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We found ≥ 1 CTCs before the first cycle of treatment with bevacizumab in 60% of the patients (n = 24).
ALDH1: aldehyde dehydrogenase 1; CTCs: circulating tumor cells; DTC: disseminated tumor cells; EMT: epithelial-mesenchymal transition; MRD: minimal residual disease; PD: progressive disease; PR: partial remission.
Based on these inferences, (1) CTCs could not pass through endothelium (extravasation) by blocking VEGF VEGFR interaction using pazopanib, (2) reducing metastatic foci in lung, (3) decreasing amount of VEGF and number of CTCs from metastatic site, (4) blocking extravasation step as vicious cycle.
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Fig. 1 CTC-iChip, developed by Ozkumur et al., capable of sorting rare CTCs from whole blood at 107 cells/s [47].
Using the 'offset reciprocal model' for successive deterioration from 0 to 5 CTC, we get hazard ratios of 3.98 (1 vs. 0 CTC), 1.58 (2 vs. 1 CTC), 1.26 (3 vs. 2 CTC), 1.15 (4 vs. 3 CTC) and 1.10 (5 vs. 4 CTC).
None of the normal control samples had >2 CTCs, 1% had 2 CTCs, and 7% had 1 CTC.
One patient with metastatic disease had 13 CTC, one had 4, another had 5 CTC, one had 1 CTC and two had 3 CTC.
Of these, 17 demonstrated no evidence of CTCs, 1 patient had 1 CTC and 1 patient had 3 CTCs.
The patient with resectable disease had 1 CTC.
In the majority of the 247 (20.6%) positive samples (median 1 CTC, range 1 256 CTC) only 1 CTC was detected (n = 148, 12.4%).
From 6 single CTC isolated from one patient, 1 CTC had TP53 R110 delC, 1 CTC showed the TP53 R110 delG mutation, and the remaining 4 single CTCs showed the wild type p53 sequence; a pool of 14 CTCs isolated from the same patient also showed TP53 R110 delC mutation.
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