Surgical Treatment for Patients with Krukenberg Tumor of Stomach Origin: Clinical Outcome and Prognostic Factors Analysis

Krukenberg tumor originated from stomach in female patients is common in clinical practice, but it is still uncertain whether surgical resection of ovarian metastases could improve the outcome. Some studies suggested that a certain group of patients could benefit from the resection of ovarian metastases. However, conclusions were different between studies and there was no data to illustrate if certain molecular markers were associated with patients’ survival. In this study, we analyzed the effects of resection of ovarian metastases, and investigated prognostic factors in 133 patients with ovarian metastases originated from stomach. Furthermore, we examined the expression of some cancer stem cells (CSCs) markers or related molecules in 64 ovarian metastases specimens and analyzed the correlation between these molecules and patients’ survival. We found that the median overall survival (mOS) of all 133 patients was 16 months, and “gastrectomy” and “without ascites” were two independent prognostic factors associated with longer survival. The mOS of the patients with gastrectomy was longer than that of patients had not undergone gastrectomy (19 vs. 9 months, p = 0.048). Patients without ascites survived longer than those with ascites (mOS: 21 vs. 13 months, p = 0.008). We also found that Sox2, CD44 or CD133 positive expression in ovarian metastases were risk factors correlated with poor survival, and Sox2 expression was an independent prognostic indicator. These results suggested that ovarian metastasectomy might help to prolong the survivor of some patients with Krukenberg tumor originated from stomach. Patients without ascites, and with resected or resectable primary gastric cancer lesion could get benefit from and be potential candidate for surgical treatment. The expression of Sox2 might serve as a prognostic indicator for predicting patients’ survival and be helpful for selecting patients in future.     

The G0/G1 Switch Gene 2 Is an Important Regulator of Hepatic Triglyceride Metabolism

Nonalcoholic fatty liver disease is associated with obesity and insulin resistance. Factors that regulate the disposal of hepatic triglycerides contribute to the development of hepatic steatosis. G₀/G₁ switch gene 2 (G0S2) is a target of peroxisome proliferator-activated receptors and plays an important role in regulating lipolysis in adipocytes. Therefore, we investigated whether G0S2 plays a role in hepatic lipid metabolism. Adenovirus-mediated expression of G0S2 (Ad-G0S2) potently induced fatty liver in mice. The liver mass of Ad-G0S2-infected mice was markedly increased with excess triglyceride content compared to the control mice. G0S2 did not change cellular cholesterol levels in hepatocytes. G0S2 was found to be co-localized with adipose triglyceride lipase at the surface of lipid droplets. Hepatic G0S2 overexpression resulted in an increase in plasma Low-density lipoprotein (LDL)/Very-Low-density (VLDL) lipoprotein cholesterol level. Plasma High-density lipoprotein (HDL) cholesterol and ketone body levels were slightly decreased in Ad-G0S2 injected mice. G0S2 also increased the accumulation of neutral lipids in cultured HepG2 and L02 cells. However, G0S2 overexpression in the liver significantly improved glucose tolerance in mice. Livers expressing G0S2 exhibited increased 6-(N-(7-nitrobenz-2-oxa-1-3-diazol-4-yl) amino)-6-deoxyglucose uptake compared with livers transfected with control adenovirus. Taken together, our results provide evidence supporting an important role for G0S2 as a regulator of triglyceride content in the liver and suggest that G0S2 may be a molecular target for the treatment of insulin resistance and other obesity-related metabolic disorders.     

Epstein-Barr Virus_Encoded LMP1 Upregulates MicroRNA-21 to Promote the Resistance of Nasopharyngeal Carcinoma Cells to Cisplatin-Induced Apoptosis by Suppressing PDCD4 and Fas-L

Approximately 30% of patients with Epstein-Barr virus (EBV)-positive advanced nasopharyngeal carcinoma (NPC) display chemoresistance to cisplatin-based regimens, but the underlying mechanisms are unclear. The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, contributes substantially to the oncogenic potential of EBV through the activation of multiple signaling pathways, and it is closely associated with a poorer prognosis for NPC. Recent studies show that EBV infection can induce the expression of many cellular miRNAs, including microRNA-21, a biomarker for chemoresistance. However, neither a link between LMP1 expression and miR-21 upregulation nor their cross talk in affecting chemoresistance to cisplatin have been reported. Here, we observed that stable LMP1-transformed NPC cells were less sensitive to cisplatin treatment based on their proliferation, colony formation, the IC₅₀ value of cisplatin and the apoptosis index. Higher levels of miR-21 were found in EBV-carrying and LMP1-positive cell lines, suggesting that LMP1 may be linked to miR-21 upregulation. These data were confirmed by our results that exogenous LMP1 increased miR-21 in both transiently and stably LMP1-transfected cells, and the knock down of miR-21 substantially reversed the resistance of the NPC cells to cisplatin treatment. Moreover, the proapoptotic factors programmed cell death 4 (PDCD4) and Fas ligand (Fas-L), which were negatively regulated by miR-21, were found to play an important role in the program of LMP1-dependent cisplatin resistance. Finally, we demonstrated that LMP1 induced miR-21 expression primarily by modulating the PI3K/AKT/FOXO3a signaling pathway. Taken together, we revealed for the first time that viral LMP1 triggers the PI3K/Akt/FOXO3a pathway to induce human miR-21 expression, which subsequently decreases the expression of PDCD4 and Fas-L, and results in chemoresistance in NPC cells.     

Compromised NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Chronic SIV/SHIV Infection

Increasing evidence indicates that antibody-dependent cellular cytotoxicity (ADCC) contributes to the control of HIV/SIV infection. However, little is known about the ADCC function of natural killer (NK) cells in non-human primate model. Here we demonstrated that ADCC function of NK cells was significantly compromised in chronic SIV/SHIV infection, correlating closely with the expression of FcγRIIIa receptor (CD16) on NK cells. CD32, another class of IgG Fc receptors, was identified on NK cells with higher expression in the infected macaques and the blockade of CD32 impacted the ability of NK cells to respond to antibody-coated target cells. The inhibition of matrix metalloproteases (MMPs), a group of enzymes normally involved in tissue/receptor remodeling, could restore NK cell-mediated ADCC with increased CD16 expression on macaque NK cells. These data offer a clearer understanding of NK cell-mediated ADCC in rhesus macaques, which will allow us to evaluate the ADCC repertoire arising from preclinical vaccination studies in non-human primates and inform us in the future design of effective HIV vaccination strategies.     

滦河流域河岸带入侵植物分布特征及其与环境的关系

根据滦河流域河岸带56个样点的植被调查,研究入侵植物种类,其组成特征、空间分布,及其与环境因子的关系.结果表明: 滦河流域河岸带共记录入侵植物26种,属12科19属,其中菊科和苋科植物为优势科,占入侵植物总数的50%,一年生植物占总数的73.1%,反枝苋、大狼杷草、小藜是出现频数最高的3种植物;样点的入侵种数、入侵强度与海拔呈显著负相关;人类活动强度对入侵植物分布有显著影响,人口密集、交通便利、人类活动频繁的平原区,水库众多的浅山区,以及中游段旅游业发达的承德市周边山区是入侵植物集中分布的区域;人口分布较稀的高原地区只出现几种宽生态幅的入侵物种.总体上,滦河流域河岸带入侵等级高的植物主要分布在400 m以下的中低海拔地区,除反枝苋外,其他高等级入侵物种尚未扩散进入高海拔地区.     

低氧生境中好氧甲烷氧化菌的缺氧耐受机理及种群结构研究进展

甲烷生物氧化在全球大气甲烷平衡和温室气体的控制中起着重要作用.氧气是甲烷生物氧化过程中的重要影响因素之一.生境中氧浓度不仅影响好氧甲烷氧化菌的种群结构、活性及甲烷碳的分配,而且好氧甲烷氧化菌在不同氧浓度下具有不同的代谢途径.理解低氧生境中好氧甲烷氧化菌的缺氧耐受机理和甲烷生物氧化过程,对甲烷驱动型生态系统的碳循环和生物多样性有着重要意义.本文以好氧甲烷氧化菌为对象,综述了低氧生境中好氧甲烷氧化菌的活性及其种群结构、好氧甲烷氧化菌的缺氧耐受机理以及低氧生境中甲烷氧化菌与非甲烷氧化菌的关系,并对今后的研究方向进行了展望.     

基于物候特征的盐渍化信息数据挖掘研究

盐渍化是影响植被和作物长势的重要因素,精确反演盐渍化的时空分布信息至关重要。基于MOD13A1-NDVI数据反演生长季开始日期(SOS)、生长季结束日期(EOS)、生长季长度(LEN)等物候参数和计算出能高精度反演盐渍化空间分布的多种植被指数、盐分指数、地形指数、干旱指数等参数后作为BP-ANN人工神经网络的输入因子来反演盐渍化信息,同时按照植被类型和地貌类型进行分区来反演盐渍化信息,以探讨盐渍化受植被和地貌类型的影响。主要结论如下:(1)盐渍化的形成受多种因素的影响,与物候参数大多呈非线性关系,不能单纯的以某拟合公式来进行表达,需要借助人工神经网络超强的非线性拟合能力来反演盐渍化信息。(2)通过深入挖掘植被物候信息,在融入物候参数后的反演精度显著提高。可决系数R2从0.68(非物候参数)增加到0.79(包括物候参数),但是需要加入地形、影像数据和土壤水分等方面的信息来更加精确的反演盐渍化信息。生物累积量指标LSI(Large seasonal integral)和SSI(Small seasonal integral)能够很好的表征盐渍化的信息。(3)划分植被类型后的盐渍化提取精度进一步提高,可决系数R~2达到了0.88。(4)以地貌特征作为类型分区后,反演结果的R~2达到了0.85,精度较高,比以植被类型作为分区的精度略小。高程较低区域的盐渍化现象普遍较重,盐渍化程度受到地形和地貌因素的影响显著。(5)农用地区域多为非盐渍化和轻度盐渍化地,稀疏植被区多为重盐渍化地。研究区的非盐渍化和轻盐渍化地、中盐渍化地和重度盐渍化地比例分别为53.42%,13.71%,32.87%。以上的研究结果提出了一种融合物候信息和非物候参数来反演盐渍化信息的方法,进行深入的协同植被物候监测盐渍化信息方面的数据挖掘,在融入了物候参数后,盐渍化的预测精度显著提高。