RESUMO
Macrophages are traditionally viewed as a key component of the immunity defense system. Recent studies have identified resident macrophages in multiple organs including the heart, in which the cells perform their crucial role on tissue repair after myocardial infarction (MI). The cardiac-specific macrophages interdigitate with cardiomyocytes particularly at the atrioventricular node region. The integrative communication between macrophage and cardiomyocytes can modulate the contractile function of the heart. Coordinated control of intracellular calcium signaling and intercellular electrical conduction via the syncytium network underlie the synchronized beating of the heart. In this review article, we introduce the concept the syncytium calcium signaling in the cardiomyocytes can modulate gene expression in the resident macrophages and their integration with the cardiomyocytes. The cardiac macrophages originate from bone marrow stem cells, migrate to local via vessel, and settle down as a naturalization process in heart. As the macrophages perform on regulating electrical conduction, and accomplish post MI non-scared completed regeneration or partial regeneration with fibrotic scar at different stage of postnatal development, we understand that multiple functions of cardiac macrophage should carry on with diverse linages. The naturalization process in heart of macrophages to the cardiomyocytes serves important roles to control of electrical signaling and calcium-dependent contractile function of the heart.
RESUMO
BACKGROUND: The current standard of care for salvage treatment of glioblastoma multiforme (GBM) is gross total resection and adjuvant chemoradiation for operable patients. Limited evidence exists to suggest that any particular treatment modality improves survival for recurrent GBM, especially if inoperable. We report our experience with fractionated stereotactic radiotherapy (fSRT) with and without chemo/immunotherapy, identifying prognostic factors associated with prolonged survival. METHODS: From 2007 to 2014, 19 patients between 29 and 78 years old (median 55) with recurrent GBM following resection and chemoradiation for their initial tumor, received 18-35 Gy (median 25) in three to five fractions via CyberKnife fSRT. Clinical target volume (CTV) ranged from 0.9 to 152 cc. Sixteen patients received adjuvant systemic therapy with bevacizumab (BEV), temozolomide (TMZ), anti-epidermal growth factor receptor (125)I-mAb 425, or some combination thereof. RESULTS: The median overall survival (OS) from date of recurrence was 8 months (2.5-61) and 5.3 months (0.6-58) from the end of fSRT. The OS at 6 and 12 months was 47 and 32%, respectively. Three of 19 patients were alive at the time of this review at 20, 49, and 58 months from completion of fSRT. Hazard ratios for survival indicated that patients with a frontal lobe tumor, adjuvant treatment with either BEV or TMZ, time to first recurrence >16 months, CTV <36 cc, recursive partitioning analysis <5, and Eastern Cooperative Oncology Group performance status <2 were all associated with improved survival (P < 0.05). There was no evidence of radionecrosis for any patient. CONCLUSION: Radiation Therapy Oncology Group (RTOG) 1205 will establish the role of re-irradiation for recurrent GBM, however our study suggests that CyberKnife with chemotherapy can be safely delivered, and is most effective in patients with smaller frontal lobe tumors, good performance status, or long interval from diagnosis.
