Expression of MSI1 and HER2 in mammary Paget's disease and their correlation with clinicopathological features and prognosis / 中华病理学杂志

Objective: To investigate the expression of MSI1 and HER2 in mammary Paget's disease, and the correlation between the expression levels of MSI1 and HER2 and the clinicopathologic characteristics and prognosis of the patients. Methods: Clinical data and paraffin-embedded specimens of 34 pairs of mammary Paget's disease and underlying breast cancer were collected at the Department of Pathology, Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University from March 2011 to December 2019. Immunohistochemistry was used to detect the expression of MSI1 and HER2 in mammary Paget's disease and the accompanying breast cancer, and to analyze the correlation between the expression levels of MSI1 and HER2 and their clinicopathologic features, as well as their influence on prognosis. Results: In mammary Paget's disease, the positive rate of MSI1 was 91.2% (31/34) and the positive rate of HER2 was 88.2% (30/34); the expression of MSI1 and HER2 was positively correlated (P=0.001, r=0.530). The expression of MSI1 was positively correlated with menopausal status (r=0.372, P=0.030) and lymph node metastasis (r=0.450, P=0.008). HER2 expression was positively correlated with menopausal status (r=0.436, P=0.010), and negatively correlated with ER expression (r=-0.365, P=0.034). The co-expression of MSI1 and HER2 was positively correlated with age (r=0.347, P=0.044) and menopausal status (r=0.496, P=0.003), and negatively correlated with ER expression (r=-0.461, P=0.006). Conclusions: MSI1 and HER2 are highly expressed in mammary Paget's disease and their expression levels are positively correlated. The correlation analysis between clinicopathological features and prognosis suggests that both of them may be involved in the occurrence and development of mammary Paget's disease and are potential therapeutic targets for mammary Paget's disease.

Effect of Metabolic Reprogramming on Toxin Eliminating Therapeutics in Targeting Lung Cancer Stem Cells / 中国实验方剂学杂志

Objective::To observe the effect of realgar nanoparticles (a representative drug in toxin eliminating therapeutics) targeting hypoxia-inducible factors (HIF), which act as effector molecules on metabolic reprogramming of lung cancer stem cells, and to explore the effect mechanism of lung cancer stem cells and metabolic reprogramming in the process of lung cancer metastasis, so as to verify the effectiveness of toxin eliminating therapeutics in the prevention and treatment of lung cancer metastasis. Method::Lung cancer A549 cells were cultured in vitro, and lung cancer stem cells were then identified and selected. The stem cells were divided into blank control group, cisplatin group (5 mg·L-1), realgar nanoparticles low, medium and high dose groups (100, 200, 400 mg·L-1). After intervention, glucose oxidase method was used to detect the effect of realgar nanoparticles on the glucose metabolism of lung cancer stem cells, real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of hypoxia-inducible factors-1α (HIF-1α), C-myc and p53, while Western blot was used to detect the expression of related proteins HIF-1α, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and enzyme linked immunosorbent assay (ELISA) was used to detect the glucose transporter 1 (GLUT1), pyruvate dehydrogenase kinase 1 (PDK1), pyruvate kinase M (PKM), phosphofructokinase(PFK), pyruvate dehydrogenase (PDH) and lactic dehydrogenase (LDH) expression. Result::As compared with the blank control group, realgar nanoparticles can reduce the glucose consumption of lung cancer stem cells, and the glucose consumption was reduced with the increase of dose in a time-and dose-dependent manner (P<0.01). Realgar nanoparticles can inhibit the mRNA expression of HIF-1α, a key factor in metabolic reprogramming of lung cancer stem cells (P<0.05, P<0.01), down-regulated C-myc mRNA and up-regulated the p53 mRNA expression (P<0.05, P<0.01), down-regulated protein expressions of PI3K, Akt, mTOR(P<0.05, P<0.01), and inhibited the expression of related enzymes GLUT1, PDK1, PFK, PKM, PDH, and LDH levels (P<0.05, P<0.01). With the increase of dose, the regulation and control ability of realgar nanoparticles gradually increased. Conclusion::Toxin eliminating therapeutics can drive the metabolic reprogramming of lung cancer stem cells by targeting HIF effector molecule, and then inhibit the invasion and metastasis of lung cancer.