It has been suggested that some unusual molecules and genes might be involved in the development of soft tissue sarcomas (STS) and that drugs targeting specific molecules and genes would selectively kill tumor cells, which have been demonstrated to be more effective approach with less side effect than traditional chemotherapy. However, most of the effective targets of STS are currently not elucidated, and the effects of trial-target therapy are mostly not satisfactory, thus multiple targeting drugs might guide a future direction for tumor therapy.

Background and purpose: Hepatocellular carcinoma (HCC) is a hypervascular tumor associated with a poor prognosis and lack of effective treatments. Consequently, identifying novel therapeutic strategies are urgently needed. We have previously shown that the kringle 1 domain of human hepatocyte growth factor (HGFK1) is a more effective anti-angiogenesis molecule than angiostatin. In this study, we observed the effects and mechanisms of HGFK1 gene on the HCC. Methods: A recombinant adeno-associated vires carrying the HGFK1 gene (rAAV-HGFK1) was constructed.HCC of rat was induced by McA-RH7777. rAAV-HGFK1 was used to treat the rat, median survival time and metastasis rate were observed. Results: Ten days after tumor cell inoculation, surgery were performed to confirm the tumor formation, PBS, rAAV-EGFP or rAAV-HGFK1 was injected directly into the tumor nodule followed by portal vein injection. Results from our study demonstrated that rAAV-HGFK1 treatment significantly prolonged the median survival time of the HCC bearing rats from 30 days (PBS and rAAV-EGFP groups) to 49 days (rAAV-HGFK1 group). More importantly rAAV-HGFK1 inhibited tumor growth and completely prevented liver, lung and peritoneal metastasis. In the controlled PBS and AAV-EGFP group, liver and peritoneal metastasis rate were both 100%, and lung metastasis rate was 100% and 83%, respectively. While there was no metastasis found in treatment group, with only 33% of ascites happened. This was most possibly due to the primary tumor in liver but not due to the metastasis. Moreover, at a higher magnification (1000×), it was clear that the HGFK1 protein was expressed mainly in the cytoplasma of liver cells. In parallel, IHC staining of CD31 also demonstrated a significantly lower level of microvessel density (MVD) (6.21±1.6) in the liver tumor of the AAV-HGFK1 treatment group, as compared to the two control PBS and AAV-EGFP groups (25.1±2.1 and 26.8±2.5, respectively, P<0.01). HE staining showed that AAV-HGFK1 treatment induced large areas of necrosis in the tumor tissues, while minimal areas of necrosis were observed in the tumor tissue in the control groups. In addition, no toxicity appeared when high dosage (4.8× 1012 vg/rat) of rAAV-HGFK1 was administered in rats. Conclusion: Results from this study demonstrated that HGFK1 inhibited the growth and metastasis of HCC and prolonged the survival time of animals with HCC through anti-angiogenesis effects. No obvious toxicity was observed. It might be the novel promising treatment for HCC and other cancers.

Objective: To investigate the expression of CD155/TIGIT in patients with osteosarcoma and its significance Methods : The expression differences of CD155 and TIGIT in tumor tissues of distant metastatic osteosarcoma patients and non⁃metastatic osteosarcoma patients were analyzed by cancer Genome Atlas ( TCGA) database.The surgically removed tissues of osteosarcoma patients were collected to prepare pathological sections and tissue chips , and the tumor tissue and cell morphology were observed by HE staining. Immunohistochemical staining was used to detect the expression of CD155 and TIGIT , and the scores were divided into high expression group and low expression group according to the scores. Chi⁃square test was used to analyze the relationship between CD155/TIG⁃IT expression and clinical features and prognosis. Results : TCGA database data showed higher expression of CD155 and TIGIT in patients with osteosarcoma accompanied by metastasis. HE staining of pathological sections revealed that tumor tissues with high expression of CD155/TIGIT contained more binuclear or multinucleated , hyperchromatic and obviously heteromorphic tumor cells. Immunohistochemical staining and score analysis of tissue chip showed that the expression of CD155 and TIGIT was correlated with clinical stage and distant metastasis ( P < 0. 05) , but not with age , sex , tumor size , pathological type and tumor necrosis rate. Conclusion CD155 and TIGIT may be one of the prognostic indicators of osteosarcoma.