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Journal ArticleDOI

Elevation of serum ferritin is associated with the outcome of patients with newly diagnosed multiple myeloma.

27 Nov 2009-The Korean Journal of Internal Medicine (Korean Association of Internal Medicine)-Vol. 24, Iss: 4, pp 368-373
TL;DR: The serum ferritin can a prognostic parameter of survival as well as disease activity in patients with multiple myeloma.
Abstract: Background/Aims: Serum ferritin is a marker of acute phase reactions and iron storage. In addition, hematologic malignancies are associated with elevated serum ferritin levels. Other studies have suggested that ferritin is a surrogate for advanced disease and has an impact on relapse, because elevated serum ferritin predicts overall survival (OS) and relapse-free survival following autologous stem cell transplantation for lymphomas. Methods: We studied 89 consecutive patients with newly diagnosed multiple myeloma to determine the value of serum ferritin in comparison with known prognostic factors. Results: The OS in the elevated serum ferritin group (≥300 ng/mL) was shorter than that in the normal serum ferritin group (<300 ng/mL, p<0.001) after a median follow-up of 25 months. In univariate analysis, elevated ferritin was correlated with poor survival in the patients (relative risk [RR], 2.588; 95% confidence interval [CI], 1.536 to 4.358; p<0.001). Furthermore, multivariate analysis showed that elevated serum ferritin was an independent predictor of mortality in patients with multiple myeloma (RR, 2.594; 95% CI, 1.403 to 4.797; p=0.002). Conclusions: The serum ferritin can a prognostic parameter of survival as well as disease activity in patients with multiple myeloma. (Korean J Intern Med 2009;24:368-373)

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Citations
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Journal ArticleDOI
TL;DR: This work highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure.
Abstract: Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions.

341 citations


Cites background from "Elevation of serum ferritin is asso..."

  • ...…Mateo- Gallego et al. 2010; McNeill et al. 2008; Menke et al. 2009; Qureshi et al. 2008; Rajpathak et al. 2009; Sharifi et al. 2008; Skinner et al. 2010; Song et al. 2009; Storey et al. 2009; Sun et al. 2008; Tsimikas et al. 2009; Valenti et al. 2010; Walker et al. 2010; Wang et al. 2010b; Yoneda…...

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Journal ArticleDOI
TL;DR: Previous studies on the physiology of iron metabolism and its role in cancer are summarized and the significance of iron regulation, and the association between iron homeostasis and carcinogenic mechanisms are discussed.
Abstract: Iron is an essential element for biological processes. Iron homeostasis is regulated through several mechanisms, from absorption by enterocytes to recycling by macrophages and storage in hepatocytes. Iron has dual properties, which may facilitate tumor growth or cell death. Cancer cells exhibit an increased dependence on iron compared with normal cells. Macrophages potentially deliver iron to cancer cells, resulting in tumor promotion. Mitochondria utilize cellular iron to synthesize cofactors, including heme and iron sulfur clusters. The latter is composed of essential enzymes involved in DNA synthesis and repair, oxidation‑reduction reactions, and other cellular processes. However, highly increased iron concentrations result in cell death through membrane lipid peroxidation, termed ferroptosis. Ferroptosis, an emerging pathway for cancer treatment, is similar to pyroptosis, apoptosis and necroptosis. In the present review, previous studies on the physiology of iron metabolism and its role in cancer are summarized. Additionally, the significance of iron regulation, and the association between iron homeostasis and carcinogenic mechanisms are discussed.

74 citations


Cites background from "Elevation of serum ferritin is asso..."

  • ...Serum ferritin may serve as a negative prognostic indicator (111,112)....

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Journal ArticleDOI
Li X, Asmitananda T1, Gao L, Gai D, Song Z, Zhang Y, Hui Ren, Yang T, Chen T, Chen M 
TL;DR: This study evaluated the efficiency of 7 tumor biomarkers, namely, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, CYFRA-21-1, CA-125, carbohydrate antigen-19.9, and ferritin, independently or in combination for the diagnosis of lung cancer, and found that combining biomarkers significantly aided in the diagnosisof lung cancer.
Abstract: The propensity for tumor biomarkers to be detected in serum at an early disease stage has become an area of interest for clinicians. This study aimed to evaluate the efficiency of 7 tumor biomarkers, namely, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA-21-1), alpha-fetoprotein, carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9), and ferritin, independently or in combination for the diagnosis of lung cancer. Electrochemiluminescence immunization was used to determine biomarker levels expressed in 530 patients with pulmonary disease and 229 healthy subjects. The observed levels of CEA, NSE, CYFRA-21-1, CA-125, and CA-19.9 in patients with pathologically confirmed lung cancer were significantly higher than those in patients with benign pulmonary disease or control subjects. Adenocarcinoma, squamous cell carcinoma, and small cell carcinoma of the lung were associated with the highest observed levels of CA-125, CYFRA-21-1, and NSE, respectively. Combining biomarkers successfully led to the diagnosis of lung cancer. CEA + NSE + CA-125 showed the highest sensitivity for small cell carcinoma, at 83.33%, whereas CEA + NSE + CYFRA-21-1 + CA-125 showed 94.11% sensitivity for squamous cell carcinoma. The combination of 6 biomarkers, namely, CEA + NSE + CYFRA-21-1 + CA-125 + ferritin + CA-19.9, showed 80.49% sensitivity for adenocarcinoma. Combining biomarkers significantly aided in the diagnosis of lung cancer. However, this increased sensitivity on combination was accompanied by a decreased specificity for lung cancer subtypes. Combining biomarkers appropriately increases their sensitivity and helps with the diagnosis of lung cancer.

62 citations


Cites background from "Elevation of serum ferritin is asso..."

  • ...Recent evidence (21-23) suggests the existence of a correlation between ferritin level and malignancy, with elevated serum ferritin levels observed in lymphoma, Hodgkin’s disease, breast cancer, ovarian cancer, and colon cancer (24-26)....

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Journal ArticleDOI
TL;DR: Findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in multiple myeloma pathophysiology, and DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling.
Abstract: Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/β-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling.

37 citations


Cites background from "Elevation of serum ferritin is asso..."

  • ...Recently, two independent groups reported that serum ferritin, which is used as a marker for iron overload, can be a negative prognostic indicator in MM [5, 6]....

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Journal ArticleDOI
TL;DR: The use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis is proposed.
Abstract: The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

29 citations

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