Urothelial overexpression of insulin‐like growth factor‐1 increases susceptibility to <i>p</i>‐cresidine‐induced bladder carcinogenesis in transgenic mice

Hursting, Stephen D.; Perkins, Susan N.; Lavigne, Jackie A.; Beltrán, Linda; Haines, Diana C.; Hill, Heather; Alvord, W. Gregory; Barrett, J. Carl; DiGiovanni, John

doi:10.1002/mc.20548

Cited by 12 publications

(6 citation statements)

References 28 publications

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“…Animal [17] and in vitro [18] studies support a role of IGF in bladder carcinogenesis. Studies in human beings conducted in the USA [7] and in Ireland [19] also provided evidence for such a link between IGF and bladder cancer.…”

Section: Discussionmentioning

confidence: 83%

Human Insulin Does Not Increase Bladder Cancer Risk

Tseng

2014

PLoS ONE

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BackgroundWhether human insulin can induce bladder cancer is rarely studied.MethodsThe reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression.ResultsThere were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122–1.366)], but not in the model adjusted for all covariates [1.063 (0.951–1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted.ConclusionsThis study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication.

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Section: Discussionmentioning

confidence: 83%

Human Insulin Does Not Increase Bladder Cancer Risk

Tseng

2014

PLoS ONE

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“…There have been several studies confirming the role of IGF-1, an anti-apoptotic peptide, in the progression of BCa. Hursting et al [17] showed that IGF-1 pathway plays a vital role in bladder carcinogenesis in transgenic mice. Long et al [18] reported that IGF-1/ERβ signalling plays an important role in promoting cisplatin resistance in BCa cells.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Lin

et al. 2020

Cancer Cell Int

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Background: Bladder cancer (BCa) is one of the important tumors that have been proven to be treatable with immunotherapy. This study aims to identify and validate a molecular prognostic index of BCa based on immunogenomic landscape analysis. Methods: The cancer genome atlas (TCGA) database and immunology database and analysis portal (ImmPort) database were used to identified differentially expressed immune-related genes (IRGs). Prognostic IRGs were screened and protein-protein interaction (PPI) network was constructed. Multivariate Cox analysis was performed to develop a molecular prognostic index of BCa. Internal and external validation were then performed in TCGA cohort and GEO cohort, respectively. Besides, we also explore the relationship between this index and clinical characteristics, immune cell infiltration and tumor microenvironment. Results: A total of 61 prognostic IRGs were identified and a molecular prognostic index was developed. The top four hub genes included MMP9, IGF1, CXCL12 and PGF. The difference in overall survival between high-risk group and low-risk group was statistically significant. The area under curve of the receiver operating characteristic (ROC) curve was 0.757, suggesting the potential for this index. Besides, Internal validation using TCGA cohort and external validation using GEO cohort indicated that this index was of great performance in predicting outcome. T cells CD8, T cells CD4 memory activated, T cells follicular helper, macrophages M0, macrophages M2 and neutrophils were significantly associated with prognosis of BCa patients. Female, high grade, stage III&IV, N1-3 and T3-4 were associated significantly with higher risk score compared with male, low grade, stage I&II, N0 and T1-2, respectively. High risk score had a positive association with higher stromal score and ESTIMATE score while high risk score had a negative association with tumor purity. Conclusions: This study identified several prognostic immune-related genes of clinical value. Besides, we developed and validated a molecular index based on immunogenomic landscape analysis, which performed well in predicting prognosis of BCa. Further researches are needed to verify the effectiveness of this index and these vital genes.

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“…Hyperinsulinemia can increase the bioactivity of insulin-like growth factor 1 (35), which may potentially mediate the association between glycemic index and bladder cancer risk. Insulin-like growth factor-1 was able to promote the p-cresidine-induced bladder tumor development in transgenic mice (36). Obesity (6) and diabetes (5), characterized with high IGF-I levels, also have been reported to be positively associated with an increased risk of bladder cancer.…”

Section: Discussionmentioning

confidence: 96%

Carbohydrates, Glycemic Index, and Glycemic Load in Relation to Bladder Cancer Risk

Zhu

Shen

et al. 2020

Front. Oncol.

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Objective: Epidemiologic studies investigating the association between dietary carbohydrates as well as glycemic index and glycemic load (markers of carbohydrate quality) and bladder cancer risk have yielded inconsistent results. The aim of the present meta-analysis is to summarize the evidence on this association. Materials and Methods: A comprehensive literature search of articles published by December 2019 was performed in PubMed, Scopus, and Web of Science databases. A random-effects model was used to calculate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results: Twelve observational studies were included in the final analysis. There was no evidence of an association between consumption of carbohydrates and bladder cancer risk (pooled OR, 1.04; 95% CI, 0.92-1.17). No statistically significant association between glycemic load and bladder cancer was likewise found (pooled OR, 1.10; 95% CI, 0.85-1.42). However, there was a significant positive association between glycemic index and bladder cancer risk (pooled OR, 1.25; 95% CI, 1.11-1.41). In the dose-response analysis, the pooled OR (95% CI) per 10 units of glycemic index per day was 1.02 (95% CI, 1.01-1.04). Conclusion: In this meta-analysis, glycemic index showed a positive linear association with bladder cancer risk.

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Urothelial overexpression of insulin‐like growth factor‐1 increases susceptibility to p‐cresidine‐induced bladder carcinogenesis in transgenic mice

Cited by 12 publications

References 28 publications

Human Insulin Does Not Increase Bladder Cancer Risk

Human Insulin Does Not Increase Bladder Cancer Risk

Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis

Carbohydrates, Glycemic Index, and Glycemic Load in Relation to Bladder Cancer Risk

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