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Xie Y, Liu F, Wu Y, Zhu Y, Jiang Y, Wu Q, Dong Z, Liu K. Inflammation in cancer: therapeutic opportunities from new insights. Mol Cancer 2025; 24:51. [PMID: 39994787 PMCID: PMC11849313 DOI: 10.1186/s12943-025-02243-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 01/20/2025] [Indexed: 02/26/2025] Open
Abstract
As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, and extracellular matrix are discussed. Since FDA-approved anti-inflammation drugs like aspirin show obvious anti-tumor effects, these drugs have unique advantages due to their relatively fewer side effects with long-term use compared to chemotherapy drugs. The characteristics make them promising candidates for cancer chemoprevention. Overall, this review discusses the role of these inflammatory molecules in carcinogenesis of cancer and new inflammation molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that have already been or are expected to be applied in clinical practice, as well as recent discoveries of the anti-tumor effect of non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. The advantages and disadvantages of their application in cancer chemoprevention are also discussed.
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Affiliation(s)
- Yifei Xie
- Department of Pathology and Forensic Medicine, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Fangfang Liu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Yunfei Wu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Yuer Zhu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
| | - Yanan Jiang
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Qiong Wu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China
| | - Zigang Dong
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China.
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China.
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China.
| | - Kangdong Liu
- State Key Laboratory of Metabolic Dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, 450052, China.
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, 450007, China.
- The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, China.
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Lu W, Aihaiti A, Abudukeranmu P, Liu Y, Gao H. Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers. Mol Cell Biochem 2025; 480:1225-1239. [PMID: 38963615 DOI: 10.1007/s11010-024-05057-2] [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: 05/27/2024] [Accepted: 06/25/2024] [Indexed: 07/05/2024]
Abstract
Gastrointestinal (GI) cancers are a major global health burden, representing 20% of all cancer diagnoses and 22.5% of global cancer-related deaths. Their aggressive nature and resistance to treatment pose a significant challenge, with late-stage survival rates below 15% at five years. Therefore, there is an urgent need to delve deeper into the mechanisms of gastrointestinal cancer progression and optimize treatment strategies. Increasing evidence highlights the active involvement of abnormal arachidonic acid (AA) metabolism in various cancers. AA is a fatty acid mainly metabolized into diverse bioactive compounds by three enzymes: cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. Abnormal AA metabolism and altered levels of its metabolites may play a pivotal role in the development of GI cancers. However, the underlying mechanisms remain unclear. This review highlights a unique perspective by focusing on the abnormal metabolism of AA and its involvement in GI cancers. We summarize the latest advancements in understanding AA metabolism in GI cancers, outlining changes in AA levels and their potential role in liver, colorectal, pancreatic, esophageal, gastric, and gallbladder cancers. Moreover, we also explore the potential of targeting abnormal AA metabolism for future therapies, considering the current need to explore AA metabolism in GI cancers and outlining promising avenues for further research. Ultimately, such investigations aim to improve treatment options for patients with GI cancers and pave the way for better cancer management in this area.
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Affiliation(s)
- Weiqin Lu
- General Surgery, Cancer Center, Department of Vascular Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | | | | | - Yajun Liu
- Aksu First People's Hospital, Xinjiang, China
| | - Huihui Gao
- Cancer Center, Department of Hospital Infection Management and Preventive Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Anson M, Poon JS, Henney AE, Riley D, Ibarbaru GH, Sieberhagen C, Cuthbertson DJ, Alam U, Hydes T. The chemoprotective effect of anti-platelet agents on cancer incidence in people with non-alcoholic fatty liver disease (NAFLD): a retrospective cohort study. BMC Med 2024; 22:574. [PMID: 39627877 PMCID: PMC11613771 DOI: 10.1186/s12916-024-03802-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 11/28/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of hepatic and extrahepatic cancers, in particular those linked to obesity. In people with chronic liver disease, aspirin may confer protection against hepatocellular carcinoma (HCC). We explore the potential chemoprotective effect of aspirin/other anti-platelet agents on obesity-related cancers, including HCC in people with NAFLD. METHODS We performed a retrospective cohort study of anonymised electronic medical records using the TriNetX network (Cambridge, MA, USA), a global federated database. We identified adults aged 18 or over with a diagnosis of NAFLD, prior to commencing antiplatelet agents. Two groups were created: antiplatelet (1) versus no antiplatelet use (2). We propensity score matched for nine variables. Antiplatelet use was defined as aspirin, ticagrelor, cangrelor, clopidogrel or prasugrel use for at least 1 year. The outcomes of interest were incidence of HCC and other obesity-related cancers. Follow-up was for 5 years. We performed subgroup analyses on aspirin users only and stratified findings for sex and age. Sensitivity analysis was conducted on individuals with 3- and 5-year aspirin exposure. RESULTS Post matching, there were 42,192 people per group. Antiplatelet use in people with NAFLD was associated with statistically significant reduction in all obesity-related cancers (HR 0.71, 95% CI 0.65-0.78, p < 0.001) and individually for HCC (HR 0.52, 95% CI 0.40-0.68, p < 0.001), breast carcinoma (HR 0.78, 95% CI 0.66-0.92, p = 0.003), pancreatic carcinoma (HR 0.61, 95% CI 0.47-0.78, p < 0.001) and colorectal carcinoma (HR 0.68, 95% CI 0.56-0.84, p < 0.001). For women, there was a significant reduction in risk of ovarian carcinoma (HR 0.75, 95% CI 0.57-0.98, p = 0.034). Aspirin monotherapy was similarly associated with reduced incidence of HCC (HR 0.46, 95% CI 0.32-0.64, p < 0.001) and all obesity-related cancers (HR 0.71, 95% CI, 0.56-0.90, p = 0.004), with benefits observed in males (HR 0.71, 95% CI 0.56-0.90, p = 0.004), females (HR 0.77, 95% CI 0.67-0.88, p < 0.001) and in older (HR 0.72, 95% CI 0.63-0.82, p < 0.001) but not younger people (HR 0.78, 95% CI 0.60-1.03, p = 0.589). CONCLUSIONS Aspirin/antiplatelet agents may have a role in primary cancer prevention in people living with NAFLD.
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Affiliation(s)
- Matthew Anson
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Jun Shang Poon
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Alex E Henney
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - David Riley
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | | | - Cyril Sieberhagen
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Daniel J Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Uazman Alam
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Theresa Hydes
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK.
- University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
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Ren X, Xin L, Peng L, Xiao Y, Zhou Z, Luo H, Zhu Z, Wei Q, Jiang Y, He H, Xiang L, Wang Y, Tang Y, Gu H. Association between sulfur microbial diet and the risk of esophageal cancer: a prospective cohort study in 101,752 American adults. Nutr J 2024; 23:139. [PMID: 39511614 PMCID: PMC11542201 DOI: 10.1186/s12937-024-01035-y] [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: 06/30/2023] [Accepted: 10/15/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Sulfur microbial diet (SMD) is a dietary pattern closely related to the intestinal load of sulfur-metabolizing microbes in humans. Diet and microbes may play an important role in the carcinogenesis of esophagus. However, epidemiological studies on SMD and esophageal cancer (EC) risk are scarce. Here, we evaluated this association based on a large American cohort. METHODS In the cohort of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a SMD score was calculated to evaluate participants' compliance of SMD pattern, with higher scores presenting greater adherence. Cox hazards regression model was used to explore the association between the SMD score and the incidence of EC, esophageal squamous cell carcinoma (ESCC), and esophageal adenocarcinoma (EA). Subgroup analyses were conducted to figure out potential modifiers interacting with SMD on EC. Sensitivity analyses were used to testify the robustness of our main result. RESULTS Among 101,752 participants, 154 EC cases, consisted of 41 ESCC cases and 97 EA cases, were identified with mean follow-up of 8.9 years. In the fully adjusted model, the highest versus the lowest quartiles of the SMD score were found to be associated with an increased risk of EC and ESCC (EC: HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HRQ4 vs. Q1: 1.41; P = 0.144 for trend). The main result remained through a series of sensitivity analyses. Subgroup analyses showed a stronger association between SMD and EC in participants with no regular consumption of aspirin (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 vs. Q1: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction). CONCLUSION Adherence to the SMD pattern may be associated with increased risks of EC and ESCC, particularly for EC in individuals who do not regularly consume aspirin.
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Affiliation(s)
- Xiaorui Ren
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Li Xin
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Linglong Peng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Yi Xiao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Zhihang Zhou
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haoyun Luo
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Zhiyong Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Qi Wei
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Yahui Jiang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Hongmei He
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Ling Xiang
- Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yaxu Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China
| | - Yunhao Tang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China.
| | - Haitao Gu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.288 Tianwen Avenue, Nan'an District, Chongqing, 400010, China.
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Jiko PA, Mohammad M, Richi FT, Islam MA, Alam S, Taher MA, Shao C, Wang S, Geng P, Mamun AA. Anti-Inflammatory, Analgesic and Anti-Oxidant Effects of Shirakiopsis Indica (Willd). Fruit Extract: A Mangrove Species in the Field of Inflammation Research. J Inflamm Res 2024; 17:5821-5854. [PMID: 39228677 PMCID: PMC11370890 DOI: 10.2147/jir.s470835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/07/2024] [Indexed: 09/05/2024] Open
Abstract
Background Shirakiopsis indica (Willd)., commonly known as Sa-Mor-Ta-Lay in Thailand, is a mangrove plant belonging to the Euphorbiaceae family. As mangrove plants' medicinal potentials are less explored, this study sought to qualitatively and quantitatively verify the bioactive components of Shirakiopsis indica fruits methanolic extract (SIF-ME) at the side of its analgesic, anti-inflammatory and anti-oxidant effects followed by in-silico studies. Methods The in-vivo assessments of analgesic activity involved the hot plate test, acetic acid-induced writhing test, and formalin-induced licking test. The anti-inflammatory efficacy was assessed through the human RBC membrane stabilization assay (HRBC), protein denaturation assay, and xylene-induced ear edema methods. Antioxidant potential was implemented by the DPPH scavenging method. Results The SIF-ME consistently displayed significant anti-nociceptive activity in a dose-dependent pattern (p < 0.05). The maximum analgesic activity was found in the highest dose (200 mg/kg; p < 0.001) in a hot plate, acetic acid-induced writhing test 43.47%, and in formalin-induced licking test in both early phase (43.3%; p < 0.01) and late phase (61.84%; p < 0.001%). The extract provided optimal protection against hemolysis (83.41% decrease) at 1000 µg/mL and significantly inhibited protein denaturation (67.34-26.05%) at doses of 1000-62.5 µg/mL. At 200 mg/kg, the extract showed dose-dependent and substantial inhibition (54.07%; p < 0.01) of xylene-induced ear edema. The in-vitro DPPH (IC50 = 469.5 µg/mL) results showed remarkable scavenging activity and concentration-dependent reducing power. The extract demonstrates no acute oral toxicity, as indicated by an LD50 value exceeding 1000 mg/kg body weight. Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS) analysis was performed which yielded sixty bioactive compounds. In-silico and molecular docking studies revealed favorable pharmacological properties, including good binding affinities and ADME/T profiles. Conclusion These results support the medicinal use of the plant, which makes it a potential source of analgesic, anti-inflammatory, and antioxidant candidates.
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Affiliation(s)
- Pair Ahmed Jiko
- Department of Chemistry, Chittagong University of Engineering & Technology, Chittagong, 4349, Bangladesh
| | - Mahathir Mohammad
- Department of Chemistry, Chittagong University of Engineering & Technology, Chittagong, 4349, Bangladesh
| | - Fahmida Tasnim Richi
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Md. Anisul Islam
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4202, Bangladesh
| | - Safaet Alam
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
- Chemical Research Division, BCSIR Dhaka Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, 1205, Bangladesh
| | - Mohammad Abdullah Taher
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
- Bangladesh Reference Institute for Chemical Measurements (BRiCM), Laboratory Road, Dhaka, 1205, Bangladesh
| | - Chuxiao Shao
- Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Shuanghu Wang
- Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Peiwu Geng
- Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
| | - Abdullah Al Mamun
- Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China
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Patel J, Khanna T, Sohal A, Dhaliwal A, Chaudhry H, Kalra S, Singh I, Dukovic D, Bains K. Impact of aspirin use on rates of metastasis in patients with esophageal cancer: insights from the National Inpatient Sample. Dis Esophagus 2024; 37:doae022. [PMID: 38525938 DOI: 10.1093/dote/doae022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 02/20/2024] [Accepted: 03/04/2024] [Indexed: 03/26/2024]
Abstract
Despite advancing treatment methods, esophageal cancer (EC) maintains a high mortality rate and poor prognosis. Through various mechanisms, aspirin has been suggested to have a chemopreventive effect on EC. However, the long-term impact, particularly regarding the rate of metastasis, needs to be further elucidated. NIS 2016-2020 was used to identify adult patients (age > 18 years) with EC using ICD-10 codes. Patients with missing demographics and mortality were excluded. Patients were stratified into two groups based on aspirin use. Data were collected on patient demographics, Elixhauser Comorbidity Index (ECI), and comorbidities (hypertension, chronic pulmonary disease, coronary artery disease (CAD), chronic kidney disease (CKD), congestive heart failure (CHF), coagulopathy, alcohol use, smoking, and obesity). The outcomes studied were rates of total metastasis, gastrointestinal (GI) metastasis, non-GI metastasis, and lymphoid metastasis. Multivariate logistic regression analysis was performed to evaluate the impact of aspirin use on various metastases after adjusting for patient demographics, comorbidities, and ECI. Out of 190,655 patients, 20,650 (10.8%) patients were aspirin users. Majority of the patients in the aspirin group were aged > 65 years (74.7%), males (82.1%), White race (84%), and had medicare insurance (71%). There was a higher incidence of diabetes, hypertension, chronic pulmonary disease, CAD, CKD, CHF, and smoking in aspirin users than non-aspirin users. Patients with aspirin users had a lower incidence of metastasis (28.9% vs. 38.7%, P < 0.001), GI metastasis (14.2% vs. 20.6%, P < 0.001), non-GI metastasis (15.1% vs. 22%, P < 0.001), and lymphoid metastasis (8.9% vs. 11.3%, P < 0.001) than non-aspirin users. After adjusting for confounding factors, patients with aspirin use had lower odds of having metastasis (aOR-0.73, 95% CI-0.70-0.77, P < 0.001). Our study noted that aspirin use is associated with a reduction in the rate of metastasis in patients with EC. These studies support the use of aspirin in patients with EC and suggest the need for further studies to understand the mechanism by which aspirin use reduces metastasis in patients with EC.
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Affiliation(s)
- Jay Patel
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA
| | - Tejasvini Khanna
- Department of Medicine, Maulana Azad Medical College, New Delhi, India
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA, USA
| | - Armaan Dhaliwal
- Department of Internal Medicine, University of Arizona, Tucson, AZ, USA
| | - Hunza Chaudhry
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA, USA
| | - Shivam Kalra
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Ishandeep Singh
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Dino Dukovic
- Ross University School of Medicine, Miramar, FL, USA
| | - Kanwal Bains
- Department of Internal Medicine, University of Arizona, Tucson, AZ, USA
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Sugiyama F, Kanda M, Shimizu D, Umeda S, Inokawa Y, Hattori N, Hayashi M, Tanaka C, Nakayama G, Kodera Y. Absence of Hypercoagulation Status after Neoadjuvant Treatment is Associated with Favorable Prognosis in Patients Undergoing Subtotal Esophagectomy for Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2024; 31:3417-3425. [PMID: 38245650 DOI: 10.1245/s10434-024-14938-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 12/29/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood. METHODS Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis. RESULTS The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337). CONCLUSIONS Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy.
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Affiliation(s)
- Fumitake Sugiyama
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Dai Shimizu
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinichi Umeda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshikuni Inokawa
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Norifumi Hattori
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Chie Tanaka
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Goro Nakayama
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Muhammad Nawawi KN, El‐Omar EM, Ali RA. Screening, Surveillance, and Prevention of Esophageal and Gastric Cancers. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:42-62. [DOI: 10.1002/9781119756422.ch3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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9
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Li S, Hoefnagel SJM, Krishnadath KK. Molecular Biology and Clinical Management of Esophageal Adenocarcinoma. Cancers (Basel) 2023; 15:5410. [PMID: 38001670 PMCID: PMC10670638 DOI: 10.3390/cancers15225410] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/10/2023] [Accepted: 11/12/2023] [Indexed: 11/26/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is a highly lethal malignancy. Due to its rising incidence, EAC has become a severe health challenge in Western countries. Current treatment strategies are mainly chosen based on disease stage and clinical features, whereas the biological background is hardly considered. In this study, we performed a comprehensive review of existing studies and discussed how etiology, genetics and epigenetic characteristics, together with the tumor microenvironment, contribute to the malignant behavior and dismal prognosis of EAC. During the development of EAC, several intestinal-type proteins and signaling cascades are induced. The anti-inflammatory and immunosuppressive microenvironment is associated with poor survival. The accumulation of somatic mutations at the early phase and chromosomal structural rearrangements at relatively later time points contribute to the dynamic and heterogeneous genetic landscape of EAC. EAC is also characterized by frequent DNA methylation and dysregulation of microRNAs. We summarize the findings of dysregulations of specific cytokines, chemokines and immune cells in the tumor microenvironment and conclude that DNA methylation and microRNAs vary with each different phase of BE, LGD, HGD, early EAC and invasive EAC. Furthermore, we discuss the suitability of the currently employed therapies in the clinic and possible new therapies in the future. The development of targeted and immune therapies has been hampered by the heterogeneous genetic characteristics of EAC. In view of this, the up-to-date knowledge revealed by this work is absolutely important for future EAC studies and the discovery of new therapeutics.
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Affiliation(s)
- Shulin Li
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
- Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands
| | | | - Kausilia Krishnawatie Krishnadath
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, 2000 Antwerpen, Belgium
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Halma MTJ, Tuszynski JA, Marik PE. Cancer Metabolism as a Therapeutic Target and Review of Interventions. Nutrients 2023; 15:4245. [PMID: 37836529 PMCID: PMC10574675 DOI: 10.3390/nu15194245] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/20/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
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Affiliation(s)
- Matthew T. J. Halma
- Department of Physics and Astronomy, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
- EbMC Squared CIC, Bath BA2 4BL, UK
| | - Jack A. Tuszynski
- Department of Physics, University of Alberta, 11335 Saskatchewan Dr NW, Edmonton, AB T6G 2M9, Canada
- Department of Data Science and Engineering, The Silesian University of Technology, 44-100 Gliwice, Poland
- DIMEAS, Politecnico di Torino, Corso Duca degli Abruzzi 24, I-1029 Turin, Italy
| | - Paul E. Marik
- Frontline COVID-19 Critical Care Alliance, Washington, DC 20036, USA
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Hackner D, Hobbs M, Merkel S, Krautz C, Weber GF, Grützmann R, Brunner M. Impact of Aspirin Intake on Postoperative Survival after Primary Pancreatic Resection of Pancreatic Ductal Adenocarcinoma-A Single-Center Evaluation. Biomedicines 2023; 11:biomedicines11051466. [PMID: 37239137 DOI: 10.3390/biomedicines11051466] [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: 04/17/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
(1) Background: The intake of aspirin (ASS) has been demonstrated to have a relevant impact on the pathogenesis, incidence and outcome in different solid gastrointestinal tumors. However, data on the effect of ASS on the short-term outcome and the long-term survival in patients with pancreatic carcinoma are still limited. (2) Methods: A total of 213 patients who underwent primary resection of PDAC at the University Hospital of Erlangen from January 2000 to December 2018 were included in this retrospective single-center study in total. Patients were stratified according to the aspirin intake into three groups: continuous aspirin intake (cASS), perioperatively interrupted aspirin intake (iASS) and no aspirin intake (no ASS) at the timepoint of surgery. The postoperative outcome as well as long-term survival were compared between the groups. (3) Results: There were no differences regarding postoperative morbidity (iASS: 54% vs. cASS: 53% vs. no ASS: 64%, p = 0.448) and in-hospital mortality (iASS: 4% vs. cASS: 10% vs. no ASS: 3%, p = 0.198) between the groups. The overall survival (OS) and disease-free survival (DFS) did not differ in the groups when comparing the ASS-intake status (OS: iASS 17.8 months vs. cASS 19.6 months vs. no ASS 21.6 months, p = 0.489; DFS: iASS 14.0 months vs. cASS 18.3 months vs. no ASS 14.7 months, p = 0.957). Multivariate analysis revealed that age (hazard ratio (HR) 2.2, p < 0.001), lymph node-positive status (HR 2.0, p < 0.001), R status 1 or 2 (HR 2.8, p < 0.001) and differentiation with a grading of 3 (HR 1.7, p = 0.005) were significant independent prognostic factors regarding the OS. Moreover, age (HR 1.5, p = 0.040), lymph node-positive status (HR 1.8, p = 0.002) and high-grade (G3) carcinomas (HR 1.5, p = 0.037) could be identified as independent prognostic parameters for DFS. (4) Conclusions: In patients undergoing primary surgery for curative resection of pancreatic carcinoma, the perioperative intake of ASS had no significant impact on postoperative outcome, overall and disease-free survival.
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Affiliation(s)
- Danilo Hackner
- Department of General and Visceral Surgery, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Mirianna Hobbs
- Department of General and Visceral Surgery, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Susanne Merkel
- Department of General and Visceral Surgery, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Christian Krautz
- Department of General and Visceral Surgery, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Georg F Weber
- Department of General and Visceral Surgery, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Robert Grützmann
- Department of General and Visceral Surgery, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Maximilian Brunner
- Department of General and Visceral Surgery, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
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12
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Khanna R, Chitme HR, Bhadoriya K, Tripathi YC, Varshney VK. In vitro and in vivo anti-inflammatory activity of Cupressus torulosa D.DON needles extract and its chemical characterization. JOURNAL OF ETHNOPHARMACOLOGY 2023; 314:116578. [PMID: 37172917 DOI: 10.1016/j.jep.2023.116578] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 04/23/2023] [Accepted: 05/01/2023] [Indexed: 05/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cupressus torulosa (family Cupressaceae), widely distributed in the north western Himalayan region of India, is a coniferous aromatic tree with various traditional uses of its aerial parts. Its needles have been used for anti-inflammatory, anticonvulsant, antimicrobial, and wound-healing properties. AIM OF THE STUDY The study aimed at investigating the previously unknown anti-inflammatory activity of the hydromethanolic extract of the needles employing in vitro and in vivo assays and scientifically validate traditional claim of their use in treatment of inflammation. Chemical characterization of the extract with the aid of UPLCQTOFMS was also of interest. MATERIALS AND METHODS C. torulosa needles were first defatted with hexane and sequentially extracted with chloroform and 25% aqueous methanol (AM). Since the presence of phenolics (TPCs, 208.21 ± 0.95 mg GAE/g needles) and flavonoids (TFCs, 84.61 ± 1.21 mg QE/g needles) was observed in the AM extract only, it was chosen for biological and chemical examinations. Acute toxicity of the AM extract on female mice was evaluated following the OECD guideline 423. In vitro anti-inflammatory activity of the AM extract was examined using egg albumin denaturation assay while carrageenan-induced paw edema and formalin-induced paw edema models at doses of 100, 200 and 400 mg/kg po were used to determine the in vivo activity of the AM extract on Wistar rats of either sex. The components of the AM extract were analyzed by UPLC-QTOF-MS method using non-targeted metabolomics approach. RESULTS AM extract was found to be non-toxic at 2000 mg/kg b.w. with no signs of abnormal locomotion, seizures and writhing. The extract demonstrated promising in vitro anti-inflammatory activity (IC50 160.01 μg/mL) compared to standard diclofenac sodium (IC50 73.94 μg/mL) in egg albumin denaturation assay. In carrageenan-induced paw edema and formalin-induced paw edema tests the extract showed significant anti- inflammatory activity (57.28% and 51.04% inhibition of paw edema, respectively) at the dose of 400 mg/kg p.o. after 4 h in comparison to the standard diclofenac sodium which displayed 61.39% and 52.90% inhibition, respectively, at the dose of 10 mg/kg p.o. after 4 h in these models. A total of 63 chemical constituents, majority of them being phenolics, were found in the AM extract of the needles. Two compounds namely monotropein (iridoid glycoside), (±)12-HETE (eicosanoid) and fraxin (coumarin glycoside) were reported to have anti-inflammatory effect. CONCLUSIONS For the first time our study demonstrated that hydro-methanolic extract of C. torulosa needles exhibit anti-inflammatory activity thereby supporting their traditional use in the treatment of inflammatory disorders. UPLCQTOFMS assisted chemical profile of the extract was also unveiled.
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Affiliation(s)
- Radhika Khanna
- Chemistry & Bioprospecting Division, Forest Research Institute, Dehradun, 248006, India.
| | - H R Chitme
- Faculty of Pharmacy, DIT University Dehradun India, India
| | - Khushaboo Bhadoriya
- Chemistry & Bioprospecting Division, Forest Research Institute, Dehradun, 248006, India
| | - Y C Tripathi
- Chemistry & Bioprospecting Division, Forest Research Institute, Dehradun, 248006, India
| | - V K Varshney
- Chemistry & Bioprospecting Division, Forest Research Institute, Dehradun, 248006, India.
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Holmberg D, Gottlieb-Vedi E, Hedberg J, Lindblad M, Mattsson F, Lagergren J. Aspirin or statin use in relation to survival after surgery for esophageal cancer: a population-based cohort study. BMC Cancer 2023; 23:375. [PMID: 37098462 PMCID: PMC10127395 DOI: 10.1186/s12885-023-10819-0] [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: 09/21/2022] [Accepted: 04/06/2023] [Indexed: 04/27/2023] Open
Abstract
BACKGROUND Adjuvant postoperative treatment with aspirin and statins may improve survival in several solid tumors. This study aimed to assess whether these medications improve the survival after curatively intended treatment (including esophagectomy) for esophageal cancer in an unselected setting. METHODS This nationwide cohort study included nearly all patients who underwent esophagectomy for esophageal cancer in Sweden from 2006 to 2015, with complete follow-up throughout 2019. Risk of 5-year disease-specific mortality in users compared to non-users of aspirin and statins was analyzed using Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI). The HRs were adjusted for age, sex, education, calendar year, comorbidity, aspirin/statin use (mutual adjustment), tumor histology, pathological tumor stage, and neoadjuvant chemo(radio)therapy. RESULTS The cohort included 838 patients who survived at least 1 year after esophagectomy for esophageal cancer. Of these, 165 (19.7%) used aspirin and 187 (22.3%) used statins during the first postoperative year. Neither aspirin use (HR 0.92, 95% CI 0.67-1.28) nor statin use (HR 0.88, 95% CI 0.64-1.23) were associated with any statistically significant decreased 5-year disease-specific mortality. Analyses stratified by subgroups of age, sex, tumor stage, and tumor histology did not reveal any associations between aspirin or statin use and 5-year disease-specific mortality. Three years of preoperative use of aspirin (HR 1.26, 95% CI 0.98-1.65) or statins (HR 0.99, 95% CI 0.67-1.45) did not decrease the 5-year disease-specific mortality. CONCLUSIONS Use of aspirin or statins might not improve the 5-year survival in surgically treated esophageal cancer patients.
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Affiliation(s)
- Dag Holmberg
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13A, 4Th Floor, 171 77, Stockholm, Sweden.
| | - Eivind Gottlieb-Vedi
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13A, 4Th Floor, 171 77, Stockholm, Sweden
| | - Jakob Hedberg
- Department of Surgical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden
| | - Mats Lindblad
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Fredrik Mattsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13A, 4Th Floor, 171 77, Stockholm, Sweden
| | - Jesper Lagergren
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Retzius Street 13A, 4Th Floor, 171 77, Stockholm, Sweden
- School of Cancer and Pharmacological Sciences, King's College London, London, UK
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Beydoun AS, Stabenau KA, Altman KW, Johnston N. Cancer Risk in Barrett's Esophagus: A Clinical Review. Int J Mol Sci 2023; 24:ijms24076018. [PMID: 37046992 PMCID: PMC10094310 DOI: 10.3390/ijms24076018] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/21/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence and is associated with a poor prognosis. Barrett's esophagus (BE) is a known precursor of esophageal adenocarcinoma. This review aims to explore Barrett's esophagus, esophageal adenocarcinoma, and the progression from the former to the latter. An overview of the definition, diagnosis, epidemiology, and risk factors for both entities are presented, with special attention being given to the areas of debate in the literature. The progression from Barrett's esophagus to esophageal adenocarcinoma is reviewed and the relevant molecular pathways are discussed. The definition of Barrett's esophagus remains debated and without international consensus. This, alongside other factors, has made establishing the true prevalence of Barrett's esophagus challenging. The degree of dysplasia can be a histological challenge, but is necessary to guide clinical management. The progression of BE to EAC is likely driven by inflammatory pathways, pepsin exposure, upregulation of growth factor pathways, and mitochondrial changes. Surveillance is maintained through serial endoscopic evaluation, with shorter intervals recommended for high-risk features.
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Affiliation(s)
- Ahmed Sam Beydoun
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Kaleigh A Stabenau
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Kenneth W Altman
- Department of Otolaryngology-Head & Neck Surgery, Geisinger Medical Center, Danville, PA 17822, USA
| | - Nikki Johnston
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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Nandi A, Das A, Dey YN, Roy KK. The Abundant Phytocannabinoids in Rheumatoid Arthritis: Therapeutic Targets and Molecular Processes Identified Using Integrated Bioinformatics and Network Pharmacology. Life (Basel) 2023; 13:life13030700. [PMID: 36983855 PMCID: PMC10053995 DOI: 10.3390/life13030700] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/30/2023] [Accepted: 02/28/2023] [Indexed: 03/08/2023] Open
Abstract
The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To the best of our knowledge, no research has been done that explains the network-pharmacology-based anti-rheumatic processes by focusing on the endocannabinoid system. Therefore, the purpose of this study is to further our understanding of the signaling pathways, associated proteins, and genes underlying RA based on the abundant natural endocannabinoids. The knowledge on how the phytocannabinoids in Cannabis sativa affect the endocannabinoid system was gathered from the literature. SwissTarget prediction and BindingDB databases were used to anticipate the targets for the phytocannabinoids. The genes related to RA were retrieved from the DisGeNET and GeneCards databases. Protein–protein interactions (high confidence > 0.7) were carried out with the aid of the string web server and displayed using Cytoscape. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis was used to perform enrichment analyses on the endocannabinoid–RA common targets. ShinyGO 0.76 was used to predict the biological processes listed in the Gene Ontology (GO) classification system. The binding affinity between the ligand and the receptors was precisely understood using molecular docking, induced-fit docking, and a molecular dynamics simulation. The network pharmacology analyses predicted that processes like response to oxygen-containing compounds and peptodyl-amino acid modification are related to the potential mechanisms of treatment for RA. These biological actions are coordinated by cancer, neuroactive ligand–receptor interaction, lipids and atherosclerosis, the calcium signaling pathway, and the Rap1 signaling pathway. According to the results of molecular docking, in the context of RA, phytocannabinoids may bind to important target proteins such PIK3CA, AKT1, MAPK9, PRKCD, BRAF, IGF1R, and NOS3. This entire study predicted the phytocannabinoids’ systemic biological characteristics. Future experimental research is needed, however, to confirm the results so far.
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Affiliation(s)
- Arijit Nandi
- Department of Pharmacology, Dr. B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur 713206, West Bengal, India
| | - Anwesha Das
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Ahmedabad, Palaj, Gandhinagar 382355, Gujarat, India
| | - Yadu Nandan Dey
- Department of Pharmacology, Dr. B.C. Roy College of Pharmacy and Allied Health Sciences, Durgapur 713206, West Bengal, India
- Correspondence: (Y.N.D.); (K.K.R.)
| | - Kuldeep K. Roy
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES University, Dehradun 248007, Uttarakhand, India
- Correspondence: (Y.N.D.); (K.K.R.)
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Hoefnagel SJ, Li S, Timmer EM, Meijer SL, Krishnadath KK. Increased PXR and Suppressed T-Cell Signaling Are Associated With Malignant Degeneration of Barrett's Esophagus. GASTRO HEP ADVANCES 2022; 2:63-71. [PMID: 39130159 PMCID: PMC11308616 DOI: 10.1016/j.gastha.2022.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 08/18/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC). To detect EAC in early stage, patients with BE undergo endoscopic surveillance. Surveillance cohorts largely consist of nondysplastic BE (NDBE) patients with a low annual progression risk (<0.5%). Predictive biomarkers for malignant progression of NDBE could improve efficacy of surveillance. Biomarker research has mostly focused on aberrant protein expression on BE epithelial cells. Moreover, insight in cell signaling driving malignant transformation is unknown. This study uses a data-driven approach to analyze tumor-stroma interaction in NDBE which progressed to high-grade dysplasia or EAC. Methods In this case-control study, we performed RNA sequencing analysis on index NDBE biopsies from 6 patients who, during long-term follow-up, progressed and 7 who did not progress to high-grade dysplasia/EAC. For control samples, squamous and duodenum tissues from BE patients were analyzed. For validation, we used quantitative PCR. Results Significant differences in BE transcriptomic profiles between progressors and nonprogressors were found by principal component and differential expression analyses. Ingenuity pathway analysis indicated that 8 cell signaling pathways were significantly upregulated in the progressors, and 14 pathways were significantly downregulated. The most interesting finding was the upregulation of the xenobiotic metabolism pregnane X receptor signaling pathway in the progressor cohort, while of the downregulated pathways in progressors, several were related to the immune system. Conclusion These novel transcriptomic insights are fundamental for developing (chemo-)preventive therapies. These could be therapies, which protect against toxins, including biles, responsible for pregnane X receptor activation or which enhance protective immune mechanisms. The identified RNA markers are promising biomarkers for improving risk stratification in surveillance programs.
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Affiliation(s)
- Sanne J.M. Hoefnagel
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Location Academic Medical Center, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Shulin Li
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Eva M. Timmer
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Sybren L. Meijer
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Pathology, Amsterdam UMC, Location Academic Medical Center, Amsterdam, the Netherlands
| | - Kausilia K. Krishnadath
- Center for Experimental and Molecular Medicine, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Location Academic Medical Center, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Laboratory of Experimental Medicine and Paediatrics, Department of Gastroenterology and Hepatology, University Hospital Antwerp, University of Antwerp, Edegem, Belgium
- Department of Gastroenterology and Hepatology, Erasmus University MC, Rotterdam, The Netherlands
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Alqudah A, Qnais EY, Wedyan MA, Oqal M, Alqudah M, AbuDalo R, AL-Hashimi N. Ceratonia siliqua leaves ethanol extracts exert anti-nociceptive and anti-inflammatory effects. Heliyon 2022; 8:e10400. [PMID: 36090223 PMCID: PMC9449564 DOI: 10.1016/j.heliyon.2022.e10400] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 08/01/2022] [Accepted: 08/17/2022] [Indexed: 11/25/2022] Open
Abstract
Background Ceratonia siliqua L. (Leguminosae) has neuroprotective, mutagenic, hypotensive, anti-bacterial, hypoglycaemic, and anti-inflammatory effects through extracts from its leaves. Therefore, the aim of this study is to assess the anti-nociceptive activity of ethanol extracts of Ceratonia siliqua leaves. Methods Ethanol extract of Ceratonia siliqua leaves were studied using well-established animal models of inflammation and pain. A hot plate latency assay (55 °C) was used to assess the analgesic effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extracts in addition to paw licking time in early and late phase using a formalin-induced paw licking assay test. Paw oedema induction using carrageenan and cotton pellet granuloma assays were used to assess the anti-inflammatory effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extract. Results The ethanol extract of Ceratonia siliqua leaves reduces paw licking time in early and late phase after formalin injection. The same effect was also observed when the hotplate test was performed. Ethanol extract of Ceratonia siliqua leaves caused dose dependent inhibition in paw oedema after the injection of carrageenan and cotton pellet granuloma in mice. These effects were not antagonized when opioid receptors were blocked by naloxone (5 mg/kg). The preliminary phytochemical analysis of the ethanol extract of Ceratonia siliqua leaves showed the presence of tannins, alkaloids, flavonoids and terpenoids. Conclusion The present data indicate that ethanol extract of Ceratonia siliqua leaves might possess anti-inflammatory and anti-nociception properties and should be considered for further therapeutic research.
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The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy. Pharmaceuticals (Basel) 2022; 15:ph15080944. [PMID: 36015092 PMCID: PMC9416713 DOI: 10.3390/ph15080944] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/27/2022] [Accepted: 07/02/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. Method: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts’ anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. Results: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites.
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Miyaki C, Lynch LM. An Update on Common Pharmaceuticals in the Prevention of Pancreatic Cancer. Cureus 2022; 14:e25496. [PMID: 35800820 PMCID: PMC9246430 DOI: 10.7759/cureus.25496] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2022] [Indexed: 01/03/2023] Open
Abstract
In this review, we aim to update readers about the most recent studies on common pharmaceuticals and their association with pancreatic cancer risk. The use of prophylactic aspirin, metformin, beta-blockers, and statins has been studied in the past but showed inconclusive results in the reduction of pancreatic cancer incidence. However, in recent studies, these medications along with combination therapy of aspirin and metformin were found to have a more significant association with decreasing risk. Given the poor prognosis of pancreatic cancer despite treatment, medication prophylaxis prevention should be considered. In this review, we hope to encourage future case-control or prospective studies on common medications that have shown great potential in delaying pancreatic cancer development.
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20
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Jiang YX, Chen Y, Sun HH, Xu SC. Effects of Cyclooxygenase-2 Inhibitors on Gastrointestinal Malignancies: a Systematic Review and Meta-analysis. Indian J Surg Oncol 2022; 13:348-355. [DOI: 10.1007/s13193-022-01547-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 05/03/2022] [Indexed: 11/24/2022] Open
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21
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Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022; 117:559-587. [PMID: 35354777 DOI: 10.14309/ajg.0000000000001680] [Citation(s) in RCA: 229] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 02/04/2022] [Indexed: 02/07/2023]
Abstract
Barrett's esophagus (BE) is a common condition associated with chronic gastroesophageal reflux disease. BE is the only known precursor to esophageal adenocarcinoma, a highly lethal cancer with an increasing incidence over the last 5 decades. These revised guidelines implement Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the definition and diagnosis of BE, screening for BE and esophageal adenocarcinoma, surveillance of patients with known BE, and the medical and endoscopic treatment of BE and its associated early neoplasia. Important changes since the previous iteration of this guideline include a broadening of acceptable screening modalities for BE to include nonendoscopic methods, liberalized intervals for surveillance of short-segment BE, and volume criteria for endoscopic therapy centers for BE. We recommend endoscopic eradication therapy for patients with BE and high-grade dysplasia and those with BE and low-grade dysplasia. We propose structured surveillance intervals for patients with dysplastic BE after successful ablation based on the baseline degree of dysplasia. We could not make recommendations regarding chemoprevention or use of biomarkers in routine practice due to insufficient data.
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22
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Tang H, Li C, Wang Y, Deng L. Sufentanil Inhibits the Proliferation and Metastasis of Esophageal Cancer by Inhibiting the NF- κB and Snail Signaling Pathways. JOURNAL OF ONCOLOGY 2021; 2021:7586100. [PMID: 34912457 PMCID: PMC8668294 DOI: 10.1155/2021/7586100] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 10/08/2021] [Accepted: 10/28/2021] [Indexed: 11/22/2022]
Abstract
Sufentanil is a μ-opioid receptor agonist, widely used in intraoperative and postoperative analgesia of esophageal cancer. This study investigated the effects of sufentanil on the proliferation, invasion, and metastasis of esophageal carcinoma cells and its molecular mechanisms. Human esophageal carcinoma cells CaES-17 and Eca-109 were cultured in vitro. Different concentrations of sufentanil (1 and 10 μmol/L) were added to the experimental group. MTT was used to detect the proliferative activity of esophageal carcinoma cells. The migration ability of esophageal carcinoma cells was measured by the scratch test. Transwell was used to detect the invasive ability of esophageal carcinoma cells. The EMT marker expression was detected by qPCR. Meanwhile, effects of sufentanil on NF-κB and Snail expression and nucleation were evaluated. Establish a subcutaneous xenograft tumor model of nude mice with esophageal carcinoma cells and evaluate the antitumor effect of sufentanil. Sufentanil can inhibit the proliferation, invasion, and migration of CaES-17 and Eca-109 cells and has a dose-dependent relationship. The molecular mechanism showed that sufentanil could upregulate the expression of E-cadherin and inhibit the expression of vimentin. Sufentanil can inhibit the expression of NF-κB and Snail, as well as the nuclear expression of NF-κB and Snail. Xenograft tumor model results showed that sufentanil could inhibit tumor proliferation and NF-κB and Snail expression in tumor tissues of nude mice. Sufentanil inhibits esophageal cancer epithelial-mesenchymal transition (EMT) by acting on NF-κB and Snail signaling pathways to inhibit proliferation and metastasis of esophageal cancer.
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Affiliation(s)
- Huiyan Tang
- Department of Oncology, XinTai People's Hospital, Taian, Shandong 271200, China
| | - Chao Li
- Department of Thoracic Surgery, Rizhao Central Hospital, Rizhao, Shandong 276800, China
| | - Yongsheng Wang
- Department of Thoracic Surgery, Gaotang County People's Hospital, Liaocheng, Shandong 252800, China
| | - Liqiang Deng
- Department of Anesthesiology, Maternal and Child Healthcare Hospital of Shandong Province, Ji'nan, Shandong 250014, China
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23
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Ferreira JC, Reis MB, Coelho GDP, Gastaldello GH, Peti APF, Rodrigues DM, Bastos JK, Campo VL, Sorgi CA, Faccioli LH, Gardinassi LG, Tefé-Silva C, Zoccal KF. Baccharin and p-coumaric acid from green propolis mitigate inflammation by modulating the production of cytokines and eicosanoids. JOURNAL OF ETHNOPHARMACOLOGY 2021; 278:114255. [PMID: 34062248 DOI: 10.1016/j.jep.2021.114255] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 05/16/2021] [Accepted: 05/25/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Green propolis is produced by Apis mellifera honeybees using Baccharis dracunculifolia D.C. (Asteraceae) as substrate. This Southern Brazilian native plant and green propolis have been used in traditional medicine to treat gastric diseases, inflammation and liver disorders. AIM OF THE STUDY Investigate the effects of baccharin (Bac) or p-coumaric acid (pCA) isolated from B. dracunculifolia D.C. (Asteraceae) over the inflammation induced by lipopolysaccharide (LPS) in vivo. MATERIALS AND METHODS Inflammation was induced by LPS injection into air-pouches in mice, which were subsequently treated with Bac or pCA. Lavage fluid was collected from air pouches for the quantification of cellular influx via microscopy, and quantification of inflammatory mediators via colorimetric methods, ELISA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS LPS-induced inflammation increased cellular influx and increased the levels of parameters related to vascular permeability and edema formation, such as nitric oxide (NO) and protein extravasation. Moreover, LPS increased the levels of cytokines and eicosanoids in the air-pouches. Importantly, both Bac and pCA suppressed the infiltration of neutrophils, production of NO and protein extravasation. Notably, the compounds promote differential regulation of cytokine and eicosanoid production. CONCLUSIONS Our results suggest that Bac from green propolis directly affects inflammation by inhibiting the production of cytokines and eicosanoids, while pCA may exert direct, but also indirect effects on inflammation by stimulating the production of regulatory effectors such as interkeukin-10 in vivo.
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Affiliation(s)
- Juliana C Ferreira
- Centro Universitário Barão de Mauá (CBM), Ribeirão Preto, São Paulo, Brazil.
| | - Mouzarllem B Reis
- Centro Universitário Barão de Mauá (CBM), Ribeirão Preto, São Paulo, Brazil.
| | - Giovanna D P Coelho
- Centro Universitário Barão de Mauá (CBM), Ribeirão Preto, São Paulo, Brazil.
| | | | - Ana Paula F Peti
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
| | - Débora M Rodrigues
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
| | - Jairo K Bastos
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
| | - Vanessa L Campo
- Centro Universitário Barão de Mauá (CBM), Ribeirão Preto, São Paulo, Brazil; Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
| | - Carlos A Sorgi
- Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
| | - Lúcia H Faccioli
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
| | - Luiz G Gardinassi
- Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil.
| | | | - Karina F Zoccal
- Centro Universitário Barão de Mauá (CBM), Ribeirão Preto, São Paulo, Brazil.
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24
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Hofer SJ, Davinelli S, Bergmann M, Scapagnini G, Madeo F. Caloric Restriction Mimetics in Nutrition and Clinical Trials. Front Nutr 2021; 8:717343. [PMID: 34552954 PMCID: PMC8450594 DOI: 10.3389/fnut.2021.717343] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/13/2021] [Indexed: 12/29/2022] Open
Abstract
The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD+ precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials.
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Affiliation(s)
- Sebastian J. Hofer
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
- Field of Excellence BioHealth, University of Graz, Graz, Austria
| | - Sergio Davinelli
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
| | - Martina Bergmann
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
| | - Giovanni Scapagnini
- Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
| | - Frank Madeo
- Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
- Field of Excellence BioHealth, University of Graz, Graz, Austria
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25
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Alkhayyat M, Kumar P, Sanaka KO, Thota PN. Chemoprevention in Barrett's esophagus and esophageal adenocarcinoma. Therap Adv Gastroenterol 2021; 14:17562848211033730. [PMID: 34434254 PMCID: PMC8381453 DOI: 10.1177/17562848211033730] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 06/29/2021] [Indexed: 02/04/2023] Open
Abstract
There has been a dramatic increase in the incidence of Barrett's esophagus and esophageal adenocarcinoma over the past several decades with a continued rise expected in the future. Several strategies have been developed for screening and surveillance of patients with Barrett's esophagus and endoscopic treatment of Barrett's associated dysplasia and early esophageal cancer; however, they have not made a substantial impact on the incidence of cancer. Herein, chemoprevention becomes an attractive idea for reducing the incidence of cancer in Barrett's patients. Several agents appear promising in preclinical and observational studies but very few have been evaluated in randomized controlled trials. Strongest evidence to date is available for proton-pump inhibitors and Aspirin that have been evaluated in a large randomized controlled trial. Other agents such as statins, metformin, ursodeoxycholic acid, and dietary supplements have insufficient evidence for chemoprevention in Barrett's patients.
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Affiliation(s)
- Motasem Alkhayyat
- Department of Internal Medicine, Cleveland
Clinic, Cleveland, OH, USA
| | - Prabhat Kumar
- Department of Gastroenterology and Hepatology,
Cleveland Clinic, Cleveland, OH, USA
| | - Krishna O. Sanaka
- Department of Gastroenterology and Hepatology,
Cleveland Clinic, Cleveland, OH, USA
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26
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Sharifi-Rad J, Quispe C, Vergara CV, Kitic D, Kostic M, Armstrong L, Shinwari ZK, Khalil AT, Brdar-Jokanović M, Ljevnaić-Mašić B, Varoni EM, Iriti M, Leyva-Gómez G, Herrera-Bravo J, Salazar LA, Cho WC. Genus Viburnum: Therapeutic Potentialities and Agro-Food-Pharma Applications. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:3095514. [PMID: 34326915 PMCID: PMC8310452 DOI: 10.1155/2021/3095514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/08/2021] [Accepted: 06/11/2021] [Indexed: 01/17/2023]
Abstract
The genus Viburnum (Adoxaceae, Dipsacales) is of scientific interest due to the chemical components and diverse biological activities found across species of the genus, which includes more than 230 species of evergreen, semievergreen, or deciduous shrubs and small trees. Although frequently used as an ornament, the Viburnum species show biological properties with health-promoting effects. Fruits, flowers, and barks of certain species are used for pharmaceutical purposes or as cooking ingredients, hence containing biochemical compounds with health-promoting activity such are carotenoids, polyphenols, and flavonoids. However, its taxonomical determination is difficult, due to its wide distribution and frequent hybridizations; therefore, an objective classification would allow us to understand its biological activity based on its phytochemical components. More than sixty phytochemical compounds have been reported, where vibsanin-type diterpenes and their derivatives are the most prevalent. Leaves and twigs of V. dilatatum contain the largest number of phytochemicals among the genus. Through preclinical evidence, this study provides insight regarding antioxidant, antibacterial, anti-inflammatory, cytotoxic, and anticancer activities of genus Viburnum.
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Affiliation(s)
- Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Cristina Quispe
- Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, Iquique 1110939, Chile
| | - Cristian Valdés Vergara
- Centro de Investigación de Estudios Avanzados del Maule, Vicerrectoría de Investigación y Postgrado, Universidad Católica del Maule, Chile
| | - Dusanka Kitic
- Faculty of Medicine, Department of Pharmacy, University of Niš, Ave. Zorana Djindjica 81, 18000 Nis, Serbia
| | - Milica Kostic
- Faculty of Medicine, Department of Pharmacy, University of Niš, Ave. Zorana Djindjica 81, 18000 Nis, Serbia
| | - Lorene Armstrong
- Departament of Pharmaceutical Sciences, State University of Ponta Grossa, 84030900, Ponta Grossa, Paraná, Brazil
| | - Zabta Khan Shinwari
- Department of Plant Sciences, Quaid-i-Azam University, Islamabad, Pakistan
- Pakistan Academy of Sciences, Islamabad, Pakistan
| | - Ali Talha Khalil
- Department of Pathology, Lady Reading Hospital Medical Teaching Institution, Peshawar (25000), KP, Pakistan
| | - Milka Brdar-Jokanović
- Institute of Field and Vegetable Crops, National Institute of the Republic of Serbia, Alternative Crops and Organic Production Department, Maksima Gorkog 30, 21000 Novi Sad, Serbia
| | - Branka Ljevnaić-Mašić
- Faculty of Agriculture, Department of Field and Vegetable Crops, University of Novi Sad, Trg Dositeja Obradovića 8, 21000 Novi Sad, Serbia
| | - Elena M. Varoni
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università Degli Studi di Milano, Via Beldiletto 1, 20142 Milan, Italy
| | - Marcello Iriti
- Dipartimento di Scienze Agrarie e Ambientali, Via Celoria 2, 20133 Milan, Italy
| | - Gerardo Leyva-Gómez
- Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México 04510, Mexico
| | - Jesús Herrera-Bravo
- Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Chile
- Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Temuco 4811230, Chile
| | - Luis A. Salazar
- Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Temuco 4811230, Chile
| | - William C. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
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27
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King R, Hayes C, Donohoe CL, Dunne MR, Davern M, Donlon NE. Hypoxia and its impact on the tumour microenvironment of gastroesophageal cancers. World J Gastrointest Oncol 2021; 13:312-331. [PMID: 34040696 PMCID: PMC8131902 DOI: 10.4251/wjgo.v13.i5.312] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 02/24/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
The malfeasant role of the hypoxic tumour microenvironment (TME) in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue to be elucidated. Gastroesophageal cancers (GOCs) represent a major burden of worldwide disease, responsible for the deaths of over 1 million people annually. Disentangling the impact of hypoxia in GOCs enables a better overall understanding of the disease pathogenesis while shining a light on novel therapeutic strategies and facilitating precision treatment approaches with the ultimate goal of improving outcomes for patients with these diseases. This review discusses the underlying principles and processes of the hypoxic response and the effect of hypoxia in promoting the hallmarks of cancer in the context of GOCs. We focus on its bidirectional influence on inflammation and how it drives angiogenesis, innate and adaptive immune evasion, metastasis, and the reprogramming of cellular bioenergetics. The contribution of the hypoxic GOC TME to treatment resistance is examined and a brief overview of the pharmacodynamics of hypoxia-targeted therapeutics is given. The principal methods that are used in measuring hypoxia and how they may enhance prognostication or provide rationale for individually tailored management in the case of tumours with significant hypoxic regions are also discussed.
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Affiliation(s)
- Ross King
- Department of Surgery, St. James’s Hospital Campus, Trinity Translational Medicine Institute, Dublin D8, Ireland
| | - Conall Hayes
- Department of Surgery, St. James’s Hospital Campus, Trinity Translational Medicine Institute, Dublin D8, Ireland
| | - Claire L Donohoe
- Department of Surgery, St. James’s Hospital Campus, Trinity Translational Medicine Institute, Dublin D8, Ireland
| | - Margaret R Dunne
- Department of Surgery, St. James’s Hospital Campus, Trinity Translational Medicine Institute, Dublin D8, Ireland
| | - Maria Davern
- Department of Surgery, St. James’s Hospital Campus, Trinity Translational Medicine Institute, Dublin D8, Ireland
| | - Noel E Donlon
- Department of Surgery, St. James’s Hospital Campus, Trinity Translational Medicine Institute, Dublin D8, Ireland
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28
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Marabotto E, Pellegatta G, Sheijani AD, Ziola S, Zentilin P, De Marzo MG, Giannini EG, Ghisa M, Barberio B, Scarpa M, Angriman I, Fassan M, Savarino V, Savarino E. Prevention Strategies for Esophageal Cancer-An Expert Review. Cancers (Basel) 2021; 13:2183. [PMID: 34062788 PMCID: PMC8125297 DOI: 10.3390/cancers13092183] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
In the last 30 years, we have witnessed a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the word. However, despite advancements in diagnostic technologies, the early detection of this cancer is rare, and its prognosis remains poor, with only about 20% of these patients surviving for 5 years. The two major forms are the esophageal squamous cell carcinoma (ESCC), which is particularly frequent in the so-called Asian belt, and the esophageal adenocarcinoma (EAC), which prevails in Western populations. This review provides a summary of the epidemiological features and risk factors associated with these tumors. Moreover, a major focus is posed on reporting and highlighting the various preventing strategies proposed by the most important international scientific societies, particularly in high-risk populations, with the final aim of detecting these lesions as early as possible and therefore favoring their definite cure. Indeed, we have conducted analysis with attention to the current primary, secondary and tertiary prevention guidelines in both ESCC and EAC, attempting to emphasize unresolved research and clinical problems related to these topics in order to improve our diagnostic strategies and management.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Gaia Pellegatta
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Milan, Italy;
| | - Afscin Djahandideh Sheijani
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Sebastiano Ziola
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Maria Giulia De Marzo
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Matteo Ghisa
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
| | - Marco Scarpa
- Clinica Chirurgica 1, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.S.); (I.A.)
| | - Imerio Angriman
- Clinica Chirurgica 1, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.S.); (I.A.)
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, 35121 Padua, Italy;
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; (E.M.); (A.D.S.); (S.Z.); (P.Z.); (M.G.D.M.); (E.G.G.); (V.S.)
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (M.G.); (B.B.)
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29
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Xie Y, Shi L, He X, Luo Y. Gastrointestinal cancers in China, the USA, and Europe. Gastroenterol Rep (Oxf) 2021; 9:91-104. [PMID: 34026216 PMCID: PMC8128023 DOI: 10.1093/gastro/goab010] [Citation(s) in RCA: 125] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 02/26/2021] [Indexed: 12/17/2022] Open
Abstract
Gastrointestinal (GI) cancers, including colorectal cancer, gastric cancer, and esophageal cancer, are a major medical and economic burden worldwide and have the largest number of new cancer cases and cancer deaths each year. Esophageal and gastric cancers are most common in developing countries, while colorectal cancer forms the major GI malignancy in Western countries. However, a great shift in the predominant GI-cancer type is happening in countries under economically transitioning and, at the same time, esophageal and gastric cancers are reigniting in Western countries due to the higher exposure to certain risk factors. The development of all GI cancers is highly associated with lifestyle habits and all can be detected by identified precancerous diseases. Thus, they are all suitable for cancer screening. Here, we review the epidemiological status of GI cancers in China, the USA, and Europe; the major risk factors and their distribution in these regions; and the current screening strategies.
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Affiliation(s)
- Yumo Xie
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Lishuo Shi
- Center for Clinical Research, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaosheng He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yanxin Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
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30
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Elliott JA, Reynolds JV. Visceral Obesity, Metabolic Syndrome, and Esophageal Adenocarcinoma. Front Oncol 2021; 11:627270. [PMID: 33777773 PMCID: PMC7994523 DOI: 10.3389/fonc.2021.627270] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 02/19/2021] [Indexed: 12/16/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) represents an exemplar of obesity-associated carcinogenesis, with a progressive increase in EAC risk with increased body mass index. In this context, there is increased focus on visceral adipose tissue and associated metabolic dysfunction, including hypertension, diabetes mellitus and hyperlipidemia, or combinations of these in the metabolic syndrome. Visceral obesity (VO) may promote EAC via both directly impacting on gastro-esophageal reflux disease and Barrett's esophagus, as well as via reflux-independent effects, involving adipokines, growth factors, insulin resistance, and the microbiome. In this review these pathways are explored, including the impact of VO on the tumor microenvironment, and on cancer outcomes. The current evidence-based literature regarding the role of dietary, lifestyle, pharmacologic and surgical interventions to modulate the risk of EAC is explored.
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Affiliation(s)
- Jessie A Elliott
- Trinity St. James's Cancer Institute, Trinity College Dublin and St. James's Hospital, Dublin, Ireland
| | - John V Reynolds
- Trinity St. James's Cancer Institute, Trinity College Dublin and St. James's Hospital, Dublin, Ireland
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Abstract
The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a result, people of certain regions of the world can be more prone to a subtype. For example, squamous cell carcinoma of the esophagus has the highest incidence in eastern Africa and eastern Asia, with smoking being a major risk factor, whereas adenocarcinoma is more prevalent in North America and western Europe, with gastroesophageal reflux disease being a leading risk factor. With that being said, adenocarcinoma and squamous cell carcinoma have similar and unfortunately poor survival rates, partly because EC is prone to early metastasis given that the esophagus does not have a serosa, as well as the superficial nature of its lymphatics compared with the rest of the gastrointestinal tract. This makes early detection of the utmost importance, and certain patients have been shown to have the benefit of screening/surveillance endoscopies, including those with Barrett's esophagus, lye-induced/caustic strictures, tylosis, and Peutz-Jeghers syndrome. Until treatments significantly improve, identifying EC at the earliest stage will have the best success for patient outcomes, and further elucidation of its pathogenesis and risk factors may lead to identifying other high-risk groups that should be screened.
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Affiliation(s)
- Michael DiSiena
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
| | - Alexander Perelman
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
| | - John Birk
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
| | - Houman Rezaizadeh
- From the Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington
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32
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RAJPUT MA, ZEHRA T, ALI F, KUMAR G. Evaluation of Antiinflammatory Activity of Ethanol Extract of Nelumbo nucifera Fruit. Turk J Pharm Sci 2021; 18:56-60. [PMID: 33633265 PMCID: PMC7957318 DOI: 10.4274/tjps.galenos.2019.47108] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 12/12/2019] [Indexed: 12/01/2022]
Abstract
OBJECTIVES In recent times, the use of natural remedies, which are rich in varieties of vitamins and flavonoids, for treatment of inflammation has increased substantially. These natural remedies are expected to be safe and economical when compared with other conventional allopathic drugs. Thus, existing research investigated the anti-inflammatory effect of Nelumbo nucifera fruit (NNF), in view of estimating its traditional and pharmacologic use against disorders associated with pain and inflammation. MATERIALS AND METHODS To estimate the antiinflammatory effect of NNF, carrageenan-induced paw edema method was employed with equally distributed (n=7) Wistar male rats (N=35). The paw edema was measured by volume displacement method with plethysmometer. RESULTS The NNF extract significantly reduced the inflammation of the paw and decreased the edema volume in rats administered carrageenan at all doses from the 3rd to 5th hour when compared to control, whose maximum percent reduction of edema was estimated as 100 mg/kg dose (that is, 73.92% at the 5th hour after administration of carrageenan). CONCLUSION NNF exhibited a strong antiinflammatory effect, due to its phytochemical constituents, including flavonoids, saponins, and tannins, all of which synergistically exert inhibitory effects on arachidonic acid metabolism, neutrophil degranulation, and enzyme systems that promote cell proliferation and regulation of complement system. However, more preclinical and clinical evaluations are mandatory to validate these findings.
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Affiliation(s)
- Muhammad Ali RAJPUT
- Multan Medical and Dental College, Department of Pharmacology, Multan, Pakistan
| | - Tabassum ZEHRA
- Liaquat National Medical College, Department of Pharmacology , Karachi, Pakistan
| | - Fizzah ALI
- Liaquat National Medical College, Department of Pharmacology , Karachi, Pakistan
| | - Gunesh KUMAR
- Liaquat University of Medical and Health Sciences, Department of Pharmacology, Sindh, Pakistan
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33
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Moayyedi P, El-Serag HB. Current Status of Chemoprevention in Barrett's Esophagus. Gastrointest Endosc Clin N Am 2021; 31:117-130. [PMID: 33213791 DOI: 10.1016/j.giec.2020.08.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Candidates for chemoprevention in Barrett's esophagus have long been suggested and there has been observational data to support many drugs, including statins, hormone replacement therapy, metformin, proton pump inhibitor therapy, and aspirin. Proton pump inhibitor therapy and aspirin are the most promising agents. Data suggest that aspirin and proton pump inhibitor therapy can decrease the risk of neoplastic progression in Barrett's esophagus. Further, the combination of aspirin and proton pump inhibitor therapy decrease all-cause mortality by approximately 33%. Future guideline groups need to evaluate the evidence rigorously, but the combination of proton pump inhibitor therapy and aspirin is promising.
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Affiliation(s)
- Paul Moayyedi
- McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
| | - Hashem B El-Serag
- Baylor College of Medicine Medical Center, McNair Campus (Clinic), 7200 Cambridge Street, 8th Floor, Suite 8B, Houston, TX 77030, USA
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Joshi SN, Murphy EA, Olaniyi P, Bryant RJ. The multiple effects of aspirin in prostate cancer patients. Cancer Treat Res Commun 2020; 26:100267. [PMID: 33360326 DOI: 10.1016/j.ctarc.2020.100267] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 12/02/2020] [Accepted: 12/07/2020] [Indexed: 01/31/2023]
Abstract
Aspirin is a commonly used medication with anti-inflammatory and analgesic properties, and it is widely used to reduce the risk of ischaemic heart disease-related events and/or cerebrovascular accidents. However, there is also evidence from epidemiological and interventional studies to suggest that regular aspirin use can reduce the risk of prostate cancer development and progression, and can reduce the risk of disease recurrence following anti-prostate cancer therapy. Aspirin use in African-American men is associated with a reduced incidence of advanced PCa and reduced disease recurrence, and there is evidence from other studies of an association between regular aspirin use and decreased PCa-related mortality. The cyclooxygenase-2 enzyme inhibited by Aspirin and other NSAIDs, and which catalyses prostaglandin synthesis and mediates inflammation, is overexpressed in prostate cancer, therefore inhibition of cyclooxygenase-2 may have direct, and indirect, therapeutic effects. This review explores the evidence suggesting that aspirin use can modify prostate cancer biology and disease characteristics, and explores the potential mechanisms underpinning the observed associations between aspirin use and modification of prostate cancer risk. It also summarises the potential for adjuvant aspirin use to combine with other therapeutic approaches such as radical surgery and radiotherapy.
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Affiliation(s)
- S N Joshi
- Medical Sciences Divisional Office, University of Oxford, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
| | - E A Murphy
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 7DQ, United Kingdom
| | - P Olaniyi
- Department of Urology, Ipswich Hospital, East Suffolk and North Essex NHS Foundation Trust, Heath Road, Ipswich IP4 5PD, United Kingdom
| | - R J Bryant
- Department of Urology, Ipswich Hospital, East Suffolk and North Essex NHS Foundation Trust, Heath Road, Ipswich IP4 5PD, United Kingdom; Department of Urology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LE, United Kingdom.
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35
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Can aspirin use reduce the risk of pancreatic cancer: an updated systematic review and meta-analysis. JOURNAL OF PANCREATOLOGY 2020. [DOI: 10.1097/jp9.0000000000000063] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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Eisa M, Sandhu A, Prakash R, Ganocy SJ, Fass R. The Risk of Acute Myocardial Infarction in Patients With Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2020; 26:471-476. [PMID: 32989184 PMCID: PMC7547190 DOI: 10.5056/jnm19192] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 06/01/2020] [Accepted: 06/09/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims A number of inflammatory mediators have been documented to be elevated in gastroesophageal reflux disease (GERD). Similar inflammatory mediators are involved in coronary artery disease. Thus, the aim of the study is to determine if GERD is a risk factor for developing acute myocardial infarction (AMI). Methods We used Explorys, a private cloud-based data store to which a number of health care systems feed information. We identified a cohort of GERD patients who have undergone an esophagogastroduodenoscopy compared to those without GERD. Incidence of AMI was studied after statistically controlling for known AMI risk factors. Results Total of 200 400 patients were included in the GERD group and 386 800 patients in non-GERD group. The primary event of AMI occurred in 17 200 patients in the GERD group (8.6%) vs 24 300 in non-GERD group (6.3%). Using logistic regression analysis and controlling for 6 major risk factors which included male gender (OR, 1.09; 95% CI, 1.07-1.11; P < 0.001), hypertension (OR, 6.53; 95% CI, 6.21-6.88; P < 0.001), hyperlipidemia (OR, 3.08; 95% CI, 2.96-3.20; P < 0.001), diabetes mellitus (OR, 1.72; 95% CI, 1.69-1.76; P < 0.001), obesity (OR, 1.02; 95% CI, 1.00-1.04; P = 0.044), and smoking (OR, 1.38; 95% CI, 1.35-1.41; P < 0.001). The odds of developing AMI in the GERD population was 1.11 (95% CI, 1.08-1.13; P < 0.001). GERD had higher odds of developing AMI than male gender or obesity in our study. Conclusions This study demonstrated that GERD is a risk factor for AMI, higher than male gender and obesity. However, the increased risk may be clinically insignificant.
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Affiliation(s)
- Mohamed Eisa
- Department of Internal Medicine, The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Annumeet Sandhu
- Department of Internal Medicine, The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Ravi Prakash
- Department of Internal Medicine, The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Stephen J Ganocy
- Center for Health Care Research and Policy, Case Western Reserve University, Cleveland, OH, USA
| | - Ronnie Fass
- Department of Internal Medicine, The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
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Association between the use of aspirin and risk of lung cancer: results from pooled cohorts and Mendelian randomization analyses. J Cancer Res Clin Oncol 2020; 147:139-151. [PMID: 32965542 DOI: 10.1007/s00432-020-03394-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 09/16/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE We aimed to elucidate the associations between aspirin use with risk of lung cancer, by conducting a meta-analysis and Mendelian randomization (MR) analyses from published Genome-Wide Association Studies (GWAS). METHODS Cohort studies, nested case-control studies, and randomized controlled trials (RCTs) investigating the impact of aspirin exposure and lung cancer incidence were included. Relative risk (RR) and its 95% confidence interval (CI) were evaluated in eligible studies. Subgroup analyses regarding gender, pathologic subtypes and smoking status were also executed. MR analyses were conducted using summary statistics obtained from two large consortia [Neale Lab and International Lung Cancer Consortium (ILCCO)] to assess the possible causal relationship of aspirin on lung cancer incidence. RESULTS Sixteen eligible studies involving 1,522,687 patients were included. The combined RR of aspirin use for the incidence of lung cancer was 0.95 (95% confidence interval (CI) 0.91-0.98). In subgroup meta-analyses, a significant protective effect was observed in squamous cell lung cancer (RR = 0.80; 95% CI 0.65-0.98). In terms of gender, the chemopreventive value was only observed among men (RR = 0.87; 95% CI 0.77-0.97). The MR risk analysis suggested a causal effect of aspirin on lung cancer incidence, with evidence of a decreased risk for overall lung cancer (OR = 0.042; 95% CI 0.003-0.564) and squamous cell lung cancer (OR = 0.002; 95% CI 1.21 × 10-5-0.301). CONCLUSION Our study provided evidence for a causal protective effect of aspirin on the risk of lung cancer incidence among men, particularly on the squamous cell lung cancer risk.
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Wu Y, Wang X, Xu F, Zhang L, Wang T, Fu X, Jin T, Zhang W, Ye L. The regulation of acetylation and stability of HMGA2 via the HBXIP-activated Akt-PCAF pathway in promotion of esophageal squamous cell carcinoma growth. Nucleic Acids Res 2020; 48:4858-4876. [PMID: 32313942 PMCID: PMC7229824 DOI: 10.1093/nar/gkaa232] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 03/02/2020] [Accepted: 04/12/2020] [Indexed: 12/16/2022] Open
Abstract
High-mobility group AT-hook 2 (HMGA2) is an architectural transcription factor that plays essential roles in embryonic development and cancer progression. However, the mechanism of HMGA2 regulation remains largely uncharacterized. Here, we demonstrate that HMGA2 can be modulated by hepatitis B X-interacting protein (HBXIP), an oncogenic transcriptional coactivator, in esophageal squamous cell carcinoma (ESCC). HMGA2 expression was positively associated with HBXIP expression in clinical ESCC tissues, and their high levels were associated with advanced tumor stage and reduced overall and disease-free survival. We found that oncogenic HBXIP could posttranslationally upregulate HMGA2 protein level in ESCC cells. HBXIP induced HMGA2 acetylation at the lysine 26 (K26), resulting in HMGA2 protein accumulation. In this process, HBXIP increased the acetyltransferase p300/CBP-associated factor (PCAF) phosphorylation and activation via the Akt pathway, then PCAF directly interacted with HMGA2, leading to HMGA2 acetylation in the cells. HMGA2 K26 acetylation enhanced its DNA binding capacity and blocked its ubiquitination and then inhibited proteasome-dependent degradation. Functionally, HBXIP-stabilized HMGA2 could promote ESCC cell growth in vitro and in vivo. Strikingly, aspirin suppressed ESCC growth by inhibiting HBXIP and HMGA2. Collectively, our findings disclose a new mechanism for the posttranslational regulation of HMGA2 mediated by HBXIP in ESCC.
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Affiliation(s)
- Yue Wu
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Xue Wang
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Feifei Xu
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Lu Zhang
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Tianjiao Wang
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Xueli Fu
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Tianzhi Jin
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Weiying Zhang
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
| | - Lihong Ye
- State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China
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Chandran R, George BP, Abrahamse H. Anti-Proliferative, Analgesic and Anti-Inflammatory Properties of Syzygium mundagam Bark Methanol Extract. Molecules 2020; 25:E2900. [PMID: 32599705 PMCID: PMC7355416 DOI: 10.3390/molecules25122900] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 06/17/2020] [Accepted: 06/19/2020] [Indexed: 12/27/2022] Open
Abstract
Cancer, pain and inflammation have long been a cause for concern amongst patients, clinicians and research scientists. There is an alarming increase in the demand for medicines suppressing these disease conditions. The present study investigates the role of Syzygium mundagam bark methanol (SMBM) extract against MCF-7 breast cancer cells, pain and inflammation. The MCF-7 cells treated with SMBM were analyzed for adenosine triphosphate (ATP), lactate dehydrogenase (LDH) levels, changes in cell morphology and nuclear damage. Hot plate, acetic acid and formalin-induced pain models were followed to determine the analgesic activity. Anti-inflammatory activity was studied using carrageenan, egg albumin and cotton pellet induced rat models. Microscopic images of cells in SMBM treated groups showed prominent cell shrinkage and nuclear damage. Hoechst stain results supported the cell death morphology. The decline in ATP (47.96%) and increased LDH (40.96%) content indicated SMBM induced toxicity in MCF-7 cells. In the in vivo study, a higher dose (200 mg/kg) of the extract was found to be effective in reducing pain and inflammation. The results are promising and the action of the extract on MCF-7 cells, pain and inflammation models indicate the potential of drugs of natural origin to improve current therapies.
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Affiliation(s)
| | | | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, Johannesburg, South Africa; (R.C.); (B.P.G.)
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García Rodríguez LA, Soriano-Gabarró M, Vora P, Cea Soriano L. Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study in the United Kingdom using The Health Improvement Network. Int J Cancer 2020; 147:2394-2404. [PMID: 32329063 PMCID: PMC7540378 DOI: 10.1002/ijc.33022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 04/03/2020] [Accepted: 04/15/2020] [Indexed: 12/12/2022]
Abstract
There is increasing interest regarding potential protective effects of low‐dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low‐dose aspirin and risk of gastric/oesophageal cancer using a population‐based primary care database in the UK. Between January 2005 and December 2015, we identified a cohort of 223 640 new users of low‐dose aspirin (75‐300 mg/day) and a matched cohort of nonusers at the start of follow‐up from The Health Improvement Network. Cohorts were followed to identify incident cases of gastric/oesophageal cancer. Nested case‐control analyses were conducted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for current vs nonuse of low‐dose aspirin using logistic regression. Current use was defined as when low‐dose aspirin lasted 0 to 90 days before the index date (event date for cases, random date for controls) and previous duration was ≥1 year. We identified 727 incident cases of gastric cancer and 1394 incident cases of oesophageal cancer. ORs (95% CIs) were 0.46 (0.38‐0.57) for gastric cancer and 0.59 (0.51‐0.69) for oesophageal cancer. The effect remained consistent with no clear change seen between previous duration of low‐dose aspirin use of 1‐3, 3‐5 or >5 years. The reduced risks was seen with 75 mg/day, and effects were consistent in lag‐time analyses. In conclusion, our results indicate that use of low‐dose aspirin is associated with a 54% reduced risk of gastric cancer and a 41% reduced risk of oesophageal cancer as supported by mechanistic data. What's new? Low‐dose aspirin may help protect against the development of gastric and oesophageal cancers. This population‐based study using data from primary care electronic health records in the United Kingdom lends further support to that idea. Compared with no use of low‐dose aspirin, daily use of low‐dose aspirin (75–300 mg) for at least one year was associated with a 54 percent reduction in gastric cancer risk and a 41 percent reduction in oesophageal cancer risk. No clear difference in effect was observed between low‐dose aspirin use for one to three years versus more than three years.
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Affiliation(s)
| | | | - Pareen Vora
- Department of Epidemiology, Bayer AG, Berlin, Germany
| | - Lucía Cea Soriano
- Department of Public Health and Maternal and Child Health, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
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Kirtonia A, Gala K, Fernandes SG, Pandya G, Pandey AK, Sethi G, Khattar E, Garg M. Repurposing of drugs: An attractive pharmacological strategy for cancer therapeutics. Semin Cancer Biol 2020; 68:258-278. [PMID: 32380233 DOI: 10.1016/j.semcancer.2020.04.006] [Citation(s) in RCA: 101] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 03/20/2020] [Accepted: 04/22/2020] [Indexed: 02/07/2023]
Abstract
Human malignancies are one of the major health-related issues though out the world and anticipated to rise in the future. The development of novel drugs/agents requires a huge amount of cost and time that represents a major challenge for drug discovery. In the last three decades, the number of FDA approved drugs has dropped down and this led to increasing interest in drug reposition or repurposing. The present review focuses on recent concepts and therapeutic opportunities for the utilization of antidiabetics, antibiotics, antifungal, anti-inflammatory, antipsychotic, PDE inhibitors and estrogen receptor antagonist, Antabuse, antiparasitic and cardiovascular agents/drugs as an alternative approach against human malignancies. The repurposing of approved non-cancerous drugs is an effective strategy to develop new therapeutic options for the treatment of cancer patients at an affordable cost in clinics. In the current scenario, most of the countries throughout the globe are unable to meet the medical needs of cancer patients because of the high cost of the available cancerous drugs. Some of these drugs displayed potential anti-cancer activity in preclinic and clinical studies by regulating several key molecular mechanisms and oncogenic pathways in human malignancies. The emerging pieces of evidence indicate that repurposing of drugs is crucial to the faster and cheaper discovery of anti-cancerous drugs.
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Affiliation(s)
- Anuradha Kirtonia
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida, 201313, India; Equal contribution
| | - Kavita Gala
- Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be University), Vile Parle West, Mumbai, 400056, India; Equal contribution
| | - Stina George Fernandes
- Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be University), Vile Parle West, Mumbai, 400056, India; Equal contribution
| | - Gouri Pandya
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida, 201313, India; Equal contribution
| | - Amit Kumar Pandey
- Amity Institute of Biotechnology, Amity University Haryana, Manesar, Haryana, 122413, India
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Ekta Khattar
- Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be University), Vile Parle West, Mumbai, 400056, India.
| | - Manoj Garg
- Amity Institute of Molecular Medicine and Stem cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida, 201313, India.
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Zappavigna S, Cossu AM, Grimaldi A, Bocchetti M, Ferraro GA, Nicoletti GF, Filosa R, Caraglia M. Anti-Inflammatory Drugs as Anticancer Agents. Int J Mol Sci 2020; 21:ijms21072605. [PMID: 32283655 PMCID: PMC7177823 DOI: 10.3390/ijms21072605] [Citation(s) in RCA: 220] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 02/07/2023] Open
Abstract
Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.
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Affiliation(s)
- Silvia Zappavigna
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.Z.); (A.M.C.); (A.G.); (M.B.); (M.C.)
| | - Alessia Maria Cossu
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.Z.); (A.M.C.); (A.G.); (M.B.); (M.C.)
- Biogem Scarl, Institute of Genetic Research, Laboratory of Molecular and Precision Oncology, 83031 Ariano Irpino, Italy
| | - Anna Grimaldi
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.Z.); (A.M.C.); (A.G.); (M.B.); (M.C.)
| | - Marco Bocchetti
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.Z.); (A.M.C.); (A.G.); (M.B.); (M.C.)
- Biogem Scarl, Institute of Genetic Research, Laboratory of Molecular and Precision Oncology, 83031 Ariano Irpino, Italy
| | - Giuseppe Andrea Ferraro
- Multidisciplinary Department of Medical and Dental Specialties, University of Campania, “Luigi Vanvitelli”, Plastic Surgery Unit, 80138 Naples, Italy; (G.A.F.); (G.F.N.)
| | - Giovanni Francesco Nicoletti
- Multidisciplinary Department of Medical and Dental Specialties, University of Campania, “Luigi Vanvitelli”, Plastic Surgery Unit, 80138 Naples, Italy; (G.A.F.); (G.F.N.)
| | - Rosanna Filosa
- Department of Science and Technology, University of Sannio, 82100 Benevento, Italy
- Consorzio Sannio Tech-AMP Biotec, 82030 Apollosa, Italy
- Correspondence:
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (S.Z.); (A.M.C.); (A.G.); (M.B.); (M.C.)
- Biogem Scarl, Institute of Genetic Research, Laboratory of Molecular and Precision Oncology, 83031 Ariano Irpino, Italy
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Moyo K, Khong TK. High-dose PPI and aspirin as chemoprevention in Barrett's oesophagus. Drug Ther Bull 2020; 58:39-40. [PMID: 31949003 DOI: 10.1136/dtb.2019.000085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Affiliation(s)
- Kuku Moyo
- Clinical Pharmacology, St George's University of London, London, UK
| | - Teck K Khong
- Clinical Pharmacology, St George's University of London, London, UK
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Majka J, Wierdak M, Szlachcic A, Magierowski M, Targosz A, Urbanczyk K, Krzysiek-Maczka G, Ptak-Belowska A, Bakalarz D, Magierowska K, Chmura A, Brzozowski T. Interaction of epidermal growth factor with COX-2 products and peroxisome proliferator-activated receptor-γ system in experimental rat Barrett's esophagus. Am J Physiol Gastrointest Liver Physiol 2020; 318:G375-G389. [PMID: 31928220 DOI: 10.1152/ajpgi.00410.2018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Mixed acidic-alkaline refluxate is a major pathogenic factor in chronic esophagitis progressing to Barrett's esophagus (BE). We hypothesized that epidermal growth factor (EGF) can interact with COX-2 and peroxisome proliferator-activated receptor-γ (PPARγ) in rats surgically prepared with esophagogastroduodenal anastomosis (EGDA) with healthy or removed salivary glands to deplete salivary EGF. EGDA rats were treated with 1) vehicle, 2) EGF or PPARγ agonist pioglitazone with or without EGFR kinase inhibitor tyrphostin A46, EGF or PPARγ antagonist GW9662 respectively, 3) ranitidine or pantoprazole, and 4) the selective COX-2 inhibitor celecoxib combined with pioglitazone. At 3 mo, the esophageal damage and the esophageal blood flow (EBF) were determined, the mucosal expression of EGF, EGFR, COX-2, TNFα, and PPARγ mRNA and phospho-EGFR/EGFR protein was analyzed. All EGDA rats developed chronic esophagitis, esophageal ulcerations, and intestinal metaplasia followed by a fall in the EBF, an increase in the plasma of IL-1β, TNFα, and mucosal PGE2 content, the overexpression of COX-2-, and EGF-EGFR mRNAs, and proteins, and these effects were aggravated by EGF and attenuated by pioglitazone. The rise in EGF and COX-2 mRNA was inhibited by pioglitazone but reversed by pioglitazone cotreated with GW9662. We conclude that 1) EGF can interact with PG/COX-2 and the PPARγ system in the mechanism of chronic esophagitis; 2) the deleterious effect of EGF involves an impairment of EBF and the overexpression of COX-2 and EGFR, and 3) agonists of PPARγ and inhibitors of EGFR may be useful in the treatment of chronic esophagitis progressing to BE.NEW & NOTEWORTHY Rats with EGDA exhibited chronic esophagitis accompanied by a fall in EBF and an increase in mucosal expression of mRNAs for EGF, COX-2, and TNFα, and these effects were exacerbated by exogenous EGF and reduced by removal of a major source of endogenous EGF with salivectomy or concurrent treatment with tyrphostin A46 or pioglitazone combined with EGF. Beneficial effects of salivectomy in an experimental model of BE were counteracted by PPARγ antagonist, whereas selective COX-2 inhibitor celecoxib synergistically with pioglitazone reduced severity of esophageal damage and protected esophageal mucosa from reflux. We propose the cross talk among EGF/EGFR, PG/COX-2, and proinflammatory cytokines with PPARγ pathway in the mechanism of pathogenesis of chronic esophagitis progressing to BE and EAC.
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Affiliation(s)
- Jolanta Majka
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Mateusz Wierdak
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Aleksandra Szlachcic
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Marcin Magierowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Aneta Targosz
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Katarzyna Urbanczyk
- Department of Pathomorphology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Gracjana Krzysiek-Maczka
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Agata Ptak-Belowska
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Dominik Bakalarz
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Katarzyna Magierowska
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Anna Chmura
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Tomasz Brzozowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
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46
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Dugalic P, Djuranovic S, Pavlovic-Markovic A, Dugalic V, Tomasevic R, Gluvic Z, Obradovic M, Bajic V, Isenovic ER. Proton Pump Inhibitors and Radiofrequency Ablation for Treatment of Barrett's Esophagus. Mini Rev Med Chem 2020; 20:975-987. [PMID: 31644405 DOI: 10.2174/1389557519666191015203636] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 06/04/2019] [Accepted: 06/25/2019] [Indexed: 02/07/2023]
Abstract
Gastroesophageal Reflux Disease (GERD) is characterized by acid and bile reflux in the distal oesophagus, and this may cause the development of reflux esophagitis and Barrett's oesophagus (BE). The natural histological course of untreated BE is non-dysplastic or benign BE (ND), then lowgrade (LGD) and High-Grade Dysplastic (HGD) BE, with the expected increase in malignancy transfer to oesophagal adenocarcinoma (EAC). The gold standard for BE diagnostics involves high-resolution white-light endoscopy, followed by uniform endoscopy findings description (Prague classification) with biopsy performance according to Seattle protocol. The medical treatment of GERD and BE includes the use of proton pump inhibitors (PPIs) regarding symptoms control. It is noteworthy that long-term use of PPIs increases gastrin level, which can contribute to transfer from BE to EAC, as a result of its effects on the proliferation of BE epithelium. Endoscopy treatment includes a wide range of resection and ablative techniques, such as radio-frequency ablation (RFA), often concomitantly used in everyday endoscopy practice (multimodal therapy). RFA promotes mucosal necrosis of treated oesophagal region via high-frequency energy. Laparoscopic surgery, partial or total fundoplication, is reserved for PPIs and endoscopy indolent patients or in those with progressive disease. This review aims to explain distinct effects of PPIs and RFA modalities, illuminate certain aspects of molecular mechanisms involved, as well as the effects of their concomitant use regarding the treatment of BE and prevention of its transfer to EAC.
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Affiliation(s)
- Predrag Dugalic
- Department of Gastroenterology and Hepatology, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Srdjan Djuranovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Pavlovic-Markovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Dugalic
- Clinical Centre of Serbia, Clinic for Surgery, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ratko Tomasevic
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Zoran Gluvic
- Department of Endocrinology and Diabetes, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Vladan Bajic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
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Basen-Engquist K, Brown P, Coletta AM, Savage M, Maresso KC, Hawk E. Lifestyle and Cancer Prevention. ABELOFF'S CLINICAL ONCOLOGY 2020:337-374.e12. [DOI: 10.1016/b978-0-323-47674-4.00022-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Targeting the COX1/2-Driven thromboxane A2 pathway suppresses Barrett's esophagus and esophageal adenocarcinoma development. EBioMedicine 2019; 49:145-156. [PMID: 31707149 PMCID: PMC7113183 DOI: 10.1016/j.ebiom.2019.10.038] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 10/18/2019] [Accepted: 10/21/2019] [Indexed: 12/20/2022] Open
Abstract
Background Barrett's esophagus (BE), a complication of gastroesophageal reflux disease (GERD), predisposes patients to esophageal adenocarcinoma (EAC). Reliable biomarkers for early detection and discovery of potential drug targets are urgently needed for improved BE and EAC patient outcomes. Methods Patient biopsy samples were evaluated for COX1/2, and thromboxane A2 synthase (TBXAS) expression. Circulating prostaglandins biosynthesis was determined using enzyme immunoassay kits. Anchorage-independent cell growth assay, crystal violet staining assay, and xenograft experiments were conducted to assess BE and EAC cell growth. A surgical mouse model of reflux (i.e., esophagoduodenostomy) was established and samples were analyzed using an enzyme immunoassay kit, immunohistochemistry, immunoblotting, or RT-PCR. Esophageal biopsy samples (pre- and post-intervention) were obtained from a randomized clinical trial in which participants were administered esomeprazole (40 mg) twice daily in combination with an acetylsalicylic acid (ASA) placebo or 81 or 325 mg ASA for 28 days. Esophageal biopsy specimens before and after the intervention period were analyzed. Findings COX2 and TBXAS are highly expressed in BE and EAC patients accompanied by a pronounced elevation of circulating TXA2 levels. ASA suppressed BE and EAC growth by targeting the TXA2 pathway. Additionally, biopsies from 49 patients (with similar baseline characteristics) showed that ASA substantially decreased serum TXA2 levels, resulting in reduced inflammation. Interpretation This study establishes the importance of the COX1/2-driven TXA2 pathway in BE and EAC pathophysiology and lays the groundwork for introducing a TXA2-targeting strategy for EAC prevention and early detection. Funding Hormel Foundation, Exact Sciences, Pentax Medical, Intromedic and National Cancer.
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Joharatnam-Hogan N, Cafferty F, Hubner R, Swinson D, Sothi S, Gupta K, Falk S, Patel K, Warner N, Kunene V, Rowley S, Khabra K, Underwood T, Jankowski J, Bridgewater J, Crossley A, Henson V, Berkman L, Gilbert D, Kynaston H, Ring A, Cameron D, Din F, Graham J, Iveson T, Adams R, Thomas A, Wilson R, Pramesh CS, Langley R. Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial. Lancet Gastroenterol Hepatol 2019; 4:854-862. [PMID: 31477558 DOI: 10.1016/s2468-1253(19)30289-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/16/2019] [Accepted: 08/01/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. METHODS The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. FINDINGS After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). INTERPRETATION Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes. FUNDING Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.
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Affiliation(s)
| | - Fay Cafferty
- MRC Clinical Trials Unit, University College London, UK
| | | | | | | | | | - Stephen Falk
- Bristol Haematology & Oncology Centre, Bristol, UK
| | | | | | | | - Sam Rowley
- MRC Clinical Trials Unit, University College London, UK
| | - Komel Khabra
- MRC Clinical Trials Unit, University College London, UK
| | | | - Janusz Jankowski
- Gastroenterology Unit, Morecambe Bay University Hospitals NHS Trust, UK; National Institute for Health and Care Excellence, London, UK
| | | | | | | | | | | | | | | | - David Cameron
- Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, Western General Hospital, Edinburgh, UK
| | - Farhat Din
- Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, Western General Hospital, Edinburgh, UK
| | - Janet Graham
- Beatson West of Scotland Cancer Centre, Glasgow, UK
| | | | | | | | | | - C S Pramesh
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Ruth Langley
- MRC Clinical Trials Unit, University College London, UK.
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Lee HJ, Park JU, Guo RH, Kang BY, Park IK, Kim YR. Anti-Inflammatory Effects of Canavalia gladiata in Macrophage Cells and DSS-Induced Colitis Mouse Model. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2019; 47:1571-1588. [PMID: 31645121 DOI: 10.1142/s0192415x19500800] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Canavalia gladiata, known as sword bean, has been used as a Chinese traditional medicine for anti-inflammatory effects. However, the action mechanisms of sword bean have not yet been clearly defined. In the present study, the whole parts of a ripened sword bean (RSB) and the green sword bean (GSB) containing bean pod were extracted with ethanol by reflux extraction. The two crude extracts (RSBE and GSBE) from RSB and GSB were validated by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis of gallic acid as a reference chemical. The anti-inflammatory effects of two sword bean extracts were extensively investigated using LPS-stimulated macrophage cells. First, RSBE and GSBE significantly inhibited the production of pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandinE2 (PGE2), and nitric oxide (NO) in LPS-induced RAW264.7 cells. RSBE and GSBE showed no cytotoxicity to RAW264.7 cells and mouse peritoneal macrophage cells. In addition, the overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) induced by LPS in RAW264.7 cells was significantly decreased by RSBE and GSBE. Western blotting and immunostaining analysis showed that RSBE and GSBE inhibited the nuclear translocation of NF-κB subunits, which correlated with the inhibitory effects on inhibitor kappa B (IκB) degradation. In dextran sulfated sodium (DSS)-induced colitis mice model, RSBE restored body weight, colon length, and the levels of pro-inflammatory cytokines, such as TNF-α, IL-6, interleukin-1β (IL-1β), and interferon-γ (IFN-γ). In addition, RSBE significantly suppressed the expression of COX-2, iNOS, and NF-κB.
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Affiliation(s)
- Hwa-Jeong Lee
- College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.,Department of Biomedical Sciences, BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea
| | - Jung Up Park
- College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Rui Hong Guo
- College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Bok Yun Kang
- College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea
| | - In-Kyu Park
- Department of Biomedical Sciences, BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea
| | - Young Ran Kim
- College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea
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