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Digestive System Diseases - Top 30 Publications

Short-term outcomes following cytoreductive surgery and heated intra-peritoneal chemotherapy at Waikato.

Pseudomyxoma peritonei is a rare disease that affects 1-2 per million population per year. Treatment with cytoreductive surgery with heated intraperitoneal chemotherapy (CRS with IPC) has been well described. The purpose of this study was to look at the short-term outcomes following CRS with IPC for all such patients treated in Waikato.

Appendicitis presenting as the first manifestation of colorectal carcinoma: a 13-year retrospective study.

Appendicitis in older adults may present as the first sign of underlying colorectal cancer. We aim to determine whether there was a difference in the rate of diagnosis of colorectal carcinoma for patients ≥45 years following a presentation with appendicitis, compared with New Zealand standardised rates.

Long non-coding RNA SPRY4-IT1 promotes proliferation and invasion by acting as a ceRNA of miR-101-3p in colorectal cancer cells.

Long non-coding RNAs are associated with a spectrum of biological processes such as gene regulation on transcriptional and post-transcriptional levels. Increasing evidence indicates that SPRY4-IT1 plays an important role in carcinogenesis, and the mechanisms whereby SPRY4-IT1 induces colorectal carcinoma progression remain largely unknown. The aim of this study is to evaluate the expression and function of SPRY4-IT1 in colorectal carcinoma. In this study, we analyzed SPRY4-IT1 expression levels in a series of colorectal carcinoma patients by quantitative reverse transcription polymerase chain reaction. Knockdown of SPRY4-IT1 by RNA interference was performed to explore its roles in cell proliferation, migration, and invasion. Our results found that SPRY4-IT1 was upregulated in human primary colorectal carcinoma tissues. Knockdown of SPRY4-IT1 inhibited colorectal carcinoma cell proliferation, migration, and invasion. Moreover, we confirmed that the expression of epithelial-mesenchymal transition-related genes was modulated through alteration of SPRY4-IT1 expression. SPRY4-IT1 could negatively regulate the expression of miR-101-3p in colorectal carcinoma cells. The bioinformatics prediction revealed putative miR-101-3p binding sites within SPRY4-IT1 transcripts. Above all, knockdown of SPRY4-IT1 could represent a rational therapeutic strategy for colorectal carcinoma.

Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats.

This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.

The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1.

Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis-associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma.

PPFIA1 is upregulated in liver metastasis of breast cancer and is a potential poor prognostic indicator of metastatic relapse.

Although the oncogenic role of PPFIA1 (liprin-α1) in breast cancer has been reported, whether its dysregulation is associated with metastasis risk or survival outcomes in breast cancer patients is not clear. Our primary data showed that PPFIA1 expression was significantly higher in liver metastatic breast tumors than in the primary tumors. Then, we tried to pool previous annotated genomic data to assess the prognostic value of PPFIA1 in distant metastasis-free survival, the risk of metastatic relapse, and metastatic relapse-free survival in breast cancer patients by data mining in two large databases, Kaplan-Meier plotter and bc-GenExMiner 4.0. Results from Kaplan-Meier plotter showed that although high PPFIA1 expression was generally associated with decreased distant metastasis-free survival in estrogen receptor+ patients, subgroup analysis only confirmed significant association in estrogen receptor+/N- (nodal negative) group (median survival, high PPFIA1 group vs low PPFIA1 cohort: 191.21 vs 236.22 months; hazard ratio: 2.23, 95% confidence interval: 1.42-3.5, p < 0.001), but not in estrogen receptor+/N+ (nodal positive) group (hazard ratio: 1.63, 95% confidence interval: 0.88-3.03, p = 0.12). In estrogen receptor- patients, there was no association between PPFIA1 expression and distant metastasis-free survival, no matter in Nm (nodal status mixed), N-, or N+ subgroups. In bc-GenExMiner 4.0, Nottingham Prognostic Index- and Adjuvant! Online-adjusted analysis validated the independent prognostic value of PPFIA1 in metastatic risks in estrogen receptor+/N- patients. Based on these findings, we infer that high PPFIA1 expression might be an independent prognostic indicator of increased metastatic relapse risk in patients with estrogen receptor+/N- breast cancer, but not in estrogen receptor+/N+ or estrogen receptor- patients.

EMP3 is induced by TWIST1/2 and regulates epithelial-to-mesenchymal transition of gastric cancer cells.

In this study, we aimed to explore new downstream effectors of TWIST1/2 in inducing epithelial-to-mesenchymal transition in gastric cancer. Bioinformatic data mining was performed using data in The Cancer Genome Atlas Stomach Adenocarcinoma. Survival curves were generated using Kaplan-Meier plotter. Gastric cancer cell lines (AGS and SGC-7901) were used as in vitro cell model to investigate the regulative effect of TWIST1/2 on epithelial membrane protein 3 expression and the progression of epithelial-to-mesenchymal transition. Results showed that TWIST1 and TWIST2 are usually co-upregulated in patients with primary gastric cancer. High TWIST1 expression is associated with worse overall survival (hazard ratio = 1.26; 95% confidence interval = 1.06-1.49; p = 0.007) and also worse first progression-free survival (hazard ratio = 1.47; 95% confidence interval = 1.18-1.82; p < 0.0001). Similarly, high TWIST2 expression is associated with unfavorable overall survival (hazard ratio = 1.71; 95% confidence interval = 1.32-2.22; p < 0.0001) and progression-free survival (hazard ratio = 1.99; 95% confidence interval = 1.45-2.72; p < 0.0001). Epithelial membrane protein 3 is negatively correlated to CDH1 expression (Pearson's r = -0.46) but is positively correlated to VIM expression (Pearson's r = 0.83). Knockdown of epithelial membrane protein 3 significantly increased E-cadherin but significantly decreased Vimentin expression in AGS cells. Gastric cancer patients with metastasis have significantly higher epithelial membrane protein 3 expression than the cases without metastasis. In addition, high epithelial membrane protein 3 expression is associated with worse overall survival (hazard ratio = 2.59; 95% confidence interval = 2.06-3.26; p < 0.0001) and also worse progression-free survival (hazard ratio = 2.21; 95% confidence interval = 1.78-2.74; p < 0.0001). In conclusion, epithelial membrane protein 3 is a downstream effector of TWIST1/2 in inducing epithelial-to-mesenchymal transition in gastric cancer. Epithelial membrane protein 3 upregulation might be associated with gastric cancer metastasis and is a potential indicator of unfavorable overall survival and progression-free survival in gastric cancer patients.

Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-β-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-β-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.

MiR-143 inhibits cell proliferation and invasion by targeting DNMT3A in gastric cancer.

Increasing evidence has suggested that MircroRNAs (miRNAs) dysregulated in pathogenesis and tumorigenicity in human cancers including gastric cancer (GC). MiR-143 had been reported to function as tumor suppressor in GC progression, however, the underlying function of miR-143 in GC still need to be well known. In the study, we revealed that miR-143 was significantly down-regulated in GC cell lines. Upregulation of miR-143 inhibited cell proliferation, invasion, S phase cell proportion and cell cycle related protein levels of Cyclin D1, CDK4 and CDK6 in GC. Furthermore, luciferase reporter assays demonstrated that DNMT3A was a direct target of miR-143 and Upregulation of miR-143 inhibited the DNMT3A mRNA and protein expression levels in GC cells. Moreover, we demonstrated that DNMT3A knockdown rescued the promoting effect of miR-143 inhibitor on cell proliferation in GC. Thus, these results demonstrated that miR-143 targeted DNMT3A in GC cells and inhibit GC tumorigenesis and progression, which may provide a novel therapeutic target of GC.

Remodeling of extracellular matrix of the lamina propria in the uninvolved human rectal mucosa 10 and 20 cm away from the malignant tumor.

In recent years, it has been demonstrated that malignancy arises and advances through the molecular interplay between tumor cells and non-malignant elements of the tumor stroma, that is, fibroblasts and extracellular matrix. However, in contrast to the mounting evidence about the role of tumor stroma in the genesis and progression of the malignant disease, there are very few data regarding the uninvolved stromal tissue in the remote surrounding of the tumor. Using the objective morphometric approach in patients with adenocarcinoma, we demonstrate the remodeling of extracellular matrix of the lamina propria in the uninvolved rectal mucosa 10 and 20 cm away from the neoplasm. We show that the representation of basic extracellular matrix constituents (reticular and collagen fibers and ground substance) is decreased. Also, the diameter of empty spaces that appear within the extracellular matrix of the lamina propria is increased. These spaces do not represent the blood or lymphatic vessel elements. Very likely, they reflect the development of tissue edema in the remote, uninvolved lamina propria of the mucosa in patients with the malignant tumor of the rectum. We hypothesize that the remodeling of extracellular matrix in lamina propria of the rectal mucosa may increase its stiffness, modulating the mechano-signal transduction, and thus promote the progression of the malignant disease.

TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.

The association of miR-126-3p, miR-126-5p and miR-664-3p expression profiles with outcomes of patients with metastatic colorectal cancer treated with bevacizumab.

MicroRNAs regulate the expression of genes involved in several important cancer-related processes including cell adhesion, proliferation, and tumour angiogenesis. Bevacizumab is routinely used in the treatment of patients with metastatic colorectal cancer, but, so far, no reliable biomarker predicting response to bevacizumab has been established. The aim of our retrospective study was to evaluate the association of miR-126-3p, miR-126-5p and miR-664-3p tumour expression levels with outcomes of patients with metastatic colorectal cancer treated with bevacizumab. The study included 63 patients. For the assessment of microRNA expression, gene-specific TaqMan assays were used. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-3p were 8.8 and 20.6 months versus 13.5 months and median overall survival was not reached for patients with high expression ( p = 0.0064 and p = 0.0027), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-5p were 9.0 and 22.2 months versus 12.0 and 23.4 months for patients with high expression ( p = 0.2113 and 0.6858), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-664-3p were 9.1 and 22.5 months versus 8.8 and 23.4 months for patients with high expression ( p = 0.2542 and p = 0.1922), respectively. The multivariable Cox proportional hazards model revealed that miR-126-3p expression was significantly associated with progression-free survival (hazard ratio = 0.28, p = 0.0053) and also with overall survival (hazard ratio = 0.18, p = 0.0046). In conclusion, the results of this study suggest that the expression of miR-126-3p in the tumour tissue was associated with outcome of metastatic colorectal cancer patients treated with bevacizumab.

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing.

Colon adenocarcinoma is the third leading cause of cancer-related deaths across the world, developing novel and non-invasive diagnostic and prognostic biomarkers for the early-stage colon adenocarcinoma at molecular level is essential. In our study, RNA-sequencing was performed to identify the differentially expressed genes and miRNAs (DEmiRNAs) in early-stage colon adenocarcinoma compared to tissues of precancerous lesions, colonic intraepithelial neoplasia. The DEmiRNA-target interaction network was constructed and functional annotation of targets of DEmiRNAs was performed. The Cancer Genome Atlas was used to verify the expression of selected differentially expressed genes. The receiver operating characteristic analyses of selected differentially expressed genes was performed. In total, 865 differentially expressed genes, 26 DEmiRNAs, and 329 DEmiRNA-target pairs were obtained. Based on the early-stage colon adenocarcinoma network, miR-548c-5p, miR-548i, and miR-548am-5p were the top three DEmiRNAs that covered most differentially expressed genes. NTRK2, DTNA, and BTG2 were the top three differentially expressed genes regulated by most DEmiRNAs. Cancer and colorectal cancer pathways were two significantly enriched pathways in early-stage colon adenocarcinoma. The common differentially expressed genes in both the pathways were AXIN2, Smad2, Smad4, PIK3R1, and BCL2. The expression levels of eight differentially expressed genes (NTRK2, DTNA, BTG2, COL11A1, Smad2, Smad4, PIK3R1, and BCL2) in The Cancer Genome Atlas database were compatible with our RNA-sequencing. All these eight differentially expressed genes and AXIN2 had the potential diagnosis value for Colon adenocarcinoma. In conclusion, a total of ten differentially expressed genes (NTRK2, DTNA, BTG2, COLCA1, COL11A1, AXIN2, Smad2, Smad4, PIK3R1, and BCL2) and four DEmiRNAs (miR-548c-5p, miR-548i, mir-424-5p, and miR-548am-5p) may be involved in the pathogenesis of early-stage colon adenocarcinoma which may make a contribution for developing new diagnostic and therapeutic strategies for early-stage colon adenocarcinoma.

High expression of nucleobindin 2 is associated with poor prognosis in gastric cancer.

Nucleobindin 2 has been reported that its high expression is associated with poor outcome and promotes cell migration and lymph node metastasis in breast cancer, colon cancer, and prostate cancer. However, we aimed to investigate the nucleobindin 2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemical analysis. In our study, nucleobindin 2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of nucleobindin 2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and clinical stage. Furthermore, the expression level of nucleobindin 2 protein was independent predictor of progression-free survival. In summary, nucleobindin 2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.

Sporamin induces apoptosis and inhibits NF-κB activation in human pancreatic cancer cells.

Sporamin, a Kunitz-type trypsin inhibitor (TI) from sweet potato tuberous roots, has demonstrated anti-tumor activity through poorly defined mechanisms. Furthermore, the effects of sporamin on pancreatic cancer have not been explored. Herein, we studied the effects of sporamin on two human pancreatic cancer cell lines, PANC-1 and BxPC-3. Sporamin significantly inhibited the cell viability and proliferation activity and induced apoptosis in PANC-1 and BxPC-3 cells. Consistently, in sporamin-treated PANC-1 and BxPC-3 cells, the anti-apoptotic proteins Bcl-2 and Bcl-XL were downregulated and the pro-apoptotic protein Bax was upregulated. Moreover, nuclear factor kappa B activation and IκBα phosphorylation were inhibited, and total IκBα expression was increased in sporamin-treated PANC-1 and BxPC-3 cells. Thus, our results suggest that the anti-tumor effects of sporamin in pancreatic cancer cells might result partly from induction of apoptosis by downregulating nuclear factor kappa B pathway.

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p < 0.05), without correlation with age, gender, smoking, drinking, tumor size, serum alpha-fetoprotein level, hepatitis B virus infection, metastasis, and invasion (p > 0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes.

Hepatocellular carcinoma is one of the most prevalent neoplasms and the leading cause of cancer-related mortality worldwide. Mitochondrial ribosomal protein S23 is encoded by a nuclear gene and participates in mitochondrial protein translation. Mitochondrial ribosomal protein S23 overexpression has been found in many types of cancer. In this study, we explored mitochondrial ribosomal protein S23 expression in primary hepatocellular carcinoma tissues compared with matched adjacent non-tumoral liver tissues using mitochondrial ribosomal protein S23 messenger RNA and protein levels collected from public databases and clinical samples. Immunohistochemistry was performed to analyze the relationship between mitochondrial ribosomal protein S23 and various clinicopathological features. The results indicated that mitochondrial ribosomal protein S23 was significantly overexpressed in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 expression was correlated with the tumor size and tumor-metastasis-node stage. Moreover, patients with high mitochondrial ribosomal protein S23 expression levels presented poorer survival rates. Mitochondrial ribosomal protein S23 was an independent prognostic factor for survival, especially at the early stage of hepatocellular carcinoma. In addition, the downregulation of mitochondrial ribosomal protein S23 decreased the proliferation of hepatocellular carcinoma in vitro and in vivo. In conclusion, we verified for the first time that mitochondrial ribosomal protein S23 expression was upregulated in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 levels can predict poor clinical outcomes in hepatocellular carcinoma, and this protein plays a key role in tumor proliferation. Therefore, mitochondrial ribosomal protein S23 may be a potential therapeutic target for hepatocellular carcinoma.

Conjugation of gold nanoparticles and recombinant human endostatin modulates vascular normalization via interruption of anterior gradient 2-mediated angiogenesis.

Several studies have revealed the potential of normalizing tumor vessels in anti-angiogenic treatment. Recombinant human endostatin is an anti-angiogenic agent which has been applied in clinical tumor treatment. Our previous research indicated that gold nanoparticles could be a nanoparticle carrier for recombinant human endostatin delivery. The recombinant human endostatin-gold nanoparticle conjugates normalized vessels, which improved chemotherapy. However, the mechanism of recombinant human endostatin-gold nanoparticle-induced vascular normalization has not been explored. Anterior gradient 2 has been reported to be over-expressed in many malignant tumors and involved in tumor angiogenesis. To date, the precise efficacy of recombinant human endostatin-gold nanoparticles on anterior gradient 2-mediated angiogenesis or anterior gradient 2-related signaling cohort remained unknown. In this study, we aimed to explore whether recombinant human endostatin-gold nanoparticles could normalize vessels in metastatic colorectal cancer xenografts, and we further elucidated whether recombinant human endostatin-gold nanoparticles could interrupt anterior gradient 2-induced angiogenesis. In vivo, it was indicated that recombinant human endostatin-gold nanoparticles increased pericyte expression while inhibit vascular endothelial growth factor receptor 2 and anterior gradient 2 expression in metastatic colorectal cancer xenografts. In vitro, we uncovered that recombinant human endostatin-gold nanoparticles reduced cell migration and tube formation induced by anterior gradient 2 in human umbilical vein endothelial cells. Treatment with recombinant human endostatin-gold nanoparticles attenuated anterior gradient 2-mediated activation of MMP2, cMyc, VE-cadherin, phosphorylation of p38, and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human umbilical vein endothelial cells. Our findings demonstrated recombinant human endostatin-gold nanoparticles might normalize vessels by interfering anterior gradient 2-mediated angiogenesis in metastatic colorectal cancer.

Portulaca oleracea extract can inhibit nodule formation of colon cancer stem cells by regulating gene expression of the Notch signal transduction pathway.

To investigate whether Portulaca oleracea extract affects tumor formation in colon cancer stem cells and its chemotherapy sensitivity. In addition, to analyze associated genetic changes within the Notch signal transduction pathway. Serum-free cultures of colon cancer cells (HT-29) and HT-29 cancer stem cells were treated with the chemotherapeutic drug 5-fluorouracil to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and note its characteristics. In addition, the effect of different concentrations of P. oleracea extract was tested on the growth of HT-29 colon cancer cells and HT-29 cancer stem cells, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The effects of P. oleracea extract on the expression of β-catenin, Notch1, and Notch2 in the HT-29 cells were studied using reverse transcription polymerase chain reaction and Western blotting. The tumor volume of the HT29 cells was two times larger than that of HT29 cancer stem cells. Treatment with P. oleracea extract inhibited the proliferation of both HT-29 cancer cells and HT-29 cancer stem cells at doses from 0.07 to 2.25 µg/mL. Apoptosis of HT-29 cancer cells and HT-29 cancer stem cells was assessed by flow cytometry; it was enhanced by the addition of P. oleracea extract. Finally, treatment with P. oleracea extract significantly downregulated the expression of the Notch1 and β-catenin genes in both cell types. The results of this study show that P. oleracea extract inhibits the growth of colon cancer stem cells in a dose-dependent manner. Furthermore, it inhibits the expression of the Notch1 and β-catenin genes. Taken together, this suggests that it may elicit its effects through regulatory and target genes that mediate the Notch signal transduction pathway.

RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.

In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.

Knockdown of calponin 2 suppressed cell growth in gastric cancer cells.

Calponin family members are actin filament-associated regulatory proteins with distinct expression patterns. Previous studies on CNN2 (calponin 2) have demonstrated that CNN2 is expressed in a broad range of tissues and cell types, exhibiting potential regulatory roles in a number of cellular activities, including cell proliferation, cell migration, and platelet adhesion. In this work, we found that both messenger RNA and protein expression levels of CNN2 were remarkably upregulated in 60%-70% of gastric cancer tissues by comparison with those of neighboring non-tumorous mucosa. By utilizing specific shCNN2 (small hairpin RNA targeting CNN2), the potential role of CNN2 in regulating AGS gastric cancer cell growth was then further investigated. AGS cells infected with shCNN2 exhibited significantly decreased cell growth ability by comparison with control cells in vitro. Moreover, while there was no obvious difference in cell cycle distribution between two groups, enhanced cell apoptosis was detected in cells with reduced CNN2 expression. Consistently, caspase 3/7 activity was also remarkably activated upon shCNN2 lentivirus infection. Taken together, our results demonstrated that knockdown of endogenous CNN2 in AGS cells could significantly activate cell apoptosis pathway and therefore suppress cell growth in vitro. The deletion of CNN2 might be a potential therapeutic approach to inhibit aggressive growth of gastric cancer.

Prevention of cancer colorectal. From stone age to the cornerstone.

Randomized clinical trial of percutaneous tibial nerve stimulation versus sham electrical stimulation in patients with faecal incontinence.

The aim was to assess the effects of percutaneous tibial nerve stimulation (PTNS) in the treatment of faecal incontinence (FI) by means of an RCT.

Diagnostic value of long noncoding RNAs for hepatocellular carcinoma: A PRISMA-compliant meta-analysis.

Increasing evidences have shown that long noncoding RNAs (lncRNAs) are involved in cancer diagnosis and prognosis. However, the overall diagnostic accuracy of lncRNAs for hepatocellular carcinoma (HCC) remains unclear. Herein, we perform a meta-analysis to assess diagnostic value of lncRNAs for HCC.

Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma.

Functional and morphological evolution of remnant pancreas after resection for pancreatic adenocarcinoma is investigated.The medical records of 45 patients who had undergone radical resection for pancreatic adenocarcinoma from March 2010 to September 2013 were reviewed retrospectively. There were 34 patients in the pancreaticoduodenectomy (PD) group and 10 patients in the distal pancreatectomy (DP) group. One patient received total pancreatectomy. The endocrine function was measured using the glucose tolerance index (GTI), which was derived by dividing daily maximum serum glucose fluctuation by daily minimum glucose. Remnant pancreas volume (RPV) was estimated by considering pancreas body and tail as a column, and head as an ellipsoid, respectively. The pancreatic atrophic index (PAI) was defined as the ratio of pancreatic duct width to total pancreas width. Representative indices of each patient were compared before and after resection up to 2 years postoperatively.The area under receiver operating characteristic curve of GTI for diagnosing DM was 0.823 (95% confidence interval, 0.699-0.948, P < .001). Overall, GTI increased on postoperative day 1 (POD#1, mean ± standard deviation, 1.79 ± 1.40 vs preoperative, 1.02 ± 1.41; P = .001), and then decreased by day 7 (0.89 ± 1.16 vs POD#1, P < .001). In the PD group, the GTI on POD#14 became lower than preoperative (0.51 ± 0.38 vs 0.96 ± 1.37; P = .03). PAI in the PD group was significantly lower at 1 month postoperatively (0.22 ± 0.12 vs preoperative, 0.38 ± 0.18; P < .001). In the PD group, RPV was significantly lower at 1 month postoperatively (25.3 ± 18.3 cm vs preoperative, 32.4 ± 20.1 cm; P = .02), due to the resolution of pancreatic duct dilatation. RPV of the DP group showed no significant change. GTI was negatively related to RPV preoperatively (r = -0.317, P = .04), but this correlation disappeared postoperatively (r = -0.044, P = .62).Pancreatic endocrine functional deterioration in pancreatic adenocarcinoma patients may in part be due to pancreatic duct obstruction and dilatation caused by the tumor. After resection, this proportion of endocrine insufficiency is corrected.

Long-term follow-up of patients with intestinal neuronal dysplasia type B: Protocol for an observational, ambispective, and comparative study.

Intestinal neuronal dysplasia type B (IND-B) is a pathological entity of the group of gastrointestinal neuromuscular diseases characterized by complex alterations in the enteric nervous system. Patients typically present with intestinal constipation, sometimes complicated by episodes of intestinal obstruction. The 2 therapeutic modalities include conservative clinical treatment and surgical treatment. Nevertheless, the results of the different therapeutic modalities are conflicting, and follow-up studies are scarce and include only a limited number of patients.This is a single-center, ambispective, observational, longitudinal, and comparative follow-up study to compare the results of conservative clinical and surgical treatments in patients with IND-B. Sixty-three patients (<15 years) who received this diagnosis will be included. These patients will be divided into 2 groups according to the type of treatment that they previously received: 29 patients in the surgical treatment group and 34 patients in the conservative treatment group. Previous data will be recovered from the medical records of the study patients, including signs and symptoms present at the time of diagnosis, particularly those related to bowel habits, and treatments undergone. Later, these patients will be invited to participate in a semistructured interview during which aspects related to the long-term functional results of the bowel habit and quality of life will be investigated after a minimum interval of 5 years posttreatment.This project aims to assess the long-term clinical evolution of patients diagnosed with IND-B and compare the results obtained following conservative clinical and surgical treatments.This protocol will provide sufficient data to analyze the long-term clinical outcome obtained through the 2 treatment modalities proposed for patients with IND-B.

Value of contrast-enhanced ultrasound in differential diagnosis of solid lesions of pancreas (SLP): A systematic review and a meta-analysis.

Contrast-enhanced ultrasound (CEUS) is considered a novel method for diagnosing pancreatic cancer, but currently, there is no conclusive evidence of its accuracy. Using CEUS in discriminating between pancreatic carcinoma and other pancreatic lesions, we aimed to evaluate the diagnostic accuracy of CEUS in predicting pancreatic tumours.

Endoscopic ultrasound guided fine needle aspiration versus endoscopic ultrasound guided fine needle biopsy in sampling pancreatic masses: A meta-analysis.

The comparison between endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound guided fine needle biopsy (EUS-FNB) for the diagnosis of pancreatic masses is still controversial. Many factors can affect the final results.

Prognostic significance of serum procalcitonin in patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization: A retrospective analysis of 509 cases.

Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, its accuracy in hepatocellular carcinoma (HCC) patients is unknown. The aim of this study was to investigate the prognostic significance of PCT in patients with unresectable HCC treated with transcatheter arterial chemoembolization (TACE).A total of 509 patients with unresectable HCC initially treated with TACE were enrolled in this retrospective study. According to quartile of the PCT values, all patients were divided into 4 groups. Overall survival (OS) was evaluated with the Kaplan-Meier method. Significant difference was estimated with the Log rank method. Univariate and multivariate analyses were used for evaluating the significance of the prognostic factor.The median follow-up period was 18 months and there were significant differences in the survival rates between the 4 groups. The HR (95% CI) for all-cause mortality comparing patients with PCT Quartile2-4 to patient with Quartile1 (HR = 1.00) were 1.353 (1.023-1.791), 1.799 (1.354-2.390), 1.960 (1.455-2.639), respectively, (P < .001). PCT level was an important prognostic factor for predicting the prognosis of patients with unresectable HCC treated with TACE.

Plasma cytokines can help to identify the development of severe acute pancreatitis on admission.

Severe acute pancreatitis (AP) is associated with high morbidity and mortality. Early severity stratification remains a challenging issue to overcome to improve outcomes. We aim to find novel plasma cytokines for the early identification of severe AP according to the revised Atlanta criteria.In this prospective observational study, 30 cytokines, screened semiquantitatively with a human multicytokine array, were submitted to quantitative determination using either microparticle-based multiplex immunoassays analyzed on a Luminex 100 platform or enzyme-linked immunosorbent assay kits. The cytokine profiles of patients and the discriminative value of cytokines for severe AP were analyzed.Plasma samples of 70 patients with AP (20 mild, 30 moderately severe, and 20 severe) were selected in this study if they were admitted within 48 hours of the onset of symptoms. Plasma from healthy volunteers was collected as the healthy control. Growth differentiation factor-15 (GDF-15) and pentraxin 3 (PTX3) on admission were independent prognostic markers for the development of severe AP and had higher discriminative powers than conventional markers (GDF-15 vs hematocrit, P = .003; GDF-15 vs C-reactive protein, P = .037; GDF-15 vs creatinine, P = .048; GDF-15 vs Acute Physiology and Chronic Health Evaluation II, P = .007; PTX3 vs hematocrit, P = .006; PTX3 vs C-reactive protein, P = .047; PTX3 vs Acute Physiology and Chronic Health Evaluation II, P = .011; PTX3 vs Bedside Index for Severity in Acute Pancreatitis, P = .048).Plasma GDF-15 and PTX3 can help to identify the development of severe AP on admission. Future work should validate their accuracy in a larger, multicenter patient cohort.