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Liu CY, Lai YR, Cheng PS, Yu WW, Wang RC, Shen WL, Chuang SS. Merkel cell carcinoma in Taiwan: a subset is chronic arsenicism-related, and the Merkel cell polyomavirus-negative cases are pathologically distinct from virus-related cases with a poorer outcome. Pathology 2025; 57:311-319. [PMID: 39939227 DOI: 10.1016/j.pathol.2024.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 09/05/2024] [Accepted: 09/27/2024] [Indexed: 02/14/2025]
Abstract
Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma of the skin, more frequent in the West than in the East. The pathogenesis is complex, with Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) light being reported to play important roles. In this retrospective study of MCC cases from Taiwan, we analysed the prognostic significance of pathological features and the status of MCPyV and retinoblastoma (Rb) expression. We retrospectively collected MCC cases from five hospitals in Taiwan from 1994 to 2022. We examined the clinical and pathological features, performed immunohistochemical studies for the large T antigen of MCPyV and Rb, and reviewed medical records from electronic data. Disease-specific survival was estimated by using the Kaplan-Meier estimate and compared between subgroups using log-rank test. The clinical and pathological features and the immunohistochemical profiles between subgroups were compared using the Fisher exact test for categorical variables. The 38 patients were mostly (71%) males, with a median age of 79. In 22 (58%) patients, the tumours occurred in sun-exposed areas. Clinically, five (13%) patients had chronic arsenicism. Histopathologically, 11 (29%) cases showed combined tumours (MCC with squamous cell carcinoma or Bowen disease/squamous carcinoma in situ). Seventeen (45%) cases were positive for MCPyV, whereas all combined tumours were negative. MCPyV-negative MCC displayed distinctive pathological features, including epidermal changes, presence of an intraepidermal MCC component, linear or single-file growth pattern, and pleomorphic nuclei. Immunohistochemically, 59% (22/37) MCC cases showed complete loss of Rb protein expression, more frequent in MCPyV-unrelated (p<0.001) and combined (p=0.014) cases, but without statistical significance among patients with chronic arsenicism, sun exposure, or disease-specific survival. MCPyV-negative cases exhibited a shorter disease-specific survival than MCPyV-positive cases (median overall survival 13 months vs not reached; p=0.041). MCPyV-negative or combined MCCs were associated with a higher disease-specific mortality and poorer prognosis. MCCs occurring in sun-shielded sites, MCPyV-negativity, and combined tumours correlated with a higher disease-specific mortality and a poorer prognosis by multivariable Cox proportional hazard model. The occurrence of MCCs with arsenic exposure was also identified. Our study showed that MCPyV-negative MCC cases in Taiwan exhibited distinctive pathological features and a poorer outcome than MCPyV-related cases. We also confirmed an association of chronic arsenicism with MCC, which might be considered as the third pathogenetic factor after MCPyV and UV light. Further studies including epidemiological and genetic investigations are warranted to elucidate the pathogenesis of MCC in Taiwan, particularly the significance of chronic arsenicism.
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Affiliation(s)
- Chih-Yi Liu
- Division of Pathology, Sijhih Cathay General Hospital, New Taipei City, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; School of Medicine, National Tsing Hua University, Hsinchu City, Taiwan
| | - Yun-Ru Lai
- Department of Anatomical Pathology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Pai-Shan Cheng
- Department of Dermatology, Chi Mei Medical Center, Tainan, Taiwan
| | - Wei-Wen Yu
- Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ren Ching Wang
- Department of Pathology, China Medical University Hospital, Taichung, Taiwan; Department of Nursing, Hung Kuang University, Taichung, Taiwan
| | - Wan-Lin Shen
- Department of Pathology, Lio Ying Chi-Mei Hospital, Tainan, Taiwan
| | - Shih-Sung Chuang
- Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
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Wang L, Qiu N, Tong S, Yu Y, Xi S, Wang F. Matrine Suppresses Arsenic-Induced Malignant Transformation of SV-HUC-1 Cells via NOX2. Int J Mol Sci 2024; 25:8878. [PMID: 39201564 PMCID: PMC11354282 DOI: 10.3390/ijms25168878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/11/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
Arsenic (As) has been classified as a carcinogen for humans. There is abundant evidence indicating that arsenic increases the risk of bladder cancer among human populations. However, the underlying mechanisms have yet to be fully understood and elucidated. NADPH oxidases (NOXs) are the main enzymes for ROS production in the body. NADPH Oxidase 2 (NOX2), which is the most distinctive and ubiquitously expressed subunit of NOXs, can promote the formation and development of tumors. The utilization of NOX2 as a therapeutic target has been proposed to modulate diseases resulting from the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Matrine has been reported to exhibit various pharmacological effects, including anti-inflammatory, antifibrotic, antitumor, and analgesic properties. However, it has not been reported whether matrine can inhibit malignant transformation induced by arsenic in uroepithelial cells through NOX2. We have conducted a series of experiments using both a sub-chronic NaAsO2 exposure rat model and a long-term NaAsO2 exposure cell model. Our findings indicate that arsenic significantly increases cell proliferation, migration, and angiogenesis in vivo and in vitro. Arsenic exposure resulted in an upregulation of reactive oxygen species (ROS), NOX2, and NLRP3 inflammasome expression. Remarkably, both in vivo and in vitro, the administration of matrine demonstrated a significant improvement in the detrimental impact of arsenic on bladder epithelial cells. This was evidenced by the downregulation of proliferation, migration, and angiogenesis, as well as the expression of the NOX2 and NLRP3 inflammasomes. Collectively, these findings indicate that matrine possesses the ability to reduce NOX2 levels and inhibit the transformation of bladder epithelial cells.
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Affiliation(s)
- Lanfei Wang
- Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, China
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China
- Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang 110122, China
| | - Nianfeng Qiu
- Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, China
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China
- Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang 110122, China
| | - Suyuan Tong
- Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, China
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China
- Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang 110122, China
| | - Yan Yu
- Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, China
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China
- Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang 110122, China
| | - Shuhua Xi
- Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, China
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China
- Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang 110122, China
| | - Fei Wang
- Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang 110122, China
- Department of Environmental Health, School of Public Health, China Medical University, Shenyang 110122, China
- Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, China Medical University, Shenyang 110122, China
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Jasmine F, Argos M, Khamkevych Y, Islam T, Rakibuz-Zaman M, Shahriar M, Shea CR, Ahsan H, Kibriya MG. Molecular Profiling and the Interaction of Somatic Mutations with Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) in a Population Exposed to Arsenic. Cells 2024; 13:1056. [PMID: 38920684 PMCID: PMC11201393 DOI: 10.3390/cells13121056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 05/31/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024] Open
Abstract
Exposure to inorganic arsenic (As) is recognized as a risk factor for non-melanoma skin cancer (NMSC). We followed up with 7000 adults for 6 years who were exposed to As. During follow-up, 2.2% of the males and 1.3% of the females developed basal cell carcinoma (BCC), while 0.4% of the male and 0.2% of the female participants developed squamous cell carcinoma (SCC). Using a panel of more than 400 cancer-related genes, we detected somatic mutations (SMs) in the first 32 NMSC samples (BCC = 26 and SCC = 6) by comparing paired (tissue-blood) samples from the same individual and then comparing them to the SM in healthy skin tissue from 16 participants. We identified (a) a list of NMSC-associated SMs, (b) SMs present in both NMSC and healthy skin, and (c) SMs found only in healthy skin. We also demonstrate that the presence of non-synonymous SMs in the top mutated genes (like PTCH1, NOTCH1, SYNE1, PKHD1 in BCC and TP53 in SCC) significantly affects the magnitude of differential expressions of major genes and gene pathways (basal cell carcinoma pathways, NOTCH signaling, IL-17 signaling, p53 signaling, Wnt signaling pathway). These findings may help select groups of patients for targeted therapy, like hedgehog signaling inhibitors, IL17 inhibitors, etc., in the future.
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Affiliation(s)
- Farzana Jasmine
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
| | - Maria Argos
- Epidemiology & Biostatistics, Global Health, University of Illinois Chicago, Chicago, IL 60612, USA
| | - Yuliia Khamkevych
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
| | - Tariqul Islam
- UChicago Research Bangladesh (URB), University of Chicago, Dhaka 1230, Bangladesh
| | | | - Mohammad Shahriar
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
| | - Christopher R. Shea
- Division of Dermatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Habibul Ahsan
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
- Department of Public Health Sciences, Biological Science Division, University of Chicago, Chicago, IL 60637, USA
| | - Muhammad G. Kibriya
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
- Department of Public Health Sciences, Biological Science Division, University of Chicago, Chicago, IL 60637, USA
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Reyna-Rodríguez IL, Garza-Davila VF, Ocampo-Candiani J, Chavez-Alvarez S. Is Merkel cell carcinoma associated with high and chronic arsenic dose exposure? An Bras Dermatol 2024; 99:292-294. [PMID: 38135559 PMCID: PMC10943291 DOI: 10.1016/j.abd.2022.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 06/14/2022] [Accepted: 06/17/2022] [Indexed: 12/24/2023] Open
Affiliation(s)
- Irving Llibran Reyna-Rodríguez
- Dermatology Department, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario "Dr. José E. Gonzalez", Monterrey, Mexico
| | - Valeria F Garza-Davila
- Dermatology Department, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario "Dr. José E. Gonzalez", Monterrey, Mexico
| | - Jorge Ocampo-Candiani
- Dermatology Department, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario "Dr. José E. Gonzalez", Monterrey, Mexico
| | - Sonia Chavez-Alvarez
- Dermatology Department, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario "Dr. José E. Gonzalez", Monterrey, Mexico.
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EFSA Panel on Contaminants in the Food Chain (CONTAM), Schrenk D, Bignami M, Bodin L, Chipman JK, del Mazo J, Grasl‐Kraupp B, Hogstrand C, Hoogenboom L(R, Leblanc J, Nebbia CS, Nielsen E, Ntzani E, Petersen A, Sand S, Vleminckx C, Wallace H, Barregård L, Benford D, Broberg K, Dogliotti E, Fletcher T, Rylander L, Abrahantes JC, Gómez Ruiz JÁ, Steinkellner H, Tauriainen T, Schwerdtle T. Update of the risk assessment of inorganic arsenic in food. EFSA J 2024; 22:e8488. [PMID: 38239496 PMCID: PMC10794945 DOI: 10.2903/j.efsa.2024.8488] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2024] Open
Abstract
The European Commission asked EFSA to update its 2009 risk assessment on arsenic in food carrying out a hazard assessment of inorganic arsenic (iAs) and using the revised exposure assessment issued by EFSA in 2021. Epidemiological studies show that the chronic intake of iAs via diet and/or drinking water is associated with increased risk of several adverse outcomes including cancers of the skin, bladder and lung. The CONTAM Panel used the benchmark dose lower confidence limit based on a benchmark response (BMR) of 5% (relative increase of the background incidence after adjustment for confounders, BMDL05) of 0.06 μg iAs/kg bw per day obtained from a study on skin cancer as a Reference Point (RP). Inorganic As is a genotoxic carcinogen with additional epigenetic effects and the CONTAM Panel applied a margin of exposure (MOE) approach for the risk characterisation. In adults, the MOEs are low (range between 2 and 0.4 for mean consumers and between 0.9 and 0.2 at the 95th percentile exposure, respectively) and as such raise a health concern despite the uncertainties.
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Ivy N, Mukherjee T, Bhattacharya S, Ghosh A, Sharma P. Arsenic contamination in groundwater and food chain with mitigation options in Bengal delta with special reference to Bangladesh. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2023; 45:1261-1287. [PMID: 35841495 DOI: 10.1007/s10653-022-01330-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 06/27/2022] [Indexed: 06/15/2023]
Abstract
Bangladesh, situated in Bengal delta, is one of the worst affected countries by arsenic contamination in groundwater. Most of the people in the country are dependent on groundwater for domestic and irrigation purposes. Currently, 61 districts out of 64 districts of Bangladesh are affected by arsenic contamination. Drinking arsenic contaminated groundwater is the main pathway of arsenic exposure in the population. Additionally, the use of arsenic-contaminated groundwater for irrigation purpose in crop fields in Bangladesh has elevated arsenic concentration in surface soil and in the plants. In many arsenic-affected countries, including Bangladesh, rice is reported to be one of the significant sources of arsenic contamination. This review discussed scenario of groundwater arsenic contamination and transmission of arsenic through food chain in Bangladesh. The study further highlighted the human health perspectives of arsenic exposure in Bangladesh with possible mitigation and remediation options employed in the country.
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Affiliation(s)
- Nishita Ivy
- School of Ecology and Environment Studies, Nalanda University, Rajgir, Nalanda, Bihar, India
| | | | - Sayan Bhattacharya
- School of Ecology and Environment Studies, Nalanda University, Rajgir, Nalanda, Bihar, India
| | - Abhrajyoti Ghosh
- Department of Biochemistry, Bose Institute, Kolkata, West Bengal, India
| | - Prabhakar Sharma
- School of Ecology and Environment Studies, Nalanda University, Rajgir, Nalanda, Bihar, India.
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Tang GT, Elakis J, Scardamaglia L. Cutaneous manifestations and treatment of arsenic toxicity: A systematic review. SKIN HEALTH AND DISEASE 2023. [PMID: 37538334 PMCID: PMC10395639 DOI: 10.1002/ski2.231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/28/2023]
Abstract
Cutaneous and systemic signs of acute and chronic arsenic poisoning may be vague. Thus, an awareness of these signs is crucial to prevent late or missed diagnoses. This is especially true in non-endemic countries where individuals may present decades after exposure, or may still be ingesting arsenic via a non-classical exposure. Existing literature emphasizes several well-known cutaneous presentations of arsenic toxicity while ignoring the complete clinical spectrum, including several rare tumours of relevance to the dermatologist. This study aims to review the existing literature on dermatological presentations of arsenic toxicity and their management in adults.
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Nail AN, Ferragut Cardoso AP, Montero LK, States JC. miRNAs and arsenic-induced carcinogenesis. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2023; 96:203-240. [PMID: 36858773 PMCID: PMC10184182 DOI: 10.1016/bs.apha.2022.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Arsenic-induced carcinogenesis is a worldwide health problem. Identifying the molecular mechanisms responsible for the induction of arsenic-induced cancers is important for developing treatment strategies. MicroRNA (miRNA) dysregulation is known to affect development and progression of human cancer. Several studies have identified an association between altered miRNA expression in cancers from individuals chronically exposed to arsenic and in cell models for arsenic-induced carcinogenesis. This chapter provides a comprehensive review for miRNA dysregulation in arsenic-induced cancer.
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Affiliation(s)
- Alexandra N Nail
- Department of Pharmacology and Toxicology, Center for Integrative Environmental Health Science, University of Louisville, Louisville, KY, United States
| | - Ana P Ferragut Cardoso
- Department of Pharmacology and Toxicology, Center for Integrative Environmental Health Science, University of Louisville, Louisville, KY, United States
| | - Lakyn K Montero
- Department of Pharmacology and Toxicology, Center for Integrative Environmental Health Science, University of Louisville, Louisville, KY, United States
| | - J Christopher States
- Department of Pharmacology and Toxicology, Center for Integrative Environmental Health Science, University of Louisville, Louisville, KY, United States.
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Deng LJ, Jia M, Luo SY, Li FZ, Fang S. Expression of Hedgehog Signaling Pathway Proteins in Basal Cell Carcinoma: Clinicopathologic Study. Clin Cosmet Investig Dermatol 2022; 15:2353-2361. [PMCID: PMC9637365 DOI: 10.2147/ccid.s389551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 10/21/2022] [Indexed: 11/07/2022]
Affiliation(s)
- Li-Jia Deng
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Meng Jia
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Si-Yu Luo
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Feng-Zeng Li
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Sheng Fang
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
- Correspondence: Sheng Fang, Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email
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Speer RM, Zhou X, Volk LB, Liu KJ, Hudson LG. Arsenic and cancer: Evidence and mechanisms. ADVANCES IN PHARMACOLOGY (SAN DIEGO, CALIF.) 2022; 96:151-202. [PMID: 36858772 PMCID: PMC10860672 DOI: 10.1016/bs.apha.2022.08.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Arsenic is a potent carcinogen and poses a significant health concern worldwide. Exposure occurs through ingestion of drinking water and contaminated foods and through inhalation due to pollution. Epidemiological evidence shows arsenic induces cancers of the skin, lung, liver, and bladder among other tissues. While studies in animal and cell culture models support arsenic as a carcinogen, the mechanisms of arsenic carcinogenesis are not fully understood. Arsenic carcinogenesis is a complex process due its ability to be metabolized and because of the many cellular pathways it targets in the cell. Arsenic metabolism and the multiple forms of arsenic play distinct roles in its toxicity and contribute differently to carcinogenic endpoints, and thus must be considered. Arsenic generates reactive oxygen species increasing oxidative stress and damaging DNA and other macromolecules. Concurrently, arsenic inhibits DNA repair, modifies epigenetic regulation of gene expression, and targets protein function due its ability to replace zinc in select proteins. While these mechanisms contribute to arsenic carcinogenesis, there remain significant gaps in understanding the complex nature of arsenic cancers. In the future improving models available for arsenic cancer research and the use of arsenic induced human tumors will bridge some of these gaps in understanding arsenic driven cancers.
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Affiliation(s)
- Rachel M Speer
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United States
| | - Xixi Zhou
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United States
| | - Lindsay B Volk
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United States
| | - Ke Jian Liu
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United States; Stony Brook Cancer Center, Renaissance School of Medicine, State University of New York Stony Brook, Stony Brook, NY, United States.
| | - Laurie G Hudson
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United States
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A Comprehensive Transcriptomic Analysis of Arsenic-Induced Bladder Carcinogenesis. Cells 2022; 11:cells11152435. [PMID: 35954277 PMCID: PMC9367831 DOI: 10.3390/cells11152435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/03/2022] [Accepted: 08/04/2022] [Indexed: 11/21/2022] Open
Abstract
Arsenic (sodium arsenite: NaAsO2) is a potent carcinogen and a known risk factor for the onset of bladder carcinogenesis. The molecular mechanisms that govern arsenic-induced bladder carcinogenesis remain unclear. We used a physiological concentration of NaAsO2 (250 nM: 33 µg/L) for the malignant transformation of normal bladder epithelial cells (TRT-HU1), exposed for over 12 months. The increased proliferation and colony-forming abilities of arsenic-exposed cells were seen after arsenic exposure from 4 months onwards. Differential gene expression (DEG) analysis revealed that a total of 1558 and 1943 (padj < 0.05) genes were deregulated in 6-month and 12-month arsenic-exposed TRT-HU1 cells. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that cell proliferation and survival pathways, such as the MAPK, PI3K/AKT, and Hippo signaling pathways, were significantly altered. Pathway analysis revealed that the enrichment of stem cell activators such as ALDH1A1, HNF1b, MAL, NR1H4, and CDH1 (p < 0.001) was significantly induced during the transformation compared to respective vehicle controls. Further, these results were validated by qPCR analysis, which corroborated the transcriptomic analysis. Overall, the results suggested that stem cell activators may play a significant role in facilitating the arsenic-exposed cells to gain a survival advantage, enabling the healthy epithelial cells to reprogram into a cancer stem cell phenotype, leading to malignant transformation.
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12
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Zakhem GA, Pulavarty AN, Lester JC, Stevenson ML. Skin Cancer in People of Color: A Systematic Review. Am J Clin Dermatol 2022; 23:137-151. [PMID: 34902111 DOI: 10.1007/s40257-021-00662-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND People of African, Asian, Hispanic or Latino, Pacific Islander, and Native Indian descent are considered people of color by the Skin of Color Society (SOCS). OBJECTIVES In this study, we assess incidence, risk factors, clinical characteristics, histopathology, treatment, and survival for skin malignancies in people of color as defined by the SOCS, by systematically reviewing the literature. METHODS An electronic literature search of the PubMed, EMBASE, and MEDLINE databases was performed. Articles published from 1 January 1990 through 12 December 2020 were included in the search. RESULTS We identified 2666 publications potentially meeting the study criteria. Titles and abstracts of these studies were reviewed and 2353 were excluded. The full text of 313 articles were evaluated and 251 were included in this review. CONCLUSION Differences in incidence, patterns, treatment, and survival exist among people of color for cutaneous malignancies. Further research and initiatives are needed to account for and mitigate these differences.
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Affiliation(s)
- George A Zakhem
- The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 222 East 41st Street, 24th Floor, New York, NY, 10017, USA
| | - Akshay N Pulavarty
- The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 222 East 41st Street, 24th Floor, New York, NY, 10017, USA
| | - Jenna C Lester
- University of California San Francisco, San Francisco, CA, USA
| | - Mary L Stevenson
- The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 222 East 41st Street, 24th Floor, New York, NY, 10017, USA.
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13
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Diba F, Khan MZH, Uddin SZ, Istiaq A, Shuvo MSR, Ul Alam ASMR, Hossain MA, Sultana M. Bioaccumulation and detoxification of trivalent arsenic by Achromobacter xylosoxidans BHW-15 and electrochemical detection of its transformation efficiency. Sci Rep 2021; 11:21312. [PMID: 34716390 PMCID: PMC8556249 DOI: 10.1038/s41598-021-00745-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 10/15/2021] [Indexed: 12/02/2022] Open
Abstract
Arsenotrophic bacteria play an essential role in lowering arsenic contamination by converting toxic arsenite [As (III)] to less toxic and less bio-accumulative arsenate [As (V)]. The current study focused on the qualitative and electrocatalytic detection of the arsenite oxidation potential of an arsenite-oxidizing bacteria A. xylosoxidans BHW-15 (retrieved from As-contaminated tube well water), which could significantly contribute to arsenic detoxification, accumulation, and immobilization while also providing a scientific foundation for future electrochemical sensor development. The minimum inhibitory concentration (MIC) value for the bacteria was 15 mM As (III). Scanning Electron Microscopy (SEM) investigation validated its intracellular As uptake capacity and demonstrated a substantial association with the MIC value. During the stationary phase, the strain’s As (III) transformation efficiency was 0.0224 mM/h. Molecular analysis by real-time qPCR showed arsenite oxidase (aioA) gene expression increased 1.6-fold in the presence of As (III) compared to the untreated cells. The immobilized whole-cell also showed As (III) conversion up to 18 days. To analyze the electrochemical oxidation in water, we developed a modified GCE/P-Arg/ErGO-AuNPs electrode, which successfully sensed and quantified conversion of As (III) into As (V) by accepting electrons; implying a functional As oxidase enzyme activity in the cells. To the best of our knowledge, this is the first report on the electrochemical observation of the As-transformation mechanism with Achromobactersp. Furthermore, the current work highlighted that our isolate might be employed as a promising candidate for arsenic bioremediation, and information acquired from this study may be helpful to open a new window for the development of a cost-effective, eco-friendly biosensor for arsenic species detection in the future.
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Affiliation(s)
- Farzana Diba
- Department of Microbiology, University of Dhaka, Dhaka, 1000, Bangladesh.,Institute of Tissue Banking and Biomaterial Research (ITBBR), Atomic Energy Research Establishment (AERE), Savar, Dhaka, 1349, Bangladesh
| | - Md Zaved Hossain Khan
- Department of Chemical Engineering, Jashore University of Science and Technology, Jashore, 7408, Bangladesh
| | - Salman Zahir Uddin
- Department of Microbiology, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Arif Istiaq
- Department of Stem Cell Biology, Faculty of Arts and Sciences, Kyushu University, Fukuoka, Japan.,Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Md Sadikur Rahman Shuvo
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - A S M Rubayet Ul Alam
- Department of Microbiology, Jashore University of Science and Technology, Jashore, 7408, Bangladesh
| | - M Anwar Hossain
- Department of Microbiology, University of Dhaka, Dhaka, 1000, Bangladesh.,Jashore University of Science and Technology, Jashore, 7408, Bangladesh
| | - Munawar Sultana
- Department of Microbiology, University of Dhaka, Dhaka, 1000, Bangladesh.
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14
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Nexus between Water Security Framework and Public Health: A Comprehensive Scientific Review. WATER 2021. [DOI: 10.3390/w13101365] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Water scarcity, together with the projected impacts of water stress worldwide, has led to a rapid increase in research on measuring water security. However, water security has been conceptualized under different perspectives, including various aspects and dimensions. Since public health is also an integral part of water security, it is necessary to understand how health has been incorporated as a dimension in the existing water security frameworks. While supply–demand and governance narratives dominated several popular water security frameworks, studies that are specifically designed for public health purposes are generally lacking. This research aims to address this gap, firstly by assessing the multiple thematic dimensions of water security frameworks in scientific disclosure; and secondly by looking into the public health dimensions and evaluating their importance and integration in the existing water security frameworks. For this, a systematic review of the Scopus database was undertaken using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A detailed review analysis of 77 relevant papers was performed. The result shows that 11 distinct dimensions have been used to design the existing water security framework. Although public health aspects were mentioned in 51% of the papers, direct health impacts were considered only by 18%, and indirect health impacts or mediators were considered by 33% of the papers. Among direct health impacts, diarrhea is the most prevalent one considered for developing a water security framework. Among different indirect or mediating factors, poor accessibility and availability of water resources in terms of time and distance is a big determinant for causing mental illnesses, such as stress or anxiety, which are being considered when framing water security framework, particularly in developing nations. Water quantity is more of a common issue for both developed and developing countries, water quality and mismanagement of water supply-related infrastructure is the main concern for developing nations, which proved to be the biggest hurdle for achieving water security. It is also necessary to consider how people treat and consume the water available to them. The result of this study sheds light on existing gaps for different water security frameworks and provides policy-relevant guidelines for its betterment. Also, it stressed that a more wide and holistic approach must be considered when framing a water security framework to result in sustainable water management and human well-being.
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15
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Bedaiwi A, Wysong A, Rogan EG, Clarey D, Arcari CM. Arsenic Exposure and Melanoma Among US Adults Aged 20 or Older, 2003-2016. Public Health Rep 2021; 137:548-556. [PMID: 33971104 PMCID: PMC9109530 DOI: 10.1177/00333549211008886] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
OBJECTIVES Chronic exposure to arsenic has been reported as a risk factor for nonmelanoma skin cancer, notably squamous cell carcinoma. However, current knowledge is limited about the association between arsenic exposure and melanoma. Our objectives were to (1) measure the association between total urinary arsenic levels and melanoma compared with nonmelanoma skin cancer and no cancer and (2) analyze the association between water source and melanoma and nonmelanoma skin cancer. METHODS We collected cross-sectional data from the 2003-2016 cycles of the National Health and Nutrition Examination Survey. We conducted univariate and multivariate logistic regressions. To evaluate the possible association of skin cancer with source of tap water, we calculated odds ratios for participants with melanoma and nonmelanoma skin cancer, compared with participants with no cancer. RESULTS White race, higher education, higher socioeconomic status, and smoking history were associated with melanoma and nonmelanoma skin cancer in the full study population. After adjusting for age and race/ethnicity, the adjusted odds ratio of participants with >50 μg/L of total urinary arsenic for melanoma or nonmelanoma skin cancer was 1.87 (95% CI, 0.58-6.05) and 2.23 (95% CI, 1.12-4.45) times higher compared with no cancer, respectively. Participants with nonmelanoma skin cancer had 2.06 increased odds of reporting a nonmunicipal water source compared with participants without cancer. CONCLUSIONS We did not find a relationship between the incidence of melanoma and exposure to arsenic among US adults. Nonmunicipal water sources were associated with nonmelanoma skin cancer and should be further investigated.
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Affiliation(s)
- Ahmed Bedaiwi
- Department of Epidemiology, College of Public Health, University
of Nebraska Medical Center, Omaha, NE, USA
| | - Ashley Wysong
- Department of Dermatology, University of Nebraska Medical Center,
Omaha, NE, USA
| | - Eleanor G. Rogan
- Department of Environmental, Agricultural & Occupational Health,
College of Public Health, University of Nebraska Medical Center, Omaha, NE,
USA
| | - Dillon Clarey
- Department of Dermatology, University of Nebraska Medical Center,
Omaha, NE, USA
| | - Christine M. Arcari
- Department of Epidemiology, College of Public Health, University
of Nebraska Medical Center, Omaha, NE, USA,Christine M. Arcari, PhD, MPH, University
of Nebraska Medical Center, College of Public Health, Department of
Epidemiology, 984355 Nebraska Medical Center, Omaha, NE 68198-4355, USA;
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16
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Li CL, Chen YC, Yang KC, Chen LW. Different histopathologic profiles and outcomes between sun-exposed BCC and non-sun-exposed BCC. Sci Rep 2020; 10:7387. [PMID: 32355183 PMCID: PMC7193595 DOI: 10.1038/s41598-020-64391-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 01/09/2020] [Indexed: 11/09/2022] Open
Abstract
Asian population is a low-risk group for basal cell carcinoma (BCC) and there is little data available in this setting. Sun-exposed BCC (SEBCC) may possess a different pathogenic mechanism from non-sun-exposed BCC (NSEBCC). To compare the histopathological profiles and outcomes between SEBCC and NSEBCC, and to assess the risk factors for tumor recurrences. Retrospective cohort study on 372 patients with pathologically diagnosed BCC from January 1, 1990 to August 31, 2017. Data were derived from a single medical center in Taiwan. SEBCC presented with higher Clark level and more high-risk factors for recurrence than NSEBCC. Nodular, micronodular, infiltrating/mixed infiltrating, basosquamous, and adenoid types were predominant in SEBCC, as superficial type in NSEBCC. Risk factors for recurrence included infiltrating/mixed-infiltrating subtypes and synchronous basosquamous cell carcinoma. No recurrence events were observed in NSEBCC. Our study showed an acceptable recurrence rate (4.2%) of the whole population after excision even under a smaller surgical margin width than suggested by current guidelines. SEBCC had a higher recurrence rate with a significantly different tumor characteristic from NSEBCC and a greater tumor depth than NSEBCC. A wider surgical margin in SEBCC than NSEBCC is suggested.
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Affiliation(s)
- Chia-Lun Li
- Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yu-Ching Chen
- Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Kuo-Chung Yang
- Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Lee-Wei Chen
- Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. .,Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. .,Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan.
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17
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Reis J, Spencer PS. Decision-making under uncertainty in environmental health policy: new approaches. Environ Health Prev Med 2019; 24:57. [PMID: 31521129 PMCID: PMC6745059 DOI: 10.1186/s12199-019-0813-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 08/27/2019] [Indexed: 01/30/2023] Open
Abstract
Decision-making in environmental health policy is a complex procedure even in well-known conditions. Thus, in the case of uncertainty, decision-making becomes a hurdle race. We address scientific uncertainty, methods to reduce uncertainty, biomedical doubt and science communication, and the role of stakeholders, activists, lobbies and media that together influence policy decisions. We also consider the major responsibility and role of the medico-scientific community in this process. This community can and should teach the principle of scientific uncertainty to all stakeholders, advise policy-makers and underline the ethical issues, considering that our brains are not only the deposit of our humanity but also the route to environmental health and societal harmony.
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Affiliation(s)
- Jacques Reis
- Faculté de Médecine, University of Strasbourg, 4 Rue Kirschleger, 67000, Strasbourg, France.
- Association RISE, 3 rue du loir, 67205, Oberhausbergen, France.
| | - Peter S Spencer
- Oregon Institute of Occupational Health Sciences and School of Medicine (Neurology), Oregon Health & Science University, Portland, OR, 97201, USA
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