Advances in immune regulation of the G protein-coupled estrogen receptor.

Estrogen and related receptors have been shown to have a significant impact on human development, reproduction, metabolism and immune regulation and to play a critical role in tumor development and treatment. Traditionally, the nuclear estrogen receptors (nERs) ERα and ERß have been thought to be involved in mediating the estrogenic effects. However, our group and others have previously demonstrated that the G protein-coupled estrogen receptor (GPER) is the third independent ER, and estrogen signaling mediated by GPER is known to play an important role in normal physiology and a variety of abnormal diseases. Interestingly, recent studies have progressively revealed GPER involvement in the maintenance of the normal immune system, abnormal immune diseases, and inflammatory lesions, which may be of significant clinical value primarily in the immunotherapy of tumors. In this article, we review current advances in GPER-related immunomodulators and provide a theoretical basis and potential clinical targets to ameliorate immune-related diseases and immunotherapy for tumors.

Copy number variants landscape of multiple cancers and clinical applications based on NGS gene panel.

BACKGROUND: The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood. METHODS: We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs. RESULTS: We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (p = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs. CONCLUSION: The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.

Radiomics Based on Dynamic Contrast-Enhanced MRI to Early Predict Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Therapy.

RATIONALE AND OBJECTIVES: To investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based radiomics at baseline and after two cycles of neoadjuvant therapy (NAT) and associated longitudinal changes for early prediction of the NAT response in patients with breast cancer. MATERIALS AND METHODS: One hundred seventeen patients with breast cancer who underwent DCE-MRI before NAT and after two cycles of NAT from April 2019 to November 2021 were enrolled retrospectively. Patients were randomly divided into a training set (n = 81) and a test set (n = 36) at a ratio of 7:3. Clinical-pathological data and the relative tumor maximum diameter regression value (diameter%) were also collected. A total of 851 radiomic features were extracted from the phase with the most pronounced tumor enhancement on DCE-MRI T1 imaging acquired both pre- and post-treatment. Delta and delta% radiomics features were also calculated. The Least Absolute Shrinkage and Selection Operator (LASSO) method was applied to select features, and a logistic regression model was used to calculate pre-NAT, early-NAT, delta, and delta% radscores and then select among four radscores to build a Fusion radiomics model. The final clinical-radiomics model was constructed by combining fusion radscores and clinical-pathological variables. The discrimination and clinical utility of the models were further evaluated and compared. RESULTS: The area under the curve (AUC) values of the fusion radiomics model based on pre-NAT, Delta, and Delta% radscores were 0.868 of 0.825. The clinical-radiomics model integrating Fusion radscores and clinical-pathological variables achieved AUC values of 0.920 of 0.884, which were higher than those of the clinical model constructed by AUC values (0.858/0.831), although no significant improvement was observed in the test set (Delong test, p = 0.196). Decision curve analysis (DCA) showed that the clinical-radiomics model demonstrated more clinical utility than the clinical model. CONCLUSION: DCE-MRI-based radiomics features may have potential for pathological complete response (pCR) prediction in the early phase of NAT. By combining radiomics features and clinical-pathological characteristics, higher diagnostic performance can be achieved.

Lidocaine prevents breast cancer growth by targeting neuronatin to inhibit nerve fibers formation.

Lidocaine has been shown to inhibit the invasion and metastasis of breast cancer, but the mechanism still remains unclear. This study explored the relationship between lidocaine and circulating seeding of breast cancer cells from the perspective of nerve fiber formation. The cell lines MDA-MB-231 and 4T1 were subcutaneously inoculated in mice to simulate the tumor self-seeding by circulating cancer cells. Lidocaine was used to treat these mice and tumor growth was observed. Silver staining was performed to observe the distribution of nerve fibers in tumor-bearing tissues, and immunohistochemical analysis was performed to observe the expression levels of nerve-related proteins. The results showed that lidocaine treatment effectively inhibited tumor growth and nerve fiber formation, and down-regulated the expression levels of protein gene product 9.5, neurofilament, nerve growth factor (NGF), and neuronatin (Nnat). Overexpression NGF and Nnat both could reverse the therapeutic effects of lidocaine. These results suggest that the effect of lidocaine on inhibiting breast cancer invasion and metastasis may be achieved by targeting Nnat, regulating the production of NGFs in cancer cells, and subsequently inhibiting the formation of nerve fibers.

Repair of Bile Duct Injury With Autologous Vein Graft and Stent.

OBJECTIVES: We investigated the effects of autologous vein transplant on bile duct injury repair, through observation of the hepatic and biliary system tissue morphology changes and animal survival after bile duct injury repair. MATERIALS AND METHODS: Rabbits were equally divided into groups. Group A had cholecystectomy and common bile duct resection (length of 0.5 cm), transplant of an autologous vein (length of 0.5 cm), and stent implant. Group B had cholecystectomy and common bile duct resection (length of 1.0 cm), transplant of an autologous vein (length of 1.0 cm), and stent implant. The third group (group C) had cholecystectomy only. RESULTS: Two rabbits died in group A and group B; all experimental animals from group C survived. Regarding liver biochemical indexes at preoperative week 1, at postoperative month 1, and at postoperative month 3, we found no significant differences (paired t test, P > .05). Liver biochemical indexes between groups were also not significantly different (P > .05). At month 3, postoperative liver pathology of experimental animals showed no significant changes and no cholestasis; biliary epithelial cells were seen in the transplant vascular. CONCLUSIONS: We conclude that autologous vein graft can effectively repair bile duct injury for a short coloboma.