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Assessment of early tumor response to cytotoxic chemotherapy with dynamic contrast-enhanced ultrasound in human breast cancer xenografts.

Wang JW, Zheng W, Liu JB, Chen Y, Cao LH, Luo RZ, Li AH, Zhou JH - PLoS ONE (2013)

Bottom Line: There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy.Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline.CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

ABSTRACT
There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD) and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI) were noticed between adriamycin-treated and control groups (P<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (P<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (P>0.05). Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001). Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.

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Related in: MedlinePlus

Immunohistochemical analysis of tumor MVD changes.A, The graph shows the changes of mean MVD in the control and treated tumors post treatment. There was significant difference in MVD between control and treatment groups on days 2, 4 and 6 (* = P<0.001). B, Representative CD34-stained sections of the control (C) and treated (T) tumors on days 0, 2, 4 and 6. Brown areas reflect positive staining of endothelial cells. Scale bars: 100 µm.
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pone-0058274-g006: Immunohistochemical analysis of tumor MVD changes.A, The graph shows the changes of mean MVD in the control and treated tumors post treatment. There was significant difference in MVD between control and treatment groups on days 2, 4 and 6 (* = P<0.001). B, Representative CD34-stained sections of the control (C) and treated (T) tumors on days 0, 2, 4 and 6. Brown areas reflect positive staining of endothelial cells. Scale bars: 100 µm.

Mentions: There was no significant difference in the tumor microvascular density (MVD) determined by immunohistochemical evaluation of endothelial cell (CD34) density between control and treatment groups before treatment (P = 0.635). In the control group, MVD increased from day 0 to day 2 although not significantly difference (P = 0.106) and then significantly increased on days 4 and 6 as compared with day 0 (P<0.05), while in the treatment group, MVD decreased from day 0 to day 2 although not significantly difference (P = 0.135), and then significantly decreased on days 4 and 6 as compared with day 0 (P<0.05). There was significant difference in MVD between control and treatment groups on days 2, 4 and 6 (P<0.001). (Figure 6).


Assessment of early tumor response to cytotoxic chemotherapy with dynamic contrast-enhanced ultrasound in human breast cancer xenografts.

Wang JW, Zheng W, Liu JB, Chen Y, Cao LH, Luo RZ, Li AH, Zhou JH - PLoS ONE (2013)

Immunohistochemical analysis of tumor MVD changes.A, The graph shows the changes of mean MVD in the control and treated tumors post treatment. There was significant difference in MVD between control and treatment groups on days 2, 4 and 6 (* = P<0.001). B, Representative CD34-stained sections of the control (C) and treated (T) tumors on days 0, 2, 4 and 6. Brown areas reflect positive staining of endothelial cells. Scale bars: 100 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585723&req=5

pone-0058274-g006: Immunohistochemical analysis of tumor MVD changes.A, The graph shows the changes of mean MVD in the control and treated tumors post treatment. There was significant difference in MVD between control and treatment groups on days 2, 4 and 6 (* = P<0.001). B, Representative CD34-stained sections of the control (C) and treated (T) tumors on days 0, 2, 4 and 6. Brown areas reflect positive staining of endothelial cells. Scale bars: 100 µm.
Mentions: There was no significant difference in the tumor microvascular density (MVD) determined by immunohistochemical evaluation of endothelial cell (CD34) density between control and treatment groups before treatment (P = 0.635). In the control group, MVD increased from day 0 to day 2 although not significantly difference (P = 0.106) and then significantly increased on days 4 and 6 as compared with day 0 (P<0.05), while in the treatment group, MVD decreased from day 0 to day 2 although not significantly difference (P = 0.135), and then significantly decreased on days 4 and 6 as compared with day 0 (P<0.05). There was significant difference in MVD between control and treatment groups on days 2, 4 and 6 (P<0.001). (Figure 6).

Bottom Line: There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy.Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline.CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

ABSTRACT
There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD) and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI) were noticed between adriamycin-treated and control groups (P<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (P<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (P>0.05). Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001). Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.

Show MeSH
Related in: MedlinePlus