Retrospective analysis of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67 changes and their clinical significance between primary breast cancer and metastatic tumors.

Objective: To explore the relationship between receptor heterogeneity and clinicopathological characteristics in 166 patients with invasive breast cancer during metastasis. Methods: We conducted a retrospective analysis of 166 patients diagnosed with metastatic breast cancer through biopsy, who were admitted to our hospital from January 2018 to December 2022. Statistical analysis was employed to assess the heterogeneity of receptors in both primary and metastatic lesions, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67, as well as their association with clinicopathological features such as tumor size, lymph node metastasis, treatment regimen, and disease-free survival. Results: The discordant expression rates of ER, PR, HER2, Ki-67 and Luminal classification between primary and metastatic lesions were 21.7%, 41.6%, 8.9%, 34.4% and 36.8%, respectively. There is a significant difference in disease-free survival between patients with consistent and inconsistent receptor status of primary and metastatic lesions, which is statistically significant. The median DFS for primary HER2(-) to metastatic HER2(+) was 84 months, which was relatively high. The Cox multivariate regression analysis revealed that the expression differences of ER, PR, HER2, and Ki67 were not influenced by endocrine therapy and chemotherapy. However, a statistically significant difference in HER2 expression was observed with targeted therapy. Tumor size was correlated with ER and Ki67 receptor status (P = 0.019, 0.016). Tumor size was not correlated with PR, and HER2 (P = 0.679, 0.440). Lymph node metastasis was not associated with changes in ER, PR, HER2, and Ki67. The discordant rates of ER, PR, HER2, and Ki-67 in patients with local recurrence were 22%, 23.7%, 5.1%, and 28.8% respectively, whereas those in patients with distant metastasis were 21.5%, 36.4%, 10.3%, and 31.8% respectively. Conclusions: The expression levels of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer exhibit heterogeneity, which is closely associated with the prognosis and treatment outcomes of patients.

Transgenic n-3 PUFAs enrichment leads to weight loss via modulating neuropeptides in hypothalamus.

Body weight is related to fat mass, which is associated with obesity. Our study explored the effect of fat-1 gene on body weight in fat-1 transgenic mice. In present study, we observed that the weight/length ratio of fat-1 transgenic mice was lower than that of wild-type mice. The serum levels of triglycerides (TG), cholesterol (CT), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and blood glucose (BG) in fat-1 transgenic mice were all decreased. The weights of peri-bowels fat, perirenal fat and peri-testicular fat in fat-1 transgenic mice were reduced. We hypothesized that increase of n-3 PUFAs might alter the expression of hypothalamic neuropeptide genes and lead to loss of body weight in fat-1 transgenic mice. Therefore, we measured mRNA levels of appetite neuropeptides, Neuropeptide Y (NPY), Agouti-related peptides (AgRP), Proopiomelanocortin (POMC), Cocaine and amphetamine regulated transcript (CART), ghrelin and nesfatin-1 in hypothalamus by real-time PCR. Compared with wild-type mice, the mRNA levels of CART, POMC and ghrelin were higher, while the mRNA levels of NPY, AgRP and nesfatin-1 were lower in fat-1 transgenic mice. The results indicate that fat-1 gene or n-3 PUFAs participates in regulation of body weight, and the mechanism of this phenomenon involves the expression of appetite neuropeptides and lipoproteins in fat-1 transgenic mice.

Phytic acid attenuates inflammatory responses and the levels of NF-κB and p-ERK in MPTP-induced Parkinson's disease model of mice.

Phytic acid (PA) is a naturally occurring constituent which exhibits protective action in Parkinson's disease (PD). Inflammation in the central nervous system (CNS) is strongly associated with neuronal death in PD. However, the molecular mechanism of the protective effect of PA in PD has not been fully elucidated. In this study, we tried to testify the protection of PA on neuron and inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model of mice and investigated the mechanism involved in them. Motor behavior test and tyrosine hydroxylase (TH) immunohistochemistry method showed PA significantly inhibited MPTP-induced dopaminergic cell loss in the substantia nigra (SN). Moreover, using immunohistochemistry method and quantitative polymerase chain reaction (qPCR), microglial activation and inducible nitric oxide synthase (iNOS) were found to be markedly repressed by PA. Via western blot assay, expressions of nuclear factor κB (NF-κB) and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly attenuated by PA. In conclusion, it is suggested that PA has a neuroprotective effect in MPTP-induced PD model and the neuroprotection is correlated with its anti-inflammatory effect which may be associated with suppression of pathways that involved in NF-κB and p-ERK.