Since this is a culture-related process, there was no difference in this regard between the cell line pairs. Recently, we published a similar analysis on the success of xenograft establishment of colorectal carcinomas with and without a cryopreservation step. In that analysis, we focused on xenografts since for colorectal carcinomas, they are much more likely successful than primary cell lines. However, for GBM, it is just the other way around. Cell lines of GBM are much easier to generate than xenografts. Not only the engraftment of tumor pieces or biopsies is very time-consuming but also it generally takes 3 regraftment steps until the xenograft acquires a GBM-like phenotype. Last but not least, tumor cell cultures provide an unlimited source of material not only for preclinical analyses but potentially also for individual vaccines basing on autologous antigenpresenting cells and tumor antigens. In the last decade, this methodology not only reached but even surpassed standard clinical procedures. This finding was further confirmed in the study performed by Goette et al. which enrolled 35 AF and 25 non-AF subjects, and demonstrated that ADMA levels were higher in AF patients compared to sinus rhythm patients. However, the question that remains is if the increased ADMA levels are a cause or result in AF? Liu et al. demonstrated that AF could increase the expression of protein arginine methyltransferease-1, which would lead to an increased ADMA concentration. The previous study also showed that ADMA levels decreased to normal values within 24 hours after AF was terminated by electrical cardioversion. These observations suggest that the higher ADMA levels may be a consequence of AF. On the other hand, ADMA was recently demonstrated to have cytokine-like properties by activating polymorphonuclear neutrophils and enhancing the release of myeloperoxidase, which may increase systemic inflammatory burden and play an important role in the pathogenesis of AF. In addition, increased serum ADMA concentrations were reported to be associated with a higher rate of AF recurrence after catheter ablation or electrical cardioversion in patients with persistent AF. These findings may imply that ADMA itself might participate in the process of atrial remodeling and result in the occurrence of AF. Based on the previous findings described above, we hypothesized that the increased ADMA levels may predispose patients to AF, which could further increase the concentration of ADMA and form a vicious cycle. The results of our study support this hypothesis. The observation of higher ADMA levels in PAF patients compared to non-AF patients suggest that ADMA is a cause of AF, and the further increased ADMA levels in non-PAF patients imply that sustained AF could result in an increased concentration of ADMA.Recent studies have suggested that apelin contributes to the pathogenesis of diabetic retinopathy. Apelin was found to play an important role in obesity-related metabolic diseases.
Apelin due to a loss of extra-chromosomal copies of the gene
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