To compare the long-term survival outcomes between laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH).
We matched patients with stage IA2 to IIA cervical cancer with known ...risk factors for recurrence who underwent ORH and LRH.
Compared with ORH (n = 263), LRH (n = 263) did not have higher risks of recurrence hazard ratio (HR) = 1.28; 95% confidence interval (CI) 0.62–2.64 or death (HR = 1.46; 95% CI 0.62–3.43). Even in patients with tumors >2 cm in diameter, the risks of recurrence (HR = 0.82; 95% CI 0.31–2.16) or death (HR = 1.01; 95% CI 0.35–2.95) were not higher for LRH than for ORH. The LRH and ORH group had 5-year recurrence-free survival rates of 92.8% and 94.4%, respectively (P = 0.499). LRH resulted in significantly lower estimated blood loss (379.6 versus 541.1 ml, P < 0.001) and shorter postoperative hospital stay (12.5 versus 20.3 days, P < 0.001). Intraoperative complication rates were similar in the two groups (6.8% versus 5.7%, P = 0.711), but postoperative complication rate was lower in the LRH than in the ORH group (9.2% versus 21%, P < 0.001).
LRH is an oncologically safe alternative to ORH and was associated with fewer postoperative complication and earlier recovery.
To cite this article: Cheong HS, Park S‐M, Kim M‐O, Park J‐S, Lee JY, Byun JY, Park BL, Shin HD, Park C‐S. Genome‐wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in ...asthmatics. Allergy 2011; 66: 637–644.
Background: In addition to the dysregulation of arachidonic acid metabolism in aspirin‐intolerant asthma (AIA), aspirin acetylsalicylic acid (ASA) exerts effects on inflammation and immunity; however, many of these effects are unknown.
Objective: The aim of the study was to evaluate the methylation status of whole genome in blood and polyp tissues with and without aspirin hypersensitivity.
Methods: Genome‐wide DNA methylation levels in nasal polyps and peripheral blood cells were examined by microarray analysis using five subjects with AIA and four subjects with aspirin‐tolerant asthma (ATA).
Results: In the nasal polyps of the patients with AIA, hypermethylation was detected at 332 loci in 296 genes, while hypomethylation was detected at 158 loci in 141 genes. Gene ontologic and pathway enrichment analyses revealed that genes involved in lymphocyte proliferation, cell proliferation, leukocyte activation, cytokine biosynthesis, cytokine secretion, immune responses, inflammation, and immunoglobulin binding were hypomethylated, while genes involved in ectoderm development, hemostasis, wound healing, calcium ion binding, and oxidoreductase activity were hypermethylated. In the arachidonate pathway, PGDS, ALOX5AP, and LTB4R were hypomethylated, whereas PTGES was hypermethylated.
Conclusion: The nasal polyps of patients with AIA have characteristic methylation patterns affecting 337 genes. The genes and pathways identified in this study may be associated with the presence of aspirin hypersensitivity in asthmatics and are therefore attractive targets for future research.
Microsatellites—simple tandem repeats present at millions of sites in the human genome—can shorten or lengthen due to a defect in DNA mismatch repair. We present here a comprehensive genome-wide ...analysis of the prevalence, mutational spectrum, and functional consequences of microsatellite instability (MSI) in cancer genomes. We analyzed MSI in 277 colorectal and endometrial cancer genomes (including 57 microsatellite-unstable ones) using exome and whole-genome sequencing data. Recurrent MSI events in coding sequences showed tumor type specificity, elevated frameshift-to-inframe ratios, and lower transcript levels than wild-type alleles. Moreover, genome-wide analysis revealed differences in the distribution of MSI versus point mutations, including overrepresentation of MSI in euchromatic and intronic regions compared to heterochromatic and intergenic regions, respectively, and depletion of MSI at nucleosome-occupied sequences. Our results provide a panoramic view of MSI in cancer genomes, highlighting their tumor type specificity, impact on gene expression, and the role of chromatin organization.
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•Analysis of genome sequencing data provides a genome-wide view of MSI in human cancers•Genes affected by MSI show tumor type specificity•Recurrent MSI in coding regions shows a high frameshift-to-in-frame ratio•MSI frequency is associated with chromatin organization and nucleosome positioning
A comprehensive analysis of data from The Cancer Genome Atlas provides a panoramic view of microsatellite instability (MSI) in colorectal and endometrial cancers, showing tumor-type-specific effects and a role for chromatin organization in determining the frequency of MSI.
Migraine carries an increased risk for cardiovascular and cerebrovascular diseases that cannot be explained by traditional cardiovascular risk factors. The circulating endothelial progenitor cell ...(EPC) number is a surrogate biologic marker of vascular function, and diminished EPC counts are associated with higher cardiovascular risk. We investigated whether abnormalities in EPC levels and functions are present in migraine patients.
Consecutive headache patients (n =166) were enrolled, including those with tension type headache (TTH; n = 74), migraine without aura (MO; n = 67), and migraine with aura (MA; n = 25). EPC colony-forming units in peripheral blood samples and migratory capacity to chemoattractants (stromal cell-derived factor 1 and vascular endothelial growth factor) and cellular senescence levels were assayed in risk factor-matched subjects (n = 6 per group).
The TTH group had more cardiovascular risk factors, more headache days, and higher Framingham risk scores than the other two groups. Mean numbers of EPC colony-forming units were 47.8 +/- 24.3 in TTH, 20.4 +/-22.2 in MO, and 8.6 +/- 10.1 in MA patients (p < 0.001 in TTH vs MO; p = 0.001 in MO vs MA). EPC colony counts of normal subjects (n = 37) were not significantly different from those with TTH. Multiple linear regression models identified only MO, MA, and the presence of migraine (MO + MA) as significant predictors of EPC levels. In addition, EPCs from migraine patients (MO and MA) showed reduced migratory capacity and increased cellular senescence compared with EPCs from TTH or normal subjects.
Circulating endothelial progenitor cell (EPC) numbers and functions are reduced in migraine patients, suggesting that EPCs can be an underlying link between migraine and cardiovascular risk.
This study examined how patients with cancer estimate caregiver burden (CB) and the association between their underestimation of CB and their caregivers' self‐ratings of their quality of life ...(CQOLC‐K; Korean version of the Caregiver Quality of Life Index‐Cancer), depression and anxiety (Korean version of the Hospital Anxiety and Depression Scale). Participants consisted of 990 patient‐caregiver dyads recruited from a nationwide cross‐sectional survey conducted in South Korea. Medical baseline data were retrieved from the hospital information systems of the participating centres. The patients with cancer who underestimated CB ranged from 18.62% (for physical CB) to 23.33% (for social CB). They had less advanced cancer, a lower income, were the caregiver's spouse, reported higher levels of family avoidance of communication about cancer, and had female caregivers. The patients' underestimation of CB was significantly related to lower CQoL and higher levels of caregiver depression and anxiety. The current study provides empirical evidence for the link between the underestimation of CB by patients with cancer and compromised caregiving experiences of cancer caregivers. Open family communication about cancer was discussed as one of several practical strategies for decreasing patients' underestimation of CB.
Novel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant ...transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor-initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy.
Microsatellite instability (MSI) refers to the hypermutability of short repetitive sequences in the genome caused by impaired DNA mismatch repair. Although MSI has been studied for decades, large ...amounts of sequencing data now available allows us to examine the molecular fingerprints of MSI in greater detail. Here, we analyse ∼8,000 exomes and ∼1,000 whole genomes of cancer patients across 23 cancer types. Our analysis reveals that the frequency of MSI events is highly variable within and across tumour types. We also identify genes in DNA repair and oncogenic pathways recurrently subject to MSI and uncover non-coding loci that frequently display MSI. Finally, we propose a highly accurate exome-based predictive model for the MSI phenotype. These results advance our understanding of the genomic drivers and consequences of MSI, and our comprehensive catalogue of tumour-type-specific MSI loci will enable panel-based MSI testing to identify patients who are likely to benefit from immunotherapy.
The motion of atoms in a solid always responds to cooling or heating in a way that is consistent with the symmetry of the given space group of the solid to which they belong. When the atoms move, the ...electronic structure of the solid changes, leading to different physical properties. Therefore, the determination of where atoms are and what atoms do is a cornerstone of modern solid-state physics. However, experimental observations of atomic displacements measured as a function of temperature are very rare, because those displacements are, in almost all cases, exceedingly small. Here we show, using a combination of diffraction techniques, that the hexagonal manganites RMnO3 (where R is a rare-earth element) undergo an isostructural transition with exceptionally large atomic displacements: two orders of magnitude larger than those seen in any other magnetic material, resulting in an unusually strong magneto-elastic coupling. We follow the exact atomic displacements of all the atoms in the unit cell as a function of temperature and find consistency with theoretical predictions based on group theories. We argue that this gigantic magneto-elastic coupling in RMnO3 holds the key to the recently observed magneto-electric phenomenon in this intriguing class of materials.
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