No abstract

Triple-negative breast carcinomas (TNBC) are characterized by particularly poor outcomes, and there are no established markers significantly associated with prognosis. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that have been recently shown to play critical roles in cancer biology. However, little is known about their mechanistic role in TNBC pathogenesis. In this report, we investigated the expression patterns of lncRNAs from TNBC tissues and matched normal tissues with Agilent Human lncRNA array. We identified 1,758 lncRNAs and 1,254 mRNAs that were differentially expressed (≥ 2-fold change), indicating that many lncRNAs are significantly upregulated or downregulated in TNBC. Among these, XR_250621.1 and NONHSAT125629 were the most upregulated and downregulated lncRNAs respectively. qRT-PCR was employed to validate the microarray analysis findings, and results were consistent with the data from the microarrays. GO and KEGG pathway analysis were applied to explore the potential lncRNAs functions, some pathways including microtubule motor activity and DNA replication were identified in TNBC pathogenesis. Our study revealed that a set of lncRNAs were differentially expressed in TNBC tissues, suggesting that they may play role in TNBC. These results shed light on lncRNAs’ biological functions and provide useful information for exploring potential therapeutic targets for breast cancer.

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

Abstract. Endoscopic thyroidectomy (ET) allows surgeons to remove a thyroid tumor from a remote site, while providing excellent results from a cosmetic viewpoint. The aim of this study was to explore the appropriateness and outcomes of ET via breast approach for the treatment of benign thyroid tumors. A total of 637 patients with benign thyroid tumors were recruited in our department. Two hundred and eighty-five patients underwent the ET via breast approach (ET group) and 352 matched control patients underwent conventional thyroidectomy (ConT group). Variables, such as surgery-related outcomes and postoperative complications, were compared between these two groups. A unilateral lobectomy was performed in 126 patients (44.2%) of the ET group and in 163 patients (46.3%) of the ConT group. A bilateral total thyroidectomy was performed in 159 patients (55.8%) of the ET group and in 189 patients (53.7%) of the ConT group. The operative time in the ET group was longer compared to the ConT group (79.9±20.10 vs. 45.4±11.90 min, P<0.001, for unilateral lobectomy; and 89.9±14.60 vs. 60.0±8.44 min, P<0.001, for bilateral total thyroidectomy). The ET group had a significantly longer mean hospital stay compared to the ConT group (5.5±0.50 vs. 5.3±0.75 days, P=0.002). There was no case of conversion to conventional open surgery in the ET group. The recurrent laryngeal nerves and parathyroid glands were identified and protected in all cases. Our results indicate that ET performed via breast is a technically feasible and safe procedure with excellent cosmetic results for patients with benign thyroid tumors.

Ferroptosis, which is characterized by intracellular iron accumulation and lipid peroxidation, is a newly described form of regulated cell death that may play a key role in tumour suppression. In the present study, we investigated the expression profiles and biological effects of fascin actin-bundling protein 1 (Fascin, gene name FSCN1) in breast cancer. In addition, bioinformatics analysis of the TCGA cancer database and gain- and loss-of-function studies showed that Fascin enhances sensitivity to erastin-induced ferroptosis. Mechanistically, Fascin directly interacts with cysteine/glutamate transporter (xCT, gene name SLC7A11) and decreases its stability via the ubiquitin-mediated proteasome degradation pathway. Furthermore, we observed that Fascin is substantially upregulated in tamoxifen-resistant breast cancer cell lines, and drug-resistant cells were also more vulnerable to erastin-induced ferroptosis. Taken together, our findings reveal a previously unidentified role of Fascin in ferroptosis by regulating xCT. Thus, ferroptosis activation in breast cancer with high Fascin level may serve as a potential treatment.