SALL4 correlates with proliferation, metastasis, and poor prognosis in prostate cancer by affecting MAPK pathway.

BACKGROUND: The mechanism involved in prostate cancer (PCa) metastasis is still poorly understood, and several oncogenes are known to regulate this process. However, the role of spalt-like transcription factor 4 (SALL4) in PCa metastasis remains unclear. METHODS: We performed RNA-sequencing to compare the mRNA expression profiles of seven localized PCa tissues and six metastatic PCa tissues. SALL4 was then identified and compared in the localized PCa and metastatic PCa. Immunohistochemical studies, qRT-PCR, and Western blot were performed to analyze the expression of SALL4 in PCa patients and cell lines. SALL4 expression and its relevance to clinical traits and prognosis were further explored in the TCGA database and in our 68 clinical samples. Subsequently, we knocked down SALL4 in DU145 and PC3 cells and performed a series of functional assays to explore the effect of SALL4 on PCa progression. Finally, protein levels of SALL4 and core components of the MAPK pathway were measured by Western blot, and cells were treated with PD0325901 to observe proliferation and metastasis. RESULTS: Significantly higher expression of SALL4 was found in metastatic PCa than in localized PCa. In addition, high SALL4 expression was significantly associated with high pathological T stage, N stage, Gleason score, and poor disease-free survival in TCGA database and in our clinical samples. Functional studies indicated that knockdown of SALL4 in DU145 and PC3 inhibited proliferation, migration, and angiogenesis. Furthermore, the ERK and P38 protein phosphorylation significantly reduced after knockdown of SALL4 in DU145 and PC3, indicating the inactivation of the MAPK signaling pathway. Finally, the proliferation and migration ability of DU145 and PC3 cells were significantly decreased after PD0325901 treatment. CONCLUSIONS: SALL4 predicts unfavorable outcome and is closely associated with PCa progression, suggesting that SALL4 may be a promising prognostic marker and potential therapeutic target for PCa.

Bacteria-Loaded Gastro-Retention Oral Delivery System for Alcohol Abuse.

Alcohol abuse is harmful to human health, and many strategies have been developed to retard this harm through protecting liver or activating relative enzymes. In this study, a new strategy of decreasing the alcohol absorption directly depending on the dealcoholization by the bacteria in the upper gastrointestinal (GI) tract was reported. To realize this, a bacteria-loaded gastro-retention oral delivery system with pore structure was constructed through emulsification/internal gelation, which could relieve acute alcohol intoxication in mice successfully. It was found that this bacteria-loaded system kept the above 30% suspension ratio in the simulated gastric fluid for 4 min, displayed good protection effect for the bacteria, and decreased the alcohol concentration from 50 to 30% below within 24 h in vitro. The in vivo imaging results demonstrated that it remained in the upper GI tract until 24 h and reduced 41.9% alcohol absorption. The mice with oral administration of the bacteria-loaded system were found with normal gait, smooth coat, and less liver damage. Although the intestinal flora distribution was influenced slightly during the oral administration, it could restore to normal levels only one day after stopping oral administration quickly, suggesting good biosafety. In conclusion, these results revealed that the bacteria-loaded gastro-retention oral delivery system might intake alcohol molecules rapidly and has huge potential in the treatment of alcohol abuse.

Development of a preoperative index-based nomogram for the prediction of hypokalemia in patients with pituitary adenoma: a retrospective cohort study.

OBJECTIVE: To develop and validate a preoperative index-based nomogram for the prediction of hypokalemia in patients with pituitary adenoma (PA). METHODS: This retrospective cohort study included 205 patients with PAs between January 2013 and April 2020 in the Sun Yat-sen Memorial Hospital, Guangzhou, China. The patients were randomly classified into either a training set (N = 143 patients) and a validation set (N = 62 patients) at a ratio of 7:3. Variables, which were identified by using the LASSO regression model were included for the construction of a nomogram, and a logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) in the training set. The area under the curve (AUC) was used to evaluate the performance of the nomogram for predicting hypokalemia. Multivariate logistic regression analysis with a restricted cubic spline analysis was conducted to identify a potential nonlinear association between the preoperative index and hypokalemia. RESULTS: The incidence of hypokalemia was 38.05%. Seven preoperative indices were identified for the construction of the nomogram: age, type of PA, weight, activated partial thromboplastin time, urea, eosinophil percentage, and plateletocrit. The AUCs of the nomogram for predicting hypokalemia were 0.856 (95% CI [0.796-0.915]) and 0.652 (95% CI [0.514-0.790]) in the training and validation sets, respectively. Restricted cubic splines demonstrated that there was no nonlinear association between hypokalemia and the selected variables. CONCLUSION: In this study, we constructed a preoperative indices-based nomogram that can assess the risk of hypokalemia after the surgical treatment of pituitary adenomas. This nomogram may also help to identify high risk patients who require close monitoring of serum potassium.

Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing.

Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases.

circFOXM1 contributes to sorafenib resistance of hepatocellular carcinoma cells by regulating MECP2 via miR-1324.

As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths around the world. Emerging studies have indicated that circular RNAs (circRNAs), which play a crucial role in HCC pathogenesis and metastasis, are differentially expressed in HCC. However, the regulatory mechanisms of circRNA on sorafenib resistance of HCC are still unknown. In our study, we identified a novel circRNA, circFOXM1, using RNA sequencing (RNA-seq) that was increased in sorafenib-resistant HCC tissues. Functionally, circFOXM1 significantly inhibited HCC growth and enhanced sorafenib toxicity in vitro. Mechanistically, circFOXM1 acted as a sponge of microRNA (miR)-1324, which is a negative regulator of MECP2, indicating that circFOXM1 downregulation would regulate sorafenib resistance of HCC via releasing more free miR-1324 and suppressing MECP2 expression. Furthermore, miR-1324 overexpression was capable of reversing the circFOXM1-induced malignant phenotypes and elevated expression of MECP2 in HCC cells. circFOXM1 partially contributed to sorafenib resistance of HCC cells through upregulating MECP2 expression by sponging miR-1324.

Two-stage laparoscopic resection of giant hepatoblastoma in infants combined with liver partial partition and artery ligation.

PURPOSE: Laparoscopic resection of giant hepatoblastoma (HB) in children has long been a subject of controversy. Here, a new procedure of two-stage laparoscopic resection of giant HB in infants was firstly reported and the feasibility was discussed. METHODS: The clinical data of three infants with HB were retrospectively reviewed, all of which received 3-5 cycles of neoadjuvant chemotherapy. Stage 1 laparoscopic selective hepatic artery ligation and liver partial partition were performed. Stage 2 laparoscopic hepatectomy was performed 2 weeks later. RESULTS: The results demonstrated that (1) the tumors shrank considerably in size and had relatively clear boundaries after neoadjuvant chemotherapy; (2) after stage 1 surgery, the tumor volume further reduced, while the intratumoral necrosis expanded; (3) 2 weeks later, stage 2 laparoscopic hepatectomy was performed successfully; (4) none of the cases had intraoperative complications such as tumor rupture, air embolism, hemorrhage, biliary fistula, or liver failure, and there was no recurrence or metastasis during follow-up. CONCLUSIONS: Two-stage laparoscopic hepatectomy associating selective hepatic artery ligation and liver partial partition for HB in infants has the benefits of small invasiveness, fast recovery, improved safety, and high feasibility. However, more cases and longer follow-up are needed to assess its long-term efficacy.

CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression.

Hepatoblastoma (HB) is a malignant embryonal tumor of the liver that consists of heterogenous populations of stem/progenitor cells. Although circular RNAs (circRNAs) play an essential role in tumor development, the effects of circRNA on the proliferation of HB cells, especially cancer stem cells (CSCs), remain unclear. We found that the circRNA, CDR1as, was highly expressed in CSC-enriched populations of HB cell lines. Results from flow cytometric and sphere-forming assays revealed that CDR1as knockdown in HB cell lines decreased the proportion of stem cells. The Cell Counting Kit-8 (CCK-8) assay, colony formation experiments, and EdU assay revealed that CDR1as knockdown in HB cell lines decreased cell growth and the colony-forming abilities. Biotin-coupled probe pull-down assays and biotin-coupled microRNA capture were conducted to evaluate the interaction between CDR1as and miR-7-5p. Dual-luciferase reporter assays demonstrated that Kruppel-like factor 4 (KLF4), expression of which is highly correlated with cancer stemness, was a target of miR-7-5p. Overall, the knockdown of CDR1as significantly inhibited the proliferation and stemness of HB cells by reducing the sponge activity on miR-7-5p and subsequently suppressing the interaction between miR-7-5p and KLF4. Results from this study suggest that CDR1as is an oncogene that effects the proliferation and stemness of HBs.

Effective surgical treatment of life-threatening huge vascular anomalies associated with thrombocytopenia and coagulopathy in infants unresponsive to drug therapy.

BACKGROUND: Systemic drug therapy is generally recommended for infant huge vascular anomalies associated with thrombocytopenia and coagulopathy, but some patients are not suitable due to drug unresponsiveness or life threatening conditions before the drug works, who will need to receive surgical treatment. This study retrospectively analyzed the clinical features, imaging features, and surgical outcomes of these patients. METHODS: The clinical data of 4 infants with huge vascular anomalies (2 vein malformations (VMs) and 2 kaposiform hemangioendothelioma (KHE)) associated with thrombocytopenia and coagulopathy treated from June 2016 to December 2017 were retrospectively analyzed. All patients received glucocorticoids, propranolol, vincristine or sirolimus treatment before admission, but the treatment was ineffective. Skin petechia, thrombocytopenia and coagulopathy were present at the time of admission. CT scanning was performed before operation. The patient's general clinical data, hematological examination results, operation time, surgical bleeding volume, blood transfusion volume and surgical complications were collected for analysis. The patients were followed up for 10-26 months. RESULTS: CT scanning results of 2 patients showed special CT features without detectable enhancement within the lesion after CT enhanced scanning and multiple phleboliths formation. Four patients underwent surgical treatment successfully. Two patients underwent complete resection of the lesion, and 2 underwent cytoreductive surgery. Preoperative clinical symptoms such as skin petechia, thrombocytopenia and coagulopathy were normal at 1 week after surgery. Postoperative pathological results showed 2 cases of KHE and 2 cases of VMs. All patients were discharged from hospital without physical dysfunction, recurrence, or death. CONCLUSIONS: Timely and appropriate surgical intervention can achieve satisfactory results for infants with huge VMs and KHE who were unresponsive to drug therapy or suffering from life-threatening occasion before the drug become effective.

miRNA-101 Suppresses Epithelial-to-Mesenchymal Transition by Targeting HMGA2 in Pancreatic Cancer Cells.

miR-101 is an outstanding tumor suppressor in various cancers, while its role in pancreatic cancer (PC) is still unknown. The aim of this study was to investigate the role of miR-101 in epithelial-to-mesenchymal transition (EMT) and its clinical relevance in PC. Our data showed that the miR-101 expression was significantly decreased in human PC tissues, compared to non-tumor counterparts (p<0.05), which was reversely correlated to clinical characteristics, including lymph node metastasis, more venous infiltration, higher expression of CA19-9 and TNM stage (p<0.05). Low miR-101 expression was also confirmed to be associated with a poorer overall survival rate in PC patients (p<0.05). We identified high-mobility group AT-hook 2 (HMGA2) gene as a putative target of miR-101 in PC by bioinformatics analysis, dual luciferase activity and western blot assay, and found that miR-101 could specifically target the HMGA2 3'-untranslated region (3'-UTR) (p<0.05). Knockdown of HMGA2 reversed EMT resembling that of miR-101 over-expression. An inverse correlation between miR-101 and HMGA2 was observed in patients with PC (p<0.05). Taken together, our findings speculated that miR-101 might act as an inhibiting factor in EMT process in PC and up-regulation of miR-101 might be considered as a potentially key molecular treatment strategy for PC patients.

SHARPIN overexpression induces tumorigenesis in human prostate cancer LNCaP, DU145 and PC-3 cells via NF-κB/ERK/Akt signaling pathway.

SHARPIN emerges higher expression in prostate cancerous tissues than in benign prostate hyperplasia by means of immunohistochemistry in our previous study. In this work, we performed the gain of function assay and find that overexpression of SHARPIN in LNCaP, DU145 and PC-3 cells promoted cell proliferation, invasiveness and reduced apoptosis. Furthermore, SHARPIN overexpression displayed elevated Bcl-2 and Survivin expression and reduced levels of Bax, cleaved caspase-3. Meanwhile, entropic expression of SHARPIN increased the levels of phosphorylated p65, IkBα, ERK and Akt, were selectively increased in these cells. Collectively, our study unraveled the ability of SHARPIN overexpression to induce tumorigenesis of prostate cancer cells through the NF-kB/ERK/Akt pathway and transformation of apoptosis-associated proteins.

Comparative Analysis of Modified Laparoscopic Swenson and Laparoscopic Soave Procedure for Short-Segment Hirschsprung Disease in Children.

INTRODUCTION: This clinical analysis compared the characteristics and outcomes of modified laparoscopic Swenson (MLSw) and laparoscopic Soave (LS) procedures for short-segment Hirschsprung disease (HD) in children. PATIENTS AND METHODS: This clinical analysis involved a retrospective series of 42 pediatric patients with HD who underwent surgery from March 2007 to July 2012. Patients were divided into two groups: the LS group (n = 15) and the MLSw group (n = 27). Preoperative, operative, and postoperative data were collected, through patient follow-up periods ranging from 12 to 48 months, to compare perioperative/operative characteristics, postoperative complications, and outcomes between the two groups. Major measurements were analyzed statistically. RESULTS: On average, the patients in the LS group had a longer operating time (mean ± standard deviation, 199 ± 60 minutes) than those in the MLSw group (148 ± 23 minutes) (p < 0.05). Blood loss was significantly less in the MLSw group (10 ± 7 mL) than in the LS group (26 ± 14 mL) (p < 0.05). There was no difference in feeding time between the two groups (p > 0.05). The MLSw group was discharged after a shorter hospitalization time (8 ± 2 days) than the LS group (12 ± 4 days) (p < 0.05). The MLSw group had lower incidences of soiling (5, 18.5% vs. 7, 46.7%) and constipation (1, 3.7% vs. 3, 20%) than the LS group in the early postoperative period, but no difference was found between the two groups in the rate of complications during the late postoperative period. CONCLUSIONS: The MLSw procedure did not increase the risk of injury to vital intrapelvic structures or the incidence of complications in surgery for short-segment HD. The early postoperative outcome was much better in the MLSw group than in the LS group, but long-term outcomes were similar. However, the MLSw procedure was simpler, resulting in reduced operating time and less intraoperative blood loss.

Activation of nuclear factor κB pathway and downstream targets survivin and livin by SHARPIN contributes to the progression and metastasis of prostate cancer.

BACKGROUND: Nuclear factor κB (NFκB) signaling is strongly associated with tumor progression, and studies have shown that SHANK-associated RH domain interacting protein (SHARPIN) is crucial for NFκB pathway activation. However, the expression and functions of SHARPIN in prostate cancer (PCa) have not yet been defined. METHODS: The expression of SHARPIN in PCa cell lines and tissues was evaluated with western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. After SHARPIN was silenced in the PCa cell lines, western blots were used to confirm that SHARPIN physically associated with components of the NFκB pathway and the downstream targets (survivin and livin). The functions of SHARPIN in cell proliferation, migration, and invasion in vitro were measured with 5-(3-carboxymethoxyphenyl)-2-(4,5-dimenthylthiazoly)-3-(4-sulfophenyl)tetrazolium, inner salt (MTS), Transwell, and invasion assays, respectively. Flow cytometry was employed to evaluate cell apoptosis. Furthermore, tumorigenesis in vivo was examined with tumorigenicity assays. RESULTS: SHARPIN expression was upregulated in PCa cell lines and tissues. The knockdown of SHARPIN or incubation with Bay 11-7082 (an NFκB inhibitor) led to dramatically decreased levels of phosphorylated IκBα and phosphorylated p65 in comparison with the control group. Downregulation of survivin and livin due to SHARPIN inhibition was attributable to transcriptional repression (P < .05). Decreases in cell viability, migration, invasion, and survival with a higher sensitivity to docetaxel in vitro and with repressed tumorigenesis in vivo were observed upon SHARPIN silencing, and this was consistent with the results from inhibition of the NFκB pathway and its downstream targets. CONCLUSION: The current study demonstrates that overexpression of SHARPIN promotes activation of the NFκB pathway and downstream targets survivin and livin, which potentially contributes to PCa development.

Overexpression of miR-122 promotes the hepatic differentiation and maturation of mouse ESCs through a miR-122/FoxA1/HNF4a-positive feedback loop.

BACKGROUND & AIMS: microRNA-122 is the only identified liver-specific miRNA and plays a crucial role in liver development, maintenance of hepatic homeostasis as well as tumourigenesis. In our previous differentiation of ESCs into hepatocytes, microRNA-122 (miR-122) was expressed at a relatively low level. Here, we aim to elucidate the effect and underlying mechanisms of miR-122 during differentiation of ESCs into hepatocytes. METHODS: Mouse ESCs were initially induced towards HPCs by activin A, FGF-4 and sodium butyrate and were subsequently transfected with a recombinant adenovirus expressing vector pAV.Ex1d-CMV>miR-122/IRES/eGFP 9 days after induction. Cells were analysed by real-time PCR, immunofluorescence, flow cytometry, microscopy and functional assays. Furthermore, microarray analysis was performed. RESULTS: We demonstrated that overexpression of miR-122 could effectively promote hepatic differentiation and maturation, as assessed by morphological and functional tests. The microarray analysis revealed that 323 genes were down-regulated, whereas 59 were up-regulated. Particularly, two liver-specific transcription factors, FoxA1 and HNF4a, were significantly up-regulated. Moreover, the expression of E-cadherin was dramatically increased and the proliferation of HPCs was suppressed, whereas knockdown of FoxA1 reduced E-cadherin expression and increased the proliferation of HPCs. In addition, the expression levels of FoxA1, HNF4a and E-cadherin in time-course transfection experiments with miR-122 were not significantly increased except in cells in which transfection with miR-122 occurred 9 days after induction. CONCLUSION: Overexpression of miR-122 at an appropriate stage could promote hepatic differentiation and maturation by regulating the balance between proliferation and differentiation, as well as the balance between EMT and MET, partially through a miR-122/FoxA1/HNF4a-positive feedback loop.

[The clinic research of the modified laparoscopic splenectomy for massive splenomegaly in the treatment of children with hematologic diseases].

OBJECTIVE: To summarize the experience and characteristics of the modified laparoscopic splenectomy for massive splenomegaly in the treatment of children with hematologic disease. METHODS: The clinical data of 30 cases of laparoscopic splenectomy for massive splenomegaly of children with hematologic disease from March 2007 to December 2011 was analyzed retrospectively. There were 18 male and 12 female patients, aging from 2 to 14 years. Primary disease included mediterranean anemia (17 cases), hereditary spherocytosis (4 cases) and idiopathic thrombocytopenic purpura (ITP, 9 cases). Dissection started with cutting off the gastrosplenic ligaments and lesser sac to fully reveal the splenic hilum, the splenic artery was clamped twice with 10 mm tiatanum clamp. When most of blood stored in the spleen back to heart through the veins and the splenic volume had already decreased, the splenic vein was ligated with 10 mm titanium clip and cut with ligsure and splenic pedicle separated. The Surgery and complication were recorded. For 1 week after surgery, the hemoglobin and platelet counts were reviewed. RESULTS: Twenty-six cases were performed successfully, and 4 cases were converted to open procedure. Of the 4 cases, 2 cases was obesity because of idiopathic thrombocytopenic purpura, 1 case was ß thalassaemia combined severe liver enlargement, and 1 case was after partial splenic embolization. In cases of laparoscopic splenectomy, operation time was 110 to 130 minutes, with an average of 120 minutes, and blood loss during operation was 35 to 180 ml, with an average of 45 ml. Compared with pre-operation, the hemoglobin of mediterranean anemia and hereditary spherocytosis patients were (92 ± 8) g/L, and blood platelet count of ITP patients was (127 ± 20)×10(9)/L, and they increased obviously at 1 week after operation (t = 4.175 and 8.253, both P = 0.000). CONCLUSION: The modified surgical method make the laparoscopic splenectomy for massive splenomegaly in many children with hematologic diseases possible, which was thought to be impossible in the past.

A modified laparoscopic splenectomy for massive splenomegaly in children with hematological disorder: a single institute retrospective clinical research.

PURPOSE: With the optimal acceptance of its clinical advantages, laparoscopic splenectomy (LS) emerged as a gold standard procedure as compared with open splenectomy (OS). However, it is still controversial and even counted as contraindication for massive splenomegaly. Here, we aim to summarize the experiences, characteristics and trends of modified LS for massive splenomegaly in children with hematological disorders. METHODS: Retrospective series of 57 pediatric patients with massive splenomegaly who underwent splenectomy from March 2007 to December 2011 were designated for this clinical analysis. The main outcome measures were dealt by statistics. For 30 cases of LS, we strictly adhered to the principle of using only three trocars to operate and initial ligation of the splenic artery, followed by retrieving the piecemeal of spleen through an accessory incision of 2-3 cm at 12 mm trocar port site. RESULTS: Of the 57 pediatric patients, 27 underwent OS and 30 underwent LS, respectively. Despite the operative time being shorter for OS than for LS (P < 0.001), the blood loss was lower in LS than in OS (P < 0.001); the time required for oral intake as well as duration of hospital stay was lower in LS than in OS (P < 0.001). Post-operatively, 7 (25.9 %) complications occurred in OS and 3 (10 %) in LS. The conversion rate of LS to OS was 13.33 % in four cases till 2009. CONCLUSIONS: Despite the conflicting reports regarding the safety of LS for massive splenomegaly, we demonstrated that our modified laparoscopic splenectomy in the treatment of children with massive splenomegaly in hematological diseases seemed to achieve the fundamental goal of less invasion; it was safe and feasible.

Selection of hepatocyte-like cells from mouse differentiated embryonic stem cells and application in therapeutic liver repopulation.

UNLABELLED: BACKGROUD/AIM: Because of the oncogenic risk, it is important to gain the homogeneous and purified cells from differentiated ESCs before transplantation. Here, we aim to select hepatocyte-like cells from differentiated ESCs, and investigate their growth, differentiation and neoplastic formation after intrahepatic transplantation. METHODS: Mouse ESCs were primarily induced by Dexamethesone, FGF-4 and HGF sequentially, then placed to a conditioning selection media consisting of 5% cholestatic sera and cultivated for 2 wks. After labeled by CFDA-SE, the selected cells were transplanted into mouse liver in therapeutic liver repopulation models. RESULTS: In the early stage of screening cultivation, most cells were suffered from apoptosis or even death. 1w later, some hepatocyte-like colony-forming units were observed, then the selected cells could grow and tend to be more mature, as assessed by morphological and functional tests. After intrahepatic transplantation, the labeled cells could proliferate and expressed albumin. Moreover, teratoma didn't form over 3 months. CONCLUSION: Our conditioning selection media could not only effectively select hepatocyte-like cells from differentiated ESCs, but further promote their growth and differentiation as well. After intrahepatic transplantation in therapeutic liver repopulation models, the selected cells could grow, differentiate and keep partial hepatic function. In particular, the transplantation was safe.

Lentivirus-mediated RNAi knockdown of prostate-specific membrane antigen suppresses growth, reduces migration ability and the invasiveness of prostate cancer cells.

Prostate-specific membrane antigen is a type II membrane protein with folate hydrolase activity produced by prostatic epithelium. It has been demonstrated that prostate-specific membrane antigen over-expression may be correlated with prostate cancer, particularly in advanced cancer. The aim of the current study was to explore the possibility of prostate-specific membrane antigen as a therapeutic target for the treatment of prostate cancer. To address this problem, lentivirus-mediated small interfering RNA was employed to reduce endogenous prostate-specific membrane antigen expression in prostate cancer cell lines­LNCaP and DU-145. Then, the tumorigenesis, migration ability and invasiveness of prostate-specific membrane antigen-reduced prostate cancer cell lines were also examined. The prostate-specific membrane antigen expression in LNCaP and DU-145 cells was persistently and markedly reduced by lentivirus-mediated RNA interference. Down-regulation of prostate-specific membrane antigen expression significantly suppressed the growth rates of LNCaP and DU-145 cells. Moreover, the specific down-regulation arrested cells in G0/G1 phase of cell cycle. Furthermore, we also observed that the silence of prostate-specific membrane antigen could decrease the migration ability and the invasiveness of LNCaP and DU-145 cells. Our investigation demonstrated that lentivirus-mediated RNA interference silencing targeting prostate-specific membrane antigen might reduce the proliferation, and induce potent antitumor activity of LNCaP and DU-145 cells. Prostate-specific membrane antigen has considerable potential as a new therapeutic target for the treatment of prostate cancer.