Aberrant BLM cytoplasmic expressionassociates with DNA damage stress and hypersensitivity to DNA-damaging agents in colorectal cancer

Background Bloom syndrome is a rare and recessive disorder characterized by loss-of-function mutations of the BLM gene, which encodes a RecQ 30–50 DNA helicase. Despite its putative tumor suppressor function, the contribution of BLM to human sporadic colorectal cancer (CRC) remains poorly understood. Methods The transcriptional regulation mechanism underlying BLM and related DNA damage response regulation in independent CRC subsets and a panel of derived cell lines was investigated by bioinformatics analysis, the transcriptomic profile, a CpG island promoter methylation assay, Western blot, and an immunolocalization assay. Results In silico analysis of gene expression data sets revealed that BLM is overexpressed in poorly differentiated CRC and exhibits a close connection with shorter relapsefree survival even after adjustment for prognostic factors and pathways that respond to DNA damage response through ataxia telangiectasia mutated (ATM) signaling. Functional characterization demonstrated that CpG island promoter hypomethylation increases BLM expression and associates with cytoplasmic BLM mislocalization and increased DNA damage response both in clinical CRC samples and in derived cancer cell lines. The DNA-damaging agent S-adenosylmethionine suppresses BLM expression, leading to the inhibition of cell growth following accumulation of DNA damage. In tumor specimens, cytoplasmic accumulation of BLM correlates with DNA damage and cH2AX and phosphorylated ATM foci and predicts long-term progression-free survival in metastatic patients treated with irinotecan. Conclusions Taken together, the findings of this study provide the first evidence that cancer-linked DNA hypomethylation and cytosolic BLM mislocalization might reflect compromised levels of DNA-repair activity and enhanced hypersensitivity to DNA-damaging agents in CRC patients

Y RNA: an overview of their role as potential biomarkers and molecular targets in human cancers

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients

Non-coding RNAs and endometrial cancer

Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular

Minimally invasive fetal autopsy using three-dimensional ultrasound. a feasibility study

We aim to evaluate a new technique for minimally invasive autopsy: the Post-Mortem Ultrasound (PM-US). Our purpose is to demonstrate its feasibility and sensitivity in detecting major congenital abnormalities as compared to conventional autopsy

Minimally invasive fetal autopsy using ultrasound: a feasibility study

We aim to evaluate a new technique for minimally invasive autopsy: the Post-Mortem Ultrasound (PM-US). Our purpose is to demonstrate its feasibility and sensitivity in detecting major congenital abnormalities as compared to conventional autopsy

Fetal fibronectin as predictor of successful induction of mid-trimester abortion.

BACKGROUND: Fetal fibronectin (FFN) in cervical secretion is one of the most effective markers of pre-term and term delivery. The presence of FFN in cervicovaginal secretions has recently been shown to reflect cervical state and an uncomplicated induction of labor at term. This study was designed to determine whether FFN could be a biochemical marker to predict the response to prostaglandins in early mid-trimester abortion. METHODS: The presence of cervical FFN was evaluated by means of qualitative rapid immunoassay in 270 patients, who required second trimester termination of pregnancy at the Department of Gynecology and Obstetrics, University of Naples 'Federico II'. According to the standard protocol of our unit, women received 1.0 mg of gemeprost intravaginally at 3-hr intervals up to a maximum of five suppositories. The induction-to-abortion interval and the percentage of successful abortions within 24 hr in women in the positive FFN group (n=19) were compared with those in the negative FFN group (n=251). RESULTS: FFN in the cervical secretions was present in seven women (10.2%) at 16-weeks gestation, in seven women (7.5%) at 17-weeks gestation, and in five women (4.5%) at 18-week gestation. Final termination rates were 13 (68.4%) in the fibronectin-positive group and 177 (70.5%) in the fibronectin-negative group. The median abortion interval was similar (14.7 versus 15.1 hr) in both groups. CONCLUSIONS: A positive cervical fetal fibronectin test does not predict a successful medical termination of pregnancy in second trimester abortion. In this setting, the role of fetal cervical fibronectin in cervical ripening is, therefore, questionable