SummaryDNA methylation profiling of TAFs reveals global demethylation and a selective impact on the TGF-β pathway. Moreover, it suggests the fibrocyte origin of a fraction of TAFs, and identifies a novel prognostic biomarker in non-small cell lung cancer.

The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal-or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by b1 integrin mechanosensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in b1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC-TAFs exhibited higher FAK (pY397), b1 expression, and ERK1/2 (pT202/Y204) than ADCTAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC-TAFs (>50%) compared with ADC-TAFs (10%-20%). In contrast, SCC-TAFs were largely serum desensitized, whereas ADC-TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC-TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or b1 integrin-dependent mechano regulation may be effective against SCC-TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC-TAFs.Implications: This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells.

Three of the four instruments tested for root planing reduced surface roughness; however, the piezosurgery ultrasonic scaler produced the smoothest surface. The termination diamond burs (40 μm) produced a rougher surface than the ultrasonic instruments and the hand curettes. Further clinical studies are needed.

To date, there is no effective tool analysis and detection of COPD syndrome, (Chronic Obstructive Pulmonary Disease) which is linked to smoking and, less frequently to toxic substances such as, the wood smoke or other particles produced by noxious gases. According to the World Health Organization (WHO) estimates of this disease show it affects more than 52 million people and kills more than 2.7 million human beings each year. In order to solve the problem, a low-cost Electronic Nose (EN) was developed at the University of Pamplona (N.S) Colombia, for this specific purpose and was applied to a sample group of patients with COPD as well as to others who were healthy. From the exhalation breath samples of these patients, the results were as expected; an appropriate classification of the patients with the disease, as well as from the healthy group was obtained.

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