The tumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation. We used mouse models of hyperglycemia and cancer and specimens from hyperglycemic breast cancer (BC) patients to demonstrate that miR-467 mediates the effects of high blood glucose on cancer inflammation and growth. Hyperglycemic patients have a higher risk of developing breast cancer. We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth (p < 0.001). Tumors from hyperglycemic mice had a two-fold increase in macrophage accumulation compared to normoglycemic controls (p < 0.001), and TAM infiltration was prevented by the miR-467 antagonist (p < 0.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs. normoglycemic patients (2.17-fold, p = 0.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold increase, p = 0.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients (p < 0.001) and increased 56-fold in adjacent normal tissue (p = 0.008). Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.
Background: Tumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation. Methods: We used mouse models of hyperglycemia and cancer and specimens from hyperglycemic breast cancer (BC) patients to demonstrate that miR-467 mediates the effects of high blood glucose on cancer inflammation and growth.Results: Hyperglycemic patients have a higher risk of developing breast cancer (BC). We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth (P<.001). Tumors from hyperglycemic mice had a 2-fold increase in macrophage accumulation compared to normoglycemic controls (P<.001), and TAM infiltration was prevented by the miR-467 antagonist (P<.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs normoglycemic patients (2.17-fold, P=.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold inc., P=.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients (P<.001) and increased 56-fold in adjacent normal tissue (P=.008). Conclusions: Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.
Background: ChatGPT is among the most popular Large Language Models (LLM), exhibiting proficiency in various standardized tests, including multiple-choice medical board examinations. However, its performance on Otolaryngology - Head and Neck Surgery (OHNS) board exams and open-ended medical board examinations has not been reported. We present the first evaluation of LLM (ChatGPT-4) on such examinations and propose a novel method to assess an artificial intelligence (AI) model's performance on open-ended medical board examination questions. Methods: Twenty-one open end questions were adopted from the Royal College of Physicians and Surgeons of Canada's sample exam to query ChatGPT-4 on April 11th, 2023, with and without prompts. A new CVSA (concordance, validity, safety, and accuracy) model was developed to evaluate its performance. Results: In an open-ended question assessment, ChatGPT-4 achieved a passing mark (an average of 75% across three trials) in the attempts. The model demonstrated high concordance (92.06%) and satisfactory validity. While demonstrating considerable consistency in regenerating answers, it often provided only partially correct responses. Notably, concerning features such as hallucinations and self-conflicting answers were observed. Conclusion ChatGPT-4 achieved a passing score in the sample exam, and demonstrated the potential to pass the Canadian Otolaryngology-Head and Neck Surgery Royal College board examination. Some concerns remain due to its hallucinations that could pose risks to patient safety. Further adjustments are necessary to yield safer and more accurate answers for clinical implementation.
ABSTRACTTumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation.Hyperglycemic patients have a higher risk of developing breast cancer (BC). We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth (P<.001). Tumors from hyperglycemic mice had a 2-fold increase in macrophage accumulation compared to normoglycemic controls (P<.001), and TAM infiltration was prevented by the miR-467 antagonist (P<.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs normoglycemic patients (2.17-fold, P=.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold inc., P=.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients (P<.001) and increased 56-fold in adjacent normal tissue (P=.008).Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.
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