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991.
992.
Yao-An Shen Chia-Yu Wang Yi-Tao Hsieh Yann-Jang Chen Yau-Huei Wei 《Cell cycle (Georgetown, Tex.)》2015,14(1):86-98
Cancer stem cells (CSCs) represent a subpopulation of tumor cells endowed with
self-renewal capacity and are considered as an underlying cause of tumor recurrence and
metastasis. The metabolic signatures of CSCs and the mechanisms involved in the regulation
of their stem cell-like properties still remain elusive. We utilized nasopharyngeal
carcinoma (NPC) CSCs as a model to dissect their metabolic signatures and found that CSCs
underwent metabolic shift and mitochondrial resetting distinguished from their
differentiated counterparts. In metabolic shift, CSCs showed a greater reliance on
glycolysis for energy supply compared with the parental cells. In mitochondrial resetting,
the quantity and function of mitochondria of CSCs were modulated by the biogenesis of the
organelles, and the round-shaped mitochondria were distributed in a peri-nuclear manner
similar to those seen in the stem cells. In addition, we blocked the glycolytic pathway,
increased the ROS levels, and depolarized mitochondrial membranes of CSCs, respectively,
and examined the effects of these metabolic factors on CSC properties. Intriguingly, the
properties of CSCs were curbed when we redirected the quintessential metabolic
reprogramming, which indicates that the plasticity of energy metabolism regulated the
balance between acquisition and loss of the stemness status. Taken together, we suggest
that metabolic reprogramming is critical for CSCs to sustain self-renewal, deter from
differentiation and enhance the antioxidant defense mechanism. Characterization of
metabolic reprogramming governing CSC properties is paramount to the design of novel
therapeutic strategies through metabolic intervention of CSCs. 相似文献
993.
994.
Fu-Zheng Wei Ziyang Cao Xi Wang Hui Wang Mu-Yan Cai Tingting Li Naoko Hattori Donglai Wang Yipeng Du Boyan Song Lin-Lin Cao Changchun Shen Lina Wang Haiying Wang Yang Yang Dan Xie Fan Wang Toshikazu Ushijima Ying Zhao Wei-Guo Zhu 《Autophagy》2015,11(12):2309-2322
Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the autophagy regulation machinery has been widely studied, the key epigenetic control of autophagy process still remains unknown. Here we report that the methyltransferase EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) epigenetically represses several negative regulators of the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) pathway, such as TSC2, RHOA, DEPTOR, FKBP11, RGS16 and GPI. EZH2 was recruited to these genes promoters via MTA2 (metastasis associated 1 family, member 2), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA2 was identified as a new chromatin binding protein whose association with chromatin facilitated the subsequent recruitment of EZH2 to silenced targeted genes, especially TSC2. Downregulation of TSC2 (tuberous sclerosis 2) by EZH2 elicited MTOR activation, which in turn modulated subsequent MTOR pathway-related events, including inhibition of autophagy. In human colorectal carcinoma (CRC) tissues, the expression of MTA2 and EZH2 correlated negatively with expression of TSC2, which reveals a novel link among epigenetic regulation, the MTOR pathway, autophagy induction, and tumorigenesis. 相似文献
995.
996.
Tingting Hu Shuqiang Weng Wenqing Tang Ruyi Xue She Chen Guoxiang Cai Yu Cai Xizhong Shen Si Zhang Ling Dong 《PloS one》2015,10(5)
MethodsWe used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method.ResultsWe reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS) (P = 0.001) and shorter disease-free survival (DFS) (P = 0.010). BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo.ConclusionsTaken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy. 相似文献
997.
Background
Bipolar disorder types I (BD I) and II (BD II) behave differently in clinical manifestations, normal personality traits, responses to pharmacotherapies, biochemical backgrounds and neuroimaging activations. How the varied emotional states of BD I and II are related to the comorbid personality disorders remains to be settled.Methods
We therefore administered the Plutchick – van Praag Depression Inventory (PVP), the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32), and the Parker Personality Measure (PERM) in 37 patients with BD I, 34 BD II, and in 76 healthy volunteers.Results
Compared to the healthy volunteers, patients with BD I and II scored higher on some PERM styles, PVP, MDQ and HCL-32 scales. In BD I, the PERM Borderline style predicted the PVP scale; and Antisocial predicted HCL-32. In BD II, Borderline, Dependant, Paranoid (-) and Schizoid (-) predicted PVP; Borderline predicted MDQ; Passive-Aggressive and Schizoid (-) predicted HCL-32. In controls, Borderline and Narcissistic (-) predicted PVP; Borderline and Dependant (-) predicted MDQ.Conclusion
Besides confirming the different predictability of the 11 functioning styles of personality disorder to BD I and II, we found that the prediction was more common in BD II, which might underlie its higher risk of suicide and poorer treatment outcome. 相似文献998.
Na Shen Cheng Liu Jiaoyuan Li Xueqin Chen Yang Yang Ying Zhu Yajie Gong Jing Gong Rong Zhong Liming Cheng Xiaoping Miao 《PloS one》2015,10(3)
It is well-established that abnormal protein phosphorylation could play an essential role in tumorgenesis by disrupting a variety of physiological processes such as cell growth, signal transduction and cell motility. Moreover, increasing numbers of phosphorylation-related variants have been identified in association with cancers. ADD1 (α-adducin), a versatile protein expressed ubiquitously in eukaryotes, exerts an important influence on membrane cytoskeleton, cell proliferation and cell-cell communication. Recently, a missense variant at the codon of ADD1’s phosphorylation site, rs4963 (Ser586Cys), was reported to modify the risk of non-cardia gastric cancer. To explore the role of ADD1-rs4963 in colorectal cancer (CRC), we conducted a case-control study with a total of 1054 CRC cases and 1128 matched controls in a Chinese population. After adjustment for variables including age, gender, smoking and drinking, it was demonstrated that this variant significantly conferred susceptibility to CRC (G versus C: OR = 1.16, 95% CI = 1.03–1.31, P = 0.016; CG versus CC: OR = 1.25, 95% CI = 1.02–1.55, P = 0.036; GG versus CC: OR = 1.35, 95% CI = 1.06–1.72, P = 0.015). We further investigated the interaction of ADD1-rs4963 with smoking or drinking exposure, but found no significant result. This study is the first report of an association between ADD1 and CRC risk, promoting our knowledge of the genetics of CRC. 相似文献
999.
Yunting Zhang Donglan Zhang Yanrui Jiang Wanqi Sun Yan Wang Wenjuan Chen Shenghui Li Lu Shi Xiaoming Shen Jun Zhang Fan Jiang 《PloS one》2015,10(3)
Introduction
A growing body of literature reveals the causal pathways between physical activity and brain function, indicating that increasing physical activity among children could improve rather than undermine their scholastic performance. However, past studies of physical activity and scholastic performance among students often relied on parent-reported grade information, and did not explore whether the association varied among different levels of scholastic performance. Our study among fifth-grade students in Shanghai sought to determine the association between regular physical activity and teacher-reported academic performance scores (APS), with special attention to the differential associational patterns across different strata of scholastic performance.Method
A total of 2,225 students were chosen through a stratified random sampling, and a complete sample of 1470 observations were used for analysis. We used a quantile regression analysis to explore whether the association between physical activity and teacher-reported APS differs by distribution of APS.Results
Minimal-intensity physical activity such as walking was positively associated with academic performance scores (β = 0.13, SE = 0.04). The magnitude of the association tends to be larger at the lower end of the APS distribution (β = 0.24, SE = 0.08) than in the higher end of the distribution (β = 0.00, SE = 0.07).Conclusion
Based upon teacher-reported student academic performance, there is no evidence that spending time on frequent physical activity would undermine student’s APS. Those students who are below the average in their academic performance could be worse off in academic performance if they give up minimal-intensity physical activity. Therefore, cutting physical activity time in schools could hurt the scholastic performance among those students who were already at higher risk for dropping out due to inadequate APS. 相似文献1000.
Brandon S. Sheffield Anna V. Tinker Yaoqing Shen Harry Hwang Hector H. Li-Chang Erin Pleasance Carolyn Ch’ng Amy Lum Julie Lorette Yarrow J. McConnell Sophie Sun Steven J. M. Jones Allen M. Gown David G. Huntsman David F. Schaeffer Andrew Churg Stephen Yip Janessa Laskin Marco A. Marra 《PloS one》2015,10(3)
Peritoneal mesothelioma is a rare and sometimes lethal malignancy that presents a clinical challenge for both diagnosis and management. Recent studies have led to a better understanding of the molecular biology of peritoneal mesothelioma. Translation of the emerging data into better treatments and outcome is needed. From two patients with peritoneal mesothelioma, we derived whole genome sequences, RNA expression profiles, and targeted deep sequencing data. Molecular data were made available for translation into a clinical treatment plan. Treatment responses and outcomes were later examined in the context of molecular findings. Molecular studies presented here provide the first reported whole genome sequences of peritoneal mesothelioma. Mutations in known mesothelioma-related genes NF2, CDKN2A, LATS2, amongst others, were identified. Activation of MET-related signaling pathways was demonstrated in both cases. A hypermutated phenotype was observed in one case (434 vs. 18 single nucleotide variants) and was associated with a favourable outcome despite sarcomatoid histology and multifocal disease. This study represents the first report of whole genome analyses of peritoneal mesothelioma, a key step in the understanding and treatment of this disease. 相似文献