“…There was a significant difference in primary tumor burden—normalized quantitative indocyanine green (ICG) hindlimb fluorescence [ 14 , 15 ]—between groups (Figure 1 , Table 2 ). High-resolution ICG measurements were unavailable in 14/120 mice, as noted in Table 2 .…”
Section: Resultsmentioning
confidence: 99%
“…While we have previously validated our methodology for measuring primary tumor and metastatic OS burden utilizing quantitative ICG angiography [ 14 , 15 ], our model has limitations. First, previous work has noted that the current safe and effective dose of 5mg/kg of ICG used in this study may not be a high enough concentration to detect small micro-metastasis [ 44 ].…”
IntroductionThe overall survival rate of patients with osteosarcoma (OS) and pulmonary metastases has remained stagnant at 15–30% for several decades. Disulfiram (DSF) is an FDA-approved aldehyde dehydrogenase inhibitor that reduces the metastatic phenotype of OS cells in vitro. Here we evaluate its in vivo efficacy, as compared to doxorubicin chemotherapy, in a previously-validated orthotopic model of metastatic OS.ResultsAll treatment groups displayed a significantly reduced quantitative OS metastatic burden compared with controls. The metastatic burden of Lo DSF-treated animals was equivalent to the DXR group. Ninety-five percent of control animals displayed evidence of metastatic disease, which was significantly greater than all treatment groups.DiscussionDisulfiram treatment resulted in a reduced burden of OS metastatic disease compared with controls. This was statistically-equivalent to doxorubicin. No additive effect was observed between these two therapies.Materials and MethodsOne-hundred twenty immunocompetent Balb/c mice received proximal tibia paraphyseal injections of 5 × 105 K7M2 murine OS cells. Therapy began three weeks after injection: saline (control), low-dose disulfiram (Lo DSF), high-dose disulfiram (Hi DSF), doxorubicin (DXR), Lo DSF + DXR, and Hi DSF + DXR. Transfemoral amputations were performed at 4 weeks. Quantitative metastatic tumor burden was measured using near-infrared indocyanine green (ICG) angiography.
“…There was a significant difference in primary tumor burden—normalized quantitative indocyanine green (ICG) hindlimb fluorescence [ 14 , 15 ]—between groups (Figure 1 , Table 2 ). High-resolution ICG measurements were unavailable in 14/120 mice, as noted in Table 2 .…”
Section: Resultsmentioning
confidence: 99%
“…While we have previously validated our methodology for measuring primary tumor and metastatic OS burden utilizing quantitative ICG angiography [ 14 , 15 ], our model has limitations. First, previous work has noted that the current safe and effective dose of 5mg/kg of ICG used in this study may not be a high enough concentration to detect small micro-metastasis [ 44 ].…”
IntroductionThe overall survival rate of patients with osteosarcoma (OS) and pulmonary metastases has remained stagnant at 15–30% for several decades. Disulfiram (DSF) is an FDA-approved aldehyde dehydrogenase inhibitor that reduces the metastatic phenotype of OS cells in vitro. Here we evaluate its in vivo efficacy, as compared to doxorubicin chemotherapy, in a previously-validated orthotopic model of metastatic OS.ResultsAll treatment groups displayed a significantly reduced quantitative OS metastatic burden compared with controls. The metastatic burden of Lo DSF-treated animals was equivalent to the DXR group. Ninety-five percent of control animals displayed evidence of metastatic disease, which was significantly greater than all treatment groups.DiscussionDisulfiram treatment resulted in a reduced burden of OS metastatic disease compared with controls. This was statistically-equivalent to doxorubicin. No additive effect was observed between these two therapies.Materials and MethodsOne-hundred twenty immunocompetent Balb/c mice received proximal tibia paraphyseal injections of 5 × 105 K7M2 murine OS cells. Therapy began three weeks after injection: saline (control), low-dose disulfiram (Lo DSF), high-dose disulfiram (Hi DSF), doxorubicin (DXR), Lo DSF + DXR, and Hi DSF + DXR. Transfemoral amputations were performed at 4 weeks. Quantitative metastatic tumor burden was measured using near-infrared indocyanine green (ICG) angiography.
“…While the authors address a variety of issues they believe to be imperfections in our methodology, we caution that a more-careful read would reveal that our execution was quite-often synchronous with their suggestions. They note previously published work from their respective institutions [1][2][3][4] has demonstrated that measuring the maximum quantitative perfusion is the most-reliable method for normalizing a variety of potentially confounding host variables. Furthermore, they assert any effort to the contrary would represent an unnecessary ''reinventing of the wheel.''…”
“…While intravenous injection makes the delivery of ICG somewhat more consistent between patients, it does not adequately control for metabolism and tissue thickness. Our group previously proposed using the maximum quantitative blood flow measured in normal tissue within the field of view as a common normalization point [1]. For any points or regions of interest highlighted within an active field, the maximum normal tissue value adjusts for delivery variance, permitting multifield and between-sample comparisons.…”
mentioning
confidence: 99%
“…Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR1 or The Association of Bone and Joint Surgeons 1 .…”
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