UNASSIGNED: 10621 Background: There is a significant site-specific variation in response to chemotherapy for @entity1 @entity5 . Whether subcutaneous non-metastatic xenograft models are representative of clinically metastatic disease remains an unanswered question. Metastatic xenograft models may be ideal and practical for preclinical anti- @entity5 drug evaluation. We evaluated intravitally the time-course efficacy of anti- @entity5 drugs at the metastatic site in the same living @entity19 using two-photon laser scanning microscopy (TPLSM). METHODS: Red fluorescent protein expressing @entity1 @entity14 cell line (HT29) was inoculated to the spleen of green fluorescent protein expressing @entity19 for experimental liver @entity3 models. @entity1487 (50 mg/kg) or @entity2600 (20 mg/kg) was administered intraperitoneally three times a week for three weeks after the confirmation of macroscopic liver metastases. TPLSM was used for intravital visualization of treatment efficacy at a magnification of over 600*. Intravital TPLSM was performed by exteriorizing and fixing the liver lobe of living @entity19 . This procedure was repeated several times for the time-course imaging of treatment efficacy on liver metastases in the same @entity19 . RESULTS: Approximately eight weeks later, HT29 cells formed macroscopic liver metastases. Under the first TPLSM, micrometastatic nodules consisting of viable @entity5 cells (red) and surrounding stroma with @entity5 vessels (green) were visualized in the living liver of living mice. After anti- @entity5 drug treatment, morphologic change of micrometastatic nodules was observed in the same @entity19 under the second TPLSM. The fragmentation of @entity5 cells surrounding residual metastatic colonies was visualized three-dimentionally. There was no apparant morphological difference in @entity5 responsiveness on liver metastases between @entity1487 and @entity2600 . CONCLUSIONS: Intravital time-course visualization of treatment efficacy in the same @entity19 using metastatic xenograft model under TLPSM could be ideal and practical for screening and evaluating new anti- @entity5 drugs with less interindividual variability.

Intravital evaluation of time-course efficacy of anticancer drugs on colorectal liver metastases in the same living XXXX using two-photon laser scanning microscopy.

@entity1 :: ('9606', 'Species') :: ['human'] @entity2600 :: ('MESH:C051890', 'Chemical') :: ['irinotecan'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'solid tumors'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5-fluorouracil']
@entity19 :: (10090,Species) :: ['mice']
