肿瘤节律化疗研究进展

1、.间接作用间接作用直接作用直接作用节律化疗节律化疗持续抑制内皮持续抑制内皮前体细胞动员前体细胞动员抑制肿瘤血管活化内皮抑制肿瘤血管活化内皮细胞生长和细胞生长和/ /或促其凋或促其凋亡亡血管反应素血管反应素1 1抑制肿瘤新生血管抑制肿瘤新生血管CD36CD36阳性阳性内皮细胞生长和内皮细胞生长和/ /或促其凋或促其凋亡亡持续抑制内皮持续抑制内皮前体细胞动员前体细胞动员.1Ang-2Ang-22346875VEGFVEGFsVeikkola T, et al. Semin Cancer Biol. 2001;20:1223-1231.Normalization hypothesis. a | Th

2、e normal vasculature is maintained by pro- and anti-angiogenic signals. b | However, in tumours, excessive amounts of pro-angiogenic factors, such as vascular endothelial growth factor (VE GF) are produced that result in a disrupted and chaotic vasculature. c | Inhibiting VE GF seems to normalize th

3、e vasculature and enable a better blood supply to be transiently established, producing a window where the access and efficacy of chemotherapeutic drugs will be increased. d | However, this window often closes, possibly as a result of over-inhibition of VEGF resulting in reduced blood supply and acc

4、ess by chemotherapeutic drugs. Alternatively, other angiogenic growth factors are secreted and result in abnormal growth of the vasculature and resistance to VE GF-based therapies. Hypothesis used to explain how anti-angiogenic drugs may stop cancer growth and synergize with chemotherapeutics:(a) An

5、ti-angiogenic drugs might induce a normalization of otherwise deficient cancer vessels, provoking a better delivery of chemotherapeutics. Part of the remodeling process would likely cause a shedding of apoptotic CECs and potentially of other vessel-related cells. Hypothesis used to explain how anti-

6、angiogenic drugs may stop cancer growth and synergize with chemotherapeutics: (b) Anti-angiogenic drugs might reduce vessel-driven tumor repopulation during free break periods of chemotherapy. . Hypothesis used to explain how anti-angiogenic drugs may stop cancer growth and synergize with chemotherapeutics: (c) Anti-angiogenic drugs might target proliferating tumor-related ECs and BM-derived CEPs.肿瘤血管密度肿瘤血管密度 节律化疗节律化疗 对照组对照组.化疗的对肿瘤细胞的化疗的对肿瘤细胞的直接杀伤作用直接杀伤作用化疗的对肿瘤间质的破坏化疗的对肿瘤间质的破坏间接