RESUMO
BACKGROUND: Angiogenesis is crucial for tissue repair and cancer progression. We investigated a panel of angiogenic cells, macroparticles and RNA transcripts before, during and after laparoscopic colectomy or open colectomy for colorectal cancer. RESULTS: Viable and apoptotic circulating endothelial cells were significantly increased after open but not after laparoscopic colectomy (p < 0.01). A significant decrease of circulating mRNA coding for VEGFR-C and D and PDGFR-ß was found after laparoscopic but not after open colectomy. METHODS: A total of 24 patients were enrolled. Viable and apoptotic circulating endothelial cells, progenitors and macroparticles were evaluated by flow cytometry. The number of copies of angiogenesis-related RNA transcripts we reevaluated by quantitative PCR. CONCLUSION: Open, but not laparoscopic colectomy, was associated with a significant post-operative increase in circulating endothelial cells, either apoptotic (likely due to surgery-related vascular damage) and viable (likely representing vascular remodeling). Circulating RNA copies coding for some angiogenic genes were significantly decreased after laparoscopic colectomy likely because of the removal of the tumor lesion. This decrease was not observed after open colectomy,were a more pronounced wave of angiogenesis related to wound healing was expected. These results indicate a relevant wave of angiogenesis-related cells and transcripts after open but not after laparoscopic colectomy.
Assuntos
Colectomia/métodos , Neoplasias Colorretais/cirurgia , Células Endoteliais/metabolismo , Laparoscopia/métodos , RNA/sangue , Idoso , Apoptose , Sobrevivência Celular , Neoplasias Colorretais/sangue , Células Endoteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Período Pós-Operatório , Período Pré-Operatório , RNA/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Fator C de Crescimento do Endotélio Vascular/genética , Fator D de Crescimento do Endotélio Vascular/genéticaRESUMO
PURPOSE: The association of chemotherapy and antiangiogenic drugs has shown efficacy in clinical oncology. However, there is a need for biomarkers that allow selection of patients who are likely to benefit from such treatment and are useful for indicating best drug combination and schedule. EXPERIMENTAL DESIGN: We investigated the predictive potential of six angiogenic molecules/transcripts and nine subpopulations of circulating endothelial cells (CEC) and progenitors (CEP) in 46 patients with advanced breast cancer treated with metronomic cyclophosphamide and capecitabine plus bevacizumab. RESULTS: Median time to progression was 281 days. Baseline CECs higher than the first quartile were associated with an increased time to progression (P = 0.021). At progression, CECs were markedly reduced (P = 0.0002). In the cohort of 15 long-term responders, who progressed later than 1 year after beginning of therapy, circulating vascular endothelial growth factor (VEGF)-A levels measured after 2 months of therapy were significantly reduced, and there were significant trends toward lower levels of PDGF-BB, CEPs, and CECs. At the time of progression, angiogenic growth factors VEGF-A and basic fibroblast growth factor were significantly increased. CONCLUSIONS: Baseline CECs (likely reflecting an active vascular turnover) predicted a prolonged clinical benefit. At the time of relapse, a pattern of decreased CECs and increased angiogenic growth factors suggested a switch toward a different type of cancer vascularization. VEGF-A and basic fibroblast growth factor levels after 2 months of therapy were also useful to identify patients whose disease was likely to progress. These biomarkers are likely to be useful for treatment selection and might be incorporated in design of future studies. (Clin Cancer Res 2009;15(24):7652-7).
