In the context of these results, we conclude that RAGE induces cardiac hypertrophy through the activation of the PKCs-ERK1/2 and NF-κB-NLRP3-IL1β signaling pathway, and suggest that RAGE-NLRP3 may be an important mediator of Ang II-induced cardiomyocyte hypertrophy. In addition, we determined that inhibition of RAGE activation with soluble RAGE (sRAGE) has a protective effect on Ang II-induced cardiomyocyte hypertrophy.

Recurrence is a common complication observed during cutaneous squamous cell carcinoma (cSCC) treatment; however, biomarkers for predicting recurrence in cSCC remain unknown. The present study aimed to investigate the predictive value of axis inhibition protein 2 (AXIN2) and SNAIL expression in cSCC recurrence. AXIN2 and SNAIL expression was evaluated using immunohistochemistry in 111 cSCC tissue samples obtained from 18 patients who presented recurrence (recurrence interval, 1-91 months) and 93 patients who did not experience recurrence following Mohs micrographic surgery (MMS) during the follow-up period (156 months). Nomogram construction was performed using patients' clinicopathological characteristics and AXIN2 and SNAIL protein expression. The results demonstrated that high AXIN2 (histoscore >100) and SNAIL (histoscore >100) expression was detected in 35 and 44 cSCC tissues, respectively. Furthermore, the expression levels of AXIN2 and SNAIL were significantly associated in patients with cSCC (P=0.001). AXIN2 and SNAIL expression levels were significantly associated with tumor size (P=0.021 and P=0.044, respectively) and recurrence of cSCC (P=0.017 and P=0.042, respectively). In addition, the results of the Kaplan-Meier curve analysis revealed that recurrence-free survival was significantly associated with tumor size (P=0.025), differentiation status (P<0.001), AXIN2 expression (P=0.001) and SNAIL expression (P=0.001). Furthermore, the results of the multivariate analysis demonstrated that age (P=0.043), AXIN2 expression (P=0.001) and SNAIL expression (P=0.045) were independent risk factors for cSCC recurrence in the present cohort. A nomogram for predicting the 1-, 2-, 3-, and 5-year recurrence-free survival was developed for patients with cSCC by including independent risk factors with a concordance index of 0.75. The results suggested that high AXIN2 and SNAIL expression may be considered as potential risk factors for cSCC recurrence. This nomogram may therefore be useful to assess the probability of recurrence in patients with cSCC following MMS.

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The incidence of renal cell carcinoma (RCC) is high, and its outcomes remain poor. Mortality is attributable largely to metastatic disease and a dearth of effective therapeutic interventions. The lungs are the most common metastatic site. To elucidate the biological mechanisms underlying pulmonary metastasis and identify superior therapeutic strategies, we developed a novel and clinically relevant murine RCC model exhibiting enhanced pulmonary metastasis. Mice underwent intrarenal implantation using luciferase-expressing Renca, a murine renal adenocarcinoma cell line. Primary renal tumor progression and development of metastatic lung lesions were monitored in live mice using bioluminescent imaging, followed by post-mortem organ assessment. Cells were isolated from pulmonary metastases for reimplantation, followed by repeat monitoring and assessment. This process was repeated once more for a total of two in vivo passages to select for pulmonary metastatic Renca cell subpopulations. However, a single round of in vivo selection was sufficient to produce a near-maximally metastatic subpopulation. Relative to Renca cell-implanted mice, subpopulation-implanted mice exhibited shorter implantation-metastasis intervals (5 days), shorter implantation-moribundity intervals (sacrificed at 18.6±2.9 versus 22.3±1.1 days), a higher number of metastatic lung lesions at 23 days (183.9±39.0 versus 172.6±38.2) and poorer survival. Implantation of cells derived from the second round of in vivo selection produced no further significant differences in the above metrics. This model consistently and efficiently recapitulates RCC pulmonary metastasis while allowing in vivo monitoring of tumor progression, thereby facilitating elucidation of the molecular mechanisms underlying pulmonary metastasis and evaluation of therapeutic modalities.