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Zhang S, Zhang XY, Zheng XC, Ye XL, Huang P, Liu WT, Jiang HJ. Downregulation of MGAT3 Promotes Benzo[ a]pyrene-Mediated Lung Carcinogenesis by Regulating Cell Invasion and Migration Activity. ACS OMEGA 2025; 10:17404-17415. [PMID: 40352502 PMCID: PMC12060035 DOI: 10.1021/acsomega.4c10682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 04/13/2025] [Accepted: 04/17/2025] [Indexed: 05/14/2025]
Abstract
Environmental chemical carcinogens are major factors in the induction of lung cancer, with benzo[a]pyrene (B[a]P) being one of the most widespread and highly carcinogenic among them. Although studies have reported that B[a]P exerts its carcinogenic effects by causing mutations, inducing cytotoxicity, and inhibiting DNA synthesis, the early molecular regulatory events and mechanisms involved in B[a]P-induced tumor initiation remain unclear. This study found that the MGAT3 gene was significantly downregulated in B[a]P-induced mouse lung tumorigenesis, suggesting its important tumor-suppressive function. Further investigation revealed that suppression of MGAT3 expression promoted the invasion and migration abilities of lung cancer cells, while overexpression of MGAT3 in these cells inhibited these effects. Western blot analysis also showed that MGAT3 regulated the expression of epithelial-mesenchymal transition markers, thereby affecting the motility of lung cancer cells. Xenograft assay also confirmed the inhibitory effect of MGAT3 overexpression on tumor proliferation. Analysis of lung cancer tissue expression further validated that MGAT3 is significantly downregulated in lung cancer tissues, and this decrease in expression is associated with a poor prognosis in lung cancer patients. Our research indicates that the suppression of MGAT3 expression and its downstream regulatory molecules plays a crucial role in lung cancer development induced by environmental chemical carcinogens.
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Affiliation(s)
- Su Zhang
- Center
for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated
People’s Hospital, Hangzhou Medical College, Shangtang Road No. 158, Hangzhou 310014, Zhejiang, China
| | - Xia-Yan Zhang
- Department
of Pharmacy, the Fifth Affiliated Hospital
of Wenzhou Medical University, Kuocang Road No. 289, Lishui 323000, Zhejiang, China
| | - Xiao-Chun Zheng
- Center
for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated
People’s Hospital, Hangzhou Medical College, Shangtang Road No. 158, Hangzhou 310014, Zhejiang, China
| | - Xiao-Lan Ye
- Center
for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated
People’s Hospital, Hangzhou Medical College, Shangtang Road No. 158, Hangzhou 310014, Zhejiang, China
| | - Ping Huang
- Center
for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated
People’s Hospital, Hangzhou Medical College, Shangtang Road No. 158, Hangzhou 310014, Zhejiang, China
| | - Wen-tong Liu
- School
of Pharmacy, Hangzhou Normal University, Binwen Road No. 481, Hangzhou 311121, Zhejiang, China
| | - Hong-juan Jiang
- Center
for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated
People’s Hospital, Hangzhou Medical College, Shangtang Road No. 158, Hangzhou 310014, Zhejiang, China
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Minacori M, Fiorini S, Perugini M, Iannetta A, Meschiari G, Chichiarelli S, Altieri F, Natali PG, Eufemi M. AhR and STAT3: A Dangerous Duo in Chemical Carcinogenesis. Int J Mol Sci 2025; 26:2744. [PMID: 40141386 PMCID: PMC11943011 DOI: 10.3390/ijms26062744] [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: 02/19/2025] [Revised: 03/13/2025] [Accepted: 03/15/2025] [Indexed: 03/28/2025] Open
Abstract
Human chemical carcinogenesis is a multistage process where chemicals or their metabolites cause irreversible changes in normal cell physiology, eventually leading to uncontrolled proliferation, transforming a normal cell into a cancerous one. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation, and immune responses. Its aberrant activation triggers tumor progression by promoting the expression of oncogenic genes; thus, STAT3 is classified as an oncoprotein. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that responds to a wide variety of chemicals, including carcinogens like dioxins, inducing genes associated with detoxification, proliferation, and immune regulation. Recent reports show that AhR plays a critical role in cancer development and maintenance. AhR may interact with signaling pathways, like the STAT3 pathway, which mediates the carcinogenic effects of several pollutants. Various chemical agents, such as industrial waste and hydrocarbon compounds, can alter the expression or signaling activity of AhR and STAT3 pathways, leading to different types of cancers. Understanding the complex STAT3-AhR network in the regulation of chemical carcinogenesis could open new avenues for cancer prevention or treatment, particularly in personalized medicine, aiming to improve life expectancy and achieving a complete cure.
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Affiliation(s)
- Marco Minacori
- Department of Biochemical Science “A. Rossi Fanelli”, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (M.M.); (S.F.); (G.M.); (S.C.); (F.A.); (M.E.)
- Department of Bioscience and Agro-Food and Environmental Technology, University of Teramo, Campus “Aurelio Saliceti”, Via R. Balzarini 1, 64100 Teramo, Italy; (M.P.); (A.I.)
| | - Sara Fiorini
- Department of Biochemical Science “A. Rossi Fanelli”, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (M.M.); (S.F.); (G.M.); (S.C.); (F.A.); (M.E.)
| | - Monia Perugini
- Department of Bioscience and Agro-Food and Environmental Technology, University of Teramo, Campus “Aurelio Saliceti”, Via R. Balzarini 1, 64100 Teramo, Italy; (M.P.); (A.I.)
| | - Annamaria Iannetta
- Department of Bioscience and Agro-Food and Environmental Technology, University of Teramo, Campus “Aurelio Saliceti”, Via R. Balzarini 1, 64100 Teramo, Italy; (M.P.); (A.I.)
| | - Giorgia Meschiari
- Department of Biochemical Science “A. Rossi Fanelli”, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (M.M.); (S.F.); (G.M.); (S.C.); (F.A.); (M.E.)
| | - Silvia Chichiarelli
- Department of Biochemical Science “A. Rossi Fanelli”, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (M.M.); (S.F.); (G.M.); (S.C.); (F.A.); (M.E.)
| | - Fabio Altieri
- Department of Biochemical Science “A. Rossi Fanelli”, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (M.M.); (S.F.); (G.M.); (S.C.); (F.A.); (M.E.)
| | - Pier Giorgio Natali
- Collegium Ramazzini, Castello di Bentivoglio, Via Saliceto, 3, 40010 Bologna, Italy
| | - Margherita Eufemi
- Department of Biochemical Science “A. Rossi Fanelli”, Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (M.M.); (S.F.); (G.M.); (S.C.); (F.A.); (M.E.)
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Liu J, Guo B, Liu Q, Zhu G, Wang Y, Wang N, Yang Y, Fu S. Cellular Senescence: A Bridge Between Diabetes and Microangiopathy. Biomolecules 2024; 14:1361. [PMID: 39595537 PMCID: PMC11591988 DOI: 10.3390/biom14111361] [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: 08/28/2024] [Revised: 10/21/2024] [Accepted: 10/24/2024] [Indexed: 11/28/2024] Open
Abstract
Cellular senescence is a state of permanent cell cycle arrest and plays an important role in many vascular lesions. This study found that the cells of diabetic patients have more characteristics of senescence, which may cause microvascular complications. Cell senescence, as one of the common fates of cells, links microangiopathy and diabetes. Cell senescence in a high-glucose environment can partially elucidate the mechanism of diabetic microangiopathy, and various types of cellular senescence induced by it can promote the progression of diabetic microangiopathy. Still, the molecular mechanism of microangiopathy-related cellular senescence has not yet been clearly studied. Building on recent research evidence, we herein summarize the fundamental mechanisms underlying the development of cellular senescence in various microangiopathies associated with diabetes. We gradually explain how cellular senescence serves as a key driver of diabetic microangiopathy. At the same time, the treatment of basic senescence mechanisms such as cellular senescence may have a great impact on the pathogenesis of the disease, may be more effective in preventing the development of diabetic microangiopathy, and may provide new ideas for the clinical treatment and prognosis of diabetic microangiopathy.
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Affiliation(s)
- Jiahui Liu
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (J.L.); (B.G.); (Q.L.); (G.Z.); (Y.W.); (N.W.); (Y.Y.)
| | - Buyu Guo
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (J.L.); (B.G.); (Q.L.); (G.Z.); (Y.W.); (N.W.); (Y.Y.)
| | - Qianqian Liu
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (J.L.); (B.G.); (Q.L.); (G.Z.); (Y.W.); (N.W.); (Y.Y.)
| | - Guomao Zhu
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (J.L.); (B.G.); (Q.L.); (G.Z.); (Y.W.); (N.W.); (Y.Y.)
| | - Yaqi Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (J.L.); (B.G.); (Q.L.); (G.Z.); (Y.W.); (N.W.); (Y.Y.)
| | - Na Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (J.L.); (B.G.); (Q.L.); (G.Z.); (Y.W.); (N.W.); (Y.Y.)
| | - Yichen Yang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China; (J.L.); (B.G.); (Q.L.); (G.Z.); (Y.W.); (N.W.); (Y.Y.)
| | - Songbo Fu
- Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou 730000, China
- Gansu Province Clinical Research Center for Endocrine Disease, Lanzhou 730000, China
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Rodriguez VI, Mammadova J, Permuth JB, Luthra A, Pena L, Friedman M, Dam A, Cappelle S, Malafa MP, Hallmon C, Miranda C, Mok SRS. Elevated Urinary Levels of Fungal and Environmental Toxins in Patients with Pancreatic Ductal Adenocarcinoma. J Gastrointest Cancer 2024; 56:4. [PMID: 39419859 PMCID: PMC11486816 DOI: 10.1007/s12029-024-01125-4] [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] [Accepted: 09/22/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Risk factors for pancreatic ductal adenocarcinoma (PDAC) include tobacco/alcohol abuse, genetic predisposition, insulin resistance, and pancreatic cysts. Despite these well-established risk factors and the screening of high-risk individuals, some people still develop PDAC. This study aims to explore a potential risk factor for PDAC by investigating the association between fungal toxins (FT) and environmental toxins (ET) and the disease. We predicted that individuals with PDAC would have higher levels of these toxins compared to healthy controls. The rationale behind this hypothesis is that exposure to FT and ET might contribute to the development of PDAC by elevating cancer risk. METHODS A pilot retrospective cohort study was conducted at Moffitt Cancer Center from 2022 to 2023. This study compared FT and ET levels, demographic data, and PDAC features between subjects with PDAC and healthy controls. RESULTS Forty subjects were enrolled in the study, comprising 20 with pancreatic ductal adenocarcinoma (PDAC) and 20 healthy controls. Baseline demographics were similar between the two groups. Among the PDAC subjects, the most common tumor location was the head of the pancreas (55%); 30% had locally advanced disease, 45% were borderline resectable, and 10% had metastatic disease. Compared to the controls, subjects with PDAC had significantly higher levels of fungal toxins (FTs) including ochratoxin, gliotoxin, and citrinin (p < 0.05). Additionally, PDAC patients had significantly elevated levels of environmental toxins (ETs) such as methyl tert-butyl ether (MTBE), xylene, styrene, acrylonitrile, perchlorate, diphenyl phosphate, bromopropane, organophosphates, acrolein, tiglylglycine, and diethylphosphate (p < 0.05). CONCLUSION Our study demonstrates that subjects with PDAC, without other risk factors, have higher FT and ET levels than controls. Further studies are needed to evaluate whether ET and FT exposure can be clinically utilized as a risk factor for PDAC development.
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Affiliation(s)
- Vanessa I Rodriguez
- Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Jamila Mammadova
- Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jennifer B Permuth
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
| | - Anjuli Luthra
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Luis Pena
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Mark Friedman
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Aamir Dam
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Saraswathi Cappelle
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Mokenge P Malafa
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Candice Hallmon
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Cassandra Miranda
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Shaffer R S Mok
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
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He Z, Pan L, Xu Q, Zhou Y, Li P, Li Z, Wang Q. Studies on the characteristics of polycyclic aromatic hydrocarbons accumulation in lipids and the disturbance of lipid metabolism of Ruditapes philippinarum. CHEMOSPHERE 2024; 364:143304. [PMID: 39251158 DOI: 10.1016/j.chemosphere.2024.143304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 09/04/2024] [Accepted: 09/06/2024] [Indexed: 09/11/2024]
Abstract
Polycyclic aromatic hydrocarbons (PAHs) constitute a class of persistent organic pollutants with strong lipophilicity, which readily accumulate within organisms and have the effect to induce disorders in lipid metabolism. The present study aimed to investigate the accumulation localization and pattern of PAHs in Ruditapes philippinarum, and to reveal the association between PAHs and lipids metabolism. The 21-day exposure experiment was conducted using a mixture of phenanthrene, chrysene, and benzo[a]pyrene (the proportion is 1:1:1) at concentrations of 0.4 μg/L, 2 μg/L, and 10 μg/L. The tissue distribution of PAHs indicated that the digestive gland was the primary site of PAHs accumulation. Meanwhile, fluorescence colocalization suggested that PAHs primarily accumulated within the lipid droplets of digestive gland cells. This study further determined the transcriptomic and lipidomic profiles of the digestive gland to analyze the key genes involved in disrupted lipid metabolism and the major lipids affected. Lipidomic analysis identified the key differential metabolites as triglycerides (TGs). Furthermore, TGs were upregulated in the digestive gland had a total carbon atom number of 50-64 and a total number of 3-9 double bonds in the acyl side chains. Biochemical analysis experiments and oil red O stained frozen sections confirmed that the content of TGs steadily increased in various tissues during the experiment, leading to an elevated digestive gland index. Changes of lipid metabolism associated genes expression level also indicated that the synthesis of lipid in digestive gland were up-regulated while the decomposition was down-regulated. This study is the first to demonstrate the cellular localization of PAHs accumulation in bivalves and confirms the pattern of variation in TGs, providing new insights into the mechanisms of PAHs bioaccumulation and lipid metabolism disruption.
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Affiliation(s)
- Zhiheng He
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China
| | - Luqing Pan
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China.
| | - Qiuhong Xu
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China
| | - Yueyao Zhou
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China
| | - Pengfei Li
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China
| | - Zeyuan Li
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China
| | - Qiaoqiao Wang
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, PR China
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Janmeda P, Jain D, Chaudhary P, Meena M, Singh D. A systematic review on multipotent carcinogenic agent, N-nitrosodiethylamine (NDEA), its major risk assessment, and precautions. J Appl Toxicol 2024; 44:1108-1128. [PMID: 38212177 DOI: 10.1002/jat.4574] [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: 10/22/2023] [Revised: 12/01/2023] [Accepted: 12/09/2023] [Indexed: 01/13/2024]
Abstract
The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.
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Affiliation(s)
- Pracheta Janmeda
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan, India
| | - Divya Jain
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan, India
| | - Priya Chaudhary
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, Rajasthan, India
| | - Mukesh Meena
- Laboratory of Phytopathology and Microbial Biotechnology, Department of Botany, Mohanlal Sukhadia University, Udaipur, Rajasthan, India
| | - Devendra Singh
- Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan, India
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Castillo-Sanchez R, Garcia-Hernandez A, Torres-Alamilla P, Cortes-Reynosa P, Candanedo-Gonzales F, Salazar EP. Benzo[a]pyrene promotes an epithelial-to-mesenchymal transition process in MCF10A cells and mammary tumor growth and brain metastasis in female mice. Mol Carcinog 2024; 63:1319-1333. [PMID: 38629425 DOI: 10.1002/mc.23726] [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: 09/21/2023] [Revised: 02/21/2024] [Accepted: 03/28/2024] [Indexed: 06/12/2024]
Abstract
Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA-MB-231 and MCF-7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.
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Affiliation(s)
- Rocio Castillo-Sanchez
- Departamento de Biologia Celular, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Ciudad de Mexico, Mexico
| | - Alejandra Garcia-Hernandez
- Departamento de Biologia Celular, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Ciudad de Mexico, Mexico
| | - Pablo Torres-Alamilla
- Departamento de Biologia Celular, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Ciudad de Mexico, Mexico
| | - Pedro Cortes-Reynosa
- Departamento de Biologia Celular, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Ciudad de Mexico, Mexico
| | - Fernando Candanedo-Gonzales
- Departamento de Patologia, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Mexico
| | - Eduardo Perez Salazar
- Departamento de Biologia Celular, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Ciudad de Mexico, Mexico
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Wismayer R, Kiwanuka J, Wabinga H, Odida M. Dietary risk factors for colorectal cancer in Uganda: a case-control study. BMC Nutr 2024; 10:88. [PMID: 38898481 PMCID: PMC11186163 DOI: 10.1186/s40795-024-00894-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 06/05/2024] [Indexed: 06/21/2024] Open
Abstract
INTRODUCTION Low-income countries in East Africa have a lower incidence of colorectal cancer (CRC) than high-income countries; however, the incidence has steadily increased in the last few decades. In Uganda, the extent to which genetic and environmental factors, particularly dietary factors, contribute to the aetiology of CRC is unclear. Therefore, the objective of our study was to determine the relationship between dietary factors and CRC in Uganda. METHODS We conducted a case-control study and recruited 128 cases and 256 controls, matched for age (± 5 years) and sex. Data regarding the frequency of consumption of the dietary factors were obtained from all the participants using an interview-based questionnaire. The potential dietary risk factors and protective factors evaluated included the type and frequency of meat consumed and the type and frequency of high-fibre foods consumed. The frequency was either 4 or more times/week, 2-3 times/week, once/week or never. Conditional logistic regression analyses were used to determine the odds ratios associated with the different risk and protective factors. RESULTS The median age (IQR) for the case participants was 55.5 (43-67.5) years, and that of the control participants was 54 (42-65) years. The male-to-female ratio was 1:1 for all the participants. Factors significantly associated with CRC cases included:- the consumption of boiled beef 2-3 times/week (aOR:3.24; 95% CI: 1.08-9.69; p < 0.035). Consumption of high-fibre foods, including:- millet for ≥ 4 times/week (aOR: 0.23; 95% CI: 0.09-0.62; p = 0.003)), spinach for ≥ 4 times/week (aOR:0.32; 95% CI: 0.11-0.97; p = 0.043), and potatoes 2-3 times/week (aOR: 0.30; 95% CI: 0.09-0.97; p = 0.044), were protective against CRC. Boiled cassava showed a tendency to reduce the likelihood of CRC when consumed ≥ 4 times/week (aOR:0.38; 95% CI: 0.12-1.18) however this did not reach statistical significance (p = 0.093). CONCLUSIONS The consumption of boiled beef increases the risk of CRC, while the intake of high-fibre foods may reduce the risk of CRC among Ugandans. We recommend nutritional educational programmes to increase public awareness regarding the protective role of a high-fibre diet and to limit the intake of cooked meat in our Ugandan population.
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Affiliation(s)
- Richard Wismayer
- Department of Surgery, Masaka Regional Referral Hospital, Masaka, Uganda.
- Department of Surgery, Faculty of Health Sciences, Equator University for Science and Technology, Masaka, Uganda.
- Department of Surgery, Faculty of Health Sciences, Habib Medical School, IUIU University, Kampala, Uganda.
- Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
| | - Julius Kiwanuka
- Department of Epidemiology and Biostatistics, School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Henry Wabinga
- Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Michael Odida
- Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
- Department of Pathology, Faculty of Medicine, Gulu University, Gulu, Uganda
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Zhou Z, Nan Y, Li X, Ma P, Du Y, Chen G, Ning N, Huang S, Gu Q, Li W, Yuan L. Hawthorn with "homology of medicine and food": a review of anticancer effects and mechanisms. Front Pharmacol 2024; 15:1384189. [PMID: 38915462 PMCID: PMC11194443 DOI: 10.3389/fphar.2024.1384189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 04/29/2024] [Indexed: 06/26/2024] Open
Abstract
Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn's anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.
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Affiliation(s)
- Ziying Zhou
- Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan, China
- College of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Yi Nan
- Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan, China
| | - Xiangyang Li
- College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, China
| | - Ping Ma
- Department of Pharmacy, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Yuhua Du
- College of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Guoqing Chen
- College of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Na Ning
- College of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Shicong Huang
- College of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Qian Gu
- College of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Weiqiang Li
- Department of Chinese Medical Gastrointestinal, The Affiliated TCM Hospital of Ningxia Medical University, Wuzhong, China
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical University, Yinchuan, China
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10
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Martins C, de Oliveira Galvão MF, Costa PM, Dreij K. Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2024; 108:104453. [PMID: 38642625 DOI: 10.1016/j.etap.2024.104453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/17/2024] [Indexed: 04/22/2024]
Abstract
Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.
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Affiliation(s)
- Carla Martins
- Associate Laboratory i4HB Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University of Lisbon, Caparica 2819 516, Portugal; UCIBIO Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University of Lisbon, Caparica 2819 516, Portugal; Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden.
| | - Marcos Felipe de Oliveira Galvão
- Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden
| | - Pedro M Costa
- Associate Laboratory i4HB Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University of Lisbon, Caparica 2819 516, Portugal; UCIBIO Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University of Lisbon, Caparica 2819 516, Portugal
| | - Kristian Dreij
- Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden.
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11
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Wu J, Gao F, Meng R, Li H, Mao Z, Xiao Y, Pu Q, Du M, Zhang Z, Shao Q, Zheng R, Wang M. Single-cell and multi-omics analyses highlight cancer-associated fibroblasts-induced immune evasion and epithelial mesenchymal transition for smoking bladder cancer. Toxicology 2024; 504:153782. [PMID: 38493947 DOI: 10.1016/j.tox.2024.153782] [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: 02/02/2024] [Revised: 03/10/2024] [Accepted: 03/15/2024] [Indexed: 03/19/2024]
Abstract
Tobacco carcinogens are recognized as critical hazard factors for bladder tumorigenesis, affecting the prognosis of patients through aromatic amines components. However, the specific function of tobacco carcinogens and systematic assessment models in the prognosis of bladder cancer remains poorly elucidated. We retrieved bladder cancer specific tobacco carcinogens-related genes from Comparative Toxicogenomic Database, our Nanjing Bladder Cancer cohort and TCGA database. Gene×Gene interaction method was utilized to establish a prognostic signature. Integrative assessment of immunogenomics, tumor microenvironments and single-cell RNA-sequencing were performed to illustrate the internal relations of key events from different levels. Finally, we comprehensively identified 33 essential tobacco carcinogens-related genes to construct a novel prognostic signature, and found that high-risk patients were characterized by significantly worse overall survival (HR=2.25; Plog-rank < 0.01). Single-cell RNA-sequencing and multi-omics analysis demonstrated that cancer-associated fibroblasts mediated the crosstalk between epithelial-mesenchymal transition progression and immune evasion. Moreover, an adverse outcome pathway framework was established to facilitate our understanding to the tobacco carcinogens-triggered bladder tumorigenesis. Our study systematically provided immune microenvironmental alternations for smoking-induced adverse survival outcomes in bladder cancer. These findings facilitated the integrative multi-omics insights into risk assessment and toxic mechanisms of tobacco carcinogens.
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Affiliation(s)
- Jiajin Wu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Fang Gao
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Rui Meng
- Department of Urology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Huiqin Li
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Zhenguang Mao
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Yanping Xiao
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Qiuyi Pu
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Mulong Du
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Zhengdong Zhang
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Qiang Shao
- Department of Urology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
| | - Rui Zheng
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
| | - Meilin Wang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Urology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
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12
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Nagaoka M, Sakai Y, Nakajima M, Fukami T. Role of carboxylesterase and arylacetamide deacetylase in drug metabolism, physiology, and pathology. Biochem Pharmacol 2024; 223:116128. [PMID: 38492781 DOI: 10.1016/j.bcp.2024.116128] [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: 12/01/2023] [Revised: 01/20/2024] [Accepted: 03/12/2024] [Indexed: 03/18/2024]
Abstract
Carboxylesterases (CES1 and CES2) and arylacetamide deacetylase (AADAC), which are expressed primarily in the liver and/or gastrointestinal tract, hydrolyze drugs containing ester and amide bonds in their chemical structure. These enzymes often catalyze the conversion of prodrugs, including the COVID-19 drugs remdesivir and molnupiravir, to their pharmacologically active forms. Information on the substrate specificity and inhibitory properties of these enzymes, which would be useful for drug development and toxicity avoidance, has accumulated. Recently,in vitroandin vivostudies have shown that these enzymes are involved not only in drug hydrolysis but also in lipid metabolism. CES1 and CES2 are capable of hydrolyzing triacylglycerol, and the deletion of their orthologous genes in mice has been associated with impaired lipid metabolism and hepatic steatosis. Adeno-associated virus-mediated human CES overexpression decreases hepatic triacylglycerol levels and increases fatty acid oxidation in mice. It has also been shown that overexpression of CES enzymes or AADAC in cultured cells suppresses the intracellular accumulation of triacylglycerol. Recent reports indicate that AADAC can be up- or downregulated in tumors of various organs, and its varied expression is associated with poor prognosis in patients with cancer. Thus, CES and AADAC not only determine drug efficacy and toxicity but are also involved in pathophysiology. This review summarizes recent findings on the roles of CES and AADAC in drug metabolism, physiology, and pathology.
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Affiliation(s)
- Mai Nagaoka
- Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan
| | - Yoshiyuki Sakai
- Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan
| | - Miki Nakajima
- Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan
| | - Tatsuki Fukami
- Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
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13
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Marumure J, Simbanegavi TT, Makuvara Z, Karidzagundi R, Alufasi R, Goredema M, Gufe C, Chaukura N, Halabowski D, Gwenzi W. Emerging organic contaminants in drinking water systems: Human intake, emerging health risks, and future research directions. CHEMOSPHERE 2024; 356:141699. [PMID: 38554874 DOI: 10.1016/j.chemosphere.2024.141699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 02/24/2024] [Accepted: 03/11/2024] [Indexed: 04/02/2024]
Abstract
Few earlier reviews on emerging organic contaminants (EOCs) in drinking water systems (DWS) focused on their detection, behaviour, removal and fate. Reviews on multiple exposure pathways, human intake estimates, and health risks including toxicokinetics, and toxicodynamics of EOCs in DWS are scarce. This review presents recent advances in human intake and health risks of EOCs in DWS. First, an overview of the evidence showing that DWS harbours a wide range of EOCs is presented. Multiple human exposure to EOCs occurs via ingestion of drinking water and beverages, inhalation and dermal pathways are discussed. A potential novel exposure may occur via the intravenous route in dialysis fluids. Analysis of global data on pharmaceutical pollution in rivers showed that the cumulative concentrations (μg L-1) of pharmaceuticals (mean ± standard error of the mean) were statistically more than two times significantly higher (p = 0.011) in South America (11.68 ± 5.29), Asia (9.97 ± 3.33), Africa (9.48 ± 2.81) and East Europe (8.09 ± 4.35) than in high-income regions (2.58 ± 0.48). Maximum cumulative concentrations of pharmaceuticals (μg L-1) decreased in the order; Asia (70.7) had the highest value followed by South America (68.8), Africa (51.3), East Europe (32.0) and high-income regions (17.1) had the least concentration. The corresponding human intake via ingestion of untreated river water was also significantly higher in low- and middle-income regions than in their high-income counterparts. For each region, the daily intake of pharmaceuticals was highest in infants, followed by children and then adults. A critique of the human health hazards, including toxicokinetics and toxicodynamics of EOCs is presented. Emerging health hazards of EOCs in DWS include; (1) long-term latent and intergenerational effects, (2) the interactive health effects of EOC mixtures, (3) the challenges of multifinality and equifinality, and (4) the Developmental Origins of Health and Disease hypothesis. Finally, research needs on human health hazards of EOCs in DWS are presented.
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Affiliation(s)
- Jerikias Marumure
- Department of Physics, Geography and Environmental Science, School of Natural Sciences, Great Zimbabwe University, Masvingo, Zimbabwe; Department of Life and Consumer Sciences, School of Agriculture and Life Sciences, College of Agriculture and Environmental Sciences, University of South Africa, South Africa
| | - Tinoziva T Simbanegavi
- Department of Soil Science and Environment, Faculty of Agriculture, Environment, and Food Systems, University of Zimbabwe, P. O. Box MP 167, Mount Pleasant, Harare, Zimbabwe
| | - Zakio Makuvara
- Department of Physics, Geography and Environmental Science, School of Natural Sciences, Great Zimbabwe University, Masvingo, Zimbabwe; Department of Life and Consumer Sciences, School of Agriculture and Life Sciences, College of Agriculture and Environmental Sciences, University of South Africa, South Africa
| | - Rangarirayi Karidzagundi
- Materials Development Unit, Zimbabwe Open University, P.O. Box MP1119 Mount Pleasant, Harare, Zimbabwe
| | - Richwell Alufasi
- Biological Sciences Department, Bindura University of Science Education, 741 Chimurenga Road, Off Trojan Road, P. Bag 1020, Bindura, Zimbabwe
| | - Marvelous Goredema
- Biological Sciences Department, Bindura University of Science Education, 741 Chimurenga Road, Off Trojan Road, P. Bag 1020, Bindura, Zimbabwe
| | - Claudious Gufe
- Department of Veterinary Technical Services, Central Veterinary Laboratories, Box CY55, 18A Borrowdale Road, Harare, Zimbabwe
| | - Nhamo Chaukura
- Department of Physical and Earth Sciences, Sol Plaatje University, Kimberley, 8301, South Africa
| | - Dariusz Halabowski
- University of Lodz, Faculty of Biology and Environmental Protection, Department of Ecology and Vertebrate Zoology, Lodz, Poland
| | - Willis Gwenzi
- Currently: Biosystems and Environmental Engineering Research Group, 380, New Adylin, Westgate, Harare, Zimbabwe; Formerly: Alexander von Humboldt Fellow & Guest/Visiting Professor, Grassland Science and Renewable Plant Resources, Faculty of Organic Agricultural Sciences, Universität Kassel, Steinstraße 19, D-37213, Witzenhausen, Germany; Formerly: Alexander von Humboldt Fellow and Guest Professor, Leibniz-Institut für Agrartechnik und Bioökonomie e.V. (ATB), Max-Eyth-Allee 100, D-14469 Potsdam, Germany.
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14
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Li M, Tang S, Peng X, Sharma G, Yin S, Hao Z, Li J, Shen J, Dai C. Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions. Antioxidants (Basel) 2024; 13:452. [PMID: 38671900 PMCID: PMC11047733 DOI: 10.3390/antiox13040452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 03/28/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
Abstract
Aflatoxin (AFT) contamination poses a significant global public health and safety concern, prompting widespread apprehension. Of the various AFTs, aflatoxin B1 (AFB1) stands out for its pronounced toxicity and its association with a spectrum of chronic ailments, including cardiovascular disease, neurodegenerative disorders, and cancer. Lycopene, a lipid-soluble natural carotenoid, has emerged as a potential mitigator of the deleterious effects induced by AFB1 exposure, spanning cardiac injury, hepatotoxicity, nephrotoxicity, intestinal damage, and reproductive impairment. This protective mechanism operates by reducing oxidative stress, inflammation, and lipid peroxidation, and activating the mitochondrial apoptotic pathway, facilitating the activation of mitochondrial biogenesis, the endogenous antioxidant system, and the nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH-associated protein 1 (KEAP1) and peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) pathways, as well as regulating the activities of cytochrome P450 (CYP450) enzymes. This review provides an overview of the protective effects of lycopene against AFB1 exposure-induced toxicity and the underlying molecular mechanisms. Furthermore, it explores the safety profile and potential clinical applications of lycopene. The present review underscores lycopene's potential as a promising detoxification agent against AFB1 exposure, with the intent to stimulate further research and practical utilization in this domain.
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Affiliation(s)
- Meng Li
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (M.L.); (S.T.); (S.Y.); (Z.H.)
| | - Shusheng Tang
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (M.L.); (S.T.); (S.Y.); (Z.H.)
| | - Xinyan Peng
- College of Life Sciences, Yantai University, Yantai 264000, China;
| | - Gaurav Sharma
- Cardiovascular and Thoracic Surgery, Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;
| | - Shutao Yin
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (M.L.); (S.T.); (S.Y.); (Z.H.)
| | - Zhihui Hao
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (M.L.); (S.T.); (S.Y.); (Z.H.)
| | - Jichang Li
- College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin 150030, China;
| | - Jianzhong Shen
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (M.L.); (S.T.); (S.Y.); (Z.H.)
| | - Chongshan Dai
- National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (M.L.); (S.T.); (S.Y.); (Z.H.)
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15
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Xia G, Zhou G, Jiang W, Chu C, Wang L, Moorthy B. Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo. Int J Mol Sci 2024; 25:3781. [PMID: 38612589 PMCID: PMC11012139 DOI: 10.3390/ijms25073781] [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: 01/23/2024] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/14/2024] Open
Abstract
Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.
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Affiliation(s)
- Guobin Xia
- Section of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas Childrens’ Hospital, Houston, TX 77030, USA; (G.X.); (W.J.); (C.C.); (L.W.)
| | - Guodong Zhou
- Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA
| | - Weiwu Jiang
- Section of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas Childrens’ Hospital, Houston, TX 77030, USA; (G.X.); (W.J.); (C.C.); (L.W.)
| | - Chun Chu
- Section of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas Childrens’ Hospital, Houston, TX 77030, USA; (G.X.); (W.J.); (C.C.); (L.W.)
| | - Lihua Wang
- Section of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas Childrens’ Hospital, Houston, TX 77030, USA; (G.X.); (W.J.); (C.C.); (L.W.)
| | - Bhagavatula Moorthy
- Section of Neonatology, Department of Pediatrics, Baylor College of Medicine and Texas Childrens’ Hospital, Houston, TX 77030, USA; (G.X.); (W.J.); (C.C.); (L.W.)
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16
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Prince S. Gene-environment interaction: why genetic enhancement might never be distributed fairly. JOURNAL OF MEDICAL ETHICS 2024; 50:272-277. [PMID: 37268408 DOI: 10.1136/jme-2023-109101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 05/19/2023] [Indexed: 06/04/2023]
Abstract
Ethical debates around genetic enhancement tend to include an argument that the technology will eventually be fairly accessible once available. That we can fairly distribute genetic enhancement has become a moral defence of genetic enhancement. Two distribution solutions are argued for, the first being equal distribution. Equality of access is generally believed to be the fairest and most just method of distribution. Second, equitable distribution: providing genetic enhancements to reduce social inequalities. In this paper, I make two claims. I first argue that the very assumption that genetic enhancements can be distributed fairly is problematic when considering our understanding of gene-environment interactions, for example, epigenetics. I then argue that arguments that genetic enhancements are permissible because the intended benefits can be distributed fairly as intended are misinformed. My first claim rests on the assertion that genetic enhancements do not enhance traits in a vacuum; genes are dependent on conducive environments for expression. If society cannot guarantee fair environments, then any benefit conferred from being genetically enhanced will be undermined. Thus, any argument that the distribution of genetic enhancements will be fair and that the technology is therefore morally permissible, is mistaken.
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Affiliation(s)
- Sinead Prince
- Faculty of Business and Law, Queensland University of Technology, Brisbane, Queensland, Australia
- Faculty of Business and Law, Queensland University of Technology, Brisbane, Queensland, Australia
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17
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Jackson KM, Jones PC, Fluke LM, Fischer TD, Thompson JF, Cochran AJ, Stern SL, Faries MB, Hoon DSB, Foshag LJ. Smoking Status and Survival in Patients With Early-Stage Primary Cutaneous Melanoma. JAMA Netw Open 2024; 7:e2354751. [PMID: 38319662 PMCID: PMC10848058 DOI: 10.1001/jamanetworkopen.2023.54751] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 11/21/2023] [Indexed: 02/07/2024] Open
Abstract
Importance While smoking is associated with a decreased incidence of cutaneous melanoma, the association of smoking with melanoma progression and death is not well defined. Objective To determine the association of smoking with survival in patients with early-stage primary cutaneous melanoma. Design, Setting, and Participants This cohort study performed a post hoc analysis of data derived from the randomized, multinational first and second Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II). Participants were accrued for MSLT-I from January 20, 1994, to March 29, 2002; MSLT-II, from December 21, 2004, to March 31, 2014. Median follow-up was 110.0 (IQR, 53.4-120.0) months for MSLT-I and 67.6 (IQR, 25.8-110.2) months for MSLT-II. Patients aged 18 to 75 years with clinical stages I or II melanoma with a Breslow thickness of 1.00 mm or greater or Clark level IV to V and available standard prognostic and smoking data were included. Analyses were performed from October 4, 2022, to March 31, 2023. Exposure Current, former, and never smoking. Main Outcomes and Measures Melanoma-specific survival of patients with current, former, and never smoking status was assessed for the entire cohort and for nodal observation and among subgroups with sentinel lymph node biopsy (SLNB)-negative and SLNB-positive findings. Results Of 6279 included patients, 3635 (57.9%) were men, and mean (SD) age was 52.7 (13.4) years. The most common tumor location was an extremity (2743 [43.7%]), and mean (SD) Breslow thickness was 2.44 (2.06) mm. Smoking status included 1077 (17.2%) current, 1694 (27.0%) former, and 3508 (55.9%) never. Median follow-up was 78.4 (IQR, 30.5-119.6) months. Current smoking was associated with male sex, younger age, trunk site, thicker tumors, tumor ulceration, and SLNB positivity. Current smoking was associated with a greater risk of melanoma-associated death by multivariable analysis for the entire study (hazard ratio [HR], 1.48 [95% CI, 1.26-1.75]; P < .001). Former smoking was not. The increased risk of melanoma-specific mortality associated with current smoking was greatest for patients with SLNB-negative melanoma (HR, 1.85 [95% CI, 1.35-2.52]; P < .001), but also present for patients with SLNB-positive melanoma (HR, 1.29 [95% CI, 1.04-1.59]; P = .02) and nodal observation (HR, 1.68 [95% CI, 1.09-2.61]; P = .02). Smoking at least 20 cigarettes/d doubled the risk of death due to melanoma for patients with SLNB-negative disease (HR, 2.06 [95% CI, 1.36-3.13]; P < .001). Conclusions and Relevance The findings of this cohort study suggest that patients with clinical stage I and II melanoma who smoked had a significantly increased risk of death due to melanoma. Smoking status should be assessed at time of melanoma diagnosis and may be considered a risk factor for disease progression.
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Affiliation(s)
- Katherine M. Jackson
- Department of Surgical Oncology, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
| | - Peter C. Jones
- Department of Surgical Oncology, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
| | - Laura M. Fluke
- Department of Surgical Oncology, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
| | - Trevan D. Fischer
- Department of Surgical Oncology, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
| | | | - Alistair J. Cochran
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles
| | - Stacey L. Stern
- Translational Molecular Medicine and Biostatistics, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
| | - Mark B. Faries
- The Angeles Clinic and Research Institute, Los Angeles, California
| | - Dave S. B. Hoon
- Translational Molecular Medicine and Biostatistics, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
| | - Leland J. Foshag
- Department of Surgical Oncology, Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
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18
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Doorenbos CSE, Jonker J, Hao J, Gore EJ, Kremer D, Knobbe TJ, de Joode AAE, Sanders JSF, Thaunat O, Niesters HGM, Van Leer-Buter CC, Bakker SJL. Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients. Viruses 2023; 15:2387. [PMID: 38140628 PMCID: PMC10748022 DOI: 10.3390/v15122387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/01/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
Torque Teno Virus (TTV) is a non-pathogenic virus that is highly prevalent among kidney transplant recipients (KTRs). Its circulating load is associated with an immunological status in KTR and is considered a promising tool for guiding immunosuppression. To allow for optimal guidance, it is important to identify other determinants of TTV load. We aimed to investigate the potential association of smoking and alcohol intake with TTV load. For this cross-sectional study, serum TTV load was measured using PCR in stable kidney transplant recipients at ≥1 year after transplantation, and smoking status and alcohol intake were assessed through questionnaires and measurements of urinary cotinine and ethyl glucuronide. A total of 666 KTRs were included (57% male). A total of 549 KTR (82%) had a detectable TTV load (3.1 ± 1.5 log10 copies/mL). In KTR with a detectable TTV load, cyclosporin and tacrolimus use were positively associated with TTV load (St. β = 0.46, p < 0.001 and St. β = 0.66, p < 0.001, respectively), independently of adjustment for potential confounders. Current smoking and alcohol intake of >20 g/day were negatively associated with TTV load (St. β = -0.40, p = 0.004 and St. β = -0.33, p = 0.009, respectively), independently of each other and of adjustment for age, sex, kidney function, time since transplantation and calcineurin inhibitor use. This strong association of smoking and alcohol intake with TTV suggests a need to account for the smoking status and alcohol intake when applying TTV guided immunosuppression in KTR.
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Affiliation(s)
- Caecilia S. E. Doorenbos
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (J.J.)
| | - Jip Jonker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (J.J.)
| | - Jiasi Hao
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Edmund J. Gore
- Department of Medical Microbiology, Division of Clinical Virology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Daan Kremer
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (J.J.)
| | - Tim J. Knobbe
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (J.J.)
| | - Anoek A. E. de Joode
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (J.J.)
| | - Jan Stephan F. Sanders
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (J.J.)
| | - Olivier Thaunat
- Department of Transplantation Nephrology and Clinical Immunology Hospices Civils de Lyon, Claude Bernard Lyon I University, INSERM Unit 1111, 69003 Lyon, France
| | - Hubert G. M. Niesters
- Department of Medical Microbiology, Division of Clinical Virology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Coretta C. Van Leer-Buter
- Department of Medical Microbiology, Division of Clinical Virology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
| | - Stephan J. L. Bakker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (J.J.)
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Tanaka T, Aoki R, Terasaki M. Potential Chemopreventive Effects of Dietary Combination of Phytochemicals against Cancer Development. Pharmaceuticals (Basel) 2023; 16:1591. [PMID: 38004456 PMCID: PMC10674766 DOI: 10.3390/ph16111591] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 11/01/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
Cancer remains a major cause of cancer-related death worldwide. Over 70% of epithelial malignancies are sporadic and are related to lifestyle. Epidemiological studies suggest an inverse correlation between cancer incidence and fruit and vegetable intake. Numerous preclinical studies using in vitro (cell lines) and in vivo animal models of oncogenesis have reported the chemopreventive effects of dietary phytochemical agents through alterations in different biomarkers and signaling pathways. However, there is contrasting evidence from preclinical studies and clinical trials. To date, the most studied compounds include curcumin, resveratrol, isoflavones, green tea extract (epigallocatechin gallate), black raspberry powder (anthocyanins and ellagitannins), bilberry extract (anthocyanins), ginger extract (gingerol derivatives), and pomegranate extract (ellagitannins and ellagic acid). Overall, the clinical evidence of the preventive effects of dietary phytochemicals against cancer development is still weak, and the amount of these phytochemicals needed to exert chemopreventive effects largely exceeds the common dietary doses. Therefore, we propose a combination treatment of natural compounds that are used clinically for another purpose in order to obtain excess inhibitory efficacy via low-dose administration and discuss the possible reasons behind the gap between preclinical research and clinical trials.
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Affiliation(s)
- Takuji Tanaka
- Department of Diagnostic Pathology, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513, Japan;
| | - Ryogo Aoki
- Department of Diagnostic Pathology, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513, Japan;
| | - Masaru Terasaki
- School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan;
- Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
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20
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Guilbaud A, Ghanegolmohammadi F, Wang Y, Leng J, Kreymerman A, Gamboa Varela J, Garbern J, Elwell H, Cao F, Ricci-Blair E, Liang C, Balamkundu S, Vidoudez C, DeMott M, Bedi K, Margulies K, Bennett D, Palmer A, Barkley-Levenson A, Lee R, Dedon P. Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans. Nucleic Acids Res 2023; 51:10829-10845. [PMID: 37843128 PMCID: PMC10639045 DOI: 10.1093/nar/gkad822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 08/27/2023] [Accepted: 09/27/2023] [Indexed: 10/17/2023] Open
Abstract
DNA damage causes genomic instability underlying many diseases, with traditional analytical approaches providing minimal insight into the spectrum of DNA lesions in vivo. Here we used untargeted chromatography-coupled tandem mass spectrometry-based adductomics (LC-MS/MS) to begin to define the landscape of DNA modifications in rat and human tissues. A basis set of 114 putative DNA adducts was identified in heart, liver, brain, and kidney in 1-26-month-old rats and 111 in human heart and brain by 'stepped MRM' LC-MS/MS. Subsequent targeted analysis of these species revealed species-, tissue-, age- and sex-biases. Structural characterization of 10 selected adductomic signals as known DNA modifications validated the method and established confidence in the DNA origins of the signals. Along with strong tissue biases, we observed significant age-dependence for 36 adducts, including N2-CMdG, 5-HMdC and 8-Oxo-dG in rats and 1,N6-ϵdA in human heart, as well as sex biases for 67 adducts in rat tissues. These results demonstrate the potential of adductomics for discovering the true spectrum of disease-driving DNA adducts. Our dataset of 114 putative adducts serves as a resource for characterizing dozens of new forms of DNA damage, defining mechanisms of their formation and repair, and developing them as biomarkers of aging and disease.
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Affiliation(s)
- Axel Guilbaud
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
| | - Farzan Ghanegolmohammadi
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
| | - Yijun Wang
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
| | - Jiapeng Leng
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
| | - Alexander Kreymerman
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
| | - Jacqueline Gamboa Varela
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
| | - Jessica Garbern
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
| | - Hannah Elwell
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
| | - Fang Cao
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
| | - Elisabeth M Ricci-Blair
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
| | - Cui Liang
- Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore
| | - Seetharamsing Balamkundu
- Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore
| | - Charles Vidoudez
- Harvard Center for Mass Spectrometry, Harvard University, Cambridge, MA 02138, USA
| | - Michael S DeMott
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
| | - Kenneth Bedi
- University of Pennsylvania Cardiovascular Institute, Philadelphia, PA, USA
| | | | - David A Bennett
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
| | - Abraham A Palmer
- Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA
- Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | | | - Richard T Lee
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
| | - Peter C Dedon
- Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
- Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore
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21
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Ji L, Cui P, Zhou S, Qiu L, Huang H, Wang C, Wang J. Advances of Amifostine in Radiation Protection: Administration and Delivery. Mol Pharm 2023; 20:5383-5395. [PMID: 37747899 DOI: 10.1021/acs.molpharmaceut.3c00600] [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] [Indexed: 09/27/2023]
Abstract
Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.
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Affiliation(s)
- Lihua Ji
- School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China
- School of Petroleum and Chemical Engineering, Changzhou University, Changzhou 213164, Jiangsu, China
| | - Pengfei Cui
- School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China
| | - Shuwen Zhou
- School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China
| | - Lin Qiu
- School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China
| | - Hai Huang
- School of Petroleum and Chemical Engineering, Changzhou University, Changzhou 213164, Jiangsu, China
| | - Cheng Wang
- School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China
| | - Jianhao Wang
- School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China
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22
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Kourie HR, Zouein J, Succar B, Mardirossian A, Ahmadieh N, Chouery E, Mehawej C, Jalkh N, kattan J, Nemr E. Genetic Polymorphisms Involved in Bladder Cancer: A Global Review. Oncol Rev 2023; 17:10603. [PMID: 38025894 PMCID: PMC10657888 DOI: 10.3389/or.2023.10603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 10/06/2023] [Indexed: 12/01/2023] Open
Abstract
Bladder cancer (BC) has been associated with genetic susceptibility. Single peptide polymorphisms (SNPs) can modulate BC susceptibility. A literature search was performed covering the period between January 2000 and October 2020. Overall, 334 articles were selected, reporting 455 SNPs located in 244 genes. The selected 455 SNPs were further investigated. All SNPs that were associated with smoking and environmental exposure were excluded from this study. A total of 197 genes and 343 SNPs were found to be associated with BC, among which 177 genes and 291 SNPs had congruent results across all available studies. These genes and SNPs were classified into eight different categories according to their function.
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Affiliation(s)
- Hampig Raphael Kourie
- Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Joseph Zouein
- Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Bahaa Succar
- Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Avedis Mardirossian
- Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Nizar Ahmadieh
- Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Eliane Chouery
- Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
| | - Cybel Mehawej
- Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
| | - Nadine Jalkh
- Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Joseph kattan
- Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Elie Nemr
- Urology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
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23
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Menz J, Götz ME, Gündel U, Gürtler R, Herrmann K, Hessel-Pras S, Kneuer C, Kolrep F, Nitzsche D, Pabel U, Sachse B, Schmeisser S, Schumacher DM, Schwerdtle T, Tralau T, Zellmer S, Schäfer B. Genotoxicity assessment: opportunities, challenges and perspectives for quantitative evaluations of dose-response data. Arch Toxicol 2023; 97:2303-2328. [PMID: 37402810 PMCID: PMC10404208 DOI: 10.1007/s00204-023-03553-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 06/21/2023] [Indexed: 07/06/2023]
Abstract
Genotoxicity data are mainly interpreted in a qualitative way, which typically results in a binary classification of chemical entities. For more than a decade, there has been a discussion about the need for a paradigm shift in this regard. Here, we review current opportunities, challenges and perspectives for a more quantitative approach to genotoxicity assessment. Currently discussed opportunities mainly include the determination of a reference point (e.g., a benchmark dose) from genetic toxicity dose-response data, followed by calculation of a margin of exposure (MOE) or derivation of a health-based guidance value (HBGV). In addition to new opportunities, major challenges emerge with the quantitative interpretation of genotoxicity data. These are mainly rooted in the limited capability of standard in vivo genotoxicity testing methods to detect different types of genetic damage in multiple target tissues and the unknown quantitative relationships between measurable genotoxic effects and the probability of experiencing an adverse health outcome. In addition, with respect to DNA-reactive mutagens, the question arises whether the widely accepted assumption of a non-threshold dose-response relationship is at all compatible with the derivation of a HBGV. Therefore, at present, any quantitative genotoxicity assessment approach remains to be evaluated case-by-case. The quantitative interpretation of in vivo genotoxicity data for prioritization purposes, e.g., in connection with the MOE approach, could be seen as a promising opportunity for routine application. However, additional research is needed to assess whether it is possible to define a genotoxicity-derived MOE that can be considered indicative of a low level of concern. To further advance quantitative genotoxicity assessment, priority should be given to the development of new experimental methods to provide a deeper mechanistic understanding and a more comprehensive basis for the analysis of dose-response relationships.
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Affiliation(s)
- Jakob Menz
- Department of Food Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
| | - Mario E Götz
- Department of Food Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Ulrike Gündel
- Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Rainer Gürtler
- Department of Food Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Kristin Herrmann
- Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Stefanie Hessel-Pras
- Department of Food Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Carsten Kneuer
- Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Franziska Kolrep
- Department of Safety in the Food Chain, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Dana Nitzsche
- Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Ulrike Pabel
- Department of Safety in the Food Chain, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Benjamin Sachse
- Department of Food Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Sebastian Schmeisser
- Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - David M Schumacher
- Department of Safety in the Food Chain, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Tanja Schwerdtle
- German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Tewes Tralau
- Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Sebastian Zellmer
- Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
| | - Bernd Schäfer
- Department of Food Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589, Berlin, Germany
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24
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Liu G, Yang Y, Kang X, Xu H, Ai J, Cao M, Liu G. A pan-cancer analysis of lipid metabolic alterations in primary and metastatic cancers. Sci Rep 2023; 13:13810. [PMID: 37612422 PMCID: PMC10447541 DOI: 10.1038/s41598-023-41107-3] [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: 07/08/2023] [Accepted: 08/22/2023] [Indexed: 08/25/2023] Open
Abstract
Metabolic reprogramming is a hallmark of cancers, but pan-cancer level roles of lipid metabolism in cancer development are remains poorly understood. We investigated the possible roles of lipid metabolic genes (LMGs) in 14 cancer types. The results indicate that: (1) there is strong evidence for increased lipid metabolism in THCA and KICH. (2) Although the overall levels of lipid metabolic processes are down-regulated in some cancer types, fatty acid synthase activity and fatty acid elongation are moderately up-regulated in more than half of the cancer types. Cholesterol synthesis is up-regulated in five cancers including KICH, BLCA, COAD, BRCA, UCEC, and THCA. (3) The catabolism of cholesterols, triglycerides and fatty acids is repressed in most cancers, but a specific form of lipid degradation, lipophagy, is activated in THCA and KICH. (4) Lipid storage is enhanced in in kidney cancers and thyroid cancer. (5) Similarly to primary tumors, metastatic tumors tend to up-regulate biosynthetic processes of diverse lipids, but down-regulate lipid catabolic processes, except lipophagy. (6) The frequently mutated lipid metabolic genes are not key LMGs. (7) We established a LMG-based model for predicting cancer prognosis. Our results are helpful in expanding our understanding of the role of lipid metabolism in cancer.
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Affiliation(s)
- Guoqing Liu
- School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
- Inner Mongolia Key Laboratory of Functional Genomics and Bioinformatics, Inner Mongolia University of Science and Technology, Baotou, China.
| | - Yan Yang
- School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China
| | - Xuejia Kang
- School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China
| | - Hao Xu
- School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China
| | - Jing Ai
- School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China
| | - Min Cao
- School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China
| | - Guojun Liu
- School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
- Inner Mongolia Key Laboratory of Functional Genomics and Bioinformatics, Inner Mongolia University of Science and Technology, Baotou, China.
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25
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Phua ZJ, MacInnis RJ, Hodge AM, Lynch BM, Hopper JL, Smith-Warner SA, Giles GG, Milne RL, Jayasekara H. Pre-diagnostic cigarette smoking and risk of second primary cancer: The Melbourne Collaborative Cohort Study. Cancer Epidemiol 2023; 85:102406. [PMID: 37390701 DOI: 10.1016/j.canep.2023.102406] [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: 03/08/2023] [Revised: 06/18/2023] [Accepted: 06/23/2023] [Indexed: 07/02/2023]
Abstract
Enhanced survival following a diagnosis of cancer has led to a steep rise in the number of individuals diagnosed with a second primary cancer. We examined the association between pre-cancer cigarette smoking and risk of second cancer in 9785 participants diagnosed with first invasive cancer after enrolment in the Melbourne Collaborative Cohort Study. Follow-up was from date of first invasive cancer until diagnosis of second primary invasive cancer, death, or 31 July 2019, whichever came first. Data on cigarette smoking was collected at enrolment (1990-94) along with information on other lifestyle factors including body size, alcohol intake and diet. We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for incident second cancer with several smoking measures, adjusted for potential confounders. After a mean follow-up of 7.3 years, 1658 second cancers were identified. All measures of smoking were associated with increased risk of second cancer. We observed a 44 % higher risk of second cancer for smokers of ≥ 20 cigarettes/day (HR=1.44, 95 % CI: 1.18-1.76), compared with never smokers. We also observed dose-dependent associations with number of cigarettes smoked (HR=1.05 per 10 cigarettes/day, 95 % CI: 1.01-1.09) and duration of smoking (HR=1.07 per 10 years, 95 % CI: 1.03-1.10). The risk of second cancer increased by 4 % per 10 pack-years of smoking (HR=1.04, 95 % CI: 1.02-1.06; p < 0.001). There was suggestive evidence of stronger associations with number of cigarettes smoked and pack-years of smoking for women (pinteraction<0.05), particularly for the highest risk categories of both variables. These associations with pre-diagnostic smoking were markedly stronger for second cancers known to be smoking-related than for others (phomogeneity<0.001). Our findings for pre-diagnostic cigarette smoking indicated increased risk of second primary cancer for cancer sites considered smoking-related, highlighting the importance of assessing smoking habits in cancer survivors.
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Affiliation(s)
- Zhi Jing Phua
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia
| | - Robert J MacInnis
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia
| | - Allison M Hodge
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia
| | - Brigid M Lynch
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia
| | - John L Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia
| | - Stephanie A Smith-Warner
- Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA 02115, USA
| | - Graham G Giles
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria 3168, Australia
| | - Roger L Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria 3168, Australia
| | - Harindra Jayasekara
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria 3010, Australia; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia; Chronic Disease and Ageing, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3168, Australia.
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26
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Yang Y, Bhargava D, Chen X, Zhou T, Dursuk G, Jiang W, Wang J, Zong Z, Katz SI, Lomberk GA, Urrutia RA, Katz JP. KLF5 and p53 comprise an incoherent feed-forward loop directing cell-fate decisions following stress. Cell Death Dis 2023; 14:299. [PMID: 37130837 PMCID: PMC10154356 DOI: 10.1038/s41419-023-05731-1] [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: 08/26/2022] [Revised: 03/01/2023] [Accepted: 03/13/2023] [Indexed: 05/04/2023]
Abstract
In response to stress, cells make a critical decision to arrest or undergo apoptosis, mediated in large part by the tumor suppressor p53. Yet the mechanisms of these cell fate decisions remain largely unknown, particularly in normal cells. Here, we define an incoherent feed-forward loop in non-transformed human squamous epithelial cells involving p53 and the zinc-finger transcription factor KLF5 that dictates responses to differing levels of cellular stress from UV irradiation or oxidative stress. In normal unstressed human squamous epithelial cells, KLF5 complexes with SIN3A and HDAC2 repress TP53, allowing cells to proliferate. With moderate stress, this complex is disrupted, and TP53 is induced; KLF5 then acts as a molecular switch for p53 function by transactivating AKT1 and AKT3, which direct cells toward survival. By contrast, severe stress results in KLF5 loss, such that AKT1 and AKT3 are not induced, and cells preferentially undergo apoptosis. Thus, in human squamous epithelial cells, KLF5 gates the response to UV or oxidative stress to determine the p53 output of growth arrest or apoptosis.
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Affiliation(s)
- Yizeng Yang
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Dharmendra Bhargava
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Xiao Chen
- Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Taicheng Zhou
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Gizem Dursuk
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Wenpeng Jiang
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Jinshen Wang
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Zhen Zong
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Sharyn I Katz
- Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA
| | - Gwen A Lomberk
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Raul A Urrutia
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
- Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Jonathan P Katz
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
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27
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Li Y, Huang Y, Yuan L, He Y, Yin G, He T, He E, Ding F, Xia H, Xu H, Liu M, Tao S. The deposition mapping of polycyclic aromatic hydrocarbons in megacity Shanghai, China. JOURNAL OF HAZARDOUS MATERIALS 2023; 443:130173. [PMID: 36257109 DOI: 10.1016/j.jhazmat.2022.130173] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 10/03/2022] [Accepted: 10/09/2022] [Indexed: 06/16/2023]
Abstract
The deposition of polycyclic aromatic hydrocarbon (PAHs) has far-reaching impacts on Earth's surface system and human health. However, a comprehensive understanding of PAHs' deposition in a high urbanized area is still lacking because of limited field measurements data and rough resolution of current models. In this research, a deposition map of PAHs with a resolution of 2 × 2 km in megacity Shanghai, China was established. Gridded annual total deposition of PAHs from July 2020 to June 2021 ranged from 385 to 10,631 ng/(m2·d), with a mean value of 2,611 ng/(m2·d). The highest PAHs deposition was found over the downtown Shanghai, which received 4.3 times the deposition flux of outlying areas. About 77 % of area in Shanghai was dominated by wet deposition which accounted for 62 % of total deposition in Shanghai. The total deposition showed a trend of summer>fall>spring>winter, which was similar to that of the amount of rain. Source apportionment and geographically weighted regression analysis showed that built-up land and human activities are key driving factors of PAHs' deposition in Shanghai. Our results suggest that intensive human activities could alter the PAHs deposition distribution in Shanghai, and improve the understanding of PAHs' environmental behavior in high urbanized area.
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Affiliation(s)
- Ye Li
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Ye Huang
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China.
| | - Lina Yuan
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Yue He
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Guoyu Yin
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Tianhao He
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Erkai He
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Fangfang Ding
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Haibin Xia
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China
| | - Haoran Xu
- Laboratory of Earth Surface Processes, College of Urban and Environmental Science, Peking University, Beijing 100871, China
| | - Min Liu
- Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China.
| | - Shu Tao
- Laboratory of Earth Surface Processes, College of Urban and Environmental Science, Peking University, Beijing 100871, China
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28
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Poudel S, Huber AD, Chen T. Regulation of Nuclear Receptors PXR and CAR by Small Molecules and Signal Crosstalk: Roles in Drug Metabolism and Beyond. Drug Metab Dispos 2023; 51:228-236. [PMID: 36116789 PMCID: PMC9900866 DOI: 10.1124/dmd.122.000858] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/16/2022] [Accepted: 08/29/2022] [Indexed: 01/31/2023] Open
Abstract
Pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are ligand-activated transcription factors that regulate the expression of drug metabolizing enzymes and drug transporters. Since their discoveries, they have been studied as important factors for regulating processes related to drug efficacy, drug toxicity, and drug-drug interactions. However, their vast ligand-binding profiles extend into additional spaces, such as endogenously produced chemicals, microbiome metabolites, dietary compounds, and environmental pollutants. Therefore, PXR and CAR can respond to an enormous abundance of stimuli, resulting in significant shifts in metabolic programs and physiologic homeostasis. Naturally, PXR and CAR have been implicated in various diseases related to homeostatic perturbations, such as inflammatory bowel disorders, diabetes, and certain cancers. Recent findings have injected the field with new signaling mechanisms and tools to dissect the complex PXR and CAR biology and have strengthened the potential for future PXR and CAR modulators in the clinic. Here, we describe the historical and ongoing importance of PXR and CAR in drug metabolism pathways and how this history has evolved into new mechanisms that regulate and are regulated by these xenobiotic receptors, with a specific focus on small molecule ligands. To effectively convey the impact of newly emerging research, we have arranged five diverse and representative key recent advances, four specific challenges, and four perspectives on future directions. SIGNIFICANCE STATEMENT: PXR and CAR are key transcription factors that regulate homeostatic detoxification of the liver and intestines. Diverse chemicals bind to these nuclear receptors, triggering their transcriptional tuning of the cellular metabolic response. This minireview revisits the importance of PXR and CAR in pharmaceutical drug responses and highlights recent results with implications beyond drug metabolism.
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Affiliation(s)
- Shyaron Poudel
- Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - Andrew D Huber
- Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - Taosheng Chen
- Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee
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29
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Ovejero-Sánchez M, González-Sarmiento R, Herrero AB. DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities. Cancers (Basel) 2023; 15:448. [PMID: 36672401 PMCID: PMC9856346 DOI: 10.3390/cancers15020448] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/12/2023] Open
Abstract
The DNA damage response (DDR), a set of signaling pathways for DNA damage detection and repair, maintains genomic stability when cells are exposed to endogenous or exogenous DNA-damaging agents. Alterations in these pathways are strongly associated with cancer development, including ovarian cancer (OC), the most lethal gynecologic malignancy. In OC, failures in the DDR have been related not only to the onset but also to progression and chemoresistance. It is known that approximately half of the most frequent subtype, high-grade serous carcinoma (HGSC), exhibit defects in DNA double-strand break (DSB) repair by homologous recombination (HR), and current evidence indicates that probably all HGSCs harbor a defect in at least one DDR pathway. These defects are not restricted to HGSCs; mutations in ARID1A, which are present in 30% of endometrioid OCs and 50% of clear cell (CC) carcinomas, have also been found to confer deficiencies in DNA repair. Moreover, DDR alterations have been described in a variable percentage of the different OC subtypes. Here, we overview the main DNA repair pathways involved in the maintenance of genome stability and their deregulation in OC. We also recapitulate the preclinical and clinical data supporting the potential of targeting the DDR to fight the disease.
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Affiliation(s)
- María Ovejero-Sánchez
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Molecular Medicine Unit, Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
- Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-Spanish National Research Council, 37007 Salamanca, Spain
| | - Rogelio González-Sarmiento
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Molecular Medicine Unit, Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
- Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-Spanish National Research Council, 37007 Salamanca, Spain
| | - Ana Belén Herrero
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
- Molecular Medicine Unit, Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
- Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-Spanish National Research Council, 37007 Salamanca, Spain
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30
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Sharma A, Shambhwani D, Pandey S, Singh J, Lalhlenmawia H, Kumarasamy M, Singh SK, Chellappan DK, Gupta G, Prasher P, Dua K, Kumar D. Advances in Lung Cancer Treatment Using Nanomedicines. ACS OMEGA 2023; 8:10-41. [PMID: 36643475 PMCID: PMC9835549 DOI: 10.1021/acsomega.2c04078] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 10/13/2022] [Indexed: 06/01/2023]
Abstract
Carcinoma of the lungs is among the most menacing forms of malignancy and has a poor prognosis, with a low overall survival rate due to delayed detection and ineffectiveness of conventional therapy. Therefore, drug delivery strategies that may overcome undesired damage to healthy cells, boost therapeutic efficacy, and act as imaging tools are currently gaining much attention. Advances in material science have resulted in unique nanoscale-based theranostic agents, which provide renewed hope for patients suffering from lung cancer. Nanotechnology has vastly modified and upgraded the existing techniques, focusing primarily on increasing bioavailability and stability of anti-cancer drugs. Nanocarrier-based imaging systems as theranostic tools in the treatment of lung carcinoma have proven to possess considerable benefits, such as early detection and targeted therapeutic delivery for effectively treating lung cancer. Several variants of nano-drug delivery agents have been successfully studied for therapeutic applications, such as liposomes, dendrimers, polymeric nanoparticles, nanoemulsions, carbon nanotubes, gold nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, hydrogels, and micelles. In this Review, we present a comprehensive outline on the various types of overexpressed receptors in lung cancer, as well as the various targeting approaches of nanoparticles.
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Affiliation(s)
- Akshansh Sharma
- Department
of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan 173229, India
| | | | - Sadanand Pandey
- Department
of Chemistry, College of Natural Sciences, Yeungnam University, Gyeongsan, Gyeongbuk 38541, South Korea
| | - Jay Singh
- Department
of Chemistry, Institute of Science, Banaras
Hindu University, Varanasi 221005, India
| | - Hauzel Lalhlenmawia
- Department
of Pharmacy, Regional Institute of Paramedical
and Nursing Sciences, Zemabawk, Aizawl, Mizoram 796017, India
| | - Murali Kumarasamy
- Department
of Biotechnology, National Institute of
Pharmaceutical Education and Research, Hajipur 844102, India
| | - Sachin Kumar Singh
- School
of Pharmaceutical Sciences, Lovely Professional
University, Phagwara 144411, India
- Faculty
of Health, Australian Research Centre in Complementary and Integrative
Medicine, University of Technology, Sydney, Ultimo-NSW 2007, Australia
| | - Dinesh Kumar Chellappan
- Department
of Life Sciences, School of Pharmacy, International
Medical University, Kuala Lumpur 57000, Malaysia
| | - Gaurav Gupta
- Department
of Pharmacology, School of Pharmacy, Suresh
Gyan Vihar University, Jaipur 302017, India
- Department
of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical
and Technical Sciences, Saveetha University, Chennai 602117, India
- Uttaranchal
Institute of Pharmaceutical Sciences, Uttaranchal
University, Dehradun 248007, India
| | - Parteek Prasher
- Department
of Chemistry, University of Petroleum &
Energy Studies, Dehradun 248007, India
| | - Kamal Dua
- Faculty
of Health, Australian Research Centre in Complementary and Integrative
Medicine, University of Technology, Sydney, Ultimo-NSW 2007, Australia
- Discipline
of Pharmacy, Graduate School of Health, University of Technology, Sydney, Ultimo-NSW 2007, Australia
| | - Deepak Kumar
- Department
of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan 173229, India
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31
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Singh J, Gautam DNS, Sourav S, Sharma R. Role of
Moringa oleifera
Lam. in cancer: Phytochemistry and pharmacological insights. FOOD FRONTIERS 2022. [DOI: 10.1002/fft2.181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Jyoti Singh
- Department of Rasa Shastra & Bhaishajya Kalpana Faculty of Ayurveda, Institute of Medical Sciences Banaras Hindu University Varanasi India
| | - Dev Nath Singh Gautam
- Department of Rasa Shastra & Bhaishajya Kalpana Faculty of Ayurveda, Institute of Medical Sciences Banaras Hindu University Varanasi India
| | - Simant Sourav
- Department of Sharira Kriya, Government Ayurvedic College and Hospital Patna India
| | - Rohit Sharma
- Department of Rasa Shastra & Bhaishajya Kalpana Faculty of Ayurveda, Institute of Medical Sciences Banaras Hindu University Varanasi India
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32
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Limbu S, Dakshanamurthy S. Predicting Chemical Carcinogens Using a Hybrid Neural Network Deep Learning Method. SENSORS (BASEL, SWITZERLAND) 2022; 22:8185. [PMID: 36365881 PMCID: PMC9653664 DOI: 10.3390/s22218185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/11/2022] [Accepted: 10/23/2022] [Indexed: 05/28/2023]
Abstract
Determining environmental chemical carcinogenicity is urgently needed as humans are increasingly exposed to these chemicals. In this study, we developed a hybrid neural network (HNN) method called HNN-Cancer to predict potential carcinogens of real-life chemicals. The HNN-Cancer included a new SMILES feature representation method by modifying our previous 3D array representation of 1D SMILES simulated by the convolutional neural network (CNN). We developed binary classification, multiclass classification, and regression models based on diverse non-congeneric chemicals. Along with the HNN-Cancer model, we developed models based on the random forest (RF), bootstrap aggregating (Bagging), and adaptive boosting (AdaBoost) methods for binary and multiclass classification. We developed regression models using HNN-Cancer, RF, support vector regressor (SVR), gradient boosting (GB), kernel ridge (KR), decision tree with AdaBoost (DT), KNeighbors (KN), and a consensus method. The performance of the models for all classifications was assessed using various statistical metrics. The accuracy of the HNN-Cancer, RF, and Bagging models were 74%, and their AUC was ~0.81 for binary classification models developed with 7994 chemicals. The sensitivity was 79.5% and the specificity was 67.3% for the HNN-Cancer, which outperforms the other methods. In the case of multiclass classification models with 1618 chemicals, we obtained the optimal accuracy of 70% with an AUC 0.7 for HNN-Cancer, RF, Bagging, and AdaBoost, respectively. In the case of regression models, the correlation coefficient (R) was around 0.62 for HNN-Cancer and RF higher than the SVM, GB, KR, DTBoost, and NN machine learning methods. Overall, the HNN-Cancer performed better for the majority of the known carcinogen experimental datasets. Further, the predictive performance of HNN-Cancer on diverse chemicals is comparable to the literature-reported models that included similar and less diverse molecules. Our HNN-Cancer could be used in identifying potentially carcinogenic chemicals for a wide variety of chemical classes.
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Affiliation(s)
| | - Sivanesan Dakshanamurthy
- Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
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33
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Nanashima A, Imamura N, Nishida T, Hiyoshi M, Uchise Y, Hamada T, Yano K, Tsuchimochi Y. A rare case of long-term survival of a patient who underwent radical operations for sextuple malignancies. Clin J Gastroenterol 2022; 15:1169-1172. [PMID: 36242750 DOI: 10.1007/s12328-022-01714-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/25/2022] [Indexed: 11/07/2022]
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34
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Vet-OncoNet: Malignancy Analysis of Neoplasms in Dogs and Cats. Vet Sci 2022; 9:vetsci9100535. [PMID: 36288148 PMCID: PMC9611943 DOI: 10.3390/vetsci9100535] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 12/02/2022] Open
Abstract
Simple Summary An overview analysis of tumors in dogs and cats, dividing them into malignant and benign, may provide previously unknown information about the biological behavior of tumors in these species and may serve many veterinarians as a support for clinical decision making. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, the analysis found that cats have a fourfold risk of malignant tumors, as in some topographies. Sex appears to play a role in the malignancy only in dogs. Some dog breeds (Pit bull and Boxer) have a higher risk of malignant tumors as opposed to Shih tzu and Yorkshire terrier. District of residence was not relevant in predicting malignancy risk. Most importantly, the risk of malignant tumors increases by 20% every three years. Abstract Analysis of canine and feline tumor malignancy data can help clinicians identify high-risk patients and make more accurate decisions. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, collected from January 2019 to December 2021 in the Vet-OncoNet Network database, this study aimed to compare the tumor malignancy profile between cats and dogs, considering animal-related factors (sex, age, and breed), topography, and geographic location using a mixed-effects logistic regression model. Cats had a higher proportion of malignant tumors (78.7%) than dogs (46.2%), and the malignancy profile was very different regarding tumors’ topographies. The mean age of malignant tumors occurred eight months later than benign ones (9.1, SD = 3.4; 9.8, SD = 3.2), in general. Species (OR = 3.96, 95%CI 3.57: 4.39) and topography (MOR = 4.10) were the two most important determinants of malignancy risk. Female dogs had a higher risk than male dogs (OR = 1.19, 95%CI 1.08: 1.31), which does not appear to be the case in cats (OR = 0.98, 95%CI 0.77: 1.23). Breed contributed significantly to differences in malignancy risk in dogs (MOR = 1.56), particularly in pit bulls and boxers. District of residence was not so relevant in predicting malignancy risk (MOR = 1.14). In both species, the risk of malignancy increased by approximately 20% every three years. It could be hypothesized that species differences in genetic structure may contribute to tumor malignancy.
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35
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Kobets T, Smith BPC, Williams GM. Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk. Foods 2022; 11:2828. [PMID: 36140952 PMCID: PMC9497933 DOI: 10.3390/foods11182828] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/07/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Commonly consumed foods and beverages can contain chemicals with reported carcinogenic activity in rodent models. Moreover, exposures to some of these substances have been associated with increased cancer risks in humans. Food-borne carcinogens span a range of chemical classes and can arise from natural or anthropogenic sources, as well as form endogenously. Important considerations include the mechanism(s) of action (MoA), their relevance to human biology, and the level of exposure in diet. The MoAs of carcinogens have been classified as either DNA-reactive (genotoxic), involving covalent reaction with nuclear DNA, or epigenetic, involving molecular and cellular effects other than DNA reactivity. Carcinogens are generally present in food at low levels, resulting in low daily intakes, although there are some exceptions. Carcinogens of the DNA-reactive type produce effects at lower dosages than epigenetic carcinogens. Several food-related DNA-reactive carcinogens, including aflatoxins, aristolochic acid, benzene, benzo[a]pyrene and ethylene oxide, are recognized by the International Agency for Research on Cancer (IARC) as causes of human cancer. Of the epigenetic type, the only carcinogen considered to be associated with increased cancer in humans, although not from low-level food exposure, is dioxin (TCDD). Thus, DNA-reactive carcinogens in food represent a much greater risk than epigenetic carcinogens.
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Affiliation(s)
- Tetyana Kobets
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
| | - Benjamin P. C. Smith
- Future Ready Food Safety Hub, Nanyang Technological University, Singapore 639798, Singapore
| | - Gary M. Williams
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
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Kumari S, Sharma S, Advani D, Khosla A, Kumar P, Ambasta RK. Unboxing the molecular modalities of mutagens in cancer. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:62111-62159. [PMID: 34611806 PMCID: PMC8492102 DOI: 10.1007/s11356-021-16726-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 09/22/2021] [Indexed: 04/16/2023]
Abstract
The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.
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Affiliation(s)
- Smita Kumari
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Sudhanshu Sharma
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Dia Advani
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Akanksha Khosla
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Pravir Kumar
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Rashmi K Ambasta
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India.
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Abstract
This essay considers the mid-twentieth century adoption of genetic explanations for three biological phenomena: nutritional adaptation, antibiotic resistance, and antibody production. This occurred at the same time as the hardening of the neo-Darwinian Synthesis in evolutionary theory. I argue that these concurrent changes reflect an ascendant narrative of genetic selfhood, which prioritized random hereditary variation and selection through competition, and marginalized physiological or environmental adaptation. This narrative was further reinforced by the Central Dogma of molecular biology and fit well with liberal political thought, with its focus on the autonomous individual. However, bringing biological findings into line with this narrative required modifying the notion of the gene to account for various kinds of non-Mendelian inheritance. Hans-Jörg Rheinberger's reflections on narrative and experiment are valuable in thinking about the friction between the postwar ideal of genetic selfhood and actual observations of how organisms adapt in response to the environment.
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Affiliation(s)
- Angela N. H. Creager
- Thomas M. Siebel Professor in the History of SciencePrinceton UniversityDepartment of History
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Rahman HH, Niemann D, Munson-McGee SH. Association between environmental toxic metals, arsenic and polycyclic aromatic hydrocarbons and chronic obstructive pulmonary disease in the US adult population. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:54507-54517. [PMID: 35303226 DOI: 10.1007/s11356-022-19695-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 03/09/2022] [Indexed: 06/14/2023]
Abstract
Associations between environmental metals and chemicals and adverse human health effects have emerged recently, but the links among environmental metals and respiratory diseases are less studied. The aim of this study was to assess 14 urinary metals (cadmium, barium, cobalt, molybdenum, mercury, cesium, manganese, antimony, lead, tin, strontium, tungsten, thallium, and uranium), seven species of arsenic (arsenous acid, arsenic acid, arsenobetaine, arsenocholine, dimethylarsinic acid, monomethylarsonic acid, and total arsenic) and seven polycyclic aromatic hydrocarbon (PAH) (1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene, 2 & 3-hydroxyphenanthrene) compounds' concentrations in urine and the correlation with chronic obstructive pulmonary disease (COPD) in the adult US population. A cross-sectional analysis using the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES) dataset was conducted. Self-questionnaires related to COPD criteria were used to identify the COPD cases. The correlation between urinary metals and PAH compounds and COPD was calculated. The total study population analyzed included 2885 adults aged 20 years and older. Seven types of urinary PAHs including 1-hydroxynaphthalene [odds ratio (OR): 1.832, 95% confidence interval (CI): 1.210, 2.775], 2-hydroxynaphthalene [OR: 3.361, 95% CI: 1.519, 7.440], 3-hydroxyfluorene [OR: 2.641, 95% CI: 1.381, 5.053], 2-hydroxyfluorene [OR: 3.628, 95% CI: 1.754, 7.506], 1-hydroxyphenanthrene [OR: 2.864, 95% CI: 1.307, 6.277], 1-hydroxypyrene [OR: 4.949, 95% CI: 2.540, 9.643] and 2 & 3-hydroxyphenanthrene [OR: 3.487, 95% CI: 1.382, 8.795] were positively associated with COPD. Urinary cadmium [OR: 12.382, 95% CI: 4.459, 34.383] and tin [OR: 1.743, 95% CI: 1.189, 2.555] showed positive associations with increased odds of COPD. The other types of urinary metals were not associated with COPD. The study observed that urinary PAHs, cadmium, and tin are significantly associated with COPD.
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Affiliation(s)
| | - Danielle Niemann
- Burrell College of Osteopathic Medicine, 3501 Arrowhead Dr, Las Cruces, NM, 88003, USA
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Wang Y, Fang T, Wang Y, Yin X, Zhang L, Zhang X, Zhang D, Zhang Y, Wang X, Wang H, Xue Y. Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer. BMC Cancer 2022; 22:635. [PMID: 35681154 PMCID: PMC9178847 DOI: 10.1186/s12885-022-09594-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 04/22/2022] [Indexed: 11/18/2022] Open
Abstract
Background The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model. Methods We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC. Results Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC. Conclusion AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09594-1.
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Affiliation(s)
- Yufei Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Tianyi Fang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Yimin Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Xin Yin
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Lei Zhang
- Department of Pathology, Harbin Medical University, Harbin, China
| | - Xinghai Zhang
- Department of Pathology, Harbin Medical University, Harbin, China
| | - Daoxu Zhang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Yao Zhang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Xibo Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Hao Wang
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China
| | - Yingwei Xue
- Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China.
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Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß. Cancers (Basel) 2022; 14:cancers14112772. [PMID: 35681752 PMCID: PMC9179891 DOI: 10.3390/cancers14112772] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 05/17/2022] [Accepted: 05/30/2022] [Indexed: 01/27/2023] Open
Abstract
Simple Summary PBDEs have been reported to have endocrine-disrupting and tumour-promoting activity; however, the effects of BDE209 (the highest brominated PBDEs) on the thyroid and the underlying mechanisms are unclear. In this study, we found that long-term exposure to BDE209 could cause chronic toxicity and potential tumourigenesis by inhibiting the expression and function of TRß, which induces the proliferation of thyroid tissue and the oncogenesis of thyroid carcinoma. These findings emphasize the damaging effects that exposure to BDE209 has on human thyroid and papillary thyroid carcinoma. Abstract Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß.
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van der Sloot KWJ, Tiems JL, Visschedijk MC, Festen EAM, van Dullemen HM, Weersma RK, Kats-Ugurlu G, Dijkstra G. Cigarette Smoke Increases Risk for Colorectal Neoplasia in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2022; 20:798-805.e1. [PMID: 33453400 DOI: 10.1016/j.cgh.2021.01.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 12/05/2020] [Accepted: 01/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel disease are at increased risk of colorectal neoplasia (CRN) due to mucosal inflammation. As current surveillance guidelines form a burden on patients and healthcare costs, stratification of high-risk patients is crucial. Cigarette smoke reduces inflammation in ulcerative colitis (UC) but not Crohn's disease (CD) and forms a known risk factor for CRN in the general population. Due to this divergent association, the effect of smoking on CRN in IBD is unclear and subject of this study. METHODS In this retrospective cohort study, 1,386 IBD patients with previous biopsies analyzed and reported in the PALGA register were screened for development of CRN. Clinical factors and cigarette smoke were evaluated. Patients were stratified for guideline-based risk of CRN. Cox-regression modeling was used to estimate the effect of cigarette smoke and its additive effect within the current risk stratification for prediction of CRN. RESULTS 153 (11.5%) patients developed CRN. Previously described risk factors, i.e. first-degree family member with CRN in CD (p-value=.001), presence of post-inflammatory polyps in UC (p-value=.005), were replicated. Former smoking increased risk of CRN in UC (HR 1.73; 1.05-2.85), whereas passive smoke exposure yielded no effect. For CD, active smoking (2.20; 1.02-4.76) and passive smoke exposure (1.87; 1.09-3.20) significantly increased CRN risk. Addition of smoke exposure to the current risk-stratification model significantly improved model fit for CD. CONCLUSIONS This study is the first to describe the important role of cigarette smoke in CRN development in IBD patients. Adding this risk factor improves the current risk stratification for CRN surveillance strategies.
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Affiliation(s)
- Kimberley W J van der Sloot
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands; Department of Epidemiology, Groningen, the Netherlands.
| | | | | | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
| | | | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands
| | | | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands
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Sarver AL, Makielski KM, DePauw TA, Schulte AJ, Modiano JF. Increased risk of cancer in dogs and humans: a consequence of recent extension of lifespan beyond evolutionarily-determined limitations? AGING AND CANCER 2022; 3:3-19. [PMID: 35993010 PMCID: PMC9387675 DOI: 10.1002/aac2.12046] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Cancer is among the most common causes of death for dogs (and cats) and humans in the developed world, even though it is uncommon in wildlife and other domestic animals. We provide a rationale for this observation based on recent advances in our understanding of the evolutionary basis of cancer. Over the course of evolutionary time, species have acquired and fine-tuned adaptive cancer protective mechanisms that are intrinsically related to their energy demands, reproductive strategies, and expected lifespan. These cancer protective mechanisms are general across species and/or specific to each species and their niche, and they do not seem to be limited in diversity. The evolutionarily acquired cancer-free longevity that defines a species' life history can explain why the relative cancer risk, rate, and incidence are largely similar across most species in the animal kingdom despite differences in body size and life expectancy. The molecular, cellular, and metabolic events that promote malignant transformation and cancerous growth can overcome these adaptive, species-specific protective mechanisms in a small proportion of individuals, while independently, some individuals in the population might achieve exceptional longevity. In dogs and humans, recent dramatic alterations in healthcare and social structures have allowed increasing numbers of individuals in both species to far exceed their species-adapted longevities (by 2-4 times) without allowing the time necessary for compensatory natural selection. In other words, the cancer protective mechanisms that restrain risk at comparable levels to other species for their adapted lifespan are incapable of providing cancer protection over this recent, drastic and widespread increase in longevity.
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Affiliation(s)
- Aaron L. Sarver
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN,Institute for Health Informatics, University of Minnesota, Minneapolis, MN,Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN
| | - Kelly M. Makielski
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN,Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN
| | - Taylor A DePauw
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN,Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN
| | - Ashley J. Schulte
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN,Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN
| | - Jaime F. Modiano
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN,Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN,Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN,Center for Immunology, University of Minnesota, Minneapolis, MN,Stem Cell Institute, University of Minnesota, Minneapolis, MN,Institute for Engineering in Medicine, University of Minnesota, Minneapolis, MN
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Steil GJ, Buzzo JLA, de Oliveira Ribeiro CA, Filipak Neto F. Polybrominated diphenyl ethers BDE-47 and BDE-99 modulate murine melanoma cell phenotype in vitro. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:11291-11303. [PMID: 34535858 DOI: 10.1007/s11356-021-16455-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 09/06/2021] [Indexed: 06/13/2023]
Abstract
Cancer is one of the leading causes of mortality worldwide. Even with the advances of pharmaceutical industry and treatments, the mortality rate for various types of cancer remains high. In particular, phenotypic alterations of tumor cells concerning drug efflux, migratory and invasive capabilities may represent a hurdle for cancer treatment and contribute to poor prognosis. In the present study, we investigated the effects of polybrominated diphenyl ethers (PBDEs) used as flame retardants on phenotypic features of melanoma cells that are important for cancer. Murine melanoma B16-F1 (less metastatic) and B16-F10 (more metastatic) cells were exposed to 0.01-1.0 nM of BDE-47 (2,2',4,4'-tetrabromodiphenyl ether), BDE-99 (2,2',4,4',5-pentabromodiphenyl ether), and the mixture of both (at 0.01 nM) for 24 h (acute exposure) and 15 days (chronic exposure). The polybrominated diphenyl ethers (PBDEs) did not affect cell viability but led to increased drug efflux transporter activity, cell migration, and colony formation, as well as overexpression of Abcc2 (ATP-binding cassette subfamily C member 2), Mmp-2 (matrix metalloproteinase-2), Mmp-9 (matrix metalloproteinase-9), and Tp53 (tumor protein p53) genes and downregulation of Timp-3 (tissue inhibitor of metalloproteinase 3) gene in B16-F10 cells. These effects are consistent with increased aggressiveness and malignancy of tumors due to exposure to the flame retardants and raise some concerns on the effects such chemicals may have on melanoma treatment and cancer prognosis.
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Affiliation(s)
- Gisleine Jarenko Steil
- Departamento de Biologia Celular, Universidade Federal do Paraná, PO Box: 19031, CEP, Curitiba, PR, 81531-980, Brazil
| | - João Luiz Aldinucci Buzzo
- Departamento de Biologia Celular, Universidade Federal do Paraná, PO Box: 19031, CEP, Curitiba, PR, 81531-980, Brazil
| | | | - Francisco Filipak Neto
- Departamento de Biologia Celular, Universidade Federal do Paraná, PO Box: 19031, CEP, Curitiba, PR, 81531-980, Brazil.
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Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice. Antioxidants (Basel) 2022; 11:antiox11010119. [PMID: 35052622 PMCID: PMC8773186 DOI: 10.3390/antiox11010119] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/16/2021] [Accepted: 12/06/2021] [Indexed: 02/06/2023] Open
Abstract
Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of fish oil (FO), significantly decreased DNA adduct formation by polycyclic aromatic hydrocarbons (PAHs). B6C3F1 male mice were fed an FO or corn oil (CO) diet, or A/J male mice were pre-fed with omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). While the B6C3F1 mice were administered two doses of a mixture of seven carcinogenic PAHs including benzo(a)pyrene (BP), the A/J mice were treated i.p. with pure benzo[a]pyrene (BP). Animals were euthanized after 1, 3, or 7 d after PAH treatment. DNA adduct levels were measured by the 32P-postlabeling assay. Our results showed that DNA adduct levels in the lungs of mice 7 d after treatment were significantly decreased in the FO or EPA/DHA groups compared with the CO group. Interestingly, both qPCR and Western blot analyses revealed that FO, DHA and EPA/DHA significantly decreased the expression of cytochrome P450 (CYP) 1B1. CYP1B1 plays a critical role in the metabolic activation of BP to DNA-reactive metabolites. qPCR also showed that the expression of some metabolic and DNA repair genes was induced by BP and inhibited by FO or omega-3 fatty acids in liver, but not lung. Our results suggest that a combination of mechanism entailing CYP1B1 inhibition and the modulation of DNA repair genes contribute to the attenuation of PAH-mediated carcinogenesis by omega 3 fatty acids.
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Moradian F, Fararouei M, Karami M, Ghelichi-Ghojogh M, Gheibi Z, Nikeghbalian Z, Akbari A, Akbari ME. Trend of geographical distribution of stomach cancer in Iran from 2004 to 2014. BMC Gastroenterol 2022; 22:4. [PMID: 34983394 PMCID: PMC8725466 DOI: 10.1186/s12876-021-02066-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 12/09/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Among different common types of cancer, gastric cancer (GC) is a worldwide health priority in both developing and developed countries. The aim of this study was to map the distribution of incident cases of GC in Iran to provide a geographical presentation of the incidence of the disease. METHODS This study used the Iranian National Cancer Registry (INCR) data from 2004 to 2014. We calculated the crude and age-standardized incidence rates of GC for each province and also defined the frequency distribution of different types and locations of GC by the provinces. RESULTS According to the results of the present study, the patients were predominantly male 49,907 (70.0%) and the most prevalent type of tumour was A1 (almost 96.4%) and C3 (2.0%). Also, a significant difference was observed between males and females in the distribution of the types of tumour (P < 0.001). In addition, a comparison of the distribution of the types of GC in Iran suggested that a significant difference exists between the provinces (P < 0.001). A significant difference was observed when the distribution of the location of GC tumors was compared between males and females and provinces (P < 0.001). Accordingly, pylori and cardia are the most common location of GC cancer among the study population (28.1% and 31.3% respectively). CONCLUSIONS The results of the current study suggested a higher rate of GC incidence in Iran when compared to the global figure in both females and males. Our study also revealed significant disparities between provinces with regard to the distribution of types, and location of GC. This may suggest involving different factors in GC in different parts of Iran. Further studies are needed to better understand the epidemiology and etiology of the disease in Iran.
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Affiliation(s)
- Farid Moradian
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Fararouei
- HIV/ADIS Research Center, School of Health, Shiraz University of Medical Science, Shiraz, Iran
| | - Maryam Karami
- School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Zahra Gheibi
- Department of Epidemiology, Shiraz University of Medical Science, Shiraz, Iran
| | - Zahra Nikeghbalian
- School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atieh Akbari
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wu K, Shi M, Pan X, Zhang J, Zhang X, Shen T, Tian Y. Decolourization and biodegradation of methylene blue dye by a ligninolytic enzyme-producing Bacillus thuringiensis: degradation products and pathway. Enzyme Microb Technol 2022; 156:109999. [DOI: 10.1016/j.enzmictec.2022.109999] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 01/13/2022] [Accepted: 01/28/2022] [Indexed: 01/17/2023]
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Terry K, Mayer DK, Wehner K. Alcohol Consumption: Discussing Potential Risks for Informed Decisions in Breast Cancer Survivors. Clin J Oncol Nurs 2021; 25:672-679. [PMID: 34800107 DOI: 10.1188/21.cjon.672-679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Alcohol consumption is a known risk factor for breast cancer. Because breast cancer survivors are already at risk for recurrence, it is important to understand whether these survivors could benefit from survivor-specific recommendations for alcohol consumption. OBJECTIVES The purpose of this article was to review primary research specific to alcohol and breast cancer survivors to see whether those who consume alcohol experience more adverse effects. METHODS This literature review examined nine cohort studies specific to breast cancer survivors, alcohol consumption, and risks for breast cancer recurrence, breast cancer-specific mortality, and second primary breast cancers. FINDINGS Current guideline recommendations of a safe limit of one drink per day or less may not protect breast cancer survivors from cancer- related adverse events. The authors recommend that breast cancer survivors be educated about the associated risks of alcohol consumption so that they can make informed decisions about usage.
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Tassinari R, Maranghi F. Rodent Model of Gender-Affirming Hormone Therapies as Specific Tool for Identifying Susceptibility and Vulnerability of Transgender People and Future Applications for Risk Assessment. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:12640. [PMID: 34886364 PMCID: PMC8656759 DOI: 10.3390/ijerph182312640] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/23/2021] [Accepted: 11/27/2021] [Indexed: 12/11/2022]
Abstract
Transgenders (TGs) are individuals with gender identity and behaviour different from the social norms; they often undergo gender-affirming hormone therapy (HT). HT for TG men involves testosterone treatment and, for TG women, oestrogen plus androgen-lowering agents. Due-but not limited-to the lifelong lasting HT, usually TG people experience several physical and behavioural conditions leading to different and specific susceptibility and vulnerability in comparison to general population, including the response to chemical contaminants present in daily life. In particular, the exposure to the widespread endocrine disrupters (EDs) may affect hormonal and metabolic processes, leading to tissue and organ damage. Since the endocrine system of TG people is overstimulated by HT and, often, the targets overlap with ED, it is reasonable to hypothesize that TG health deserves special attention. At present, no specific tools are available to study the toxicological effects of environmental contaminants, including EDs, and the potential long-term consequences of HT on TG people. In this context, the development of adequate and innovative animal models to mimic gender-affirming HT have a high priority, since they can provide robust data for hazard identification in TG women and men, leading to more reliable risk assessment.
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Affiliation(s)
- Roberta Tassinari
- Center for Gender-Specific Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy;
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Cheng ES, Weber M, Steinberg J, Yu XQ. Lung cancer risk in never-smokers: An overview of environmental and genetic factors. Chin J Cancer Res 2021; 33:548-562. [PMID: 34815629 PMCID: PMC8580800 DOI: 10.21147/j.issn.1000-9604.2021.05.02] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 09/17/2021] [Indexed: 01/22/2023] Open
Abstract
Lung cancer is the leading cause of cancer-related mortality globally, accounting for 1.8 million deaths in 2020. While the vast majority are caused by tobacco smoking, 15%-25% of all lung cancer cases occur in lifelong never-smokers. The International Agency for Research on Cancer (IARC) has classified multiple agents with sufficient evidence for lung carcinogenesis in humans, which include tobacco smoking, as well as several environmental exposures such as radon, second-hand tobacco smoke, outdoor air pollution, household combustion of coal and several occupational hazards. However, the IARC evaluation had not been stratified based on smoking status, and notably lung cancer in never-smokers (LCINS) has different epidemiological, clinicopathologic and molecular characteristics from lung cancer in ever-smokers. Among several risk factors proposed for the development of LCINS, environmental factors have the most available evidence for their association with LCINS and their roles cannot be overemphasized. Additionally, while initial genetic studies largely focused on lung cancer as a whole, recent studies have also identified genetic risk factors for LCINS. This article presents an overview of several environmental factors associated with LCINS, and some of the emerging evidence for genetic factors associated with LCINS. An increased understanding of the risk factors associated with LCINS not only helps to evaluate a never-smoker's personal risk for lung cancer, but also has important public health implications for the prevention and early detection of the disease. Conclusive evidence on causal associations could inform longer-term policy reform in a range of areas including occupational health and safety, urban design, energy use and particle emissions, and the importance of considering the impacts of second-hand smoke in tobacco control policy.
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Affiliation(s)
- Elvin S Cheng
- The Daffodil Centre, the University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW 2011, Australia
| | - Marianne Weber
- The Daffodil Centre, the University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW 2011, Australia
| | - Julia Steinberg
- The Daffodil Centre, the University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW 2011, Australia
| | - Xue Qin Yu
- The Daffodil Centre, the University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW 2011, Australia
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Chavda VP, Ertas YN, Walhekar V, Modh D, Doshi A, Shah N, Anand K, Chhabria M. Advanced Computational Methodologies Used in the Discovery of New Natural Anticancer Compounds. Front Pharmacol 2021; 12:702611. [PMID: 34483905 PMCID: PMC8416109 DOI: 10.3389/fphar.2021.702611] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 07/21/2021] [Indexed: 12/15/2022] Open
Abstract
Natural chemical compounds have been widely investigated for their programmed necrosis causing characteristics. One of the conventional methods for screening such compounds is the use of concentrated plant extracts without isolation of active moieties for understanding pharmacological activity. For the last two decades, modern medicine has relied mainly on the isolation and purification of one or two complicated active and isomeric compounds. The idea of multi-target drugs has advanced rapidly and impressively from an innovative model when first proposed in the early 2000s to one of the popular trends for drug development in 2021. Alternatively, fragment-based drug discovery is also explored in identifying target-based drug discovery for potent natural anticancer agents which is based on well-defined fragments opposite to use of naturally occurring mixtures. This review summarizes the current key advancements in natural anticancer compounds; computer-assisted/fragment-based structural elucidation and a multi-target approach for the exploration of natural compounds.
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Affiliation(s)
- Vivek P Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, L.M. College of Pharmacy, Ahmedabad, India
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, Kayseri, Turkey.,ERNAM-Nanotechnology Research and Application Center, Erciyes University, Kayseri, Turkey
| | - Vinayak Walhekar
- Department of Medicinal Chemistry, Bharati Vidyapeeth's Poona College of Pharmacy, Pune, India
| | - Dharti Modh
- Department of Medicinal Chemistry, Bharati Vidyapeeth's Poona College of Pharmacy, Pune, India
| | - Avani Doshi
- Department of Chemistry, SAL Institute of Pharmacy, Ahmedabad, India
| | - Nirav Shah
- Department of Pharmaceutics, SAL Institute of Pharmacy, Ahmedabad, India
| | - Krishna Anand
- Faculty of Health Sciences and National Health Laboratory Service, Department of Chemical Pathology, School of Pathology, University of the Free State, Bloemfontein, South Africa
| | - Mahesh Chhabria
- Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, Ahmedabad, India
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