MicroRNAs作为肺癌的治疗靶标

肺癌是当今世界的主要致死原因之一,亟待新的治疗方法.近年来,microRNAs已成为调节基因表达的关键因子之一.许多研究表明,microRNAs几乎参与肺癌癌变过程的每一阶段,包括肿瘤的发展、细胞凋亡、癌细胞的侵袭和转移,以及抗癌药物的耐药.MicroRNA的强制表达或抑制可调节癌变过程中的生物学改变,表明了microRNAs在肺癌中具有治疗潜能.本社论总结调节肺癌癌变过程的一些重要microRNAs的最新报道,并阐释其作用机制,介绍一些调控microRNAs作用的方法,并探讨了microRNAs作为肺癌治疗靶标的前景.     

Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever.     

Comparison of bleomycin and radiation in the G2 assay of chromatid breaks

Purpose: To compare bleomycin with radiation in the G2 chromatid break assay. Controversy exists in the literature about whether G2 bleomycin chromatid‐break sensitivity links with cancer predisposition in the same way as the G2 chromatid radiosensitivity test (the so‐called ‘G2 assay’). Although bleomycin is referred to as a ‘radiomimetic’ agent, it differs from radiation in the way the damage is induced.

Materials and methods: Epstein–Barr virus‐immortalized lymphoblastoid cell lines from two head and neck squamous cell carcinoma patients, two breast cancer patients, two ataxia‐telangiectasia patients and two normal control persons were used. Chromosomal damage was determined in cells exposed to 0.3‐Gy radiation or 5?mU?ml^?1 bleomycin. The numbers of chromatid breaks per cell and of aberrations per cell (i.e. breaks and gaps) were determined.

Results: A strong positive correlation was found between the two different damage inducers (r=0.99; p<0.001). This correlation was similar for both the breaks per cell and the total aberrations per cell. Inclusion of gaps in the scoring of chromatid breaks was associated with a higher variability of the data, but this did not influence the outcome of this study.

Conclusions: Both bleomycin and radiation give the same sensitivity phenotypes as determined by the G2 assay of chromatid breaks. Thus, when no radiation facility is present, bleomycin seems to be a good alternative to radiation for this type of assay.     

Use of Restriction Endonucleases to Study Relationships between DNA Double-strand Breaks,Chromosomal Aberrations and Other End-points in Mammalian Cells

Summary

Some of the cellular effects of radiation, such as mutations, chromosomal aberrations and cell killing, can be mimicked by inducing ‘pure’ double-strand breaks (dsb) in DNA of cells with restriction endonucleases (RE), although the chemical structure of the ends of dsb induced by RE are likely to differ from those induced by X-rays. Chromosomal aberrations are induced by treatment of cells with a variety of RE at all stages of the cell cycle. The frequency with which RE induce dsb in the DNA may be one factor determining the number of aberrations induced. However, the structure of the dsb generated may also determine the frequencies of aberrations induced. RE which generate ‘cohesive-ended’ dsb in the DNA have been shown to induce lower frequencies of aberrations than those causing ‘blunt-ended’ dsb, when inactivated Sendai virus is used to permeabilize cells. Other methods, involving a hypertonic shock to the treated cells, have led to results in which there is little or no difference in the effectiveness between the two types of dsb. It is argued here that the use of treatments which cause a hypertonic shock may influence the frequencies of aberrations induced.