additionally, epoetin alfa administration prolonged survival and reduced morbidity and mortality in the 5T33 MM tumor model. Those investigators suggested that epoetin alfa may have antitumor activity in addition to its hematopoietic effects. Overall, these preclinical findings suggest that correction of anemia by rHuEPO can increase tumor sensitivity to both radiation therapy and chemotherapy and that epoetin alfa may exert an immunomodulatory effect in multiple myeloma.
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PMID:rHuEPO and treatment outcomes: the preclinical experience. 1559 22

Cancer patients are frequently anemic. Treatment of anemic patients with erythropoiesis-stimulating proteins (ESPs) such as epoetin and darbepoetin is associated with benefits that include a reduced transfusion risk and improved quality of life. The recent reports of two randomized trials in which ESP treatment was associated with a decreased survival raised valid concerns regarding the safety of these agents in oncology practice. Reports of erythropoietin receptors on non-hematologic human tumor cells have increased the level of concern and provided a relatively simple model for the effects of ESPs on tumor progression and resistance to treatment. This article reviews available data, which lead to a number of conclusions: 1) the two trials suggesting a negative impact on survival have serious methodologic issues that may compromise interpretation; 2) when used to treat rather than prevent anemia in cancer patients, ESPs show no significant negative impact on survival outcomes; 3) with the exception of erythroleukemia cell lines, the presence of functional erythropoietin receptors on human tumor cells has not been conclusively shown; and 4) a sound theoretical basis exists, supported by preclinical evidence, that any effect of ESP therapy on tumor outcomes may depend on baseline hemoglobin levels, with different effects when anemic and non-anemic individuals are treated. For the present, it is prudent to withhold ESP therapy unless hemoglobin concentrations fall below 12 g/dL and to titrate treatment to maintain a target of 12 g/dL, with adjustments in therapy to insure that levels do not exceed 13 g/dL.
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PMID:Cancer patient survival and erythropoietin. 1631 10

Anemia is highly prevalent in patients with cancer and its impact on quality of life and long-term outcome in these patients is well documented. Recombinant human erythropoietins, or epoetins, have been used to treat cancer-related or antitumor therapy-induced anemia for many years. Through a combination of clinical studies and extensive experience in the real-life clinical setting, epoetin beta has been shown to be efficacious and well tolerated, increasing hemoglobin levels, reducing the need for transfusion and improving quality of life. This favorable efficacy and safety profile has been demonstrated across a broad range of malignancy types, irrespective of the treatment used (platinum or non-platinum based). The effect of treatment with epoetin beta is rapid, with mean hemoglobin increases of 1 g/dl seen as early as 4 weeks following the start of therapy. Furthermore, there is no evidence that epoetin beta negatively affects overall survival or tumor progression in anemic patients with cancer. The approved 30,000 IU once-weekly dosing regimen (as opposed to the 10,000 IU three-times weekly regimen) provides greater convenience and may result in improved treatment compliance.
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PMID:Epoetin beta in oncology: examining the current evidence. 1655 69

Erythropoietin emerged as the biggest drug in oncology despite never having demonstrated a survival benefit in patients with cancer. Two phase III clinical trials reported more than 3 years ago that erythropoietin adversely affected cancer survival rates, due mainly to tumor progression. Despite changes to the product label for erythropoietins in 2004, clinical practice remained unchanged until recent weeks when, following reports of three new phase III studies and a phase II trial, a "black box warning" for erythropoietin products was issued by the Food and Drug Administration (FDA). Whether erythropoietin products can be considered safe when used for FDA-approved indications is currently at issue; however, addressing this question will be difficult until the mechanisms of erythropoietin-stimulated tumor progression are understood. A thorough evaluation of materials from clinical trials already completed may shed new light on how erythropoietin promotes cancer progression. Until these issues are resolved, oncologists should inform their patients of erythropoietin's potential adverse impact on cancer progression and survival. Disclosure of potential conflicts of interest is found at the end of this article.
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PMID:Erythropoietin in cancer: presumption of innocence? 1746 82

Erythropoietin (EPO) has long been recognized as the major hematopoietic cytokine regulating normal erythropoiesis. Moreover, there is a growing interest in the non-erythropoietic, tissue-protective effects of EPO. Because of its potential to correct anemia, EPO has been increasingly prescribed to cancer patients. However, although recombinant human Epo (rHuEPO) significantly reduces the risk for red blood cell transfusions in cancer patients, recent clinical studies have reported decreased survival and disease control following rHuEPO treatment in patients with different cancer types. The issue of EPOR expression in tumor cells is critical in this respect. The expression of EPOR in tumor cells raises the possibility that exogenous rHuEPO may directly influence tumor growth or sensitivity to chemo-radiation therapy. In addition, EPOR expression in endothelial cells suggests what potential effects EPO may have on tumor capillaries, such as the stimulation of angiogenesis. However, as experimental studies reveal, the overall direct effect of EPO-EPOR signaling on cancer progression and therapy is not a straightforward one. The current paper provides an update on the biology of EPO, and discusses its utility in the treatment of cancer patients.
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PMID:Erythropoietin in cancer: an update. 1878 55

Anemia is a common complication of systemic anti-cancer treatment. In this context epoetin beta, like other erythropoiesis-stimulating agents (ESAs), has demonstrable efficacy in raising Hb concentration and reducing the requirement for red cell transfusion. Consequently ESA therapy has gained increasing prominence in the management of chemotherapy-related anemia. However, recent trial data have suggested a higher rate of thromboembolic events, enhanced tumor progression and reduced survival in some patients with cancer who receive ESA therapy. In response, regulatory authorities have mandated increasingly restrictive label changes. In light of these new developments we consider the current role of epoetin beta in the management of chemotherapy-related anemia.
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PMID:Recombinant human epoetin beta in the treatment of chemotherapy-related anemia. 1943 15

Erythropoietin-stimulating agents (ESAs) were originally designed to replace endogenous erythropoietin in patients with anemia secondary to renal failure. Their use has subsequently been expanded to include patients with anemia of other causes, including cancer patients, in whom deficiency of erythropoietin, per se, is not the primary cause of anemia. Although early studies showed promise of ESA administration in reducing the need for transfusions and improving the quality of life in cancer patients, several large randomized clinical trials have recently shown a potential detrimental effect of ESA administration on tumor progression and survival in these patients. These studies have called into question the safety of ESAs as supportive therapy in patients being treated for oncologic conditions. However, numerous questions remain to be addressed regarding the design of these studies, the effect of various targeted hemoglobin levels, and the potential biologic mechanisms proposed to explain promotion of tumor progression and reduced survival.
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PMID:Erythroid-stimulating agents in cancer therapy: potential dangers and biologic mechanisms. 1963 5

Erythropoietin receptors (EpoRs) are expressed in a large percentage of cells in many human malignancies, including endometrial adenocarcinoma. In such tumors, administration of recombinant human erythropoietin (rhEpo) during radiotherapy and chemotherapy may oppose tumor progression by interfering with growth and invasion pathways. In the present study, a strong EpoR expression was demonstrated in 58.8% of 72 stage I endometrial adenocarcinomas, and this pattern was linked with a high degree of tumor differentiation (p=0.01), deep myometrial invasion (p=0.04) and, marginally, with poor prognosis (p=0.06). In addition, a strong association with the immunohistochemical expression of hypoxia-inducible factor 1alpha (HIF1alpha) and the downstream angiogenic protein vascular endothelial growth factor (VEGF) was noted. In multivariate analysis, HIF1alpha, but not EpoR, was associated with the depth of myometrial invasion (p=0.04) and marginally with prognosis (p=0.07). It is concluded that EpoR are common constituents of endometrial adenocarcinomas and are related to tumor aggressiveness, although this is probably a result of their involvement in an active HIF pathway.
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PMID:Erythropoietin receptors in endometrial carcinoma as related to HIF1{alpha} and VEGF expression. 1977 3


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