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Wang Y, Wu G, Wang Y, Xiao F, Yin H, Yu L, Shehzad Q, Zhang H, Jin Q, Wang X. Association of erythrocyte fatty acid compositions with the risk of pancreatic cancer: A case-control study. Lipids 2025; 60:51-63. [PMID: 39397372 DOI: 10.1002/lipd.12420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 09/13/2024] [Accepted: 09/16/2024] [Indexed: 10/15/2024]
Abstract
Pancreatic cancer (PC) is one of the most fatal malignancies, which has attracted scientists to investigate its etiology and pathogenesis. Nevertheless, the association between erythrocyte fatty acids and PC risk remains unclear. This study aimed to evaluate the association between levels of erythrocyte fatty acids and PC risk. The erythrocyte fatty acid compositions of 105 PC patients and 120 controls were determined by gas chromatography. Cases and controls were frequency matched by age and sex. Multivariable conditional logistic regression model and restricted cubic spline were applied to estimate the odds ratio with 95% confidence interval (OR, 95% CI) of erythrocyte fatty acids and PC risk. Our main findings indicated a significant negative association between levels of erythrocyte total monounsaturated fatty acids (MUFA) and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of PC (ORT3-T1 = 0.30 [0.14, 0.63] and ORT3-T1 = 0.15 [0.06, 0.33], respectively). In contrast, erythrocyte n-6 polyunsaturated fatty acids, specifically linoleic acid (LA) and arachidonic acid (AA) levels, were positively associated with PC incidence (RT1-T3 = 4.24 [1.97, 9.46] and ORT1-T3 = 4.53 [2.09, 10.20]). Total saturated fatty acid (SFA), especially high levels of palmitic acid (16:0), was positively associated with the risk of PC (ORT3-T1 = 3.25 [1.53, 7.08]). Our findings suggest that levels of different types of fatty acids in erythrocytes may significantly alter PC susceptibility. Protective factors against PC include unsaturated fatty acids such as n-3 PUFA and MUFA.
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Affiliation(s)
- Yongjin Wang
- State Key Laboratory of Food Science and Resources, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi, China
- Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Gangcheng Wu
- State Key Laboratory of Food Science and Resources, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Yandan Wang
- State Key Laboratory of Food Science and Resources, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi, China
- Department of Research and Development, Jiahe Foods Industry Co., Ltd, Suzhou, China
| | - Feng Xiao
- Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Hongming Yin
- Department of Laboratory Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Le Yu
- State Key Laboratory of Food Science and Resources, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi, China
- Department of Research and Development, Jiahe Foods Industry Co., Ltd, Suzhou, China
- Department of Dairy Technology and Equipment Research, National Center of Technology Innovation for Dairy, Hohhot, China
| | - Qayyum Shehzad
- School of Fundamental Sciences, Massey University, Palmerston North, New Zealand
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Hui Zhang
- State Key Laboratory of Food Science and Resources, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Qingzhe Jin
- State Key Laboratory of Food Science and Resources, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xingguo Wang
- State Key Laboratory of Food Science and Resources, International Joint Research Laboratory for Lipid Nutrition and Safety, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi, China
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Wang T, Zhou D, Hong Z. Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2025; 6:e70030. [PMID: 39764565 PMCID: PMC11702502 DOI: 10.1002/mco2.70030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 11/11/2024] [Accepted: 11/12/2024] [Indexed: 03/17/2025] Open
Abstract
Sarcopenia is defined as a muscle-wasting syndrome that occurs with accelerated aging, while cachexia is a severe wasting syndrome associated with conditions such as cancer and immunodeficiency disorders, which cannot be fully addressed through conventional nutritional supplementation. Sarcopenia can be considered a component of cachexia, with the bidirectional interplay between adipose tissue and skeletal muscle potentially serving as a molecular mechanism for both conditions. However, the underlying mechanisms differ. Recognizing the interplay and distinctions between these disorders is essential for advancing both basic and translational research in this area, enhancing diagnostic accuracy and ultimately achieving effective therapeutic solutions for affected patients. This review discusses the muscle microenvironment's changes contributing to these conditions, recent therapeutic approaches like lifestyle modifications, small molecules, and nutritional interventions, and emerging strategies such as gene editing, stem cell therapy, and gut microbiome modulation. We also address the challenges and opportunities of multimodal interventions, aiming to provide insights into the pathogenesis and molecular mechanisms of sarcopenia and cachexia, ultimately aiding in innovative strategy development and improved treatments.
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Affiliation(s)
- Tiantian Wang
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
| | - Dong Zhou
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
| | - Zhen Hong
- Department of NeurologyWest China Hospital of Sichuan UniversityChengduSichuanChina
- Institute of Brain Science and Brain‐Inspired Technology of West China HospitalSichuan UniversityChengduSichuanChina
- Department of NeurologyChengdu Shangjin Nanfu HospitalChengduSichuanChina
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Wang H, Chan YL, Chiu YH, Wu TH, Hsia S, Wu CJ. Supplementation with Fish Oil and Selenium Protects Lipolytic and Thermogenic Depletion of Adipose in Cachectic Mice Treated with an EGFR Inhibitor. Cells 2024; 13:1485. [PMID: 39273055 PMCID: PMC11394147 DOI: 10.3390/cells13171485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/27/2024] [Accepted: 09/02/2024] [Indexed: 09/15/2024] Open
Abstract
Lung cancer and cachexia are the leading causes of cancer-related deaths worldwide. Cachexia is manifested by weight loss and white adipose tissue (WAT) atrophy. Limited nutritional supplements are conducive to lung cancer patients, whereas the underlying mechanisms are poorly understood. In this study, we used a murine cancer cachexia model to investigate the effects of a nutritional formula (NuF) rich in fish oil and selenium yeast as an adjuvant to enhance the drug efficacy of an EGFR inhibitor (Tarceva). In contrast to the healthy control, tumor-bearing mice exhibited severe cachexia symptoms, including tissue wasting, hypoalbuminemia, and a lower food efficiency ratio. Experimentally, Tarceva reduced pEGFR and HIF-1α expression. NuF decreased the expression of pEGFR and HIF-2α, suggesting that Tarceva and NuF act differently in prohibiting tumor growth and subsequent metastasis. NuF blocked LLC tumor-induced PTHrP and expression of thermogenic factor UCP1 and lipolytic enzymes (ATGL and HSL) in WAT. NuF attenuated tumor progression, inhibited PTHrP-induced adipose tissue browning, and maintained adipose tissue integrity by modulating heat shock protein (HSP) 72. Added together, Tarceva in synergy with NuF favorably improves cancer cachexia as well as drug efficacy.
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Affiliation(s)
- Hang Wang
- Department of Nutrition, Hung-Kuang University, Taichung 433304, Taiwan
| | - Yi-Lin Chan
- Department of Life Science, Chinese Culture University, Taipei 111396, Taiwan;
| | - Yi-Han Chiu
- Department of Microbiology, Soochow University, Taipei 111002, Taiwan;
| | - Tsung-Han Wu
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung 204006, Taiwan;
- Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, Taiwan
| | - Simon Hsia
- Taiwan Nutraceutical Association, Taipei 104483, Taiwan;
| | - Chang-Jer Wu
- Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, Taiwan
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
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Ghoreishy SM, Zeraattalab-Motlagh S, Amiri Khosroshahi R, Hemmati A, Noormohammadi M, Mohammadi H. Dose-Dependent Impacts of Omega-3 Fatty Acids Supplementation on Anthropometric Variables in Patients With Cancer: Results From a Systematic Review and Meta-Analysis of Randomized Clinical Trials. Clin Nutr Res 2024; 13:186-200. [PMID: 39165286 PMCID: PMC11333147 DOI: 10.7762/cnr.2024.13.3.186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/16/2024] [Accepted: 07/19/2024] [Indexed: 08/22/2024] Open
Abstract
Meta-analyses have been conducted with conflicting results on this topic. Due to missing several eligible studies in previous meta-analysis by Lam et al., we conducted an extensive systematic review and dose-response meta-analysis of randomized controlled trials in this regard. A comprehensive search was conducted across various databases, including MEDLINE/PubMed, ISI Web of Knowledge, Scopus, and Google Scholar, until November 2023. Based on the analysis of 33 studies comprising 2,047 individuals, it was found that there was a significant increase in body weight for each 1 g/day increase in omega-3 lipids (standardized MD [SMD], 0.52 kg; 95% confidence interval [CI], 0.31, 0.73; I2 = 95%; Grading of Recommendations Assessment, Development and Evaluation [GRADE] = low). Supplementation of omega-3 fatty acids did not yield a statistically significant impact on body mass index (BMI) (SMD, 0.12 kg/m2; 95% CI, -0.02, 0.27; I2 = 79%; GRADE = very low), lean body mass (LBM) (SMD, -0.02 kg; 95% CI, -0.43, 0.39; I2 = 97%; GRADE = very low), fat mass (SMD, 0.45 kg; 95% CI, -0.25, 1.15; I2 = 96%; GRADE = low), and body fat (SMD, 0.30%; 95% CI, -0.90, 1.51; I2 = 96%; GRADE = very low). After excluding 2 studies, the findings were significant for BMI. Regarding the results of the dose-response analysis, body weight increased proportionally by increasing the dose of omega-3 supplementation up to 4 g/day. Omega-3 fatty acid supplementation can improve body weight, but not BMI, LBM, fat mass, or body fat in cancer patients; large-scale randomized trials needed for more reliable results. Trial Registration PROSPERO Identifier: CRD42023395341.
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Affiliation(s)
- Seyed Mojtaba Ghoreishy
- Student Research Committee, School of Public Health, Iran University of Medical Sciences, Tehran 14665-354, Iran
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran 14665-354, Iran
| | | | - Reza Amiri Khosroshahi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14155-6117, Iran
| | - Amirhossein Hemmati
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14155-6117, Iran
| | - Morvarid Noormohammadi
- Student Research Committee, School of Public Health, Iran University of Medical Sciences, Tehran 14665-354, Iran
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran 14665-354, Iran
| | - Hamed Mohammadi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14155-6117, Iran
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Sha H, Zhu W. Employing Bidirectional Two-Sample Mendelian Randomization Analysis to Verify the Potential of Polyunsaturated Fatty Acid Levels in the Prevention of Pancreatic Cancer. Curr Issues Mol Biol 2024; 46:6041-6051. [PMID: 38921031 PMCID: PMC11202278 DOI: 10.3390/cimb46060360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/04/2024] [Accepted: 06/05/2024] [Indexed: 06/27/2024] Open
Abstract
Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables and issues of reverse causation. This study used a two-way two-sample Mendelian randomization (MR) method to test the hypothesized genetic causal relationship between PUFAs and PC risk. Data from an extensive genome-wide association study (GWAS) were analyzed, focusing on FAω3 and FAω6 levels, their ratios, and DHA as variables and PC incidence as outcomes. This relationship was comprehensively evaluated using related MR methods, such as inverse variance weighting (IVW), MR Egger, and weighted median (WM). This study finds a significant negative correlation between FAω3 and DHA levels and PC risk, while FAω6 levels show no significant correlation. Interestingly, the ratio of FAω6 to FAω3 was positively associated with increased risk of PC. Neither the MR Egger nor the MR-PRESSO tests detected significant pleiotropy, nor did the Cochrane's Q test show significant heterogeneity. Leave-one-out analyzes further confirmed the robustness of these results. Using MR analysis of two samples, this study provides genetic causal evidence that FAω3 and DHA levels reduce the risk of PC, whereas the ratio of FAω6 to FAω3 increases the risk of PC. These insights highlight the potential utility of supplementing FAω3 and DHA or altering PUFAs in developing PC prevention strategies.
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Affiliation(s)
| | - Weifeng Zhu
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nangchang 330006, China;
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Hesketh SJ. Advancing cancer cachexia diagnosis with -omics technology and exercise as molecular medicine. SPORTS MEDICINE AND HEALTH SCIENCE 2024; 6:1-15. [PMID: 38463663 PMCID: PMC10918365 DOI: 10.1016/j.smhs.2024.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 01/15/2024] [Accepted: 01/20/2024] [Indexed: 03/12/2024] Open
Abstract
Muscle atrophy exacerbates disease outcomes and increases mortality, whereas the preservation of skeletal muscle mass and function play pivotal roles in ensuring long-term health and overall quality-of-life. Muscle atrophy represents a significant clinical challenge, involving the continued loss of muscle mass and strength, which frequently accompany the development of numerous types of cancer. Cancer cachexia is a highly prevalent multifactorial syndrome, and although cachexia is one of the main causes of cancer-related deaths, there are still no approved management strategies for the disease. The etiology of this condition is based on the upregulation of systemic inflammation factors and catabolic stimuli, resulting in the inhibition of protein synthesis and enhancement of protein degradation. Numerous necessary cellular processes are disrupted by cachectic pathology, which mediate intracellular signalling pathways resulting in the net loss of muscle and organelles. However, the exact underpinning molecular mechanisms of how these changes are orchestrated are incompletely understood. Much work is still required, but structured exercise has the capacity to counteract numerous detrimental effects linked to cancer cachexia. Primarily through the stimulation of muscle protein synthesis, enhancement of mitochondrial function, and the release of myokines. As a result, muscle mass and strength increase, leading to improved mobility, and quality-of-life. This review summarises existing knowledge of the complex molecular networks that regulate cancer cachexia and exercise, highlighting the molecular interplay between the two for potential therapeutic intervention. Finally, the utility of mass spectrometry-based proteomics is considered as a way of establishing early diagnostic biomarkers of cachectic patients.
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David A, Lev-Ari S. Targeting the Gut Microbiome to Improve Immunotherapy Outcomes: A Review. Integr Cancer Ther 2024; 23:15347354241269870. [PMID: 39223798 PMCID: PMC11369881 DOI: 10.1177/15347354241269870] [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] [Revised: 03/18/2024] [Accepted: 07/19/2024] [Indexed: 09/04/2024] Open
Abstract
The following narrative review embarks on a comprehensive exploration of the role played by the gut microbiome within the Diet-Microbiota-Immunity (DMI) tripartite, aiming to enhance anti-cancer immunotherapy efficacy. While revolutionizing cancer treatment, resistance to immunotherapy and immune-related adverse events (irAEs) remain challenges. The tumor microenvironment (TME), shaped by cancer cells, influences immunotherapy resistance. The gut microbiome, influenced by genetics, environment, diet, and interventions, emerges as a critical player in TME reshaping, thereby modulating immune responses and treatment outcomes. Dietary patterns like the Mediterranean diet, caloric restriction modifications, and specific nutritional components show promise in influencing the tumor microenvironment and gut microbiome for better treatment outcomes. Antibiotics, disrupting gut microbiota diversity, may compromise immunotherapy efficacy. This review emphasizes the need for tailored nutritional strategies to manipulate microbial communities, enhance immune regulation, and improve immunotherapy accessibility while minimizing side effects. Ongoing studies investigate the impact of dietary interventions on cancer immunotherapy, pointing toward promising developments in personalized cancer care. This narrative review synthesizes existing knowledge and charts a course for future investigations, presenting a holistic perspective on the dynamic interplay between dietary interventions, the gut microbiome, and cancer immunotherapy within the DMI tripartite.
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Affiliation(s)
- Adi David
- Tal Center for Integrative Medicine, Institute of Oncology, Sheba Medical Center, Ramat-Gan, Israel
| | - Shaked Lev-Ari
- Ella Lemelbaum Institute For Immuno-Oncology, Sheba Medical Center, Ramat-Gan, Israel
- Education Authority, Sheba Medical Center, Ramat-Gan, Israel
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Nishie K, Nishie T, Sato S, Hanaoka M. Update on the treatment of cancer cachexia. Drug Discov Today 2023; 28:103689. [PMID: 37385369 DOI: 10.1016/j.drudis.2023.103689] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 06/09/2023] [Accepted: 06/21/2023] [Indexed: 07/01/2023]
Abstract
Cancer cachexia is a complex multifaceted syndrome involving functional impairment and changes in body composition that cannot be reversed by nutritional support. Cancer cachexia is characterized by decreased skeletal muscle mass, increased lipolysis, and decreased food intake. Cancer cachexia decreases chemotherapy tolerance as well as quality of life. However, because no fully effective interventions are available, cancer cachexia remains an unmet need in cancer treatment. In recent years, several discoveries and treatments for cancer cachexia have been studied, and guidelines have been published. We believe that the development of effective strategies for the diagnosis and treatment of cancer cachexia will lead to breakthroughs in cancer treatment.
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Affiliation(s)
- Kenichi Nishie
- Department of Respiratory Medicine, Iida Municipal Hospital, 438 Yawatamachi Iida Nagano, 395-0814, Japan; The First Department of Internal Medicine, Shinshu University School of Medicine, Japan.
| | - Tomomi Nishie
- The Faculty of Pharmaceutical Sciences, Ritsumeikan University, Japan
| | - Seiichi Sato
- Department of Pharmaceutics, Iida Municipal Hospital, Japan
| | - Masayuki Hanaoka
- The First Department of Internal Medicine, Shinshu University School of Medicine, Japan
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Barbosa-Cortés L, Martínez-Vieyra X, Mejía-Aranguré JM, López-Alarcón M, Martin-Trejo J, Delgadillo-Portillo S, Guzmán-Castro B, Delgadillo-Portillo J, Atilano-Miguel S, Rodríguez-Cruz M, Maldonado-Hernández J, Añoveros-Barrera A, Solís-Labastida KA, Espinoza-Hernández L, Nuñez-Villegas NN, Jiménez-Hernández E, Bautista-Martínez BA, Juárez-Moya A, Hernández-Piñón Z, Pérez-Casillas RX. Pilot study on the effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on body composition in children with acute lymphoblastic leukemia: randomized clinical trial. Clin Nutr 2023; 42:1759-1769. [PMID: 37549598 DOI: 10.1016/j.clnu.2023.06.022] [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: 01/16/2023] [Revised: 06/02/2023] [Accepted: 06/22/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND N-3 polyunsaturated fatty acids (LCPUFA-ω3), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) might have beneficial effects on lean mass and fat mass synthesis. OBJECTIVE To investigate the effect of LCPUFA-ω3 supplementation on body composition changes in children with acute lymphoblastic leukemia (ALL) at remission and three months (3 mo) after supplementation. METHODS This randomized controlled trial enrolled 72 children (3-13 y) with newly diagnosed ALL (placebo group [500 mg sunflower oil]: 36 patients; LCPUFA-ω3 group [225 mg DHA, 45 mg EPA]: 36 patients). LCPUFA-ω3 was administered at 0.100 g/kg of body weight/day for 3 mo. Both groups were provided with an oral milkshake supplement. MAIN OUTCOMES AND MEASURES Body composition was measured at diagnosis, remission, and 3 months after supplementation by dual-energy X-ray absorptiometry (DXA). Red blood cell fatty acid analyses were performed with gas chromatography. Student's t test compared the percentage changes in body weight, total body fat percentage (TBFP), and lean body mass (LBM) between the groups. The Mann-Whitney U test was used to compare the groups, and the Friedman range test and Wilcoxon signed rank test were used for intratreatment comparisons. Spearman correlation coefficients were calculated for LBM and erythrocyte LCPUFA-ω3 content. RESULTS LBM decreased significantly in both groups. This loss was greater in the placebo group than in the LCPUFA-ω3 group at remission (p = 0.044) and at 3 months of supplementation (p = 0.039). There were significant and progressive increases in DHA and EPA concentrations in the LCPUFA-ω3 group (p < 0.001). LBM at remission was directly correlated with increased DHA (r = 0.487, p = 0.034) and EPA (r = 0.499, p = 0.030) erythrocytes in the LCPUFA-ω3 group. CONCLUSION At ALL diagnosis and during the first three months of treatment, 100 mg/kg of body weight/d DHA and EPA decreased LBM loss and allowed the incorporation of fatty acids into cell membranes (clinicaltriasl.gov #: NCT01051154).
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Affiliation(s)
- Lourdes Barbosa-Cortés
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México.
| | - Ximena Martínez-Vieyra
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Juan Manuel Mejía-Aranguré
- Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Ciudad de México, México; Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México
| | - Mardia López-Alarcón
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Jorge Martin-Trejo
- Servicio de Hematología, Unidad Médica de Alta Especialidad /(UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Suily Delgadillo-Portillo
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Brenda Guzmán-Castro
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Jazmín Delgadillo-Portillo
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Salvador Atilano-Miguel
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Maricela Rodríguez-Cruz
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Jorge Maldonado-Hernández
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Ana Añoveros-Barrera
- Unidad de Investigación Médica en Nutrición, Unidad Médica de Alta Especialidad (UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Karina A Solís-Labastida
- Servicio de Hematología, Unidad Médica de Alta Especialidad /(UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Laura Espinoza-Hernández
- Departamento de Hematología Pediátrica, Unidad Médica de Alta Especialidad (UMAE), Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Nora N Nuñez-Villegas
- Departamento de Hematología Pediátrica, Unidad Médica de Alta Especialidad (UMAE), Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Elva Jiménez-Hernández
- Departamento de Hematología Pediátrica, Unidad Médica de Alta Especialidad (UMAE), Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Benito A Bautista-Martínez
- Servicio de Hematología, Unidad Médica de Alta Especialidad /(UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Azalia Juárez-Moya
- Servicio de Hematología, Unidad Médica de Alta Especialidad /(UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Zayra Hernández-Piñón
- Servicio de Hematología, Unidad Médica de Alta Especialidad /(UMAE), Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
| | - Ruy Xavier Pérez-Casillas
- Departamento de Hematología Pediátrica, Unidad Médica de Alta Especialidad (UMAE), Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México
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10
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Frenkel M, David A, Sapire K, Hausner D. Complementary and Integrative Medicine in Pancreatic Cancer. Curr Oncol Rep 2023; 25:231-242. [PMID: 36735141 DOI: 10.1007/s11912-023-01370-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE OF REVIEW Pancreatic cancer has high mortality and morbidity rates, associated with the issues of typically late diagnosis and the limited effectiveness of current treatments. Patients tend to experience multiple symptoms that can include anxiety, fear, depression, fatigue, weakness, peripheral neuropathy, and abdominal pain, which reduce quality of life (QoL) and may compromise the treatment continuum. Many of those symptoms are amenable to complementary and integrative medicine (CIM) therapies as a part of supportive and palliative care. This article reviews research findings on the beneficial effect of use of CIM modalities in regard to pancreatic cancer, with emphasis on pancreatic ductal adenocarcinoma (PDAC). RECENT FINDINGS Given the often-poor prognosis of the disease, patients with PDAC often seek integrative therapies to help manage the disease itself, to provide support through cancer treatment and its symptoms, and to provide emotional stress relief. Data is accumulating in the past few years on the potential benefits of CIM to the management of pancreatic cancer symptoms and treatment side effects, in order to augment supportive care. This data reveal that nutrition counselling; digestive enzyme therapy; microbiome support; dietary supplements; lifestyle interventions (physical activity and circadian health/sleep hygiene) appear to improve QoL of these patients through reduced symptom burden and meeting psychological needs, such as distress and fatigue. Acupuncture, mindfulness, yoga, reflexology, massage, and homeopathy may also contribute to symptom reduction, both physical and psychological, in all stages of the disease. There is supporting evidence that some CIM modalities may alleviate side effects and symptoms related to pancreatic cancer and its treatment, suggesting that practitioners might consider integrating these modalities in certain situations encountered in the treatment of pancreatic cancer. Further investigation is needed to define the optimal integration of CIM into the treatment and supportive care of patients affected by pancreatic cancer.
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Affiliation(s)
- Moshe Frenkel
- Complementary and Integrative Medicine Service, Oncology Division, Rambam Health Care Campus, Haifa, Israel.
| | - Adi David
- Tal Center for Integrative Medicine, Institute of Oncology, Chaim Sheba Medical Center, Ramat-Gan, Israel
| | - Kenneth Sapire
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - David Hausner
- Tal Center for Integrative Medicine, Institute of Oncology, Chaim Sheba Medical Center, Ramat-Gan, Israel.,Palliative Care Service, Chaim Sheba Medical Center, Ramat Gan, Israel
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11
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Lam CS, Koon HK, Loong HHF, Chung VCH, Cheung YT. Associations of dietary supplement use with all-cause and cause-specific mortality in patients diagnosed with cancer: a large prospective cohort study in the UK Biobank. Eur J Nutr 2023; 62:879-889. [PMID: 36318282 DOI: 10.1007/s00394-022-03044-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
PURPOSE Despite the increasing popularity of supplement use among the cancer community, the current evidence on its effect on mortality in large studies is inconclusive. This study examined the association of dietary supplement use with mortality risk in a large population-based cohort. METHODS This prospective cohort study analyzed data from the UK Biobank on participants who were diagnosed with cancer before July 31, 2019 and self-reported whether they had regular intake of dietary supplements (vitamins, minerals, or non-vitamin non-mineral [NVNM] supplements) after cancer diagnosis. The associations between the use of supplements with mortality were analyzed using Cox proportional hazards models, adjusting for confounders (sociodemographic factors, lifestyle and comorbidities). RESULTS This analysis included 30,239 participants (mean age: 60.0 years; 61.9% female). Over half (57.8%) were supplement users. At a median follow-up of 11.9 years, 5577 all-cause deaths were registered. A marginal protective effect of supplement use on the risk of all-cause (adjusted hazard ratio [aHR] = 0.95, 95% CI = 0.90-0.99) and cancer (aHR = 0.89, 95% CI = 0.83-0.95) mortality were found, but not the risk of mortality due to other causes. In subgroup analyses, only NVNM dietary supplements were significantly associated with a lower risk of all-cause mortality (aHR = 0.88, 95% CI = 0.83-0.93). Both vitamins (aHR = 0.93, 95% CI = 0.87-0.99) and NVNM dietary supplements (aHR = 0.88, 95% CI = 0.82-0.94) were associated with a modest decrease in cancer mortality which were marginally significant. CONCLUSIONS This is one of the largest cohort studies that identified the associations of dietary supplements with survival in the cancer population. However, the associations are small and should be interpreted cautiously due to the variations among different supplements and the small effect size. Future studies should investigate the effect of individual supplements, particularly NVNM supplements, on improving other cancer-related outcomes.
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Affiliation(s)
- Chun Sing Lam
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Ho Kee Koon
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Herbert Ho-Fung Loong
- Department of Clinical Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Vincent Chi-Ho Chung
- School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yin Ting Cheung
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
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12
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An Investigation of the Prognostic Role of Genes Related to Lipid Metabolism in Head and Neck Squamous Cell Carcinoma. Int J Genomics 2023; 2023:9708282. [PMID: 36818393 PMCID: PMC9937776 DOI: 10.1155/2023/9708282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 01/06/2023] [Accepted: 01/27/2023] [Indexed: 02/12/2023] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) has become a prevalent malignancy, and its incidence and mortality rate are increasing worldwide. Accumulating evidence has indicated that lipid metabolism-related genes (LMRGs) are involved in the occurrence and development of HNSCC. This study investigated the latent association of lipid metabolism with HNSCC and established a prognostic signature based on LMRGs. A prognostic risk model composed of eight differentially expressed LMRGs (PHYH, CYP4F8, INMT, ELOVL6, PLPP3, BCHE, TPTE, and STAR) was constructed through The Cancer Genome Atlas database. Then, ELOVL6 expression was validated in oral squamous cell carcinoma (OSCC), which is a common type of HNSCC, by immunohistochemical analysis. ELOVL6 expression in the OSCC II/III group was significantly higher than that in the other three groups (normal, dysplasia, and OSCC I), and OSCC patients with high ELOVL6 expression had poorer survival than those with low ELOVL6 expression. In summary, the LMRG-based prognostic feature had prognostic predictive capacity. ELOVL6 may be a potential prognostic factor for HNSCC patients.
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13
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Emanuel A, Krampitz J, Rosenberger F, Kind S, Rötzer I. Nutritional Interventions in Pancreatic Cancer: A Systematic Review. Cancers (Basel) 2022; 14:2212. [PMID: 35565341 PMCID: PMC9101959 DOI: 10.3390/cancers14092212] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/24/2022] [Accepted: 04/27/2022] [Indexed: 02/04/2023] Open
Abstract
(1) Background: Pancreatic cancer (PaCa) is directly related to malnutrition, cachexia and weight loss. Nutritional interventions (NI) are used in addition to standard therapy. The aim of this systematic review is to provide an overview of the types of NI and their effects. (2) Methods: We included RCTs with at least one intervention group receiving an NI and compared them with a control group with no NI, placebo or alternative treatment on cachexia, malnutrition or weight loss in patients with PaCa. Any available literature until 12 August 2021 was searched in the Pubmed and Cochrane databases. RCTs were sorted according to NI (parenteral nutrition, enteral nutrition, dietary supplements and mixed or special forms). (3) Results: Finally, 26 studies with a total of 2720 patients were included. The potential for bias was mostly moderate to high. Parenteral nutrition is associated with a higher incidence of complications. Enteral nutrition is associated with shorter length of stay in hospital, lower rate and development of complications, positive effects on cytokine rates and lower weight loss. Dietary supplements enriched with omega-3 fatty acids lead to higher body weight and lean body mass. (4) Conclusions: Enteral nutrition and dietary supplements with omega-3 fatty acids should be preferred in nutritional therapy of PaCa patients.
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Affiliation(s)
- Aline Emanuel
- Division of Nutrition Sciences, German University of Applied Sciences for Prevention and Health Management (DHfPG), 66123 Saarbruecken, Germany;
| | - Julia Krampitz
- Division of Psychology and Pedagogy, German University of Applied Sciences for Prevention and Health Management (DHfPG), 66123 Saarbruecken, Germany;
- Institute of Psychology, University of Innsbruck, 6020 Innsbruck, Austria
| | - Friederike Rosenberger
- Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, 69120 Heidelberg, Germany;
- Division of Health Sciences, German University of Applied Sciences for Prevention and Health Management (DHfPG), 66123 Saarbruecken, Germany;
| | - Sabine Kind
- Division of Health Sciences, German University of Applied Sciences for Prevention and Health Management (DHfPG), 66123 Saarbruecken, Germany;
| | - Ingeborg Rötzer
- Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital, 69120 Heidelberg, Germany;
- Clinic for Oncology and Haemotology, Northwest Hospital, UCT-Cancer University Center, 60488 Frankfurt am Main, Germany
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14
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Ikeno Y, Inomata M, Tsukimura Y, Suzuki Y, Takeuchi H, Harada Y, Kon R, Ikarashi N, Chiba Y, Yamada T, Kamei J, Sakai H. Eicosapentaenoic acid suppresses cisplatin-induced muscle atrophy by attenuating the up-regulated gene expression of ubiquitin. J Nutr Biochem 2022; 103:108953. [PMID: 35121023 DOI: 10.1016/j.jnutbio.2022.108953] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/15/2021] [Accepted: 01/04/2022] [Indexed: 10/19/2022]
Abstract
Previously it was shown that cisplatin causes muscle atrophy. Under this condition, cisplatin increased the expression of atorogenes, such as muscle ring finger 1 and atrogin-1 (also known as muscle atrophy F-box protein), in mouse skeletal muscle. It was reported recently that ubiquitin (Ub) and ubiquitinated protein levels in skeletal muscle were also up-regulated in cisplatin-induced muscle atrophy, and cisplatin-induced ubiquitinated proteins were degraded by the 26S proteasome pathway. Eicosapentaenoic acid (EPA) is effective against skeletal muscle atrophy in mice. However, it is unclear how EPA suppresses the Ub-proteasome pathway. In this study, the effect of EPA on cisplatin-induced muscle atrophy in mice was examined. Mice were intraperitoneally injected with cisplatin or vehicle control once daily for 4 days. EPA or its vehicle was orally administered 30 min before cisplatin administration. Cisplatin systemic administration induced decrease in muscle mass, myofiber diameter, and increase in Ub genes and ubiquitinated proteins in mouse skeletal muscle were recovered by co-treatment with EPA. However, weight loss and up-regulated atrogenes induced by cisplatin were not changed by co-treatment with EPA in skeletal muscle. In this study, EPA attenuated cisplatin-induced muscle atrophy via down-regulation of up-regulated Ub gene expression. Although further clinical studies are needed, EPA administration can be effective in the development of muscle atrophy in cisplatin-treated patients.
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Affiliation(s)
- Yohei Ikeno
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Maya Inomata
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Yuka Tsukimura
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Yuta Suzuki
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Hiroto Takeuchi
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Yui Harada
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Risako Kon
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Nobutomo Ikarashi
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Yoshihiko Chiba
- Laboratory of Molecular Biology and Physiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Takeshi Yamada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Junzo Kamei
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan
| | - Hiroyasu Sakai
- Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501, Japan.
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15
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Tao X, Zhou Q, Rao Z. Efficacy of ω-3 Polyunsaturated Fatty Acids in Patients with Lung Cancer Undergoing Radiotherapy and Chemotherapy: A Meta-Analysis. Int J Clin Pract 2022; 2022:6564466. [PMID: 35910071 PMCID: PMC9303080 DOI: 10.1155/2022/6564466] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/11/2022] [Accepted: 06/11/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Radiotherapy and chemotherapy in patients with lung cancer can lead to a series of problems such as malnutrition and inflammatory reaction. Some studies have shown that ω-3 polyunsaturated fatty acids (PUFAs) could improve malnutrition and regulate inflammatory reaction in these patients, but no relevant meta-analysis exists. METHODS We systematically searched randomized controlled trials of ω-3 PUFAs in the adjuvant treatment of lung cancer in the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang databases. Relevant outcomes were extracted, and we pooled standardized mean differences (SMDs) using a random or fixed-effects model. The risk of bias was evaluated according to the Cochrane Handbook (version 15.1). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS A total of 7 studies were included. The SMDs (95% CI) of body weight change, albumin change, energy intake, and protein intake at the end of intervention were 1.15 (0.50, 1.80), 0.60 (0.11, 1.09), 0.39 (-0.10, 0.89), and 0.27 (-0.04, 0.58), respectively. The SMDs (95% CI) of CRP change and TNF-α change were -3.44 (-6.15, -0.73) and -1.63 (-2.53, -0.73), respectively. CONCLUSIONS ω-3 PUFAs can improve nutritional status and regulate indicators of inflammation in patients with lung cancer undergoing radiotherapy and chemotherapy. This study was registered in the PROSPERO (registration number: CRD42022307699).
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Affiliation(s)
- Xin Tao
- Department of Clinical Nutrition, Suining Central Hospital, Suining, China
| | - Qiang Zhou
- Department of Oncology, Suining Central Hospital, Suining, China
| | - Zhiyong Rao
- Department of Clinical Nutrition, West China Hospital of Sichuan University, Chengdu, China
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Abstract
ABSTRACT Diet and exercise interventions may help reverse malnutrition and muscle wasting common in pancreatic cancer. We performed a scoping review to identify the knowledge gaps surrounding diet and exercise interventions. We searched PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, Embase, ProQuest Theses and Dissertations, and Google Scholar using the umbrella terms of "pancreatic cancer," "diet/nutrition," and "exercise." Included were articles reporting on ambulatory adults with diagnosed pancreatic cancer. Excluded were studies examining prevention and/or risk, animal, or cell lines. Of the 15,708 articles identified, only 62 met the final inclusion criteria. Almost half of the articles were randomized controlled studies (n = 27). Most studies were from the United States (n = 20). The majority examined dietary interventions (n = 41), with 20 assessing the use of omega-3 fatty acids. Exercise interventions were reported in 13 studies, with 8 examining a diet and exercise intervention. Most studies were small and varied greatly in terms of study design, intervention, and outcomes. We identified 7 research gaps that should be addressed in future studies. This scoping review highlights the limited research examining the effect of diet and exercise interventions in ambulatory patients with pancreatic cancer.
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17
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Aquila G, Re Cecconi AD, Brault JJ, Corli O, Piccirillo R. Nutraceuticals and Exercise against Muscle Wasting during Cancer Cachexia. Cells 2020; 9:E2536. [PMID: 33255345 PMCID: PMC7760926 DOI: 10.3390/cells9122536] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/17/2020] [Accepted: 11/18/2020] [Indexed: 12/12/2022] Open
Abstract
Cancer cachexia (CC) is a debilitating multifactorial syndrome, involving progressive deterioration and functional impairment of skeletal muscles. It affects about 80% of patients with advanced cancer and causes premature death. No causal therapy is available against CC. In the last few decades, our understanding of the mechanisms contributing to muscle wasting during cancer has markedly increased. Both inflammation and oxidative stress (OS) alter anabolic and catabolic signaling pathways mostly culminating with muscle depletion. Several preclinical studies have emphasized the beneficial roles of several classes of nutraceuticals and modes of physical exercise, but their efficacy in CC patients remains scant. The route of nutraceutical administration is critical to increase its bioavailability and achieve the desired anti-cachexia effects. Accumulating evidence suggests that a single therapy may not be enough, and a bimodal intervention (nutraceuticals plus exercise) may be a more effective treatment for CC. This review focuses on the current state of the field on the role of inflammation and OS in the pathogenesis of muscle atrophy during CC, and how nutraceuticals and physical activity may act synergistically to limit muscle wasting and dysfunction.
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Affiliation(s)
- Giorgio Aquila
- Neuroscience Department, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy; (G.A.); (A.D.R.C.)
- Italian Institute for Planetary Health, IIPH, 20156 Milan, Italy;
| | - Andrea David Re Cecconi
- Neuroscience Department, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy; (G.A.); (A.D.R.C.)
- Italian Institute for Planetary Health, IIPH, 20156 Milan, Italy;
| | - Jeffrey J. Brault
- Indiana Center for Musculoskeletal Health, Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Oscar Corli
- Italian Institute for Planetary Health, IIPH, 20156 Milan, Italy;
- Oncology Department, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy
| | - Rosanna Piccirillo
- Neuroscience Department, Mario Negri Institute for Pharmacological Research IRCCS, 20156 Milan, Italy; (G.A.); (A.D.R.C.)
- Italian Institute for Planetary Health, IIPH, 20156 Milan, Italy;
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18
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Jentzsch V, Davis JAA, Djamgoz MBA. Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management. Cancers (Basel) 2020; 12:E3096. [PMID: 33114159 PMCID: PMC7690843 DOI: 10.3390/cancers12113096] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/09/2020] [Indexed: 02/07/2023] Open
Abstract
The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating 'western' clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main 'hallmarks of cancer'. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials.
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Affiliation(s)
- Valerie Jentzsch
- Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; (V.J.); (J.A.A.D.)
- Business School, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
| | - James A. A. Davis
- Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; (V.J.); (J.A.A.D.)
| | - Mustafa B. A. Djamgoz
- Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London SW7 2AZ, UK; (V.J.); (J.A.A.D.)
- Biotechnology Research Centre, Cyprus International University, Haspolat, Nicosia, TRNC, Mersin 10, Turkey
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19
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Roeland EJ, Bohlke K, Baracos VE, Bruera E, del Fabbro E, Dixon S, Fallon M, Herrstedt J, Lau H, Platek M, Rugo HS, Schnipper HH, Smith TJ, Tan W, Loprinzi CL. Management of Cancer Cachexia: ASCO Guideline. J Clin Oncol 2020; 38:2438-2453. [DOI: 10.1200/jco.20.00611] [Citation(s) in RCA: 154] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
PURPOSE To provide evidence-based guidance on the clinical management of cancer cachexia in adult patients with advanced cancer. METHODS A systematic review of the literature collected evidence regarding nutritional, pharmacologic, and other interventions, such as exercise, for cancer cachexia. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and systematic reviews of RCTs published from 1966 through October 17, 2019. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS The review included 20 systematic reviews and 13 additional RCTs. Dietary counseling, with or without oral nutritional supplements, was reported to increase body weight in some trials, but evidence remains limited. Pharmacologic interventions associated with improvements in appetite and/or body weight include progesterone analogs and corticosteroids. The other evaluated interventions either had no benefit or insufficient evidence of benefit to draw conclusions on efficacy. Limitations of the evidence include high drop-out rates, consistent with advanced cancer, as well as variability across studies in outcomes of interest and methods for outcome assessment. RECOMMENDATIONS Dietary counseling may be offered with the goals of providing patients and caregivers with advice for the management of cachexia. Enteral feeding tubes and parenteral nutrition should not be used routinely. In the absence of more robust evidence, no specific pharmacological intervention can be recommended as the standard of care; therefore, clinicians may choose not to prescribe medications specifically for the treatment of cancer cachexia. Nonetheless, when it is decided to trial a drug to improve appetite and/or improve weight gain, currently available pharmacologic interventions that may be used include progesterone analogs and short-term (weeks) corticosteroids.
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Affiliation(s)
| | - Kari Bohlke
- American Society of Clinical Oncology, Alexandria, VA
| | | | | | | | | | - Marie Fallon
- Edinburgh Oncology Centre, University of Edinburgh, UK
| | - Jørn Herrstedt
- Zealand University Hospital Roskilde and University of Copenhagen, Denmark
| | - Harold Lau
- University of Calgary, Calgary, Alberta, Canada
| | - Mary Platek
- Roswell Park Comprehensive Cancer Center and D’Youville College, Buffalo, NY
| | - Hope S. Rugo
- University of California San Francisco, San Francisco, CA
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20
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Roeland EJ, Bohlke K, Baracos VE, Bruera E, del Fabbro E, Dixon S, Fallon M, Herrstedt J, Lau H, Platek M, Rugo HS, Schnipper HH, Smith TJ, Tan W, Loprinzi CL. Management of Cancer Cachexia: ASCO Guideline. J Clin Oncol 2020. [DOI: 10.1200/jco.20.00611 10.1200/jco.20.00611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
PURPOSE To provide evidence-based guidance on the clinical management of cancer cachexia in adult patients with advanced cancer. METHODS A systematic review of the literature collected evidence regarding nutritional, pharmacologic, and other interventions, such as exercise, for cancer cachexia. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and systematic reviews of RCTs published from 1966 through October 17, 2019. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS The review included 20 systematic reviews and 13 additional RCTs. Dietary counseling, with or without oral nutritional supplements, was reported to increase body weight in some trials, but evidence remains limited. Pharmacologic interventions associated with improvements in appetite and/or body weight include progesterone analogs and corticosteroids. The other evaluated interventions either had no benefit or insufficient evidence of benefit to draw conclusions on efficacy. Limitations of the evidence include high drop-out rates, consistent with advanced cancer, as well as variability across studies in outcomes of interest and methods for outcome assessment. RECOMMENDATIONS Dietary counseling may be offered with the goals of providing patients and caregivers with advice for the management of cachexia. Enteral feeding tubes and parenteral nutrition should not be used routinely. In the absence of more robust evidence, no specific pharmacological intervention can be recommended as the standard of care; therefore, clinicians may choose not to prescribe medications specifically for the treatment of cancer cachexia. Nonetheless, when it is decided to trial a drug to improve appetite and/or improve weight gain, currently available pharmacologic interventions that may be used include progesterone analogs and short-term (weeks) corticosteroids.
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Affiliation(s)
| | - Kari Bohlke
- American Society of Clinical Oncology, Alexandria, VA
| | | | | | | | | | - Marie Fallon
- Edinburgh Oncology Centre, University of Edinburgh, UK
| | - Jørn Herrstedt
- Zealand University Hospital Roskilde and University of Copenhagen, Denmark
| | - Harold Lau
- University of Calgary, Calgary, Alberta, Canada
| | - Mary Platek
- Roswell Park Comprehensive Cancer Center and D’Youville College, Buffalo, NY
| | - Hope S. Rugo
- University of California San Francisco, San Francisco, CA
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Ma Y, Wang J, Li Q, Cao B. The Effect of Omega-3 Polyunsaturated Fatty Acid Supplementations on anti-Tumor Drugs in Triple Negative Breast Cancer. Nutr Cancer 2020; 73:196-205. [PMID: 32223441 DOI: 10.1080/01635581.2020.1743873] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Triple-negative breast cancer (TNBC) comprises about 10-20% of all diagnosed breast cancers. Increasing evidence shows that the omega-3 polyunsaturated fatty acids (ω-3PUFAs), docosahexaenoic acid and eicosapentaenoic acid, can influence the development, progression, and prognosis of TNBC In Vivo and In Vitro; however, clinical evidence supporting the effect of ω-3PUFAs on TNBC is lacking. Research has demonstrated that ω-3PUFAs can induce apoptosis in breast cancer cells by inhibiting the PI3K/AKT signal transduction pathway, and that ω-3PUFAs can improve the effectiveness of chemotherapy drugs. Using ω-3PUFA supplementation in addition to pharmacotherapy in the treatment of breast cancer may result in enhanced anti-tumor effects that will be particularly applicable to difficult to treat phenotypes such as TNBC. The aim of the current review was to summarize the evidence-base supporting the antitumor effects of omega-3 PUFAs in TNBC.
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Affiliation(s)
- Yingjie Ma
- Department of Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Jing Wang
- Department of Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Qin Li
- Department of Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Bangwei Cao
- Department of Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
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22
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Šunderić M, Robajac D, Gligorijević N, Miljuš G, Nedić O, Smilkov K, Ackova DG, Rudić-Grujić V, Penezić A. Is There Something Fishy About Fish Oil? Curr Pharm Des 2020; 25:1747-1759. [PMID: 31298156 DOI: 10.2174/1381612825666190705185800] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 06/27/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUND Fish is consumed as food worldwide and is considered as a rich source of essential nutrients required for a healthy life. Supplementation with fish oil has been adopted as a solution to prevent or cure many pathophysiological states and diseases by both the professionals and the civil population. The beneficial effects are, however, being questioned, as some controversial results were obtained in clinical and population studies. METHODS Critical evaluation of studies regarding known effects of fish oil, both in favour of its consumption and related controversies. RESULTS From the literature review, contradictory allegations about the positive action of the fish oil on human health emerged, so that a clear line about its beneficial effect cannot be withdrawn. CONCLUSION Scientific results on the application of fish oil should be taken with caution as there is still no standardised approach in testing its effects and there are significantly different baselines in respect to nutritional and other lifestyle habits of different populations.
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Affiliation(s)
- Miloš Šunderić
- Department of Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia
| | - Dragana Robajac
- Department of Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia
| | - Nikola Gligorijević
- Department of Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia
| | - Goran Miljuš
- Department of Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia
| | - Olgica Nedić
- Department of Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia
| | - Katarina Smilkov
- Department of Pharmacy, Faculty of Medical Sciences, University Goce Delcev, Stip, R, North Macedonia
| | - Darinka Gjorgieva Ackova
- Department of Pharmacy, Faculty of Medical Sciences, University Goce Delcev, Stip, R, North Macedonia
| | - Vesna Rudić-Grujić
- Department of Hygiene and Human Health, Public Health Institute Republic of Srpska, Medical Faculty, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
| | - Ana Penezić
- Department of Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia
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Ma Y, Yu J, Li Q, Su Q, Cao B. Addition of docosahexaenoic acid synergistically enhances the efficacy of apatinib for triple-negative breast cancer therapy. Biosci Biotechnol Biochem 2019; 84:743-756. [PMID: 31889475 DOI: 10.1080/09168451.2019.1709789] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The current study aimed to investigate the antitumor and antiangiogenesis effects of apatinib in triple-negative breast cancer in vitro and also whether the combination of docosahexaenoic acid (DHA) and apatinib is more effective than apatinib monotherapy. The cell counting kit-8 assay was used to measure cell proliferation. Flow cytometry was utilized to determine the cell apoptosis rate. A wound healing assay was utilized to assess cell migration. Western blot analysis was carried out to determine the effects of apatinib and DHA on Bcl-2, BAX, cleaved caspase-3, caspase-3, phosphorylated protein kinase B (p-Akt), and Akt expression. DHA in combination with apatinib showed enhanced inhibitory effects on cell proliferation and migration compared with apatinib or DHA monotherapy. Meanwhile, DHA combined with apatinib strongly increased the cell apoptosis percentage. DHA was observed to enhance the antitumor and antiangiogenesis effects of apatinib via further downregulation of p-Akt expression.Abbreviations: FITC: fluorescein isothiocyanate; PI: propidium iodide.
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Affiliation(s)
- Yingjie Ma
- Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Junxian Yu
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China
| | - Qin Li
- Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Qiang Su
- Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
| | - Bangwei Cao
- Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P. R. China
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24
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Satogami K, Tseng PT, Su KP, Takahashi S, Ukai S, Li DJ, Chen TY, Lin PY, Chen YW, Matsuoka YJ. Relationship between polyunsaturated fatty acid and eating disorders: Systematic review and meta-analysis. Prostaglandins Leukot Essent Fatty Acids 2019; 142:11-19. [PMID: 30773209 DOI: 10.1016/j.plefa.2019.01.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 01/02/2019] [Accepted: 01/10/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVES Eating disorders result in poor nutrition, poor physical conditions and even suicidality and mortality. Although polyunsaturated fatty acids (PUFAs) have attracted attention in the emerging field of nutritional psychiatry, their role in eating disorders remains unknown. This meta-analysis investigates the differences of PUFA levels between patients with eating disorders and healthy controls, and the potentially beneficial effects of PUFAs in such patients. METHODS We conducted a systematic literature search and meta-analysis under the random effects model. RESULT Eleven studies were included in the current meta-analysis. Compared with controls, 379 patients with eating disorders had significantly higher plasma levels of alpha-linolenic acid, eicosapentaenoic acid, stearidonic acid, osbond acid, palmitoleic acid, oleic acid, and total omega-3 fatty acids; and lower levels of total omega-6 fatty acids and omega-6/omega-3 ratio. Eating disorders were associated with significantly higher red blood cell membrane levels of palmitoleic acid and oleic acid and lower levels of adrenic acid, arachidonic acid, and total omega-6 fatty acids. In addition, PUFA supplements were associated with a benefit to body weight outcomes but not disease severity and mood symptoms in interventional trials. DISCUSSION This meta-analysis indicates abnormal levels of PUFAs in peripheral blood tissues in patients with eating disorders. The relationship between PUFAs and eating disorders should be interpreted cautiously considering the specific lipid metabolism under starvation state. To investigate the role of PUFAs on psychopathological and therapeutic effects in eating disorders, further larger clinical studies are warranted.
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Affiliation(s)
- Kazumi Satogami
- Department of Neuropsychiatry, Wakayama Medical University, Wakayama, Japan
| | - Ping-Tao Tseng
- WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan
| | - Kuan-Pin Su
- College of Medicine, China Medical University, Taichung, Taiwan; Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
| | - Shun Takahashi
- Department of Neuropsychiatry, Wakayama Medical University, Wakayama, Japan
| | - Satoshi Ukai
- Department of Neuropsychiatry, Wakayama Medical University, Wakayama, Japan
| | - Dian-Jeng Li
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Addiction Science, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan
| | - Tien-Yu Chen
- Department of Psychiatry, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
| | - Pao-Yen Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yen-Wen Chen
- Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan
| | - Yutaka J Matsuoka
- College of Medicine, China Medical University, Taichung, Taiwan; Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, Tokyo, Japan
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25
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Rattanachaiwong S, Singer P. Indirect calorimetry as point of care testing. Clin Nutr 2019; 38:2531-2544. [PMID: 30670292 DOI: 10.1016/j.clnu.2018.12.035] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 12/10/2018] [Accepted: 12/29/2018] [Indexed: 02/06/2023]
Abstract
Determining energy requirement is a fundamental of nutrition support. Indirect calorimetry (IC) has been long recognized as the gold standard for assessing basal or resting energy expenditure (REE). The measurement of REE is recommended particularly in the situation where adjustment of energy provision is critical. The result of the IC measurement can lead to changes in treatment and since the change can be carried out immediately at the bedside, this may be considered as point-of-care testing. Beyond the nutritional aspects, studies of energy expenditure with IC have brought out more understanding of the metabolic changes during the natural course of diseases or conditions as well as those related to the intervention. The literature in various disease states has shown that changes in energy expenditure may reveal hidden metabolic information that might be translated into clinical information and have the potential of being both prognostic indicators and/or treatment targets.
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Affiliation(s)
- Sornwichate Rattanachaiwong
- Division of Clinical Nutrition, Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand.
| | - Pierre Singer
- Department of General Intensive Care, Rabin Medical Center, Petah Tikva and Sackler School of Medicine, Tel Aviv University, Israel
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26
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Yakovenko A, Cameron M, Trevino JG. Molecular therapeutic strategies targeting pancreatic cancer induced cachexia. World J Gastrointest Surg 2018; 10:95-106. [PMID: 30622678 PMCID: PMC6314860 DOI: 10.4240/wjgs.v10.i9.95] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 11/01/2018] [Accepted: 11/27/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) induced cachexia is a complex metabolic syndrome associated with significantly increased morbidity and mortality and reduced quality of life. The pathophysiology of cachexia is complex and poorly understood. Many molecular signaling pathways are involved in PC and cachexia. Though our understanding of cancer cachexia is growing, therapeutic options remain limited. Thus, further discovery and investigation of the molecular signaling pathways involved in the pathophysiology of cachexia can be applied to development of targeted therapies. This review focuses on three main pathophysiologic processes implicated in the development and progression of cachexia in PC, as well as their utility in the discovery of novel targeted therapies.
Skeletal muscle wasting is the most prominent pathophysiologic anomaly in cachectic patients and driven by multiple regulatory pathways. Several known molecular pathways that mediate muscle wasting and cachexia include transforming growth factor-beta (TGF-β), myostatin and activin, IGF-1/PI3K/AKT, and JAK-STAT signaling. TGF-β antagonism in cachectic mice reduces skeletal muscle catabolism and weight loss, while improving overall survival. Myostatin/activin inhibition has a great therapeutic potential since it plays an essential role in skeletal muscle regulation. Overexpression of insulin-like growth factor binding protein-3 (IGFBP-3) leads to increased ubiquitination associated proteolysis, inhibition of myogenesis, and decreased muscle mass in PC induced cachexia. IGFBP-3 antagonism alleviates muscle cell wasting.
Another component of cachexia is profound systemic inflammation driven by pro-cachectic cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon gamma (INF-γ). IL-6 antagonism has been shown to reduce inflammation, reduce skeletal muscle loss, and ameliorate cachexia. While TNF-α inhibitors are clinically available, blocking TNF-α signaling is not effective in the treatment of cancer cachexia. Blocking the synthesis or action of acute phase reactants and cytokines is a feasible therapeutic strategy, but no anti-cytokine therapies are currently approved for use in PC. Metabolic alterations such as increased energy expenditure and gluconeogenesis, insulin resistance, fat tissue browning, excessive oxidative stress, and proteolysis with amino acid mobilization support tumor growth and the development of cachexia. Current innovative nutritional strategies for cachexia management include ketogenic diet, utilization of natural compounds such as silibinin, and supplementation with ω3-polyunsaturated fatty acids. Elevated ketone bodies exhibit an anticancer and anticachectic effect. Silibinin has been shown to inhibit growth of PC cells, induce metabolic alterations, and reduce myofiber degradation. Consumption of ω3-polyunsaturated fatty acids has been shown to significantly decrease resting energy expenditure and regulate metabolic dysfunction.
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Affiliation(s)
- Anastasiya Yakovenko
- University of Florida College of Medicine, Gainesville, Florida 32610, United States
| | - Miles Cameron
- University of Florida College of Medicine, Gainesville, Florida 32610, United States
| | - Jose Gilberto Trevino
- Department of Surgery, University of Florida Health Sciences Center, Gainesville, Florida 32610, United States
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27
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Woodworth-Hobbs ME, Perry BD, Rahnert JA, Hudson MB, Zheng B, Russ Price S. Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy. Physiol Rep 2018; 5. [PMID: 29199180 PMCID: PMC5727283 DOI: 10.14814/phy2.13530] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 11/08/2017] [Indexed: 12/21/2022] Open
Abstract
Lipid accumulation in skeletal muscle results in dysregulation of protein metabolism and muscle atrophy. We previously reported that treating C2C12 myotubes with palmitate (PA), a saturated fatty acid, increases the overall rate of proteolysis via activation of the ubiquitin-proteasome and autophagy systems; co-treatment with the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents the PA-induced responses. Others have reported that PA induces endoplasmic reticulum (ER) stress which initiates the unfolded protein response (UPR), a collective group of responses that can lead to activation of caspase-mediated proteolysis and autophagy. Presently, we tested the hypothesis that DHA protects against PA-induced ER stress/UPR and its atrophy-related responses in muscle cells. C2C12 myotubes were treated with 500 μmol/L PA and/or 100 μmol/L DHA for 24 h. Proteins and mRNA associated with ER stress/UPR, autophagy, and caspase-3 activation were evaluated. PA robustly increased the phosphorylation of protein kinase R (PKR)-like ER kinase (PERK) and eukaryotic initiation factor 2α (eIF2α). It also increased the mRNAs encoding activating transcription factor 4 (ATF4), spliced X-box binding protein 1 (XBP1s), C/EBP homologous protein (CHOP), and autophagy-related 5 (Atg5) as well as the protein levels of the PERK target nuclear factor erythroid 2-related factor (Nrf2), CHOP, and cleaved (i.e., activated) caspase-3. Co-treatment with DHA prevented all of the PA-induced responses. Our results indicate that DHA prevents PA-induced muscle cell atrophy, in part, by preventing ER stress/UPR, a process that leads to activation of caspase-mediated proteolysis and an increase in expression of autophagy-related genes.
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Affiliation(s)
- Myra E Woodworth-Hobbs
- Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia.,Renal Division, Department of Medicine, Emory University, Atlanta, Georgia
| | - Ben D Perry
- Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.,Atlanta VA Medical Center, Decatur, Georgia
| | - Jill A Rahnert
- Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.,Atlanta VA Medical Center, Decatur, Georgia
| | - Matthew B Hudson
- Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.,University of Delaware, Department of Kinesiology and Applied Physiology, Newark, Delaware
| | - Bin Zheng
- Renal Division, Department of Medicine, Emory University, Atlanta, Georgia
| | - S Russ Price
- Renal Division, Department of Medicine, Emory University, Atlanta, Georgia.,Atlanta VA Medical Center, Decatur, Georgia.,Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina
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28
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Hansra DM, McIntyre K, Ramdial J, Sacks S, Patrick CS, Cutler J, McIntyre B, Feister K, Miller M, Taylor AK, Farooq F, de Mayolo JA, Ahn E. Evaluation of How Integrative Oncology Services Are Valued between Hematology/Oncology Patients and Hematologists/Oncologists at a Tertiary Care Center. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2018; 2018:8081018. [PMID: 29849727 PMCID: PMC5925032 DOI: 10.1155/2018/8081018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 12/28/2017] [Accepted: 01/04/2018] [Indexed: 11/20/2022]
Abstract
Evidence regarding opinions on integrative modalities by patients and physicians is lacking. Methods. A survey study was conducted assessing how integrative modalities were valued among hematology/oncology patients and hematologists and oncologists at a major tertiary medical center. Results. 1008 patients and 55 physicians were surveyed. With the exception of support groups, patients valued nutrition services, exercise therapy, spiritual/religious counseling, supplement/herbal advice, support groups, music therapy, and other complimentary medicine services significantly more than physicians (P ≤ 0.05). Conclusion. With the exception of support groups, patients value integrative modalities more than physicians. Perhaps with increasing education, awareness, and acceptance by providers and traditional institutions, integrative modalities could be equally valued between patients and providers. It is possible that increased availability and utilization of integrative oncology modalities at tertiary hospital sites could improve patient satisfaction, quality of life, and other clinical endpoints.
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Affiliation(s)
- D. M. Hansra
- Cancer Treatment Centers of America, Atlanta, GA, USA
- Jackson Memorial Hospital, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - K. McIntyre
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - J. Ramdial
- Jackson Memorial Hospital, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - S. Sacks
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - C. S. Patrick
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - J. Cutler
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - B. McIntyre
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - K. Feister
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - M. Miller
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - A. K. Taylor
- Miller School of Medicine, University of Miami, Miami, FL, USA
| | - F. Farooq
- Jackson Memorial Hospital, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | | | - E. Ahn
- Cancer Treatment Centers of America, Atlanta, GA, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
- Miller School of Medicine, University of Miami, Miami, FL, USA
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Eibl G, Cruz-Monserrate Z, Korc M, Petrov MS, Goodarzi MO, Fisher WE, Habtezion A, Lugea A, Pandol SJ, Hart PA, Andersen DK. Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer. J Acad Nutr Diet 2018; 118:555-567. [PMID: 28919082 PMCID: PMC5845842 DOI: 10.1016/j.jand.2017.07.005] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 07/10/2017] [Indexed: 02/06/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.
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Salibay CJ, Rewerska J, Gupta S, Ree N. Primary Carcinosarcoma of the Pancreas With CD10-Positive Sarcoma Component. J Investig Med High Impact Case Rep 2017; 5:2324709617740906. [PMID: 29152519 PMCID: PMC5680943 DOI: 10.1177/2324709617740906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/04/2017] [Accepted: 09/22/2017] [Indexed: 12/14/2022] Open
Abstract
Carcinosarcomas of the pancreas are rare entities with a dismal prognosis. We report a rare case of pancreatic carcinosarcoma in a 49-year-old African American female who underwent a total abdominal hysterectomy with right salpingo-oophorectomy and exploration of the pancreatic mass. The surgery revealed a sclerotic mass in the body and tail of the pancreas that was surgically unresectable, and a pancreatic biopsy confirmed the pathology of pancreatic carcinosarcoma. Histologically, the lesion showed a high-grade spindle cell sarcoma and adjacent moderately differentiated adenocarcinoma. On immunohistochemical examination, the carcinomatous component was positive for epithelial markers, and the sarcomatous component was focally positive for SMA and desmin. In addition, the sarcomatous component showed diffuse immunoreactivity for CD10 with a surrounding myofibroblastic proliferation. Reports have associated expression of CD10 in pancreatic stellate cells with increased tumor aggressiveness. In this article, we report a case of pancreatic carcinosarcoma that shows sarcomatous CD10 immunoexpression with higher Ki67 labeling in the sarcoma than the carcinoma raising the question if the sarcomatous component could be potentiating the aggressiveness of the carcinomatous component.
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Affiliation(s)
- Christine J Salibay
- University of Illinois at Chicago Hospital and Health Sciences System, Chicago, IL, USA
| | - Julia Rewerska
- University of Illinois at Chicago Hospital and Health Sciences System, Chicago, IL, USA
| | - Shweta Gupta
- John H Stroger Jr. Hospital of Cook County, Chicago, IL, USA
| | - Nicholas Ree
- John H Stroger Jr. Hospital of Cook County, Chicago, IL, USA
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31
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Bruggeman AR, Kamal AH, LeBlanc TW, Ma JD, Baracos VE, Roeland EJ. Cancer Cachexia: Beyond Weight Loss. J Oncol Pract 2017; 12:1163-1171. [PMID: 27858548 DOI: 10.1200/jop.2016.016832] [Citation(s) in RCA: 146] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is limited by adverse effects. For the practicing oncologist, early identification and management of cachexia is critical. Oncologists must recognize cachexia beyond weight loss alone, focusing instead on body composition and physical functioning. In fact, becoming emaciated is a late sign of cachexia that characterizes its refractory stage. Given that cachexia is a multifactorial syndrome, it requires early identification and polymodal intervention, including optimal cancer therapy, symptom management, nutrition, exercise, and psychosocial support. Consequently, oncologists have a role in ensuring that these resources are available to their patients. In addition, in light of the promising investigational agents, it remains imperative to refer patients with cachexia to clinical trials so that available options can be expanded to effectively treat this pervasive problem.
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Affiliation(s)
- Andrew R Bruggeman
- University of California at San Diego, San Diego, CA; Duke University Medical Center; and Duke University School of Medicine, Durham, NC; and University of Alberta, Edmonton, Alberta, Canada
| | - Arif H Kamal
- University of California at San Diego, San Diego, CA; Duke University Medical Center; and Duke University School of Medicine, Durham, NC; and University of Alberta, Edmonton, Alberta, Canada
| | - Thomas W LeBlanc
- University of California at San Diego, San Diego, CA; Duke University Medical Center; and Duke University School of Medicine, Durham, NC; and University of Alberta, Edmonton, Alberta, Canada
| | - Joseph D Ma
- University of California at San Diego, San Diego, CA; Duke University Medical Center; and Duke University School of Medicine, Durham, NC; and University of Alberta, Edmonton, Alberta, Canada
| | - Vickie E Baracos
- University of California at San Diego, San Diego, CA; Duke University Medical Center; and Duke University School of Medicine, Durham, NC; and University of Alberta, Edmonton, Alberta, Canada
| | - Eric J Roeland
- University of California at San Diego, San Diego, CA; Duke University Medical Center; and Duke University School of Medicine, Durham, NC; and University of Alberta, Edmonton, Alberta, Canada
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Abstract
Introduction Cachexia is a common complication of many and varied chronic disease processes, yet it has received very little attention as an area of clinical research effort until recently. We sought to survey the contemporary literature on published research into cachexia to define where it is being published and the proportion of output classified into the main types of research output. Methods I searched the PubMed listings under the topic research term "cachexia" and related terms for articles published in the calendar years of 2015 and 2016, regardless of language. Searches were conducted and relevant papers extracted by two observers, and disagreements were resolved by consensus. Results There were 954 publications, 370 of which were review articles or commentaries, 254 clinical observations or non-randomised trials, 246 original basic science reports and only 26 were randomised controlled trials. These articles were published in 478 separate journals but with 36% of them being published in a core set of 23 journals. The H-index of these papers was 25 and there were 147 papers with 10 or more citations. Of the top 100 cited papers, 25% were published in five journals. Of the top cited papers, 48% were review articles, 18% were original basic science, and 7% were randomised clinical trials. Discussion This analysis shows a steady but modest increase in publications concerning cachexia with a strong pipeline of basic science research but still a relative lack of randomised clinical trials, with none exceeding 1000 patients. Research in cachexia is still in its infancy, but the solid basic science effort offers hope that translation into randomised controlled clinical trials may eventually lead to effective therapies for this troubling and complex clinical disease process.
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Ramalho R, Ramalho P, Couto N, Pereira P. Omega-3 therapeutic supplementation in a patient with metastatic adenocarcinoma of the pancreas with muscle mass depletion. Eur J Clin Nutr 2017; 71:795-797. [PMID: 28378854 DOI: 10.1038/ejcn.2017.47] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 02/22/2017] [Accepted: 02/24/2017] [Indexed: 02/07/2023]
Abstract
Pancreatic adenocarcinoma has an extremely poor prognosis. With the best available treatments, the median overall survival duration is still less than 1 year. Most patients develop anorexia and major muscle mass loss that interfere with chemotherapy tolerance and survival. In this paper, we present a case in which these problems were a major concern. A multidisciplinary approach with chemotherapy and close nutritional support permitted better control of the disease and longer survival. We also review the literature on nutritional interventions that show an improvement in quality of life and survival in these patients.
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Affiliation(s)
- R Ramalho
- Instituto Superior de Ciências da Saúde Egas Moniz, Nutrition Consultation, Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
- Centro de Investigação Interdisciplinar Egas Moniz (CiiEM). Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
- Grupo de Estudos em Nutrição Aplicada (GENA)-ISCSEM, Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
| | - P Ramalho
- Instituto Superior de Ciências da Saúde Egas Moniz, Nutrition Consultation, Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
- Grupo de Estudos em Nutrição Aplicada (GENA)-ISCSEM, Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
| | - N Couto
- Champalimaud Foundation, Champalimaud Clinic Centre - Digestive Cancer Unit. Avenida Brasília, Lisboa, Portugal
| | - P Pereira
- Instituto Superior de Ciências da Saúde Egas Moniz, Nutrition Consultation, Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
- Centro de Investigação Interdisciplinar Egas Moniz (CiiEM). Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
- Grupo de Estudos em Nutrição Aplicada (GENA)-ISCSEM, Campus Universitário Quinta da Granja, Monte de Caparica, Portugal
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Chagas TR, Borges DS, de Oliveira PF, Mocellin MC, Barbosa AM, Camargo CQ, Del Moral JÂG, Poli A, Calder PC, Trindade EBSM, Nunes EA. Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial. J Hum Nutr Diet 2017; 30:681-692. [PMID: 28374923 DOI: 10.1111/jhn.12471] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. METHODS Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. RESULTS SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). CONCLUSIONS These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy.
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Affiliation(s)
- T R Chagas
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.,Laboratory of Investigation in Chronic Diseases, Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - D S Borges
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - P F de Oliveira
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - M C Mocellin
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - A M Barbosa
- Laboratory of Investigation in Chronic Diseases, Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.,Multicenter Post-Graduation Program in Physiological Sciences, Department of Physiology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - C Q Camargo
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.,Laboratory of Investigation in Chronic Diseases, Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - J Â G Del Moral
- Ambulatory Care Clinic and Oncologic Center, Professor Polydoro Ernani de São Thiago University Hospital, Florianópolis, Santa Catarina, Brazil
| | - A Poli
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - P C Calder
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, UK
| | - E B S M Trindade
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - E A Nunes
- Graduate Program in Nutrition, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.,Laboratory of Investigation in Chronic Diseases, Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.,Multicenter Post-Graduation Program in Physiological Sciences, Department of Physiology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
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Gong J, Sachdev E, Robbins LA, Lin E, Hendifar AE, Mita MM. Statins and pancreatic cancer. Oncol Lett 2017; 13:1035-1040. [PMID: 28454210 DOI: 10.3892/ol.2017.5572] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 09/22/2016] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer remains among the most lethal cancers, despite ongoing advances in treatment for all stages of the disease. Disease prevention represents another opportunity to improve patient outcome, with metabolic syndrome and its components, such as diabetes, obesity and dyslipidemia, having been recognized as modifiable risk factors for pancreatic cancer. In addition, statins have been shown to potentially reduce pancreatic cancer risk and to improve survival in patients with a combination of metabolic syndrome and pancreatic cancer. Furthermore, preclinical studies have demonstrated that statins exhibit antitumor effects in pancreatic cancer cell lines in vitro and animal models in vivo, in addition to delaying the progression of pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma (PDAC) and inhibiting PDAC formation in conditional K-Ras mutant mice. The mechanisms by which statins produce anticancer effects remain poorly understood, although appear to involve inhibition of the mevalonate/cholesterol synthesis pathway, thus blocking the synthesis of intermediates important for prenylation and activation of the Ras/mitogen-activated protein kinase 1 signaling pathway. Furthermore, statins have been identified to modulate the phosphoinositide 3-kinase/Akt serine/threonine kinase 1 and inflammation signaling pathways, and to alter the expression of genes involved in lipid metabolism, which are important for PDAC growth and proliferation. In addition, statins have been demonstrated to exhibit further antitumor mechanisms in a number of other cancer types, which are beyond the scope of the present review. In the present review, current evidence highlighting the potential of statins as chemopreventive agents in pancreatic cancer is presented, and the antitumor mechanisms of statins elucidated thus far in this disease are discussed.
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Affiliation(s)
- Jun Gong
- Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA
| | - Esha Sachdev
- Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Lori A Robbins
- Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Emily Lin
- Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, USA
| | - Andrew E Hendifar
- Department of Internal Medicine, Division of Medical Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Monica M Mita
- Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Ma YJ, Liu L, Xiao J, Cao BW. Perioperativeω-3 Polyunsaturated Fatty Acid Nutritional Support in Gastrointestinal Cancer Surgical Patients: A Systematic Evaluation. Nutr Cancer 2016; 68:568-76. [DOI: 10.1080/01635581.2016.1158291] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Klek S. Omega-3 Fatty Acids in Modern Parenteral Nutrition: A Review of the Current Evidence. J Clin Med 2016; 5:E34. [PMID: 26959070 PMCID: PMC4810105 DOI: 10.3390/jcm5030034] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Revised: 02/10/2016] [Accepted: 03/01/2016] [Indexed: 12/21/2022] Open
Abstract
Intravenous lipid emulsions are an essential component of parenteral nutrition regimens. Originally employed as an efficient non-glucose energy source to reduce the adverse effects of high glucose intake and provide essential fatty acids, lipid emulsions have assumed a larger therapeutic role due to research demonstrating the effects of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) on key metabolic functions, including inflammatory and immune response, coagulation, and cell signaling. Indeed, emerging evidence suggests that the effects of omega-3 PUFA on inflammation and immune response result in meaningful therapeutic benefits in surgical, cancer, and critically ill patients as well as patients requiring long-term parenteral nutrition. The present review provides an overview of the mechanisms of action through which omega-3 and omega-6 PUFA modulate the immune-inflammatory response and summarizes the current body of evidence regarding the clinical and pharmacoeconomic benefits of intravenous n-3 fatty acid-containing lipid emulsions in patients requiring parenteral nutrition.
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Affiliation(s)
- Stanislaw Klek
- Stanley Dudrick's Memorial Hospital, General Surgery Unit, Skawina 32-050, Poland.
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38
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Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy. J Clin Med 2016; 5:jcm5020015. [PMID: 26821053 PMCID: PMC4773771 DOI: 10.3390/jcm5020015] [Citation(s) in RCA: 196] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 01/15/2016] [Accepted: 01/19/2016] [Indexed: 12/24/2022] Open
Abstract
Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy.
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Ishida J, Konishi M, Saito M, Springer J. Hypermetabolism: should cancer types, pathological stages and races be considered in assessing metabolism and could elevated resting energy expenditure be the therapeutic target in patients with advanced cancer? J Cachexia Sarcopenia Muscle 2015; 6:391-2. [PMID: 26674220 PMCID: PMC4670748 DOI: 10.1002/jcsm.12080] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 09/25/2015] [Indexed: 12/16/2022] Open
Affiliation(s)
- Junichi Ishida
- Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen Göttingen, Germany
| | - Masaaki Konishi
- Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen Göttingen, Germany
| | - Masakazu Saito
- Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen Göttingen, Germany
| | - Jochen Springer
- Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen Göttingen, Germany
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