No abstract

Developing an artificial extracellular matrix that closely mimics the native tissue microenvironment is important for use as both a cell culture platform for controlling cell fate and an in vitro model system for investigating the role of the cellular microenvironment. Electrospinning, one of the methods for fabricating structures that mimic the native ECM, is a promising technique for creating fibrous platforms. It is well-known that align or randomly distributed electrospun fibers provide cellular contact guidance in a single pattern. However, native tissues have hierarchical structures, i.e., topographies on the micro- and nanoscales, rather than a single structure. Thus, we fabricated randomly distributed nanofibrous (720 ± 80 nm in diameter) platforms via a conventional electrospinning process, and then we generated microscale grooves using a femtosecond laser ablation process to develop engineered fibrous platforms with patterned hierarchical topographies. The engineered fibrous platforms can regulate cellular adhesive morphology, proliferation, and distinct distribution of focal adhesion proteins. Furthermore, confluent myoblasts cultured on the engineered fibrous platforms revealed that the direction of myotube assembly can be controlled. These results indicate that our engineered fibrous platforms may be useful tools in investigating the roles of nano- and microscale topographies in the communication between cells and ECM.

BackgroundNon-small-cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations may exhibit primary resistance to EGFR tyrosine kinase inhibitor (TKI). We aimed to examine genomic alterations associated with de novo resistance to gefitinib in a prospective study of NSCLC patients.MethodsOne-hundred and fifty two patients with activating EGFR mutations were included in this study and 136 patients' tumor sample were available for targeted sequencing of genomic alterations in 22 genes using the Colon and Lung Cancer panel (Ampliseq, Life Technologies).ResultsAll 132 patients with EGFR mutation were treated with gefitinib for their treatment of advanced NSCLC. Twenty patients showed primary resistance to EGFR TKI, and were classified as non-responders. A total of 543 somatic single-nucleotide variants (498 missense, 13 nonsense) and 32 frameshift insertions/deletions, with a median of 3 mutations per sample. TP53 was most commonly mutated (47%) and mutations in SMAD4 was also common (19%), as well as DDR2 (16%), PIK3CA (15%), STK11 (14%), and BRAF (7%). Genomic mutations in the PI3K/Akt/mTOR pathway were commonly found in non-responders (45%) compared to responders (27%), and they had significantly shorter progression-free survival and overall survival compared to patients without mutations (2.1 vs. 12.8 months, P=0.04, 15.7 vs. not reached, P<0.001). FGFR 1-3 alterations, KRAS mutations and TP53 mutations were more commonly detected in non-responders compared to responders.ConclusionGenomic mutations in the PI3K/Akt/mTOR pathway were commonly identified in non-responders and may confer resistance to EGFR TKI. Screening lung adenocarcinoma patients with clinical cancer gene test may aid in selecting out those who show primary resistance to EGFR TKI (NCT01697163).

Abstract. abnormal expression of let-7a microrna (mirna) in non-small cell lung cancer (nSclc) cells and tissue has been previously reported. our objective was to investigate whether let-7a mirna is aberrantly expressed in the blood of nSclc patients. using real-time Pcr (rT-Pcr), we analyzed let-7a mirna in archived whole blood from 65 participants, 35 of whom had nSclc and 30 of whom did not. using rT-Pcr, we also investigated the expression of let-7a mirna in nSclc cell lines (a549 and Hcc 1588), a normal human lung fibroblast cell line (WI-38) and in 40 human nSclc tissues. The 2 -ddct of let-7a mirna in the blood of normal subjects and those with nSclc was 3242.49±355.28 and 747.85±177.74, respectively. The relative expression of let-7a mirna in the a549 and Hcc 1588 cancer cell lines was approximately 0.3 and 0.35, respectively, compared to WI-38 cells. The 2 -ddct of let-7a mirna in the normal human lung tissues and human nSclc tissues was 42.30±3.98 and 27.73±3.86, respectively. let-7a mirnas were underexpressed in the blood of nSclc patients, as well as nSclc cells and nSclc tissues, compared to normal controls. The possibility of using let-7a mirna as a serologic marker for lung cancer warrants further study.

MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression in human diseases, including lung cancer. miRNAs have oncogenic and nononcogenic functions in lung cancer. In this study, we report the identification of a novel miRNA, miR-7515, from lung cancer cells. The novel miR-7515 was characterized using various predictive programs and experimental methods. miR-7515 was able to forming a stem-loop structure and its sequence was conserved in mammals. The expression level of miR-7515 in lung cancer cells and tissues was profiled using TaqMan miRNA assays. miR-7515 was downregulated in lung cancer compared with normal human lung cells and tissues. The target of miR-7515 was determined using a dual luciferase reporter assay. IntroductionThe first microRNA (miRNA) was discovered in Caenorhabditis elegans, (1, 2) and there are currently more than 1,500 human miRNAs listed in miRBase (http://microrna.sanger.ac.uk/index.shtml; ref. 3). miRNAs are endogenous noncoding RNAs that are 18 to 25 nucleotides (nt) in length and are derived from 60 to 80 nt precursor miRNAs refs. 4,5). The stepwise processing of miRNAs requires the double strand-specific ribonuclease (Drosha), the RNase III enzyme Dicer, and the

Myasthenia gravis (MG) is often complicated by respiratory failure, known as a myasthenic crisis. However, most of the patients who develop respiratory symptoms do so during the late course of disease and have other neurological signs and symptoms. However, in some patients respiratory failure is the initial presenting symptom. We report the case of a 68-year-old woman with MG who presented with isolated respiratory failure as her first presenting symptom. As illustrated by this case, it is important to consider neuromuscular disorders in cases of unexplained respiratory failure. (Korean J Intern Med 2010;25:101-104)

No abstract

No abstract