Tele-ICU: the way forward in geriatric care?

Aging population is set to increase in the near future, and will need specialized care when admitted to ICUs. The elderly are beset with chronic conditions, such as cardiovascular, COPD, diabetes, renal complications and depression. Specialist opinions can now be made available through telemedicine facilities. Tele-ICU is a specialized hub consisting of highly skilled staff trained in critical care able to deliver timely, quality care service to patients admitted to ICUs in remote areas using highly advanced information technology services. These specialists in the tele-ICU hub are able to analyze and gather data arriving at timely interventional management decisions and provide this vital feedback to the nursing staff and doctors manning remote ICU locations where specialized intensivist may not be available. Known clinical benefits of such a system include better patient outcomes, reduced medical errors, mortality and reduced hospital length of stay. The main disadvantage in implementation could be the upfront high cost involved, for which low-cost models are being explored. In the face of delivering such remote care, it is up to the local health policy to make legislative changes to include associated legal and ethical issues. Considering the burgeoning aging population, tele-ICU could become the way forward in delivering geriatric critical care.

Identification of potential biomarkers for clear cell renal cell carcinoma based on microRNA-mRNA pathway relationships.

BACKGROUND: MicroRNAs (miRNAs) play important roles in tumor genesis. miRNA dysregulation has been widely studied and demonstrated in clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We applied a newly proposed method for selecting miRNAs that discriminate between healthy controls and cancers. We initially extracted different miRNAs and mRNAs and then selected miRNA-mRNA dysregulation pairs. The pathways that involved mRNAs were acquired according to the functional enrichment. We integrated the miRNAs, mRNAs, and pathways and constructed the miRNA-mRNA pathway relationships based on the derived significant miRNAs. RESULTS: We acquired 566 antiregulated miRNA-mRNA pairs including 56 miRNAs and 485 mRNAs. Three significant pathways related to ccRCC, namely, arginine and proline metabolism, aldosterone-regulated sodium reabsorption, and oxidative phosphorylation, were observed. Based on the miRNA-mRNA pathway relationships, five significant miRNAs were identified as potential biomarkers: hsa-miR-425, hsa-miR-136, hsa-miR-335, hsa-miR-340, and hsa-miR-320d. CONCLUSION: This integrative network approach revealed important miRNAs in the ccRCC that can identify specific disease biomarkers, which can be used as targets for cancer treatment.

Tamoxifen represses miR-200 microRNAs and promotes epithelial-to-mesenchymal transition by up-regulating c-Myc in endometrial carcinoma cell lines.

Although tamoxifen (TAM), a selective estrogen receptor modulator, has been widely used in the treatment of hormone-responsive breast cancer, its estrogen-like effect increases the risk of endometrial cancer. However, the molecular mechanisms of TAM-induced endometrial carcinoma still remain unclear. In this report, we explored the role of microRNAs (miRNAs) in TAM-induced epithelial-mesenchymal transition (EMT) in ECC-1 and Ishikawa endometrial cancer cell lines and found miR-200 is involved in this process via the regulation of c-Myc. When treated with TAM, ECC-1 and Ishikawa cells were characterized by higher invasiveness and motility and underwent EMT. miR-200, a miRNA family with tumor suppressive functions in a wide range of cancers, was found reduced in response to TAM treatment. Consistent with zinc finger E-box binding homeobox 2, which was confirmed as a direct target of miR-200b in endometrial cancer cell lines, some other key factors of EMT such as Snail and N-cadherin increased, whereas E-cadherin decreased in the TAM-treated cells, contributing to TAM-induced EMT in these endometrial cancer cells. In addition, we showed that c-Myc directly binds to and represses the promoter of miR-200 miRNAs, and its up-regulation in TAM-treated endometrial cancer cells leads to the down-regulation of miR-200 and eventually to EMT. Collectively, our data suggest that TAM can repress the miR-200 family and induce EMT via the up-regulation of c-Myc in endometrial cancer cells. These findings describe a possible mechanism of TAM-induced EMT in endometrial cancer and provide a potential new therapeutic strategy for it.

TSA suppresses miR-106b-93-25 cluster expression through downregulation of MYC and inhibits proliferation and induces apoptosis in human EMC.

Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to decrease proliferation and increase apoptosis in different cancer cells. A significant number of genes have been identified as potential effectors responsible for the anti-tumor function of HDAC inhibitor. However, the molecular mechanisms of these HDAC inhibitors in this process remain largely undefined. In the current study, we searched for microRNAs (miRs) that were affected by HDAC inhibitor trichostatin (TSA) and investigated their effects in endometrial cancer (EMC) cells. Our data showed that TSA significantly inhibited the growth of EMC cells and induced their apoptosis. Among the miRNAs that altered in the presence of TSA, the miR-106b-93-25 cluster, together with its host gene MCM7, were obviously down-regulated in EMC cells. p21 and BIM, which were identified as target genes of miR-106b-93-25 cluster, increased in TSA treated tumor cells and were responsible for cell cycle arrest and apoptosis. We further identified MYC as a regulator of miR-106b-93-25 cluster and demonstrated its down-regulation in the presence of TSA resulted in the reduction of miR-106b-93-25 cluster and up-regulation of p21 and BIM. More important, we found miR-106b-93-25 cluster was up-regulated in clinical EMC samples in association with the overexpression of MCM7 and MYC and the down-regulation of p21 and BIM. Thus our studies strongly indicated TSA inhibited EMC cell growth and induced cell apoptosis and cell cycle arrest at least partially through the down-regulation of the miR-106b-93-25 cluster and up-regulation of it's target genes p21 and BIM via MYC.

Estrogen-induced dimerization and activation of ERα-fused caspase-8: artificial reversal of the estrogenic hormone effect in carcinogenesis.

The cascade of caspase processing and activation is the core of apoptotic cell signaling. Initiator caspases are activated by adaptor-mediated clustering, which allows the intermolecular autoprocessing of the zymogens in close proximity. Caspase-8, the prototypical initiator critically involved in apoptosis induced by varied extrinsic stimuli, is physiologically recruited via a classical FasL/Fas/FADD pathway. Meanwhile, artificial models of caspase-8 activation have been proposed via inducible dimerization of a heterologous domain fused to the zymogen. Here, we describe the generation of a chimeric protein of caspase-8 and the ligand-binding domain (LBD) of estrogen receptor α (ERα), which dimerizes and undergoes autocleavage upon engagement by the ligand, estradiol. Breast cancer cells expressing this fusion protein exhibit apoptotic cell death in vitro and suppressed tumor growth in xenograft nude mice models in response to the administration of estrogen. Thus, the suicidal caspase-8/ERα-LBD protein, which reverses the mitogenic effects of estrogens, has potential to provide novel approaches to treating estrogen-dependent and -independent breast cancers.