Synthesis of Size-Tunable Hollow Polypyrrole Nanostructures and Their Assembly into Folate-Targeting and pH-Responsive Anticancer Drug-Delivery Agents.

Chemotherapeutic drugs currently used in clinical settings have high toxicity, low specificity, and short half-lives. Herein, polypyrrole-based anticancer drug nanocapsules were prepared by tailoring the size of the nanoparticles with a template method, controlling drug release by means of an aromatic imine, increasing nanoparticle stability through PEGylation, and improving tumor-cell selectivity by folate mediation. The nanoparticles were characterized by TEM and dynamic light scattering. α-Folate receptor expression levelsof tumor cells and normal cells were investigated by western blot and quantitative polymerase chain reaction analyses. Flow cytometry and fluorescence imaging were used to verify the cell uptake of the different-sized nanoparticles. From the different-sized polypyrrole nanoparticles, the optimally functionalized nanoparticles of 180 nm hydrodynamic diameter were chosen and further usedfor in vitroandin vivotests. The nanoparticles showed excellent biocompatibility and the drug-loaded nanoparticles exhibited effective inhibition of tumor cell growth in vitro. Moreover, the drug-loaded nanoparticles showed substantially enhanced accumulation in tumor regions and effectively inhibitedin vivotumor growth. Furthermore, the nanoparticles showed reduced doxorubicin-induced toxicity andno significant side effects in normal organs of tumor-bearing mice, as measured by body-weight shifts and evaluationof drug distribution. Overall, the functionalized nanoparticles are promising nanocarriers for tumor-targeting drug delivery.

Multifunctional halloysite nanotubes for targeted delivery and controlled release of doxorubicin in-vitro and in-vivo studies.

The current state of cancer therapy encourages researchers to develop novel efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier candidates due to their unique nanoscale (40-80 nm in diamter and 200-500 nm in length) and hollow lumen, as well as good biocompatibility and low cost. In our study, we prepared a type of folate-mediated targeting and redox-triggered anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically transported to tumor sites due to the over-expressed folate-receptors on the surface of cancer cells. Furthermore, it can then be released by the reductive agent glutathione (GSH) in cancer cells where the content of GSH is nearly 103-fold higher than in the extracellular matrix. A series of methods have demonstrated that per-thiol-ß-cyclodextrin (ß-CD-(SH)7) was successfully combined with HNTs via a redox-responsive disulfide bond, and folic acid-polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through the strong complexation between ß-CD/Ad. In vitro studies indicated that the release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h, while only 40% of DOX was released in phosphate buffer solution (PBS) even after 79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over-expressed folate-receptor cancer cells and significantly accelerate the apoptosis of cancer cells compared to non-targeted HNTs. In vivo studies further verified that the targeted HNTs had the best therapeutic efficacy and no obvious side effects for tumor-bearing nude mice, while free DOX showed damaging effects on normal tissues. In summary, this novel nanocarrier system shows excellent potential for targeted delivery and controlled release of anticancer drugs and provides a potential platform for tumor therapy.

MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths owing to its high rate of postoperative recurrence and metastasis. New research is continuously identifying novel metastasis-associated oncogenes and tumor suppressor genes. miRNAs are noncoding RNAs that regulate protein synthesis post-translationally. miR-130b is one of several miRNAs involved in tumor metastasis. However, the role of miR-130b in HCC remains controversial. Here, we demonstrate that miR-130b is highly expressed in HCC and that it correlates with tumor number, vascular invasion, and TNM stage-important predictors of postoperative recurrence and metastases. Moreover, high levels of miR-130b predicted poor overall and disease-free survival of HCC patients, and in vitro and in vivo research revealed that knockdown or overexpression of miR-130b inhibited and promoted proliferation and metastasis of HCC cells, respectively. We identified PTEN as a direct functional target of miR-130b using miRNA databases and a dual luciferase report assay. Next, using a gain and loss assay and epithelial-mesenchymal transition (EMT) relative assays, we show that miR-130b may promote proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Collectively, our data suggests that miR-130b may have prognostic value in HCC. Additionally, the miR-130b/PTEN/p-AKT/HIF-1α axis identified in this study provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC.

Clinicopathological characteristics of unicentric retroperitoneal Castleman's disease: a study of 14 cases.

BACKGROUND: The objectives of this study are to investigate the clinicopathological characteristics and prognosis analysis of unicentric retroperitoneal Castleman's disease (CD), and to improve the level of diagnosis and treatment of unicentric retroperitoneal CD. METHODS: The clinical data of 14 patients with unicentric retroperitoneal CD undergoing surgery from September 2007 to March 2014 were retrospectively reviewed. RESULTS: There were six males and eight females with a median age of 39 years old (range 15-58). Only three patients had a clinical manifestation of abdominal pain, and one patient associated with myasthenia gravis. All patients underwent surgical resection. The mean operation time was 137 min with a range of 72-472 min. The mean blood loss was 143 ml (range 50-500 ml). The CD was confirmed by histopathology. There were hyaline vascular (HV) type of CD in 13 cases, and mixed type of CD in one case. The mean hospital stay was 17.9 days with a mean postoperation hospital stay of 9.2 days. The duration of follow-up ranged from 21 to 99 months for 14 cases. All the 14 patients were alive without recurrence. CONCLUSIONS: Unicentric retroperitoneal CD is a rare disease that is often misdiagnosed due to the absence of specific clinical manifestations. The final diagnosis depends on pathologic examination. Complete surgical resection of the tumor is the best therapeutic alternative for unicentric CD.

MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase.

UNLABELLED: Hepatocellular carcinoma (HCC) is a highly invasive tumor with frequent intrahepatic or pulmonary metastasis, which is the main reason for high recurrence and poor survival of HCC after liver resection. However, the mechanisms for metastasis remain incompletely clear. Given that microRNAs (miRNAs) are implicated in HCC progression, we explored a potential role of miRNAs in metastasis by performing miRNA expression profiling in three subtypes of HCC with different metastatic potentials. We discovered miR-331-3p as one of most significantly overexpressed miRNAs and highly associated with metastasis of HCC. Increased expression of miR-331-3p was correlated with poor long-term survival of HCC. We provided both in vivo and in vitro evidence demonstrating that miR-331-3p promoted proliferation and metastasis of HCC cells. Using an integrated approach, we uncovered that PH domain and leucine-rich repeat protein phosphatase (PHLPP) was a novel target of miR-331-3p. Indeed, the miR-331-3p-mediated effects were antagonized by reexpression of PHLPP or mimicked by silencing of PHLPP. We further showed that miR-331-3p-mediated inhibition of PHLPP resulted in stimulation of protein kinase B (AKT) and subsequent epithelial mesenchymal transition (EMT). Finally, inhibition of miR-331-3p through a jetPEI-mediated delivery of anti-miR-331-3p vector resulted in marked inhibition of proliferation and metastasis of HCC in xenograft mice. CONCLUSION: miR-331-3p promotes proliferation and EMT-mediated metastasis of HCC through suppression of PHLPP-mediated dephosphorylation of AKT. Our work implicates miR-331-3p as a potential prognostic biomarker and a novel therapeutic target.

Body Mass Index and Waistline are Predictors of Survival for Hepatocellular Carcinoma After Hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide especially in China. This article aimed to evaluate the influence of body mass index (BMI) and waistline on complications, postoperative death, and long-term survival in patients undergoing surgery for HCC. MATERIAL AND METHODS: 136 patients were enrolled and divided into 4 groups: group A, BMI <25; group B, BMI ≥25; group C, waistline <90 cm in males or waistline <80 cm in females; group D, waistline ≥90 cm in males or waistline ≥80 cm in females. Clinical pathological features and surgical outcomes of these patients were analyzed retrospectively. RESULTS: There were no significant differences in postoperative complication rate and postoperative death between group A and group B, although pulmonary infection showed a significant difference between 2 groups (P=0.017). Vascular invasion, waistline, and BMI are the independent prognostic factors for long-term survival. The disease-free survival curves after hepatectomy showed no statistically significant difference between group A and group B. Group C had the better overall survival than group D, and group A had the better overall survival than group B. CONCLUSIONS: BMI and waistline are both independent prognostic factors for long-term survival of HCC after hepatectomy. Waistline is more important than BMI in predicting the disease-free survival of HCC after hepatectomy.

Surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus: a novel classification.

BACKGROUND: The hepatic resection for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) which is not uncommon at clinic continues to be debated. Our study introduced a novel classification of HCC with PVTT and compared the outcomes of surgical treatment between different groups. METHODS: From January 2008 to December 2012, a total of 56 cases of HCC with PVTT underwent liver resection combined with thrombectomy. Clinical pathological features and surgical data of these patients were retrospectively studied. The patients were divided into two groups. Cumulative overall and disease-free survival curves of the patients were compared according to different groups. RESULTS: Sixteen patients (28.6%) belonging to group A were compared to 40 patients (71.4%) belonging to group B. The rates of capsular formation and tumor number showed differences between the two groups (P = 0.047, P = 0.032). Group A had more liver cirrhosis than group B (P = 0.047). The patients with large blood loss (≥1,000) were more in group A, as well. There was no significant difference in complications between the two groups except the ascites (P = 0.028). The 1-year overall survival rate of group A after liver resection was 31.5%. The 1-, 3-, and 5-year overall survival rates of group B were 62.3%, 16.1%, and 5.2%, respectively. For further study, group B had significantly better overall survival than group A (P = 0.033). Group A had significantly higher incidence of recurrence than group B (P = 0.021). CONCLUSIONS: Liver resection combined with thrombectomy for HCC with PVTT can get better outcome in the HCC patients with PVTT involving only one branch (left/right) of portal vein (group B) compared to patients with PVTT involving the main portal vein trunk or both the left and right portal veins (group A).

Liver resection for young patients with large hepatocellular carcinoma: a single center experience from China.

BACKGROUND: To investigate retrospectively the clinicopathological characteristics and outcomes of young patients with large hepatocellular carcinoma after hepatectomy. METHODS: From January 2003 to December 2012, a total of 153 patients with large hepatocellular carcinoma (HCC) who received liver resection were included in the study. The clinicopathological features were analyzed retrospectively. The perioperative data were compared between those aged <40 years (the young group) and those aged >40 years (the older group). Prognostic factors and long-term survival were evaluated. RESULTS: The young group had more hepatitis B virus-related HCC than the older group (87.2% vs 66.3%, P = 0.031). In the young group, 15 patients (21.5%) were overweight (body mass index 25 to 29.9 kg/m2) or obese (body mass index ≥30 kg/m2), and 38 patients (45.8%) were overweight or obese in the older group (P = 0.032). Other clinicopathological characteristics were similar between the two groups. The perioperative data showed that the older group had more pulmonary infection after hepatectomy. Vascular invasion and high Edmondson-Steiner grade were the independent prognostic factors for long-term survival. There was no statistical difference between the young group and the older group in overall survival and disease-free survival (P = 0.109 and P = 0.087, respectively). CONCLUSIONS: Liver resection for young patients with large HCC was safe and efficacious and should be recommended.

SIN1 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition.

BACKGROUND: Stress-activated protein kinase (SAPK) interacting protein 1 (SIN1) is essential for early embryonic development and is the key regulator of Akt, which plays an important role in various pathological conditions such as cancer. However, the biological function and clinical significance of SIN1 in hepatocellular carcinoma (HCC) remains unknown. METHODS: Real-time quantitative reverse-transcriptase polymerase chain reaction analysis, western blot analysis, and immunohistochemical staining were used to test the expression level of SIN1, and its correlation with clinicopathologic parameters as well as the prognosis for patients with HCC were analyzed. In addition, the biological function and molecular mechanisms of SIN1 in HCC were investigated. RESULTS: SIN1 levels were elevated predominantly in HCC tissues, and its level in solitary large HCC was significantly lower than those in nodular HCC (P = .016), but showed no significant differences between solitary large HCC and small HCC (P > .05). Levels of SIN1 were up-regulated in highly metastatic HCC cell lines (HCCLM3 and MHCC97-H), whereas their invasion and migration significantly decreased after depletion of SIN1. High expression of SIN1 was associated with tumor number (P = .012), capsular formation (P = .037), and venous invasion (P = .023) and was an independent risk factor for overall survival (P = .046). Finally, SIN1 was capable of promoting invasion and metastasis of HCC by facilitating epithelial-mesenchymal transition. CONCLUSIONS: The current findings suggest that SIN1 plays an important role in HCC invasion and metastasis by facilitating epithelial-mesenchymal transition.

Hepatectomy for huge hepatocellular carcinoma: single institute's experience.

BACKGROUND: The surgical resection of huge hepatocellular carcinoma (HCC) is still controversial. This study was designed to introduce our experience of liver resection for huge HCC and evaluate the safety and outcomes of hepatectomy for huge HCC. METHODS: A total of 258 hepatic resections for the patients with huge HCC were analysed retrospectively from December 2002 to December 2011. The operative outcomes were compared with 293 patients with HCC >5.0 cm but <10.0 cm in diameter. Prognostic factors for long-term survival were evaluated by univariate and multivariate analyses. RESULTS: The 1-, 3-, 5-year overall survival rates after liver resection were 84, 62, and 33 %. Overall survival and disease-free survival in huge HCC group and HCC >5.0 cm but <10.0 cm group were similar (P = 0.751, P = 0.493). Solitary huge HCC group has significantly a more longer overall and disease-free survival time than nodular huge HCC (P = 0.026, P = 0.022). Univariate and multivariate analysis revealed that the types of tumour, vascular invasion, and UICC stage were independent prognostic factors for overall survival (P = 0.047, P = 0.037, P = 0.033). CONCLUSIONS: Hepatic resection can be performed safely for huge HCC with a low mortality and favorable survival outcomes. Solitary huge HCC has the better surgical outcomes than nodular huge HCC.

Bacterial synthesis of PbS nanocrystallites in one-step with L-cysteine serving as both sulfur source and capping ligand.

The green bacterial biosynthesis of lead sulfide nanocrystallites by L-cysteine-desulfurizing bacterium Lysinibacillus sphaericus SH72 was demonstrated in this work. Nanocrystals formed by this bacterial method were characterized using the mineralogical and morphological approaches. The results revealed that the microbially synthesized PbS nanocrystals assume a cubic structure, and are often aggregated as spheroids of about 105 nm in size. These spheroids are composed of numerous nanoparticles with diameter 5-10 nm. Surface characterization of the bacterial nanoparticles with FTIR spectroscopy shows that the L-cysteine coats the surface of PbS nanoparticle as a stabilizing ligand. The optical features of the PbS nanocrystallites were assessed by UV-Vis spectroscopy and PL spectroscopy. The maximum absorption wavelength of the bacterial PbS particles occurs at 240 nm, and the photoluminescence emission band ranges from 375 to 550 nm. The band gap energy is calculated to be 4.36 eV, compared to 0.41 eV for the naturally occurring bulk PbS, with this clear blue shift attributable to the quantum size effect.

Role of cantharidin in the activation of IKKα/IκBα/NF­κB pathway by inhibiting PP2A activity in cholangiocarcinoma cell lines.

Cantharidin (CAN), a potent inhibitor of serine/threonine­protein phosphatase 2A (PP2A), is widely used in clinical practice, particularly in the treatment of advanced cancer due to its specific action on these types of cancer. In the present study, the inhibitory effect of CAN was examined in two cholangiocarcinoma cell lines (QBC939 and Hucc­t1). Following treatment with CAN, cell viability was effectively reduced in QBC939 and Hucc­t1 cells and normal human intrahepatic biliary epithelial cells. However, a slight increase in reactive oxygen species levels in QBC939 cells treated with CAN was observed post­treatment. CAN significantly inhibited cell migration and invasion in a dose­dependent manner. Western blot analysis demonstrated that the nuclear factor­κB (NF­κB) pathway was stimulated by CAN, which was confirmed by the upregulated phosphorylation levels of inhibitor of NF­κB kinase subunit α (IKKα) and NF­κB inhibitor α (IκBα) in cells, and an increased NF­κB p65 subunit level in the nucleus. The expression levels of 72 kDa type IV collagenase (MMP2) and matrix metalloproteinase 9 (MMP9) were downregulated by CAN. Notably, there was a negative association between MMP2 and MMP9 expression levels, and NF­κB p65, although NF­κB p65 regulates the expression of MMP2 and MMP9 and has a positive association with these proteins in various types of cancer. Notably, it was observed that CAN exerted specific inhibition on PP2A activity and thereby resulted in the activation of the IKKα/IκBα/NF­κB pathway. Therefore, CAN­induced cell inhibition maybe partially dependent on the activation of the IKKα/IκBα/NF­κB pathway. In conclusion, it was demonstrated that CAN selectively and effectively inhibited cholangiocarcinoma cell migration and invasion. The present study may provide a novel insight into the use of CAN as a therapeutic candidate in the treatment of cholangiocarcinoma.

Prognostic value of increased expression of RACO-1 in patients with hepatitis B-related hepatocellular carcinoma.

RING domain AP-1 coactivator-1 (RACO-1) is a coactivator that links c-Jun to growth factor signaling and is essential for AP-1 function. This study aimed to investigate the expression and clinical significance of RACO-1 protein in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in China. A total of 136 tissue samples of HBV-related HCC were detected by immunohistochemistry (including 76 patients in training cohort and 60 patients in validation cohort). Correlation between RACO-1 expression and clinicopathologic features of HBV-related HCC was analyzed in both the cohorts. RACO-1 expression was significantly higher in HBV-related HCC tissues than in adjacent non-tumor liver tissues. All the patients were divided into two groups: the low expression group and the high expression group. RACO-1 expression was significantly related to vascular invasion (P=0.021), tumor numbers (P=0.046), International Union for Cancer Control/American Joint Committee on Cancer stage (P=0.006), cirrhosis (P=0.046), capsular (P=0.039), and Barcelona Clinic Liver Cancer stage (P=0.041) in training cohort. The validation cohort showed the same results. The high RACO-1 expression was the independent prognostic factor for HBV-related HCC patients in both training cohort and validation cohort. Our data implicate RACO-1 as a novel prognostic marker and a potential therapeutic target for HBV-related HCC.

Decrease of RBM4 indicates poor prognosis in patients with hepatocellular carcinoma after hepatectomy.

RNA-binding motif 4 (RBM4) has been reported to play an important role in many human tumors such as lung cancer, breast cancer, ovarian cancer and gastric cancer by regulating alternative splicing and messenger RNA (mRNA) translation. However, little is known about the role of RBM4 in the development of hepatocellular carcinoma (HCC). This study aimed to investigate the expression of RBM4 in HCC tissues. Expression of RBM4 was detected by immunohistochemistry in 95 cases of HCC. Correlations of RBM4 expression with the overall survival and disease-free survival of HCC were also studied. Patients with high RBM4 expression had better overall survival rate and disease-free survival rate than those with low RBM4 expression (P<0.001, P=0.007, respectively). RBM4 expression, together with tumor numbers, capsular formation, vascular invasion and Barcelona clinic liver cancer (BCLC) stage, was an independent prognostic factor for overall survival rate and disease-free survival rate of HCC. Our data implicate RBM4 as a novel prognostic marker and a potential therapeutic target for HCC.

Interconnectivity of macroporous molecularly imprinted polymers fabricated by hydroxyapatite-stabilized Pickering high internal phase emulsions-hydrogels for the selective recognition of protein.

Hydroxyapatite hybridized molecularly imprinted polydopamine polymers with selective recognition of bovine hemoglobin (BHb) were successfully prepared via Pickering oil-in-water high internal phase emulsions-hydrogels and molecularly imprinting technique. The emulsions were stabilized by hydroxyapatite of which the wettability was modified by 3-methacryloxypropyltrimethoxysilane. The materials were characterized by SEM, IR and TGA. The results showed that the BHb imprinted polymers based on Pickering hydrogels (Hydro-MIPs) possess macropores ranging from 20µm to 50µm, and their large numbers of amino groups and hydroxyl groups result in a favorable adsorption capacity for BHb. The maximum adsorption capacity of Hydro-MIPs for BHb was 438mg/g, 3.27 times more than that of the non-imprinted polymers (Hydro-NIPs). The results indicated that Hydro-MIPs possessing well-defined hierarchical porous structures exhibited outstanding recognition behavior towards the target protein molecules. This work provided a promising alternative method for the fabrication of polymer materials with tunable and interconnected pores structures for the separation and purification of protein in vitro.

JARID2 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition through PTEN/AKT signaling.

JARID2 is crucial for maintenance of pluripotency and differentiation of embryonic stem cells. However, little is known about the role of JARID2 in metastasis of hepatocellular carcinoma (HCC). This study found that JARID2 expression was significantly higher in HCC tissues than that in adjacent non-tumor liver tissues (ANLTs), and its expression level correlated with HCC metastasis. High JARID2 expression was significantly correlated with multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05) and indicated poor prognosis of HCC in training and validation cohorts (all P < 0.05) totaling 182 patients. High JARID2 expression was an independent and significant risk factor for disease-free survival (DFS; P = 0.017) and overall survival (OS; P = 0.041) after curative liver resection in training cohort, and also validated as an independent and significant risk factor for DFS (P = 0.033) and OS (P = 0.031) in validation cohort. Moreover, down-regulation of JARID2 dramatically inhibited HCC cell migration, invasion, proliferation in vitro and metastasis in vivo, whereas overexpression of JARID2 significantly increased migration, invasion, proliferation in vitro and metastasis in vivo. Mechanistically, the data showed that JARID2 exerted its function by repressing PTEN expression through increasing H3K27 trimethylation (H3K27me3) at PTEN promoter region, which subsequently resulted in activation of protein kinase B (AKT) and enhanced epithelial-mesenchymal transition (EMT). In conclusion, this study revealed that JARID2 promotes invasion and metastasis of HCC by facilitating EMT through PTEN/AKT signaling.

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis.

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

YMO1 suppresses invasion and metastasis by inhibiting RhoC signaling and predicts favorable prognosis in hepatocellular carcinoma.

Previous studies have shown that 4.1 proteins, which are deregulated in many cancers, contribute to cell adhesion and motility. Yurt/Mosaic eyes-like 1 (YMO1) is a member of 4.1 protein family but it is unclear whether YMO1 plays a role in tumor invasion. This study aimed to investigate the effects of YMO1 on hepatocellular carcinoma (HCC) and attempted to elucidate the underlying molecular mechanisms. YMO1 expression in HCC tissues and its correlation with clinicopathological features and postoperative prognosis was analyzed. The results showed that YMO1 was down-regulated in the highly metastatic HCC cell line and in human tumor tissues. Underexpression of YMO1 indicated poor prognosis of HCC patients. Restoration of YMO1 expression caused a significant decrease in cell migration and invasiveness in vitro. In vivo study showed that YMO1 reduced liver tumor invasion and metastasis in xenograft mice. YMO1 directly inhibited RhoC activation. YMO1 expression in HCC was regulated by PAX5. Analysis of YMO1 expression levels in human HCC patients revealed a significant correlation of YMO1 expression with PAX5 and RhoC. Our findings revealed that YMO1 predicts favorable prognosis and the data suggest that YMO1 suppresses tumor invasion and metastasis by inhibiting RhoC activity.

Reduced Histone H3 Acetylation in CD4(+) T Lymphocytes: Potential Mechanism of Latent Autoimmune Diabetes in Adults.

Aims. Latent autoimmune diabetes in adults (LADA) is the result of gene-environment interactions. Histone acetylation regulates gene expression and maybe interpret how environmental factors modify LADA. Hence, we studied the histone acetylation patterns in CD4(+) T lymphocytes from LADA patients. Methods. Blood CD4(+) T lymphocytes from 28 patients with LADA and 28 healthy controls were obtained to detect histone H3 acetylation and H4 acetylation. The gene expression of histone acetyltransferases (P300 and CREBBP) and histone deacetylases (HDAC1, HDAC2, and HDAC7) was measured by real-time polymerase chain reaction (RT-PCR). Results. Compared to healthy controls, reduced global H3 acetylation was observed in LADA patients' CD4(+) T lymphocytes (P < 0.05). Global level of H4 acetylation was not statistically different. Among LADA, CD4(+) T lymphocytes H3 acetylation was associated with glycosylated hemoglobin (HbA1c) and GADA titer. Compared to healthy controls, the expression of histone acetyltransferases CREBBP in LADA patients was downregulated, and the expression of histone deacetylases HDAC1 and HDAC7 was upregulated. Conclusion. A concerted downregulation of histone H3 acetylation was found in CD4(+) T lymphocytes of LADA patients, and this might provide evidence of a novel epigenetic explanation for the pathogenesis of LADA and its complications.