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Sun C, Gui J, Sheng Y, Huang L, Zhu X, Huang K. Specific signaling pathways mediated programmed cell death in tumor microenvironment and target therapies. Discov Oncol 2025; 16:776. [PMID: 40377777 PMCID: PMC12084487 DOI: 10.1007/s12672-025-02592-2] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 05/06/2025] [Indexed: 05/18/2025] Open
Abstract
Increasing evidence has shown that programmed cell death (PCD) plays a crucial role in tumorigenesis and cancer progression. The components of PCD are complex and include various mechanisms such as apoptosis, necroptosis, alkaliptosis, oxeiptosis, and anoikis, all of which are interrelated in their functions and regulatory pathways. Given the significance of these processes, it is essential to conduct a comprehensive study on PCD to elucidate its multifaceted nature. Key signaling pathways, particularly the caspase signaling pathway, the RIPK1/RIPK3/MLKL pathway, and the mTOR signaling pathway, are pivotal in regulating PCD and influencing tumor progression. In this review, we briefly describe the generation mechanisms of different PCD components and focus on the regulatory mechanisms of these three major signaling pathways within the context of global PCD. Furthermore, we discuss various tumor therapeutic compounds that target different signaling axes of these pathways, which may provide novel strategies for effective tumor therapy and help improve patient outcomes in cancer treatment.
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Affiliation(s)
- Chengpeng Sun
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1, Minde Road, Donghu District, Nanchang, 330006, Jiangxi, China
- HuanKui Academy, Jiangxi Medical College, Nanchang, 330031, China
| | - Jiawei Gui
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1, Minde Road, Donghu District, Nanchang, 330006, Jiangxi, China
- HuanKui Academy, Jiangxi Medical College, Nanchang, 330031, China
| | - Yilei Sheng
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1, Minde Road, Donghu District, Nanchang, 330006, Jiangxi, China
- HuanKui Academy, Jiangxi Medical College, Nanchang, 330031, China
| | - Le Huang
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1, Minde Road, Donghu District, Nanchang, 330006, Jiangxi, China
- Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, 330006, Jiangxi, China
| | - Xingen Zhu
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1, Minde Road, Donghu District, Nanchang, 330006, Jiangxi, China.
- Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, 330006, Jiangxi, China.
- JXHC Key Laboratory of Neurological Medicine, Nanchang, 330006, Jiangxi, China.
- Institute of Neuroscience, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
| | - Kai Huang
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1, Minde Road, Donghu District, Nanchang, 330006, Jiangxi, China.
- Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, 330006, Jiangxi, China.
- JXHC Key Laboratory of Neurological Medicine, Nanchang, 330006, Jiangxi, China.
- Institute of Neuroscience, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
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2
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Izzo AA, Stefanska B. Natural products and cancer: From drug discovery to prevention and therapy. Br J Pharmacol 2025; 182:2069-2074. [PMID: 40122586 DOI: 10.1111/bph.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2025] Open
Abstract
LINKED ARTICLES This article is part of a themed issue Natural Products and Cancer: From Drug Discovery to Prevention and Therapy. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.10/issuetoc.
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Affiliation(s)
- Angelo A Izzo
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Barbara Stefanska
- Faculty of Land and Food Systems, Food, Nutrition and Health Program, The University of British Columbia, Vancouver, Canada
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3
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Ren J, Yan G, Yang L, Kong L, Guan Y, Sun H, Liu C, Liu L, Han Y, Wang X. Cancer chemoprevention: signaling pathways and strategic approaches. Signal Transduct Target Ther 2025; 10:113. [PMID: 40246868 PMCID: PMC12006474 DOI: 10.1038/s41392-025-02167-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 12/01/2024] [Accepted: 02/04/2025] [Indexed: 04/19/2025] Open
Abstract
Although cancer chemopreventive agents have been confirmed to effectively protect high-risk populations from cancer invasion or recurrence, only over ten drugs have been approved by the U.S. Food and Drug Administration. Therefore, screening potent cancer chemopreventive agents is crucial to reduce the constantly increasing incidence and mortality rate of cancer. Considering the lengthy prevention process, an ideal chemopreventive agent should be nontoxic, inexpensive, and oral. Natural compounds have become a natural treasure reservoir for cancer chemoprevention because of their superior ease of availability, cost-effectiveness, and safety. The benefits of natural compounds as chemopreventive agents in cancer prevention have been confirmed in various studies. In light of this, the present review is intended to fully delineate the entire scope of cancer chemoprevention, and primarily focuses on various aspects of cancer chemoprevention based on natural compounds, specifically focusing on the mechanism of action of natural compounds in cancer prevention, and discussing in detail how they exert cancer prevention effects by affecting classical signaling pathways, immune checkpoints, and gut microbiome. We also introduce novel cancer chemoprevention strategies and summarize the role of natural compounds in improving chemotherapy regimens. Furthermore, we describe strategies for discovering anticancer compounds with low abundance and high activity, revealing the broad prospects of natural compounds in drug discovery for cancer chemoprevention. Moreover, we associate cancer chemoprevention with precision medicine, and discuss the challenges encountered in cancer chemoprevention. Finally, we emphasize the transformative potential of natural compounds in advancing the field of cancer chemoprevention and their ability to introduce more effective and less toxic preventive options for oncology.
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Affiliation(s)
- Junling Ren
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Guangli Yan
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Le Yang
- State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou, China
| | - Ling Kong
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Yu Guan
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Hui Sun
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.
| | - Chang Liu
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Lei Liu
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Ying Han
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Xijun Wang
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.
- State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou, China.
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Porfyris O, Detopoulou P, Adamantidi T, Tsoupras A, Papageorgiou D, Ioannidis A, Rojas Gil AP. Phytochemicals as Chemo-Preventive and Therapeutic Agents Against Bladder Cancer: A Comprehensive Review. Diseases 2025; 13:103. [PMID: 40277814 PMCID: PMC12026019 DOI: 10.3390/diseases13040103] [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: 01/23/2025] [Revised: 03/15/2025] [Accepted: 03/25/2025] [Indexed: 04/26/2025] Open
Abstract
Bladder cancer has a high incidence worldwide and is characterized by a high recurrence rate, metastatic potential, and a significant socioeconomic burden. Conventional treatment modalities usually exhibit serious adverse complications, which also negatively affect patients' quality of life. In the context of exploring new treatment approaches with fewer side effects, the utilization of natural compounds as alternative and/or complementary therapeutic options seems appealing. In the present study, the potential use and effects of various bioactive phytochemicals, including curcumin, resveratrol, epigallocatechin, genistein, and several others, in bladder cancer treatment are thoroughly reviewed. A special focus is given to their potential to beneficially modulate important molecular signaling pathways and mechanisms affecting cell survival, proliferation, migration, and apoptosis, which play a crucial role in the pathogenesis of bladder cancer, such as the PI3K/AKT/mTOR, Ras/Raf/MEK/MAPK, Wnt/β-Catenin, Notch, Hedgehog, Hippo, JAK2/STAT3, and PAF/PAF-receptor pathways. Nevertheless, most studies have been conducted in cell cultures and animal models. Due to differences in genetics and metabolism, more clinical trials are needed to ensure the bio-efficacy of these phytochemicals in humans.
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Affiliation(s)
- Orestis Porfyris
- Laboratory of Basic Health Sciences, Department of Nursing, Faculty of Health Sciences, University of the Peloponnese, Akadimaikou GK, 3 Building OAED, 22100 Tripoli, Greece; (O.P.); (A.I.)
| | - Paraskevi Detopoulou
- Department of Nutritional Science and Dietetics, Faculty of Health Sciences, University of Peloponnese, New Building, Antikalamos, 24100 Kalamata, Greece;
| | - Theodora Adamantidi
- Hephaestus Laboratory, School of Chemistry, Faculty of Sciences, Democritus University of Thrace, Kavala University Campus, 65404 Kavala, Greece; (T.A.); (A.T.)
| | - Alexandros Tsoupras
- Hephaestus Laboratory, School of Chemistry, Faculty of Sciences, Democritus University of Thrace, Kavala University Campus, 65404 Kavala, Greece; (T.A.); (A.T.)
| | - Dimitris Papageorgiou
- Department of Nursing, Faculty of Health Sciences, University of Peloponnese Panarcadian Hospital of Tripoli, Red Cross Terminal (Administrative Services) 2nd Floor, 22100 Tripoli, Greece;
| | - Anastasios Ioannidis
- Laboratory of Basic Health Sciences, Department of Nursing, Faculty of Health Sciences, University of the Peloponnese, Akadimaikou GK, 3 Building OAED, 22100 Tripoli, Greece; (O.P.); (A.I.)
| | - Andrea Paola Rojas Gil
- Laboratory of Basic Health Sciences, Department of Nursing, Faculty of Health Sciences, University of the Peloponnese, Akadimaikou GK, 3 Building OAED, 22100 Tripoli, Greece; (O.P.); (A.I.)
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5
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Lagoa R, Rajan L, Violante C, Babiaka SB, Marques-da-Silva D, Kapoor B, Reis F, Atanasov AG. Application of curcuminoids in inflammatory, neurodegenerative and aging conditions - Pharmacological potential and bioengineering approaches to improve efficiency. Biotechnol Adv 2025; 82:108568. [PMID: 40157560 DOI: 10.1016/j.biotechadv.2025.108568] [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: 12/11/2024] [Revised: 03/21/2025] [Accepted: 03/22/2025] [Indexed: 04/01/2025]
Abstract
Curcumin, a natural compound found in turmeric, has shown promise in treating brain-related diseases and conditions associated with aging. Curcumin has shown multiple anti-inflammatory and brain-protective effects, but its clinical use is limited by challenges like poor absorption, specificity and delivery to the right tissues. A range of contemporary approaches at the intersection with bioengineering and systems biology are being explored to address these challenges. Data from preclinical and human studies highlight various neuroprotective actions of curcumin, including the inhibition of neuroinflammation, modulation of critical cellular signaling pathways, promotion of neurogenesis, and regulation of dopamine levels. However, curcumin's multifaceted effects - such as its impact on microRNAs and senescence markers - suggest novel therapeutic targets in neurodegeneration. Tetrahydrocurcumin, a primary metabolite of curcumin, also shows potential due to its presence in circulation and its anti-inflammatory properties, although further research is needed to elucidate its neuroprotective mechanisms. Recent advancements in delivery systems, particularly brain-targeting nanocarriers like polymersomes, micelles, and liposomes, have shown promise in enhancing curcumin's bioavailability and therapeutic efficacy in animal models. Furthermore, the exploration of drug-laden scaffolds and dermal delivery may extend the pharmacological applications of curcumin. Studies reviewed here indicate that engineered dermal formulations and devices could serve as viable alternatives for neuroprotective treatments and to manage skin or musculoskeletal inflammation. This work highlights the need for carefully designed, long-term studies to better understand how curcumin and its bioactive metabolites work, their safety, and their effectiveness.
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Affiliation(s)
- Ricardo Lagoa
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal; Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials LSRE-LCM, Associate Laboratory in Chemical Engineering ALiCE, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; Applied Molecular Biosciences Unit UCIBIO, Institute for Health and Bioeconomy i4HB, NOVA University of Lisbon, 2829-516 Caparica, Portugal.
| | - Logesh Rajan
- Department of Pharmacognosy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, Tamil Nadu, India.
| | - Cristiana Violante
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal
| | - Smith B Babiaka
- Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon; Department of Microbial Bioactive Compounds, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, 72076 Tübingen, Germany.
| | - Dorinda Marques-da-Silva
- School of Technology and Management, Polytechnic Institute of Leiria, Morro do Lena-Alto do Vieiro, 2411-901 Leiria, Portugal; Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials LSRE-LCM, Associate Laboratory in Chemical Engineering ALiCE, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
| | - Bhupinder Kapoor
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
| | - Flávio Reis
- Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research iCBR, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology CIBB, University of Coimbra, 3000-548 Coimbra, Portugal; Clinical Academic Center of Coimbra, 3004-531 Coimbra, Portugal.
| | - Atanas G Atanasov
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, 05-552 Magdalenka, Poland; Laboratory of Natural Products and Medicinal Chemistry LNPMC, Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences SIMATS, Thandalam, Chennai, India; Ludwig Boltzmann Institute Digital Health and Patient Safety, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
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6
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Neira M, Mena C, Torres K, Simón L. The Potential Benefits of Curcumin-Enriched Diets for Adults with Colorectal Cancer: A Systematic Review. Antioxidants (Basel) 2025; 14:388. [PMID: 40298630 PMCID: PMC12024020 DOI: 10.3390/antiox14040388] [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: 02/16/2025] [Revised: 03/20/2025] [Accepted: 03/22/2025] [Indexed: 04/30/2025] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Conventional treatments such as chemotherapy and radiotherapy are often associated with severe side effects and limited effectiveness. Curcumin, a polyphenol derived from Curcuma longa, has demonstrated anti-inflammatory and anticancer properties. A systematic review of the recent scientific literature followed PRISMA guidelines to evaluate the benefits of a curcumin-enriched diet for adults with colorectal cancer. Articles published between 2018 and 2024 were retrieved from PubMed, SciELO, Google Scholar, and Scopus. Studies meeting the inclusion criteria focused on curcumin, adults, and colorectal cancer outcomes. The administration of curcumin-containing products was associated with improved survival rates, enhanced quality of life, tumor reduction, and anti-inflammatory effects. A curcumin-enriched diet shows potential as an effective adjunct therapy for CRC patients, though its limited bioavailability and potential side effects, such as gastrointestinal discomfort, pose challenges. Addressing these limitations through larger cohorts, extended study durations, and improved formulations to enhance bioavailability is essential. Such efforts could enable the development of personalized dietary recommendations for CRC management.
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Affiliation(s)
| | | | - Keila Torres
- Escuela de Nutrición y Dietética, Universidad Finis Terrae, Santiago 7501015, Chile; (M.N.); (C.M.)
| | - Layla Simón
- Escuela de Nutrición y Dietética, Universidad Finis Terrae, Santiago 7501015, Chile; (M.N.); (C.M.)
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Fumarola S, Cianfruglia L, Cecati M, Giammarchi C, Vaiasicca S, Gasparrini M. Polyphenol Intake in Elderly Patients: A Novel Approach to Counteract Colorectal Cancer Risk? Int J Mol Sci 2025; 26:2497. [PMID: 40141143 PMCID: PMC11942013 DOI: 10.3390/ijms26062497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/06/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Colorectal cancer (CRC) accounts for approximately 10% of all cancers worldwide with an incidence of approximately 60% in patients older than 70 years. In the elderly, the definition of a better therapeutic strategy depends on several factors including the patient's frailty and comorbidity status, life expectancy, and chemotherapy tolerance. In older patients, adverse drug reactions require a reduction in the dose of treatment, resulting in worse oncologic outcomes. In recent years, an increasing number of studies have focused on the potential effects of polyphenols on human health and their use in cancer therapy. In this comprehensive review, we searched the major databases and summarized experimental data of the most important polyphenols in the CRC chemoprevention, with a focus on the molecular mechanisms involved and the antitumor effects in the elderly population. In vitro and in vivo studies have shown that polyphenols exert chemopreventive activity by modulating cell signaling, resulting in the inhibition of cancer development or progression. However, the efficacy seen in experimental studies has not been confirmed in clinical trials, mainly due to their low bioavailability and non-toxic doses. Further research is needed to increase polyphenol bioavailability and reduce side effects in order to suggest their possible use to increase the efficacy of chemotherapeutic treatment.
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Affiliation(s)
- Stefania Fumarola
- Advanced Technology Center for Aging Research, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale di Ricovero e Cura per Anziani (IRCCS-INRCA), 60121 Ancona, Italy; (S.F.); (L.C.)
| | - Laura Cianfruglia
- Advanced Technology Center for Aging Research, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale di Ricovero e Cura per Anziani (IRCCS-INRCA), 60121 Ancona, Italy; (S.F.); (L.C.)
| | - Monia Cecati
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy;
| | - Cinzia Giammarchi
- Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale di Ricovero e Cura per Anziani (IRCCS-INRCA), 60121 Ancona, Italy;
| | - Salvatore Vaiasicca
- Center for Neurobiology of Aging, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale di Ricovero e Cura per Anziani (IRCCS-INRCA), 60121 Ancona, Italy
| | - Massimiliano Gasparrini
- Department of Agriculture, Food and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
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8
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Tang X, He M, Ren Y, Ji M, Yan X, Zeng W, Lv Y, Li Y, He Y. Traditional Chinese Medicine formulas-based interventions on colorectal carcinoma prevention: The efficacies, mechanisms and advantages. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:119008. [PMID: 39471879 DOI: 10.1016/j.jep.2024.119008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/08/2024] [Accepted: 10/26/2024] [Indexed: 11/01/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Traditional Chinese Medicine Formulas (TCMFs) represent a distinctive medical approach to disease treatment and have been utilized in clinical practice for treating intestinal diseases for thousands of years. Recently, TCMFs have received increasing attention due to their advantages of high efficiency, safety, as well as low toxicity, providing promising strategies for preventing colorectal carcinoma (CRC). Nonetheless, the potential mechanism of TCMFs in preventing CRC has not been fully elucidated. AIM OF THE STUDY The literature from the past three years was reviewed to highlight the therapeutic effects and underlying mechanisms of TCMFs in preventing CRC. MATERIALS AND METHODS The keywords have been searched, including "traditional Chinese medicine formulas," "herb pairs," "Herbal plant-derived nanoparticles," et al. in "PubMed" and "China National Knowledge Infrastructure (CNKI)," and screened published articles related to the treatment of intestinal precancerous lesions. This review primarily examined the effectiveness and mechanisms of TCMFs in treating intestinal precancerous lesions, highlighting their significant potential in preventing CRC. RESULTS Gegen Qinlian decoction, Shaoyao decoction, Wu Wei Wan, etc., exert substantial therapeutic effects on intestinal precancerous lesions. These therapeutic effects are demonstrated by a reduction in disease activity index scores, suppression of intestinal inflammation, and preservation of body weight and intestinal function, all of which contribute to the effective prevention of CRC. Besides, the classic Chinese herbal pairs and the extracellular vesicle-like nanoparticles of herbaceous plants have demonstrated superior efficacy in the treatment of intestinal precancerous lesions. Mechanistically, protecting the epithelial barrier, regulating gut microbiota as well as related metabolism, modulating macrophage polarization, and maintaining immune balance contribute to the role of TCMFs in CRC prevention. CONCLUSIONS This review demonstrates the great potential and mechanism of TCMFs in CRC prevention and provides a scientific basis for their utilization in CRC prevention.
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Affiliation(s)
- Xiaojuan Tang
- School of biomedical sciences, Hunan University, Changsha, 410012, Hunan, China; Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China.
| | - Min He
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Yuan Ren
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Meng Ji
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Xiaoqi Yan
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China
| | - Wen Zeng
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Yuan Lv
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China
| | - Yongmin Li
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China
| | - Yongheng He
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, 410006, Hunan, China; Hunan Academy of Chinese Medicine, Changsha, 410006, Hunan, China; Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
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9
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López-Gómez L, Uranga JA. Polyphenols in the Prevention and Treatment of Colorectal Cancer: A Systematic Review of Clinical Evidence. Nutrients 2024; 16:2735. [PMID: 39203871 PMCID: PMC11357634 DOI: 10.3390/nu16162735] [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: 07/08/2024] [Revised: 08/02/2024] [Accepted: 08/14/2024] [Indexed: 09/03/2024] Open
Abstract
Polyphenols are plant metabolites with potential anti-inflammatory and anti-proliferative effects, which may be advantageous for disorders like colorectal cancer (CRC). Despite promising in vitro and in vivo evidence, human clinical trials have yielded mixed results. The present study aimed to evaluate the clinical evidence of polyphenols for CRC prevention or treatment. A systematic review was performed according to PRISMA. Based on a PROSPERO registered protocol (CRD42024560044), online databases (PubMed and COCHRANE) were utilized for the literature search. A total of 100 studies articles were initially identified. After reviewing, 12 studies with a low risk of bias were selected, examining the effect of a variety of compounds. Curcumin demonstrated promise in various trials, mainly decreasing inflammatory cytokines, though results varied, and it did not lower intestinal adenomas or improve outcomes after chemotherapy. Neither epigallocatechin gallate nor artepillin C reduced the incidence of adenomas. Finally, fisetin seemed to improve the inflammatory status of patients under chemotherapy (5-fluorouracil). In summary, although certain polyphenols appear to exert some effect, their role in the prevention or treatment of CRC is inconclusive, and more clinical studies under more controlled conditions are needed.
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Affiliation(s)
- Laura López-Gómez
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain;
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain
| | - Jose Antonio Uranga
- Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain;
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain
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10
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Brockmueller A, Ruiz de Porras V, Shakibaei M. Curcumin and its anti-colorectal cancer potential: From mechanisms of action to autophagy. Phytother Res 2024; 38:3525-3551. [PMID: 38699926 DOI: 10.1002/ptr.8220] [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: 01/03/2024] [Revised: 04/06/2024] [Accepted: 04/10/2024] [Indexed: 05/05/2024]
Abstract
Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy is an evolutionarily highly conserved degradation pathway involved in a variety of cellular processes, such as the maintenance of cellular homeostasis and clearance of foreign bodies, and its imbalance is associated with many diseases. However, the role of autophagy in CRC progression remains controversial, as it has a dual function, affecting either cell death or survival, and is associated with cellular senescence in tumor therapy. Indeed, numerous data have been presented that autophagy in cancers serves as an alternative to cell apoptosis when the latter is ineffective or in apoptosis-resistant cells, which is why it is also referred to as programmed cell death type II. Curcumin, one of the active constituents of Curcuma longa, has great potential to combat CRC by influencing various cellular signaling pathways and epigenetic regulation in a safe and cost-effective approach. This review discusses the efficacy of curcumin against CRC in vitro and in vivo, particularly its modulation of autophagy and apoptosis in various cellular pathways. While clinical studies have assessed the potential of curcumin in cancer prevention and treatment, none have specifically examined its role in autophagy. Nonetheless, we offer an overview of potential correlations to support the use of this polyphenol as a prophylactic or co-therapeutic agent in CRC.
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Affiliation(s)
- Aranka Brockmueller
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Vicenç Ruiz de Porras
- CARE Program, Germans Trias i Pujol Research Institute (IGTP), Barcelona, Spain
- Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (B·ARGO), Barcelona, Spain
- GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
| | - Mehdi Shakibaei
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany
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Gilad O, Tulchinsky H, Kariv R. Surveillance and Management of Pouch Neoplasia in Familial Adenomatous Polyposis: A Systematic Review. Dis Colon Rectum 2024; 67:S82-S90. [PMID: 37878460 DOI: 10.1097/dcr.0000000000003122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2023]
Abstract
BACKGROUND Patients with familial adenomatous polyposis often require prophylactic colectomy with IPAA to treat or reduce the risk of colorectal neoplasia. However, after surgery, patients are still at some risk of developing pouch polyps and even cancer in both handsewn and stapled anastomoses. Management relies mainly on endoscopic or surgical interventions, whereas chemopreventive agents have a limited role in the management and prevention of pouch neoplasia. Novel endoscopic techniques are evolving and may gradually overtake surgical intervention in selected cases. Because familial adenomatous polyposis is relatively rare, there is a scarcity of data regarding the natural history of pouch polyps and cancer in this population. OBJECTIVE This systematic literature review aims to describe the evolution, characteristics, various treatment modalities and their outcomes, and recommended surveillance strategies of pouch neoplasia. DATA SOURCES PubMed and Cochrane databases and the International Ileal Pouch Consortium (for expert opinion). STUDY SELECTION Studies published between 1990 and 2023 in English were included. Studies reporting neoplastic outcomes of only patients with IBD-related pouch neoplasia were excluded. MAIN OUTCOME MEASURES Incidence of pouch neoplasia and its outcomes (successful resections, surgical complications, and mortality). RESULTS Thirty-five studies were included. LIMITATIONS Most studies focused on patients with IBD-related pouch neoplasia; there were scarce data regarding polyposis patients only. Most cohorts were small and retrospective. Data on interventions were mainly descriptive, and no randomized controlled trials were available. CONCLUSIONS Pouch adenomas are common and well managed by endoscopic resections because advanced endoscopic techniques are becoming more available. Additional data are required for defining updated recommendations for either endoscopic or surgical intervention. Pouch cancer is a very rare event and may arise despite surveillance. Continued endoscopic surveillance is key in cancer prevention and early detection. The outcome of cancer cases is poor, and management in a referral center should be advised with tumor board discussions. See video from symposium .
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Affiliation(s)
- Ophir Gilad
- Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hagit Tulchinsky
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Revital Kariv
- Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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12
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Zaffaroni G, Mannucci A, Koskenvuo L, de Lacy B, Maffioli A, Bisseling T, Half E, Cavestro GM, Valle L, Ryan N, Aretz S, Brown K, Buttitta F, Carneiro F, Claber O, Blanco-Colino R, Collard M, Crosbie E, Cunha M, Doulias T, Fleming C, Heinrich H, Hüneburg R, Metras J, Nagtegaal I, Negoi I, Nielsen M, Pellino G, Ricciardiello L, Sagir A, Sánchez-Guillén L, Seppälä TT, Siersema P, Striebeck B, Sampson JR, Latchford A, Parc Y, Burn J, Möslein G. Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision. Br J Surg 2024; 111:znae070. [PMID: 38722804 PMCID: PMC11081080 DOI: 10.1093/bjs/znae070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 02/12/2024] [Accepted: 02/25/2024] [Indexed: 05/12/2024]
Abstract
BACKGROUND Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. METHODS A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). RESULTS One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. CONCLUSION These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.
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Affiliation(s)
- Gloria Zaffaroni
- Center for Hereditary Tumors, Bethesda Hospital, Duisburg, Germany
- Faculty of Medicine and Surgery, University of Milan, Milan, Italy
| | - Alessandro Mannucci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Koskenvuo
- Department of Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Borja de Lacy
- Department of Gastrointestinal Surgery, Hospital Clinic of Barcelona, Barcelona, Spain
| | - Anna Maffioli
- Faculty of Medicine and Surgery, University of Milan, Milan, Italy
- Department of General Surgery, Sacco Hospital, ASST Fatebenefratelli Sacco, Milan, Italy
| | - Tanya Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Elizabeth Half
- Cancer Prevention and Hereditary GI Cancer Unit, Rambam Health Care Campus, Haifa, Israel
| | - Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Valle
- Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, IDIBELL, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Neil Ryan
- The College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK
| | - Stefan Aretz
- Institute of Human, Genetics, Medical Faculty, University of Bonn and National Center for Hereditary Tumour Syndromes, University Hospital Bonn, Bonn, Germany
| | - Karen Brown
- Leicester Cancer Research Centre, University of Leicester, Leicester, UK
| | - Francesco Buttitta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IRCCS University Hospital of Bologna, Policlinico di Sant’Orsola, Bologna, Italy
| | - Fatima Carneiro
- Faculty of Medicine of Porto University, Centro Hospitalar Universitário de São João, Ipatimup, Porto, Portugal
| | - Oonagh Claber
- Department of Clinical Genetics, Northern Genetics Service, Newcastle upon Tyne, UK
| | - Ruth Blanco-Colino
- Department of Gastrointestinal Surgery, Vall d’Hebron University Hospital, Barcelona, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maxime Collard
- Department of Digestive Surgery, Hôpital Saint-Antoine, Sorbonne University, APHP, Paris, France
| | - Emma Crosbie
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Miguel Cunha
- Department of Surgery, Algarve Universitary Hospital Center, Colorectal SurgeryGroup, Portimao, Portugal
| | - Triantafyllos Doulias
- Department of Colorectal Surgery, Colchester Hospital, East Suffolk and North Essex NHS Foundation Trust, Colchester, UK
- Colorectal Surgery Department, Kettering Hospital, University Hospitals of Northamptonshire, Kettering, Northamptonshire, UK
- Department of Genetics and Genome Biology, Honorary Lecturer in the Leicester Cancer Research Centre, Leicester, UK
| | - Christina Fleming
- Department of Colorectal Surgery, University Hospital Limerick, Limerick, Ireland
| | - Henriette Heinrich
- Department for Gastroenterology and Hepatology, Clarunis Universitäres Bauchzentrum, Universitätsspital Basel, Basel, Switzerland
| | - Robert Hüneburg
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
- National Center for Hereditary Tumour Syndromes, University Hospital Bonn, Bonn, Germany
| | - Julie Metras
- Department of Digestive Surgery, Hôpital Saint-Antoine, Sorbonne University, APHP, Paris, France
| | - Iris Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ionut Negoi
- Department of General Surgery, Carol Davila University of Medicine and Pharmacy Bucharest, Emergency Hospital of Bucharest, Bucharest, Romania
| | - Maartje Nielsen
- Clinical Genetics Department, Leiden University Medical Center, Leiden, The Netherlands
| | - Gianluca Pellino
- Department of Gastrointestinal Surgery, Vall d’Hebron University Hospital, Barcelona, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
- Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Luigi Ricciardiello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- IRCCS University Hospital of Bologna, Policlinico di Sant’Orsola, Bologna, Italy
| | | | - Luis Sánchez-Guillén
- Department of Gastrointestinal Surgery, Elche General University Hospital, Elche, Alicante, Spain
- Miguel Hernández University, Elche, Spain
| | - Toni T Seppälä
- Department of Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland
- Faculty of Medicine and Health Technology, University of Tampere and TAYS Cancer Centre, Tampere, Finland
- iCAN Precision Medicine Flagship, University of Helsinki, Helsinki, Finland
| | - Peter Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Julian R Sampson
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK
| | - Andrew Latchford
- Polyposis Registry, St Mark’s Hospital, Harrow, UK
- Department of Surgery and Cancer, Imperial College, London, UK
| | - Yann Parc
- Department of Digestive Surgery, Hôpital Saint-Antoine, Sorbonne University, APHP, Paris, France
| | - John Burn
- Newcastle University Translational and Clinical Research Institute, Centre for Life, Newcastle upon Tyne, UK
| | - Gabriela Möslein
- Center for Hereditary Tumors, Bethesda Hospital, Duisburg, Germany
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Gilad O, Muller C, Kupfer SS. Chemoprevention in Inherited Colorectal Cancer Syndromes. Clin Colon Rectal Surg 2024; 37:172-179. [PMID: 38606042 PMCID: PMC11006448 DOI: 10.1055/s-0043-1770384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/13/2024]
Abstract
Cancer prevention in hereditary gastrointestinal predisposition syndromes relies primarily on intensive screening (e.g., colonoscopy) or prophylactic surgery (e.g., colectomy). The use of chemopreventive agents as an adjunct to these measures has long been studied both in the general population and in hereditary cancer patients, in whom the risk of malignancy, and therefore the potential risk reduction, is considerably greater. However, to date only few compounds have been found to be effective, safe, and tolerable for widespread use. Furthermore, many of the studies involving these rare syndromes suffer from small sample sizes, heterogeneous patient cohorts, short follow-up duration, and lack of standardized endpoints, creating challenges to draw generalizable conclusion regarding efficacy. The following review summarizes the current data on various chemopreventive compounds used in Lynch syndrome and familial adenomatous polyposis in addition to several agents that are currently being investigated.
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Affiliation(s)
- Ophir Gilad
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, Illinois
| | - Charles Muller
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois
| | - Sonia S. Kupfer
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, Illinois
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14
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Xia Y, Sun M, Huang H, Jin WL. Drug repurposing for cancer therapy. Signal Transduct Target Ther 2024; 9:92. [PMID: 38637540 PMCID: PMC11026526 DOI: 10.1038/s41392-024-01808-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/05/2024] [Accepted: 03/19/2024] [Indexed: 04/20/2024] Open
Abstract
Cancer, a complex and multifactorial disease, presents a significant challenge to global health. Despite significant advances in surgical, radiotherapeutic and immunological approaches, which have improved cancer treatment outcomes, drug therapy continues to serve as a key therapeutic strategy. However, the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects, and thus there remains a critical need to develop novel cancer therapeutics. One promising strategy that has received widespread attention in recent years is drug repurposing: the identification of new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective, proven to be safe, and can significantly expedite the drug development process due to their already established safety profiles. In light of this, the present review offers a comprehensive overview of the various methods employed in drug repurposing, specifically focusing on the repurposing of drugs to treat cancer. We describe the antitumor properties of candidate drugs, and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment. In addition, we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery. We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen. To conclude, we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.
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Affiliation(s)
- Ying Xia
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, PR China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, PR China
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, PR China
- Division of Gastroenterology and Hepatology, Department of Medicine and, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Ming Sun
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, PR China
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, PR China
| | - Hai Huang
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, PR China.
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, PR China.
| | - Wei-Lin Jin
- Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China.
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15
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Ross SA, Emenaker NJ, Kumar A, Riscuta G, Biswas K, Gupta S, Mohammed A, Shoemaker RH. Green Cancer Prevention and Beyond. Cancer Prev Res (Phila) 2024; 17:107-118. [PMID: 38251904 PMCID: PMC10911807 DOI: 10.1158/1940-6207.capr-23-0308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/13/2023] [Accepted: 01/18/2024] [Indexed: 01/23/2024]
Abstract
The concept of green chemoprevention was introduced in 2012 by Drs. Jed Fahey and Thomas Kensler as whole-plant foods and/or extract-based interventions demonstrating cancer prevention activity. Refining concepts and research demonstrating proof-of-principle approaches are highlighted within this review. Early approaches included extensively investigated whole foods, including broccoli sprouts and black raspberries showing dose-responsive effects across a range of activities in both animals and humans with minimal or no apparent toxicity. A recent randomized crossover trial evaluating the detoxification of tobacco carcinogens by a broccoli seed and sprout extract in the high-risk cohort of current smokers highlights the use of a dietary supplement as a potential next-generation green chemoprevention or green cancer prevention approach. Challenges are addressed, including the selection of dose, duration and mode of delivery, choice of control group, and standardization of the plant food or extract. Identification and characterization of molecular targets and careful selection of high-risk cohorts for study are additional important considerations when designing studies. Goals for precision green cancer prevention include acquiring robust evidence from carefully controlled human studies linking plant foods, extracts, and compounds to modulation of targets for cancer risk reduction in individual cancer types.
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Affiliation(s)
- Sharon A. Ross
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Nancy J. Emenaker
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Amit Kumar
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Gabriela Riscuta
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Kajal Biswas
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
| | - Shanker Gupta
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
| | - Altaf Mohammed
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
| | - Robert H. Shoemaker
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
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16
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Moon DO. Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management. Int J Mol Sci 2024; 25:2911. [PMID: 38474160 DOI: 10.3390/ijms25052911] [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: 01/30/2024] [Revised: 02/28/2024] [Accepted: 02/29/2024] [Indexed: 03/14/2024] Open
Abstract
This paper delves into the diverse and significant roles of curcumin, a polyphenolic compound from the Curcuma longa plant, in the context of cancer and inflammatory diseases. Distinguished by its unique molecular structure, curcumin exhibits potent biological activities including anti-inflammatory, antioxidant, and potential anticancer effects. The research comprehensively investigates curcumin's molecular interactions with key proteins involved in cancer progression and the inflammatory response, primarily through molecular docking studies. In cancer, curcumin's effectiveness is determined by examining its interaction with pivotal proteins like CDK2, CK2α, GSK3β, DYRK2, and EGFR, among others. These interactions suggest curcumin's potential role in impeding cancer cell proliferation and survival. Additionally, the paper highlights curcumin's impact on inflammation by examining its influence on proteins such as COX-2, CRP, PDE4, and MD-2, which are central to the inflammatory pathway. In vitro and clinical studies are extensively reviewed, shedding light on curcumin's binding mechanisms, pharmacological impacts, and therapeutic application in various cancers and inflammatory conditions. These studies are pivotal in understanding curcumin's functionality and its potential as a therapeutic agent. Conclusively, this review emphasizes the therapeutic promise of curcumin in treating a wide range of health issues, attributed to its complex chemistry and broad pharmacological properties. The research points towards curcumin's growing importance as a multi-faceted natural compound in the medical and scientific community.
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Affiliation(s)
- Dong-Oh Moon
- Department of Biology Education, Daegu University, 201, Daegudae-ro, Gyeongsan-si 38453, Gyeongsangbuk-do, Republic of Korea
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Noor A, Shafi S, Sehar N, Qadir I, Bilquees, Rashid S, Arafah A, Rasool S, Dar NJ, Masoodi MH, Rehman MU. Curcuminoids as Cell Signaling Pathway Modulators: A Potential Strategy for Cancer Prevention. Curr Med Chem 2024; 31:3093-3117. [PMID: 37559247 DOI: 10.2174/0929867331666230809100335] [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: 09/13/2022] [Revised: 02/23/2023] [Accepted: 03/03/2023] [Indexed: 08/11/2023]
Abstract
Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidence reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoid, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/β-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoid also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoid against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKβ, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology- based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.
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Affiliation(s)
- Aneeza Noor
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Saimeena Shafi
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Nouroz Sehar
- Centre for Translational and Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi 110062, India
| | - Insha Qadir
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Bilquees
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, Al Kharj, 11942, Saudi Arabia
| | - Azher Arafah
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Saiema Rasool
- Department of School Education, Govt. of Jammu & Kashmir, Srinagar, J&K 190001, India
| | - Nawab John Dar
- Cellular Neurobiology Laboratory (CNB-P), Salk Institute, 10010 N. Torrey Pines Rd., La Jolla, CA92037, USA
| | - Mubashir Hussain Masoodi
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Muneeb U Rehman
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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Luo P, Shi W, Cheng X, Yang J, Pei G, Dong J. Which Drugs are More Effective in Preventing Familial Adenomatous Polyposis Progression based on Network Meta-analysis? Curr Pharm Des 2024; 30:1548-1563. [PMID: 38698755 DOI: 10.2174/0113816128289465240422074745] [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: 11/16/2023] [Accepted: 03/15/2024] [Indexed: 05/05/2024]
Abstract
BACKGROUND Familial adenomatous polyposis (FAP) is an inherited disorder. At present, an increasing number of medications are being employed to treat FAP; however, only a few have been assessed for their efficacy and safety. Therefore, this study aimed to conduct a network meta-analysis to compare the therapeutic outcomes and adverse drug reactions of all FAP-associated medications. METHODS Six relevant databases were searched to identify pertinent randomized controlled trials (RCTs), and information on the dosage and frequency of various drugs was extracted. Additionally, data on changes in polyp counts and dimensions, as well as treatment-related adverse reactions for different medications were collected. The Bayesian method was employed to directly or indirectly compare the impact of different treatment regimens on changes in polyp numbers and diameters, and the safety of the drugs was investigated. RESULTS CXB at 16 mg/kg/day significantly reduced polyp numbers. Celecoxib at 8 mg/kg/day and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) were effective for tolerant FAP patients. Additionally, EPAFFA 2 g daily and sulindac (150 mg twice daily) plus erlotinib (75 mg/day) emerged as the most effective for reducing polyp size. CONCLUSION The most effective treatment for reducing the number of colorectal polyps is celecoxib 16 mg/kg/day. On the other hand, a daily dosage of 2 g EPA-FFA demonstrates the best results in terms of decreasing colorectal polyp diameter.
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Affiliation(s)
- Pei Luo
- Colorectal Surgery Department, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan, China
| | - Wenjun Shi
- Colorectal Surgery Department, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan, China
| | - Xianshuo Cheng
- Colorectal Surgery Department, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan, China
| | - Jun Yang
- Colorectal Surgery Department, The First Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan, China
| | - Gen Pei
- Colorectal Surgery Department, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan, China
| | - Jian Dong
- Colorectal Surgery Department, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650106, Yunnan, China
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Lin WR, Liu WQ, Meng XY, Liu XT, Kou ZY, Li WL, Yang J. Identification of driving genes of familial adenomatous polyposis by differential gene expression analysis and weighted gene co-expression network analysis. Technol Health Care 2024; 32:1675-1696. [PMID: 38073344 PMCID: PMC11091565 DOI: 10.3233/thc-230719] [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: 06/01/2023] [Accepted: 10/07/2023] [Indexed: 05/12/2024]
Abstract
BACKGROUND Despite the advancement of new screening strategies and the advances in pharmacological therapies, the cancerization rates of familial adenomatous polyposis (FAP) are stable and even increased in the last years. Therefore, it necessitates additional research to characterize and understand the underlying mechanisms of FAP. OBJECTIVE To determine the genes that drive the pathogenesis of familial adenomatous polyposis (FAP). METHODS We performed on a cohort (GSE111156) gene profile, which consist of four group of gene expressions (the gene expressions of cancer, adenoma and normal tissue of duodenal cancer from patients with FAP were defined as Case N, Case A and Case C respectively, while that of adenoma tissue from patients with FAP who did not have duodenal cancer was Ctrl A). Tracking Tumor Immunophenotype (TIP) website was applied to reveal immune infiltration profile and signature genes of FAP. We merged the genes of key module (pink and midnight module) with signature genes to obtained the biomarkers related with FAP pathogenesis. The expression of these five biomarkers in FAP intratumoral region (IT) and tumor rim (TR) was detected with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS In total, 220, 23 and 63 DEGs were determined in Cases C, A and N, in comparison to Ctrl A. In total, 196 and 10 DEGs were determined in Cases C and A, separately, as compared to Case N. A total of four biomarkers including CCL5, CD3G, CD2 and TLR3 were finally identified associated with pink module, while only one biomarker (KLF2) associated with midnight module was identified. All biomarkers were evidently raised in FAP IT tissues utilizing qRT-PCR. CONCLUSION We identified five potential biomarkers for pathogenesis of FAP to understand the fundamental mechanisms of FAP progression and revealed some probable targets for the diagnosis or treatment of FAP.
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Affiliation(s)
- Wan-Rong Lin
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Wei-Qing Liu
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Department of Internal Medicine-Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Xuan-Yu Meng
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Xiao-Ting Liu
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Zhi-Yong Kou
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Wen-Liang Li
- Colorectal Cancer Clinical Research Center, Third Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China
| | - Jun Yang
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
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21
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Tan S, Ou Y, Yang Y, Huang S, Chen S, Gao Q. Preventive effects of chemical drugs on recurrence of colorectal adenomas: systematic review and Bayesian network meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:62-75. [PMID: 37942763 DOI: 10.1097/meg.0000000000002676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
BACKGROUND The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs. METHODS We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs. RESULTS Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs. CONCLUSION DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings.
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Affiliation(s)
- Shufa Tan
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Yan Ou
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Yunyi Yang
- Shanghai University of Traditional Chinese Medicine, Shanghai
| | - Shuilan Huang
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Shikai Chen
- Shaanxi University of Traditional Chinese Medicine, Xianyang
| | - Qiangqiang Gao
- Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, China
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Chevalier E, Benamouzig R. Chemoprevention in hereditary digestive neoplasia: A comprehensive review. Therap Adv Gastroenterol 2023; 16:17562848231215585. [PMID: 38050626 PMCID: PMC10693784 DOI: 10.1177/17562848231215585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 10/23/2023] [Indexed: 12/06/2023] Open
Abstract
Hereditary syndromes, such as familial adenomatous polyposis (FAP), MUTYH polyposis or Lynch syndrome, are particularly predisposing to the development of colorectal cancer. These situations have necessitated the development of adapted prevention strategies based largely on reinforced endoscopic surveillance and the search for complementary prevention strategies. This is the case for chemoprevention, which is the long-term administration of chemical agents limiting carcinogenesis, used as primary or secondary prophylaxis. The aim of this review is to present the available literature and the latest advances in chemoprevention in patients with FAP or MUTYH and other polyposis as well as in patients with Lynch syndrome. The main conclusions of the few available guidelines in these situations are also discussed.
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Affiliation(s)
- Eugénie Chevalier
- Department of Gastroenterology and Digestive Oncology, Avicenne Hospital, Bobigny, France
| | - Robert Benamouzig
- Department of Gastroenterology and Digestive Oncology, Avicenne Hospital, AP-HP, Paris Nord la Sorbonne University, 125 Rue de Stalingrad, Bobigny 93000, France
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23
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Niu C, Zhang J, Okolo P. Greasing the Wheels of Pharmacotherapy for Colorectal Cancer: the Role of Natural Polyphenols. Curr Nutr Rep 2023; 12:662-678. [PMID: 38041707 DOI: 10.1007/s13668-023-00512-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/21/2023] [Indexed: 12/03/2023]
Abstract
PURPOSE OF REVIEW The main purpose of this review, mainly based on preclinical studies, is to summarize the pharmacological and biochemical evidence regarding natural polyphenols against colorectal cancer and highlight areas that require future research. RECENT FINDINGS Typically, colorectal cancer is a potentially preventable and curable cancer arising from benign precancerous polyps found in the colon's inner lining. Colorectal cancer is the third most common cancer, with a lifetime risk of approximately 4 to 5%. Genetic background and environmental factors play major roles in the pathogenesis of colorectal cancer. Theoretically, a multistep process of colorectal carcinogenesis provides enough time for anti-tumor pharmacotherapy of colorectal cancer. Chronic colonic inflammation, oxidative stress, and gut microbiota imbalance have been found to increase the risk for colorectal cancer development by creating genotoxic stress within the intestinal environment to generate genetic mutations and epigenetic modifications. Currently, numerous natural polyphenols have shown anti-tumor properties against colorectal cancer in preclinical research, especially in colorectal cancer cell lines. In this review, the current literature regarding the etiology and epidemiology of colorectal cancer is briefly outlined. We highlight the findings of natural polyphenols in colorectal cancer from in vitro and in vivo studies. The scarcity of human trials data undermines the clinical use of natural polyphenols as anti-colorectal cancer agents, which should be undertaken in the future.
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Affiliation(s)
- Chengu Niu
- Internal Medicine Residency Program, Rochester General Hospital, Rochester, NY, 14621, USA.
| | - Jing Zhang
- Rainier Springs Behavioral Health Hospital, Vancouver, 98686, USA
| | - Patrick Okolo
- Division of Gastroenterology, Rochester General Hospital, Rochester, NY, 14621, USA
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Joshi P, Bisht A, Paliwal A, Dwivedi J, Sharma S. Recent updates on clinical developments of curcumin and its derivatives. Phytother Res 2023; 37:5109-5158. [PMID: 37536946 DOI: 10.1002/ptr.7974] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 06/19/2023] [Accepted: 07/15/2023] [Indexed: 08/05/2023]
Abstract
Curcumin, a natural polyphenol, derived from Curcuma longa L. is extensively studied by various researchers across the globe and has established its immense potential in the management of several disorders at clinical level. The underlying mechanism of curcumin involves regulation of various molecular targets, namely, inflammatory cytokines, transcription factor, apoptotic genes, growth factors, oxidative stress biomarkers, and protein kinases. In clinical trials, curcumin as an adjuvant has significantly boost-up the efficacy of many proven drugs in the management of arthritis, neurodegenerative disorder, oral infection, and gastrointestinal disorders. Moreover, clinical studies have suggested curcumin as an appropriate candidate for the prevention and/or management of various cancers via regulation of signaling molecules including NF-kB, cytokines, C-reactive protein, prostaglandin E2, Nrf2, HO-1, ALT, AST, kinases, and blood profiles. This article highlights plethora of clinical trials that have been conducted on curcumin and its derivatives in the management of several ailments. Besides, it provides recent updates to the investigators for conducting future research to fulfill the current gaps to expedite the curcumin utility in clinical subjects bearing different pathological states.
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Affiliation(s)
- Priyanka Joshi
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
| | - Akansha Bisht
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
| | - Ajita Paliwal
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
| | - Jaya Dwivedi
- Department of Chemistry, Banasthali Vidyapith, Banasthali, Rajasthan, India
| | - Swapnil Sharma
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India
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Enayati A, Soghi A, Butler AE, Rizzo M, Sahebkar A. The Effect of Curcumin on the Gut-Brain Axis: Therapeutic Implications. J Neurogastroenterol Motil 2023; 29:409-418. [PMID: 37814431 PMCID: PMC10577457 DOI: 10.5056/jnm23065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/23/2023] [Accepted: 08/11/2023] [Indexed: 10/11/2023] Open
Abstract
The gut-brain axis describes the bidirectional communication between the gut, the enteric nervous system, and the central nervous system. The gut-brain axis has attracted increasing attention owing to its regulatory effect on dysbiosis and a wide range of related diseases. Several types of nutrients, such as curcumin, have been proposed as regulators of the dysbiotic state, and preclinical experiments have suggested that curcumin is not only beneficial but also safe. This review focuses on the interplay between curcumin and the gut microbiota. Moreover, it provides a comprehensive review of the crosstalk between the gut-brain axis and disease, whilst also discussing curcumin-mediated gut-brain axis-dependent and -independent signaling about modulation of gut microbiota dysbiosis. This will help to define the utility of curcumin as a novel therapeutic agent to regulate intestinal microflora dysbiosis.
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Affiliation(s)
- Ayesheh Enayati
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Aida Soghi
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Alexandra E Butler
- Research Department, Royal College of Surgeons in Ireland, Adliya, Bahrain
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, Palermo, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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26
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Stone JK, Mehta NA, Singh H, El-Matary W, Bernstein CN. Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome. Fam Cancer 2023; 22:413-422. [PMID: 37119510 DOI: 10.1007/s10689-023-00334-3] [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: 01/23/2023] [Accepted: 04/18/2023] [Indexed: 05/01/2023]
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome predisposing affected individuals to gastrointestinal (GI) cancers through a high burden of polyposis. Colorectal cancer rates reach 100% by the age of 45, making early colectomy a mainstay of treatment. While most patients undergo colectomy at an early age, ongoing screening and surveillance of the upper gastrointestinal tract and rectal pouch must continue throughout adulthood. Endoscopic therapy of gastric, duodenal, ampullary and rectal pouch polyps is critical to reduce morbidity and cancer related mortality. Management of these lesions is not uniform, and is dependent on their location, size, histology, and risk of malignant potential. Medical therapies targeting pathways that reduce the malignant progression of pre-cancerous lesions have been studied for many years. While studies on the use of aspirin and non-steroidal anti-inflammatories (NSAIDs) in chemoprevention have shown encouraging results in Lynch syndrome and primary colorectal cancer, the potential benefits of these medications have not been duplicated in FAP cohorts. While data remains limited on chemoprevention in FAP, a number of randomized trials are currently underway examining targeted therapies with the potential to slow the progression of the disease. This review aims to provide an in-depth review of the literature on current endoscopic options and chemopreventive therapies targeting FAP. While the endoscopic management has robust data for its use, chemoprevention in FAP is still in its infancy. The complementary use of chemopreventive agents and endoscopic therapy for FAP patients is quickly becoming a growing and exciting area of research.
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Affiliation(s)
- J K Stone
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
| | - N A Mehta
- Center for Interventional and Therapeutic Endoscopy, Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA
| | - H Singh
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
- Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada
| | - W El-Matary
- Section of Pediatric Gastroenterology, Department of Pediatrics, Max Rady College of Medicine, Winnipeg, MB, Canada
| | - C N Bernstein
- Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
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Kyriakidis F, Kogias D, Venou TM, Karlafti E, Paramythiotis D. Updated Perspectives on the Diagnosis and Management of Familial Adenomatous Polyposis. Appl Clin Genet 2023; 16:139-153. [PMID: 37600856 PMCID: PMC10439286 DOI: 10.2147/tacg.s372241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 07/31/2023] [Indexed: 08/22/2023] Open
Abstract
Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome marked by extensive colorectal polyposis and a high risk of colorectal cancer (CRC). Having access to screening and enrollment programs can improve survival for patients with FAP by enabling them to undergo surgery before the development of colorectal cancer. Provided that there are a variety of surgical options available to treat colorectal polyps in patients with adenomatous polyposis, the appropriate surgical option for each patient should be considered. The gold-standard treatment to reduce this risk is prophylactic colectomy, typically by the age of 40. However, colectomy is linked to morbidity and constitutes an ineffective way at preventing extra-colonic disease manifestations, such as desmoid disease, thyroid malignancy, duodenal polyposis, and cancer. Moreover, extensive studies have been conducted into the use of chemopreventive agents to prevent disease progression and delay the necessity for a colectomy as well as the onset of extracolonic disease. The ideal chemoprevention agent should demonstrate a biologically plausible mechanism of action and provide safety, easy tolerance over an extended period of time and a lasting and clinically meaningful effect. Although many pharmaceutical and non-pharmaceutical products have been tested through the years, there has not yet been a chemoprevention agent that meets these criteria. Thus, it is necessary to develop new FAP agents that target novel pathways, such as the mTOR pathway. The aim of this article is to review the prior literature on FAP in order to concentrate the current and future perspectives of diagnosis and treatment. In conclusion, we will provide an update on the diagnostic and therapeutic options, surgical or pharmaceutical, while focusing on the potential treatment strategies that could further reduce the risk of CRC.
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Affiliation(s)
- Filippos Kyriakidis
- Second Chemotherapy Department, Theagenio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Dionysios Kogias
- First Department of Internal Medicine, University General Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Theodora Maria Venou
- Second Chemotherapy Department, Theagenio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Eleni Karlafti
- Emergency Department, AHEPA General University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Daniel Paramythiotis
- First Propaedeutic Surgery Department, AHEPA University General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Kyriakidis F, Kogias D, Venou TM, Karlafti E, Paramythiotis D. Updated Perspectives on the Diagnosis and Management of Familial Adenomatous Polyposis. Appl Clin Genet 2023; Volume 16:139-153. [DOI: https:/doi.org/10.2147/tacg.s372241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025] Open
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29
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Frieler M, Moore M, Longacre ML. Primary and Secondary Prevention Interventions to Reduce Risk Factors Associated with Colorectal Cancer in High-Risk Groups: a Systematic Literature Review. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2023; 38:738-751. [PMID: 36826735 DOI: 10.1007/s13187-023-02273-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/10/2023] [Indexed: 06/02/2023]
Abstract
In the USA, colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths. Certain groups in the USA are at an increased risk of developing CRC, including those with a genetic risk and family history. The purpose of this project was to synthesize primary and secondary prevention interventions for individuals who are at high risk of CRC due to family history or genetic predisposition. This study systematically reviewed articles from PubMed, Google Scholar, and EBSCO using specific search terms to find relevant articles. Sixteen articles were identified for full-text review, which were categorized as non-drug interventions (n = 7) and drug interventions (n = 9). Non-drug interventions focused primarily on increasing screening in those with a first-degree relative (FDR) with CRC or those with Lynch syndrome (LS). Interventions that increased CRC screening often had a tailored component and were otherwise varied in study designs and intervention type. Drug interventions focused on the use of NSAIDs on patients with familial adenomatous polyposis (FAP). Studies showed very little racial and ethnic diversity. Findings suggest that tailored interventions are particularly effective in increasing CRC screening, and greater diversity of sample is needed with respect to race and ethnicity.
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Affiliation(s)
- Madison Frieler
- Department of Public Health, Arcadia University, 450 Easton Rd, Glenside, PA, 19038, USA
| | - McKenna Moore
- Department of Public Health, Arcadia University, 450 Easton Rd, Glenside, PA, 19038, USA
| | - Margaret L Longacre
- Department of Public Health, Arcadia University, 450 Easton Rd, Glenside, PA, 19038, USA.
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Mishra AP, Singh P, Yadav S, Nigam M, Seidel V, Rodrigues CF. Role of the Dietary Phytochemical Curcumin in Targeting Cancer Cell Signalling Pathways. PLANTS (BASEL, SWITZERLAND) 2023; 12:plants12091782. [PMID: 37176840 PMCID: PMC10180989 DOI: 10.3390/plants12091782] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/19/2023] [Accepted: 04/22/2023] [Indexed: 05/15/2023]
Abstract
The diarylheptanoid curcumin [(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione] is one of the phenolic pigments responsible for the yellow colour of turmeric (Curcuma longa L.). This phytochemical has gained much attention in recent years due to its therapeutic potential in cancer. A range of drug delivery approaches have been developed to optimise the pharmacokinetic profile of curcumin and ensure that it reaches its target sites. Curcumin exhibits numerous biological effects, including anti-inflammatory, cardioprotective, antidiabetic, and anti-aging activities. It has also been extensively studied for its role as a cancer chemopreventive and anticancer agent. This review focusses on the role of curcumin in targeting the cell signalling pathways involved in cancer, particularly via modulation of growth factors, transcription factors, kinases and other enzymes, pro-inflammatory cytokines, and pro-apoptotic and anti-apoptotic proteins. It is hoped that this study will help future work on the potential of curcumin to fight cancer.
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Affiliation(s)
- Abhay Prakash Mishra
- Department of Pharmacology, Faculty of Health Science, University of Free State, Bloemfontein 9300, South Africa
| | - Pratichi Singh
- Department of Biosciences, School of Basic and Applied Sciences, Galgotias University, Greater Noida 203201, Uttar Pradesh, India
| | - Shikha Yadav
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida 203201, Uttar Pradesh, India
| | - Manisha Nigam
- Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal 246174, Uttarakhand, India
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
| | - Celia Fortuna Rodrigues
- LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
- ALiCE-Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
- TOXRUN-Toxicology Research Unit, Cooperativa de Ensino Superior Politécnico e Universitário-CESPU, 4585-116 Gandra PRD, Portugal
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Lepore Signorile M, Grossi V, Fasano C, Simone C. Colorectal Cancer Chemoprevention: A Dream Coming True? Int J Mol Sci 2023; 24:7597. [PMID: 37108756 PMCID: PMC10140862 DOI: 10.3390/ijms24087597] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Colorectal cancer (CRC) is one of the deadliest forms of cancer worldwide. CRC development occurs mainly through the adenoma-carcinoma sequence, which can last decades, giving the opportunity for primary prevention and early detection. CRC prevention involves different approaches, ranging from fecal occult blood testing and colonoscopy screening to chemoprevention. In this review, we discuss the main findings gathered in the field of CRC chemoprevention, focusing on different target populations and on various precancerous lesions that can be used as efficacy evaluation endpoints for chemoprevention. The ideal chemopreventive agent should be well tolerated and easy to administer, with low side effects. Moreover, it should be readily available at a low cost. These properties are crucial because these compounds are meant to be used for a long time in populations with different CRC risk profiles. Several agents have been investigated so far, some of which are currently used in clinical practice. However, further investigation is needed to devise a comprehensive and effective chemoprevention strategy for CRC.
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Affiliation(s)
- Martina Lepore Signorile
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Valentina Grossi
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Candida Fasano
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
| | - Cristiano Simone
- Medical Genetics, National Institute of Gastroenterology—IRCCS “Saverio de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy; (M.L.S.); (C.F.)
- Medical Genetics, Department of Precision and Regenerative Medicine and Jonic Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
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Kunnumakkara AB, Hegde M, Parama D, Girisa S, Kumar A, Daimary UD, Garodia P, Yenisetti SC, Oommen OV, Aggarwal BB. Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials. ACS Pharmacol Transl Sci 2023; 6:447-518. [PMID: 37082752 PMCID: PMC10111629 DOI: 10.1021/acsptsci.2c00012] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Indexed: 03/08/2023]
Abstract
Turmeric (Curcuma longa) has been used for thousands of years for the prevention and treatment of various chronic diseases. Curcumin is just one of >200 ingredients in turmeric. Almost 7000 scientific papers on turmeric and almost 20,000 on curcumin have been published in PubMed. Scientific reports based on cell culture or animal studies are often not reproducible in humans. Therefore, human clinical trials are the best indicators for the prevention and treatment of a disease using a given agent/drug. Herein, we conducted an extensive literature survey on PubMed and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The keywords "turmeric and clinical trials" and "curcumin and clinical trials" were considered for data mining. A total of 148 references were found to be relevant for the key term "turmeric and clinical trials", of which 70 were common in both PubMed and Scopus, 44 were unique to PubMed, and 34 were unique to Scopus. Similarly, for the search term "curcumin and clinical trials", 440 references were found to be relevant, of which 70 were unique to PubMed, 110 were unique to Scopus, and 260 were common to both databases. These studies show that the golden spice has enormous health and medicinal benefits for humans. This Review will extract and summarize the lessons learned about turmeric and curcumin in the prevention and treatment of chronic diseases based on clinical trials.
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Affiliation(s)
- Ajaikumar B. Kunnumakkara
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Mangala Hegde
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Dey Parama
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Sosmitha Girisa
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Aviral Kumar
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Uzini Devi Daimary
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Prachi Garodia
- Integrative
Research Center, Miami, Florida 33125, United States
| | - Sarat Chandra Yenisetti
- Department
of Zoology, Drosophila Neurobiology Laboratory, Nagaland University (Central), Lumami, Nagaland-798627, India
| | - Oommen V. Oommen
- Department
of Computational Biology and Bioinformatics, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala-695581, India
| | - Bharat B. Aggarwal
- Inflammation
Research Center, San Diego, California 92109, United States
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Panknin TM, Howe CL, Hauer M, Bucchireddigari B, Rossi AM, Funk JL. Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Int J Mol Sci 2023; 24:4476. [PMID: 36901908 PMCID: PMC10003109 DOI: 10.3390/ijms24054476] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 02/12/2023] [Accepted: 02/21/2023] [Indexed: 02/26/2023] Open
Abstract
Medicinal properties of turmeric (Curcuma longa L.), a plant used for centuries as an anti-inflammatory, are attributed to its polyphenolic curcuminoids, where curcumin predominates. Although "curcumin" supplements are a top-selling botanical with promising pre-clinical effects, questions remain regarding biological activity in humans. To address this, a scoping review was conducted to assess human clinical trials reporting oral curcumin effects on disease outcomes. Eight databases were searched using established guidelines, yielding 389 citations (from 9528 initial) that met inclusion criteria. Half focused on obesity-associated metabolic disorders (29%) or musculoskeletal disorders (17%), where inflammation is a key driver, and beneficial effects on clinical outcomes and/or biomarkers were reported for most citations (75%) in studies that were primarily double-blind, randomized, and placebo-controlled trials (77%, D-RCT). Citations for the next most studied disease categories (neurocognitive [11%] or gastrointestinal disorders [10%], or cancer [9%]), were far fewer in number and yielded mixed results depending on study quality and condition studied. Although additional research is needed, including systematic evaluation of diverse curcumin formulations and doses in larger D-RCT studies, the preponderance of current evidence for several highly studied diseases (e.g., metabolic syndrome, osteoarthritis), which are also clinically common, are suggestive of clinical benefits.
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Affiliation(s)
| | - Carol L. Howe
- The University of Arizona Health Science Library, Tucson, AZ 85724, USA
| | - Meg Hauer
- College of Medicine, University of Arizona, Tucson, AZ 85724, USA
| | | | - Anthony M. Rossi
- Department of Physiology, Honors College, University of Arizona, Tucson, AZ 85724, USA
| | - Janet L. Funk
- Department of Medicine and School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ 85724, USA
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de Oliveira LMG, Carreira RB, de Oliveira JVR, do Nascimento RP, Dos Santos Souza C, Trias E, da Silva VDA, Costa SL. Impact of Plant-Derived Compounds on Amyotrophic Lateral Sclerosis. Neurotox Res 2023; 41:288-309. [PMID: 36800114 DOI: 10.1007/s12640-022-00632-1] [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: 09/23/2022] [Revised: 09/23/2022] [Accepted: 12/29/2022] [Indexed: 02/18/2023]
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by progressive motor neuron degeneration. Conventional therapies for ALS are based on treatment of symptoms, and the disease remains incurable. Molecular mechanisms are unclear, but studies have been pointing to involvement of glia, neuroinflammation, oxidative stress, and glutamate excitotoxicity as a key factor. Nowadays, we have few treatments for this disease that only delays death, but also does not stop the neurodegenerative process. These treatments are based on glutamate blockage (riluzole), tyrosine kinase inhibition (masitinib), and antioxidant activity (edaravone). In the past few years, plant-derived compounds have been studied for neurodegenerative disorder therapies based on neuroprotection and glial cell response. In this review, we describe mechanisms of action of natural compounds associated with neuroprotective effects, and the possibilities for new therapeutic strategies in ALS.
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Affiliation(s)
- Lucas Matheus Gonçalves de Oliveira
- Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil
| | - Rodrigo Barreto Carreira
- Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil
| | - Juciele Valeria Ribeiro de Oliveira
- Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil
| | - Ravena Pereira do Nascimento
- Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil
| | - Cleide Dos Santos Souza
- Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
| | | | - Victor Diogenes Amaral da Silva
- Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil.
| | - Silvia Lima Costa
- Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-100, Brazil.
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Lei F, Li P, Chen T, Wang Q, Wang C, Liu Y, Deng Y, Zhang Z, Xu M, Tian J, Ren W, Li C. Recent advances in curcumin-loaded biomimetic nanomedicines for targeted therapies. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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36
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Chen L, Ye L, Hu B. Hereditary Colorectal Cancer Syndromes: Molecular Genetics and Precision Medicine. Biomedicines 2022; 10:3207. [PMID: 36551963 PMCID: PMC9776295 DOI: 10.3390/biomedicines10123207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 11/28/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Hereditary CRC syndromes account for approximately 5-10% of all CRC, with a lifetime risk of CRC that approaches 50-80% in the absence of endoscopic or surgical treatment. Hereditary CRC syndromes can be phenotypically divided into polyposis and non-polyposis syndrome, mainly according to the conditions of polyps. The typical representatives are familial adenomatous polyposis (FAP) and Lynch syndromes (LS), respectively. Over the past few decades, molecular genetics enhanced the discovery of cancer-predisposing genes and revolutionized the field of clinical oncology. Hereditary CRC syndromes have been a key part of this effort, with data showing that pathogenic variants are present in up to 10% of cases. Molecular phenotypes of tumors can not only help identify individuals with genetic susceptibility to CRC but also guide the precision prevention and treatment for the development of CRC. This review emphasizes the molecular basis and prevention strategies for hereditary CRC syndromes.
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Affiliation(s)
| | | | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
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Zhu LR, Zheng W, Gao Q, Chen T, Pan ZB, Cui W, Cai M, Fang H. Epigenetics and genetics of hepatoblastoma: Linkage and treatment. Front Genet 2022; 13:1070971. [PMID: 36531231 PMCID: PMC9748487 DOI: 10.3389/fgene.2022.1070971] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 11/14/2022] [Indexed: 09/10/2024] Open
Abstract
Hepatoblastoma is a malignant embryonal tumor with multiple differentiation modes and is the clearest liver malignancy in children. However, little is known about genetic and epigenetic events in Hepatoblastoma. Increased research has recently demonstrated, unique genetic and epigenetic events in Hepatoblastoma, providing insights into its origin and precise treatment. Some genetic disorders and congenital factors are associated with the risk of Hepatoblastoma development, such as the Beckwith-Wiedemann syndrome, Familial Adenomatous polyposis, and Hemihypertrophy. Epigenetic modifications such as DNA modifications, histone modifications, and non-coding RNA regulation are also essential in the development of Hepatoblastoma. Herein, we reviewed genetic and epigenetic events in Hepatoblastoma, focusing on the relationship between these events and cancer susceptibility, tumor growth, and prognosis. By deciphering the genetic and epigenetic associations in Hepatoblastoma, tumor pathogenesis can be clarified, and guide the development of new anti-cancer drugs and prevention strategies.
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Affiliation(s)
- Li-ran Zhu
- Anhui Institute of Pediatric Research, Anhui Provincial Children’s Hospital, Hefei, China
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China
- Science Island Branch, Graduate School of University of Science and Technology of China, Hefei, China
| | - Wanqun Zheng
- Department of Chinese Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qun Gao
- Department of Pediatric Oncology Surgery, Anhui Provincial Children’s Hospital, Hefei, China
| | - Tianping Chen
- Department of Hematology and Oncology, Anhui Provincial Children’s Hospital, Hefei, China
| | - Zhu-bin Pan
- Department of General Surgery, Anhui Provincial Children’s Hospital, Hefei, China
| | - Wei Cui
- Department of Scientific Research and Education, Anhui Provincial Children’s Hospital, Anhui Institute of Pediatric Research, Hefei, China
| | - Ming Cai
- Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
| | - Hui Fang
- Anhui Institute of Pediatric Research, Anhui Provincial Children’s Hospital, Hefei, China
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Efficacy of Wholistic Turmeric Supplement on Adenomatous Polyps in Patients with Familial Adenomatous Polyposis-A Randomized, Double-Blinded, Placebo-Controlled Study. Genes (Basel) 2022; 13:genes13122182. [PMID: 36553450 PMCID: PMC9777742 DOI: 10.3390/genes13122182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/05/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022] Open
Abstract
Several studies have demonstrated that curcumin can cause the regression of polyps in familial adenomatous polyposis (FAP), while others have shown negative results. Wholistic turmeric (WT) containing curcumin and additional bioactive compounds may contribute to this effect. We performed a double-blinded, randomized, controlled trial to assess the efficacy of WT in FAP patients. Ten FAP patients were randomly assigned to receive either WT or placebo for 6 months. Colonoscopies were performed at baseline and after 6 months. The polyp number and size, as well as the cumulative polyp burden, were assessed. No differences were noted between the groups in terms of changes from the baseline's polyp number, size, or burden. However, stratifying the data according to the right vs. left colon indicated a decrease in the median polyp number (from 5.5 to 1.5, p = 0.06) and polyp burden (from 24.25 mm to 11.5 mm, p = 0.028) in the left colon of the patients in the WT group. The adjusted left polyp number and burden in the WT arm were lower by 5.39 (p = 0.034) and 14.68 mm (p = 0.059), respectively. Whether WT can be used to reduce the polyp burden of patients with predominantly left-sided polyps remains to be seen; thus, further larger prospective trials are required.
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Jiang M, Qi Y, Huang W, Lin Y, Li B. Curcumin Reprograms TAMs from a Protumor Phenotype towards an Antitumor Phenotype via Inhibiting MAO-A/STAT6 Pathway. Cells 2022; 11:3473. [PMID: 36359867 PMCID: PMC9655729 DOI: 10.3390/cells11213473] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/20/2022] [Accepted: 10/28/2022] [Indexed: 07/30/2023] Open
Abstract
M1 phenotype macrophages have anticancer characteristics, whereas M2 phenotype macrophages promote tumor growth and metastasis. A higher M1/M2 ratio, therefore, has a beneficial effect on the tumor immune microenvironment, thereby inhibiting tumor growth. The natural alkaloid curcumin is found to have anticancer properties. However, the mechanism remains unclear. In this study, a cell co-culture system and M2 macrophage model were used to evaluate the effects of curcumin on tumor-associated macrophage (TAM) phenotypes. Our results demonstrate that curcumin reprogrammed the M2 macrophages by reducing the level of anti-inflammatory cytokines (TGF-β, Arg-1, and IL-10) and an M2 surface marker (CD206) induced by Cal27 cells or IL-4, as well as upregulating proinflammatory cytokines (TNF-α, iNOS, and IL-6) and an M1 surface marker (CD86). The in vitro assays suggested that curcumin treatment suppressed the migration and invasion of the Cal27 cells induced by the M2-like macrophages. Mechanistically, the repolarization of TAMs may be attributed to the inhibition of monoamine oxidase A (MAO-A)/STAT6 signaling after curcumin treatment. Collectively, our results show that the anticancer effects of curcumin could be explained by reprogramming TAMs from a protumor phenotype towards an antitumor phenotype.
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Affiliation(s)
- Mingjing Jiang
- Liaoning Provincial Key Laboratory of Oral Diseases, Experimental Teaching Center, School and Hospital of Stomatology, China Medical University, Shenyang 110001, China
| | - Ying Qi
- Liaoning Provincial Key Laboratory of Oral Diseases, Experimental Teaching Center, School and Hospital of Stomatology, China Medical University, Shenyang 110001, China
| | - Wei Huang
- Liaoning Provincial Key Laboratory of Oral Diseases, Experimental Teaching Center, School and Hospital of Stomatology, China Medical University, Shenyang 110001, China
| | - Ying Lin
- Liaoning Provincial Key Laboratory of Oral Diseases, Experimental Teaching Center, School and Hospital of Stomatology, China Medical University, Shenyang 110001, China
| | - Bo Li
- Liaoning Provincial Key Laboratory of Oral Diseases, Experimental Teaching Center, School and Hospital of Stomatology, China Medical University, Shenyang 110001, China
- Jilin Provincial Key Laboratory of Oral Biomedical Engineering, Department of Oral Anatomy and Physiology, Hospital of Stomatology, Jilin University, Changchun 130021, China
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40
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Wang M, Liu X, Chen T, Cheng X, Xiao H, Meng X, Jiang Y. Inhibition and potential treatment of colorectal cancer by natural compounds via various signaling pathways. Front Oncol 2022; 12:956793. [PMID: 36158694 PMCID: PMC9496650 DOI: 10.3389/fonc.2022.956793] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal cancer (CRC) is a common type of malignant digestive tract tumor with a high incidence rate worldwide. Currently, the clinical treatment of CRC predominantly include surgical resection, postoperative chemotherapy, and radiotherapy. However, these treatments contain severe limitations such as drug side effects, the risk of recurrence and drug resistance. Some natural compounds found in plants, fungi, marine animals, and bacteria have been shown to inhibit the occurrence and development of CRC. Although the explicit molecular mechanisms underlying the therapeutic effects of these compounds on CRC are not clear, classical signaling transduction pathways such as NF-kB and Wnt/β-catenin are extensively regulated. In this review, we have summarized the specific mechanisms regulating the inhibition and development of CRC by various types of natural compounds through nine signaling pathways, and explored the potential therapeutic values of these natural compounds in the clinical treatment of CRC.
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Affiliation(s)
- Mingchuan Wang
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xianjun Liu
- College of Food Engineering, Jilin Engineering Normal University, Changchun, China
| | - Tong Chen
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xianbin Cheng
- Department of Thyroid Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Huijie Xiao
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xianglong Meng
- Department of Burns Surgery, The First Hospital of Jilin University, Changchun, China
| | - Yang Jiang
- Department of Gastrointestinal Colorectal and Anal Surgery, The China-Japan Union Hospital of Jilin University, Changchun, China
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Kiran RP, Kochhar GS, Kariv R, Rex DK, Sugita A, Rubin DT, Navaneethan U, Hull TL, Ko HM, Liu X, Kachnic LA, Strong S, Iacucci M, Bemelman W, Fleshner P, Safyan RA, Kotze PG, D'Hoore A, Faiz O, Lo S, Ashburn JH, Spinelli A, Bernstein CN, Kane SV, Cross RK, Schairer J, McCormick JT, Farraye FA, Chang S, Scherl EJ, Schwartz DA, Bruining DH, Philpott J, Bentley-Hibbert S, Tarabar D, El-Hachem S, Sandborn WJ, Silverberg MS, Pardi DS, Church JM, Shen B. Management of pouch neoplasia: consensus guidelines from the International Ileal Pouch Consortium. Lancet Gastroenterol Hepatol 2022; 7:871-893. [PMID: 35798022 DOI: 10.1016/s2468-1253(22)00039-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/18/2022] [Accepted: 01/27/2022] [Indexed: 02/07/2023]
Abstract
Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise.
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Affiliation(s)
- Ravi P Kiran
- Division of Colorectal Surgery, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Gursimran S Kochhar
- Division of Gastroenterology, Hepatology, and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Revital Kariv
- Department of Gastroenterology, Tel Aviv Sourasky Medical Center and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Douglas K Rex
- Indiana University School of Medicine, Indianapolis, IN, USA
| | - Akira Sugita
- Department of Clinical Research and Department of inflammatory Bowel Disease, Yokohama Municipal Citizens Hospital Yokohama, Japan
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Udayakumar Navaneethan
- IBD Center and IBD Interventional Unit, Center for Interventional Endoscopy, Orlando Health, Orlando, FL, USA
| | - Tracy L Hull
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Huaibin Mabel Ko
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Xiuli Liu
- Department of Pathology and Immunology, Washington University, St Louis, MO, USA
| | - Lisa A Kachnic
- Department of Radiation Oncology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Scott Strong
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, NIHR Birmingham Biomedical Research Centre, University Hospitals NHS Foundation Trust, University of Birmingham, UK
| | - Willem Bemelman
- Department of Surgery, Academic Medical Center, Amsterdam, Netherlands
| | - Philip Fleshner
- Division of Colorectal Surgery, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Rachael A Safyan
- Division of Hematology and Oncology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Paulo G Kotze
- IBD Outpatients Clinic, Catholic University of Paraná, Curitiba, Brazil
| | - André D'Hoore
- Department of Abdominal Surgery, University Hospital Leuven, Belgium
| | - Omar Faiz
- Department of Surgery, St Mark's Hospital and Academic Institute, Harrow and Department of Surgery and Cancer, Imperial College London, London, UK
| | - Simon Lo
- Pancreatic and Biliary Disease Program, Digestive Diseases, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Jean H Ashburn
- Department of Surgery, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University and IRCCS Humanitas Research Hospital, Division Colon and Rectal Surgery, Rozzano, Milan, Italy
| | - Charles N Bernstein
- University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, MB, Canada
| | - Sunanda V Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Raymond K Cross
- Inflammatory Bowel Disease Program, University of Maryland School of Medicine, MD, USA
| | - Jason Schairer
- Department of Gastroenterology, Henry Ford Health System, Detroit, MI, USA
| | - James T McCormick
- Division of Colon and Rectal Surgery, Allegheny Health Network, Pittsburgh, PA, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Shannon Chang
- Inflammatory Bowel Disease Center, NYU Langone Health, NYU Grossman School of Medicine, New York, NY, USA
| | - Ellen J Scherl
- Jill Roberts Center for IBD, Gastroenterology and Hepatology, Weill Cornell Medicine and NewYork Presbyterian Hospital, New York, NY, USA
| | - David A Schwartz
- Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jessica Philpott
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA
| | - Stuart Bentley-Hibbert
- Department of Radiology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Dino Tarabar
- IBD Clinical Center, University Hospital Center Dr Dragiša Mišović, Belgrade, Serbia
| | - Sandra El-Hachem
- Division of Gastroenterology, Hepatology, and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - William J Sandborn
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Mark S Silverberg
- Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, ON, Canada
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - James M Church
- Division of Colorectal Surgery, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA
| | - Bo Shen
- Center for Interventional Inflammatory Bowel Disease, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA.
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Abstract
The traditional approach of one-size-fits-all for colorectal cancer has been replaced by personalized interventions to an individual's unique genetic, molecular, and environmental profile, seeking to identify high-risk individuals who would benefit from individualized screening and surveillance. This change in approach is due, in part, to emerging technologies, such as next-generation DNA sequencing.
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Muhammad N, Usmani D, Tarique M, Naz H, Ashraf M, Raliya R, Tabrez S, Zughaibi TA, Alsaieedi A, Hakeem IJ, Suhail M. The Role of Natural Products and Their Multitargeted Approach to Treat Solid Cancer. Cells 2022; 11:cells11142209. [PMID: 35883653 PMCID: PMC9318484 DOI: 10.3390/cells11142209] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/08/2022] [Accepted: 07/13/2022] [Indexed: 02/07/2023] Open
Abstract
Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, herbs, and other natural products have been used as healing agents. Likewise, most of the medicinal ingredients accessible today are originated from the natural resources. Regardless of achievements, developing bioactive compounds and drugs from natural products has remained challenging, in part because of the problem associated with large-scale sequestration and mechanistic understanding. With significant progress in the landscape of cancer therapy and the rising use of cutting-edge technologies, we may have come to a crossroads to review approaches to identify the potential natural products and investigate their therapeutic efficacy. In the present review, we summarize the recent developments in natural products-based cancer research and its application in generating novel systemic strategies with a focus on underlying molecular mechanisms in solid cancer.
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Affiliation(s)
- Naoshad Muhammad
- Department of Radiation Oncology, School of Medicine, Washington University, Saint Louis, MO 63130, USA;
| | | | - Mohammad Tarique
- Department of Child Health, University of Missouri, Columbia, MO 65211, USA;
| | - Huma Naz
- Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USA;
| | - Mohammad Ashraf
- Department of Chemistry, Bundelkhand University Jhansi, Jhansi 284128, Uttar Pradesh, India;
| | - Ramesh Raliya
- IFFCO Nano Biotechnology Research Center, Kalol 382423, Gujarat, India;
| | - Shams Tabrez
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.T.); (T.A.Z.)
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Torki A. Zughaibi
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.T.); (T.A.Z.)
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Ahdab Alsaieedi
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Israa J. Hakeem
- Department of Biochemistry, College of Science, University of Jeddah, Jeddah 21959, Saudi Arabia;
| | - Mohd Suhail
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.T.); (T.A.Z.)
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Correspondence:
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Zimmermann-Klemd AM, Reinhardt JK, Winker M, Gründemann C. Phytotherapy in Integrative Oncology-An Update of Promising Treatment Options. Molecules 2022; 27:3209. [PMID: 35630688 PMCID: PMC9143079 DOI: 10.3390/molecules27103209] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/02/2022] [Accepted: 05/10/2022] [Indexed: 02/06/2023] Open
Abstract
Modern phytotherapy is part of today's conventional evidence-based medicine and the use of phytopharmaceuticals in integrative oncology is becoming increasingly popular. Approximately 40% of users of such phytopharmaceuticals are tumour patients. The present review provides an overview of the most important plants and nature-based compounds used in integrative oncology and illustrates their pharmacological potential in preclinical and clinical settings. A selection of promising anti-tumour plants and ingredients was made on the basis of scientific evidence and therapeutic practical relevance and included Boswellia, gingko, ginseng, ginger, and curcumin. In addition to these nominees, there is a large number of other interesting plants and plant ingredients that can be considered for the treatment of cancer diseases or for the treatment of tumour or tumour therapy-associated symptoms. Side effects and interactions are included in the discussion. However, with the regular and intended use of phytopharmaceuticals, the occurrence of adverse side effects is rather rare. Overall, the use of defined phytopharmaceuticals is recommended in the context of a rational integrative oncology approach.
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Affiliation(s)
- Amy M. Zimmermann-Klemd
- Translational Complementary Medicine, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland; (A.M.Z.-K.); (M.W.)
| | - Jakob K. Reinhardt
- Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland;
| | - Moritz Winker
- Translational Complementary Medicine, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland; (A.M.Z.-K.); (M.W.)
| | - Carsten Gründemann
- Translational Complementary Medicine, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland; (A.M.Z.-K.); (M.W.)
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Wanjiang W, Xin C, Yaxing C, Jie W, Hongyan Z, Fei N, Chengmin L, Chengjian F, Jichao Y, Jiangkai L. Curcumin Improves Human Umbilical Cord-Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Outcomes After Spinal Cord Injury. Cell Mol Neurobiol 2022; 42:1241-1252. [PMID: 33247374 PMCID: PMC11441298 DOI: 10.1007/s10571-020-01018-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 11/18/2020] [Indexed: 11/28/2022]
Abstract
Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is thought to be a promising strategy for treating spinal cord injury (SCI). However, the low survival rate of transplanted hUC-MSCs limits their clinical application in cell replacement therapy. Curcumin can suppress inflammation after SCI; however, it remains unknown whether curcumin can modulate the survival of transplanted hUC-MSCs. In this study, to investigate whether curcumin could strengthen the therapeutic effects of hUC-MSC transplantation on SCI, we induced hUC-MSC apoptosis with TNF-α, transplanted hUC-MSC into SCI rats, and assessed the antiapoptotic effect and mechanism of curcumin. LDH release analysis and flow cytometry demonstrated that TNF-α led to hUC-MSC apoptosis and that curcumin increased the hUC-MSC survival rate in a dose-dependent manner. In addition, we showed that the phosphorylation levels of ERK1/2, JNK, and P38 were upregulated in apoptotic hUC-MSCs, while curcumin increased the phosphorylation of ERK1/2 but did not activate JNK or P38, and these effects were reversed by the p42/44 antagonist U0126. Furthermore, we found that the motor function scores and number of surviving HNA-positive cells were significantly increased after curcumin and hUC-MSC transplantation therapy 8 weeks post-SCI, while U0126 markedly attenuated these effects. These data confirmed that curcumin suppressed hUC-MSC apoptosis through the ERK1/2 signaling pathway and that combined curcumin and hUC-MSC treatment improved motor function in rats after SCI. The current research provides a strong basis for hUC-MSC replacement therapy in conjunction with curcumin in the treatment and management of SCI in humans.
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Affiliation(s)
- Wu Wanjiang
- Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Army Medical University), Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing, 400038, China
| | - Chen Xin
- Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Army Medical University), Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing, 400038, China
| | - Chen Yaxing
- Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Army Medical University), Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing, 400038, China
| | - Wang Jie
- Department of Neurology, Southwest Hospital, Third Military Medical University (Army Medical University), 29 Gaotanyan Street, Chongqing, 400038, China
| | - Zhang Hongyan
- Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Army Medical University), Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing, 400038, China
| | - Ni Fei
- Department of Field Nursing, School of Nursing, Third Military Medical University (Army Medical University), Chongqing, 400038, China
| | - Ling Chengmin
- Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Army Medical University), Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing, 400038, China
| | - Feng Chengjian
- Department of Medical Engineering, 958th Hospital of the People's Liberation Army, Chongqing, 400038, China
| | - Yuan Jichao
- Department of Neurology, Southwest Hospital, Third Military Medical University (Army Medical University), 29 Gaotanyan Street, Chongqing, 400038, China.
| | - Lin Jiangkai
- Department of Neurosurgery, Institute of Neurosurgery, Key Laboratory of Neurotrauma Prevention and Treatment, Army Medical University), Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing, 400038, China.
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Aelvoet AS, Buttitta F, Ricciardiello L, Dekker E. Management of familial adenomatous polyposis and MUTYH-associated polyposis; new insights. Best Pract Res Clin Gastroenterol 2022; 58-59:101793. [PMID: 35988966 DOI: 10.1016/j.bpg.2022.101793] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/21/2021] [Accepted: 03/08/2022] [Indexed: 02/07/2023]
Abstract
Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are rare inherited polyposis syndromes with a high colorectal cancer (CRC) risk. Therefore, frequent endoscopic surveillance including polypectomy of relevant premalignant lesions from a young age is warranted in patients. In FAP and less often in MAP, prophylactic colectomy is indicated followed by lifelong endoscopic surveillance of the retained rectum after (sub)total colectomy and ileal pouch after proctocolectomy to prevent CRC. No consensus is reached on the right type and timing of colectomy. As patients with FAP and MAP nowadays have an almost normal life-expectancy due to adequate treatment of colorectal polyposis, challenges in the management of FAP and MAP have shifted towards the treatment of duodenal and gastric adenomas as well as desmoid treatment in FAP. Whereas up until recently upper gastrointestinal surveillance was mostly diagnostic and patients were referred for surgery once duodenal or gastric polyposis was advanced, nowadays endoscopic treatment of premalignant lesions is widely performed. Aiming to reduce polyp burden in the colorectum as well as in the upper gastrointestinal tract, several chemopreventive agents are currently being studied.
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Affiliation(s)
- Arthur S Aelvoet
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
| | - Francesco Buttitta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.
| | - Luigi Ricciardiello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam Cancer Center Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
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Amintas S, Dupin C, Boutin J, Beaumont P, Moreau-Gaudry F, Bedel A, Krisa S, Vendrely V, Dabernat S. Bioactive food components for colorectal cancer prevention and treatment: A good match. Crit Rev Food Sci Nutr 2022; 63:6615-6629. [PMID: 35128990 DOI: 10.1080/10408398.2022.2036095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Colorectal cancer (CRC) is the third most frequent cancer worldwide, accounts for about 10% of the total cancer cases, and ranks as the second cause of death by cancer. CRC is more prevalent in developed countries in close causal relation with occidental diets. Due to anatomy, the diet has a strong impact on CRC. High contents in meat are acknowledged risk factors whereas a diet rich in fruits and vegetables is an established CRC protective factor. Fruits and vegetables contain numerous Bioactive Food Components (BFCs), physiologically active food compounds, beneficial on health. Preventive and therapeutic benefits of BFCs in cancer have increasingly been reported over the past 20 years. BFCs show both chemopreventive and anti-tumor properties in CRC but more interestingly, abundant research describes BFCs as enhancers of conventional cancer treatments. Despite these promising results, their clinical transferability is slowed down by bioavailability interrogations and their poorly understood hormetic effect. In this review, we would like to reposition BFCs as well-fitted for applications in CRC. We provide a synthetic overview of trustworthy BFC applications in CRC, with a special highlight on combinatory approaches and conventional cancer treatment potentiation strategies.
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Affiliation(s)
- Samuel Amintas
- Bordeaux University, Bordeaux, France
- INSERM U1312, BoRdeaux institute In onCology - BRIC, Bordeaux, France
- Tumor Biology and Tumor Bank Laboratory, Bordeaux University Hospital, Bordeaux, France
| | - Charles Dupin
- Bordeaux University, Bordeaux, France
- INSERM U1312, BoRdeaux institute In onCology - BRIC, Bordeaux, France
- Radiotherapy Department, Bordeaux University Hospital, Bordeaux, France
| | - Julian Boutin
- Bordeaux University, Bordeaux, France
- INSERM U1312, BoRdeaux institute In onCology - BRIC, Bordeaux, France
- Biochemistry Laboratory, Bordeaux. University Hospital, Bordeaux, France
| | | | - François Moreau-Gaudry
- Bordeaux University, Bordeaux, France
- INSERM U1312, BoRdeaux institute In onCology - BRIC, Bordeaux, France
- Biochemistry Laboratory, Bordeaux. University Hospital, Bordeaux, France
| | - Aurélie Bedel
- Bordeaux University, Bordeaux, France
- INSERM U1312, BoRdeaux institute In onCology - BRIC, Bordeaux, France
- Biochemistry Laboratory, Bordeaux. University Hospital, Bordeaux, France
| | | | - Véronique Vendrely
- Bordeaux University, Bordeaux, France
- INSERM U1312, BoRdeaux institute In onCology - BRIC, Bordeaux, France
- Radiotherapy Department, Bordeaux University Hospital, Bordeaux, France
| | - Sandrine Dabernat
- Bordeaux University, Bordeaux, France
- INSERM U1312, BoRdeaux institute In onCology - BRIC, Bordeaux, France
- Biochemistry Laboratory, Bordeaux. University Hospital, Bordeaux, France
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Macaron C, Mankaney GN, Haider M, Mouchli M, Hurley K, Burke CA. Chemoprevention Considerations in Patients with Hereditary Colorectal Cancer Syndromes. Gastrointest Endosc Clin N Am 2022; 32:131-146. [PMID: 34798982 DOI: 10.1016/j.giec.2021.08.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Secondary prevention of colorectal neoplasia with chemoprevention is long-studied area of research and clinical use in patients with the 2 most common hereditary colorectal cancer syndromes including Lynch syndrome and familial adenomatous polyposis. No medication is currently approved for use for the prevention of colorectal polyps or cancer in either the general population or individuals with the hereditary colorectal cancer syndromes. Emerging data in animal models and limited data in humans suggest vaccines may be the next breakthrough for neoplasia prevention in patients with hereditary colorectal cancer. Clinicians must acknowledge chemoprevention is an adjunct and does not supplant endoscopic surveillance.
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Affiliation(s)
- Carole Macaron
- Department of Gastroenterology, Hepatology and Nutrition, Desk A 30, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Gautam N Mankaney
- Department of Gastroenterology and Hepatology, Virginia Mason Franciscan Health, 1100 9th Avenue, Seattle, WA 98101, USA
| | - Mahnur Haider
- John W. Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, #8016, New Orleans, LA 70112, USA
| | - Mohamad Mouchli
- Department of Gastroenterology, Hepatology and Nutrition, Desk A 30, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Karen Hurley
- Center for Behavioral Health, Desk P57, 9500 Euclid Avenue, Cleveland, OH 44195, USA
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Desk A 30, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Colorectal Surgery, Sanford R. Weiss MD Center for Hereditary Gastrointestinal Neoplasia, Digestive Disease and Surgical Institute, Cleveland Clinic, Cleveland, OH, USA.
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Kumar A, Hegde M, Parama D, Kunnumakkara AB. Curcumin: The Golden Nutraceutical on the Road to Cancer Prevention and Therapeutics. A Clinical Perspective. Crit Rev Oncog 2022; 27:33-63. [PMID: 37183937 DOI: 10.1615/critrevoncog.2023045587] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Cancer is considered as the major public health scourge of the 21st century. Although remarkable strides were made for developing targeted therapeutics, these therapies suffer from lack of efficacy, high cost, and debilitating side effects. Therefore, the search for safe, highly efficacious, and affordable therapies is paramount for establishing a treatment regimen for this deadly disease. Curcumin, a known natural, bioactive, polyphenol compound from the spice turmeric (Curcuma longa), has been well documented for its wide range of pharmacological and biological activities. A plethora of literature indicates its potency as an anti-inflammatory and anti-cancer agent. Curcumin exhibits anti-neoplastic attributes via regulating a wide array of biological cascades involved in mutagenesis, proliferation, apoptosis, oncogene expression, tumorigenesis, and metastasis. Curcumin has shown a wide range of pleiotropic anti-proliferative effect in multiple cancers and is a known inhibitor of varied oncogenic elements, including nuclear factor kappa B (NF-κB), c-myc, cyclin D1, Bcl-2, VEGF, COX-2, NOS, tumor necrosis factor alpha (TNF-α), interleukins, and MMP-9. Further, curcumin targets different growth factor receptors and cell adhesion molecules involved in tumor growth and progression, making it a most promising nutraceutical for cancer therapy. To date, curcumin-based therapeutics have completed more than 50 clinical trials for cancer. Although creative experimentation is still elucidating the immense potential of curcumin, systematic validation by proper randomized clinical trials warrant its transition from lab to bedside. Therefore, this review summarizes the outcome of diverse clinical trials of curcumin in various cancer types.
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Affiliation(s)
- Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam-781039, India
| | - Mangala Hegde
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam-781039, India
| | - Dey Parama
- Cancer Biology Laboratory, DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences & Bioengineering, Indian Institute of Technology Guwahati, Assam-781039, India
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam-781039, India
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Dibba P, Kothari M, Grosman I. Prebiotics, Probiotics, and Dietary Supplements. NUTRITION, WEIGHT, AND DIGESTIVE HEALTH 2022:169-192. [DOI: 10.1007/978-3-030-94953-2_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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