The association between telomere length (TL) in peripheral blood cells and cancer risk remains inconclusive. We carried out a meta-analysis on prospective studies. The study-specific RR estimates were first transformed to a common comparable scale and then were pooled by a random-effects model. The dataset was composed of 13,894 cases and 71,672 controls from 28 studies in 25 articles. In the comparison of the longest versus shortest third of TL, we observed a marginally positive association between longer TL and higher risk of total cancers [OR = 1.086; 95% confidence interval (CI), 0.952-1.238]. Subgroup analyses showed that the association was stronger in lung cancer ( = 3; OR = 1.690; 95% CI, 1.253-2.280), in men ( = 6; OR = 1.302; 95% CI, 1.120-1.514) and in studies with more precise methods for DNA extraction (phenol-chloroform, salting-out or magnetic bead, = 6, OR = 1.618; 95% CI, 1.320-1.985) and TL measurement (multiplex Q-PCR, = 8; OR = 1.439; 95% CI, 1.118-1.852). Our meta-analysis suggested longer TL in peripheral blood cells is a likely risk factor for lung cancer or cancers in men. Accurate DNA extraction and TL measurement methods make it more liable to find significant associations between TL and cancer risk and thus should be taken into consideration in future epidemiologic studies. .
ObjectiveMicroRNAs (miRNAs) play a vital role in pathogenesis and progression of many cancers, including cervical cancer. However, importance of serum level of miR-101 in cervical cancer has rarely been studied. In the present study, clinical significance and prognostic value of serum miR-101 for cervical cancer was investigated.MethodsAssociation between miR-101 level in cervical cancer tissues and prognosis of patients was analyzed by using data retrieved from The Cancer Genome Atlas (TCGA) database, which was followed with our clinical study in which miR-101 serum level comparison between cervical cancer patients and healthy controls was conducted by real-time quantitative polymerase chain reaction (PCR).ResultsTCGA database demonstrated that miR-101 was down-regulated in cervical cancer tissues compared with normal cervical tissues, and univariate Cox regression analysis indicated that decreased miR-101 expression was a highly significant negative risk factor. Similar trend was found in the serum miR-101. Serum level of miR-101 was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.003), lymph node metastasis (p=0.001), and serum squamous cell carcinoma antigen (SCC-Ag) level >4 (p=0.007). The overall survival time of cervical cancer patients with a higher level of serum miR-101 was significantly longer than that of patients with a lower level of serum miR-101. Moreover, multivariate Cox regression analysis indicated that the down-regulated serum level of miR-101 was an independent predictor for the unfavorable prognosis of cervical cancer.ConclusionSerum level of miR-101 is closely associated with metastasis and prognosis of cervical cancer; and, hence could be a potential biomarker and prognostic predictor for cervical cancer.
The development of vehicles driving foreign DNA into the cell nucleus is essential for effective cellular gene transfer applications. We report that noncovalent binding of nuclear localization signal (NLS) peptides to plasmid DNA enhances nuclear uptake of the DNA and promotes germline integration, inheritance, and expression of a single copy of a luciferase reporter gene in zebrafish. As few as 10 DNA-NLS complexes (0.06 fg plasmid DNA) cytoplasmically injected are sufficient to produce germline-transgenic zebrafish bearing a single copy of the transgene. This corresponds to a 10(5)-fold reduction in DNA concentration compared to commonly used procedures. Use of 10(3) or 10(4) DNA-NLS complexes augments the number of transgene integrations, which occur mostly within 1-4 distinct insertion sites in the genome. In situ hybridization analyses and transmission studies show that transgene integration into the germline and somatic tissues is mosaic, and that the extent of mosaicism is negatively correlated with the amount of DNA-NLS injected. In addition, a larger proportion of zebrafish harboring a single copy of the transgene expresses luciferase, albeit at a 10-fold lower level than those containing numerous transgene insertions. The data demonstrate the potential use of nuclear targeting peptides noncovalently bound to vector DNA to enhance the efficiency of biotechnological nonviral gene transfer applications.
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