New insight for metformin against bladder cancer

El‐Arabey, Amr Ahmed

doi:10.1186/s41021-017-0074-z

Cited by 21 publications

(10 citation statements)

References 88 publications

(90 reference statements)

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“…There have been many reports of the versatile nature of metformin in the inhibition of cancer. 28 – 30 Our previous study confirmed the effects of metformin in the suppression of HIF-1α expression and the subsequent enhancement of the therapeutic effects of cisplatin. 23 In addition, metformin is a clinically approved drug which may have great potential for future clinical trials if the capacity to re-sensitize tumors to gefitinib is shown.…”

Section: Resultssupporting

confidence: 73%

Metformin sensitizes hypoxia-induced gefitinib treatment resistance of HNSCC via cell cycle regulation and EMT reversal

Yin¹,

Zheng²,

Song³

et al. 2018

CMAR

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ObjectivesThe objectives of this study were to explore the mechanisms of metformin sensitization to hypoxia-induced gefitinib treatment in resistant head and neck squamous cell carcinoma (HNSCC) and evaluate the effects of this combined treatment strategy.MethodsThe effects of gefitinib treatment on HNSCC were measured under normoxic and hypoxic conditions. The relationship between hypoxia and cell cycle and epithelial–mesenchymal transition (EMT) in tumor cells were analyzed. Palbociclib and LY294002 were used in combination with gefitinib to evaluate the effects on HNSCC cell cytotoxicity during hypoxia. Finally, metformin was used to evaluate the sensitizing effects of gefitinib treatment on HNSCC in vivo and in vitro.ResultsCell viability and apoptosis assays demonstrated a significant difference in HNSCC cells treated with gefitinib between the normoxia and hypoxia groups. Hypoxia induced the expression of cyclin D1, decreased the percentage of cells in G1, and promoted the EMT of tumor cells. Both palbociclib and LY294002 enhanced gefitinib-induced cytotoxicity of HNSCC cells under hypoxic conditions. Encouragingly, metformin sensitized HNSCC to gefitinib treatment in vivo and in vitro.ConclusionHypoxia promotes G1–S cell cycle progression and EMT in HNSCC, resulting in gefitinib treatment resistance. Metformin sensitizes HNSCC to gefitinib treatment, which might serve as a novel combined treatment strategy.

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Section: Resultssupporting

confidence: 73%

Metformin sensitizes hypoxia-induced gefitinib treatment resistance of HNSCC via cell cycle regulation and EMT reversal

Yin¹,

Zheng²,

Song³

et al. 2018

CMAR

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“…The comorbidities related to the risk of bladder cancer considered in this study were diabetes mellitus (DM) (ICD-9-CM code 250), [ 17 ] hypertension (ICD-9-CM codes 401–405), [ 18 ] obesity (body mass index > 27) (ICD-9-CM codes 278 and 278.0), [ 19 ] chronic obstructive pulmonary disease (COPD) (as a proxy of smoking; ICD-9-CM codes 490–496), [ 20 ] and uremia (ICD-9-CM code 586). [ 21 ] Medications related to the risk of bladder cancer were aspirin (ATC codes B01AC06 and N02BA01), [ 22 ] nonsteroidal anti-inflammatory drugs (NSAIDs) (ATC code M01A), [ 23 ] metformin (ATC code A10BA02), [ 24 ] rosiglitazone (ATC code A10BG02), [ 25 ] and pioglitazone (ATC codeA10BG03). [ 25 ]…”

Section: Methodsmentioning

confidence: 99%

Increased risk of bladder cancer in young adult men with hyperlipidemia

et al. 2021

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A high-cholesterol diet increases the risk of bladder cancer. The purpose of this nationwide longitudinal population-based retrospective cohort study is to investigate whether hyperlipidemia is a risk factor for bladder cancer. Data from Taiwan National Health Insurance Database were analyzed. The primary study end point was the occurrence of newly diagnosed bladder cancer. The relative risk of bladder cancer in a hyperlipidemia cohort was compared with that in an age- and gender-matched non-hyperlipidemia cohort by using the Cox proportional hazards regression model. Cox regression analyses were further adjusted by the propensity score. Our data revealed that the hyperlipidemia cohort (n = 33,555) had a significantly higher subsequent risk of bladder cancer than did the non-hyperlipidemia cohort (n = 33,555) (adjusted hazard ratio [HR] = 1.37, P = .005) after propensity score adjustment. Subgroup analyses revealed that men in the hyperlipidemia cohort had a significantly higher subsequent risk of bladder cancer than did those in the non-hyperlipidemia cohort (adjusted HR = 1.36, P = .040). However, the risk of bladder cancer was not significantly different between women in the hyperlipidemia cohort and those in the non-hyperlipidemia cohort. Subgroup analyses further revealed that the risk of bladder cancer was significantly higher in men aged 20 to 39 years in the hyperlipidemia cohort than in those in the non-hyperlipidemia cohort (adjusted HR = 5.45, P = .029). In conclusion, hyperlipidemia is a risk factor for bladder cancer in young adult men.

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“…It is noteworthy that HER2 expression has been reported in various pediatric cancers including Wilm's tumor; however, in comparison with adult cancers, several features of HER2 such as expression pattern and clinical outcome perhaps are different in pediatric cancers [171]. Fascinatingly, there are many similarities in the risk factors of pancreatic and urinary bladder cancers such as tobacco use and obesity-related conditions like diabetes and metabolic syndrome [172], [173], [174], [175], [176].…”

Section: Tumors Of the Genitourinary/excretory Organsmentioning

confidence: 99%

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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Abstract:Obesity is associated with the risk of several health disorders including certain cancers. Among obesity-related cancers, postmenopausal breast carcinoma is a well-studied one. Apart from an increase in certain types of lipids in obesity, excess adipose tissue releases many hormone-like cytokines/adipokines, which are usually pro-inflammatory in nature. Leptin is one of such adipokines and significantly linked with the intracellular signaling pathways of other growth factors such as insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2). In general, HER2 is overexpressed in roughly 30% of breast carcinomas; its presence indicates aggressive tumor behavior. Conversely, HER2 has certain effects in normal conditions such as differentiation of preadipocytes, cardiovascular health and vitamin D metabolism. HER2 has no known endogenous ligand, but it may form dimers with other three members of the epidermal growth factor receptor (EGFR) family and can activate downstream signaling pathways. Furthermore, HER2 is intimately connected with several enzymes, e.g. fatty acid synthase (FASN), phosphatidylinositol 3-kinase (PI3K), AKT and mechanistic target of rapamycin (mTOR), all of which play significant regulatory roles in lipogenic pathways or lipid metabolism. In obesity-related carcinogenesis, characteristics like insulin resistance and elevated IGF-1 are commonly observed. Both IGF-1 and leptin can modulate EGFR and HER2 signaling pathways. Although clinical studies have shown mixed results, the behavior of HER2+ tumor cells including HER2 levels can be altered by several factors such as obesity, leptin and fatty acids. A precise knowledge is useful in new therapeutic approaches against HER+ tumors.

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New insight for metformin against bladder cancer

Cited by 21 publications

References 88 publications

Metformin sensitizes hypoxia-induced gefitinib treatment resistance of HNSCC via cell cycle regulation and EMT reversal

Metformin sensitizes hypoxia-induced gefitinib treatment resistance of HNSCC via cell cycle regulation and EMT reversal

Increased risk of bladder cancer in young adult men with hyperlipidemia

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

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