This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Background: As the survival rate of cancer patients increases, the clinical importance of rehabilitation provided by healthcare professionals also increases. However, the evidence supporting the relevance of rehabilitation programs is insufficient. This study aimed to review the literature on effectiveness in physical function, quality of life (QOL) or fatigue of supervised physical rehabilitation in patients with advanced cancer. Methods: A systematic review and meta-analysis was conducted following the Cochrane guidelines. We narratively described the results when meta-analysis was not applicable or appropriate. Literature databases including Ovid-MEDLINE, Ovid-EMBASE, and the Cochrane Library, as well as several Korean domestic databases, were searched up to June 2017 for studies that investigated the effectiveness of supervised physical rehabilitation programs on physical function, QOL or fatigue in patients with advanced cancer. The quality of the selected studies was evaluated independently by paired reviewers. Results: Eleven studies with 922 participants were finally selected among 2,459 articles. The meta-analysis revealed that after physical exercise, the physical activity level and strength of patients with advanced cancer increased significantly. The QOL showed a statistically significant improvement after physical rehabilitation according to the European Organization for Research and Treatment of Cancer version C30. Though some of measurements about cardiovascular endurance or strength in several studies were not able to be synthesized, each study reported that they were significantly improved after receiving rehabilitation. Conclusion Supervised physical rehabilitation for patients with advanced cancer is effective in improving physical activity, strength, and QOL. However, more trials are needed to prove the effectiveness of supervised exercise and to strengthen the evidence.