Study on breast cancer animal model of tumor-micro vessel variation before and after the chemotherapy by contrast enhanced ultrasound quantitative analysis

Pak J Pharm Sci. 2016 Jul;29(4 Suppl):1407-13.

Abstract

Aim to discuss whether the contrast enhanced ultrasound (CEUS) can effectively monitor the efficacy on neoadjuvant chemotherapy of breast cancer or not by analyzing the indicators on chemotherapy CEUS and breast cancer tumor biology, especially tumor microcirculation indicator on animal mode. Human breast cancer cell lines MCF-7 are planted under the skins of nude mice. By simulating clinical neoadjuvant chemotherapy regimen periodically inject CMF (cyclophosphamide, methotrexate and fluorouracil) into the experimental group, and normal saline into the control group. Then detect the data from CEUS and record the parameters: maximum intensity (IMAX), rise time (RT), time to peak (TTP) and mean transit time (mTT). Execute animal after CEUS, obtain tumor biological indicator and record parameters: micro vessel density (MVD), vascular endothelial growth factor receptors 1/2/3/4 (VEGFR-1/2/3/4) and tumor cells. In the aspect of tumor biological indicator, the experimental group after the first drug delivery: inter- and intra-group comparisons of VEGFR-1/4drop significantly. The experimental group after the second drug delivery: inter- and intra-group comparisons of MVD, VEGFR-1/3/4drop significantly. In the aspect of parameters on tumor CEUS, the experimental group after the first drug delivery: inter- and intra-group comparisons of IMAX drop significantly. The experimental group after the second drug delivery: inter- and intra-group comparisons of IMAX decrease steeply; while inter-and intra-group comparisons of TTP rise significantly. There are great changes about the intra-group comparisons of the number of tumor cells before and after the experiment. In the process of chemotherapy, it maintains the consistency of the changes of CEUS parameters IMAX and TTP, tumor microcirculation indicators MVD and VEGFR-1/3/4 and tumor cells. So CEUS has a potential to make an early prediction on the efficacy of neoadjuvant chemotherapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Capillaries / diagnostic imaging*
  • Capillaries / pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoadjuvant Therapy
  • Receptors, Vascular Endothelial Growth Factor / genetics
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Ultrasonography
  • Vascular Endothelial Growth Factor A

Substances

  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • Receptors, Vascular Endothelial Growth Factor