The chick embryo chorioallantoic membrane as a model to study tumor metastasis
ABSTRACT Tumor metastasis represents a major problem in the treatment of patients with different cancers. Specific phenotype and behavior
of metastatic cells derive from specific molecular mechanisms involved in consecutive steps of the metastatic process. Several
invitro and invivo experimental models have been utilized, but they cannot completely reproduce and characterize each step
of the metastatic process. This review article is focused on the chick embryo chorioallantoic membrane as an invivo model
to study the metastatic process.
Article: Chick Chorioallantoic Membrane (CAM) Assay as an In Vivo Model to Study the Effect of Newly Identified Molecules on Ovarian Cancer Invasion and Metastasis.[show abstract] [hide abstract]
ABSTRACT: The majority of ovarian cancer patients present with advanced disease and despite aggressive treatment, prognosis remains poor. Significant improvement in ovarian cancer survival will require the development of more effective molecularly targeted therapeutics. Commonly, mouse models are used for the in vivo assessment of potential new therapeutic targets in ovarian cancer. However, animal models are costly and time consuming. Other models, such as the chick embryo chorioallantoic membrane (CAM) assay, are therefore an attractive alternative. CAM assays have been widely used to study angiogenesis and tumor invasion of colorectal, prostate and brain cancers. However, there have been limited studies that have used CAM assays to assess ovarian cancer invasion and metastasis. We have therefore developed a CAM assay protocol to monitor the metastatic properties of ovarian cancer cells (OVCAR-3, SKOV-3 and OV-90) and to study the effect of potential therapeutic molecules in vivo. The results from the CAM assay are consistent with cancer cell motility and invasion observed in in vitro assays. Our results demonstrate that the CAM assay is a robust and cost effective model to study ovarian cancer cell metastasis. It is therefore a very useful in vivo model for screening of potential novel therapeutics.International Journal of Molecular Sciences 01/2012; 13(8):9959-70. · 2.60 Impact Factor
Article: The clinical predictive factors for subsequent distant metastasis in patients with locoregionally advanced oral squamous cell carcinoma.[show abstract] [hide abstract]
ABSTRACT: OBJECTIVES: Only a small portion of the patients with locoregionally advanced oral squamous cell carcinoma (OSCC) experience subsequent distant metastasis. This study is to evaluate the occurrence of distant metastasis after curative treatment and to explore the predictive factors for subsequent distant metastasis in patients with locoregionally advanced OSCC. MATERIALS AND METHODS: The medical records of all patients with locoregionally advanced OSCC without distant metastasis at the time of diagnosis (AJCC stage III, IV but not IVC) who underwent curative surgery with or without adjuvant radiation between 2004 and 2009 were retrospectively reviewed. RESULTS: A total of 628 patients were enrolled, including 562 male and 66 female patients. The 5-year distant metastasis rate was 13.2%. The 5-year disease-free and overall survival rates were 57.0% and 60.3%, respectively. Multivariate analyses revealed that poorly differentiated tumors (HR=2.3 (1.16-4.53), p=0.02) and contralateral neck metastasis (HR=7.55 (3.20-17.83), p<0.001) were independent adverse factors for distant metastasis-free survival. The 5-year distant metastasis rates of 447 patients with well-differentiated tumors, 140 patients with moderately differentiated tumors and 41 patients with poorly differentiated tumors were 12.1%, 18.2%, and 34.1%, respectively. The 5-year distant metastasis rates of 227 patients without neck metastasis, 350 patients with ipsilateral neck metastasis and 51 patients with contralateral neck metastasis were 6.7%, 15.1%, and 55.3%, respectively. CONCLUSIONS: Poorly differentiated tumors and contralateral neck metastasis were independent factors for subsequent distant metastasis in patients with locoregionally advanced OSCC.Oral Oncology 11/2012; · 2.86 Impact Factor
Article: Exploitation of chick embryo environments to reprogram MYCN-amplified neuroblastoma cells to a benign phenotype, lacking detectable MYCN expression.[show abstract] [hide abstract]
ABSTRACT: Neuroblastoma is a paediatric cancer that arises from the sympathetic ganglia (SG) or adrenal gland. Tumours that occur in patients under 18 months of age have a particularly good prognosis and frequently undergo spontaneous regression. This led to the hypothesis that developmental cues in the youngest patients may prompt belated differentiation and/or apoptosis of the tumour cells. To test our hypothesis, we have injected MYCN-amplified neuroblastoma cells into the extra embryonic veins of chick embryos at embryonic day 3 (E3) and E6 and analysed the response of these Kelly cells at E10 and E14. Amplification of the MYCN gene occurs in up to 30% of tumours and is normally associated with a very poor prognosis. Kelly cells injected at E3 follow neural crest pathways and integrate into neural locations such as SG and the enteric nervous system although never into the adrenal gland. Additionally they migrate to non-neural locations such as the heart, meninges, jaw regions and tail. The cells respond to their respective microenvironments and in SG, some cells differentiate, they show reduced cell division and crucially all cells have undetectable MYCN expression by E10. In non-neural locations, cells form more rapidly dividing clumps and continue to express MYCN. The downregulation of MYCN is dependent on continuous and direct interaction with the sympathetic ganglion environment. We propose that the MYCN-amplicon in the Kelly cells retains the ability to correctly interpret the environmental cues leading to downregulation of MYCN.Oncogenesis. 01/2012; 1:e24.