Search

TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment.

Yongyuan Li,1,2,* Hongjie Liu,3,* Yu Cui,1 Hekai Chen,1 Xuejun Cui,1 Jianping Shao,1 Feng Su,1 Xianghui He2 1Department of General Surgery, The Fifth Central Hospital, Tianjin 300450, People’s Republic of China; 2Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of China; 3Department of Radiology, The Fifth Central Hospital, Tianjin 300450, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianghui HeDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of ChinaEmail tjmughyy@163.comBackground: Gastric cancer (GC) is one of the most common and lethal malignancies worldwide. Therefore, a better understanding of the mechanism of its malignant progression and chemoresistance will be helpful for the treatment of patients with GC.Methods: The gene expression profiles downloaded from GEO database and the TargetScan Human were used to identify the key regulation model based on miRNA by bioinformatics analyses. The regulation of miRNA to target was clarified by luciferase assay, qPCR, and Western blotting. Then, the in vitro and in vivo experiments were further conducted by overexpression or knockdown of miRNA and/or target to examine the regulation effects and clarify the mechanism.Results: In the present study, miR-424-3p was identified to be differentially expressed among normal gastric, GC, and chemoresistant GC tissues. Target analysis results indicated that ABCC2, a chemoresistance-related gene, was a regulated target of miR-424-3p. The in vitro and in vivo experiment results further demonstrated that miR-424-3p relied on ABCC2-induced chemoresistance to promote GC proliferation and metastasis.Conclusion: Overall, this study revealed that miR-424-3p contributed to the malignant progression and chemoresistance of GC. Thus, miR-424-3p could be a potential target for the treatmen

Yizeng Wang, Yuanchao Liu, Xiaoning Wang, Xin Li, Ruoyu Jiang, Xianghui He Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, People’s Republic of China Background: Among patients with papillary thyroid carcinoma (PTC), 30%–80% have cervical lymph node (LN) metastases, which are most commonly located in the central compartment. However, preoperative ultrasonography identifies malignant central compartment LNs in only 20%–30% of cases. We aimed to evaluate the diagnostic value of intraoperative thyroglobulin (Tg) measurement in fine-needle aspirates (FNA-Tg) of suspicious metastatic LNs. Methods: In total, 75 patients (75 LNs) with PTC or suspected PTC were enrolled in this study. Suspicious metastatic LNs were isolated intraoperatively, and FNA-Tg was performed. Then, the Tg values were compared with the corresponding pathological results and preoperative ultrasonography. Results: In total, 37 LNs were diagnosed as malignant, and 38 were benign. According to the receiver operating characteristic (ROC) curve, the optimal cutoff value of intraoperative FNA-Tg was 147.5 ng/mL (sensitivity, 81.1%; specificity, 100%; p=0.000). The sensitivity and specificity for detecting central compartment LN metastasis were 77.78% (21/27) and 100% (36/36), respectively. The corresponding sensitivity of preoperative ultrasonography was lower than that of FNA-Tg (p=0.000). Serum Tg-antibody (Ab), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) were not significantly associated with FNA-Tg values. There was no statistical correlation between preoperative serum Tg and intraoperative FNA-Tg (p=0.451). Conclusion: Intraoperative FNA-Tg levels of suspicious metastatic cervical LNs can be useful for diagnosing metastatic PTC. Intraoperative LN-FNA-Tg may have an important role in determining which surgical procedure to perform. Keywords: papillary thyroid carcinoma

Shakil Ameerudden, Xianghui HeDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaAbstract: Parathyroid crisis, also known as a parathyroid storm, is a rare and serious complication of primary hyperparathyroidism. Four cases are reported here in which patients presented to hospital with general complaints due to hypercalcemia secondary to hyperparathyroidism. Blood test results upon admission showed high levels of serum calcium and parathyroid hormone, and medical treatment initiated to lower the calcium level was ineffective. After relevant investigations, each patient underwent surgical exploration of the parathyroid glands, followed by excision of a pathological parathyroid tumor. There was a prompt decrease in parathyroid hormone level immediately after surgery. Histology reports revealed that patients had parathyroid adenoma. All patients recovered after surgery, with serum calcium levels restored back to normal and with resolution of all symptoms of hypercalcemia. This report illustrates how often this disease is initially misdiagnosed, and how prompt appropriate surgical treatment provides the best outcome for the patient.Keywords: parathyroid crisis, hypercalcemia, hyperparathyroidism, hypercalcemic crisis, parathyroid adenoma

Immuno-gene therapy is a promising approach for the control of cancer. Because of the essential role in activating and expanding T cell responses to antigens, cytokines are comprehensively studied for cancer therapy. The efficacy of cancer immunotherapy is diminished by the fact that spontaneous tumors often downregulate antigen expression and/or presentation. The density of tumor antigen in conjunction with major histocompatibility complex (MHC) class I molecules on the cell surface affects cytotoxic T cell (CTL) function. In this study, we have developed a novel approach to augment the effect of cytokine-based cancer immuno-gene therapy through the coupling of antigen expression/presentation with cytokine production by expression of antigen epitopes within cytokine signal peptides. We first investigated the possibility of modifying cytokine signal peptides with antigen epitopes without aborting function. We inserted the genes encoding the MHC class I restricted antigenic epitopes of chicken ovalbumin (OVA), tyrosinase related protein 2 (TRP-2), and oncoprotein HER2 into the signal sequence of the interleukin-2 (IL-2) gene, replacing part of the signal sequence at different positions. Our results showed that these modified signal peptides still functioned, as indicated by cytokine secretion. We then demonstrated that an antigen epitope contained within the modified signal peptide could be processed properly and presented on the tumor cell surface. Furthermore, using a murine melanoma model, we studied the effect of antigen epitope modified IL-2 and IFN-gamma on the immuno-gene therapy of malignancy. Tumor cells showed enhanced immunogenicity as indicated by increased susceptibility to CTL lysis in vitro and decreased tumor growth in vivo after gene modification with the antigen epitope-containing cytokine expression vectors. Vaccination with TRP-2 epitope-containing IFN-gamma gene-modified B16 cells resulted in protection against wild type tumor challenge. In addit