ABSTRACT
Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.
ABSTRACT
To examine the effect of VAE and open surgery on the postoperativelocal recurrence of benign phyllodes tumors of breast and to investigate the clinical efficacy of VAE in the treatment of benign phyllodes tumors. The clinical data of 128 patients with benign phyllodes tumors of breast admitted to the Guangdong Women and Children Hospital from January 2013 to January 2018 were retrospectively analyzed. All patients were female, aged (37.7±9.1) years (range: 16 to 56 years). Eighty patients underwent ultrasound-guided VAE (minimally invasive group) and 48 patients underwent open surgery (open group). The -test, χ(2) test or Fisher exact probability method were used to compare the clinical characteristics of the two groups of patients. Logistic regression was used to analyze the prognostic factors of postoperative local recurrence. The maximum diameter of tumor in the minimally invasive group was smaller than that in the open group ((20.6±7.4) mm . (42.0±2.0) mm, -7.173, 0.000). The follow-up time was (36.4±1.8) months (range: 12 to 71 months). There were 7 cases of local recurrences during the follow-up period. The local recurrence rates in the minimally invasive and open groups were 5.0% (4/80) and 6.3% (3/48). The results of multivariate analysis showed that the maximum tumor diameter of 25 mm was an independent prognosis factor for postoperativelocal recurrence (0.122, 95: 0.016 to 0.901, 0.039). While surgical procedure, age, menopausal status and history of fibroadenomas in the ipsilateral breast is not an independent prognostic factor for postoperative local recurrence. In the minimally invasive surgery group, the local recurrence rates were 2.9% (2/69) and 2/11 in patients with tumor maximum diameters<25 mm and ≥25 mm, respectively. Local recurrence of breast benign phyllodes tumors is closely related to the tumor size. For patients with tumor diameter25 mm, the postoperative local recurrence rate of VAE is low, which can be used in clinical practice. Intraoperative complete resection to achieve a negative surgical margin should be guaranteed to avoid local recurrence.
ABSTRACT
Central urotensin II (UII) may participate in the regulation of cardiovascular functions by stimulating sympathy pathway. However, the central mechanism remained unknown. Recent studies have shown that brain reactive oxygen species (ROS) mediate the sympatho-excitatory effects. In the present study, we tested the hypothesis that ROS mediate central cardiovascular effects of UII. Experiments were conducted in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Immunocytochemistry, intracerebroventricular (icv) infusion and lucigenin-enhanced chemiluminescence assay were employed to detect UII receptor expression and ROS level, respectively. The following results were obtained: (1) Expressions of UII receptors of rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS) were increased in SHR rats compared with WKY rats (P < 0.05). (2) UII (icv) significantly increased mean arterial pressure (MAP) (P < 0.05), and the effect of UII was significantly more pronounced in SHR rats than that in WKY rats (P < 0.05); (3) Tempol (a superoxide dismutase mimic) or Urantide (an antagonist of UII receptor) pretreatments eliminated the pressor effect of UII (P < 0.05) in SHR rats; (4) Brain superoxide level was increased in UII-treated SHR rats compared with that in cerebrospinal fluid (CSF)-treated SHR rats (P < 0.05). These results indicate that ROS mediate central cardiovascular effects of UII in SHR rats and provide evidence for a novel relationship between UII and ROS.