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The poor outcome of cancer gene therapy in clinical trials relates in part to insufficient gene delivery to tumor sites. Mesenchymal stem cells (MSCs) represent a new tool for the delivery of therapeutic agents to tumor cells. This study used an orthotopic nude mice model of hepatocellular carcinoma (HCC) to evaluate the potential of genetically modified human MSCs (hMSCs), to function as an effective delivery vehicle for therapeutic genes. hMSCs derived from the bone marrow were efficiently engineered to express human pigment epithelium-derived factor (PEDF) by lentiviral transduction, then tested in vitro for high-level expression and bioactivity of the transgenic protein. The preferential homing of hMSCs toward HCC was confirmed by in vitro and in vivo migration assays. in vivo efficacy experiments showed that intravenous (i.v.) injection of PEDF-expressing hMSCs significantly suppressed both the growth of primary liver tumors and the development of pulmonary metastases. Moreover, hMSCs-based PEDF gene delivery moderately increased the systemic levels of human PEDF. Immunohistochemistry of primary liver tumors demonstrated lower microvessel density in mice treated with hMSCs-PEDF than in control mice. This is the first study to show the potential of hMSCs as an effective delivery vehicle for therapeutic genes in the treatment of HCC.

The authors Jing Liang and Xiao-quan Xu contributed equally to this article.Objective: To differentiate pre-invasive lesion from invasive pulmonary adenocarcinoma (IPA) appearing as ground-glass nodules (GGNs) using CT features. Methods: 149 GGNs were enrolled in this study, with 74 pure GGNs (p-GGNs) and 75 mixed GGNs (m-GGNs). Firstly, univariate analysis was used to analyse the difference of CT features between pre-invasive lesion and IPA. Then, multivariate analysis was conducted to identify variables that could independently differentiate pre-invasive lesion from IPA. Receiver operating characteristic curve analysis was performed to evaluate the differentiating value of identified variables. Results: In the p-GGNs, multivariate analysis showed that the amount of blood vessels was an independent risk factor. Using the amount of blood vessels "$1" as the diagnostic criterion, we could diagnose IPA with a sensitivity of 100%. Using the amount of blood vessels "50" as the diagnostic criterion, we could diagnose pre-invasive lesions with a specificity of 100%. In the m-GGNs, multivariate analysis showed that the volume of solid portion (V Solid ) and pleural indentation were two independent risk factors. One further model was constructed using these two variables: model 5 2.508 3 (V Solid 1 1.407) 3 (pleural indentation 2 1.016). Using the new model, improved diagnostic ability was achieved compared with using V Solid or pleural indentation alone. Conclusion: The amount of blood vessels through the p-GGNs would be an important criterion during clinical management, while V Solid and pleural indentation seemed important for m-GGNs. Moreover, the new model could further improve the differentiating value for m-GGNs. Advances in knowledge: CT features are useful in differentiating pre-invasive lesion from IPA appearing as GGNs. INTRODUCTIONAccording to the new pathological classification constituted in 2011, lung adenocarcinoma was divided into the preinvasive lesion group and the invasive pulmonary adenocarcinoma (IPA) group.1,2 Significant difference existed between these two groups regarding the surgical method and the scope of lymph node dissection.2-5 Sublobar resection could be acceptable for pre-invasive lesion, while the standard surgical treatment for IPA should be lobectomy.2-5 Skip metastases involving mediastinal lymph nodes, without hilar lymph nodes appeared mostly in the IPA group, thus the scope of lymph node dissection for the IPA group should be larger than for the pre-invasive lesion group.2-5 Therefore, accurate differentiation between preinvasive and IPA lesions before surgery was crucial, particularly for surgery planning, prognosis assessment and doctor-patient communication.

The long noncoding RNAs (lncRNAs) have long been clarified to participate in hepatocellular carcinoma (HCC) as a biomarker. We carried out the present study in order to identify HCC-related lncRNAs and elucidate the functional roles in the development and progression of HCC. Our previous study has provided that LINC01225 may be an HCC-related gene. Here, we verified that LINC01225 was upregulated in HCC. Knockdown of LINC01225 resulted in inhibited cell proliferation and invasion with activated apoptosis and cell cycle arrest in vitro. Overexpression of LINC01225 in LINC01225 knockdown cells presented that attenuated cell proliferation and invasion were restored and enhanced. Subcutaneous and tail vein/intraperitoneal injection xenotransplantation model in vivo validated reduced tumor progression and metastasis. Investigation of mechanism found that LINC01225 could bind to epidermal growth factor receptor (EGFR) and increase the protein level of EGFR, and subsequently fine tune the EGFR/Ras/Raf-1/MEK/MAPK signaling pathway. Analysis with clinicopathological information suggested a high expression of LINC01225 is positively associated with poor prognosis. We also proved that LINC01225 was stably expressed in serum and can act as a novel biomarker in predicting the diagnosis of HCC. As a conclusion, LINC01225 plays a crucial role in HCC and can act as a biomarker for the diagnosis and prognosis of HCC.