Two tumor specimens were cultured ex vivo: (a) GSK1120212 (0.1 microM) alone induced apoptosis concomitantly with pS6 decrease; (b) everolimus (1microM) or BKM120 (0.1microM) alone exerted ...antiproliferative but no cytotoxic effects; (c) combinations resulted in higher caspase 3 levels and decrease pS6 than MEKi alone.
Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models ...as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies.
► PlGF inhibition phenocopies genetic deficiency in tumor models and ocular angiogenesis ► PlGF inhibition blocks vessel abnormalization rather than density in certain tumors ► Anti-mouse and anti-human PlGF antibodies are specific and efficacious ► Anti-PlGF treatment lacks efficacy in some cancer models
Curative surgery of synchronous peritoneal metastases (PM) and colorectal liver metastases (LM) has been recently investigated as feasible option. When synchronous peritoneal and liver resection is ...not achievable, the sequence of the surgery remains unknown. Our hypothesis was that liver resection (LR) promotes peritoneal growth resulting in a non-resectable PM. We sought to analyse the effects of major LR and liver regeneration after hepatectomy in a murine model of PM and the associated angiogenesis.
Murine model of colorectal PM in Balb/C mice was developed by intraperitoneal injection of different CT-26 tumour cell concentrations. Five days after the injection, mice were randomized into three groups: 68% hepatectomy group, sham laparotomy and control group without surgery. On post-operative days 1, 5 and 20, PM was evaluated macroscopically, tumour growth and liver regeneration by immunohistochemistry, and angiogenesis by immunofluorescence. Circulating progenitor cells, plasmatic cytokines and digestive arterial blood flow velocity measurements were also analysed.
Reproducible murine model of limited colorectal PM was obtained. Surgery induced PM increases and promoted neo-angiogenesis. Major hepatectomy influence the tumour growth in the late phase after surgery, the extent of extra-peritoneal metastasis and the increase of Ki-67 expression in the remnant liver.
This animal model confirms the pro-tumoural and pro-angiogenic role of surgery, laparotomy and major LR, which promotes the increase of angiogenic factors and their participation in PM growth. These results suggest that peritoneal resection should be first step in the case of two-step liver and peritoneal surgery for patients with colorectal PM and LM.
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