The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistry.

BACKGROUND: Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure. METHODS: We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1. RESULTS: Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p < 0.0001). Further confirmation of elevated TPI1 mRNA expression was obtained from external datasets, comparing 251 LSCC tissue samples to 136 non-LSCC tissue samples (standardized mean difference = 1.06). The upregulated TPI1 mRNA demonstrated a high discriminative ability between LSCC and non-LSCC tissue (area under the curve = 0.91; sensitivity = 0.87; specificity = 0.79), suggesting its potential as a predictive marker for poor prognosis (p = 0.037). Lower infiltration abundance was found for plasma cells, naïve B cells, monocytes, and neutrophils in TPI-high expression LSCC tissue. Glycolysis and cell cycle were significantly enriched pathways for both LSCC tissue and single cells, where heat shock protein family B member 1, TPI1, and enolase 1 occupied a central position. Four outgoing communication patterns and two incoming communication patterns were identified from the intercellular communication networks. TPI1 was predicted as an oncogene in LSCC, with CRISPR scores less than -1 across 71.43% of the LSCC cell lines. TPI1 was positively correlated with the half maximal inhibitory concentration of gemcitabine and cladribine. CONCLUSIONS: TPI1 is dramatically overexpressed in LSCC than in normal tissue, and the high expression of TPI1 may promote LSCC deterioration through its metabolic and non-metabolic functions. This study contributes to advancing our knowledge of LSCC pathogenesis and may have implications for the development of targeted therapies in the future.

ITGB4 Serves as an Identification and Prognosis Marker Associated with Immune Infiltration in Small Cell Lung Carcinoma.

Integrin beta 4 (ITGB4) is a vital factor for numerous cancers. However, no reports regarding ITGB4 in small cell lung carcinoma (SCLC) have been found in the existing literature. This study systematically investigated the expression and clinical value of ITGB4 in SCLC using multi-center and large-sample (n = 963) data. The ITGB4 expression levels between SCLC and control tissues were compared using standardized mean difference and Wilcoxon rank-sum test. The clinical significance of the gene in SCLC was observed using Cox regression and Kaplan-Meier curves. ITGB4 is overexpressed in multiple cancers and represents significant value in distinguishing among cancer samples (AUC = 0.91) and predicting the prognoses (p < 0.05) of patients with different cancers. In contrast, decreased ITGB4 mRNA expression was determined in SCLC (SMD < 0), and this finding was further confirmed at protein levels using in-house specimens (p < 0.05). This decrease in expression may be attributed to the regulatory role of estrogen receptor 1. ITGB4 may participate in the progression of SCLC by affecting several signaling pathways (e.g., tumor necrosis factor signaling pathway) and a series of immune cells (e.g., dendritic cells) (p < 0.05). The gene may serve as a potential marker for predicting the disease status (AUC = 0.97) and prognoses (p < 0.05) of patients with SCLC. Collectively, ITGB4 was identified as an identification and prognosis marker associated with immune infiltration in SCLC.

Clinicopathological value of hematopoietic cell kinase overexpression in laryngeal squamous cell carcinoma tissues.

Laryngeal squamous cell carcinoma (LSCC) is the most lethal cancer in head and neck tumors. Although hematopoietic cell kinase (HCK) has been proven to be an oncogene in several solid tumors, its roles in LSCC remain obscure. This is the first study to evaluate the clinical value of HCK in LSCC, with the aim of exploring its expression status and potential molecular mechanisms underlying LSCC. LSCC tissue-derived gene chips and RNA-seq data were collected for a quantitive integration of HCK mRNA expression level. To confirm the protein expression level of HCK, a total of 82 LSCC tissue specimens and 56 non-tumor laryngeal epithelial controls were collected for in-house tissue microarrays and immunohistochemical staining. Kaplan-Meier curves were generated to determine the ability of HCK in predicting overall survival, progress-free survival, and disease-free survival of LSCC patients. LSCC overexpressed genes and HCK co-expressed genes were intersected to preliminarily explore the enriched signaling pathways of HCK. It was noticed that HCK mRNA was markedly overexpressed in 323 LSCC tissues compared with 196 non-LSCC controls (standardized mean difference = 0.81, p < 0.0001). Upregulated HCK mRNA displayed a moderate discriminatory ability between LSCC tissues and non-tumor laryngeal epithelial controls (area under the curve = 0.78, sensitivity = 0.76, specificity = 0.68). The higher expression level of HCK mRNA could predict worse overall survival and disease-free survival for LSCC patients (p = 0.041 and p = 0.013). Lastly, upregulated co-expression genes of HCK were significantly enriched in leukocyte cell-cell adhesion, secretory granule membrane, and extracellular matrix structural constituent. Immune-related pathways were the predominantly activated signals, such as cytokine-cytokine receptor interaction, Th17 cell differentiation, and Toll-like receptor signaling pathway. In conclusion, HCK was upregulated in LSCC tissues and could be utilized as a risk predictor. HCK may promote the development of LSCC by disturbing immune signaling pathways.

Clinicopathologic Significance and Prognostic Value of Programmed Cell Death Ligand 1 (PD-L1) in Patients With Hepatocellular Carcinoma: A Meta-Analysis.

Background: There is still a dispute over an issue of the clinical pathology and prognostic of programmed cell death ligand 1 (PD-L1) in hepatocellular carcinoma (HCC) patients. Here, we undertook this meta-analysis to survey the conceivable role of PD-L1 in HCC. Method: We searched databases like MEDLINE, EMBASE, and Google Scholar for relevant studies published in English up to February 13, 2018. We implemented the appraisal of the eligible studies according to the choice criterion. We used Hazard ratio (HR) and its 95% confidence interval (95% CI) to evaluate the prognostic role of PD-L1 for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS). Odds ratio (OR) and the corresponding 95% CI were calculated to evaluate the connection between PD-L1 and clinicopathological features. Publication bias was tested. Results: 13 studies, which published range from 2009 to 2017 were contained in this meta-analysis, involving 1,843 patients with HCC. The results indicated that high PD-L1 could predict shorter OS (HR = 1.57, 95% CI: 1.09-2.27, P < 0.00001) as well as poorer DFS (HR = 2.07, 95% CI: 1.20-3.58, P = 0.009). Additionally, high PD-L1 expression was correlated to liver cirrhosis (OR = 1.66, 95% CI: 1.10-2.50, P = 0.02), poorer tumor Barcelona Clinical Liver Cancer (BCLC) stage (OR = 0.30, 95% CI: 0.10-0.88, P = 0.03) and portal vein invasion (OR = 1.96, 95% CI: 1.04-3.68, P = 0.04), but had no correlation with age, gender, tumor size, number of tumors, AFP, vascular invasion, HBVs-Ag, Anti-HCV, differentiation or TNM stage. Besides, no significant publication bias was found among these identified studies. Conclusion: The meta-analysis suggested that PD-L1 overexpression could foresee worse OS and DFS in HCC. Moreover, the PD-L1 expression has to bear on liver cirrhosis, portal vein invasion, and BCLC stage.

Pterostilbene inhibits MTA1/HDAC1 complex leading to PTEN acetylation in hepatocellular carcinoma.

PURPOSE: The aim of this study is to investigate the inhibition of cancer growth by pterostilbene through Metastasis-Associated Protein 1 (MTA1) and the histone deacetylase 1 (HDAC1) complex in hepatocellular carcinoma (HCC). METHODS: We investigate the antitumor effects of pterostilbene (PTER) in HCC. The SMMC-7721 hepatoma cell line was cultured and treated with PTER for different time depending on the experiment. After treatment, we tested the cellular expression of proteins by Western blot and the expression of MTA1 mRNA by real-time PCR. And the immunoprecipitation was performed to confirm the acetylation in PTEN. Animal models have been established to confirm the anti-cancer effects of PTER. RESULTS: PTER treatment could downregulate the expression of MTA1, and HDAC1 and elevates the Ac-PTEN ratio in tumors. The results suggest that PTER can decrease the expression of MTA1 and destabilize the MTA1/HDAC1 complex allowing acetylation/activation of PTEN on Lys402 site. The expression of MTA1 may be linked to cell apoptosis and invasion in HCC. CONCLUSION: We demonstrated that PTER suppressed the growth, and invasion of HCC and was effective in regulating the levels of the MTA1/HDAC1/NuRD complex, promoting PTEN acetylation and apoptosis in HCC. Our findings suggest that the novel epigenetic nature of PTER anticancer activity opens up new avenues for primary chemoprevention, as well as anticancer and antimetastatic treatment.

Pterostilbene increases PTEN expression through the targeted downregulation of microRNA-19a in hepatocellular carcinoma.

Pterostilbene (Pter) is reported to exhibit an anticancer effect in hepatocellular carcinoma (HCC). In order to explore the anticancer mechanism in HCC cells, the present study aimed to investigate whether pterostilbene (Pter) may increase phosphatase and tensin homolog (PTEN) expression through targeted downregulation of microRNA (miRNA/miR)-19a in hepatocellular carcinoma (HCC). The proliferation, apoptosis and cell cycle was analyzed in the SMMC­7721 HCC cell line by MTT assays and flow cytometry methods. Cells were divided into five treatment groups: Pter treatment, miR­19a inhibitor transfection, Pter + miR­19a inhibitor, negative control transfection and blank control. The expression of miR­19a and PTEN was detected by reverse transcription­quantitative polymerase chain reaction and western blot analysis following treatment. Furthermore, a luciferase reporter gene assay was performed to determine whether the PTEN gene was a direct target of miR­19a. The results demonstrated that Pter treatment or miR­19a inhibitor transfection downregulated miR­19a and induced PTEN/Akt pathway regulation, which led to proliferation inhibition, cell cycle arrest in the S phase, increased apoptosis and reduced cell invasion. These results indicated that Pter may increase PTEN expression through the direct downregulation of miR­19a in HCC. Therefore, miR­19a may have potential as a novel molecular marker for HCC and Pter may be a promising clinical target with the potential to be developed as a HCC therapy.

Upregulation of DARS2 by HBV promotes hepatocarcinogenesis through the miR-30e-5p/MAPK/NFAT5 pathway.

BACKGROUND: Infection with the hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). The osmoregulatory transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown to play an important role in the development of many types of human cancers. The role of NFAT5 in HBV-associated HCC has never previously been investigated. METHODS: We compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC samples, adjacent nontumor tissues and different hepatoma cell lines by quantitative real-time polymerase chain reaction and /or Western blot. Clinical data of HCC patients for up to 80 months were analyzed. The regulatory mechanisms upstream and convergent downstream pathways of NFAT5 in HBV-associated HCC were investigated by ChIP-seq, MSP, luciferase report assay and bioinformation anaylsis. RESULTS: We first found that higher levels of NFAT5 expression predict a good prognosis, suggesting that NFAT5 is a potential tumor-suppressing gene, and verified that NFAT5 promotes hepatoma cell apoptosis and inhibits cell growth in vitro. Second, our results showed that HBV could suppress NFAT5 expression by inducing hypermethylation of the AP1-binding site in the NFAT5 promoter in hepatoma cells. In addition, HBV also inhibited NFAT5 through miR-30e-5p targeted MAP4K4, and miR-30e-5p in turn inhibited HBV replication. Finally, we demonstrated that NFAT5 suppressed DARS2 by directly binding to its promoter. DARS2 was identified as an HCC oncogene that promotes HCC cell cycle progression and inhibits HCC cell apoptosis. CONCLUSION: HBV suppresses NFAT5 through the miR-30e-5p/mitogen-activated protein kinase (MAPK) signaling pathway upstream of NFAT5 and inhibits the NFAT5 to enhance HCC tumorigenesis via the downstream target genes of DARS2.

Tumoricidal activities of pterostilbene depend upon destabilizing the MTA1-NuRD complex and enhancing P53 acetylation in hepatocellular carcinoma.

The present study aimed to assess the tumoricidal effect of metastasis-associated protein 1 (MTA1) induced by pterostilbene (PTER) in hepatocellular carcinoma (HCC). The SMMC-7721 hepatoma cell line was treated with PTER. Following treatment, the mRNA transcript abundance of MTA1 was measured using quantitative polymerase chain reaction. Additionally, cell viability was determined using an MTT assay, and protein expression was measured through western blotting. Cell invasion, motility and apoptosis, as well as the cell cycle, were also investigated. Following PTER treatment, MTA1, histone deacetylase (HDAC) 1 and HDAC2 were downregulated, whereas the ratio of acetyl-p53 to total p53 was increased in HCC cells. Cell viability decreased as the PTER dose increased. MTA1 may be associated with proliferation, motility, invasion and metastasis in HCC cells. PTER appeared to repress cell proliferation, trigger apoptosis, induce cell cycle arrest, and inhibit motility and invasion via MTA1 in human liver cancer cells. The results of the present study demonstrated that PTER can downregulate the MTA1-nucleosome remodeling and deacetylase complex, and enhance p53 acetylation to inhibit the growth of tumor cells in HCC.

Effects of microRNA-126 on cell proliferation, apoptosis and tumor angiogenesis via the down-regulating ERK signaling pathway by targeting EGFL7 in hepatocellular carcinoma.

This study intends to explore the effects of microRNA-126 (miR-126) on cell proliferation, apoptosis, and tumor angiogenesis in hepatocellular carcinoma (HCC) by regulating epidermal growth factor-like domain 7 (EGFL7) through extracellular signal-regulated kinase (ERK) signaling. HCC tissues and adjacent normal tissues were obtained from 184 HCC patients. HCC cells were separately transfected with recombinant plasmids. Western blotting and qRT-PCR were applied to detect miR-126 and EGFL7, ERK, Fas/FasL, Bcl-2, Caspase mRNA and protein levels. CCK8 and TUNEL were performed to determinate cell proliferation and apoptosis. Flow cytometry was used to analyze cell cycle distribution. Rats model of HCC was constructed, and tumor weight and the number of new blood vessels were recorded after 3 weeks of tumor transplantation. Compared with the adjacent normal tissues, HCC tissues exhibited lower miR-126 expression, and higher EGFL7, and ERK mRNA and protein levels. Overexpression of miR-126 in HCC cell lines suppressed EGFL7, ERK, Bcl-2, and P-ERK, and increased apoptotic-associated proteins Fas/FasL and Caspase-3, and it inhibited cell proliferation and induced cell apoptosis. Overexpression of miR-126 in nude mice resulted in reduced tumor weight and less new blood vessels in tumors. The inhibition of miR-126 decreased cell apoptosis, and enhanced cell proliferation and tumor angiogenesis. This study demonstrates that miR-126 might decrease cell proliferation, induce apoptosis, and inhibit tumor angiogenesis in HCC by inhibiting EGFL7 via down-regulating the ERK signaling pathway.

Hepatogenic differentiation from human adipose-derived stem cells and application for mouse acute liver injury.

Adipose-derived stem cells (ADSCs) derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm, and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, human ADSCs were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD71, CD73, CD90, CD105, CD166, CYP3A4, and ALB were detected by immunofluorescence assays. Human ADSCs were cultured in a specific hepatogenesis differentiation medium containing HGF, bFGF, nicotinamide, ITS, and oncostatin M for hepatogenic differentiation. The hepatocyte markers were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Hepatocytes derived from ADSCs or ADSCs were transplanted into the mice of liver injury for observation cells colonization and therapy in liver tissue. The result demonstrated that human ADSCs were positive for the CD13, CD71, CD73, CD90, CD105, and CD166 but negative for hepatocyte markers, ALB and CYP3A4. After hepatogenic differentiation, the hepatocytes were positive for liver special markers, gene expression level showed a time-lapse increase with induction time. Human ADSCs or ADSCs-derived hepatocyte injected into the vein could improve liver function repair and functionally rescue the CCl4-treated mice with liver injury, but the ADSCs transplantation was better than ADSCs-derived hepatocyte transplantation. In conclusion, our research shows that a population of hepatocyte can be specifically generated from human ADSCs and that cells may allow for participation in tissue-repair.

Long non-coding RNA PTENP1 interacts with miR-193a-3p to suppress cell migration and invasion through the PTEN pathway in hepatocellular carcinoma.

Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, was previously reported to be a tumour suppressor in some cancer types. However, the precise effects mediated by PTENP1 transcripts within intricate regulatory networks involving molecular interactions with PTEN and tumorigenicity in hepatocellular carcinoma (HCC) remains elusive. Here, we identify the critical biological functions of PTENP1 and discuss whether PTENP1 could directly interact with miR-193a-3p to affect the progression of HCC both in vitro and in vivo. We demonstrated that PTENP1 level in the HCC tissues was significantly lower compared with those in the adjacent normal tissues. And PTENP1 was able to repress cell invasion, metastasis, and proliferation capacity in HCC cell lines. The overexpression of PTENP1 inhibited HCC growth both in vitro and in vivo. There were a binding sequence and direct interaction between PTENP1 and miR-193a-3p. PTENP1 as an endogenous sponge interacted with miR-193a-3p, leading to regulate the downstream PTEN/Akt pathway. These results suggested that PTENP1 with its suppression effect might serve as novel biomarkers and potent therapeutic strategies in HCC.

Selective CDK7 inhibition with BS-181 suppresses cell proliferation and induces cell cycle arrest and apoptosis in gastric cancer.

Cyclin-dependent kinase (CDK) family members have been considered as attractive therapeutic targets for cancer. In this study, we aim to investigate the anticancer effects of a selective CDK7 inhibitor, BS-181, in gastric cancer (GC) cell line. Human GC cells (BGC823) were cultured with or without BS-181 at different concentrations for 24-72 hours. BS-181 significantly reduced the activity of CDK7 with downregulation of cyclin D1 and XIAP in GC cells. Treatment with BS-181 induced cell cycle arrest and apoptosis. The expression of Bax and caspase-3 was significantly increased, while Bcl-2 expression was decreased in cells treated with BS-181. In addition, the inhibition of CDK7 with BS-181 resulted in reduced rates of proliferation, migration, and invasion of gastric cells. Those results demonstrated the anticancer activities of selective CDK7 inhibitor BS-181 in BGC823 cells, suggesting that CDK7 may serve as a novel therapeutic target or the treatment of GC.

The long noncoding RNA, EGFR-AS1, a target of GHR, increases the expression of EGFR in hepatocellular carcinoma.

LncRNA has provided an important new perspective regarding gene regulation. Both the expression and activation of EGFR have been proven to be under the tight control of the GHR pathway. EGFR-AS1 has been found to inhibit the expression of EGFR. GHR-siRNA and EGFR-AS1-siRNA were transfected into HCC cell lines, and a series of WB, q-PCR, and IF experiments was conducted to evaluate whether EGFR-AS1 participated in the regulation of GHR and EGFR. We found that impeded expression of GHR decreased the expression of EGFR and EGFR-AS1 in vivo and in vitro. Then, it was verified that EGFR and EGFR-AS1 were relatively upregulated in HCC tissue, and they were significantly related to some clinical characteristics and patient prognosis. Furthermore, EGFR-AS1 was determined to promote HCC development by improving the ability of invasion and proliferation of HCC cells in vitro, and it was also found to affect the cell cycle. Our study identified that EGFR-AS1 may promote HCC genesis and development. EGFR-AS1 may act as a prognostic factor in HCC. More importantly, we observed that the inhibition of EGFR-AS1 in HCC cells significantly impeded cell proliferation and invasion in vivo, which might provide a potential possibility for targeted therapy of HCC.

Antiperistaltic Side-to-Side Ileorectal Anastomosis is Associated with a Better Short-Term Fecal Continence and Quality of Life in Slow Transit Constipation Patients.

BACKGROUND: Surgical treatment of refractory slow transit constipation (STC) is traditionally performed using end-to-side ileorectal anastomosis (SE-IRA) with total abdominal colectomy (TAC). Antiperistaltic side-to-side (SS) IRA is suggested to be a superior approach. Employing a well-characterized cohort of STC patients, we compared the postoperative outcomes of the 2 surgical approaches. METHODS: A total of 42 patients underwent TAC for refractory idiopathic STC. Twenty patients were treated using traditional SE-IRA whereas 22 patients were treated using SS-IRA. Patients were evaluated at 3 and 6 months as well as at 1 and 2 years after surgery. Both groups were compared for patient characteristics, perioperative data and quality of life. Cleveland Clinic Incontinence Score (CCIS) and Gastrointestinal Quality of Life Index (GQILI) were adopted for evaluating postoperative recovery. RESULTS: Both study groups were comparable with respect to general patient characteristics, disease severity and post-operative complications. Fewer than 30% of all patients reported substantial dissatisfaction with surgical outcomes in both the groups. The SS-IRA group was associated with a lower postoperative CCIS (p < 0.05) and a better GQILI (p < 0.05) than that of the SE-IRA group during early follow-up examinations. CONCLUSION: In this study, SS-IRA was superior to traditional SE-IRA for the treatment of STC with respect to post-operative outcomes, and especially during early follow-up.

Effect of portal vein ligation on tumor growth and liver regeneration in rat cirrhotic liver lobes.

The aim of the present study was to investigate the effect of portal vein ligation (PVL) on the tumor growth rate and liver regeneration in rat cirrhotic liver lobes. A total of 45 male Wistar rats were randomly divided into PVL, hepatic tumor (HT) and HT + PVL groups (n=15 per group). Liver regeneration and tumor growth in ligated and non-ligated lobes were evaluated prior to and following PVL. In addition, serum alanine transaminase, total bilirubin levels and liver tissue samples were evaluated. The results indicated that PVL induced apparent hypertrophy in normal and HT rats. However, the ratio of non-ligated lobes to total liver weight or body weight in the HT + PVL group was significantly lower when compared with the PVL group (P<0.05). Compared with the HT group, the tumor growth rate in the ligated lobes of the HT + PVL group significantly increased (P<0.05). However, tumor growth in the non-ligated lobes exhibited no statistically significant difference between the HT and HT + PVL groups. In addition, Knodell scores indicated that fibrosis was more apparent in the non-ligated lobes of the HT + PVL group when compared with the HT group (P<0.05). Therefore, tumor growth was accelerated in ligated lobes following PVL, but not in non-ligated lobes. PVL also induced liver regeneration in cirrhotic liver lobes with lower efficiency than that in the non-cirrhotic lobes. However, hypertrophy in the contralateral cirrhotic lobes appeared to be non-functional.

Suppression of angiogenesis and tumor growth in vitro and in vivo using an anti-angiopoietin-2 single-chain antibody.

Hepatocellular carcinomas (HCCs) are tumors with a highly developed vascular architecture. HCC cells require access to blood vessels for growth and metastasis; therefore, the inhibition of angiogenesis represents a potential therapeutic target for HCC that may reduce the mortality and morbidity from HCC. Various attempts to develop an anti-angiogenic therapy have been made in past decades; however, modest results have been achieved in clinical trials and the challenge of HCC treatment remains. Single-chain antibodies (scFv) are characterized by low molecular weight, low immunogenicity, high penetration and a short half-life, and are easy to produce on a large scale by genetic engineering. Accordingly, an scFv against a specific angiogenic regulator, such as angiopoietin (Ang), may be a promising anti-angiogenic therapy for HCC. Our previous study indicated that an imbalanced expression of angiopoietin-2 (Ang-2) vs. angiopoietin-1 (Ang-1) in HCCs contributes to initiation of neovascularization and promotes the angiogenesis and progression of HCCs. Therefore, we suggest that specific Ang-2-targeting interventions may be valuable in the treatment of HCC via remodeling the neovascular network and changing the tumor microenvironment. In this study, a prokaryotic expression vector of Ang-2 was constructed and purified human Ang-2 protein was isolated. An scFv against human Ang-2 (scFv-Ang2) was identified and purified via phage display technology, and the effects of scFv-Ang2 in vitro and in vivo on HCC in nude mice were evaluated. The results show that scFv-Ang2 inhibits vascular endothelial growth factor (VEGF) and Ang-2 induces the proliferation, migration and tubule formation of human umbilical vein endothelial cells (HUVECs) in vitro. In the in vivo assay, statistical indices, including tumor weight and volume, metastases to lungs, CD31 expression and the microvessel density (MVD) count in the scFv-Ang2-treated group of mice were significantly lower than those in the control group (P<0.05). In conclusion, the successfully generated scFv-Ang2 showed significant inhibitory effects on the angiogenesis and tumor growth of human HCC in vitro and in vivo.

Operable severe obstructive jaundice: how should we use pre-operative biliary drainage?

Obstructive jaundice is a common surgical problem, and surgery in jaundiced patients is associated with a higher risk of postoperative complications than surgery in non-jaundiced patients. However, the efficacy of pre-operative biliary drainage (PBD) for patients with obstructive jaundice remains controversial. Many studies have been unable to confirm the benefit of PPB and have suggested that it should not be performed routinely. While we agree that routine PBD is not recommended for all jaundiced patients, we believe that it is useful for certain subgroups; however, there are no clear guidelines regarding its application in these subgroups. We suggest that further large and detailed randomised control studies should focus on formulating codes and standards of PBD for patients with operable conditions causing severe obstructive jaundice.

Current role of surgery for the treatment of fulminant Clostridium difficile colitis.

OBJECTIVE: This review discusses the current status and progress in studies on fulminant Clostridium difficile colitis (FCDC), including the definition, risk factor, diagnostic role of CT, surgical treatment, postoperative mortality, and new therapeutic strategy. DATA SOURCES: A literature search was conducted mainly in Medline and PubMed published in English between January 2000 and May 2011. The search terms were "ulminant Clostridium difficile colitis" "reatment", "urgery" and "ortality" RESULTS: Recent studies show that the overall mortality rate for FCDC remains high despite early surgical intervention. It has been difficult to identify the real value for surgical intervention in patients with FCDC due to the absence of prospective, randomized studies. Early recognition of patients with FCDC will help a clinician decide the need for treatment in an intensive care setting, multi-disciplinary consultation, and appropriate therapeutic selection. Some studies emphasize the importance of early recognition and emergent surgery at a less severe stage. Monoclonal antibody therapy and intravenous immunoglobulin treatment may be useful for the treatment of FCDC. CONCLUSIONS: Present studies do not provide strong evidence for guiding the surgical treatment of FCDC; hence, creation of collaborative research networks is crucial in order to undertake large prospective multi-center studies for improvement in overall survival.

5-Aza-2<-deoxycytidine induces hepatoma cell apoptosis via enhancing methionine adenosyltransferase 1A expression and inducing S-adenosylmethionine production.

In hepatocellular cancer (HCC), lack of response to chemotherapy and radiation treatment can be caused by a loss of epigenetic modifications of cancer cells. Methionine adenosyltransferase 1A is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation. Therefore, drugs releasing epigenetic repression have been proposed to reverse this process. We studied the effect of the demethylating reagent 5-aza-2<-deoxycitidine (5-Aza-CdR) on MAT1A gene expression, DNA methylation and S-adenosylmethionine (SAMe) production in the HCC cell line Huh7. We found that MAT1A mRNA and protein expression were activated in Huh7 cells with the treatment of 5-Aza-CdR; the status of promoter hypermethylation was reversed. At the same time, MAT2A mRNA and protein expression was significantly reduced in Huh7 cells treated with 5-Aza-CdR, while SAMe production was significantly induced. However, 5-Aza-CdR showed no effects on MAT2A methylation. Furthermore, 5-Aza-CdR inhibited the growth of Huh7 cells and induced apoptosis and through down-regulation of Bcl-2, up-regulation of Bax and caspase-3. Our observations suggest that 5-Aza- CdR exerts its anti-tumor effects in Huh7 cells through an epigenetic change involving increased expression of the methionine adenosyltransferase 1A gene and induction of S-adenosylmethionine production.