Rat TGF-β1 ELISA Kit

Stem cell therapy in combination with genetic modification (e.g., transfection with the coding sequence for the connexin 43 gene, GJA1) may solve the problems associated with the occurrence of additional (secondary) stimulation in the post-infarcted heart (arrhythmia). Human skeletal muscle-derived stem/progenitor cells (SkMDS/PCs) were transfected with the pCiNeo-GJA1 plasmid at an efficiency of approximately 96%. Gene overexpression was assessed using qPCR, and subsequent analysis revealed that GJA1 expression increased more than 40-fold in SkMDS/PCs transfected with the appropriate coding sequence (SkMDS/PCsCX43) compared to that of the 'native' SkMDS/PCs control (SkMDS/PCsWT). Enhanced (4-fold) protein expression of connexin-43 was also confirmed by Western immunoblotting. Furthermore, using the arrhythmic score, we demonstrated the positive effects of SkMDS/PCsCX43 cell intervention in reducing additional secondary stimulations in rat post-infarcted hearts compared with that of wildtype cell delivery. Selected gene responses (Kcnq1, Cacna1c, Ncx1, Serca2a, and Tgfb1) showed significantly altered expression profiles in the rat myocardium upon intervention with SkMDS/PCsCX43. The genetic modification of human skeletal muscle-derived stem/progenitor cells with connexin-43 prevented the proarrhythmic effects of myogenic implanted stem cells on the host myocardium and positively influenced myocardial gene expression profiles in respect to myocardium conductivity.

Purpose: TGF beta 1 plays a critical role in inflammation and immune responses and treatment response and survival. TGF beta 1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP). Experimental Design: We determined tumor HPV16 status and genotyped three TGF beta 1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chemoradiation. Univariate and multivariable Cox models were used to evaluate the associations between the three polymorphisms and survival. Results: Overall, 85% of patients (482 of 564) had HPV16-positive SCCOP. We found that TGFb1 rs1982073 had statistically significant associations with survival, whereas TGF beta 1 rs1800469 and TGF beta 1 rs1800471 did not. Patients with TGF beta 1 rs1982073 CT/CC variant genotypes had significantly better over-all, disease-specific, and disease-free survival compared with those with the corresponding common homozygous TT genotype (all log-rank: P < 0.001). Furthermore, these genotypes were significantly associated with an approximately 5 times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Moreover, the stratified analyses by tumor HPV status indicated that the significant effects of TGF beta 1 rs1982073 polymorphism on survival were found among HPV16-positive SCCOP patients only. Finally, the functional relevance of these variants was further characterized. Conclusions: Our findings support that the TGF beta 1 rs1982073 polymorphism plays a significant role in the prognosis of SCCOP, especially in HPV16-positive SCCOP patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings. Clin Cancer (C) 2018 AACR.