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Zhang Z, Ma Z, Wang X, Zhou Y, Wu R, Shen Y, Li N, Jia Q, Zhang H, Li W, Zheng W. Specific molecular imaging of BALB/c model mice with Graves' ophthalmopathy based on high expression of insulin-like growth factor 1 receptor. Ann Nucl Med 2025; 39:388-397. [PMID: 39920417 PMCID: PMC11914231 DOI: 10.1007/s12149-024-02013-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/20/2024] [Indexed: 02/09/2025]
Abstract
OBJECTIVE At present, most of the targeted imaging based on insulin-like growth factor 1 receptor (IGF-1R) is for tumor research, and there is no IGF-1R-targeted imaging for Graves' ophthalmopathy(GO). This study aims to develop a peptide probe, 99mTc-ZIGF1R:4551-GGGC, targeting the IGF-1R, and to achieve specific imaging in Graves' disease (GD) animal models exhibiting GO. METHODS 99mTc-ZIGF1R:4551-GGGC probe was synthesized using a direct labeling method and its labeling efficiency assessed via instant thin-layer chromatography (ITLC). Western blot analysis confirmed the overexpression of IGF-1R in malignant melanoma B16F10 cells. Subsequent SPECT/CT whole-body imaging of B16F10 tumor-bearing mice evaluated the probe's targeting accuracy. In addition, a GO model was established using an electroporation immunoassay, followed by serological and histopathological examinations. The GO models then underwent 99mTc-ZIGF1R:4551-GGGC SPECT/CT imaging to assess eye-targeted imaging capabilities. RESULTS The peptide probe exhibited a labeling efficiency exceeding 90%. Both GD and GO models were effectively created via electroporation immunoassay. Imaging results indicated significant accumulation and retention of the peptide probes in the tumors of B16F10 tumor-bearing mice. In the GO models, probe uptake was predominantly observed in retrobulbar tissues, contrasting with primary accumulation in the lungs and gastrointestinal tract in normal mice, where only minimal tracer was observed in retrobulbar tissues. Notably, GO mice demonstrated higher probe uptake and prolonged retention. CONCLUSION This study successfully established GD and GO models, reducing the duration of the immune cycle. Moreover, a peptide probe targeting IGF-1R was synthesized, enabling specific imaging of retrobulbar tissues in GO models.
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Affiliation(s)
- Zhiting Zhang
- Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Chest Hospital, Tianjin, China
| | - Ziyu Ma
- Tianjin Medical University General Hospital, Tianjin, China
| | - Xuan Wang
- Tianjin Medical University General Hospital, Tianjin, China
| | - Yaqian Zhou
- Tianjin Medical University General Hospital, Tianjin, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruixin Wu
- Tianjin Medical University General Hospital, Tianjin, China
- Shanghai Tenth People's Hospital, Shanghai, China
| | - Yiming Shen
- Tianjin Medical University General Hospital, Tianjin, China
| | - Ning Li
- Tianjin Medical University General Hospital, Tianjin, China
| | - Qiang Jia
- Tianjin Medical University General Hospital, Tianjin, China
| | | | - Wei Li
- Tianjin Medical University General Hospital, Tianjin, China.
| | - Wei Zheng
- Tianjin Medical University General Hospital, Tianjin, China.
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Asmaz ED, Tan M, Genç AI, Teker HT, Ceylani T. Rejuvenating the gut: young plasma therapy improves cell proliferation, IGF-I and IGF-IR expression, and immune defense in aged male rats jejunum. Biogerontology 2025; 26:62. [PMID: 39969630 PMCID: PMC11839702 DOI: 10.1007/s10522-025-10204-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 02/11/2025] [Indexed: 02/20/2025]
Abstract
It is well known that aging affects many systems in the body. The digestive system is one of the systems most affected by aging. In our study, we examined the effects of young plasma treatment on cell proliferation, growth factors, immune defense and histological parameters in the jejunum of aged male rats. For this purpose, aged male Sprague Dawley rats (24 months, n = 7) were treated with pooled plasma (0.5 ml/day, intravenously for 30 days) collected from young (5 weeks, n = 51) rats. Aged rats that received young plasma treatment were grouped as the experimental group, while aged rats formed the control group. At the end of the experiment, the jejunums of the groups were collected and histological parameters such as villus height, crypt depth, total mucosal thickness and surface absorption areas were measured and compared. In addition, cell proliferation index and proliferation intensity in the crypt glands of the jejunum were evaluated with proliferating cell nuclear antigen and expressions of growth factors such as insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) expression and effects of immunoglobulin A (IgA), which plays a role in the defense of the digestive system against microorganisms, were examined. In the experimental group, an increase in histological parameters, IGF-R and IGF-IR expression, proliferation density, proliferation index and IgA expression density and IgA cell count were observed compared to the control group. These results suggest that young plasma treatment has a positive effect on the digestive system and may be a potential therapeutic for tissue regeneration.
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Affiliation(s)
- Ender Deniz Asmaz
- Faculty of Medicine, Department of Histology and Embryology, Ankara Medipol University, Ankara, Turkey.
- Department of Electrical&Computer Engineering, Boston University, Biomedical Engineering Graduate Medical Sciences, Boston, MA, 02215, USA.
| | - Murat Tan
- Department of General Surgery, Istanbul Demiroglu Bilim University, Istanbul, Turkey
| | - Aysun Inan Genç
- Faculty of Science, Department of Biology, Kastamonu University, Kastamonu, Turkey
| | - Hikmet Taner Teker
- Faculty of Medicine, Department of Medical Biology and Genetics, Ankara Medipol University, Ankara, Turkey
| | - Taha Ceylani
- Department of Food Processing, Muş Alparslan University, Muş, Turkey.
- Department of Molecular Biology and Genetics, Muş Alparslan University, Muş, Turkey.
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Loktionova MV, Mohammadian M, Choopani R, Kheiri S, Mohammadian-Hafshejani A. Investigating the relationship between insulin use and all-cause mortality, breast cancer mortality, and recurrence risk in diabetic patients with breast cancer: A comprehensive systematic review and meta-analysis. PLoS One 2024; 19:e0314565. [PMID: 39636922 PMCID: PMC11620406 DOI: 10.1371/journal.pone.0314565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 11/12/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND The co-occurrence of breast cancer and diabetes presents complex clinical challenges, as each condition may influence the progression and management of the other, potentially worsening patient outcomes. This study aims to examine the association between insulin use and the risks of all-cause mortality, breast cancer-specific mortality, and recurrence in diabetic patients with breast cancer. METHODS A systematic review and meta-analysis were conducted using studies identified from multiple databases, including Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase. The meta-analysis approach was used to estimate the relative risk (RR) of the relationship between insulin use and the risks of all-cause mortality, breast cancer-specific mortality, and recurrence in diabetic patients with breast cancer. Heterogeneity among studies was assessed using statistical tests such as the Chi-square test, I2, and forest plots. Meta-regression and sensitivity analyses were performed to explore sources of heterogeneity. The quality of the included studies was assessed using the Newcastle-Ottawa Scale checklist. Data were analyzed using Stata version 17 (Stata Corp, College Station, Texas). RESULTS Data from 22 studies conducted between 2002 and 2023, with a total of 159,674 participants, were analyzed. Nineteen studies were rated as high quality, and three as moderate quality. Diabetic patients with breast cancer who received insulin had a 1.65 (95% CI: 1.36-2.02; P < 0.001; I2 = 89.7%) times higher risk of overall mortality compared to those who did not use insulin. Meta-regression revealed that sample size and study quality were significant contributors to heterogeneity (P ≤ 0.10). Furthermore, insulin use was associated with a 1.22 (95% CI: 1.05-1.42; P = 0.009; I2 = 37.9%) times higher risk of breast cancer-specific mortality. For breast cancer recurrence, insulin use was associated with a 1.45 (95% CI: 1.19-1.77; P < 0.001; I2 = 3.4%) times higher risk. Sensitivity analysis confirmed the stability of the results across all outcomes. CONCLUSION This meta-analysis provides strong evidence that insulin use in diabetic patients with breast cancer is associated with increased risks of overall mortality, breast cancer-specific mortality, and recurrence. These findings underscore the need for careful consideration of insulin therapy in this patient population.
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Affiliation(s)
- Marina V. Loktionova
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
| | - Mahdi Mohammadian
- MSc in Epidemiology, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Roya Choopani
- Assistant Professor of Neonatal-Perinatal Medicine, Department of Pediatrics, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Soleiman Kheiri
- Professor of Biostatistics, Department of Epidemiology and Biostatistics, School of Public Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Abdollah Mohammadian-Hafshejani
- Assistant Professor of Epidemiology, Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Liu B, Wang Y. Predictive value of IGF-1/IGFBP-3 ratio for thyroid nodules in type 2 diabetic mellitus. Front Endocrinol (Lausanne) 2024; 15:1444279. [PMID: 39444449 PMCID: PMC11496060 DOI: 10.3389/fendo.2024.1444279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 09/23/2024] [Indexed: 10/25/2024] Open
Abstract
Aims To explore the predictive value of the IGF-1/IGFBP-3 ratio for the presence of thyroid nodules in patients with type 2 diabetes mellitus (T2DM). Methods This observational study prospectively enrolled patients with T2DM at the Second Hospital of Jilin University between May 2021 and January 2022. Thyroid nodule (TN) status was determined by ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of the serum IGF-1/IGFBP-3 molar ratio for TNs. Multivariable logistic regression analysis was conducted to identify risk factors for thyroid nodules in patients with T2DM. Results A total of 122 patients (mean age ± standard deviation: 52.57 ± 11.71 years; 74 males) were enrolled. 37.7% (n=46) of patients did not have TNs, while 62.3% (n=76) had TNs. The duration of diabetes, age, and HDL-C level were significantly higher in the T2DM group with TNs compared to the group without TNs (all P < 0.05). The area under the ROC curve (AUC) for the combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio in predicting TNs in T2DM patients was 0.619 (P < 0.001). Additionally, multivariable logistic regression analysis revealed that the duration of diabetes, age, fasting plasma glucose (FPG), fasting insulin (FINS), thyroid-stimulating hormone (TSH), IGF-1, and IGFBP-3 levels were independent risk factors for thyroid nodules, while the serum IGF-1/IGFBP-3 molar ratio level was an independent protective factor for thyroid nodules in patients with T2DM (all P < 0.05). Conclusion The combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio may have a better predictive value for TNs in T2DM patients than using any single marker alone. The duration of diabetes, age, FPG, FINS, TSH, IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio levels were independently associated with thyroid nodules in patients with T2DM.
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Affiliation(s)
| | - Yanjun Wang
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun, China
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Sasamoto N, Hathaway CA, Townsend MK, Terry KL, Trabert B, Tworoger SS. Prospective Analysis of Circulating Biomarkers and Ovarian Cancer Risk in the UK Biobank. Cancer Epidemiol Biomarkers Prev 2024; 33:1347-1355. [PMID: 39007864 PMCID: PMC11446659 DOI: 10.1158/1055-9965.epi-24-0319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 04/22/2024] [Accepted: 07/11/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND Risk factors have a limited ability to predict individuals at high risk of developing ovarian cancer among average-risk women, highlighting the need for discovery of novel biomarkers. In the UK Biobank, we investigated serum biomarkers commonly measured in clinical laboratory tests and ovarian cancer risk. METHODS We conducted a prospective analysis of 20 serum biomarkers and ovarian cancer risk in 232,037 female UK Biobank participants (including 1,122 incident ovarian cancer cases diagnosed from 2006 to 2020). Multivariable adjusted Cox proportional hazards models were used to examine associations between biomarkers and ovarian cancer risk overall and by histotype. FDR was used to account for multiple testing. RESULTS Overall, higher levels of insulin-like growth factor (IGF)-1 [RRquartile 4 vs. 1 = 0.73; 95% confidence interval (CI), 0.60-0.87; P-trend = 0.002/FDR = 0.04], HbA1c (RRquartile 4 vs. 1 = 0.74; 95% CI, 0.62-0.89; P-trend = 0.002/FDR = 0.04), and alanine aminotransferase (RRquartile 4 vs. 1 = 0.76; 95% CI, 0.63-0.91; P-trend = 0.002/FDR = 0.04) were significantly associated with lower ovarian cancer risk. When stratified by histotype, higher IGF1 levels were associated with lower risk of serous (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.58-0.91; P-trend = 0.01/FDR = 0.20) and clear cell tumors (RRquartile 4 vs. 1 = 0.18; 95% CI, 0.07-0.49; P-trend = 0.001/FDR = 0.02), and higher HbA1c levels were associated with lower risk of serous tumors (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.59-0.90; P-trend = 0.004/FDR = 0.08). CONCLUSIONS We observed that higher levels of circulating IGF1, HbA1c, and alanine aminotransferase were associated with lower ovarian cancer risk. IMPACT These results suggest metabolism of glucose/amino acid and insulin/IGF1 signaling pathway may be contributing to ovarian carcinogenesis. Further research is needed to replicate our findings and elucidate how systemic changes in metabolism impact ovarian carcinogenesis.
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Affiliation(s)
- Naoko Sasamoto
- Department of Obstetrics and Gynecology, Brigham and Women’s Hospital and Harvard Medical School, Boston Massachusetts
| | | | - Mary K. Townsend
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida
- Division of Oncological Sciences and the Knight Cancer Institute, Oregon Health and Science University School of Medicine, Portland, Oregon
| | - Kathryn L. Terry
- Department of Obstetrics and Gynecology, Brigham and Women’s Hospital and Harvard Medical School, Boston Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health
| | - Britton Trabert
- Department of Obstetrics and Gynecology, University of Utah and Huntsman Cancer Institute
| | - Shelley S. Tworoger
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida
- Division of Oncological Sciences and the Knight Cancer Institute, Oregon Health and Science University School of Medicine, Portland, Oregon
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Flaibam B, da Silva MF, de Mélo AHF, Carvalho PH, Galland F, Pacheco MTB, Goldbeck R. Non-animal protein hydrolysates from agro-industrial wastes: A prospect of alternative inputs for cultured meat. Food Chem 2024; 443:138515. [PMID: 38277934 DOI: 10.1016/j.foodchem.2024.138515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 01/17/2024] [Accepted: 01/18/2024] [Indexed: 01/28/2024]
Abstract
In light of the growing demand for alternative protein sources, laboratory-grown meat has been proposed as a potential solution to the challenges posed by conventional meat production. Cultured meat does not require animal slaughter and uses sustainable production methods, contributing to animal welfare, human health, and environmental sustainability. However, some challenges still need to be addressed in cultured meat production, such as the use of fetal bovine serum for medium supplementation. This ingredient has limited availability, increases production costs, and raises ethical concerns. This review explores the potential of non-animal protein hydrolysates derived from agro-industrial wastes as substitutes for critical components of fetal bovine serum in cultured meat production. Despite the lack of standardization of hydrolysate composition, the potential benefits of this alternative protein source may outweigh its disadvantages. Future research holds promise for increasing the accessibility of cultured meat.
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Affiliation(s)
- Bárbara Flaibam
- Bioprocess and Metabolic Engineering Laboratory, Department of Food Engineering and Technology, School of Food Engineering, University of Campinas (UNICAMP), Rua Monteiro Lobato, 80, Campinas, SP 13083-862, Brazil
| | - Marcos F da Silva
- Bioprocess and Metabolic Engineering Laboratory, Department of Food Engineering and Technology, School of Food Engineering, University of Campinas (UNICAMP), Rua Monteiro Lobato, 80, Campinas, SP 13083-862, Brazil
| | - Allan H Félix de Mélo
- Bioprocess and Metabolic Engineering Laboratory, Department of Food Engineering and Technology, School of Food Engineering, University of Campinas (UNICAMP), Rua Monteiro Lobato, 80, Campinas, SP 13083-862, Brazil
| | - Priscila Hoffmann Carvalho
- Bioprocess and Metabolic Engineering Laboratory, Department of Food Engineering and Technology, School of Food Engineering, University of Campinas (UNICAMP), Rua Monteiro Lobato, 80, Campinas, SP 13083-862, Brazil
| | - Fabiana Galland
- Institute of Food Technology (ITAL), Avenida Brasil, 2880, PO Box 139, Campinas, SP 13070-178, Brazil
| | | | - Rosana Goldbeck
- Bioprocess and Metabolic Engineering Laboratory, Department of Food Engineering and Technology, School of Food Engineering, University of Campinas (UNICAMP), Rua Monteiro Lobato, 80, Campinas, SP 13083-862, Brazil.
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Fu S, Ke H, Yuan H, Xu H, Chen W, Zhao L. Dual role of pregnancy in breast cancer risk. Gen Comp Endocrinol 2024; 352:114501. [PMID: 38527592 DOI: 10.1016/j.ygcen.2024.114501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/15/2024] [Accepted: 03/20/2024] [Indexed: 03/27/2024]
Abstract
Reproductive history is one of the strongest risk factors for breast cancer in women. Pregnancy can promote short-term breast cancer risk, but also reduce a woman's lifetime risk of breast cancer. Changes in hormone levels before and after pregnancy are one of the key factors in breast cancer risk. This article summarizes the changes in hormone levels before and after pregnancy, and the roles of hormones in mammary gland development and breast cancer progression. Other factors, such as changes in breast morphology and mammary gland differentiation, changes in the proportion of mammary stem cells (MaSCs), changes in the immune and inflammatory environment, and changes in lactation before and after pregnancy, also play key roles in the occurrence and development of breast cancer. This review discusses the dual effects and the potential mechanisms of pregnancy on breast cancer risk from the above aspects, which is helpful to understand the complexity of female breast cancer occurrence.
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Affiliation(s)
- Shiting Fu
- Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang 330031, China
| | - Hao Ke
- Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang 330031, China
| | | | - Huaimeng Xu
- Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang 330031, China
| | - Wenyan Chen
- Department of Medical Oncology, The Third Hospital of Nanchang, Nanchang 330009, China
| | - Limin Zhao
- Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang 330031, China.
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Vitale E, Rizzo A, Santa K, Jirillo E. Associations between "Cancer Risk", "Inflammation" and "Metabolic Syndrome": A Scoping Review. BIOLOGY 2024; 13:352. [PMID: 38785834 PMCID: PMC11117847 DOI: 10.3390/biology13050352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/08/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Individuals with metabolic syndrome exhibit simultaneously pro-thrombotic and pro-inflammatory conditions which more probably can lead to cardiovascular diseases progression, type 2 diabetes mellitus, and some types of cancer. The present scoping review is aimed at highlighting the association between cancer risk, inflammation, and metabolic syndrome. METHODS A search strategy was performed, mixing keywords and MeSH terms, such as "Cancer Risk", "Inflammation", "Metabolic Syndrome", "Oncogenesis", and "Oxidative Stress", and matching them through Boolean operators. A total of 20 manuscripts were screened for the present study. Among the selected papers, we identified some associations with breast cancer, colorectal cancer, esophageal adenocarcinoma, hepatocellular carcinoma (HCC), and cancer in general. CONCLUSIONS Cancer and its related progression may also depend also on a latent chronic inflammatory condition associated with other concomitant conditions, including type 2 diabetes mellitus, metabolic syndrome, and obesity. Therefore, prevention may potentially help individuals to protect themselves from cancer.
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Affiliation(s)
- Elsa Vitale
- Scientific Directorate, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Alessandro Rizzo
- Medical Oncology, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy;
| | - Kazuki Santa
- Faculty of Medical Science, Juntendo University, 6-8-1 Hinode, Urayasu 279-0013, Chiba, Japan;
| | - Emilio Jirillo
- Scuola di Medicina, University of Bari, 70121 Bari, Italy;
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Wang H, Ruan S, Wu Z, Yan Q, Chen Y, Cui J, Zhang Z, Huang S, Hou B, Zhang C. Prognostic significance of glucose-lipid metabolic index in pancreatic cancer patients with diabetes mellitus. Cancer Med 2024; 13:e7108. [PMID: 38523554 PMCID: PMC10961598 DOI: 10.1002/cam4.7108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 12/22/2023] [Accepted: 03/04/2024] [Indexed: 03/26/2024] Open
Abstract
BACKGROUND The incidence of pancreatic cancer (PC) is higher in diabetic patients due to disturbances in glucose and lipid metabolism caused by insulin resistance (IR). However, the effect of diabetes as well as IR on the prognosis of PC patients remains inconclusive. Our study aims to assess the impact of IR on the prognosis of PC patients with diabetes. METHODS We conducted a retrospective analysis of 172 PC patients with diabetes in our institute from 2015 to 2021. Prognostic assessment was performed using univariate/multifactorial analysis and survival analysis. The predictive efficacy of metabolic indices was compared using receiver operator characteristic (ROC) curve analysis. RESULTS One hundred twenty-one of 172 patients died during follow-up, with a median follow-up of 477 days and a median overall survival (OS) of 270 days. Survival analysis showed a significant difference in OS by IR related parameters, which were triglyceride-glucose index (TyG), triglyceride-glucose index-body mass index (TyG-BMI), and triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c). The ROC curve indicated that TyG, TyG-BMI, and TG/HDL-c had prognostic efficacy for PC with diabetes. We next optimized TyG-BMI and obtained a new parameter, namely glucose-lipid metabolism index (GLMI), and the patients were classified into GLMI low group and high group based on the calculated cutoff value. The GLMI high group had higher TyG, TyG-BMI, TyG/HDL-c, BMI, TG, total cholesterol (TC), TC/HDL-c, fasting plasma glucose, CA199, and more advanced tumor stage compared to low group. Univariate and multivariate analyses showed that GLMI was an independent prognostic factor. Furthermore, the patients of GLMI high group had worse OS compared to low group and the ROC curves showed GLMI had better predictive ability than TyG and TyG-BMI. CONCLUSIONS IR is associated with the outcome of PC patients with diabetes and higher level of IR indicates worse prognosis. GLMI has a good predictive value for PC with diabetes.
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Affiliation(s)
- Hailiang Wang
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- Department of Hepatobiliary SurgeryWeihai Central Hospital, Qingdao UniversityWeihaiChina
- The Second School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Shiye Ruan
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- The Second School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Zelong Wu
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- The Second School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Qian Yan
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- School of Medicine South China University of TechnologyGuangzhouChina
| | - Yubin Chen
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- School of Medicine South China University of TechnologyGuangzhouChina
| | - Jinwei Cui
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- School of Medicine South China University of TechnologyGuangzhouChina
| | - Zhongyan Zhang
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- The Second School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Shanzhou Huang
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- The Second School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
- School of Medicine South China University of TechnologyGuangzhouChina
| | - Baohua Hou
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- The Second School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
- School of Medicine South China University of TechnologyGuangzhouChina
- Department of General SurgeryHeyuan People's HospitalHeyuanChina
| | - Chuanzhao Zhang
- Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina
- The Second School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
- School of Medicine South China University of TechnologyGuangzhouChina
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Behrooz AB, Cordani M, Fiore A, Donadelli M, Gordon JW, Klionsky DJ, Ghavami S. The obesity-autophagy-cancer axis: Mechanistic insights and therapeutic perspectives. Semin Cancer Biol 2024; 99:24-44. [PMID: 38309540 DOI: 10.1016/j.semcancer.2024.01.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 01/19/2024] [Accepted: 01/29/2024] [Indexed: 02/05/2024]
Abstract
Autophagy, a self-degradative process vital for cellular homeostasis, plays a significant role in adipose tissue metabolism and tumorigenesis. This review aims to elucidate the complex interplay between autophagy, obesity, and cancer development, with a specific emphasis on how obesity-driven changes affect the regulation of autophagy and subsequent implications for cancer risk. The burgeoning epidemic of obesity underscores the relevance of this research, particularly given the established links between obesity, autophagy, and various cancers. Our exploration delves into hormonal influence, notably INS (insulin) and LEP (leptin), on obesity and autophagy interactions. Further, we draw attention to the latest findings on molecular factors linking obesity to cancer, including hormonal changes, altered metabolism, and secretory autophagy. We posit that targeting autophagy modulation may offer a potent therapeutic approach for obesity-associated cancer, pointing to promising advancements in nanocarrier-based targeted therapies for autophagy modulation. However, we also recognize the challenges inherent to these approaches, particularly concerning their precision, control, and the dual roles autophagy can play in cancer. Future research directions include identifying novel biomarkers, refining targeted therapies, and harmonizing these approaches with precision medicine principles, thereby contributing to a more personalized, effective treatment paradigm for obesity-mediated cancer.
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Affiliation(s)
- Amir Barzegar Behrooz
- Department of Human Anatomy and Cell Science, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada; Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Marco Cordani
- Department of Biochemistry and Molecular Biology, School of Biology, Complutense University, Madrid, Spain; Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain
| | - Alessandra Fiore
- Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Verona, Italy
| | - Massimo Donadelli
- Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Verona, Italy
| | - Joseph W Gordon
- Department of Human Anatomy and Cell Science, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada; Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada
| | - Daniel J Klionsky
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
| | - Saeid Ghavami
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA; Faculty of Medicine in Zabrze, University of Technology in Katowice, 41-800 Zabrze, Poland; Research Institute of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, Manitoba, Canada; Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
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11
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Nimptsch K, Aydin EE, Chavarria RFR, Janke J, Poy MN, Oxvig C, Steinbrecher A, Pischon T. Pregnancy associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) but not PAPP-A are associated with circulating total IGF-1 in a human adult population. Sci Rep 2024; 14:1770. [PMID: 38245583 PMCID: PMC10799854 DOI: 10.1038/s41598-024-52074-8] [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: 07/05/2023] [Accepted: 01/12/2024] [Indexed: 01/22/2024] Open
Abstract
The pappalysins pregnancy associated plasma protein-A (PAPP-A) and -A2 (PAPP-A2) act as proteinases of insulin-like growth factor-1 (IGF-1) binding proteins, while stanniocalcin-2 (STC2) was identified as a pappalysin inhibitor. While there is some evidence from studies in children and adolescents, it is unclear whether these molecules are related to concentrations of IGF-1 and its binding proteins in adults. We investigated cross-sectionally the association of circulating PAPP-A, PAPP-A2 and STC2 with IGF-1 and its binding proteins (IGFBPs) in 394 adult pretest participants (20-69 years) of the German National Cohort Berlin North study center. Plasma PAPP-A, PAPP-A2, total and free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-5 and STC2 were measured by ELISAs. The associations of PAPP-A, PAPP-A2 and STC2 with IGF-1 or IGFBPs were investigated using multivariable linear regression analyses adjusting for age, sex, body mass index and pretest phase. We observed significant inverse associations of PAPP-A2 (difference in concentrations per 0.5 ng/mL higher PAPP-A2 levels) with total IGF-1 (- 4.3 ng/mL; 95% CI - 7.0; - 1.6), the IGF-1:IGFBP-3 molar ratio (- 0.34%; 95%-CI - 0.59; - 0.09), but not free IGF-1 and a positive association with IGFBP-2 (11.9 ng/mL; 95% CI 5.0; 18.8). PAPP-A was not related to total or free IGF-1, but positively associated with IGFBP-5. STC2 was inversely related to total IGF-1, IGFBP-2 and IGFBP-3 and positively to IGFBP-1. This first investigation of these associations in a general adult population supports the hypothesis that PAPP-A2 as well as STC2 play a role for IGF-1 and its binding proteins, especially for total IGF-1. The role of PAPP-A2 and STC2 for health and disease in adults warrants further investigation.
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Affiliation(s)
- Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
| | - Elif Ece Aydin
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Rafael Francisco Rios Chavarria
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Core Facility Biobank, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Matthew N Poy
- John Hopkins University, All Children's Hospital, St. Petersburg, FL, USA
| | - Claus Oxvig
- Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
| | - Astrid Steinbrecher
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Core Facility Biobank, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
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12
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Qiu X, Lu R, He Q, Chen S, Huang C, Lin D. Metabolic signatures and potential biomarkers for the diagnosis and treatment of colon cancer cachexia. Acta Biochim Biophys Sin (Shanghai) 2023; 55:1913-1924. [PMID: 37705348 PMCID: PMC11294056 DOI: 10.3724/abbs.2023151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 06/29/2023] [Indexed: 09/15/2023] Open
Abstract
Cancer cachexia (CAC) is a debilitating condition that often arises from noncachexia cancer (NCAC), with distinct metabolic characteristics and medical treatments. However, the metabolic changes and underlying molecular mechanisms during cachexia progression remain poorly understood. Understanding the progression of CAC is crucial for developing diagnostic approaches to distinguish between CAC and NCAC stages, facilitating appropriate treatment for cancer patients. In this study, we establish a mouse model of colon CAC and categorize the mice into three groups: CAC, NCAC and normal control (NOR). By performing nuclear magnetic resonance (NMR)-based metabolomic profiling on mouse sera, we elucidate the metabolic properties of these groups. Our findings unveil significant differences in the metabolic profiles among the CAC, NCAC and NOR groups, highlighting significant impairments in energy metabolism and amino acid metabolism during cachexia progression. Additionally, we observe the elevated serum levels of lysine and acetate during the transition from the NCAC to CAC stages. Using multivariate ROC analysis, we identify lysine and acetate as potential biomarkers for distinguishing between CAC and NCAC stages. These biomarkers hold promise for the diagnosis of CAC from noncachexia cancer. Our study provides novel insights into the metabolic mechanisms underlying cachexia progression and offers valuable avenues for the diagnosis and treatment of CAC in clinical settings.
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Affiliation(s)
- Xu Qiu
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Ruohan Lu
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Qiqing He
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Shu Chen
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
| | - Caihua Huang
- Research and Communication Center of Exercise and HealthXiamen University of TechnologyXiamen361005China
| | - Donghai Lin
- Key Laboratory for Chemical Biology of Fujian ProvinceMOE Key Laboratory of Spectrochemical Analysis and InstrumentationCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China
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13
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Liu W, Xia J, Du Q, Wang J, Mei T, Qin T. Clinico-pathological characteristics of IGFR1 and VEGF-A co-expression in early and locally advanced-stage lung adenocarcinoma. J Cancer Res Clin Oncol 2023; 149:16365-16376. [PMID: 37702808 DOI: 10.1007/s00432-023-05371-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 08/29/2023] [Indexed: 09/14/2023]
Abstract
BACKGROUND Although targeted therapies and immunotherapy have achieved significant clinical benefits in patients with certain pathological types of lung cancer. However, prognosis for patients with lung adenocarcinoma still remains unsatisfactory. It is of extremely importance to find ideal prognostic indicators to predict the prognosis of lung adenocarcinoma patients, especially for patients with early and locally advanced-stage lung adenocarcinoma. The purpose of this study is to elucidate the significance of Insulin-like growth factor receptor 1 (IGFR1) and Vascular endothelial growth factor A (VEGF-A) expression in predicting progression-free survival (PFS) and overall survival (OS) in patients with early and locally advanced-stage lung adenocarcinoma. METHODS In this study, IGFR1 and VEGF-A expression on 119 specimens of patients early and locally advanced-stage lung adenocarcinoma were analyzed by immunohistochemistry with an H-score system. RESULTS Both high IGFR1 expression and VEGF-A expression patients were resulted in 59 (49.6%) separately. The numbers and proportions of IGFR1-&VEGF-A- subgroup, IGFR1-&VEGF-A+ subgroup, IGFR1+&VEGF-A- subgroup and IGFR1+&VEGF-A+ subgroup are 23 (19.3%), 37 (31.1%), 37 (31.1%) and 22 (18.5%) respectively. High IGFR1 expression was significantly associated with both poor PFS and OS of all patients in a univariate analysis. Multivariable analysis showed that patients with IGFR1+&VEGF-A+ expression exhibited a worst PFS and OS in the subgroup of lung adenocarcinoma patients with EGFR mutation. CONCLUSIONS These results suggest that IGFR1+&VEGF-A+ is expected to be a disadvantageous factor for prognosis in the subgroup of EGFR mutation in patients with early and locally advanced-stage lung adenocarcinoma. What's more, this study may provide the theoretical possibility to screen optimal population for a combination therapy with anti-VEGF and anti-IGFR1 in patients with early and locally advanced-stage lung adenocarcinoma.
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Affiliation(s)
- Wenting Liu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Junling Xia
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Tianjin Cancer Hospital Airport Hospital, Tianjin, People's Republic of China
| | - Qingwu Du
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Jingya Wang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Ting Mei
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China
- Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
- Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Tingting Qin
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China.
- Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.
- Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China.
- Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People's Republic of China.
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14
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Sharma N, Dhingra R. Clinical potentials of metformin in cancer therapy. JOURNAL OF DIABETOLOGY 2023; 14:186-192. [DOI: 10.4103/jod.jod_84_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 09/28/2023] [Indexed: 01/05/2025] Open
Abstract
Abstract
Diabetes is a prevalent metabolic disorder that results in several comorbidities including cancer. Cancer becomes the most severe complication of diabetes patients. Growing evidence proved that impaired glucose homeostasis is an independent risk factor for the occurrence of various types of cancers including liver, pancreatic, gastric (stomach), colorectal, kidney, and breast cancers, and influences cancer prognosis. Diabetes mellitus and cancer have a bidirectional relationship, thus there is a need to look for drugs that can be beneficial in treating both diseases. Therefore, more research is focusing on evaluating the role of antihyperglycemic agents in the treatment of various types of cancers. Metformin, an FDA-approved first-line antihyperglycemic agent can be used as a monotherapy or as an adjuvant to chemotherapeutic agents in the treatment of various types of cancer. However, the exact mechanism of metformin as an anticancer agent is still unknown, the majority of the described putative mechanisms focus on promoting the activity of the AMP-activated protein kinase (AMPK) pathway. This review article thus gives insights into the prognosis of cancer in diabetes patients and aims to explore the possible mechanism of action of metformin in the prevention and treatment of cancer.
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Affiliation(s)
- Nidhi Sharma
- Department of Pharmacy, School of Medical and Allied Sciences, G.D. Goenka University, Sohna, Haryana, India
| | - Richa Dhingra
- Department of Pharmacy, School of Medical and Allied Sciences, G.D. Goenka University, Sohna, Haryana, India
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15
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Chung GE, Yu SJ, Yoo J, Cho Y, Lee K, Shin DW, Kim YJ, Yoon J, Han K, Cho EJ. Differential risk of 23 site-specific incident cancers and cancer-related mortality among patients with metabolic dysfunction-associated fatty liver disease: a population-based cohort study with 9.7 million Korean subjects. Cancer Commun (Lond) 2023; 43:863-876. [PMID: 37337385 PMCID: PMC10397567 DOI: 10.1002/cac2.12454] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 04/30/2023] [Accepted: 06/05/2023] [Indexed: 06/21/2023] Open
Abstract
INTRODUCTION Although an association between metabolic dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all- and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease. METHODS Using the Korean National Health Insurance Service database, we stratified the participants into three groups: (1) single-etiology MAFLD (S-MAFLD) or MAFLD of pure metabolic origin; (2) mixed-etiology MAFLD (M-MAFLD) or MAFLD with additional etiological factor(s) (i.e., concomitant liver diseases and/or heavy alcohol consumption); and (3) non-MAFLD. Hepatic steatosis and fibrosis were defined using the fatty liver index and the BARD score, respectively. Cox proportional hazards regression was performed to estimate the risk of cancer events. RESULTS Among the 9,718,182 participants, the prevalence of S-MAFLD and M-MAFLD was 29.2% and 6.7%, respectively. During the median 8.3 years of follow-up, 510,330 (5.3%) individuals were newly diagnosed with cancer, and 122,774 (1.3%) cancer-related deaths occurred among the entire cohort. Compared with the non-MAFLD group, the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group (incidence, adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02-1.04; mortality, aHR = 1.06; 95% CI: 1.04-1.08) and highest among patients with M-MAFLD group (incidence, aHR = 1.31; 95% CI: 1.29-1.32; mortality, aHR = 1.45; 95% CI: 1.42-1.48, respectively). The M-MAFLD with fibrosis group (BARD score ≥ 2) showed the highest relative risk of all-cancer incidence (aHR = 1.38, 95% CI = 1.36-1.39), followed by the M-MAFLD without fibrosis group (aHR = 1.09, 95% CI = 1.06-1.11). Similar trends were observed for cancer-related mortality. CONCLUSIONS MAFLD classification, by applying additional etiologies other than pure metabolic origin, can be used to identify a subgroup of patients with poor cancer-related outcomes.
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Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine and Healthcare Research InstituteSeoul National University Hospital Healthcare System Gangnam CenterSeoulRepublic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
| | - Jeong‐Ju Yoo
- Department of Gastroenterology and HepatologySoonchunhyang University Bucheon HospitalBucheonGyeonggi‐doRepublic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary CancerNational Cancer CenterGoyangGyeonggi‐doRepublic of Korea
| | - Kyu‐na Lee
- Department of Biomedicine & Health ScienceCatholic University of KoreaSeoulRepublic of Korea
| | - Dong Wook Shin
- Department of Family Medicine/ Supportive care centerSamsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
- Department of Clinical Research Design and Evaluation/Department of Digital HealthSamsung Advanced Institute for Health ScienceSeoulRepublic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
| | - Jung‐Hwan Yoon
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial ScienceSoongsil UniversitySeoulRepublic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
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Li Z, Shen G, Shi M, Zheng Y, Guan Y, Xin Y, Wang M, Zhao F, Ren D, Zhao J. Association between high body mass index and prognosis of patients with early-stage breast cancer: A systematic review and meta-analysis. CANCER PATHOGENESIS AND THERAPY 2023; 1:205-215. [PMID: 38327841 PMCID: PMC10846319 DOI: 10.1016/j.cpt.2023.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 03/10/2023] [Accepted: 03/28/2023] [Indexed: 02/09/2024]
Abstract
Background A high body mass index (BMI) can indicate overweight or obesity and is a crucial risk factor for breast cancer survivors. However, the association between high BMI and prognosis in early-stage breast cancer (EBC) remains unclear. We aimed to assess the effects of high BMI on the prognosis of patients with EBC. Methods The PubMed, Embase, and Cochrane Library databases and proceedings of major oncological conferences related to the effects of BMI on the prognosis of breast cancer were searched up to November 2021. Fixed- and random-effects models were used for meta-analyses. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were extracted from the included literature. Results Twenty retrospective cohort studies with 33,836 patients with EBC were included. Overweight patients had worse DFS (HR: 1.16, 95% CI: 1.05-1.27, P = 0.002) and OS (HR: 1.20; 95% CI: 1.09-1.33, P < 0.001). Obesity also had adverse effects on DFS (HR: 1.17, 95% CI: 1.07-1.29, P = 0.001) and OS (HR: 1.30, 95% CI: 1.17-1.45, P < 0.001). Likewise, patients with high BMI had worse DFS (HR: 1.16, 95% CI: 1.08-1.26, P < 0.001) and OS (HR: 1.25, 95% CI: 1.14-1.39, P < 0.001). In subgroup analyses, overweight had adverse effects on DFS (HR: 1.11, 95% CI: 1.04-1.18, P = 0.001) and OS (HR: 1.18, 95% CI: 1.11-1.26, P < 0.001) in multivariate analyses, whereas the relationship that overweight had negative effects on DFS (HR: 1.21, 95% CI: 0.99-1.48, P = 0.058) and OS (HR: 1.39, 95% CI: 0.92-2.10, P = 0.123) was not statistically significant in univariate analysis. By contrast, obesity had adverse effects on DFS (HR: 1.21, 95% CI: 1.06-1.38, P = 0.004 and HR: 1.14, 95% CI: 1.08-1.22, P < 0.001) and OS (HR: 1.33, 95% CI: 1.15-1.54, P < 0.001 and HR: 1.23, 95% CI: 1.15-1.31, P < 0.001) in univariate and multivariate analyses, respectively. Conclusions Compared with normal weight, increased body weight (overweight, obesity, and high BMI) led to worse DFS and OS in patients with EBC. Once validated, these results should be considered in the development of prevention programs.
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Affiliation(s)
| | | | | | - Yonghui Zheng
- Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qinghai University and the Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, China
| | - Yumei Guan
- Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qinghai University and the Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, China
| | - Yuanfang Xin
- Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qinghai University and the Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, China
| | - Miaozhou Wang
- Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qinghai University and the Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, China
| | - Fuxing Zhao
- Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qinghai University and the Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, China
| | - Dengfeng Ren
- Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qinghai University and the Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, China
| | - Jiuda Zhao
- Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qinghai University and the Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, China
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Hord TK, Tanner AR, Kennedy VC, Lynch CS, Winger QA, Rozance PJ, Anthony RV. Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis. Life (Basel) 2023; 13:1261. [PMID: 37374044 PMCID: PMC10302269 DOI: 10.3390/life13061261] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/19/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
While fetal growth is dependent on many factors, optimal placental function is a prerequisite for a normal pregnancy outcome. The majority of fetal growth-restricted (FGR) pregnancies result from placental insufficiency (PI). The insulin-like growth factors (IGF1 and IGF2) stimulate fetal growth and placental development and function. Previously, we demonstrated that in vivo RNA interference (RNAi) of the placental hormone, chorionic somatomammotropin (CSH), resulted in two phenotypes. One phenotype exhibits significant placental and fetal growth restriction (PI-FGR), impaired placental nutrient transport, and significant reductions in umbilical insulin and IGF1. The other phenotype does not exhibit statistically significant changes in placental or fetal growth (non-FGR). It was our objective to further characterize these two phenotypes by determining the impact of CSH RNAi on the placental (maternal caruncle and fetal cotyledon) expression of the IGF axis. The trophectoderm of hatched blastocysts (9 days of gestation, dGA) were infected with a lentivirus expressing either a non-targeting sequence (NTS RNAi) control or CSH-specific shRNA (CSH RNAi) prior to embryo transfer into synchronized recipient ewes. At ≈125 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies. Nutrient uptakes were determined, and tissues were harvested at necropsy. In both CSH RNAi non-FGR and PI-FGR pregnancies, uterine blood flow was significantly reduced (p ≤ 0.05), while umbilical blood flow (p ≤ 0.01), both uterine and umbilical glucose and oxygen uptakes (p ≤ 0.05), and umbilical concentrations of insulin and IGF1 (p ≤ 0.05) were reduced in CSH RNAi PI-FGR pregnancies. Fetal cotyledon IGF1 mRNA concentration was reduced (p ≤ 0.05) in CSH RNAi PI-FGR pregnancies, whereas neither IGF1 nor IGF2 mRNA concentrations were impacted in the maternal caruncles, and either placental tissue in the non-FGR pregnancies. Fetal cotyledon IGF1R and IGF2R mRNA concentrations were not impacted for either phenotype, yet IGF2R was increased (p ≤ 0.01) in the maternal caruncles of CSH RNAi PI-FGR pregnancies. For the IGF binding proteins (IGFBP1, IGFBP2, IGFBP3), only IGFBP2 mRNA concentrations were impacted, with elevated IGFBP2 mRNA in both the fetal cotyledon (p ≤ 0.01) and maternal caruncle (p = 0.08) of CSH RNAi non-FGR pregnancies. These data support the importance of IGF1 in placental growth and function but may also implicate IGFBP2 in salvaging placental growth in non-FGR pregnancies.
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Affiliation(s)
- Taylor K. Hord
- College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA
| | - Amelia R. Tanner
- College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA
| | - Victoria C. Kennedy
- College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA
| | - Cameron S. Lynch
- College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA
| | - Quinton A. Winger
- College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA
| | - Paul J. Rozance
- Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Russell V. Anthony
- College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA
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Zhao JQ, Ma QP, Wei YF, Zheng G, Zou BJ, Du ZD, Gao S, Yan S, Qin X, Gong TT, Zhao YH, Wu QJ. Nutrients-Rich Food Index Scores and the Overall Survival of Ovarian Cancer Patients: Results from the Ovarian Cancer Follow-Up Study, a Prospective Cohort Study. Nutrients 2023; 15:nu15030717. [PMID: 36771422 PMCID: PMC9920592 DOI: 10.3390/nu15030717] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/27/2023] [Accepted: 01/27/2023] [Indexed: 02/02/2023] Open
Abstract
Background: The nutrients-rich food (NRF) index provides a score of diet quality. Although high diet quality is associated with survival of ovarian cancer (OC), the associations between NRF index scores and OC survival remain unevaluated. Methods: The prospective cohort study enrolled 703 women with newly diagnosed epithelial OC to assess the correlations between NRF index scores and overall survival (OS) in OC patients. Dietary consumption was evaluated through a food frequency questionnaire and diet quality was calculated based on NRF index scores, including three limited nutrients and six (NRF6.3), nine (NRF9.3), or eleven (NRF11.3) benefit nutrients. All-cause deaths were ascertained through medical records combined with active follow-up. Immunohistochemistry (IHC) analyses were conducted to evaluate the expression of IHC indicators (including Estrogen Receptor, Progesterone Receptor, p53, Vimentin, and Wilms' tumor 1), which were identified by two independent pathologists. The Cox proportional hazards regression models were applied for estimating the hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, we performed the penalized cubic splines model to assess the curvilinear associations of NRF index scores with OC survival. Results: During the median follow-up of 37.17 (interquartile: 24.73-50.17) months, 130 deaths were documented. Compared to the lowest tertiles, the highest tertile of index scores [NRF9.3 (HR = 0.63, 95% CI = 0.41-0.95), NRF6.3 (HR = 0.59, 95% CI = 0.39-0.89), and NRF11.3 (HR = 0.57, 95% CI = 0.38-0.87)] were correlated to better OS, showing an obvious linear trend (all p trend < 0.05). Interestingly, the curvilinear association between the NRF6.3 index score and OC survival was also observed (p non-linear < 0.05). Subgroup analyses, stratified by clinical, demographic, and IHC features, showed similar risk associations as the unstratified results. Furthermore, there were significant multiplicative interactions between NRF index scores and Progestogen Receptors as well as Wilms' tumor 1 expressions (all p interaction < 0.05). Conclusions: Higher NRF index scores were associated with an improved OS in OC patients.
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Affiliation(s)
- Jun-Qi Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Qi-Peng Ma
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Gang Zheng
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Bing-Jie Zou
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Zong-Da Du
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Shi Yan
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Xue Qin
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Yu-Hong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Correspondence: (Y.-H.Z.); (Q.-J.W.); Tel.: +86-24-96615-13652 (Y.-H.Z.); +86-24-96615-13652 (Q.-J.W.)
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China
- Correspondence: (Y.-H.Z.); (Q.-J.W.); Tel.: +86-24-96615-13652 (Y.-H.Z.); +86-24-96615-13652 (Q.-J.W.)
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Palui R, Sridharan K, Kamalanathan S, Sahoo J, Naik D. Growth hormone and gastrointestinal malignancy: An intriguing link. World J Gastrointest Pathophysiol 2023; 14:1-11. [PMID: 36743656 PMCID: PMC9896462 DOI: 10.4291/wjgp.v14.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/25/2022] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Growth hormone (GH) excess is associated with several systemic complications, one of which is the increased risk of neoplastic processes particularly of the gastrointestinal (GI) tract. Among the GI neoplasms, the most reported association is with benign and malignant neoplasms of the colon. In the majority of published literature, an increased incidence of GI neoplasms, both colonic adenomas as well as colorectal carcinoma is reported. However, the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls. Many studies have reported an association of colorectal neoplasms with GH levels. Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1 (IGF-1) signaling. Both GH and IGF-1 have proliferative, anti-apoptotic, and angiogenic effects on the systemic tissues leading to cellular proliferation. Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel, altered bile acids, deranged local immune response, shared genetic susceptibility factors and hyperinsulinemia. In view of the increased risk association, most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy. Recommendations for further follow-up colonoscopy differ but broadly, the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess. Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy, most cohort studies do not show an increased risk.
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Affiliation(s)
- Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur 713212, West Bengal, India
| | - Kalyani Sridharan
- Department of Endocrinology, All India Institute of Medical Science, Rishikesh 249203, Uttarakhand, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Dukhabandhu Naik
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
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20
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Clinical Significance of Tie-2-Expressing Monocytes/Macrophages and Angiopoietins in the Progression of Ovarian Cancer-State-of-the-Art. Cells 2022; 11:cells11233851. [PMID: 36497114 PMCID: PMC9737633 DOI: 10.3390/cells11233851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/03/2022] Open
Abstract
Tumour growth and metastasis are specific to advanced stages of epithelial ovarian cancer (EOC). Tumour angiogenesis is an essential part of these processes. It is responsible for providing tumours with nutrients, metabolites, and cytokines and facilitates tumour and immune cell relocation. Destabilised vasculature, a distinctive feature of tumours, is also responsible for compromising drug delivery into the bulk. Angiogenesis is a complex process that largely depends on how the tumour microenvironment (TME) is composed and how a specific organ is formed. There are contrary reports on whether Tie-2-expressing monocytes/macrophages (TEMs) reported as the proangiogenic population of monocytes have any impact on tumour development. The aim of this paper is to summarise knowledge about ovarian-cancer-specific angiogenesis and the unique role of Tie-2-expressing monocytes/macrophages in this process. The significance of this cell subpopulation for the pathophysiology of EOC remains to be investigated.
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21
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Dobrică EC, Banciu ML, Kipkorir V, Khazeei Tabari MA, Cox MJ, Simhachalam Kutikuppala LV, Găman MA. Diabetes and skin cancers: Risk factors, molecular mechanisms and impact on prognosis. World J Clin Cases 2022; 10:11214-11225. [PMID: 36387789 PMCID: PMC9649529 DOI: 10.12998/wjcc.v10.i31.11214] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/20/2022] [Accepted: 09/21/2022] [Indexed: 02/05/2023] Open
Abstract
Diabetes and skin cancers have emerged as threats to public health worldwide. However, their association has been less intensively studied. In this narrative review, we explore the common risk factors, molecular mechanisms, and prognosis of the association between cutaneous malignancies and diabetes. Hyperglycemia, oxidative stress, low-grade chronic inflammation, genetic, lifestyle, and environmental factors partially explain the crosstalk between skin cancers and this metabolic disorder. In addition, diabetes and its related complications may interfere with the appropriate management of cutaneous malignancies. Antidiabetic medication seems to exert an antineoplastic effect, however, future large, observation studies with a prospective design are needed to clarify its impact on the risk of malignancy in diabetes. Screening for diabetes in skin cancers, as well as close follow-up for the development of cutaneous malignancies in subjects suffering from diabetes, is warranted.
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Affiliation(s)
- Elena-Codruta Dobrică
- Doctoral School, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania
| | - Madalina Laura Banciu
- Department of Dermatology, "Elias" University Emergency Hospital, Bucharest 011461, Romania
| | - Vincent Kipkorir
- Department of Human Anatomy, University of Nairobi, College of Health Sciences, Nairobi 00100, Kenya
| | | | - Madeleine Jemima Cox
- University of New South Wales, University of New South Wales, Sydney 2052, Australia
| | | | - Mihnea-Alexandru Găman
- Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest 050474, Romania
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Gunel NS, Yildirim N, Ozates NP, Oktay LM, Bagca BG, Sogutlu F, Ozsaran A, Korkmaz M, Biray Avci C. Investigation of cytotoxic and apoptotic effects of disodium pentaborate decahydrate on ovarian cancer cells and assessment of gene profiling. MEDICAL ONCOLOGY (NORTHWOOD, LONDON, ENGLAND) 2022; 40:8. [PMID: 36308567 DOI: 10.1007/s12032-022-01870-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/20/2022] [Indexed: 01/17/2023]
Abstract
After revealing the anti-cancer properties of boron, which is included in the category of essential elements for human health by the World Health Organization, the therapeutic potential of boron compounds has been begun to be evaluated, and its molecular effect mechanisms have still been among the research subjects. In ovarian cancer, mutations or amplifications frequently occur in the PI3K/Akt/mTOR pathway components, and dysregulation of this pathway is shown among the causes of treatment failure. In the present study, it was aimed to investigate the anti-cancer properties of boron-containing DPD in SKOV3 cells, which is an epithelial ovarian cancer model, through PI3K/AKT/mTOR pathway. The cytotoxic activity of DPD in SKOV3 cells was evaluated by WST-1 test, apoptotic effect by Annexin V and JC-1 test. The gene expressions associated with PI3K/AKT/mTOR pathway were determined by real-time qRT-PCR. In SKOV3 cells, the IC50 value of DPD was found to be 6.7 mM, 5.6 mM, and 5.2 mM at 24th, 48th and 72nd hour, respectively. Compared with the untreated control group, DPD treatment was found to induce apoptosis 2.6-fold and increase mitochondrial membrane depolarization 4.5-fold. DPD treatment was found to downregulate PIK3CA, PIK3CG, AKT2, IGF1, IRS1, MAPK3, HIF-1, VEGFC, CAB39, CAB39L, STRADB, PRKAB2, PRKAG3, TELO2, RICTOR, MLST8, and EIF4B genes and upregulate TP53, GSK3B, FKBP8, TSC2, ULK1, and ULK2 genes. These results draw attention to the therapeutic potential of DPD, which is frequently exposed in daily life, in epithelial ovarian cancer and show that it can be a candidate compound in combination with chemotherapeutics.
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Affiliation(s)
- Nur Selvi Gunel
- Department of Medical Biology, Medicine Faculty, Ege University, Izmir, Turkey
| | - Nuri Yildirim
- Department of Obstetrics and Gynecology, Medicine Faculty, Ege University, Izmir, Turkey
| | | | - Latife Merve Oktay
- Department of Medical Biology, Medicine Faculty, Ege University, Izmir, Turkey
| | - Bakiye Goker Bagca
- Department of Medical Biology, Medicine Faculty, Adnan Menderes University, Izmir, Turkey
| | - Fatma Sogutlu
- Department of Medical Biology, Medicine Faculty, Ege University, Izmir, Turkey
| | - Aydin Ozsaran
- Department of Obstetrics and Gynecology, Medicine Faculty, Ege University, Izmir, Turkey
| | - Mehmet Korkmaz
- Department of Medical Biology, Medicine Faculty, Celal Bayar University, Manisa, Turkey
| | - Cigir Biray Avci
- Department of Medical Biology, Medicine Faculty, Ege University, Izmir, Turkey.
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23
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In Vitro Antimitotic and Hypoglycemic Effect Study and Acute Toxicity Assessment of the Aqueous and Organic Extracts of Chamaerops humilis L. var. argentea Andre. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4303506. [PMID: 36277886 PMCID: PMC9586795 DOI: 10.1155/2022/4303506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 09/26/2022] [Indexed: 11/18/2022]
Abstract
Background. Chamaerops humilis L. var. argentea Andre is a plant widely spread in the region of Taza (North-East of Morocco); it is used in traditional phytotherapy against cancer, diabetes, inflammations, cardiovascular and respiratory diseases, and for the treatment of digestive disorders. Objective and Methods. The objective of our work is to contribute firstly, to the study of the in vitro antimitotic potential by the phytotest of Lepidium sativum and the evaluation of the in vitro antidiabetic activity of three enzymes (α-amylase, α-glucosidase, and β-galactosidase) on nine aqueous and organic extracts prepared from the leaves of Chamaerops humilis. In addition, a correlation study was carried out on the chemical composition and the antimitotic and antidiabetic activities of Chamaerops humilis leaves. Then, we tested the acute toxicity of the decocted extract and the ethanolic extract. Results. The results of the antimitotic activity showed that the decocted extract showed a higher inhibitory activity than the other aqueous extracts (IC50 = 9.624 × 103 ± 95.97 μg/mL); for the organic extracts, the ethanolic extract and ethanolic macerated expressed the highest values for the cell growth inhibition test with an IC50 of 5.638 × 103 ± 22.61 and 5.599 × 103 ± 45.51 μg/mL with statistically nonsignificant difference. Regarding the antidiabetic activity, the decocted showed a higher inhibitory activity than the other aqueous extracts for α-amylase (IC50 = 1.781 · 105 ± 358.30 μg/mL), α-glucosidase (2.540 × 102 ± 3.14 μg/mL), and β-galactosidase (7.118 × 102 ± 16.13 μg/mL); the ethanolic extract also revealed the highest inhibitory activity for α-amylase (IC50 = 8.902 × 103 ± 57.81 μg/mL), α-glucosidase (2.216 × 102 ± 1.39 μg/mL), and β-galactosidase (2.003 × 102 ± 7.41 μg/mL). A strong correlation was recorded between the antimitic activity and the inhibitory capacity of β-galactosidase and between these two activities and the chemical composition of Chamaerops humilis leaves. The acute toxicity study showed that the decocted and the ethanolic extract are weakly toxic with an LD50 greater than or equal to 5000 mg/kg. Conclusion. Chamaerops humilis could become a good source in traditional herbal medicine.
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Huang HY, Lu TW, Liang HL, Hsu WH, Sung YW, Lee MY. Antiplatelet agents aspirin and dipyridamole, and the risk of different carcinoma in patients with type 2 diabetes mellitus: A Taiwan retrospective cohort study. Medicine (Baltimore) 2022; 101:e30468. [PMID: 36123870 PMCID: PMC9478216 DOI: 10.1097/md.0000000000030468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Studies have shown aspirin decreases the risk of some cancers. However, the evidence reported the association between aspirin and cancer risk in the diabetic population. In this study, we investigate whether aspirin and dipyridamole decrease the risk of cancer in patients with type 2 diabetes. A total of 5308 patients with type 2 diabetes were identified by the National Health Insurance from 1998 to 2000 and followed up until 2013. The demographic characteristics among nondipyridamole nor aspirin, aspirin, and dipyridamole users were analyzed by using the χ(2) test. Cox proportional hazard regression models were used to determine the independent effects of no aspirin nor dipyridamole, aspirin, and dipyridamole users on the risk of different cancer. After adjustment with multiple covariates, both low and high doses of aspirin and dipyridamole decrease liver cancer with risk ratios of 0.56 (95% CI, 0.37-0.83), 0.14 (95% CI, 0.05-0.39), 0.61 (95% CI, 0.38-0.99), and 0.28 (95% CI, 0.12-0.66), respectively. Both low and high doses of aspirin decrease any types of cancer with risk ratios of 0.79 (95% CI, 0.64-0.98) and 0.49 (95% CI, 0.34-0.70), respectively. Therefore, we conclude aspirin may decrease any types of cancer and liver cancer, and dipyridamole may decrease the risk of liver cancer in patients with type 2 diabetes.
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Affiliation(s)
- Hsing-Yi Huang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tz-Wen Lu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiu-Ling Liang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wei-Hao Hsu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ya-Wen Sung
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Mei-Yueh Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- *Correspondence: Mei-Yueh Lee, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan (e-mail: )
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25
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George S, Jean-Baptiste W, Yusuf Ali A, Inyang B, Koshy FS, George K, Poudel P, Chalasani R, Goonathilake MR, Waqar S, Mohammed L. The Role of Type 2 Diabetes in Pancreatic Cancer. Cureus 2022; 14:e26288. [PMID: 35898377 PMCID: PMC9308974 DOI: 10.7759/cureus.26288] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 06/24/2022] [Indexed: 11/05/2022] Open
Abstract
The incidence of type 2 diabetes mellitus (T2DM) and its potential complications, such as cancers, are increasing worldwide at an astounding rate. There are many factors such as obesity, diabetes, alcohol consumption, and the adoption of sedentary lifestyles that are driving pancreatic cancer (PC) to become one of the leading causes of cancer mortality in the United States. PC is notorious for its generic symptoms and late-stage presentation with rapid metastasis. The connection between T2DM and the risk of PC development is multifaceted and complex. Some of the proposed theories reveal that chronic inflammation, insulin resistance, hyperinsulinemia, hyperglycemia, and abnormalities in the insulin and insulin-like growth factor axis (IGF) contribute to the disease association between these two conditions. This literature review aims to highlight relevant studies and explore the molecular mechanisms involved in the etiology of diabetes and its impact on PC development, as well as the role of anti-diabetic agents on PC. Despite extensive studies, the exact interaction between T2DM and PC remains obscure and will need further investigation. According to current knowledge, there is a substantial link between diabetes, obesity, and dietary patterns in the development and progression of PC. Consequently, focusing our efforts on preventive measures by reducing modifiable risk factors remains the most effective strategy to reduce the risk of PC at this time. Antidiabetic drugs can have various effects on the occurrence and prognosis of PC with metformin offering a clear benefit of inhibiting PC and insulin increasing the risk of PC. The development of future novel therapies will require a deeper knowledge of the triggering mechanisms and interplay between these two disease states.
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Meth EMS, van Egmond LT, Moulin TC, Cedernaes J, Rosqvist F, Benedict C. Association of Daily Eating Duration and Day-To-Day Variability in the Timing of Eating With Fatal Cancer Risk in Older Men. Front Nutr 2022; 9:889926. [PMID: 35619965 PMCID: PMC9127957 DOI: 10.3389/fnut.2022.889926] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 04/07/2022] [Indexed: 11/13/2022] Open
Abstract
Meal timing has significant effects on health. However, whether meal timing is associated with the risk of developing and dying of cancer is not well-researched in humans. In the present study, we used data from 941 community-dwelling men aged 71 years who participated in the Uppsala Longitudinal Study of Adult Men to examine the association of meal timing with cancer morbidity and fatal cancer. The following meal timing variables were derived from 7-day food diaries: (i) daily eating duration, i.e., the time between the first and last eating episode of an arbitrary day; (ii) the calorically weighted midpoint of the daily eating interval, a proxy of when the eating window typically occurs during an arbitrary day; and (iii) the day-to-day variability in the timing of eating. We also assessed the reported daily energy intake reliability using the Goldberg method. During a mean observational period of 13.4 years, 277 men (29.4%) were diagnosed with cancer. Furthermore, 191 men (20%) died from cancer during 14.7 years of follow-up. As shown by Cox regression adjusted for potential confounders (e.g., smoking status and daily energy intake), men with reliable dietary reports whose daily eating intervals were on average 13 h long had a 2.3-fold greater fatal cancer risk than men whose daily eating windows were on average about 11 h long. We also found that men with an average day-to-day variability in the timing of eating of 48 to 74 min had a 2- to 2.2-fold higher fatal cancer risk than those with the lowest average day-to-day variability in the timing of eating (i.e., 23 min). No clear associations were found in men with inadequate dietary reports, emphasizing the need to consider the reliability of dietary records in nutritional epidemiology. To fully unlock its potential, studies are needed to test whether recommendations to time-restrict the 24-h eating interval and reduce day-to-day variability in the timing of eating can meaningfully alter the risk of death due to cancer.
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Affiliation(s)
- Elisa M S Meth
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Thiago C Moulin
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Jonathan Cedernaes
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden.,Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Fredrik Rosqvist
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - Christian Benedict
- Sleep Science Laboratory, Department of Pharmaceutical Biosciences, Molecular Neuropharmacology, Uppsala University, Uppsala, Sweden
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Overview of the Composition of Whole Grains’ Phenolic Acids and Dietary Fibre and Their Effect on Chronic Non-Communicable Diseases. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19053042. [PMID: 35270737 PMCID: PMC8910396 DOI: 10.3390/ijerph19053042] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/22/2022] [Accepted: 02/26/2022] [Indexed: 02/01/2023]
Abstract
Chronic non-communicable diseases are the major cause of death globally. Whole grains are recommended in dietary guidelines worldwide due to increasing evidence that their consumption can improve health beyond just providing energy and nutrients. Epidemiological studies have suggested that the incorporation of whole grains, as part of a healthy diet, plays a key role in reducing one’s risk for cardiovascular diseases (CVDs), obesity, type 2 diabetes (T2D) and cancer. Phenolic acids and dietary fibre are important components found in whole grains that are largely responsible for these health advantages. Both phenolic acids and dietary fibre, which are predominantly present in the bran layer, are abundant in whole-grain cereals and pseudo-cereals. Several studies indicate that whole grain dietary fibre and phenolic acids are linked to health regulation. The main focus of this study is two-fold. First, we provide an overview of phenolic acids and dietary fibres found in whole grains (wheat, barley, oats, rice and buckwheat). Second, we review existing literature on the linkages between the consumption of whole grains and the development of the following chronic non-communicable diseases: CVDs, obesity, T2D and cancer. Altogether, scientific evidence that the intake of whole grains reduces the risk of certain chronic non-communicable disease is encouraging but not convincing. Based on previous studies, the current review encourages further research to cover the gap between the emerging science of whole grains and human health.
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Relevance of miR-223 as Potential Diagnostic and Prognostic Markers in Cancer. BIOLOGY 2022; 11:biology11020249. [PMID: 35205115 PMCID: PMC8869096 DOI: 10.3390/biology11020249] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/31/2022] [Accepted: 02/03/2022] [Indexed: 12/21/2022]
Abstract
In 1993, the discovery of microRNAs in Caenorhabditis elegans (C. elegans) altered the paradigmatic view of RNA biology and post-transcriptional gene regulation. Further study revealed the role of microRNAs in disease development and progression. In particular, this review highlights microRNA-223 (miR-223 or miRNA-223) expression in malignant neoplastic disorders. miR-223 expression controls aspects of hematopoiesis and apoptosis, and cell proliferation, migration, and invasion. miR-223 regulates a number of gene targets, including cytoplasmic activation/proliferation-associated protein-1 (Caprin-1), insulin-like growth factor-1 receptor (IGF-1R), and other cell proliferation- and cell cycle-associated genes. Several studies have proposed miR-223 as a novel biomarker for early cancer diagnosis. Here, we emphasize miR-223′s role in the development and progression of cancer.
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Guo XF, Zhou YL, Liu M, Wang ZW, Gui JF. Integrated application of Iso-seq and RNA-seq provides insights into unsynchronized growth in red swamp crayfish (Procambarus clarkii). AQUACULTURE REPORTS 2022; 22:101008. [DOI: 10.1016/j.aqrep.2022.101008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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30
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Dusingize JC, Law MH, Pandeya N, Neale RE, Ong JS, MacGregor S, Whiteman DC, Olsen CM. Genetically determined cutaneous nevi and risk of cancer. Int J Cancer 2021; 150:961-968. [PMID: 34778946 DOI: 10.1002/ijc.33874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 10/14/2021] [Accepted: 10/22/2021] [Indexed: 01/07/2023]
Abstract
Numerous epidemiologic studies have reported positive associations between higher nevus counts and internal cancers. Whether this association represents a true relationship or is due to bias or confounding by factors associated with both nevus counts and cancer remains unclear. We used germline genetic variants for nevus count to test whether this phenotypic trait is a risk-marker for cancer. We calculated polygenic risk scores (PRS) for nevus counts using individual-level data in the UK Biobank (n = 394 306) and QSkin cohort (n = 17 427). The association between the nevus PRS and each cancer site was assessed using logistic regression adjusted for the effects of age, sex and the first five principal components. In both cohorts, those in the highest nevus PRS quartile had higher risks of melanoma than those in the lowest quartile (UK Biobank odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.29-1.55; QSkin OR 1.58, 95% CI: 1.29-1.94). We also observed increases in risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with higher nevus PRS quartiles (BCC UK Biobank OR 1.38, 95% CI: 1.33-1.44; QSkin OR 1.20, 95% CI: 1.05-1.38 and SCC UK Biobank OR 1.41, 95% CI: 1.28-1.55; QSkin OR 1.44, 95% CI: 1.19-1.77). We found no consistent evidence that nevus count PRS were associated with risks of developing internal cancers. We infer that associations between nevus counts and internal cancers reported in earlier observational studies arose because of unmeasured confounding or other biases.
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Affiliation(s)
- Jean Claude Dusingize
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Matthew H Law
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.,Faculty of Health, Queensland University of Technology (QUT), Brisbane, Australia
| | - Nirmala Pandeya
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.,School of Public Health, University of Queensland, Brisbane, Australia
| | - Rachel E Neale
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.,School of Public Health, University of Queensland, Brisbane, Australia
| | - Jue-Sheng Ong
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Stuart MacGregor
- Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - David C Whiteman
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Catherine M Olsen
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Australia
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Hou X, Wang L, Zhao F, Liu X, Gao H, Shi L, Yan H, Wang L, Zhang L. Genome-Wide Expression Profiling of mRNAs, lncRNAs and circRNAs in Skeletal Muscle of Two Different Pig Breeds. Animals (Basel) 2021; 11:ani11113169. [PMID: 34827901 PMCID: PMC8614396 DOI: 10.3390/ani11113169] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/04/2021] [Accepted: 11/04/2021] [Indexed: 01/02/2023] Open
Abstract
Simple Summary Variation exists in muscle-related traits, such as muscle growth and meat quality, between obese and lean pigs. In this study, the transcriptome profiles of skeletal muscle between Beijing Blackand Yorkshire pigs were characterized to explore the molecular mechanism underlying skeletal muscle-relatedtraits. Gene Ontology (GO) and KEGG pathway enrichment analyses showed that differentially expressed mRNAs, lncRNAs, and circRNAs involved in skeletal muscle development and fatty acid metabolism played a key role in the determination of muscle-related traits between different pig breeds. These results provide candidate genes responsible for muscle phenotypic variation and are valuable for pig breeding. Abstract RNA-Seq technology is widely used to analyze global changes in the transcriptome and investigate the influence on relevant phenotypic traits. Beijing Black pigs show differences in growth rate and meat quality compared to western pig breeds. However, the molecular mechanisms responsible for such phenotypic differences remain unknown. In this study, longissimus dorsi muscles from Beijing Black and Yorkshire pigs were used to construct RNA libraries and perform RNA-seq. Significantly different expressions were observed in 1051 mRNAs, 322 lncRNAs, and 82 circRNAs. GO and KEGG pathway annotation showed that differentially expressed mRNAs participated in skeletal muscle development and fatty acid metabolism, which determined the muscle-related traits. To explore the regulatory role of lncRNAs, the cis and trans-target genes were predicted and these lncRNAswere involved in the biological processes related to skeletal muscle development and fatty acid metabolismvia their target genes. CircRNAs play a ceRNA role by binding to miRNAs. Therefore, the potential miRNAs of differentially expressed circRNAs were predicted and interaction networks among circRNAs, miRNAs, and key regulatory mRNAs were constructed to illustrate the function of circRNAs underlying skeletal muscle development and fatty acid metabolism. This study provides new clues for elucidating muscle phenotypic variation in pigs.
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32
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Liu H, Gu H, Kutbi EH, Tan SC, Low TY, Zhang C. Association of IGF-1 and IGFBP-3 levels with gastric cancer: A systematic review and meta-analysis. Int J Clin Pract 2021; 75:e14764. [PMID: 34469629 DOI: 10.1111/ijcp.14764] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/22/2021] [Accepted: 08/10/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Many studies have investigated the association between serum IGF-1 and IGFBP levels with gastric cancer (GC), but the results remained inconclusive. In this work, we performed a systematic review and meta-analysis to examine the precise association of serum levels of IGF-1 and IGFBP with GC. METHODS A comprehensive systematic search was carried out in PubMed/MEDLINE, SCOPUS, Web of Science, and EMBASE databases for (nested) case-control studies that reported the levels of IGF-1 and IGFBP in GC cases and healthy controls, from inception until October 2020. Weighted mean difference (WMD) was calculated for estimating combined effect size. Subgroup analysis was performed to identify the source of heterogeneity among studies. RESULTS We found eight and five eligible studies (with 1541 participants) which provided data for IGF-1 and IGFBP, respectively. All studies on IGFBP reported the IGFBP-3 isoform. The pooled results indicate that GC patients had significantly lower serum IGF-1 [WMD = -26.21 ng/mL (95% CI, -45.58 to -6.85; P = .008)] and IGFBP-3 [WMD = -0.41 ng/mL (95% CI, -0.80 to -0.01; P = .04; I2 = 89.9%; P < .001)] levels than those in healthy subjects. Significant heterogeneity was observed in the association, which could be attributed to the sample size of the studies. CONCLUSIONS In conclusion, our study reveals a significantly lower level of IGF-1 and IGFBP-3 in GC patients compared with healthy control subjects.
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Affiliation(s)
- Hongyu Liu
- Department of Pathology, Qiqihar Hospital Affiliated to Southern Medical University, Qiqihar, China
| | - Huxia Gu
- Department of Network Information, Fuling Central Hospital of Chongqing city, Chongqing, China
| | - Emad H Kutbi
- Biorepository Department, Biomedical Research Administration, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Shing Cheng Tan
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Teck Yew Low
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Chong Zhang
- Department of Pathology, Fuling Central Hospital of Chongqing city, Chongqing, China
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Jun H, Lee J, Lee HA, Kim SE, Shim KN, Jung HK, Jung SA, Moon CM. Fasting Blood Glucose Variability and Unfavorable Trajectory Patterns Are Associated with the Risk of Colorectal Cancer. Gut Liver 2021; 16:423-432. [PMID: 34593671 PMCID: PMC9099386 DOI: 10.5009/gnl210048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 05/24/2021] [Accepted: 06/29/2021] [Indexed: 11/04/2022] Open
Abstract
Background/Aims The relationship between fasting blood glucose (FBG) variability and colorectal cancer (CRC) remains ill-defined. This study aimed to evaluate the association of FBG variability with CRC risk in the healthy population without overt diabetes. Methods In the data from the Korean National Health Insurance Service-Health Screening Cohort, we included individuals examined by FBG testing at least 3 times between 2002 and 2007. FBG variability was calculated using standard deviation (SD) and coefficient of variation (CV). Results Regarding FBG variability, an increase in the quintile of SD or CV was independently associated with CRC risk (all p for trend <0.01). When the change in FBG was classified into six trajectory patterns, unfavorable trajectory patterns (high stable and upward) were significantly associated with increased CRC risk (hazard ratio [HR] 2.30, p=0.003; HR 1.19, p=0.007, respectively). In subgroup analyses according to the sex, a significant association between FBG variability (SD or CV) and CRC risk was observed in men but not in women. The high stable and upward pattern were also associated with CRC risk in men (HR 2.47, p=0.002; HR 1.21, p=0.012) but not in women. Conclusions This study identified that FBG variability and unfavorable trajectory patterns were significantly associated with increased CRC risk in the healthy population without overt diabetes. Our findings suggest that FBG variability as well as FBG itself may be a predictive factor for the development of CRC.
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Affiliation(s)
- Hyoju Jun
- Department of Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Jieun Lee
- Department of Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | | | - Ki-Nam Shim
- Department of Internal Medicine, Seoul, Korea
| | | | | | - Chang Mo Moon
- Department of Internal Medicine, Seoul, Korea.,Inflammation-Cancer Microenvironment Research Center, Ewha Womans University College of Medicine, Seoul, Korea
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Artico LL, Laranjeira ABA, Campos LW, Corrêa JR, Zenatti PP, Carvalheira JBC, Brambilla SR, Nowill AE, Brandalise SR, Yunes JA. Physiologic IGFBP7 levels prolong IGF1R activation in acute lymphoblastic leukemia. Blood Adv 2021; 5:3633-3646. [PMID: 34438446 PMCID: PMC8945593 DOI: 10.1182/bloodadvances.2020003627] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 04/06/2021] [Indexed: 02/07/2023] Open
Abstract
Insulin and insulin-like growth factors (IGFs) are mitogenic and prosurvival factors to many different cell types, including acute lymphoblastic leukemia (ALL). Circulating IGFs are bound by IGF binding proteins (IGFBPs) that regulate their action. IGFBP7 is an IGFBP-related protein (IGFBP-rP) that in contrast to other IGFBPs/IGFBP-rPs features higher affinity for insulin than IGFs and was shown to bind the IGF1 receptor (IGF1R) as well. The role of IGFBP7 in cancer is controversial: on some tumors, it functions as an oncogene, whereas in others, it functions as a tumor suppressor. In childhood ALL, higher IGFBP7 expression levels were associated with worse prognosis. Here we show that IGFBP7 exerts mitogenic and prosurvival autocrine effects on ALL cells that were dependent on insulin/IGF. IGFBP7 knockdown or antibody-mediated neutralization resulted in significant attenuation of ALL cell viability in vitro and leukemia progression in vivo. IGFBP7 was shown to prolong the surface retention of the IGF1R under insulin/IGF1 stimulation, resulting in sustained IGF1R, insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation. Conversely, the insulin receptor was readily internalized and dephosphorylated on insulin stimulation, despite IGFBP7 addition. The affinity of homodimeric IGF1R for insulin is reportedly >100 times lower than for IGF1. In the presence of IGFBP7, however, 25 ng/mL insulin resulted in IGF1R activation levels equivalent to that of 5 ng/mL IGF1. In conclusion, IGFBP7 plays an oncogenic role in ALL by promoting the perdurance of IGF1R at the cell surface, prolonging insulin/IGF stimulation. Preclinical data demonstrate that IGFBP7 is a valid target for antibody-based therapeutic interventions in ALL.
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Affiliation(s)
- Leonardo Luís Artico
- Centro Infantil Boldrini, Campinas, Brazil
- Graduate Program in Genetics and Molecular Biology, Biology Institute, State University of Capinas
| | | | - Livia Weijenborg Campos
- Centro Infantil Boldrini, Campinas, Brazil
- Graduate Program in Genetics and Molecular Biology, Biology Institute, State University of Capinas
| | - Juliana Ronchi Corrêa
- Centro Infantil Boldrini, Campinas, Brazil
- Graduate Program in Genetics and Molecular Biology, Biology Institute, State University of Capinas
| | | | | | | | | | | | - José Andrés Yunes
- Centro Infantil Boldrini, Campinas, Brazil
- Departamento de Genética Médica, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil
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Ku MS, Liu CY, Hsu CY, Chiu HM, Chen HH, Chan CC. Association of Ambient Fine Particulate Matter (PM 2.5) with Elevated Fecal Hemoglobin Concentration and Colorectal Carcinogenesis: A Population-Based Retrospective Cohort Study. Cancer Control 2021; 28:10732748211041232. [PMID: 34525876 PMCID: PMC8450689 DOI: 10.1177/10732748211041232] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
The roles of ambient fine particulate matter (PM2.5) in the prevention of colorectal cancer (CRC) have been scarcely highlighted as there is short of empirical evidence regarding the influences of PM2.5 on multistep carcinogenic processes of CRC. A retrospective cohort design with multistate outcomes was envisaged by linking monthly average PM2.5 concentrations at 22 city/county level with large-scale cohorts of cancer-screened population to study the influences of PM2.5 on short-term inflammatory process and multistep carcinogenic processes of CRC. Our study included a nationwide CRC screening cohort of 4,628,995 aged 50-69 years who attended first screen between 2004 and 2009 and continued periodical screens until 2016. We aimed to illustrate the carcinogenesis of PM2.5 related to CRC by applying both hierarchical logistical and multistate Markov regression models to estimate the effects of air pollution on fecal immunochemical test (FIT) positive (a proxy of inflammatory marker) and pre-clinical and clinical states of CRC in the nationwide cohort. We found a significant association of high PM2.5 exposure and FIT-positive by an increased risk of 11% [95% confidence interval (CI), 10-12]. PM2.5 enhanced the risk of being preclinical state by 14% (95% CI, 10-18) and that of subsequent progression from pre-clinical to clinical state by 21% (95% CI, 14-28). Furthermore, the elevated risks for CRC carcinogenesis were significantly higher for people living in high PM2.5 pollution areas in terms of yearly averages and the number days above 35 µg/m3 than those living in low PM2.5 pollution areas. We concluded that both short-term and long-term PM2.5 exposure were associated with multistep progression of CRC, which were useful to design precision primary and secondary prevention strategies of CRC for people who are exposed to high PM2.5 pollution.
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Affiliation(s)
- Mei-Sheng Ku
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, 33561National Taiwan University, Taipei, Taiwan.,Institute of Environmental and Occupational Health Science, College of Public Health, 33561National Taiwan University, Taipei, Taiwan
| | - Chen-Yu Liu
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, 33561National Taiwan University, Taipei, Taiwan.,Institute of Environmental and Occupational Health Science, College of Public Health, 33561National Taiwan University, Taipei, Taiwan
| | - Chen-Yang Hsu
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, 33561National Taiwan University, Taipei, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, 33561National Taiwan UniversityHospital, Taipei, Taiwan
| | - Hsiu-Hsi Chen
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, 33561National Taiwan University, Taipei, Taiwan.,Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, 33561National Taiwan University, Taipei, Taiwan
| | - Chang-Chuan Chan
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, 33561National Taiwan University, Taipei, Taiwan.,Institute of Environmental and Occupational Health Science, College of Public Health, 33561National Taiwan University, Taipei, Taiwan
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36
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Song DW, Ro WB, Sur JH, Seung BJ, Kang HM, Kim JW, Park SH, Park HM. Evaluation of circulating IGF-I and IGFBP-3 as biomarkers for tumors in dogs. J Vet Sci 2021; 22:e77. [PMID: 34697923 PMCID: PMC8636663 DOI: 10.4142/jvs.2021.22.e77] [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: 06/16/2021] [Revised: 08/05/2021] [Accepted: 08/31/2021] [Indexed: 11/23/2022] Open
Abstract
Background Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. Objectives This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. Methods The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). Results The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5–175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5–79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2–57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6–70.5]) in healthy dogs. Conclusions The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.
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Affiliation(s)
- Doo-Won Song
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Woong-Bin Ro
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Jung-Hyang Sur
- Department of Veterinary Pathology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Byung-Joon Seung
- Department of Veterinary Pathology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Hyun-Min Kang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Jong-Won Kim
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - See-Hyoung Park
- Department of Biological and Chemical Engineering, Hongik University, Sejong 30016, Korea
| | - Hee-Myung Park
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
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Ciminera AK, Shuck SC, Termini J. Elevated glucose increases genomic instability by inhibiting nucleotide excision repair. Life Sci Alliance 2021; 4:4/10/e202101159. [PMID: 34426491 PMCID: PMC8385305 DOI: 10.26508/lsa.202101159] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 12/23/2022] Open
Abstract
Exposure to chronic, elevated glucose inhibits nucleotide excision repair, which leads to accumulation of DNA glycation adducts, increased DNA strand breaks, and activation of the DNA damage response. We investigated potential mechanisms by which elevated glucose may promote genomic instability. Gene expression studies, protein measurements, mass spectroscopic analyses, and functional assays revealed that elevated glucose inhibited the nucleotide excision repair (NER) pathway, promoted DNA strand breaks, and increased levels of the DNA glycation adduct N2-(1-carboxyethyl)-2ʹ-deoxyguanosine (CEdG). Glycation stress in NER-competent cells yielded single-strand breaks accompanied by ATR activation, γH2AX induction, and enhanced non-homologous end-joining and homology-directed repair. In NER-deficient cells, glycation stress activated ATM/ATR/H2AX, consistent with double-strand break formation. Elevated glucose inhibited DNA repair by attenuating hypoxia-inducible factor-1α–mediated transcription of NER genes via enhanced 2-ketoglutarate–dependent prolyl hydroxylase (PHD) activity. PHD inhibition enhanced transcription of NER genes and facilitated CEdG repair. These results are consistent with a role for hyperglycemia in promoting genomic instability as a potential mechanism for increasing cancer risk in metabolic disease. Because of the pleiotropic functions of many NER genes beyond DNA repair, these results may have broader implications for cellular pathophysiology.
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Affiliation(s)
- Alexandra K Ciminera
- Department of Molecular Medicine, Beckman Research Institute at City of Hope, Duarte, CA, USA.,Irell and Manella Graduate School of Biomedical Sciences, City of Hope, Duarte, CA, USA
| | - Sarah C Shuck
- Department of Molecular Medicine, Beckman Research Institute at City of Hope, Duarte, CA, USA
| | - John Termini
- Department of Molecular Medicine, Beckman Research Institute at City of Hope, Duarte, CA, USA
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Xue Y, Wang P, Jiang F, Yu J, Ding H, Zhang Z, Pei H, Li B. A Newly Identified lncBCAS1-4_1 Associated With Vitamin D Signaling and EMT in Ovarian Cancer Cells. Front Oncol 2021; 11:691500. [PMID: 34422647 PMCID: PMC8377733 DOI: 10.3389/fonc.2021.691500] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 07/14/2021] [Indexed: 11/13/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) were identified rapidly due to their important role in many biological processes and human diseases including cancer. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its analogues are widely applied as preventative and therapeutic anticancer agents. However, the expression profile of lncRNAs regulated by 1α,25(OH)2D3 in ovarian cancer remains to be clarified. In the present study, we found 606 lncRNAs and 102 mRNAs that showed differential expression (DE) based on microarray data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DE genes were mainly enriched in TGF-β, MAPK, Ras, PI3K-Akt, and Hippo signaling pathways, as well as the vitamin D-related pathway. We further assessed the potential lncRNAs that linked vitamin D signaling with EMT, and lncBCAS1-4_1 was identified in the first time. Moreover, we found that the most upregulated lncBCAS1-4_1 showed 75% same transcripts with CYP24A1 (metabolic enzyme of 1α,25(OH)2D3). Finally, the lncBCAS1-4_1 gain-of-function cell model was established, which demonstrated that the knockdown of lncBCAS1-4_1 inhibited the proliferation and migration of ovarian cancer cells. Furthermore, lncBCAS1-4_1 could resist the antitumor effect of 1α,25(OH)2D3, which was associated with upregulated ZEB1. These data provide new evidences that lncRNAs served as a target for the antitumor effect of 1α,25(OH)2D3.
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Affiliation(s)
- Yaqi Xue
- Deparment of Nutrition and Food Hygiene, Medical College of Soochow University, Suzhou, China.,Department of Clinical Nutrition, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Ping Wang
- Deparment of Nutrition and Food Hygiene, Medical College of Soochow University, Suzhou, China
| | - Fei Jiang
- Deparment of Nutrition and Food Hygiene, Medical College of Soochow University, Suzhou, China
| | - Jing Yu
- Deparment of Nutrition and Food Hygiene, Medical College of Soochow University, Suzhou, China
| | - Hongmei Ding
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zengli Zhang
- Deparment of Nutrition and Food Hygiene, Medical College of Soochow University, Suzhou, China
| | - Hailong Pei
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Centre of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China
| | - Bingyan Li
- Deparment of Nutrition and Food Hygiene, Medical College of Soochow University, Suzhou, China
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Crudele L, Piccinin E, Moschetta A. Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis. Nutrients 2021; 13:2101. [PMID: 34205356 PMCID: PMC8234141 DOI: 10.3390/nu13062101] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/14/2021] [Accepted: 06/16/2021] [Indexed: 12/11/2022] Open
Abstract
The prevalence of being overweight and obese has been expanded dramatically in recent years worldwide. Obesity usually occurs when the energetic introit overtakes energy expenditure from metabolic and physical activity, leading to fat accumulation mainly in the visceral depots. Excessive fat accumulation represents a risk factor for many chronic diseases, including cancer. Adiposity, chronic low-grade inflammation, and hyperinsulinemia are essential factors of obesity that also play a crucial role in tumor onset. In recent years, several strategies have been pointed toward boundary fat accumulation, thus limiting the burden of cancer attributable to obesity. While remodeling fat via adipocytes browning seems a tempting prospect, lifestyle interventions still represent the main pathway to prevent cancer and enhance the efficacy of treatments. Specifically, the Mediterranean Diet stands out as one of the best dietary approaches to curtail visceral adiposity and, therefore, cancer risk. In this Review, the close relationship between obesity and cancer has been investigated, highlighting the biological mechanisms at the basis of this link. Finally, strategies to remodel fat, including browning and lifestyle interventions, have been taken into consideration as a major perspective to limit excess body weight and tumor onset.
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Affiliation(s)
- Lucilla Crudele
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (L.C.); (E.P.)
- Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Elena Piccinin
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (L.C.); (E.P.)
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (L.C.); (E.P.)
- INBB, National Institute for Biostructures and Biosystems, 00136 Rome, Italy
- National Cancer Center, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
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Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer. Int J Mol Sci 2021; 22:ijms22126434. [PMID: 34208601 PMCID: PMC8234711 DOI: 10.3390/ijms22126434] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/04/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.
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Yu X, Chen C, Song X, Guo Y, Tong Y, Zhao Y, Song Z. Glycosylated Hemoglobin as an Age-Specific Predictor and Risk Marker of Colorectal Adenomas in Non-Diabetic Adults. Front Endocrinol (Lausanne) 2021; 12:774519. [PMID: 34803930 PMCID: PMC8595137 DOI: 10.3389/fendo.2021.774519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 10/14/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Diabetes is a risk factor for colorectal neoplasms. The association between the level of glycosylated hemoglobin (HbA1c) and the risk of colorectal adenomas (CRAs) in non-diabetic adults needs to be investigated. METHODS A cross-sectional study was performed on non-diabetic adults with normal HbA1c level who underwent colonoscopy between January 2010 and December 2016 during health check-ups in our hospital in China. The association between HbA1c level and CRAs was assessed by multiple logistic regression models stratified by age group (<40, ≥40 and <50, and ≥50 years old). The age group-specified thresholds for HbA1c on elevated risk of CRAs were estimated using the piecewise logistic regression. RESULTS Among the 2,764 subjects, 445 (16.1%) had CRA. The prevalence of CRA varied across the three age groups. A higher HbA1c level was found to be significantly associated with increased CRA risk in the 40-50 years group (odds ratio [OR]=1.70, 95% confidence interval [CI] 1.04-2.78, p=0.035) after adjusting for other related factors, while this association was borderline significant among the 50 years and older group (OR=1.57, 95% CI 0.97-2.54, p=0.067). Based on the piecewise logistic regression analysis results, the thresholds for HbA1c on elevated risk of CRA were 5.44% for the 40-50 years group and 4.81% for the 50 years and older group, respectively. CONCLUSIONS Higher levels of HbA1c, even within the normal range, were associated with elevated CRA risk among non-diabetic adults. The threshold effects of HbA1c on the risk of CRA varied across different age groups, and early screening colonoscopy might be needed for individuals in their 40s and with HbA1c levels ≥5.44%.
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Affiliation(s)
- Xinyan Yu
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chen Chen
- Department of Big Data in Health Science, School of Public Health, Zhejiang University, Hangzhou, China
- Center for Biostatistics, Bioinformatics, and Big Data, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxiao Song
- Department of Endocrinology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yi Guo
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yuling Tong
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yi Zhao
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhenya Song
- Department of General Practice and Health Management Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- *Correspondence: Zhenya Song,
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Kiesel L, Eichbaum C, Baumeier A, Eichbaum M. Obesity Epidemic-The Underestimated Risk of Endometrial Cancer. Cancers (Basel) 2020; 12:E3860. [PMID: 33371216 PMCID: PMC7767192 DOI: 10.3390/cancers12123860] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/13/2020] [Accepted: 12/15/2020] [Indexed: 12/24/2022] Open
Abstract
Endometrial cancer (EC) is the most frequently observed malignant gynecologic disease in developed countries. There is a strong association between the established risk factor obesity and the incidence of EC. Furthermore, the rate of women with a body mass index (BMI) > 30 kg/m2 is increasing worldwide, correspondingly leading to a higher prevalence of EC. Understanding the adipose tissue as an endocrine organ, elementary pathophysiological pathways of tumorigenesis have been revealed. This includes the fundamental role of hyperglycemia, insulin resistance, and hyperestrogenemia, as well as interactions with a chronic proinflammatory microenvironment. Therapeutic options potentially include metformin or bariatric surgery. Moreover, changes in individual lifestyle such as weight reduction, physical activity, and an awareness of healthy nutrition are effective in preventing the disease.
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Affiliation(s)
- Ludwig Kiesel
- Department of Gynecology and Obstetrics, University of Münster Medical School, Albert-Schweitzer-Campus 1, 48149 Münster, Germany;
| | - Christine Eichbaum
- Department of Gynecology and Obstetrics, University of Frankfurt Medical School, Theodor-Stern-Kai 7, 60596 Frankfurt, Germany;
| | - Ariane Baumeier
- Department of Gynecology and Obstetrics, University of Münster Medical School, Albert-Schweitzer-Campus 1, 48149 Münster, Germany;
| | - Michael Eichbaum
- Department of Gynecology and Obstetrics, Helios Dr. Horst-Schmidt-Kliniken Wiesbaden, Ludwig-Erhard-Str. 100, 65199 Wiesbaden, Germany
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Liu CT, Xu YW, Guo H, Hong CQ, Huang XY, Luo YH, Yang SH, Chu LY, Li EM, Peng YH. Serum Insulin-Like Growth Factor Binding Protein 7 as a Potential Biomarker in the Diagnosis and Prognosis of Esophagogastric Junction Adenocarcinoma. Gut Liver 2020; 14:727-734. [PMID: 31822054 PMCID: PMC7667930 DOI: 10.5009/gnl19135] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 09/18/2019] [Accepted: 10/30/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND/AIMS Esophagogastric junction adenocarcinoma (EJA) is a malignant tumor associated with high morbidity and has attracted increasing attention due to a rising incidence and low survival rate. Pathological biopsy is the gold standard for diagnosis, but noninvasive and effective tests are lacking, resulting in diagnoses at advanced stages. This study explored the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in EJA. METHODS A total of 120 EJA patients and 88 normal controls were recruited, and their serum levels of IGFBP7 were measured by enzymelinked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value, and Pearson chi-square analysis was used to evaluate the correlation between IGFBP7 and clinical parameters. Kaplan- Meier survival analysis was carried out to assess the effect of IGFBP7 on overall survival (OS). RESULTS The levels of IGFBP7 were higher in both early- and late-stage EJA patients than in normal controls (p<0.001). The area under the ROC curve for EJA patients was 0.794 (95% confidence interval [CI], 0.733 to 0.854), with a cutoff value of 2.716 ng/mL, a sensitivity of 63.3% (95% CI, 54.0% to 71.8%) and a specificity of 90.9% (95% CI, 82.4% to 95.7%). For the diagnosis of early-stage EJA, the same cutoff value and specificity were obtained, but the sensitivity of IGFBP7 was 54.3% (95% CI, 36.9% to 70.8%). Patients with low IGFBP7 protein expression had lower OS than those with high expression (p=0.034). The multivariate analysis showed that IGFBP7 is an independent prognostic factor for EJA (p=0.011). CONCLUSIONS Serum IGFBP7 acts as a potential diagnostic and prognostic marker for EJA.
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Affiliation(s)
- Can-Tong Liu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, China
| | - Hong Guo
- Departments of Radiation Oncology, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Chao-Qun Hong
- Departments of Oncological Laboratory Research, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Xin-Yi Huang
- Precision Medicine Research Center, Shantou University Medical College, Shantou, China
| | - Yu-Hao Luo
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Shi-Han Yang
- Department of Dermatology and Venereology, Shantou Central Hospital, Shantou, China
| | - Ling-Yu Chu
- Precision Medicine Research Center, Shantou University Medical College, Shantou, China
| | - En-Min Li
- Precision Medicine Research Center, Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
- Precision Medicine Research Center, Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, China
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Dragano NRV, Fernø J, Diéguez C, López M, Milbank E. Reprint of: Recent Updates on Obesity Treatments: Available Drugs and Future Directions. Neuroscience 2020; 447:191-215. [PMID: 33046217 DOI: 10.1016/j.neuroscience.2020.08.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In the last thirty years, obesity has reached epidemic proportions and is now regarded as a major health issue in contemporary society trending to serious economic and social burdens. The latest projections of the World Health Organization are alarming. By 2030, nearly 60% of the worldwide population could be either obese or overweight, highlighting the needs to find innovative treatments. Currently, bariatric surgery is the most effective way to efficiently lower body mass. Although great improvements in terms of recovery and patient care were made in these surgical procedures, bariatric surgery remains an option for extreme forms of obesity and seems unable to tackle obesity pandemic expansion. Throughout the last century, numerous pharmacological strategies targeting either peripheral or central components of the energy balance regulatory system were designed to reduce body mass, some of them reaching sufficient levels of efficiency and safety. Nevertheless, obesity drug therapy remains quite limited on its effectiveness to actually overcome the obesogenic environment. Thus, innovative unimolecular polypharmacology strategies, able to simultaneously target multiple actors involved in the obesity initiation and expansion, were developed during the last ten years opening a new promising avenue in the pharmacological management of obesity. In this review, we first describe the clinical features of obesity-associated conditions and then focus on the outcomes of currently approved drug therapies for obesity as well as new ones expecting to reach the clinic in the near future.
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Affiliation(s)
- Nathalia R V Dragano
- NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 15706, Spain.
| | - Johan Fernø
- Hormone Laboratory, Haukeland University Hospital, N-5021 Bergen, Norway
| | - Carlos Diéguez
- NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 15706, Spain
| | - Miguel López
- NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 15706, Spain
| | - Edward Milbank
- NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 15706, Spain.
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Current Perspectives on Therapies, Including Drug Delivery Systems, for Managing Glioblastoma Multiforme. ACS Chem Neurosci 2020; 11:2962-2977. [PMID: 32945654 DOI: 10.1021/acschemneuro.0c00555] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Glioblastoma multiforme (GBM), a standout among the most dangerous class of central nervous system (CNS) cancer, is most common and is an aggressive malignant brain tumor in adults. In spite of developments in modality therapy, it remains mostly incurable. Consequently, the need for novel systems, strategies, or therapeutic approaches for enhancing the assortment of active agents meant for GBM becomes an important criterion. Currently, cancer research focuses mainly on improving the treatment of GBM via diverse novel drug delivery systems. The treatment options at diagnosis are multimodal and include radiation therapy. Moreover, significant advances in understanding the molecular pathology of GBM and associated cell signaling pathways have opened opportunities for new therapies. Innovative treatment such as immunotherapy also gives hope for enhanced survival. The objective of this work was to collect and report the recent research findings to manage GBM. The present review includes existing novel drug delivery systems and therapies intended for managing GBM. Reported novel drug delivery systems and diverse therapies seem to be precise, secure, and relatively effective, which could lead to a new track for the obliteration of GBM.
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Baizig NM, Wided BA, Amine OE, Gritli S, ElMay M. The Clinical Significance of IGF-1R and Relationship with Epstein-Barr Virus Markers: LMP1 and EBERs in Tunisian Patients with Nasopharyngeal Carcinoma. Ann Otol Rhinol Laryngol 2020; 129:1011-1019. [PMID: 32468823 DOI: 10.1177/0003489420929362] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVES Tunisia is in the endemic area of nasopharyngeal carcinoma. Epstein-Barr virus (EBV) based assays have been commonly used as standard markers for screening and monitoring the disease. So, it is very important to find novel factors for the early diagnostic and prognostic evaluation of this cancer. The aim of the study was to evaluate the expression of IGF-1R (Insulin Growth Factor Receptor 1), LMP 1 (Latent Membrane Protein 1) and EBERs (EBV encoded RNAs) in order to determine their correlation with clinicopathologic parameters and survival rates in patients with nasopharyngeal carcinoma (NPC). We also looked for the relationship between these biomarkers. METHODS IGF-1R and LMP1 expression was performed by means of immunohistochemical method and EBERs were detected using in situ hybridization of paraffin embedded tumor tissues of 94 patients with nasopharyngeal carcinoma and 45 non-cancerous nasopharyngeal mucosa samples. RESULTS Our findings demonstrated that IGF-1R was over expressed in 47.87% of NPC patients and only in 2.22% of controls. Positive LMP1 expression was detected in 56.38% of NPC patients and all NPC patients were positive for the EBV-encoded RNAs staining. A statistically significant positive correlation was observed between IGF-1R expression and the tumor size (P < .001). Kaplan-Meier survival curves showed that NPC patients with a strong IGF-1R expression level have shorter median and 5-year Overall Survival than those with weak expression rates (100.15 vs 102.68 months, P = .08). In addition, median and 5-year Disease-Free Survival was significantly lower in the LMP1 positive NPC patients than in the LMP1 negative ones (53.38 vs 93.37 months, P = .03). Moreover, LMP1 expression correlated strongly with IGF-1R expression (P = .018). The relationship between these two biomarkers could influence patient survival. CONCLUSION IGF1-R and LMP1 could be valuable prognostic markers in Tunisian NPC patients.
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Affiliation(s)
- Nehla Mokni Baizig
- Immuno-Histo-Cytology Laboratory, Salah Azaiz Cancer Institute, Tunis, Tunisia
| | - Ben Ayoub Wided
- Department of statistics and medical informatics, Salah Azaiz Cancer Institute, Tunis, Tunisia
| | - Olfa El Amine
- Immuno-Histo-Cytology Laboratory, Salah Azaiz Cancer Institute, Tunis, Tunisia
| | - Said Gritli
- ENT Department, Salah Azaiz Cancer Institute, Tunis, Tunisia
| | - Michele ElMay
- Research Unit 17/ ES/13, Faculty of Medicine, Tunis, University of Tunis El Manar, Tunisia
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Odutola MK, Nnakelu E, Giles GG, van Leeuwen MT, Vajdic CM. Lifestyle and risk of follicular lymphoma: a systematic review and meta-analysis of observational studies. Cancer Causes Control 2020; 31:979-1000. [DOI: 10.1007/s10552-020-01342-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 08/13/2020] [Indexed: 12/21/2022]
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Zhu Y, Wang T, Wu J, Huang O, Zhu L, He J, Li Y, Chen W, Chen X, Shen K. Associations Between Circulating Insulin-Like Growth Factor 1 and Mortality in Women With Invasive Breast Cancer. Front Oncol 2020; 10:1384. [PMID: 32974138 PMCID: PMC7466632 DOI: 10.3389/fonc.2020.01384] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/30/2020] [Indexed: 01/26/2023] Open
Abstract
Background: Studies on the association between circulating insulin-like growth factor 1 (IGF1) and prognosis of breast cancer are limited. Whether this association is modified by insulin levels and clinical characteristics is unclear. Methods: Serum concentrations of IGF1 as well as IGF binding protein 3 (IGFBP3), IGF1/IGFBP3 ratio, insulin, and C-peptide were prospectively examined in 2,682 invasive breast cancer patients who received surgery in Ruijin Hospital, Shanghai, between 2012 and 2017. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence associated with different levels of IGF1 and other biomarkers with multivariable adjustment. Results: Compared with patients with low IGF1, patients with high IGF1 had a significantly lower risk of all-cause mortality (HR, 0.53; 95% CI, 0.29–0.96) and a borderline lower risk of breast cancer-specific mortality (HR, 0.53; 95% CI, 0.27–1.02). The inverse association between IGF1 and all-cause mortality was consistent across stratification subgroups but was more pronounced among patients with high insulin (HR, 0.40; 95% CI, 0.18–0.89), were premenopausal (HR, 0.34; 95% CI, 0.12–0.97), with a tumor size >2 cm (HR, 0.35; 95% CI, 0.17–0.73), with positive lymph node (HR, 0.49; 95% CI, 0.25–0.98), and with a high Ki-67 level (HR, 0.49; 95% CI, 0.26–0.95) (all P for interaction >0.05). No significant associations were found for IGFBP3, IGF1/IGFBP3 ratio, insulin, and C-peptide levels with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence. Conclusion: Circulating IGF1 was inversely and independently associated with all-cause mortality in invasive breast cancer patients, and this association was consistent across clinical risk factors.
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Affiliation(s)
- Yifei Zhu
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tiange Wang
- Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiayi Wu
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ou Huang
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Zhu
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianrong He
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yafen Li
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiguo Chen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaosong Chen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kunwei Shen
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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van de Pol JAA, George L, van den Brandt PA, Baldewijns MMLL, Schouten LJ. Etiologic heterogeneity of clear-cell and papillary renal cell carcinoma in the Netherlands Cohort Study. Int J Cancer 2020; 148:67-76. [PMID: 32638386 PMCID: PMC7689694 DOI: 10.1002/ijc.33193] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/18/2020] [Accepted: 06/19/2020] [Indexed: 12/14/2022]
Abstract
At present, mostly case‐control and retrospective studies have investigated the association between etiologic risk factors and the development of histologic subtypes of renal cell carcinoma (RCC). Therefore, we assessed the heterogeneity between body mass index (BMI), cigarette smoking, alcohol consumption and hypertension across clear‐cell RCC (ccRCC) and papillary RCC (pRCC) risk in the prospective Netherlands Cohort Study on diet and cancer. In 1986, 120 852 participants aged 55 to 69 completed a self‐administered questionnaire on diet and other risk factors for cancer. Participants were followed up for cancer through record linkage. Tumor histology was assessed through centralized revision by two experienced uropathologists. After 20.3 years of follow‐up, 384 histologically verified RCC cases, including 315 ccRCC and 46 pRCC cases and 4144 subcohort members were eligible for case‐cohort analysis. Hazard ratios and 95% confidence intervals were estimated by multivariable‐adjusted proportional hazards models. Overall, BMI was associated positively with ccRCC risk, but inversely with pRCC risk. Cigarette smoking was associated with an increased ccRCC, but a decreased pRCC risk. Alcohol consumption was inversely associated with both ccRCC and pRCC risk. Hypertension was associated with an increased risk of both ccRCC and pRCC. Statistically significant etiologic heterogeneity was observed for BMI, BMI change since age 20, and smoking duration in current smokers across ccRCC and pRCC risk. In conclusion, we observed potential heterogeneity for BMI, BMI change and smoking duration across ccRCC and pRCC risk. What's new? Etiologic risk factors for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) include alcohol consumption, body mass index (BMI), cigarette smoking, and hypertension. Little is known, however, about variability in how these factors affect the development of RCC histologic subtypes. In this population‐based prospective cohort study, examination of variability in associations between established etiologic factors and RCC histologic subtypes revealed significant heterogeneity between BMI and ccRCC and pRCC risk and between risk of these subtypes and smoking duration in current smokers. The findings provide novel insight into relationships between etiologic heterogeneity and mechanisms of RCC development.
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Affiliation(s)
- Jeroen A A van de Pol
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Lisa George
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Piet A van den Brandt
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.,Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | - Marcella M L L Baldewijns
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.,Department of Histopathology, University Hospital Gasthuisberg, Leuven, Belgium
| | - Leo J Schouten
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
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Li X, Wu W, Giovannucci E, Stampfer MJ, Gao X, Han J. Cutaneous nevi and internal cancer risk: Results from two large prospective cohorts of US women. Int J Cancer 2020; 147:14-20. [PMID: 31593602 DOI: 10.1002/ijc.32703] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 09/08/2019] [Accepted: 09/11/2019] [Indexed: 12/29/2022]
Abstract
Elevated cutaneous nevus number has been linked to longer telomeres. Recently, a large systematic Mendelian randomization study identified a significant positive association between telomere length and risk of cancer. Here, we hypothesized that higher nevus count, as a phenotypic marker of longer telomere, may be associated with increased risk of internal cancer, and prospectively examined the association between nevus count and total as well as site-specific cancer risk among participants in the Nurses' Health Study (NHS, 1986-2012) and the Nurses' Health Study 2 (NHS2, 1989-2013) using Cox proportional hazards models. During 3,900,264 person-years of follow-up, we documented a total of 23,004 internal cancer cases (15,484 in the NHS and 7,520 in the NHS2). Compared to participants who had no nevi, the multivariate hazard ratios of total cancer (excluding skin cancer) were 1.06 (95% confidence interval [CI], 1.03-1.09) for women with 1-5 nevi, 1.08 (95% CI, 1.03-1.15) for those who had 6-14 nevi and 1.19 (95% CI, 1.05-1.35) for those with 15 or more nevi (p trend <0.0001). Moreover, because nevus count has been associated with risk of breast cancer previously, we conducted a secondary analysis by excluding breast cancer from the outcomes of interest. The results were very similar to those of our primary analysis. For individual cancer, most of the associations with nevus count were positive but not statistically significant. In conclusion, we identified the number of cutaneous nevi as a phenotypic marker associated with internal cancer risk, which may be explained by telomere biology.
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Affiliation(s)
- Xin Li
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN.,Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN
| | - Wenting Wu
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
| | - Edward Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Meir J Stampfer
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Xiang Gao
- Department of Nutritional Sciences, College of Health and Human Development, Pennsylvania State University, State College, PA
| | - Jiali Han
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN.,Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN
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