Circular RNA Circ_0001322 inhibits gastric cancer progression by modulating the miR-1264/QKI axis and suppressing the Hedgehog pathway.

Circular RNA hsa_circ_0001322 (circ1322) was demonstrated to be significantly reduced in expression in gastric cancer patients in our previous study, and changes in its expression were significantly correlated with lymph node metastasis. However, the underlying workings of circ1322 in gastric cancer are still not fully understood. Therefore, to confirm the effect of circ1322 on gastric cancer, we examined the expression of circ1322 in gastric cancer cells and tissues. The results showed that circ1322 was lowly expressed in GC tissues and cells. Subsequently, we further performed cellular assays and animal experiments, which showed that Circ1322 upregulation inhibited GC cell proliferation, migration and invasion. while promoting GC cell apoptosis, and inhibited tumor growth in mice. The direct targeting of circ1322 to miR-1264 was confirmed by bioinformatics prediction and validation of luciferase reporter gene assay. Circ1322 can act as a miR-1264 sponge to alleviate the inhibitory effect of miR-1264 on its target gene, QKI. miR-1264 regulates the expression of QKI and the activity of the hedgehog pathway. That is, circ1322 may act as a competing endogenous RNA (ceRNA) to inhibit the hedgehog pathway by targeting the miR-1264/QKI axis, which in turn promotes GC progression.

MicroRNA-204-3p represses colon cancer cells proliferation, migration, and invasion by targeting HMGA2.

Colon cancer is a detrimental neoplasm of the digestive tract. MicroRNAs (miRNAs) as central regulators have been discovered in colon cancer. Nonetheless, the impact of miR-204-3p on colon cancer remains indistinct. The research attempted to uncover the impacts of miR-204-3p on colon cancer cells growth, migration, and invasion. miR-204-3p expression level in colon cancer tissues and diverse colon cancer cell lines were testified by the quantitative real-time polymerase chain reaction. Exploration of the impacts of miR-204-3p on cell growth, migration, invasion, and their associated factors through assessment of CCK-8, flow cytometry, Transwell, and western blot, respectively. High mobility group AT-hook 2 (HMGA2) expression was then detected in Caco-2 cells after miR-204-3p mimic and inhibitor transfection, additionally dual-luciferase activity was implemented to further uncover the correlation between HMGA2 and miR-204-3p. The impact of HMGA2 on Caco-2 cell growth, migration, and invasion was finally assessed. We found that repression of miR-204-3p was discovered in colon cancer tissues and HCT116, SW480, Caco-2, HT29 and SW620 cell lines. MiR-204-3p overexpression mitigated Coca-2 cell viability, facilitated apoptosis, simultaneously adjusted CyclinD1 and cleaved caspase-3 expression. Cell migration, invasion, and the associated factors were all suppressed by miR-204-3p overexpression. Reduction of HMGA2 was presented in Caco-2 cells with miR-204-3p mimic transfection, and HMGA2 was predicated to be a target gene of miR-204-3p. Besides, HMGA2 silence showed the inhibitory effect on Caco-2 cells growth, migration, and invasion. In conclusion, miR-204-3p repressed colon cancer cell growth, migration, and invasion through targeting HMGA2.

Co-expression of LAG3 and TIM3 identifies a potent Treg population that suppresses macrophage functions in colorectal cancer patients.

Regulatory T (Treg) cells are critical suppressors of inflammation and are thought to exert mainly deleterious effects in cancers. In colorectal cancer (CRC), Foxp3+ Treg accumulation in tumors was associated with poor prognosis. Hence, we examined the circulating Treg cells in CRC patients. Compared to controls, CRC patients presented mild upregulations in CD4+ CD25+/hi T cells and in the more canonical CD4+ CD25+/hi Foxp3+ Treg cells in peripheral blood mononuclear cells. Both of these Treg populations could be roughly divided into lymphocyte activation gene 3 negative T cell immunoglobulin and mucin-domain containing-3 negative (LAG3- TIM3- ) and LAG3+ TIM3+ subsets. In CRC patients, the LAG3+ TIM3+ subset represented approximately half of CD4+ CD25+/hi T cells and greater than 60% of CD4+ CD25+/hi Foxp3+ Treg cells, which was significantly more frequent than in healthy controls. Compared to the LAG3- TIM3- CD4+ CD25+/hi T cells, the LAG3+ TIM3+ CD4+ CD25+/hi T cells presented considerably higher transforming growth factor-ß and slightly higher interleukin (IL)-10 secretion, together with higher cytotoxic T-lymphocyte associated protein 4 and Foxp3 expression levels. Notably, macrophages following incubation with LAG3- TIM3- CD4+ CD25+/hi T cells and LAG3+ TIM3+ CD4+ CD25+/hi T cells displayed different characteristics. Macrophages incubated with LAG3+ TIM3+ CD4+ CD25+/hi T cells presented lower expression of major histocompatibility complex class II, CD80, CD86, and tumor necrosis factor-α but higher expression of IL-10, than macrophages incubated with LAG3- TIM3- CD4+ CD25+/hi T cells. Together, our investigations demonstrated that CRC patients presented an enrichment of circulating Treg cells, in which the LAG3+ TIM3+ subset exhibited more potent expression of inhibitory molecules, and furthermore, the LAG3+ TIM3+ Treg cells could suppress the proinflammatory activation of macrophages more potently than the LAG3- TIM3- Treg cells.

Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population.

BACKGROUND: Elucidating the genetic basis underlying hepatic gene expression variability is of importance to understand the aetiology of the disease and variation in drug metabolism. To date, no genome-wide expression quantitative trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the largest ethnic group in the world. METHODS: We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue samples (n=64). The data were then compared with published eQTL data from a Caucasian population. We then performed correlations between these eQTLs with important pharmacogenes, and genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs), in particular those identified in the Asian population. RESULTS: Our analyses identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide significance level (p=10⁻8). Both cis- and trans-eQTLs in the Asian population were also more likely to be eQTLs in Caucasians (p<10⁻4). Enrichment analyses revealed that trait-associated GWAS-SNPs were enriched within the eQTLs identified in our data, so were the GWAS-SNPs specifically identified in Asian populations in a separate analysis (p<0.001 for both). We also found that hepatic expression of very important pharmacogenetic (VIP) genes (n=44) and a manually curated list of major genes involved in pharmacokinetics (n=341) were both more likely to be controlled by eQTLs (p<0.002 for both). CONCLUSIONS: Our study provided, for the first time, a comprehensive hepatic eQTL analysis in a non-European population, further generating valuable data for characterising the genetic basis of human diseases and pharmacogenetic traits.

A Novel Scoring System in Predicting Prognosis After Adjuvant FOLFOX Chemotherapy in Gastric Cancer.

Purpose: To evaluate the impact of neutrophil-to-lymphocyte ratio (NLR) and preoperative prognostic nutritional index (PNI) on prognosis of gastric cancer (GC) after adjuvant FOLFOX chemotherapy. Materials and Methods: Data on 749 GC patients who received operation after by adjuvant FOLFOX chemotherapy between January 2013 and December 2015 were enrolled in this study, retrospectively. Receiver-operating characteristic curve analysis was employed to assess optimal cutoff thresholds for PNI and NLR. The GC subjects having a low PNI (<52.8) and high NLR (>1.79) received a score of 2. Any variable that met these standards was scored as 1. If none of the two variables met these standards of the patient was assigned a score of 0. Correlation between PNI-NLR score and GC stage was also evaluated. Results: The mean overall survival (OS) and 5-year OS rate for subjects with PNI-NLR = 2 was lower than those of subjects with PNI-NLR = 1, or 0 (40.9% vs. 52.1%, 76.4% [46.0 vs. 61.0], 68.0 months, p ≤ 0.001). In multivariate analyses, the PNI-NLR score (p ≤ 0.001) and WHO grade (p ≤ 0.001) showed potential to independently influence OS. Conclusions: High PNI-NLR scores can independently affect worse prognosis of GC. Thus, it can be utilized to differentiate low risk from high risk subjects.

Reduced expression of PER3 is associated with incidence and development of colon cancer.

BACKGROUND: Period 3 (PER3), a circadian regulation protein, influences cell cycle, growth, and differentiation. The aim of the present study was to determine whether PER3 expression is associated with colon cancer incidence and progression. METHODS: PER3 expression was analyzed in the normal and cancerous tissues from patients with colon cancer by establishing a long serial analysis of gene expression (SAGE) database as well as by real-time PCR and immunohistochemistry. RESULTS: As compared with normal tissue, a 2.8-fold decrease in PER3 mRNA levels in colon cancerous tissue was observed. Real-time PCR analysis revealed that PER3 mRNA levels in tumor tissues were lower than in normal tissues (P < 0.001) in both patients with colon tumor and those with rectal tumor. In addition, PER3 expression was related to multiple clinicopathologic factors, including tumor location, differentiation, and stage. Furthermore, the incidence of death was higher in subjects with PER3-negative tumors (P = 0.025); the estimated overall survival time was 71.5 ± 2.2 months and 58.6 ± 5.0 months in subjects with PER3-positive and PER3-negative tumors, respectively (P = 0.020). CONCLUSIONS: PER3 may play a role in colon cancer progression.

Forkhead box M1 recruits FoxP3+ Treg cells to induce immune escape in hilar cholangiocarcinoma.

OBJECTIVE: Hilar cholangiocarcinoma (HCCA) is a malignancy related to chronic biliary tract inflammation. Tumor immune escape is a necessary process of tumorigenesis. Forkhead box M1 (FoxM1) could affect the progression of various carcinomas. This study attempted to elaborate on the mechanism of FoxM1 in HCCA immune escape. METHODS: HCCA cell lines were collected to measure the expression of FoxM1 and FoxP3. CD8+ T cells were extracted to establish the co-culture system with HCCA cells and Treg cells. pcDNA3.1-FoxM1 or si-FoxP3 was transfected into HCCA cells in the co-culture system. HCCA cell viability, mobility, and invasiveness as well as levels of transforming growth factor (TGF)-ß and interleukin (IL)-6 were evaluated. The binding relation between FoxM1 and FoxP3 promoter was verified. HCCA cells with pcDNA3.1-FoxM1 were subcutaneously injected into mice to establish the xenograft mouse models. RESULTS: FoxM1 and FoxP3 were overexpressed in HCCA cells. The co-culture of CD8+ T and HCCA cells inhibited HCCA cell activity and Treg cells limited CD8+ T killing. FoxM1 overexpression strengthened the inhibiting role of Treg cells in CD8+ T killing, upregulated TGF-ß and IL-6 levels, and encouraged HCCA immune escape. FoxM1 bound to the FoxP3 promoter region to promote FoxP3 transcription. Silencing of FoxP3 neutralized the promoting role of FoxM1 overexpression in Treg cell immunosuppression and HCCA cell immune escape. FoxM1 aggravated tumor development, upregulated FoxP3 expression, increased Treg cells, and reduced CD8+ T cells. CONCLUSION: FoxM1 bound to the FoxP3 promoter region to promote FoxP3 transcription and recruited FoxP3+ Treg cells, thereby inducing HCCA immune escape.

Interleukin-22 promotes PD-L1 expression via STAT3 in colon cancer cells.

Blocking the expression of programmed cell death ligand 1 (PD-L1) is a promising approach for the treatment of colon cancer. The binding of PD-L1 to its receptor programmed cell death 1 (PD-1) on immune cells leads to the apoptosis of activated T cells and causes immune escape. However, there is a limited number of patients with colon cancer that can benefit from the inhibition of PD-L1, and the regulation of PD-L1 expression is poorly understood in colon cancer. The present study demonstrated that interleukin-22 (IL-22) and PD-L1 were upregulated in colon cancer tissues and there was a positive correlation between IL-22 expression and PD-L1 expression. In the present study, exogenous IL-22 was found to upregulate PD-L1 expression via the signal transducer and activator of transcription 3 signaling pathway in human colon cancer cells (DLD-1 and primary colon cancer cells). The results of the present study revealed a novel regulatory mechanism of PD-L1 expression in colon cancer, which provides a theoretical basis for decreasing the immune tolerance of colon cancer via IL-22 overexpression.

Proteomic analysis of pancreatic ductal adenocarcinoma compared with normal adjacent pancreatic tissue and pancreatic benign cystadenoma.

BACKGROUND: Dual expression of potential biomarkers in both benign and malignant pancreatic tumors was a major obstacle in the development of diagnostic biomarkers of early pancreatic cancer. METHODS: To better understand the limitations of potential protein biomarkers in pancreatic cancer, we employed two-dimensional difference gel electrophoresis technology and tandem mass spectrometry to study protein expression profiles in pancreatic cancer tissues, benign pancreatic adenoma and normal adjacent pancreas. Seven differently expressed proteins were selected for validation by Western blot and/or immunohistochemistry. RESULTS: 21 spots were overexpressed and 24 spots were downexpressed in pancreatic cancer compared with benign and normal adjacent tissues. Our study demonstrated that three candidate pancreatic ductal adenocarcinoma biomarkers identified in previous studies, fructose-bisphosphate aldolase A, alpha-smooth muscle actin and vimentin, were also overexpressed in pancreatic cystadenoma, which might lower their further utility as biomarkers for pancreatic cancer. Aflatoxin B(1) aldehyde reductase (AKR7A2) was confirmed to be only highly expressed in pancreatic cancer, not in normal adjacent pancreas and benign tumors. CONCLUSIONS: The protein profile pattern of pancreatic cystadenoma was more similar to normal adjacent pancreas than pancreatic cancer. We identified panels of the upregulated proteins in pancreatic cancer, which have not been reported in prior proteomic studies. AKR7A2 may be a novel potential biomarker for pancreatic cancer.

Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy.

OBJECTIVE: This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. METHODS: A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), α-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. RESULTS: Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. CONCLUSIONS: Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.

Effects of silencing the DUSP1 gene using lentiviral vector-mediated siRNA on the release of proinflammatory cytokines through regulation of the MAPK signaling pathway in mice with acute pancreatitis.

The present study investigated the effects of dual specificity phosphatase 1 (DUSP1) gene silencing using lentiviral vector-mediated small interfering (si)RNA on the release of proinflammatory cytokines through the regulation of the mitogen­activated protein kinase (MAPK) signaling pathway in mice with acute pancreatitis (AP). Two siRNA­DUSP1 sequences and one scramble siRNA sequence were designed, and the expression of DUSP1 was detected using western blot analysis to screen for the one with a higher interference rate. An AP mouse model was established, and KM mice were assigned to either a control, siRNA, AP, AP+PD98059, AP+scramble, AP+siRNA or AP+PD98059+siRNA group. The expression of proinflammatory cytokines, including tumor necrosis factor (TNF)­α, interleukin (IL)­1ß and IL­6, high mobility group box 1 (HMGB1), and S100A12 in serum samples were detected using an enzyme­linked immunosorbent assay at 12, 24 and 48 h post­modeling. The serum amylase levels were also detected. The expression levels of DUSP1, TNF­α, IL­1ß, IL­6, HMGB1, S100A12, phosphorylated (p­) extracellular signal­regulated kinase (ERK), p­c­Jun N­terminal kinase (JNK), p­p38, ERK, JNK and p38 in pancreatic, liver, kidney and lung tissues were detected using reverse transcription­quantitative polymerase chain reaction and western blot analysis. Compared with the control group, the siRNA group demonstrated marginally upregulated serum amylase, lipase, urinary trypsinogen­2, and proinflammatory cytokines, HMGB1 and S100A12 in serum and tissues, with no statistically significant difference, elevated expression levels of p­ERK, p­JNK and p­p38, and decreased expression of DUSP1. The other five groups demonstrated increased expression levels of TNF­α, IL­1ß, IL­6, HMGB1, S100A12, amylase, lipase and urinary trypsinogen­2 in serum, and increased expression levels of DUSP1, TNF­α, IL­1ß, IL­6, HMGB1, S100A12, p­ERK, p­JNK and p­p38 in tissues. Compared with the AP group, the AP+PD98059+siRNA group had decreased expression of DUSP1 in tissues, whereas the AP+PD98059 group had decreased serum expression levels of TNF­α, IL­1ß, IL­6, HMGB1, S100A12 and amylase, lipase and urinary trypsinogen­2. The expression levels of TNF­α, IL­1ß, IL­6, HMGB1, S100A12, p­ERK, p­JNK, p­p38 in tissues, and edema of pancreatic tissue were alleviated, whereas the opposite results were observed in the AP+siRNA group with the decreased expression of DUSP1. The results suggested that DUSP1 gene silencing promoted the release of proinflammatory cytokines through activation of the MAPK signaling pathway in mice with AP.

T-cell immunoglobulin mucin-3 as a potential inducer of the epithelial-mesenchymal transition in hepatocellular carcinoma.

T-cell immunoglobulin mucin (TIM)-3 is an important member of the TIM gene family, which was thought to contribute to the progression of numerous types of cancer, including hepatocellular carcinoma (HCC); however, the mechanism underlying TIM-3 functions in HCC progression has not yet been extensively investigated. The present study aimed to investigate the function of TIM-3 in the metastasis of HCC and to determine whether the alteration of TIM-3 expression levels regulated the epithelial-mesenchymal transition (EMT) occurrence of HCC, using epithelial (E)-cadherin, neuronal (N)-cadherin, matrix metallopeptidase-9 (MMP-9), Twist 1, Slug, Snail, and Smad as EMT biomarkers. The results demonstrated that upregulation of TIM-3 using TIM-3 lentiviral activation particles (5 µl) increased cell migration and invasion, which was decreased in TIM-3 short interfering RNA-infected cells (10 µM, 3 µl) correspondingly. SMMC-7721 HCC cells were used as the control. EMT was aggravated in TIM-3 upregulated SMMC-7721 cells, which was attenuated in the TIM-3 interference group, accompanied by an alteration of E-cadherin, N-cadherin, MMP-9, Twist 1, Slug, Snail and Smad expression levels. The data presented suggests that TIM-3 serves an essential role in the metastasis of HCC, the mechanism of which was associated with EMT occurrence. Interference of TIM-3 is expected to be an effective means to prevent and control EMT, and further the metastasis of HCC.

Donors FMO3 polymorphisms affect tacrolimus elimination in Chinese liver transplant patients.

AIM: Flavin-containing monooxygenase (FMO) variants were potentially involved in tacrolimus metabolism in kidney transplantion. The influences of FMO3 genotypes on tacrolimus elimination in Chinese liver transplant patients remained unclear. PATIENTS & METHODS: FMO3 SNPs and CYP3A5 rs776746 were analyzed in 110 Chinese patients. RESULTS: Donor FMO3 rs1800822 allele T and rs909530 allele T were associated with fast tacrolimus elimination. Combination of polymorphisms of donor FMO3 rs1800822 and rs909530 genotype impacted on tacrolimus elimination (p = 0.0221). The number of donor rs1800822 allele T and rs909530 allele T was confirmed to be an independent predictor of the tacrolimus concentration-to-dose ratios for weeks 2, 3 and 4 in the multivariate analysis. CONCLUSION: Donor's FMO3 polymorphisms might affect tacrolimus elimination.

MicroRNA-187 inhibits tumor growth and metastasis via targeting of IGF-1R in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the primary and most frequently occurring type of malignant liver cancer, accounting for 70-85% of total liver cancer cases worldwide. It has previously been demonstrated that the aberrant expression of microRNAs (miR) contributes to carcinogenesis and progression of various human malignancies, including HCC. However, mechanisms underlying the differential expression and specific roles of miR­187 in HCC remain to be elucidated, particularly regarding how the modulation of malignant phenotypes in HCC cells occurs. The present study demonstrated that miR­187 was significantly downregulated in HCC tissues and cell lines. Restoration of miR­187 expression inhibited cell proliferation, migration and invasion in HCC. Furthermore, insulin­like growth factor 1 receptor (IGF­1R) was demonstrated to act as a direct target gene of miR­187 in HCC. IGF­1R knockdown mimicked the effects of miR­187 overexpression in HCC, resulting in a significant inhibition of cell proliferation, migration and invasion. The results of the present study demonstrated that miR­187 acted as a tumor suppressor in HCC progression via direct targeting of IGF­1R. miR­187 may therefore exhibit the potential to act as a novel and therapeutic target for HCC treatment in the future.

MicroRNA-17 induces epithelial-mesenchymal transition consistent with the cancer stem cell phenotype by regulating CYP7B1 expression in colon cancer.

MicroRNA-17 (miRNA-17/miR­17) expression has been confirmed to be significantly higher in colorectal cancer tissues than in normal tissues. However, its exact role in colorectal cancer has not yet been fully elucidated. In this study, we found that miR-17 not only promoted epithelial-mesenchymal transition (EMT), but also promoted the formation of a stem cell-like population in colon cancer DLD1 cells. We also wished to determine the role of cytochrome P450, family 7, subfamily B, polypeptide 1 (CYP7B1) in CRC. miR-17 was overexpressed using a recombinant plasmid and CYP7B1 was silenced by transfection with shRNA. Western blot analysis was used to determine protein expression in the DLD1 cells and in tumor tissues obtained from patients with colon cancer. Our results revealed that miR­17 overexpression led to the degradation of CYP7B1 mRNA expression in DLD1 cells. In addition, we found that the silencing of CYB7B1 promoted EMT and the formation of a stem cell-like population in the cells. Thus, our findings demonstrate that miR­17 induces EMT consistent with the cancer stem cell phenotype by regulating CYP7B1 expression in colon cancer.

Association of the GLB1 rs4678680 genetic variant with risk of HBV-related hepatocellular carcinoma.

Accumulated evidences demonstrated that GLB1 is involved in cell senescence and cancer development. The GLB1 rs4678680 single nucleotide polymorphism (SNP) has been identified as a hepatocellular carcinoma (HCC) susceptibility polymorphism by a genome-wide association study in Korean population previously. However, little or nothing was known about its involvement and functional significance in hepatitis B viruses (HBV)-related HCC in Chinese. Therefore, we investigated the association between the GLB1 rs4678680 SNP and HBV-related HCC risk as well as its biological function in vivo. Genotypes were determined in two independent case-control sets from two medical centers of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The potential regulation role the rs4678680 genetic variant on GLB1 expression was examined with HCC and normal liver tissues. We found that The rs4678680 G allele was showed to be risk allele; individuals with the TG genotype had an OR of 1.51 (95% CI = 1.10-2.07, P = 0.010, Shandong set) or 1.49 (95% CI = 1.11-1.99, P = 0.008, Jiangsu set) for developing HBV-related HCC, respectively, compared with individuals with the TT genotype. This association was more pronounced in males, individuals aged older than 57 years and drinkers (all P < 0.05). In the genotype-phenotype correlation analyses of fifty-six human liver tissue samples, rs4678680 TG or GG was associated with a statistically significant increase of GLB1 mRNA expression (P < 0.05). Our data indicated that the GLB1 rs4678680 SNP contributes to susceptibility to develop HBV-related HCC, highlighting the involvement of GLB1 and cell senescence in etiology of HCC.

Liver transplantation for recurrent posthepatectomy malignant hepatic angiomyolipoma: a case report.

Hepatic angiomyolipomas (AMLs) are typically benign tumors containing varying amounts of smooth muscle cells, adipose tissue, and vessels, and are commonly found in the kidney and occasionally in the liver. The preoperative diagnosis of hepatic AML is primarily made from imaging and fine-needle aspiration biopsy results, though limited experience for such diagnoses can result in misdiagnosis. Some uncommon features of hepatic AML have been reported in the literature without an objective or qualitative consensus. As the majority of cases are benign, conservative treatment of AMLs is recommended. However, in rare cases, liver transplantation has been implemented. Only five cases of malignant hepatic AML have been reported. We report a rare case of recurrent posthepatectomy malignant hepatic AML that was misdiagnosed as liver cancer in a 37-year-old woman, which was treated by liver transplantation. The imaging and pathologic findings are presented in order to provide a more concise description to aid in future diagnoses.

Musashi-2 promotes hepatitis Bvirus related hepatocellular carcinoma progression via the Wnt/ß-catenin pathway.

Our recent study observed that the expression of Musashi-2 (MSI2), a member of the Musashi family, was up-regulated in hepatitis B virus (HBV) related hepatocellular carcinoma parenchymal cells. Using quantitative PCR, tissue microarray (TMA) and immunohistochemical staining, we evaluated MSI2 mRNA and protein levels in tumor tissues from patients with different stages of hepatocellular carcinoma with paired adjacent noncancerous sample sets. The following techniques were used to further investigate MSI2 function and its potential molecular mechanism: RNAi, wound healing assay, Transwell assay, quantitative PCR and western blot analysis. Immunohistochemical detection of MSI2 on a TMA containing 106 paired specimens showed that increased cytoplasmic and nuclear MSI2 staining was significantly associated with tumor size, tumor differentiation, recurrence, TNM stage, vessel invasion and Ki-67 proliferative index. Patients with MSI2-positive tumors had a significantly higher disease recurrence rate and poorer survival than patients with MSI2-negative tumors after radical surgery. Based on univariate analysis, MSI2 expression showed an unfavorable influence on both disease-free survival and overall survival. Multivariate analysis revealed that higher MSI2 expression, together with tumor size, tumor differentiation, tumor thrombus, and Ki-67 expression were independent predictors of overall survival. With MSI2 knockdown, hepatoma cell migration and invasion were inhibited and the expression of ß-catenin, T cell factor (TCF) and lymphoid enhancer factor (LEF) were dysregulated. Thus, we propose that MSI2 may predict unfavorable outcomes in hepatitis B virus related hepatocellular carcinoma and promote cancer progression via the Wnt/ß-catenin signaling pathway.

Surgical strategy for isolated caudate lobectomy: experience with 16 cases.

Introduction. Surgical resection is the most effective treatment for neoplasm in the caudate lobe. Isolated caudate lobectomy is still a challenge for hepatobiliary surgeons. No widely accepted surgical strategy for the procedure has been developed yet. Objective. To get a better understanding of isolated caudate lobectomy and to optimize the procedure. Materials and Methods. 16 cases of isolated caudate lobectomy were reviewed to summarize the surgical experience. Results. All the 16 cases of isolated caudate lobectomy were carried out successfully, among which left side approach was adopted in two cases (12.5%), right side approach in three cases (18.75%), and both sides approach in 11 cases (68.75%). No severe complications occurred. Conclusion. The majority of neoplasms confined to the caudate lobe can be resected safely by left and right side approach with proper anatomic surgical procedure, usually in the sequence of mobilization, outflow control, inflow control, and division of the hepatic parenchyma. Fully mobilizing the caudate lobe from the inferior vena cava (IVC) is of great importance. Division of the retrohepatic ligament and the venous ligament facilitated the procedure.

Overexpression of eIF3e is correlated with colon tumor development and poor prognosis.

EIF3e is a component of the eukaryotic translation initiation factor 3 (eIF-3) complexes, which is an essential factor for initiation of protein synthesis in mammalian cells. Translational control plays key roles in the complex mechanism of cancer development and progression. However, the clinical significance of eIF3e in colon cancer remains to be elucidated. We analyzed the eIF3e expression in a tissue microarray (TMA), which contained 173 colon cancer tissues paired with adjacent normal mucosa and lymph node metastasis. The expression of eIF3e was significantly elevated in colon cancer tissues in comparison with those in adjacent normal mucosa (P < 0.001) and lymph node metastasis (P < 0.001). The high expression of eIF3e in colon cancer was significantly correlated with tumor size (P < 0.001), lymph node involvement (P < 0.001), distant metastasis (P < 0.001), clinical stage (P < 0.001), histopathologic classification (P < 0.001), and vessel invasion (P = 0.036). Univariate and multivariate analysis revealed that eIF3e is an independent prognosis factor for overall survival and disease-free survival in colon cancer. Down-regulation of eIF3e in vitro inhibited colon cancer cell proliferation, clonality and promoted cell apoptosis. Taken together, high eIF3e expression may contribute to tumor progression and predict poor prognosis in colon cancer.