Ye, Hong* Dotaz Zobrazit nápovědu
BACKGROUND: We aimed to systematically summarize the diagnostic and prognostic value of circulating/tissue miR21 in patients with colorectal cancer. METHODS: An original study was conducted to explore the potential value of circulating miR21 in colorectal cancer diagnosis and tissue miR21 in colorectal cancer prognosis. PUBMED and EMBASE were searched (to August, 2013) to identify eligible studies. To explore the diagnostic performance of circulating miR21, meta-analysis methods were used to pool sensitivity, specificity, positive and negative likelihood ratio, diagnostic OR and to construct a summary ROC curve. For prognostic meta-analysis, study-specific HRs of tissue miR21 for survival were summarized. Subgroup and sensitivity analyses were applied to explore heterogeneity. RESULTS: Finally, 14 studies (including our study) were included in the meta-analyses. The pooled sensitivity, specificity, and AUC of circulating miR21 were 0.76 [95% confidence interval (CI), 0.59-0.88], 0.81 (95% CI, 0.76-0.85), and 0.81 (95% CI, 0.78-0.85) in diagnosing colorectal cancer. Patients with higher expression of tissue miR21 had significant inferior overall survival (OS; pooled HR, 1.56; 95% CI, 1.16-2.11) and disease-free survival (DFS; pooled HR, 1.35; 95% CI, 1.08-1.69). The individual participant data (IPD) meta-analysis demonstrated that tissue miR21 level was independently associated with worse colorectal cancer OS (HR, 1.69; 95% CI, 1.07-2.67; P = 0.023), whereas this association seems to be confined to males (P = 0.007) but not for females (P = 0.845). CONCLUSIONS: Circulating miR21 level has potential value for colorectal cancer early detection, whereas high tissue miR21 level is associated with adverse colorectal cancer prognosis. IMPACT: miR21 is a promising biomarker for early detection and prognosis of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 23(12); 2783-92. ©2014 AACR.
We synthesized Fe foams using water suspensions of micrometric Fe2O3 powder by reducing and sintering the sublimated Fe oxide green body to Fe under 5% H2/Ar gas. The resultant Fe foam showed aligned lamellar macropores replicating the ice dendrites. The compressive behavior and deformation mechanism of the synthesized Fe foam were studied using an acoustic emission (AE) method, with which we detected sudden localized structural changes in the Fe foam material. The evolution of the deformation mechanism was elucidated using the adaptive sequential k-means (ASK) algorithm; specifically, the plastic deformation of the cell struts was followed by localized cell collapse, which eventually led to fracturing of the cell walls. For potential biomedical applications, the corrosion and biocompatibility characteristics of the two synthesized Fe foams with different porosities (50% vs. 44%) were examined and compared. Despite its larger porosity, the superior corrosion behavior of the Fe foam with 50% porosity can be attributed to its larger pore size and smaller microscopic surface area. Based on the cytotoxicity tests for the extracts of the foams, the Fe foam with 44% porosity showed better cytocompatibility than that with 50% porosity.
- MeSH
- akustika * MeSH
- biokompatibilní materiály chemie toxicita MeSH
- buněčné linie MeSH
- difrakce rentgenového záření MeSH
- elektrochemie metody MeSH
- fibroblasty MeSH
- koroze MeSH
- myši MeSH
- pevnost v tlaku MeSH
- poréznost MeSH
- testování materiálů MeSH
- viskoelastické látky chemie MeSH
- železité sloučeniny chemie MeSH
- železo chemie toxicita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. METHODS: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. RESULTS: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. CONCLUSION: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.
- MeSH
- dospělí MeSH
- intrakraniální arteriovenózní malformace * radioterapie chirurgie MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- radiochirurgie * MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVE: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). METHODS: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. RESULTS: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. CONCLUSIONS: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.
- MeSH
- dospělí MeSH
- intrakraniální arteriovenózní malformace * diagnostické zobrazování radioterapie chirurgie MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- radiochirurgie * škodlivé účinky metody MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBPα (CCAAT/enhancer binding protein α) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBPα suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBPα expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBPα expression and positive expression of the oncogenic protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic value. We also generated a lung-specific mouse model of C/EBPα deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBPα-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBPα is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBPα loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBPα and high BMI1.
- MeSH
- adenokarcinom genetika metabolismus patologie terapie MeSH
- lidé MeSH
- mutace genetika MeSH
- myši knockoutované MeSH
- myši MeSH
- nádory plic genetika metabolismus patologie terapie MeSH
- PRC1 genetika metabolismus MeSH
- protein alfa vázající zesilovač transkripce CCAAT genetika metabolismus MeSH
- protoonkogenní proteiny genetika metabolismus MeSH
- regulace genové exprese u nádorů genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.
- MeSH
- autoimunita genetika MeSH
- autoimunitní nemoci * epidemiologie genetika MeSH
- chřipka lidská * epidemiologie genetika MeSH
- lidé MeSH
- narkolepsie * chemicky indukované genetika MeSH
- vakcíny proti chřipce * škodlivé účinky MeSH
- virus chřipky A, podtyp H1N1 * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
- MeSH
- dítě MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- genová ontologie MeSH
- genové regulační sítě MeSH
- jednonukleotidový polymorfismus MeSH
- kohortové studie MeSH
- kojenec MeSH
- kouření škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 15 genetika MeSH
- lokus kvantitativního znaku genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory plic genetika MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- reprodukovatelnost výsledků MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
- MeSH
- adenokarcinom genetika MeSH
- běloši genetika MeSH
- celogenomová asociační studie * MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- homeostáza telomer genetika MeSH
- jednonukleotidový polymorfismus MeSH
- kouření epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokus kvantitativního znaku MeSH
- mapování chromozomů MeSH
- nádory plic epidemiologie etnologie genetika MeSH
- senioři MeSH
- zdraví rodiny MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
- MeSH
- fylogeneze MeSH
- lidé MeSH
- Mononegavirales * genetika MeSH
- viry * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
