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991.
David Martino Yuk Jin Loke Lavinia Gordon Miina Ollikainen Mark N Cruickshank Richard Saffery Jeffrey M Craig 《Genome biology》2013,14(5):R42
Background
The extent to which development- and age-associated epigenetic changes are influenced by genetic, environmental and stochastic factors remains to be discovered. Twins provide an ideal model with which to investigate these influences but previous cross-sectional twin studies provide contradictory evidence of within-pair epigenetic drift over time. Longitudinal twin studies can potentially address this discrepancy.Results
In a pilot, genome-scale study of DNA from buccal epithelium, a relatively homogeneous tissue, we show that one-third of the CpGs assayed show dynamic methylation between birth and 18 months. Although all classes of annotated genomic regions assessed show an increase in DNA methylation over time, probes located in intragenic regions, enhancers and low-density CpG promoters are significantly over-represented, while CpG islands and high-CpG density promoters are depleted among the most dynamic probes. Comparison of co-twins demonstrated that within-pair drift in DNA methylation in our cohort is specific to a subset of pairs, who show more differences at 18 months. The rest of the pairs show either minimal change in methylation discordance, or more similar, converging methylation profiles at 18 months. As with age-associated regions, sites that change in their level of within-pair discordance between birth and 18 months are enriched in genes involved in development, but the average magnitude of change is smaller than for longitudinal change.Conclusions
Our findings suggest that DNA methylation in buccal epithelium is influenced by non-shared stochastic and environmental factors that could reflect a degree of epigenetic plasticity within an otherwise constrained developmental program. 相似文献992.
Anthony D. Saleh Brittany A. Simone Juan Palazzo Jason E. Savage Yuri Sano Tu Dan Lianjin Jin Colin E. Champ Shuping Zhao Meng Lim Frederica Sotgia Kevin Camphausen Richard G. Pestell James B. Mitchell Michael P. Lisanti Nicole L. Simone 《Cell cycle (Georgetown, Tex.)》2013,12(12):1955-1963
Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories provided more significant tumor regression than alternate day feeding. At the molecular level, tumors treated with CR and IR showed less proliferation and more apoptosis. cDNA array analysis demonstrated the IGF-1R pathway plays a key role in achieving this physiologic response, and multiple members of the IGF-1R pathway including IGF-1R, IRS, PIK3ca and mTOR were found to be downregulated. The innovative use of CR as a novel therapeutic option has the potential to change the biology of tumors and enhance the opportunity for clinical benefit in the treatment of patients with TNBC. 相似文献
993.
Youn-Sang Jung Su-Jin Lee Sun-Hye Lee Ji-Yun Chung Youn Jin Jung Sang Hyun Hwang Nam-Chul Ha Bum-Joon Park 《Cell cycle (Georgetown, Tex.)》2013,12(14):2277-2290
Renal cell carcinomas (RCCs) are frequently occurring genitourinary malignancies in the aged population. A morphological characteristic of RCCs is an irregular nuclear shape, which is used to index cancer grades. Other features of RCCs include the genetic inactivation of the von Hippel-Lindau gene, VHL, and p53 genetic-independent inactivation. An aberrant nuclear shape or p53 suppression has not yet been demonstrated. We examined the effect of progerin (an altered splicing product of the LMNA gene linked to Hutchinson Gilford progeria syndrome; HGPS) on the nuclear deformation of RCCs in comparison to that of HGPS cells. In this study, we showed that progerin was suppressed by pVHL and was responsible for nuclear irregularities as well as p53 inactivation. Thus, progerin suppression can ameliorate nuclear abnormalities and reactivate p53 in response to genotoxic addition. Furthermore, we found that progerin was a target of pVHL E3 ligase and suppressed p53 activity by p14/ARF inhibition. Our findings indicate that the elevated expression of progerin in RCCs results from the loss of pVHL and leads to p53 inactivation through p14/ARF suppression. Interestingly, we showed that progerin was expressed in human leukemia and primary cell lines, raising the possibility that the expression of this LMNA variant may be a common event in age-related cancer progression. 相似文献
994.
995.
Yuelian Sun Kim Overvad Wei Jin Zhou Jin Liang Zhu Jørn Olsen 《Birth defects research. Part B, Developmental and reproductive toxicology》2013,98(2):154-163
Cancer risk in parents may be related to congenital malformations (CMs) in their children if they share genetic susceptibility or environmental exposure that may be teratogenic and carcinogenic. We conducted a population‐based cohort study based on Danish register data. We identified 795,607 mothers and 781,424 fathers who had all their children between 1977 and 2007 in Denmark. Information on CM was obtained from the Danish Hospital Registry and information on cancer was obtained from the Danish Cancer Registry. Parents were followed from the birth of their first child until the diagnosis of cancer, death, emigration, or December 31, 2007. We used Cox regression models to estimate hazard ratios (HRs) for cancer including cancer in specific organs in mothers and fathers. Overall, 75,701 (9.5%) mothers and 72,724 (9.3%) fathers had at least one child diagnosed with CMs within the first year of life. Neither mothers (HR = 1.04; 95% CI: 0.99–1.04) nor fathers (HR = 1.03; 95% CI: 0.98–1.09) who had a child with a CM had a higher overall risk of cancer. Mothers (HR = 0.76, 95% CI: 0.58–1.00) or fathers (HR = 0.89, 95% CI: 0.66–1.19) who had a child with a chromosomal malformation had a lower overall cancer risk. The findings also showed a higher risk for some specific types of cancer in parents who had children with a CM in the specific system. Some, or perhaps all, of these findings may be due to chance caused by multiple comparisons. We present all results on paper or online to provide clues for further research and to avoid publication bias. 相似文献
996.
997.
Robotic Partial Nephrectomy for Renal Tumors Larger than 4 cm: A Systematic Review and Meta-analysis
Liangkuan Bi Caixia Zhang Kaiwen Li Xinxiang Fan Kewei Xu Jinli Han Hai Huang Hao Liu Wen Dong Xiangyun Yang Jian Huang Tianxin Lin 《PloS one》2013,8(10)
Background
With the establishment of minimally invasive surgery in society, the robot has been increasingly widely used in the urologic field, including in partial nephrectomy. This study aimed to comprehensively summarize the currently available evidence on the feasibility and safety of robotic partial nephrectomy for renal tumors of >4 cm.Method and Findings
An electronic database search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed. This systematic review and meta-analysis was based on all relevant studies that assessed robotic partial nephrectomy for renal tumors of >4 cm. Five studies were included. The meta-analysis involved 3 studies from 11 institutions including 154 patients, while the narrative review involved the remaining 2 studies from 5 institutions including 64 patients. In the meta-analysis, the mean ischemic time, operation time, and console time was 28, 319, and 189 minutes, respectively. The estimated blood loss and length of stay was 317 ml and 3.8 days, respectively. The rates of conversion, positive margins, intraoperative complications, postoperative complications, hilar clamping, and collecting system repair were 7.0%, 3.5%, 7.0%, 9.8%, 93.9%, and 47.5%, respectively. The narrative review showed results similar to those of the meta-analysis.Conclusions
Robotic partial nephrectomy is feasible and safe for renal tumors of >4 cm with an acceptable warm ischemic time, positive margin rate, conversion rate, complication rate, operation time, estimated blood loss, and length of stay. 相似文献998.
The functional deficiencies of bone marrow-derived mesenchymal stem cells (MSCs) may contribute to the aging process and age-related diseases, such as osteoporosis. Although it has been reported that microRNAs (miRNAs) played an important role in mechanisms of gene regulation of aging, and their expression profiles in MSCs osteogenic differentiation were established in recent years, but it is still elusive for the dynamic patterns of miRNAs in aging process. Importantly, the miRNAs in aged bone tissue had not been yet reported so far. Here, we combined high through-put sequencing with computational techniques to detect miRNAs dynamics in MSCs and bone tissue of age-related osteoporosis. Among the detected miRNAs, 59 identified miRNAs in MSCs and 159 in bone showed significantly differential expressions. And more importantly, there existed 8 up-regulated and 30 down-regulated miRNAs in both MSCs and bone during the aging process, with the majority having a trend of down-regulation. Furthermore, after target prediction and KEGG pathway analysis, we found that their targeted genes were significantly enriched in pathways in cancer, which are complex genetic networks, comprise of a number of age-related pathways. These results strongly suggest that these analyzed miRNAs may be negatively involved in age-related osteoporosis, given that most of them showed a decreased expression, which could lay a good foundation for further functional analysis of these miRNAs in age-related osteoporosis. 相似文献
999.
Hong Wu Hong Zeng Aiping Dong Fengling Li Hao He Guillermo Senisterra Alma Seitova Shili Duan Peter J. Brown Masoud Vedadi Cheryl H. Arrowsmith Matthieu Schapira 《PloS one》2013,8(12)
Polycomb repressive complex 2 (PRC2) is an important regulator of cellular differentiation and cell type identity. Overexpression or activating mutations of EZH2, the catalytic component of the PRC2 complex, are linked to hyper-trimethylation of lysine 27 of histone H3 (H3K27me3) in many cancers. Potent EZH2 inhibitors that reduce levels of H3K27me3 kill mutant lymphoma cells and are efficacious in a mouse xenograft model of malignant rhabdoid tumors. Unlike most SET domain methyltransferases, EZH2 requires PRC2 components, SUZ12 and EED, for activity, but the mechanism by which catalysis is promoted in the PRC2 complex is unknown. We solved the 2.0 Å crystal structure of the EZH2 methyltransferase domain revealing that most of the canonical structural features of SET domain methyltransferase structures are conserved. The site of methyl transfer is in a catalytically competent state, and the structure clarifies the structural mechanism underlying oncogenic hyper-trimethylation of H3K27 in tumors harboring mutations at Y641 or A677. On the other hand, the I-SET and post-SET domains occupy atypical positions relative to the core SET domain resulting in incomplete formation of the cofactor binding site and occlusion of the substrate binding groove. A novel CXC domain N-terminal to the SET domain may contribute to the apparent inactive conformation. We propose that protein interactions within the PRC2 complex modulate the trajectory of the post-SET and I-SET domains of EZH2 in favor of a catalytically competent conformation. 相似文献
1000.
Huiying He Dong Han Hailan Feng Hong Qu Shujuan Song Baojing Bai Zhenting Zhang 《PloS one》2013,8(11)