MYBL2 regulates de novo purine synthesis by transcriptionally activating IMPDH1 in hepatocellular carcinoma cells.

BACKGROUND: Metabolic reprogramming is a hallmark of cancer, alteration of nucleotide metabolism of hepatocellular carcinoma (HCC) is not well-understood. MYBL2 regulates cell cycle progression and hepatocarcinogenesis, its role in metabolic regulation remains elusive. PATIENTS AND METHODS: Copy number, mRNA and protein level of MYBL2 and IMPDH1 were analyzed in HCC, and correlated with patient survival. Chromatin Immunoprecipitation sequencing (Chip-seq) and Chromatin Immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) were used to explore the relationship between MYBL2 and IMPDH1. Metabolomics were used to analyze how MYBL2 affected purine metabolism. The regulating effect of MYBL2 in HCC was further validated in vivo using xenograft models. RESULTS: The Results showed that copy-number alterations of MYBL2 occur in about 10% of human HCC. Expression of MYBL2, IMPDH1, or combination of both were significantly upregulated and associated with poor prognosis in HCC. Correlation, ChIP-seq and ChIP-qPCR analysis revealed that MYBL2 activates transcription of IMPDH1, while knock-out of MYBL2 retarded IMPDH1 expression and inhibited proliferation of HCC cells. Metabolomic analysis post knocking-out of MYBL2 demonstrated that it was essential in de novo purine synthesis, especially guanine nucleotides. In vivo analysis using xenograft tumors also revealed MYBL2 regulated purine synthesis by regulating IMPDH1, and thus, influencing tumor progression. CONCLUSION: MYBL2 is a key regulator of purine synthesis and promotes HCC progression by transcriptionally activating IMPDH1, it could be a potential candidate for targeted therapy for HCC.

Duodenal gastrointestinal stromal tumors: A retrospective study based on a 13 years experience of a single center in China.

AIM: Duodenal gastrointestinal stromal tumors (GISTs) constitute a small rare subset. This study aims to analyze the prognostic differences between duodenal and jejunoileal GISTs and evaluate the clinical treatment and prognostic characteristics of patients with duodenal GISTs. METHODS: Data of patients with primary duodenal or jejunoileal GISTs were collected. Patients were matched through propensity score matching (PSM). Perioperative and long-term outcomes of patients with duodenal GISTs were compared based on surgical approach. RESULTS: Altogether, 101 duodenal and 219 jejunoileal GISTs were identified. In patients with duodenal GISTs, 79 (78%) underwent local resection (LR) and 22 (22%) underwent pancreaticoduodenectomy (PD). Patients undergoing PD had a longer postoperation stay (18.5 vs 13 days, P = 0.001) and more complications (Clavien-Dindo I-II complications for PD vs LR, 31.8 vs 15.2%; Clavien-Dindo III-V complications for PD vs LR, 22.7 vs. 2.5%; P < 0.001). There was no difference in recurrence-free survival (RFS) (P = 0.8) or overall survival (OS) (P = 0.9) when comparing patients who underwent LR versus PD. Multivariable analysis showed that tumor size >5 cm was the only independent predictor of shorter RFS (P = 0.004) and OS (P = 0.012). After matching, there was no significant difference in RFS and OS between patients with duodenal versus jejunoileal GISTs (both P > 0.05). CONCLUSION: The prognosis of duodenal and jejunoileal GISTs are similar. Recurrence and OS of duodenal GISTs primarily depend on tumor size. For duodenal GISTs, LR is associated with comparable long-term survival when compared to PD, but with superior short-term outcomes.

Clinicopathological Characteristics and Prognosis of Hepatoid Adenocarcinoma of the Stomach: Evaluation of a Pooled Case Series.

Hepatoid adenocarcinoma of the stomach (HAS) is an extremely rare and unique gastric malignancy. The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis. We retrospectively reviewed clinical data of 34 HAS patients treated at our institution between January 2010 and December 2016, as well as 294 cases reported prior to 2017 in research databases. Among these patients, 45.6% (115/252) had lesions in the gastric antrum and 77.0% (235/305) were male. Elevated levels of serum alpha-fetoprotein (AFP) were detected in most patients (75/93, 80.6%). Vascular invasion (199/286, 69.6%), lymph node metastasis (222/283, 78.4%), and preoperative distant metastasis (121/328, 36.9%) were commonly observed. The 5-year disease-free survival (DFS) and disease-specific survival (DSS) were 20.7% and 29.2%, respectively. DFS and DSS of patients receiving neoadjuvant therapy were significantly higher than those of patients receiving postoperative adjuvant therapy [DFS: P<0.001, hazard ratio (HR)=-1.831, 95% confidence interval (CI): 0.060-0.429; DSS: P<0.001, HR=-2.185, 95% CI: 0.032-0.401]. In conclusion, HAS exhibits distinct clinicopathological characteristics and a strikingly worse prognosis when compared with common gastric cancer. Complete surgery, early pTNM stage, and adjuvant therapy may predict a more favorable prognosis. Neoadjuvant therapy is strongly recommended for patients with lymph node metastasis or/and preoperative distant metastasis.

The prognostic value of AGR2 expression in solid tumours: a systematic review and meta-analysis.

The prognostic value of anterior gradient-2 (AGR2) in tumours remains inconclusive. Here, we systematically reviewed the literature evidence and assessed the association between AGR2 expression and prognosis in solid tumours. The primary outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS). All analyses were performed by STATA 12.0, with the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) as the effect size estimate. A total of 20 studies containing 3285 cases were included. Pooled analyses revealed that AGR2 overexpression had an unfavourable impact on OS (HR 1.93, 95% CI 1.32-2.81) and time to tumour progression (TTP) (DFS/RFS/PFS) (HR 1.60 95% CI 1.06-2.40) in solid tumour patients. Subgroup analyses indicated that AGR2 overexpression in breast cancer patients was significantly associated with poor OS (HR 3.02, 95% CI 1.03-8.81) and TTP (HR 1.93, 95% CI 1.17-3.20). Excluding breast cancer, AGR2 overexpression was also found to have a significant correlation with poor OS in the remaining solid tumour patients (HR 1.51, 95% CI 1.04-2.19). Overall, AGR2 might be a potential biomarker to predict prognosis in solid tumour patients.

Comparison of infrared canopy temperature in a rubber plantation and tropical rain forest.

Canopy temperature is a result of the canopy energy balance and is driven by climate conditions, plant architecture, and plant-controlled transpiration. Here, we evaluated canopy temperature in a rubber plantation (RP) and tropical rainforest (TR) in Xishuangbanna, southwestern China. An infrared temperature sensor was installed at each site to measure canopy temperature. In the dry season, the maximum differences (Tc - Ta) between canopy temperature (Tc) and air temperature (Ta) in the RP and TR were 2.6 and 0.1 K, respectively. In the rainy season, the maximum (Tc - Ta) values in the RP and TR were 1.0 and -1.1 K, respectively. There were consistent differences between the two forests, with the RP having higher (Tc - Ta) than the TR throughout the entire year. Infrared measurements of Tc can be used to calculate canopy stomatal conductance in both forests. The difference in (Tc - Ta) at three gc levels with increasing direct radiation in the RP was larger than in the TR, indicating that change in (Tc - Ta) in the RP was relatively sensitive to the degree of stomatal closure.

Water use efficiency in a primary subtropical evergreen forest in Southwest China.

We calculated water use efficiency (WUE) using measures of gross primary production (GPP) and evapotranspiration (ET) from five years of continuous eddy covariance measurements (2009-2013) obtained over a primary subtropical evergreen broadleaved forest in southwestern China. Annual mean WUE exhibited a decreasing trend from 2009 to 2013, varying from ~2.28 to 2.68 g C kg H2O-1. The multiyear average WUE was 2.48 ± 0.17 (mean ± standard deviation) g C kg H2O-1. WUE increased greatly in the driest year (2009), due to a larger decline in ET than in GPP. At the diurnal scale, WUE in the wet season reached 5.1 g C kg H2O-1 in the early morning and 4.6 g C kg H2O-1 in the evening. WUE in the dry season reached 3.1 g C kg H2O-1 in the early morning and 2.7 g C kg H2O-1 in the evening. During the leaf emergence stage, the variation of WUE could be suitably explained by water-related variables (relative humidity (RH), soil water content at 100 cm (SWC_100)), solar radiation and the green index (Sgreen). These results revealed large variation in WUE at different time scales, highlighting the importance of individual site characteristics.

Molecular mechanisms of chemoresistance in gastric cancer.

Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness of chemotherapy, which results in treatment failure. Resistance to chemotherapy can be present intrinsically before the administration of chemotherapy or it can develop during chemotherapy. The mechanisms of chemotherapy resistance in gastric cancer are complex and multifactorial. A variety of factors have been demonstrated to be involved in chemoresistance, including the reduced intracellular concentrations of drugs, alterations in drug targets, the dysregulation of cell survival and death signaling pathways, and interactions between cancer cells and the tumor microenvironment. This review focuses on the molecular mechanisms of chemoresistance in gastric cancer and on recent studies that have sought to overcome the underlying mechanisms of chemoresistance.

Clinicopathologic features and prognosis of primary gastrointestinal stromal tumor patients under 35 years of age: A 10-year retrospective study.

OBJECTIVES: To investigate gastrointestinal stromal tumor (GIST) clinicopathologic characteristics in young adults. METHODS: Clinicopathologic data from GIST patients under 35 years diagnosed at our hospital from January 2005 to December 2014 were retrospectively collected. RESULTS: Thirty-one (5.3%, 31/585) patients were included; 17 (54.8%) were female. The most common presentation and primary tumor site were gastrointestinal bleeding (n = 18, 58.1%) and the small intestine (n = 13, 41.9%), respectively. Fifteen (48.4%) GISTs were classified as having a high relapse risk; two (6.4%), intermediate; nine (29.0%), low; and five (16.1%), very low. All patients underwent tumor resection. With a median follow-up of 51 months for 20 (64.5%) patients, 12 (60%) were given imatinib methylate as adjuvant therapy. One (5%) patient died of peritoneal GIST dissemination, four (20%) developed abdominal recurrences, two (10%) had hepatic metastasis, and thirteen (65%) were disease free. The 5-year disease-free survival rate was 51.2%. CONCLUSIONS: GISTs rarely occur in young adults. The most common location is the small intestine. A slight female predominance was observed in the current study. Adjuvant therapy longer than the recommended duration may be beneficial for GISTs with a high relapse risk. Combined targeted therapy and surgery is appropriate for recurrent and metastatic GISTs in select patients. J. Surg. Oncol. 2016;114:977-981. © 2016 Wiley Periodicals, Inc.

Spatial distribution and historical records of mercury sedimentation in urban lakes under urbanization impacts.

China is assumed one of the largest contributors to the world's total mercury (Hg) emissions, with a rapid increase in anthropogenic Hg emissions. However, little is known about Hg fate and transport in urban areas of China. In this study, total Hg contents in surface (0-5 cm) sediments from lakes in 14 parks (3 in the central urban core (CUC) area, 5 in the developed urban (DDU) area, 2 in the developing urban (DIU) area, and 4 in the suburban (SU) area) and (210)Pb-dated sediment cores from lakes in 5 parks (3 in the CUC and 2 in the DDU) in Shanghai were assessed to compare current patterns (urbanization effect) with the historical records of Hg emissions over the past century. Total Hg content in surface sediments showed a clear urbanization pattern. Dated sediment cores revealed a 2-3 fold increase in total Hg content, while Hg fluxes exponentially increased from ~1900 to present and accelerated since 1990 when China's economy and urbanization booms started. Anthropogenic Hg fluxes in post-2000 ranged from 253 to 1452 µg m(-2) yr(-1), 2-7 times greater than preindustrial (pre-1900) Hg fluxes. Total Hg and Pb contents in both surface sediments and sediment cores were highly correlated and Hg flux in sediment cores also significantly correlated with annual coal consumption in the period 1949-2008. The significant correlations suggest that coal combustion is a major source of Hg emission in Shanghai.

Role of Kasai procedure in surgery of hilar bile duct strictures.

AIM: To assess the application of the Kasai procedure in the surgical management of hilar bile duct strictures. METHODS: Ten consecutive patients between 2005 and 2011 with hilar bile duct strictures who underwent the Kasai procedure were retrospectively analyzed. Kasai portoenterostomy with the placement of biliary stents was performed in all patients. Clinical characteristics, postoperative complications, and long-term outcomes were analyzed. All patients were followed up for 2-60 mo postoperatively. RESULTS: Patients were classified according to the Bismuth classification of biliary strictures. There were two Bismuth III and eight Bismuth IV lesions. Six lesions were benign and four were malignant. Of the benign lesions, three were due to post-cholecystectomy injury, one to trauma, one to inflammation, and one to inflammatory pseudotumor. Of the malignant lesions, four were due to hilar cholangiocarcinoma. All patients underwent Kasai portoenterostomy with the placement of biliary stents. There were no perioperative deaths. One patient experienced anastomotic leak and was managed conservatively. No other complications occurred perioperatively. During the follow-up period, all patients reported a good quality of life. CONCLUSION: The Kasai procedure combined with biliary stents may be appropriate for patients with hilar biliary stricture that cannot be managed by standard surgical methods.