Type-2 diabetes mellitus-associated cancer risk: In pursuit of understanding the possible link

Vulichi, Srinivasa Rao; Runthala, Ashish; Begari, Nagaraju; Kumar, Rupak; Rao, C. Venkata; Kapila, Suman; Chippada, Appa Rao; Sistla, Durga Srinivasa Murthy

doi:10.1016/j.dsx.2022.102591

Cited by 7 publications

(4 citation statements)

References 70 publications

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“…[14] Additionally, during the high FBG state, the phosphoinositide-3-kinase (PI-3K), hyperglycemia-associated transcriptional, post-transcriptional factors, and AMP-activated protein kinase probably also contribute to the advancement of cancer. [8] For instance, because the PI-3K singling pathway is crucial for the energy consumption of tumor cells, inhibiting PI-3K could effectively hinder the tumor growth. [15] In hyperglycemia, the integrity of the cellular DNA can be drastically jeopardized, the expression of messenger RNA, long non-coding RNA, and microRNA can be modified, and the post-translational modifications like acetylation can also be altered.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have suggested that hyperglycemia may contribute to the cancer progression, though no substantial evidence indicates the possible link among them. [8] The prediction value of fasting blood-glucose (FBG) for cancer patients is still under investigation due to the rarely relevant study. Additionally, the nutrition and inflammatory status of patients are linked to their outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Fasting Blood Glucose-Based Novel Predictors in Predicting Prognosis for Pancreatic Neuroendocrine Neoplasms Patients

Yu,

Fu,

Yang

et al. 2024

Preprint

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Objective: To explore three novel fasting blood glucose (FBG)-based novel indicators, including FBG-to-albumin ratio (FAR), FBG-to-lymphocytes ratio (FLR), and FBG-to-hemoglobin ratio (FHR), in predicting prognosis and detecting metastasis for patients with pancreatic neuroendocrine neoplasms after resection. Materials and methods: A total of 178 pNEN patients underwent surgical resection were included in this study. Receiver operating characteristic (ROC) curves were used to evaluate the diagnosis values of FAR, FLR, and FHR, and the cut-off values were obtained for further analyses. Univariate and multivariate analyses were conducted to determine the independent predictors. The Kaplan-Meier method was used to evaluate the progression-free survival (PFS) and overall survival (OS) of the pNEN patients. Results: The optimal cut-off values of FAR, FLR, and FHR were 0.17, 2.85, and 0.028, respectively. As for PFS, the area under the curve (AUC) was 0.693 for FAR, 0.690 for FLR, and 0.661 for FHR, respectively. The AUC was 0.770, 0.692, and 0.715 accordingly for OS. The groups with lower FAR, FLR, and FHR were significantly associated with prolonged PFS and OS (p < 0.05). In patients with metastasis, the lower FAR group was correlated with significantly longer PFS and OS (p = 0.022 and 0.002, respectively). The FLR was an independent predictor of PFS in pNEN patients, and the FAR was a predictor of OS. FAR was an independent indicator of PFS in patients with metastasis. Conclusion: Preoperative FAR, FLR, and FHR are effective in predicting the prognosis of pNEN patients and detecting the synchronous metastases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fasting Blood Glucose-Based Novel Predictors in Predicting Prognosis for Pancreatic Neuroendocrine Neoplasms Patients

Yu,

Fu,

Yang

et al. 2024

Preprint

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“…The AGE–RAGE interactions and binding of RAGE with various other ligands not only contributes to the exacerbation of oxidative stress but also to the over-expression of RAGEs themselves. The signaling pathways arising from AGE–RAGE interactions are implicated in a variety of pathological disorders, including neurodegeneration, cardiovascular diseases, cancer, diabetic neuropathy, diabetic retinopathy and diabetes [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 50 ]. Furthermore, in Parkinson’s Disease (PD) cases, microglial cell-mediated neuroinflammation and α-synuclein aggregation are exacerbated upon the binding of RAGE to receptors on α-synuclein fibrils on microglia [ 34 ].…”

Section: Receptors For Advanced Glycation Endproducts (Rage)mentioning

confidence: 99%

“…Although pathogenesis due to AGEs is multifactorial, recently it has been recognized that a key factor in the pathogenesis of AGEs is through their binding to receptors for Advanced Glycation Endproducts (RAGE), which results in a deleterious activation of a cascade of signaling events, and the formation of pro-inflammatory cytokines that triggers further oxidative stress and an excessive build-up of AGEs and RAGE. That is, the higher concentration of AGEs would lead to the increased expression of RAGE and this vicious cycle leads to the onset of neurodegenerative diseases, including AD, ALS, progression of the secondary effects of TBI, diabetes, atherosclerosis, rheumatoid arthritis, and cancers [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Other endogenous ligands, including high mobility group box1 (MGB1) proteins, also contribute to the RAGE-induced inflammatory responses (through intracellular signaling activation of the TLR4/NF-κB/interleukin pathway), as demonstrated in the TBI animal models [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

RAGE Inhibitors in Neurodegenerative Diseases

2023

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Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer’s disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood–brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE–RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE–RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE–RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.

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