BackgroundIn spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC) patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells.MethodsWe constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7.ResultsCXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo.ConclusionsIncreased CXCR7 expression was found in hepatocellular carcinoma tissues. Knockdown of CXCR7 expression by transfected with CXCR7shRNA significantly inhibits SMMC-7721 cells invasion, adhesion and angiogenesis. Finally, down-regulation of CXCR7 expression lead to a reduction of tumor growth in a xenograft model of HCC. This study provides new insights into the significance of CXCR7 in invasion and angiogenesis of HCC.

Extracellular matrix (ECM) is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronic acid (HA) is a component of the ECM, and hyaluronidase (HAase) is a HA-degrading endoglycosidase. Levels of HAase are elevated in many cancers. Hyaluronidase-1 (HYAL1) is the major tumor-derived HAase. In this study, we detected HYAL1 expression levels in breast cancer cells and tissues, and measured the amount HAase activity in breast cancer cells. Compared with nonmalignant breast cell line HBL-100 and normal breast tissues, HYAL1 were overexpressed in breast cancer cell lines MDA-MB-231, MCF-7, invasive duct cancer tissues and metastatic lymph nodes, respectively. Accordingly, the amount HAase activity in MDA-MB-231 and MCF-7 was higher than that in HBL-100. In addition, knockdown of HYAL1 expression in MDA-MB-231 and MCF-7 cells resulted in decreased cell growth, adhesion, invasion and angiogenesis potential. Meantime, the HYAL1 knockdown markedly inhibited breast cancer cell xenograft tumor growth and microvessel density. Further studies showed that the HYAL1, HYAL2 and HA were elevated in breast cancer, and HYAL1 could downregulate HA expression. In conclusion, HYAL1 may be a potential prognostic marker and therapeutic target in breast cancer.Extracellular matrix (ECM) is closely correlated with tumor cell growth, proliferation, metastasis and angiogenesis, etc. Hyaluronic acid (HA) is a component of the ECM. It is a nonsulfated glycosaminoglycan made up of repeating disaccharide units, D-glucuronic acid and N-acetyl-D-glucosamine. HA keeps tissues hydrated and maintains osmotic balance and cartilage integrity.

Purpose: To explore the risk factors that may predict the lymph node metastasis potential of these lesions and new prevention strategies in papillary thyroid carcinoma patients. Materials and Methods: In total, 9,369 papillary thyroid carcinoma patients with 37.17% lymph node metastasis were analyzed (Revman 5.3 software) in this study. The PubMed and Embase databases were used for searching works systematically that were published through to January 22, 2020. Results: Several factors were related to the increased risk of lymph node metastasis in patients with papillary thyroid carcinoma: age <45 years (pooled OR = 1.52, 95% CI = 1.14-2.01, p < 0.00001); gender = male (pooled OR = 1.68, 95% CI = 1.51-1.87, p < 0.00001); multifocality (pooled OR = 2.05, 95% CI = 1.45-2.89, p < 0.0001); tumor size ≥1.0 cm (pooled OR = 3.53, 95% CI = 2.62-4.76, p < 0.00001); tumor location at the upper pole 1/3 (pooled OR =1.46, 95% CI = 1.04-2.04, p = 0.03); capsular invasion + (pooled OR = 3.48, 95% CI = 1.69-7.54, p = 0.002); and extrathyroidal extension + (pooled OR = 2.03, 95% CI= 1.78-2.31, p < 0.00001). However, tumor bilaterality (pooled OR = 0.85, 95% CI = 0.54-1.34, p = 0.49) and Hashimoto's thyroditis (pooled OR = 1.08, 95% CI = 0.79-1.49, p = 0.62) showed no correlation with lymph node metastasis in papillary thyroid carcinoma patients. Conclusion: The systematic review and meta-analysis defined several significant risk factors of lymph node metastasis in papillary thyroid cancer patients: age (<45 years), gender (male), multifocality, tumor size (>1 cm), tumor location (1/3 upper), capsular invasion, and extra thyroidal extension. Bilateral tumors and Hashimoto's thyroiditis were unrelated to lymph node metastasis in patients with papillary thyroid cancer.

Tubular epithelial loss has been shown to be responsible for the formation of atubular glomeruli leading to nephron decomposition and interstitial fibrosis in obstructive uropathy. Cells undergoing apoptosis and autophagic cell death play an important role in this process, yet the mechanisms are not fully understood. In this study, we aimed to investigate whether autophagy cooperating with apoptosis is associated with mitochondrial damage and whether oxidative stress plays an important role in the loss of tubular epithelium following unilateral ureteral obstruction. In this model, we demonstrated that there is coexistence of autophagy and apoptosis with tubular atrophy in obstructed proximal tubules. After unilateral ureteral obstruction (UUO), autophagy in proximal tubular cells was enhanced steadily up to 7 days in the obstructed kidney and declined thereafter, while apoptosis was induced in a time-dependent manner from 3 to 14 days. Mitochondrial structure and number also changed during UUO. Lipid peroxidation products, NOX4, and NADPH oxidase activity were also increased in the obstructed renal cortex, and peaked at 7 days. In vitro, we showed that H2O2 induced mitochondrial injury leading to autophagy and apoptosis through the Beclin 1 pathway and interference with Bcl-2 expression. Thus, our data demonstrate that oxidative stress leading to mitochondrial damage and driven autophagy-dependent cell death and apoptosis are important mechanisms of tubular decomposition in obstructive nephropathy.