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Liu S, Wei W, Wang J, Chen T. Theranostic applications of selenium nanomedicines against lung cancer. J Nanobiotechnology 2023; 21:96. [PMID: 36935493 PMCID: PMC10026460 DOI: 10.1186/s12951-023-01825-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 02/18/2023] [Indexed: 03/21/2023] Open
Abstract
The incidence and mortality rates of lung cancer are among the highest in the world. Traditional treatment methods include surgery, chemotherapy, and radiotherapy. Although rapid progress has been achieved in the past decade, treatment limitations remain. It is therefore imperative to identify safer and more effective therapeutic methods, and research is currently being conducted to identify more efficient and less harmful drugs. In recent years, the discovery of antitumor drugs based on the essential trace element selenium (Se) has provided good prospects for lung cancer treatments. In particular, compared to inorganic Se (Inorg-Se) and organic Se (Org-Se), Se nanomedicine (Se nanoparticles; SeNPs) shows much higher bioavailability and antioxidant activity and lower toxicity. SeNPs can also be used as a drug delivery carrier to better regulate protein and DNA biosynthesis and protein kinase C activity, thus playing a role in inhibiting cancer cell proliferation. SeNPs can also effectively activate antigen-presenting cells to stimulate cell immunity, exert regulatory effects on innate and regulatory immunity, and enhance lung cancer immunotherapy. This review summarizes the application of Se-based species and materials in lung cancer diagnosis, including fluorescence, MR, CT, photoacoustic imaging and other diagnostic methods, as well as treatments, including direct killing, radiosensitization, chemotherapeutic sensitization, photothermodynamics, and enhanced immunotherapy. In addition, the application prospects and challenges of Se-based drugs in lung cancer are examined, as well as their forecasted future clinical applications and sustainable development.
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Affiliation(s)
- Shaowei Liu
- Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Weifeng Wei
- Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jinlin Wang
- Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
| | - Tianfeng Chen
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Jinan University, Guangzhou, 510632, China.
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Ehudin MA, Golla U, Trivedi D, Potlakayala SD, Rudrabhatla SV, Desai D, Dovat S, Claxton D, Sharma A. Therapeutic Benefits of Selenium in Hematological Malignancies. Int J Mol Sci 2022; 23:ijms23147972. [PMID: 35887320 PMCID: PMC9323677 DOI: 10.3390/ijms23147972] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/09/2022] [Accepted: 07/12/2022] [Indexed: 12/14/2022] Open
Abstract
Supplementing chemotherapy and radiotherapy with selenium has been shown to have benefits against various cancers. This approach has also been shown to alleviate the side effects associated with standard cancer therapies and improve the quality of life in patients. In addition, selenium levels in patients have been correlated with various cancers and have served as a diagnostic marker to track the efficiency of treatments or to determine whether these selenium levels cause or are a result of the disease. This concise review presents a survey of the selenium-based literature, with a focus on hematological malignancies, to demonstrate the significant impact of selenium in different cancers. The anti-cancer mechanisms and signaling pathways regulated by selenium, which impart its efficacious properties, are discussed. An outlook into the relationship between selenium and cancer is highlighted to guide future cancer therapy development.
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Affiliation(s)
- Melanie A. Ehudin
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - Upendarrao Golla
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Devnah Trivedi
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Shobha D. Potlakayala
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Sairam V. Rudrabhatla
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Dhimant Desai
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Sinisa Dovat
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - David Claxton
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Arati Sharma
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Correspondence:
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Alkan B, Durucan C. Complete chemical and structural characterization of selenium-incorporated hydroxyapatite. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 33:5. [PMID: 34950967 PMCID: PMC8702414 DOI: 10.1007/s10856-021-06631-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 11/19/2021] [Indexed: 06/14/2023]
Abstract
Hydroxyapatite (HAp) has long been used as synthetic bone tissue replacement material. Recent advances in this area have led to development of dual-functional bioceramics exhibiting high biocompability/osteoconductivity together with the therapeutic effect. Selenium, in that respect, is an effective therapeutic agent with promising antioxidant activity and anticancer effects. In this study, selenium-incorporated hydroxyapatite (HAp:Se) particles have been synthesized by modified aqueous precipitation method using calcium (Ca(NO3)2·4H2O) and phosphate ((NH4)2HPO4) salts and sodium selenite (Na2SeO3). The effects of selenium incorporation and post-synthesis calcination treatment (900-1100 °C) on physical, chemical properties and crystal structure of resultant HAp powders have been investigated. Complete chemical identification was performed with spectroscopical analyses including Fourier transform infrared and x-ray photoelectron spectroscopy to elucidate the mechanism and chemical nature of selenium incorporation in HAp. Meanwhile, detailed x-ray diffraction studies by Rietveld refinement have conducted to explain changes in the HAp crystal structure upon selenium incorporation.
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Affiliation(s)
- Baris Alkan
- Department of Metallurgical and Materials Engineering, Middle East Technical University, 06800, Ankara, Turkey
- BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, 06800, Ankara, Turkey
| | - Caner Durucan
- Department of Metallurgical and Materials Engineering, Middle East Technical University, 06800, Ankara, Turkey.
- BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, 06800, Ankara, Turkey.
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Chrysochou E, Koukoulakis K, Kanellopoulos PG, Sakellari A, Karavoltsos S, Dassenakis M, Minaidis M, Maropoulos G, Bakeas E. Human serum elements' levels and leukemia: A first pilot study from an adult Greek cohort. J Trace Elem Med Biol 2021; 68:126833. [PMID: 34371329 DOI: 10.1016/j.jtemb.2021.126833] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 06/30/2021] [Accepted: 07/30/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND The present study focuses on the evaluation of potential relationships between trace elements and acute and chronic types of leukemia, via the determination of their levels in human blood serum. METHODS A total of 199 serum samples from a Greek cohort were examined, including both leukemia cases and controls. Elements' analysis was carried out using inductively coupled plasma mass spectrometry (ICP-MS) and demographic features such as age, gender, smoking habits and area of residence were recorded and statistically treated applying Shapiro-Wilk, Kolmogorov-Smirnov, Mann Whitney and Kruskal Wallis tests (p < 0.05). Spearman correlation and principal component analysis (PCA) were also performed to investigate possible associations. RESULTS The results demonstrated significantly higher (p < 0.05) trace elements concentrations in cases' serum compared to that of controls excluding Ba, with Cu (median concentration 1295 μg L-1) being the most abundant in cases. Additionally, concentration of toxic Pb and Cd were found at seven and four fold higher concentrations in cases, respectively. Among the trace elements examined, only Rb (164 μg L-1) was detected in higher concentrations in controls. Ba, Cd and Co presented the lowest concentrations (lower than 1 μg L-1). PCA was performed for overall and classified data, indicating a stronger relation among the toxic As, Cd, Ni and Pb in cases than controls, particularly referring to smokers and industrial sites' residents. Hematological parameters and factors such as age and gender did not present any significant outcome or correlation. CONCLUSIONS The findings from this pilot study suggest a potential relationship between metals and leukemia, especially concerning the toxic ones. Results from the employed source apportionment tools imply that smoking and atmospheric degradation may be positively related with higher metal serum levels in leukemia patients.
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Affiliation(s)
- Eirini Chrysochou
- Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografos, Panepistimiopolis, Athens, 15784, Greece.
| | - Konstantinos Koukoulakis
- Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografos, Panepistimiopolis, Athens, 15784, Greece.
| | - Panagiotis Georgios Kanellopoulos
- Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografos, Panepistimiopolis, Athens, 15784, Greece.
| | - Aikaterini Sakellari
- Laboratory of Environmental Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografos, Panepistimiopolis, Athens, 15784, Greece.
| | - Sotirios Karavoltsos
- Laboratory of Environmental Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografos, Panepistimiopolis, Athens, 15784, Greece.
| | - Manos Dassenakis
- Laboratory of Environmental Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografos, Panepistimiopolis, Athens, 15784, Greece.
| | | | | | - Evangelos Bakeas
- Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografos, Panepistimiopolis, Athens, 15784, Greece.
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Park SJ, Yim GW, Paik H, Lee N, Lee S, Lee M, Kim HS. Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer: study protocol for a phase III, double-blind, randomized study. J Gynecol Oncol 2021; 32:e73. [PMID: 34132071 PMCID: PMC8362815 DOI: 10.3802/jgo.2021.32.e73] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/03/2021] [Accepted: 05/15/2021] [Indexed: 12/12/2022] Open
Abstract
Background The second-line chemotherapy using paclitaxel, carboplatin, and bevacizumab for treating platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer frequently cause chemotherapy-induced peripheral neuropathy (CIPN), which is significantly associated with deterioration of quality of life. Despite the potential of some agents to prevent and treat CIPN, and there is still a lack of evidence of the effect. Although selenium has been suggested as an antioxidant candidate to prevent CIPN, there are insufficient data regarding its effect due to its low dose by oral administration. Thus, we hypothesized intravenous administration of high-dose selenium (2,000 µg/day) at each cycle of the second-line chemotherapy would prevent and reduce CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer. Method This trial is an investigator-initiated, phase III, double-blinded, randomized controlled trial to evaluate the efficacy and safety of intravenous administration of high-dose selenium (2,000 µg/day) for preventing CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer who receive paclitaxel, carboplatin, and bevacizumab. A total of 68 patients will be randomly assigned to the experimental and control groups at a 1:1 ratio. As the primary endpoint, the incidence rate of CIPN three months after six cycles of chemotherapy will be compared between the two groups according to the combined criteria of neuropathy using the World Health Organization-CIPN criteria and Common Terminology Criteria for Adverse Events version 5.0. As secondary endpoints, we will compare adverse events, patient-reported quality of life, and requirement of concomitant drugs for reducing CIPN between the two groups. Trial Registration ClinicalTrials.gov Identifier: NCT04201561
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Affiliation(s)
- Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Ga Won Yim
- Department of Obstetrics and Gynecology, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Haerin Paik
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Nara Lee
- Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
| | - Seungmee Lee
- Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Korea
| | - Maria Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
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Hu W, Zhao C, Hu H, Yin S. Food Sources of Selenium and Its Relationship with Chronic Diseases. Nutrients 2021; 13:nu13051739. [PMID: 34065478 PMCID: PMC8160805 DOI: 10.3390/nu13051739] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/18/2021] [Accepted: 05/18/2021] [Indexed: 12/16/2022] Open
Abstract
Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.
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Dehghani M, Shokrgozar N, Ramzi M, Kalani M, Golmoghaddam H, Arandi N. The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with diffuse large B cell lymphoma (DLBCL). Cancer Immunol Immunother 2021; 70:2961-2969. [PMID: 33721055 DOI: 10.1007/s00262-021-02889-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 02/09/2021] [Indexed: 11/30/2022]
Abstract
For many decades, selenium (Se) has been known as a potential anti-cancer agent that can also improve the function of immune cells in a variety of solid tumors. However, there is no report on the role of Se on CD4+ T cell subsets like CD4+CD25+FOXP3+ regulatory T cells (Tregs) in lymphoma patients. In this randomized clinical trial, we investigated the effect of 3-month Se consumption on the frequency of CD4+CD25+FOXP3+ Tregs and the expression of immune checkpoint receptors in thirty-two non-Hodgkin lymphoma (NHL) patients (16 patients with Se (Se+) and 16 without Se (Se-) consumption) with diffuse large B-cell lymphoma (DLBCL) subtype at stable remission. The change in the frequency of Tregs and expression of immune checkpoint receptors including CTLA-4, LAG-3, TIM-3, and PD-L1 genes were evaluated after 3 months in both groups using flow cytometry and SYBR Green Real-time PCR method, respectively. The results showed that the frequency of CD4+CD25+FOXP3+ Tregs and expression of immune checkpoint receptors did not significantly change after 3-month Se consumption in DLBCL patients. However, alteration in the frequency of CD4+CD25-FOXP3+ Treg subsets was positively correlated with change in CTLA-4, LAG-3, and TIM-3 expression in the Se+ group. Three-month Se supplementation did not prevent relapse in Se+ group. Taken together, Se supplementation alone did not affect the frequency of CD4+CD25+FOXP3+ Tregs, expression of checkpoint receptors, and prevention of relapse in DLBCL patients at stable remission phase but might influence the functional properties of other Treg subsets like CD4+CD25-FOXP3+ Tregs.
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Affiliation(s)
- Mehdi Dehghani
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Hematology and Medical Oncology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negin Shokrgozar
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mani Ramzi
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Hematology and Medical Oncology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Kalani
- Department of Immunology, Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Golmoghaddam
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nargess Arandi
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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Ohanian M, Telouk P, Kornblau S, Albarede F, Ruvolo P, Tidwell RSS, Plesa A, Kanagal-Shamanna R, Matera EL, Cortes J, Carson A, Dumontet C. A heavy metal baseline score predicts outcome in acute myeloid leukemia. Am J Hematol 2020; 95:422-434. [PMID: 31944361 DOI: 10.1002/ajh.25731] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 11/26/2019] [Accepted: 01/08/2020] [Indexed: 02/06/2023]
Abstract
Despite abundant epidemiological data linking metals to leukemia and other cancers, baseline values of toxic and essential metals in patients with leukemia and the clinical impact of these metals remain unknown. Thus, we sought to quantify metal values in untreated patients with acute myeloid leukemia (AML) and controls and determine the impact of metal values on AML patients' survival. Serum samples from patients with untreated AML and controls at Hospices Civils de Lyon were analyzed and compared for trace metals and copper isotopic abundance ratios with inductively coupled plasma mass spectrometry. Survival analysis was performed as a function of metal values, and a multi-metal score was developed for patients with AML. Serum samples were collected from 67 patients with untreated AML and 94 controls. Most patients had intermediate-risk cytogenetics (63.1%) without FLT3 internal tandem duplication mutations (75.6%) or NPM1 mutations (68.1%). Most metal values differed significantly between AML and control groups. Patients with lower magnesium and higher cadmium values had the worst survival rates, with only 36% surviving at 6 months (P = .001). The adverse prognostic effect of this combination was maintained on multivariate analysis. Based on this, we developed a novel metal score, which accounts for multiple relative abnormalities in the values of five toxic and five essential metals. Patients with a higher metal score had significantly worse survival, which was maintained on multivariate analysis (P = .03). This baseline metal scoring system was also prognostic when we applied it to a separate population of front-line AML patients.
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Affiliation(s)
- Maro Ohanian
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Philippe Telouk
- Department of Géosciences, École Normal Supérieure de Lyon, Lyon, France
| | - Steven Kornblau
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Francis Albarede
- Department of Géosciences, École Normal Supérieure de Lyon, Lyon, France
| | - Peter Ruvolo
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Rebecca S S Tidwell
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Adriana Plesa
- CRCL, INSERM 1052/CNRS 5286, Hospices Civils de Lyon, Lyon, France
| | - Rashmi Kanagal-Shamanna
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Eva-Laure Matera
- CRCL, INSERM 1052/CNRS 5286, Hospices Civils de Lyon, Lyon, France
| | | | - Arch Carson
- Department of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas
| | - Charles Dumontet
- CRCL, INSERM 1052/CNRS 5286, Hospices Civils de Lyon, Lyon, France
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Knox SJ, Jayachandran P, Keeling CA, Stevens KJ, Sandhu N, Stamps-DeAnda SL, Savic R, Shura L, Buyyounouski MK, Grimes K. Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer. Transl Oncol 2019; 12:1525-1531. [PMID: 31454725 PMCID: PMC6717060 DOI: 10.1016/j.tranon.2019.08.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/02/2019] [Accepted: 08/05/2019] [Indexed: 11/26/2022] Open
Abstract
In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain before and after treatment. The half-life of selenite was 18.5 hours. There were no adverse events attributable to selenite until the 33 mg dose level, at which the primary toxicities were grade 1 GI side effects. One patient treated with 49.5 mg had grade 2 GI toxicity. Although this was not a DLT, it was felt that the highest acceptable dose in this patient population was 33 mg. Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression. Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11-78%. Doses up to 33 mg selenite were well tolerated in combination with RT. A randomized, well controlled study is needed at the 33 mg dose level to determine if selenite results in clinically meaningful improvements in the response to palliative RT.
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Affiliation(s)
- Susan J Knox
- Department of Radiation Oncology, Stanford University, Stanford, CA.
| | - Priya Jayachandran
- Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA
| | | | - Kathryn J Stevens
- Departments of Diagnostic Radiology, Stanford University, Stanford, CA
| | - Navjot Sandhu
- Department of Radiation Oncology, Stanford University, Stanford, CA
| | | | - Rada Savic
- Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA
| | - Lei Shura
- Department of Radiation Oncology, Stanford University, Stanford, CA
| | | | - Kevin Grimes
- Chemical and Systems Biology, Stanford University, Stanford, CA
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Farhood B, Mortezaee K, Motevaseli E, Mirtavoos-Mahyari H, Shabeeb D, Eleojo Musa A, Sanikhani NS, Najafi M, Ahmadi A. Selenium as an adjuvant for modification of radiation response. J Cell Biochem 2019; 120:18559-18571. [PMID: 31190419 DOI: 10.1002/jcb.29171] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 05/20/2019] [Accepted: 05/23/2019] [Indexed: 01/06/2023]
Abstract
Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.
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Affiliation(s)
- Bagher Farhood
- Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Keywan Mortezaee
- Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Elahe Motevaseli
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanifeh Mirtavoos-Mahyari
- Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Dheyauldeen Shabeeb
- Department of Physiology, College of Medicine, University of Misan, Misan, Iraq
| | - Ahmed Eleojo Musa
- Department of Medical Physics, Tehran University of Medical Sciences, Tehran, Iran
| | - Nafiseh Sadat Sanikhani
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amirhossein Ahmadi
- Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
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Evans SO, Jacobson GM, Goodman HJB, Bird S, Jameson MB. Comparative Safety and Pharmacokinetic Evaluation of Three Oral Selenium Compounds in Cancer Patients. Biol Trace Elem Res 2019; 189:395-404. [PMID: 30187284 DOI: 10.1007/s12011-018-1501-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 08/30/2018] [Indexed: 02/07/2023]
Abstract
Selenium (Se) compounds have demonstrated anticancer properties in both preclinical and clinical studies, with particular promise in combination therapy where the optimal form and dose of selenium has yet to be established. In a phase I randomised double-blinded study, the safety, tolerability and pharmacokinetic (PK) profiles of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l-methionine (SLM) were compared in patients with chronic lymphocytic leukaemia and a cohort of patients with solid malignancies. Twenty-four patients received 400 μg of elemental Se as either SS, MSC or SLM for 8 weeks. None of the Se compounds were associated with any significant toxicities, and the total plasma Se AUC of SLM was markedly raised in comparison to MSC and SS. DNA damage assessment revealed negligible genotoxicity, and some minor reductions in lymphocyte counts were observed. At the dose level used, all three Se compounds are well-tolerated and non-genotoxic. Further analyses of the pharmacodynamic effects of Se on healthy and malignant peripheral blood mononuclear cells will inform the future evaluation of higher doses of these Se compounds. The study is registered under the Australian and New Zealand Clinical Trials Registry No: ACTRN12613000118707.
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Affiliation(s)
- Stephen O Evans
- Department of Biological Sciences, University of Waikato, Hamilton, New Zealand
- Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand
| | - Gregory M Jacobson
- Department of Biological Sciences, University of Waikato, Hamilton, New Zealand
| | - Hugh J B Goodman
- Regional Cancer Centre, Waikato Hospital, Private Bag 3200, Hamilton, 3240, New Zealand
| | - Steve Bird
- Department of Biological Sciences, University of Waikato, Hamilton, New Zealand
| | - Michael B Jameson
- Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand.
- Regional Cancer Centre, Waikato Hospital, Private Bag 3200, Hamilton, 3240, New Zealand.
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Lobb RJ, Jacobson GM, Cursons RT, Jameson MB. The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells. Int J Mol Sci 2018; 19:ijms19103167. [PMID: 30326581 PMCID: PMC6214079 DOI: 10.3390/ijms19103167] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/02/2018] [Accepted: 10/11/2018] [Indexed: 01/17/2023] Open
Abstract
Selenium, a trace element with anticancer properties, can reduce harmful toxicities of chemotherapy and radiotherapy without compromising efficacy. However, the dose-response relationship in normal versus malignant human cells is unclear. We evaluated how methylseleninic acid (MSA) modulates the toxicity and efficacy of chemotherapy and radiation on malignant and non-malignant human mononuclear blood cells in vitro. We specifically investigated its effects on endoplasmic reticulum stress induction, intracellular glutathione concentration, DNA damage and viability of peripheral blood mononuclear cells and THP1 monocytic leukaemia cells in response to radiation, cytosine arabinoside or doxorubicin chemotherapy. MSA, at lower concentrations, induced protective responses in normal cells but cytotoxic effects in malignant cells, alone and in conjunction with chemotherapy or radiation. However, in normal cells higher concentrations of MSA were directly toxic and increased the cytotoxicity of radiation but not chemotherapy. In malignant cells higher MSA concentrations were generally more effective in combination with cancer treatments. Thus, optimal MSA concentrations differed between normal and malignant cells and treatments. This work supports clinical reports that selenium can significantly reduce dose-limiting toxicities of anticancer therapies and potentially improve efficacy of anticancer treatments. The optimal selenium compound and dose is not yet determined.
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Affiliation(s)
- Richard J Lobb
- Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
| | - Gregory M Jacobson
- Department of Biological Sciences, University of Waikato, Hamilton 3216, New Zealand.
| | - Ray T Cursons
- Department of Biological Sciences, University of Waikato, Hamilton 3216, New Zealand.
| | - Michael B Jameson
- Oncology Department, Waikato Hospital, Hamilton 3204, New Zealand.
- Waikato Clinical Campus, Faculty of Medical and Health Sciences, University of Auckland, Hamilton 3204, New Zealand.
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13
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Song M, Kumaran MN, Gounder M, Gibbon DG, Nieves-Neira W, Vaidya A, Hellmann M, Kane MP, Buckley B, Shih W, Caffrey PB, Frenkel GD, Rodriguez-Rodriguez L. Phase I trial of selenium plus chemotherapy in gynecologic cancers. Gynecol Oncol 2018; 150:478-486. [PMID: 30068487 DOI: 10.1016/j.ygyno.2018.07.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 06/27/2018] [Accepted: 07/01/2018] [Indexed: 10/28/2022]
Abstract
PURPOSE Preclinical studies performed in our laboratory have shown that high-dose selenium inhibits the development of carboplatin drug resistance in an ovarian cancer mouse xenograft model. Based on these data, as well as the potential serious toxicities of supranutritional doses of selenium, a phase I trial of a combination of selenium/carboplatin/paclitaxel was designed to determine the maximum tolerated dose, safety, and effects of selenium on carboplatin pharmacokinetics in the treatment of chemo-naive women with gynecologic cancers. Correlative studies were performed to identify gene targets of selenium. METHODS Chemo-naïve patients with gynecologic malignancy received selenious acid IV on day 1 followed by carboplatin IV and paclitaxel IV on day 3. A standard 3 + 3 dose-escalating design was used for addition of selenium to standard dose chemotherapy. Concentrations of selenium in plasma and carboplatin in plasma ultrafiltrate were analyzed. RESULTS Forty-five patients were enrolled and 291 treatment cycles were administered. Selenium was administered as selenious acid to 9 cohorts of patients with selenium doses ranging from 50 μg to 5000 μg. Grade 3/4 toxicities included neutropenia (66.7%), febrile neutropenia (2.2%), pain (20.0%), infection (13.3%), neurologic (11.1%), and pulmonary adverse effects (11.1%). The maximum tolerated dose of selenium was not reached. Selenium had no effect on carboplatin pharmacokinetics. Correlative studies showed post-treatment downregulation of RAD51AP1, a protein involved in DNA repair, in both cancer cell lines and patient tumors. CONCLUSION Overall, the addition of selenium to carboplatin/paclitaxel chemotherapy is safe and well tolerated, and does not alter carboplatin pharmacokinetics. A 5000 μg dose of elemental selenium as selenious acid is suggested as the dose to be evaluated in a phase II trial.
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Affiliation(s)
- Mihae Song
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Muthu N Kumaran
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Murugesan Gounder
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Darlene G Gibbon
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Wilberto Nieves-Neira
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Ami Vaidya
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Mira Hellmann
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Michael P Kane
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Brian Buckley
- Rutgers Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854, United States
| | - Weichung Shih
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Paula B Caffrey
- Department of Biological Sciences, Rutgers University, 195 University Avenue, Newark, NJ 07102, United States; Department of Biological and Environmental Sciences, 250 University Avenue, California University of PA, California, PA 15419, United States
| | - Gerald D Frenkel
- Department of Biological Sciences, Rutgers University, 195 University Avenue, Newark, NJ 07102, United States
| | - Lorna Rodriguez-Rodriguez
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States; Rutgers-Robert Wood Johnson Medical School, Department of Obstetrics, Gynecology and Reproductive Sciences, 125 Paterson Street, New Brunswick, NJ 08901, United States.
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Selenium in Radiation Oncology-15 Years of Experiences in Germany. Nutrients 2018; 10:nu10040483. [PMID: 29652817 PMCID: PMC5946268 DOI: 10.3390/nu10040483] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 04/05/2018] [Accepted: 04/11/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction: Se measurement and supplementation in radiation oncology is a controversial issue. The German Working Group Trace Elements and Electrolytes in Oncology (AKTE) has conducted a number of studies on this issue, which are summarized in this review. Strategies have been tested and developed, aiming to stratify the patients with a potential need for supplemental Se and how best to monitor Se supplementation with respect to health effects and risks. Methods: We analyzed blood and tissue Se-levels of different tumor patients (n = 512). Two randomized phase III clinical studies were conducted for testing a potential radioprotective effect of supplemental Se during radiation therapy in patients with uterine cancer (n = 81) and head and neck tumor patients (n = 39). Results: A relative Se deficit in whole blood or serum was detected in the majority of tumor patients (carcinomas of the uterus, head and neck, lung, rectal or prostate cancer). In prostate cancer, tissue Se concentrations were relatively elevated in the carcinoma centre as compared to the surrounding compartment or as compared to tumor samples from patients with benign prostatic hyperplasia. Adjuvant Se supplementation successfully corrected Se-deficiency in the patients analyzed and decreased radiotherapy-induced diarrhea in a randomized study of radiotherapy patients with carcinomas of the uterus. Survival data imply that Se supplementation did not interfere with radiation success. Some positive effects of supplemental Se in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy were noted in a second randomized trial in patients with head and neck cancer. We have not observed any adverse effects of supplemental Se in our studies. Conclusions: Se supplementation yielded promising results concerning radioprotection in tumor patients and should be considered as a promising adjuvant treatment option in subjects with a relative Se deficit.
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Gröber U, Holzhauer P, Kisters K, Holick MF, Adamietz IA. Micronutrients in Oncological Intervention. Nutrients 2016; 8:163. [PMID: 26985904 PMCID: PMC4808891 DOI: 10.3390/nu8030163] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 02/16/2016] [Accepted: 02/24/2016] [Indexed: 12/14/2022] Open
Abstract
Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Depending on the type of malignancy and the gender 30%-90% of the cancer patients supplement their diets with antioxidant and immuno-stabilizing micronutrients, such as selenium, vitamin C, and vitamin D, often without the knowledge of the treating physician. From the oncological viewpoint, there are justifiable concerns that dietary supplements decrease the effectiveness of chemotherapy and radiotherapy. Recent studies, however, have provided increasing evidence that treatment is tolerated better-with an increase in patient compliance and a lower rate of treatment discontinuations-when micronutrients, such as selenium, are added as appropriate to the patient's medication. Nutritional supplementation tailored to an individual's background diet, genetics, tumor histology, and treatments may yield benefits in subsets of patients. Clinicians should have an open dialogue with patients about nutritional supplements. Supplement advice needs to be individualized and come from a credible source, and it is best communicated by the physician.
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Affiliation(s)
- Uwe Gröber
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
| | - Peter Holzhauer
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
- Interdisziplinäres onkologisches Zentrum (IOZ), München, Nußbaumstrasse 12, München 80336, Germany.
- Klinik Bad Trissl, Innere Medizin II-Onkologie und Komplementärmedizin, Oberaudorf 83080, Germany.
| | - Klaus Kisters
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
- St. Anna Hospital, Medizinische Klinik I, Herne, Hospitalstrasse 19, Herne 44649, Germany.
| | - Michael F Holick
- Boston University Medical Center, 85 East Newton Street M-1033, Boston, MA 02118, USA.
| | - Irenäus A Adamietz
- Klinik für Strahlentherapie und Radio-Onkologie, Ruhr Universität Bochum (RUB), Hölkeskampring 40, Herne 44625, Germany.
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Mix M, Singh AK, Tills M, Dibaj S, Groman A, Jaggernauth W, Rustum Y, Jameson MB. Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck. World J Clin Oncol 2015; 6:166-173. [PMID: 26468453 PMCID: PMC4600191 DOI: 10.5306/wjco.v6.i5.166] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 05/09/2015] [Accepted: 06/01/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether selenomethionine (SLM) reduces mucositis incidence in patients with head and neck squamous cell cancer (HNSCC) undergoing concurrent chemoradiation (CRT). METHODS In this multi-institutional, randomized, double-blind phase II trial, patients with Stage III or IV HNSCC received SLM 3600 μg/m(2) or placebo twice daily for 7 d prior to CRT, once daily during CRT, and daily for 3 wk following CRT. CRT consisted of 70 Gy at 2 Gy per fraction with cisplatin 100 mg/m(2) IV on days 1, 22, and 43. RESULTS Eighteen patients were randomized, 10 received SLM, and there were no differences in baseline factors. There was no difference in mucositis or patient-reported side effects between groups. There was no difference in overall or relapse-free survival at 12 mo. CONCLUSION Addition of SLM to CRT for HNSCC was well-tolerated but did not lower the incidence of severe mucositis or improve quality of life or survival outcomes.
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17
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Mix M, Ramnath N, Gomez J, Groot CD, Rajan S, Dibaj S, Tan W, Rustum Y, Jameson MB, Singh AK. Effects of selenomethionine on acute toxicities from concurrent chemoradiation for inoperable stage III non-small cell lung cancer. World J Clin Oncol 2015; 6:156-165. [PMID: 26468452 PMCID: PMC4600190 DOI: 10.5306/wjco.v6.i5.156] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/06/2015] [Accepted: 06/18/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To prospectively determine the safety and tolerability of oral L-selenomethionine (SLM) with concurrent chemoradiation (CCRT) for Stage III non-small cell lung cancer (NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use. METHODS Sixteen patients with stage III NSCLC were accrued to this single arm, phase II study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly IV paclitaxel 50 mg/m(2) followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients (19%), pneumonitis in 0, leukopenia in 2 (12.5%), and anemia in 1 (6%); the latter two were significantly reduced when compared to the protocol-stated expected rate of 35% (P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo (95%CI: 3.3-21.5). CONCLUSION There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.
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18
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Misra S, Boylan M, Selvam A, Spallholz JE, Björnstedt M. Redox-active selenium compounds--from toxicity and cell death to cancer treatment. Nutrients 2015; 7:3536-56. [PMID: 25984742 PMCID: PMC4446766 DOI: 10.3390/nu7053536] [Citation(s) in RCA: 216] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Revised: 04/24/2015] [Accepted: 05/05/2015] [Indexed: 11/29/2022] Open
Abstract
Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.
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Affiliation(s)
- Sougat Misra
- Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
| | - Mallory Boylan
- Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, P.O. Box 41270, Lubbock, TX 79409-1270, USA.
| | - Arun Selvam
- Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
| | - Julian E Spallholz
- Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, P.O. Box 41270, Lubbock, TX 79409-1270, USA.
| | - Mikael Björnstedt
- Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
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Muecke R, Micke O, Schomburg L, Buentzel J, Adamietz IA, Huebner J. Serum selenium deficiency in patients with hematological malignancies: is a supplementation study mandatory? Acta Haematol 2014; 132:256-8. [PMID: 24903215 DOI: 10.1159/000360903] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 02/26/2014] [Indexed: 11/19/2022]
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20
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Gröber U, Mücke R, Adamietz I, Holzhauer P, Kisters K, Büntzel J, Micke O. Komplementärer Einsatz von Antioxidanzien und Mikronährstoffen in der Onkologie. DER ONKOLOGE 2013. [DOI: 10.1007/s00761-012-2385-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Fritz H, Kennedy D, Fergusson D, Fernandes R, Cooley K, Seely A, Sagar S, Wong R, Seely D. Selenium and lung cancer: a systematic review and meta analysis. PLoS One 2011; 6:e26259. [PMID: 22073154 PMCID: PMC3208545 DOI: 10.1371/journal.pone.0026259] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2011] [Accepted: 09/23/2011] [Indexed: 11/29/2022] Open
Abstract
Background Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies. Methods and Findings Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (≥121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61–1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70–3.24); and all-cause-death, OR 0.93 (95%CI 0.79–1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy. Conclusions Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context.
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Affiliation(s)
- Heidi Fritz
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
| | - Deborah Kennedy
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, The University of Toronto, Toronto, Ontario, Canada
| | - Dean Fergusson
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Rochelle Fernandes
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Laboratory Medicine and Pathobiology (LMP), The University of Toronto, Toronto, Ontario, Canada
| | - Kieran Cooley
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, The University of Toronto, Toronto, Ontario, Canada
| | - Andrew Seely
- Department of Surgery, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Stephen Sagar
- Juravinski Cancer Centre and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Raimond Wong
- Juravinski Cancer Centre and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Dugald Seely
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- * E-mail:
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22
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Asfour IA, El-kholy NM, Ayoub MS, Ahmed MB, Bakarman AA. Selenium and glutathione peroxidase status in adult Egyptian patients with acute myeloid leukemia. Biol Trace Elem Res 2009; 132:85-92. [PMID: 19458925 DOI: 10.1007/s12011-009-8401-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2009] [Accepted: 04/30/2009] [Indexed: 11/28/2022]
Abstract
This study was undertaken to evaluate selenium (Se) and glutathione peroxidase (GPX) status in patients with newly diagnosed acute myeloid leukemia (AML) before and after induction therapy. Twenty-five patients with newly diagnosed AML and 15 healthy age- and sex-matched control subjects were included in this study. Serum Se level by the graphite furnace atomic absorption spectrometric technique and GPX activity by an adaptation of Beutler method was performed for the patients before and after receiving the induction therapy. Serum Se level was significantly lower in patients with AML versus control subjects (63.1 ± 8.8 versus 77 ± 8.8 μg/L before therapy with a P value <0.01 and 69 ± 6.8 versus 77 ± 8.8 μg/L after therapy with a P value <0.01).GPX activity was significantly lower in patients with AML versus control subjects (1.6 ± 0.4 versus 3.4 ± 0.7 μ/g protein pretreatment with a P value <0.01 and 1.9 ± 0.6 versus 3.4 ± 0.7 μ/g protein post induction treatment with P value <0.01).Se level and GPX activity significantly increased in AML patients after treatment. Patients who accomplished complete remission after induction harbored significantly higher Se levels than resistant patients before and after treatment. There was no significant correlation between serum Se level and GPX activity. Decreased Se level and reduced GPX activity in AML patients support the association of carcinogenesis and subnormal Se states.
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Affiliation(s)
- Inas A Asfour
- Clinical Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Ain Shams University, Cairo, Egypt
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Asfour IA, El-Tehewi MM, Ahmed MH, Abdel-Sattar MA, Moustafa NN, Hegab HM, Fathey OM. High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin's lymphoma. Biol Trace Elem Res 2009; 127:200-10. [PMID: 18953506 DOI: 10.1007/s12011-008-8240-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2008] [Accepted: 09/15/2008] [Indexed: 12/11/2022]
Abstract
The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the apoptosis of lymphoma cells in patients with non-Hodgkin's lymphoma (NHL). Forty patients with newly diagnosed NHL were randomly divided into two groups. Group I received standard chemotherapy, whereas group II received adjuvant sodium selenite 0.2 mg kg(-1) day(-1) for 7 days in addition to chemotherapy. Flow cytometry was used for monitoring of lymphoma cells apoptosis at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant increase in percentage of apoptotic lymphoma cells after therapy in group II (78.9 +/- 13.3% versus 58.9 +/- 18.9%, p < 0.05). In addition, patients who received sodium selenite treatment demonstrated statistically significant increase in percentage of reduction of cervical and axillary lymphadenopathy, decrease in splenic size, and decreased percentage of bone marrow infiltration. Also, we found a statistically significant decrease in cardiac ejection fraction (CEF) in group I and no reduction in CEF in patients who received sodium selenite 'group II', denoting the cardioprotective effect of selenium. It is concluded that sodium selenite administration at the dosage and duration chosen has synergistic effect to chemotherapy in inducing apoptosis and, consequently, could improve clinical outcome.
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Affiliation(s)
- Inas A Asfour
- Department of Internal Medicine and Clinical Hematology, Clinical Hematology Unit, Ain-Shams Faculty of Medicine, Ain-Shams University, Cairo, Egypt
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