Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells.

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell-related genes were identified. The drug-herb-active compound-target gene-disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.

SATB2 is a Promising Biomarker for Identifying a Colorectal Origin for Liver Metastatic Adenocarcinomas.

SATB2 (Special AT-rich sequence-binding protein 2) has recently been shown to be a specific biomarker of colorectal cancer (CRC). The aim of this study was to investigate the diagnostic potential of SATB2 as a means of detecting a CRC origin for liver metastases. SATB2 expression was examined in a resection cohort of 101 CRC and 273 non-CRC adenocarcinoma samples using immunohistochemistry (IHC). The diagnostic accuracy of CRC origins of liver metastases based on SATB2 and a three marker panel of SATB2, CK20 and CDX2 was evaluated using an independent cohort of 192 liver biopsies. IHC showed 97 of the 101 (96.0%) primary CRC samples were SATB2 positive, compared to only 6 of the 273 (2.1%) samples of other cancer types. The sensitivity, specificity and AUC values of SATB2 expression in resection samples were 97%, 97.1% and 0.977, respectively. Meanwhile, for the liver biopsy samples, the sensitivity, specificity and AUC values of a CRC liver metastases was 92.2%, 97.8% and 0.948 for SATB2, 95.1%, 91.0% and 0.959 for CK20, and 100%, 85.4% and 0.976 for CDX2, respectively. Further analysis demonstrated that all three-marker positivity was detected in 92/103 (89.3%) CRC and 2/89 (2.2%) non-CRC liver metastases sampled by biopsy. Our findings suggest that SATB2, as measured by IHC, could serve as a promising diagnostic biomarker of CRC metastases. Combining evaluation of SATB2 with CK20 and CDX2 to form a three marker panel further improved the detection of metastatic CRCs in liver biopsy tissues.

High Residual Tumor Rate for Early Breast Cancer Patients Receiving Vacuum-assisted Breast Biopsy.

Purpose: The objective of study is aiming to investigate the residual tumor rate after Vacuum-assisted Breast Biopsy (VABB) for early breast cancer excision and the efficacy of mammogram and ultrasound in detecting residual tumor. Methods: Patients who underwent VABB and were confirmed with breast cancer in Sun Yat-sen University Cancer Center from 2010 to 2015 were reviewed retrospectively. The residual tumor rate determined by histological examination was calculated, and then was compared with the results estimated by mammogram and ultrasound which were performed post VABB but before subsequent surgery. Univariate and multivariate analysis (logistic regression) were carried out to identify the independent risk factors associated with residual tumor. Results: In total, 126 eligible patients with early breast cancer were recruited for this study, of whom 79 (62.7%) had residual tumor and 47 (37.3 %) underwent complete excision. The residual tumor rates for lesions < 10mm, lesions 10 to 20 mm and lesions >20mm in size were 55.0%, 68.9% and 53.1%, respectively. The complete excision rates estimated by mammogram and ultrasound were 76.5% and 73.9%, with a negative predictive value of only 46.2% and 50.6%, respectively. In the multivariate logistic regression analysis, no specific factors were found associated with risk of residual tumor (all P > 0.05). Conclusions: There was a high residual tumor rate after VABB in early breast cancer. Both mammogram and ultrasound could not effectively detect the residual tumor after VABB.