Retraction Note to: SOX2 oncogenes amplified and operate to activate AKT signalling in gastric cancer and predict immunotherapy responsiveness.

The Editor-in-Chief is retracting this article (Tian et al 2014) due to concerns regarding peer review, authorship and originality of the article.

Long non-coding RNA PTENP1 inhibits proliferation and migration of breast cancer cells via AKT and MAPK signaling pathways.

We aimed to investigate the influence of long non-coding RNA (lncRNA) PTEN pseudogene-1 (PTENP1) on the proliferation, migration and cycle of breast cancer cells and its mechanism. Lentiviral vectors expressing PTENP1 were synthesized and breast cancer cells MCF7 were transfected with LV003-GFP-PTENP1 and LV003-GFP, respectively. The proliferation capacities of breast cancer cells were detected using CCK-8 assay, and the migration capacities of breast cancer cells were detected using scratch assay; flow cytometry was used to detect the cell cycles and Western blot was used to detect the expression levels of cyclin A2, CDK2, p-p44/42 MAPK, t-p44/42 MAPK, p-p38 MAPK, t-p38 MAPK, p-AKT, t-AKT in AKT and MAPK pathways. The absorbance values (A450) of cells in experimental group at 48 and 72 h were 1.4±0.3 and 2.3±0.47, respectively, which were significantly lower than those in control group (3.2±0.39, 3.4±0.58) (P<0.05). The number of cell colonies in experimental group was (48±13), which was significantly lower than that in control group (159±16) (P<0.01). The cell migration rate in experimental group was 22.8±3.3%, which was significantly lower than that in control group 61.8±5.2% (P<0.01). Western blot detection showed that the expression levels of cyclin A2, CDK2, p-AKT, p-p44/42 MAPK and p-p38 MAPK in experimental group were significantly decreased compared with those in control group. LncRNA PTENP1 can inhibit the proliferation and migration of breast cancer cells via the AKT and MAPK signaling pathways.

Sclareolide enhances gemcitabine­induced cell death through mediating the NICD and Gli1 pathways in gemcitabine­resistant human pancreatic cancer.

Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc­1 and ASPC­1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine­resistant cells (GR­HPCCs). The anticancer effect of gemcitabine combined with sclareolide was then assessed. Epithelial to mesenchymal transition (EMT), human equilibrative nucleoside transporter 1 (hENT1) and ribonucleoside diphosphate reductase 1 (RRM1) were detected in the HPCCs and GR­HPCCs, and the mechanisms were investigated. Sclareolide resensitized the GR­HPCCs to gemcitabine. The expression levels of hENT1 and RRM1 were lower and higher, respectively, in GR­HPCCs, compared with HPCCs. Sclareolide upregulated hENT1, downregulated RRM1 and inhibited gemcitabine­induced EMT through the TWIST1/Slug pathway in the GR­HPCCs. In addition, sclareolide mediated the NOTCH 1 intracellular cytoplasmic domain (NICD)/glioma­associated oncogene 1 (Gli1) pathway, which triggered TWIST1/Slug­hENT1/RRM1 signaling and resensitized GR­HPCCs to gemcitabine. Finally, sclareolide resensitized GR­HPCCs to gemcitabine through inducing apoptosis; in vivo, the co­administraion of sclareolide and gemcitabine effectively suppressed tumor growth. Sclareolide may be a novel agent in combination with gemcitabine for the treatment of gemcitabine­resistant pancreatic cancer, which resensitizes GR­HPCCs to gemcitabine through mediating NICD and Gli1.

Interaction Between Gastric Carcinoma Cells and Neural Cells Promotes Perineural Invasion by a Pathway Involving VCAM1.

BACKGROUND: Perineural invasion (PNI) is one of the important routes for local spread of gastric carcinoma associated with poor prognosis. However, the exact cellular characteristics and molecular mechanisms of PNI are still unclear. AIM: To identify the interaction between gastric carcinoma cells and neural cells, and whether vascular cell adhesion molecule-1 (VCAM1) is involved in this process. METHODS: We adopted in vitro cell coculture assays to investigate the cellular and molecular interaction between gastric cancer cells and neural cells. RESULTS: We find upregulation of VCAM1 in clinical gastric cancer tissue samples. In in vitro tumor-neural cell coculture system, gastric cancer cells with high level of VCAM1 promote proliferation of neural progenitor cells and induce the process outgrowth and branching of neural cells. Reciprocally, neural cells enhance neurotropic migration and mobility of tumor cells. Repressing VCAM1 function through VCAM1 blocking antibody can attenuate these effects. CONCLUSIONS: Our study indicates that VCAM1 is significantly involved in tumor invasion via mediating nerve-tumor interaction, which is a mutually beneficial process. It is possible that interaction between neural cells and tumor cells might contribute to PNI of gastric carcinoma. Inhibiting the activity of VCAM1 could be a potential strategy targeting PNI in gastric carcinoma therapy.

SOX2 oncogenes amplified and operate to activate AKT signaling in gastric cancer and predict immunotherapy responsiveness.

INTRODUCTION: Gastric cancer is the second leading cause of cancer mortality in the world. Whether the oncogene, amplified on chromosome 3q26, SOX2, a master transcriptional regulator of stemness, operate to drive strong growth phenotype in gastric cancer were unknown. MATERIALS AND METHODS: The gene expression changes of SOX2 in human gastric cancer tissues compared with non-cancerous tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of SOX2 in gastric cancer. Moreover, we discovered that SOX2 promoted cancer cell proliferation in vitro/vivo and SOX2 expression correlated with elevated AKT phosphorylation in gastric cancer, while the AKT phosphorylation was required for SOX2's oncogenic effects. Next, our data point to the usefulness of SOX2 overexpression, as a new predictive marker for responsiveness to trastuzumab. CONCLUSION: SOX2 is a commonly activated tumor promoter that activate AKT signaling in gastric cancer and a new predictive marker for targeted therapy.

Robotic surgery twice performed in the treatment of hilar cholangiocarcinoma with deep jaundice: delayed right hemihepatectomy following the right-hepatic vascular control.

OBJECTIVE: To explore and find a new method to treat hilar cholangiocarcinoma with deep jaundice assisted by Da Vinci robot. METHODS: A hilar cholangiocarcinoma patient of type Bismuch-Corlette IIIa was found with deep jaundice (total bilirubin: 635 µmol/L). On the first admission, we performed Da Vinci robotic surgery including drainage of left hepatic duct, dissection of right hepatic vessels (right portal vein and right hepatic artery), and placement of right-hepatic vascular control device. Three weeks later on the second admission when the jaundice disappeared we occluded right-hepatic vascular discontinuously for 6 days and then sustained later. On the third admission after 3 weeks of right-hepatic vascular control, the right hemihepatectomy was performed by Da Vinci robot for the second time. RESULTS: The future liver remnant after the right-hepatic vascular control increased from 35% to 47%. The volume of left lobe increased by 368 mL. When the total bilirubin and liver function were all normal, right hemihepatectomy was performed by Da Vinci robot 10 weeks after the first operation. The removal of atrophic right hepatic lobe with tumor in bile duct was found with no pathologic cancer remaining in the margin. The patient was followed up at our outpatient clinic every 3 months and no tumor recurrence occurs by now (1 y). CONCLUSIONS: Under the Da Vinci robotic surgical system, a programmed treatment can be achieved: first, the hepatic vessels were controlled gradually together with biliary drainage, which results in liver's partial atrophy and compensatory hypertrophy in the other part. Then a radical hepatectomy could be achieved. Such programmed hepatectomy provides a new treatment for patients of hilar cholangiocarcinoma with deep jaundice who have the possibility of radical heptolobectomy.

Dynamic use of B-type natriuretic peptide-guided acute coronary syndrome therapy.

BACKGROUND: Very few studies have evaluated the potential of using B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as surrogate markers to guide clinical interventional or conservative therapy decisions. AIM: : The aim of the current study was to evaluate the potential of using BNP and NT-proBNP as surrogate markers to guide clinical interventional or conservative therapy decisions. METHODS: We identified randomized controlled trials that randomized patients with acute coronary syndrome (ACS) of unstable angina and myocardial infarction without ST-segment elevation ACS to early invasive therapy versus a more conservative approach by systematic search of articles and databases. RESULTS: Five randomized controlled trials with a total of 8125 patients and with a mean duration of 11.2 months were included in the meta-analysis. At a mean follow-up of 11.2 months, the incidence of all-cause mortality was 5.9% in the early invasive group, compared with 6.8% in the conservative group (risk ratio = 0.74; 95% confidence interval, 0.59-0.86; P = 0.001). CONCLUSIONS: In summary, BNP/NT-proBNP-guided management of ACS is significantly improved by early invasive therapy by improving long-term survival and reducing nonfatal myocardial infarction for unstable angina. However, there does not seem to be a clear benefit of using such a strategy over existing clinical recommendations.

A prognostic biomarker for gastric cancer with lymph node metastases.

Gastric cancer is one of the leading causes of tumor-related deaths in China. The tumor, node, metastasis (TNM) classification system is useful for predicting clinical prognosis of patients with gastric cancer. However, determining the presence of lymph node involvement in the early stages of gastric cancer is difficult without biopsy. Therefore, it is necessary to identify novel serum biomarkers for TNM cancer staging and prognostic follow-up. In this study, we have reported fibrinopeptide-A (FPA) with alanine truncation at the N-terminal as a novel biomarker to differentiate gastric cancer with and without lymph node metastases. We analyzed 369 individual serum samples including gastric cancer patients without lymph node metastases (n = 33), gastric cancer patients with lymph node metastases (n = 157; confirmed by pathology), and age- and sex-matched healthy individuals (n = 179). The data showed that 85.4% of patients with lymph node metastases were positive for FPA with alanine truncation at the N-terminal (degAla-FPA, 1,465.63 Da), as determined by tandem mass spectrometry (MS). Using degAla-FPA as the biomarker, the sensitivity was 85.4% for gastric cancer patients with lymph node metastases, and the specificity was 100% for gastric cancer patients without lymph node metastases. The high sensitivity and specificity achieved with serum degAla-FPA levels indicated that MS technology could facilitate the discovery of a novel and quantitative prognostic biomarker for gastric cancer with lymph node involvement.

XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population: a meta-analysis.

PURPOSE: Numerous studies have evaluated the association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population. However, the results have been inconsistent. We therefore here examined whether the XRCC1 Arg399Gln gene polymorphism confers hepatocellular carcinoma risk by conducting a meta-analysis. METHODS: PubMed, Google scholar and China National Knowledge Infrastructure databases were searched for eligible articles in English and Chinese that were published before April 2012. RESULTS: 6 studies involving 1,246 patients with hepatocellular carcinoma and 1,953 controls were included. The association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma in the Chinese Han population was significant under GG vs AA (OR = 1.48, 95% CI = 1.13 to 1.94). Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. CONCLUSIONS: In the Chinese Han population, the XRCC1 Arg399Gln gene polymorphism is associated with an increased hepatocellular carcinoma risk.

Duodenum is important for the sphincter of Oddi motor response to cholecystokinin octapeptide in conscious dogs.

BACKGROUND: We investigated the role of the duodenum in the sphincter of Oddi response to cholecystokinin-octapeptide (CCK-OP), using conscious dogs. METHODS: In controls, a cannula was inserted into the duodenum opposite the papilla for retrograde manometry. In the duodenectomy group, the entire duodenum was resected, while preserving the papilla, which was implanted into the jejunum, and the cannula was placed. Sphincter motility was recorded after bolus injections of 20 and 100 ng/kg of CCK-OP. RESULTS: CCK-OP at 20 ng/kg produced sphincter relaxation followed by contraction in the controls, but produced no changes after duodenectomy. CCK-OP at 100 ng/kg caused strong contractions followed by relaxation in the controls, but caused only contractions after duodenectomy. CONCLUSIONS: (1) Relaxation and delayed contraction of the sphincter induced by 20 ng/kg of CCK-OP require the presence of the duodenum; (2) early contractions of the sphincter induced by 100 ng/kg of CCK-OP do not require the duodenum; (3) the duodenum plays an important role in the actions of CCK-OP on sphincter motility.

Role of duodenum on sphincter of Oddi motility in conscious dogs.

Our aim was to determine the role of the duodenum in controlling sphincter of Oddi motility using conscious dogs after total duodenectomy. In a control group (N = 6), a cannula was implanted into the duodenum opposite to the papilla to allow retrograde sphincter manometry. In a duodenectomy group (N = 6), the papillae were preserved at total duodenectomy and sutured to thejejunum anastomosed to the stomach (neoduodenum). The cannula was implanted opposite to the implanted papillae. Interdigestive and postprandial sphincter and duodental or neoduodenal motility were recorded by manometric and myoelectric methods. Duodenectomy disrupted sphincter cyclic motility associated with the intestinal migrating motor complex and increased sphincter activity throughout the cycle. Sphincter activity increased immediately after feeding and did not differ between the two groups. In conclusion, during the interdigestive period, the duodenum has a distinct role in regulating sphincter cyclic motility. The initiation of the fed pattern of sphincter motility does not need the duodenum.