G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells

Natori, Takenori; Sata, Masataka; Washida, Miwa; Hirata, Yasunobu; Nagai, Ryozo; Makuuchi, Masatoshi

doi:10.1016/s0006-291x(02)02335-5

Cited by 182 publications

(145 citation statements)

References 17 publications

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“…25 CRC patients also displayed higher levels of G-CSF which has been reported to stimulate angiogenesis and promotes tumor growth. 28 More surprising were the observed higher levels IFN-g which has been reported to exert tumor-suppressive functions protecting the host against tumor formation. 5,10,29,30 However its activity is probably counteracted in the presence of several opposing signals such as those exerted by the other cytokines found to be increased in patients.…”

Section: Discussionmentioning

confidence: 99%

Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors

Crucitti

Corbi

Tomaiuolo

et al. 2015

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors

Crucitti

Corbi

Tomaiuolo

et al. 2015

Cancer Biology & Therapy

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“…Our results suggest that a similar process can also occur independently of tumor with drug-induced up-regulation of multiple proangiogenic growth factors. In this regard, a number of studies have shown that angiogenesis can be induced or amplified by G-CSF (18), SCF (19), SDF-1␣ (20), and osteopontin (21), by diverse mechanisms, including mobilization of circulating bone-marrow-derived proangiogenic cell populations (22), such as endothelial progenitor cells (23). Such effects could conceivably contribute to the rapid vascular ''rebound'' in mouse tumors observed within 1 week of terminating therapy with an RTKI similar in nature to sunitinib (16), results that could clearly have implications for whether a continuous vs. discontinuous schedule of treatment using such drugs would be superior.…”

Section: Discussionmentioning

confidence: 99%

Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy

Ebos

Lee

Christensen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

340

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Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit. A postulated mechanism for these changes is that they are tumor-dependent, resulting from drug-induced decreases in vascular function, increases in tumor hypoxia, and changes in hypoxia-regulated genes. However, here we report that an identical pattern of change is observed in normal nontumor-bearing mice treated with SU11248/sunitinib, a small-molecule inhibitor of VEGF and PDGF RTKs. The changes were dose-dependent, plateaued after 4 days of consecutive treatment, reversed after discontinuation of therapy, and correlated with antitumor activity. Altered protein expression was found in a broad variety of tissues, and dose-dependent elevations were observed of several plasma proteins previously unassociated with this class of inhibitor, including G-CSF, SDF-1␣, SCF, and osteopontin. Our results suggest that observed sunitinib-induced molecular plasma changes, including those both directly and indirectly targeted by drug, represent a systemic tumor-independent response to therapy and may correlate with the most efficacious antitumor doses, potentially having utility for defining the optimal biologic dose range for this drug class but not as predictive markers of tumor response or clinical benefit. They may also be relevant to drug-associated toxicities, drug resistance, and observed rapid tumor (re)growth seen after cessation of therapy.angiogenesis ͉ optimal biological dosing ͉ SU11248 ͉ surrogate biomarkers

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“…Furthermore, our results were accompanied by a total absence of toxicity and in a heavily pretreated, irinotecan-resistant population with progressive disease. Moreover, G-CSF was not administered to patients receiving metronomic irinotecan chemotherapy and as such this could have an advantage, not only in terms of cost but also in terms of avoiding the possibility that the exogenous G-CSF might promote angiogenesis by mobilising circulating endothelial progenitor cells (CEPs) (Natori et al, 2002;Shaked and Kerbel, 2007). Our results suggest that metronomic irinotecan chemotherapy could work through a mechanism of action that is not related to the direct cytotoxic effect on tumour cells but rather through an antiangiogenic activity targeting proliferating endothelial cells as shown in the preclinical setting.…”

Section: Discussionmentioning

confidence: 99%

A pharmacokinetic and pharmacodynamic study on metronomic irinotecan in metastatic colorectal cancer patients

et al. 2008

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The pharmacokinetics (PK) and pharmacodynamics (PD) of metronomic irinotecan have not been studied in cancer patients. The aim of the study is to investigate the PK/PD profile of irinotecan/SN-38 administered by metronomic schedule. Twenty chemotherapyrefractory or chemotherapy-resistant patients with metastatic colorectal carcinoma were enrolled. Irinotecan was infused continuously as follows: irinotecan 1.4 mg m À2 day À1 (n ¼ 7), 2.8 mg m À2 day À1 (n ¼ 5) and 4.2 mg m À2 day À1 (n ¼ 8). Drug levels were examined by HPLC, whereas ELISAs and real-time RT-PCR were used, respectively, for the measurement of plasma levels and gene expression in peripheral blood mononuclear cells of vascular endothelial growth factor/thrombospondin-1. Pharmacokinetic analysis demonstrated that the steady-state levels (C ss ) of SN-38 were between 1 and 3.3 ng ml À1 . From a PD point of view, higher thrombospondin-1 (TSP-1) plasma levels (153.4±30.1 and 130.4±9.2% at day 49 vs pretreatment values at 1.4 and 2.8 mg m À2 day À1 dose levels, respectively) and increased gene expression in PBMC were found during the metronomic irinotecan infusion, especially at the lower doses. Four patients (20%) obtained a stable disease (median 3.9 months) despite progressing during previous standard irinotecan schedule. Toxicities 4grade 1 were not observed. Metronomic irinotecan administration is very well tolerated and induces an increase of gene expression and plasma concentration of TSP-1 at low plasma SN-38 concentrations.

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G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells

Cited by 182 publications

References 17 publications

Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors

Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors

Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy

A pharmacokinetic and pharmacodynamic study on metronomic irinotecan in metastatic colorectal cancer patients

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