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Christopher W Wong

Publications and source records attributed to Christopher W Wong.

4 recordsLinked to original sources
PubMed2004

Rapid apoptosis in the pulmonary vasculature distinguishes non-metastatic from metastatic melanoma cells.

The presence of metastases indicates an ominous prognosis in patients with malignancies, yet the factors that distinguish metastatic from non-metastatic tumors remain poorly understood. Here we pursued the hypothesis that apoptosis in vivo would distinguish metastatic cells from non-metastatic cells and developed a novel method for observation of apoptosis induction in living cells. One hour after the infusion of metastatic or non-metastatic human melanoma or transformed rat embryo fibroblasts, arrest of tumor cells in the pulmonary vasculature was equivalent. In order to demonstrate the induction of apoptosis in living cells, we observed the translocation of cytoplasmic BAD-GFP fusion proteins to the mitochondria during apoptosis. Microscopic observation of the tumor cells transfected with BAD-GFP in isolated lung preparations after intravenous injection into nu/nu mice revealed translocation of BAD-GFP in many more of the arrested, non-metastatic melanoma or transformed rat embryo cells over 4-24 h than of the metastatic cells. TUNEL staining confirmed enhanced apoptosis by non-metastatic tumor cells after injection in vivo. Metastatic melanoma cells or metastatic embryo fibroblasts were better able to negotiate the barrier of survival in the circulation after pulmonary arrest than non-metastatic cells confirming the hypothesis that susceptibility to apoptosis after arrest in the pulmonary vasculature distinguishes metastatic from non-metastatic cells and introducing a new assay for in vivo induction of apoptosis.

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PubMed2004

Tracking the evolution of the SARS coronavirus using high-throughput, high-density resequencing arrays.

Mutations in the SARS-Coronavirus (SARS-CoV) can alter its clinical presentation, and the study of its mutation patterns in human populations can facilitate contact tracing. Here, we describe the development and validation of an oligonucleotide resequencing array for interrogating the entire 30-kb SARS-CoV genome in a rapid, cost-effective fashion. Using this platform, we sequenced SARS-CoV genomes from Vero cell culture isolates of 12 patients and directly from four patient tissues. The sequence obtained from the array is highly reproducible, accurate (>99.99% accuracy) and capable of identifying known and novel variants of SARS-CoV. Notably, we applied this technology to a field specimen of probable SARS and rapidly deduced its infectious source. We demonstrate that array-based resequencing-by-hybridization is a fast, reliable, and economical alternative to capillary sequencing for obtaining SARS-CoV genomic sequence on a population scale, making this an ideal platform for the global monitoring of SARS-CoV and other small-genome pathogens.

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PubMed2002

Intravascular location of breast cancer cells after spontaneous metastasis to the lung.

In this study, we examined the hypothesis that early pulmonary metastases form within the vasculature. We introduced primary tumors in immunocompromised mice by subcutaneous injection of murine breast carcinoma cells (4T1) expressing green fluorescent protein. Isolated ventilated and perfused lungs from these mice were examined at various times after tumor formation by fluorescent microscopy. The vasculature was visualized by counterstaining with 1,1-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI)-acetylated low-density lipoprotein. These experiments showed that metastatic cells derived by spontaneous metastases were intravascular, and that early colony formation was intravascular. The location of the tumor cells was confirmed by deconvolution analysis. This work extends our previous study(1) that sarcoma cells injected intravenously form intravascular colonies to spontaneous metastasis and to a carcinoma model system. Many of the tumor cells seen were single implying that tumor cells may travel as single cells. These results support a model for pulmonary metastasis in mice in which 1) tumor cells can attach to lung endothelium soon after arrival; 2) surviving tumor cells proliferate intravascularly in this model; and 3) extravasation of the tumor occurs when intravascular micrometastatic foci outgrow the vessels they are in.

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