Guosheng Tan

MiR-1180 promotes apoptotic resistance to human hepatocellular carcinoma via activation of NF-κB signaling pathway

Apoptosis resistance in human hepatocellular carcinoma (HCC) is a significant factor in carcinogenesis. Therefore, understanding the molecular mechanisms involved in apoptosis resistance is crucial for developing anticancer therapies. Importantly, small non-coding microRNAs (miRNAs) have been reported as key biomarkers for detecting tumour onset and progression. In the present study, we demonstrate that miR-1180 is upregulated in HCC. Ectopic expression of miR-1180 has an anti-apoptotic effect in HCC, while miR-1180 inhibition increases cell apoptosis, both in vitro and in vivo. Moreover, our results show that miR-1180 directly targets key inhibitors of the nuclear factor (NF)-κB signaling pathway (i.e., OTUD7B and TNIP2) and the pro-apoptotic Bcl-2 associated death promoter (BAD) protein by post-transcriptional downregulation. Therefore, the anti-apoptotic function of miR-1180 in HCC may occur through NF-κB pathway activation via downregulation of its negative regulators. In conclusion, our study reveals the critical role of miR-1180 during apoptosis resistance in HCC.

DDR2 facilitates hepatocellular carcinoma invasion and metastasis via activating ERK signaling and stabilizing SNAIL1

BackgroundSeveral studies have found that DDR2 is up-regulated in many tumor types and facilitates tumor progression. However, the role of DDR2 in hepatocellular carcinoma (HCC) progression and its downstream signaling pathways remain unclear.MethodsDDR2 expression was assessed in several cell lines and 112 pairs of HCC and matched adjacent noncancerous liver tissues. Clinical significance of DDR2 in HCC was analyzed. Phosphorylated DDR2 (p-DDR2) expression was detected by immunoblotting to evaluate its correlation with DDR2. The effect of DDR2 on HCC cell migration and invasion were examined. Cycloheximide chase experiments were performed to detect the half-life of SNAIL1. Moreover, DDR2 expression was detected by immunohistochemistry to evaluate its correlation with SNAIL1. The regulatory effect of DDR2 on ERK signaling, SNAIL1, EMT, MT1-MMP and MMP2 was confirmed by immunoblotting. The effect of type I collagen on DDR2/ERK2/SNAIL1 signaling was assessed.ResultsDDR2 was more highly expressed in HCC than in non-HCC tissues. DDR2 overexpression was correlated with clinicopathological features of poor prognosis. Clinical analysis revealed that DDR2 is an independent prognostic marker for predicting overall survival and disease free survival of HCC patients. Overexpression of DDR2 is associated with p-DDR2 amplification. In vitro studies showed that DDR2 facilitates HCC cell invasion, migration and EMT via activating ERK2 and stabilizing SNAIL1. DDR2 can up-regulate MT1-MMP and MMP2 expression through ERK2/SNAIL1 signaling in HCC. Additionally, collagen I can induce DDR2/ERK2/SNAIL1 signaling activation in HCC cells.ConclusionsOur findings suggest that DDR2 plays an important role in promoting HCC cell invasion and migration, and may serve as a novel therapeutic target in HCC.

Mir-765 promotes cell proliferation by downregulating INPP4B expression in human hepatocellular carcinoma.

microRNAs (miRNAs) dysregulation is widely involved in cancer progression and contributed to sustained cell proliferation by directly targeting multiple targets. Therefore, better understanding the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In our study, we found that mir-765 is upregulated in both hepatocellular carcinoma (HCC) cell lines and tissues, compared to human normal liver cell line and adjacent non-cancerous tissues, respectively. Overexpression of mir-765 increased HCC cells proliferation and tumorigenicity, whereas inhibition of mir-765 reverses this effect. Furthermore, we demonstrated that INPP4B as a direct target of mir-765 and ectopic expression of mir-765 repressed INPP4B expression, resulting in upregulation of p-AKT, Cyclin D1, and downregulation of p-FOXO3a, p21 expression in HCC. Strikingly, we found that silencing the expression of INPP4B is the essential biological function of miR-765 during HCC cell proliferation. Collectively, our findings reveal that miR-765 is a potential onco-miR that participates in carcinogenesis of human HCC by suppressing INPP4B expression, and might represent a potential therapeutic target for HCC patients.

Percutaneous computed tomography-guided cryoablation for recurrent retroperitoneal soft tissue sarcoma: a study of safety and efficacy

Aims To evaluate the use of computed tomography image-guided percutaneous cryoablation for recurrent retroperitoneal soft tissue sarcomas (RPSs). Results Adverse events were limited to grades 1 and 2, included fever (n = 19), local pain (n = 11), emesis (n = 10), frostbite (n = 6), and nerve injury (n = 1). Fever was more frequent in the large tumor group (15.8%) than in small tumor group (1.9%) (P = 0.008). Median PFS and OS were 37.0 ± 7.7 months (range, 4–39 months) and 43.0 ± 5.9 months (range, 6–54 months), respectively. PFS and OS were significantly longer in the small tumor group than in the large tumor group (P = 0.011 and P = 0.015, respectively), but the response rate (82.7% vs. 72.8%, P = 0.240) did not differ significantly. On univariate analysis, tumor size, tumor invasion grade, and distant metastasis were significant prognostic factors for PFS and OS. On multivariate analysis, a tumor size ≥10 cm was an independent negative prognostic factor for PFS and OS after cryoablation (HR: 3.98, 95% CI: 1.27–12.50, P = 0.018 and HR: 4.33, 95% CI: 1.41–13.26, P = 0.010, respectively). Materials and Methods Data from 72 patients with recurrent RPSs who underwent percutaneous cryoablation were reviewed retrospectively. The prognostic factors for progression-free survival (PFS), overall survival (OS), and efficacy based on mRECIST criteria were analysis. Adverse events were compared according to tumor size (<10 and ≥10 cm). Conclusion Minimally invasive percutaneous cryoablation was safe and efficacious for recurrent RPSs.

Temporary reduction and slow recovery of integrin ανβ3 in endometrium after uterine arterial embolization.

OBJECTIVE We aimed to study the effect of uterine arterial embolization (UAE) on the level of endometrial integrin ανβ3 in guinea pigs. STUDY DESIGN A total of 55 female guinea pigs were randomly divided into a sham group (n=10) and a UAE group (n=45). The animals in the UAE group were further divided into three subgroups, A1, A2 and A3, with 15 subjects in each subgroup. Bilateral UAE was performed in the UAE group by injection of 40-120 μm and 100-300 μm microspheres. Uterine tissue samples were collected three days after ovulation, i.e., one menstrual cycle after UAE for A1 group, two menstrual cycles after UAE for A2 group and three menstrual cycles after UAE for A3 group. Levels of endometrial integrin ανβ3 were tested by immunohistochemistry with mean optical density (MOD) analysis. Serum levels of estradiol and progesterone were measured before sample collection. RESULTS The MOD values for integrin ανβ3 levels in endometrial glands were 0.393 ± 0.039, 0.253 ± 0.032, 0.319 ± 0.034, 0.365 ± 0.032 for the sham, A1, A2 and A3 groups respectively; in endometrial luminal epithelium they were 0.386 ± 0.036, 0.242 ± 0.035, 0.308 ± 0.042, 0.355 ± 0.031 for the sham, A1, A2 and A3 groups respectively. For both endometrial glands and luminal epithelium, ανβ3 levels in the sham group were statistically significantly higher than those in the A1, A2 and A3 groups (p(1)<0.001, p(2)<0.001, p(3)<0.05); and they were significantly higher in the A2 group than in A1 group (p<0.001), also in the A3 group than in A2 group (p<0.001). The levels of estradiol and progesterone in blood serum both had no significant differences among the groups (p>0.05). CONCLUSIONS UAE is associated with a decrease in endometrial integrin ανβ3 levels. The decrease would negatively affect endometrial receptivity, but might be transient and reversible.

Transketolase contributes to hepatocellular carcinoma migration, invasion, angiogenesis, and tumorigenesis

Racial disparities in transcatheter aortic valve replacement (TAVR) implantation results from several factors, including socioeconomic disparities, inherent biases in healthcare provision, fewer referrals to specialists and language barriers in some minority populations. In this review article, we discuss the current data on the racial disparities in TAVR, explore the prevalence of aortic stenosis in different demographics in the United States and we proffer practical solutions to these problems.Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer death around the world; as the survival of patients with HCC is persistently low, new regulatory factors should be identified to provide new therapeutic targets. The role of the thiamine-dependent enzyme transketolase (TKT) in tumor progression has not been well-studied. In this study, we investigated the role of TKT in HCC progression. Methods: TKT expression in HCC tissues was analyzed using immunohistochemistry (IHC), and the relationship between TKT level and clinical outcome was examined using the Kaplan–Meier method and the log-rank test. The role of TKT in HCC progression was investigated using the wound healing assay, Transwell assay, chicken chorioallantoic membrane (CAM) assay, soft agar assay, and a xenograft tumor model. Promoter methylation levels in HCC cells and normal LO2 liver cells were examined using bisulfite genomic sequencing. Results: TKT was upregulated in HCC tissues and cells. Patients with high TKT expression had poor outcome. TKT overexpression promoted HCC migration, invasion, angiogenesis, and tumorigenesis, while TKT knockdown reduced these effects. In addition, we found lower TKT promoter methylation in HCC tissues and cells, indicating that TKT was upregulated in HCC tissues and cells. Conclusions: Our study demonstrates that TKT is an oncogene in hepatocellular tumorigenesis, and provides a new HCC therapeutic target.Racial disparities in transcatheter aortic valve replacement (TAVR) implantation results from several factors, including socioeconomic disparities, inherent biases in healthcare provision, fewer referrals to specialists and language barriers in some minority populations. In this review article, we discuss the current data on the racial disparities in TAVR, explore the prevalence of aortic stenosis in different demographics in the United States and we proffer practical solutions to these problems.