Experimental Study on Residual Tumor Angiogenesis after Cryoablation

  • Ma, Chun-Hua ;
  • Jiang, Rong ;
  • Li, Jin-Duo ;
  • Wang, Bin ;
  • Sun, Li-Wei ;
  • Lv, Yuan
  • Published : 2014.03.30


Objective: To explore the mechanism and significance of tumor angiogenesis by observing changes of microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in residual tumor tissues after cryoablation. Materials and Methods: A total of 18 nude mice xenograft models with transplanted lung adenocarcinoma cell line A549 were established and randomly divided into 3 groups when the maximum diameter of tumor reached 1 cm: control, cisplatin (DDP) and cryoablation. The nude mice were sacrificed after 21-d cryoablation to obtain the tumor tissues. Then immunohistochemistry was applied to determine MVD and the expression of VEGF in tumor tissues. Results: The tumor volumes of control group, DDP group and cryoablation group were $1.48{\pm}0.14cm^3$, $1.03{\pm}0.12cm^3$ and $0.99{\pm}0.06cm^3$ respectively and the differences were significant (P<0.01), whereas MVD values were $21.1{\pm}0.86$, $24.7{\pm}0.72$ and $29.2{\pm}0.96$ (P<0.01) and the positive expression rates of VEGF were $36.2{\pm}1.72%$, $39.0{\pm}1.79%$ and $50.8{\pm}2.14%$ (P<0.01), respectively, showing that MVD was proportional to the positive expression of VEGF (r=0.928, P<0.01). Conclusions: Cryoablation can effectively inhibit tumor growth, but tumor angiogenesis significantly increases in residual tumors, with high expression of VEGF playing an important role in the residual tumor angiogenesis.


Cryoablation;transplanted tumor;A549 lung adenocarcinoma cells;VEGF;microvessel density


  1. Ueda M, Terai Y, Kurnagai K, et al (1999). Correlation between tumor angiogenesis and expression of thymidine phosphorylase, and patient outcome in uterine cervical carcinoma. Hum Pathol, 30, 1389-94.
  2. Madjd Z, Akbari ME, Zarnani AH, et al (2014). Expression of EMSY, a novel BRCA2-link protein, is associated with lymph node metastasis and increased tumor size in breast carcinomas. Asian Pac J Cancer Prev, 15, 1783-9.
  3. Tang M, Hou YL, Kang QQ, et al (2014). All-trans-retinoic Acid promotes iodine uptake via up- regulating the sodium iodide symporter in medullary thyroid cancer stem cells. Asian Pac J Cancer Prev, 15 1859-62.
  4. Wong YP, Shah SA, Shaari N, et al (2014). Comparative analysis between multilevel sectioning with conventional haematoxylin and eosin staining and immunohistochemistry for detecting nodal micrometastases with stage i and ii colorectal cancers. Asian Pac J Cancer Prev, 15, 1725-30.
  5. Gage AA, Baust J (1998). Mechanisms of tissue injury in cryosurgery. Cryobiology, 37, 171 -86.
  6. Diao CY, Guo HB, Ouyang YR, et al (2014). Screening for metastatic osteosarcoma biomarkers with a DNA microarray. Asian Pac J Cancer Prev, 15, 1817-22.
  7. Erdogan B, Cicin I (2014). Medical treatment of breast cancer bone metastasis: from bisphosphonates to targeted drugs. Asian Pac J Cancer Prev, 15, 1503-10.
  8. Folkman J (1990). What is the ecidence that tumors are angiogenesis dependent. J Natl Cancer Inst, 82, 4-6.
  9. Hanahan D, Folkman J (1996). Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell, 86, 353-64.
  10. Kimura M, Rabbani Z, Mouraviev V, et al (2010). Morphology of hypoxia following cryoablation in a prostate cancer murine model: its relationship to necrosis, apoptosis and, microvessel density. Cryobiology, 61, 148-54.
  11. Li X, Feng GS, Zheng CS, et al (2002). Laboratory experiment of the effect of transcatheter arterial chemoembolization on tumor angiogenesis. Chin J Radiol, 36, 689-93.
  12. Li YL, Cai XG (2013). Vascular endothelial growth factor and its receptor and the progress of lung cancer treatment. Med Recap, 19, 272-4.
  13. Liang J, Qian Y, Xu D, et al (2013). Serum tumor markers, hypoxia-inducible factor-1$\alpha$ HIF-1$\alpha$ and vascular endothelial growth factor, in patients with non- small cell lung cancer before and after intervention. Asian Pac J Cancer Prev, 14, 3851-4.
  14. Cao F, Hu YW, Li P, et al (2013). Lymphangiogenic and angiogenic microvessel density in chinese patients with gastric carcinoma: correlation with clinicopathologic parameters and prognosis. Asian Pac J Cancer Prev, 14, 4549-52.
  15. Das M, Wakelee H (2012). Targeting VEGF in lung cancer. Expert Opin Ther Targets, 16, 395-406.

Cited by

  1. Expression of Hypoxia-inducible Factor Prolyl Hydroxylase 3 HIFPH3 in Human Non-small Cell Lung Cancer (NSCLC) and Its Correlation with Prognosis vol.15, pp.14, 2014,
  2. Impact of tumor histology and grade on treatment success of percutaneous renal cryoablation vol.35, pp.4, 2017,
  3. Impact of Interventional Oncology Therapies on Tumor Microenvironment and Strategies to Enhance Their Efficacy vol.210, pp.3, 2018,