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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and identification of novel targets is necessary for its diagnosis and treatment. This study aimed to investigate the biological function and clinical significance of tweety homolog 3 (TTYH3) in HCC. TTYH3 overexpression promoted cell proliferation, migration, and invasion and inhibited HCCM3 and Hep3B cell apoptosis. TTYH3 promoted tumor formation and metastasis

Background: A considerable part of colorectal cancer (CRC) patients also have chronic hepatitis B (CHB), esp. in Asia. The effect of concomitant active CHB on the hazard of colorectal liver metastasis (CRLM) remains unclear. To evaluate the effect of concomitant active CHB on the risk of CRLM. Methods: The medical record of all newly diagnosed CRC patients who were hospitalized to the three hospitals between January 2010 to January 2016 were reviewed, the prevalence of synchronous CRLM (synCRLM) were retrospectively studied. Totally 7187 cases of newly diagnosed CRC, including 368 cases with concomitant CHB were recruited. The prevalence of synCRLM in HBsAg+/HBeAg+ patients was compared to that in HBsAg+/HBeAg- patients. Significant risk factors for synCRLM were analyzed by logistic regression analysis. Results: The overall prevalence of synCRLM was 8.72% (627/7187) and was significantly higher in HBsAg+ patients (43/368) than HBsAg- patients (576/6742) (11.68% vs. 8.54%, P=0.037; χ2 test).In 368 HBsAg+ patients, 365 patients also had HBeAg information. synCRLM was also more prevalent inHBsAg+/HBeAg+ patients (13/69) compared to HBsAg+/HBeAg- patients (30/296) (18.84% vs. 10.14%, P=0.043; χ 2 test). In univariate and multivariate logistic regression analysis, HBeAg positivity was the second strongest predictor of synCRLM (multivariate: OR, 2.622, P=0.020) after CEA. (univariate: OR, 2.920, P=0.001). Conclusions: HBeAg positivity is a clinical risk factor for CRLM that can be readily identified and addressed. Whether anti-CHB treatment can decrease the risk of CRLM worth carefully-designed prospective trials to define.

Chemo-gene therapy is an emerging synergetic modality for the treatment of cancers. Herein, we developed pH-responsive multifunctional DNA nanomicelles (DNMs) as delivery vehicles for controllable release of doxorubicin (Dox) and anaplastic lymphoma kinase (ALK)-specific siRNA for the chemo-gene synergetic therapy of anaplastic large cell lymphoma (ALCL). Methods: DNMs were synthesized by performing in situ rolling circle amplification (RCA) on the amphiphilic primer-polylactide (PLA) micelles, followed by functionalization of pH-responsive triplex DNA via complementary base pairing. The anticancer drug Dox and ALK-specific siRNA were co-loaded to construct Dox/siRNA/DNMs for chemo-gene synergetic cancer therapy. When exposed to the acidic microenvironment (pH below 5.0), C-G·C+ triplex structures were formed, leading to the release of Dox and siRNA for gene silencing to enhance the chemosensitivity in ALCL K299 cells. The chemo-gene synergetic anticancer effect of Dox/siRNA/DNMs on ALCL was evaluated in vitro and in vivo. Results: The pH-responsive DNMs exhibited good monodispersity at different pH values, good biocompatibility, high drug loading capacity, and excellent stability even in the human serum. With the simultaneous release of anticancer drug Dox and ALK-specific siRNA in response to pH in the tumor microenvironment, the Dox/siRNA/DNMs demonstrated significantly higher treatment efficacy for ALCL compared with chemotherapy alone, because the silencing of ALK gene expression mediated by siRNA increased the chemosensitivity of ALCL cells. From the pathological analysis of tumor tissue, the Dox/siRNA/DNMs exhibited the superiority in inhibiting tumor growth, low toxic side effects and good biosafety. Conclusion: DNMs co-loaded with Dox and ALK-specific siRNA exhibited significantly enhanced apoptosis of ALCL K299 cells in vitro and effectively inhibited tumor growth in vivo without obvious toxicity, providing a potential strategy in the development of nanomedicines for synergetic cancer therapy.