Biomedical subjects

Yumei Feng

Publications and source records attributed to Yumei Feng.

3 recordsLinked to original sources

PubMed2005

Characterization of a monoclonal antibody that antagonizes the function of human endostatin.

Endostatin, a 20-kDa proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis and tumor growth. The anti-angiogenic effects of endostatin include inhibition of endothelial cell migration and proliferation, and inhibition of the activity of MMP2. Structure-function analysis of endostatin that implies this contravention function buried in separate fragments of endostatin introduces new issues into the understanding of the structure-function relationship of endostatin. We developed and characterized a novel murine MAb, 4E7, to human endostatin, which antagonizes the function of endostatin. As we show here, MAb 4E7 blocks the anti-migration/adhesion effects of endostatin in vitro and the anti-angiogenesis effect of endostatin in vivo, but the inhibition effect of endostatin on endothelial cell proliferation is not affected by MAb4E7. These results suggest that the anti-migration and anti-proliferation functions of endostatin may have distinct structural foundations.

Animals↗

PubMed2004

Alkali burn causes aldehyde dehydrogenase 3A1 (ALDH3A1) decrease in mouse cornea.

PURPOSE: Aldehyde dehydrogenase 3A1 (ALDH3A1) is the most abundant soluble protein component in the mouse cornea, produced mainly by corneal epithelial cells. High levels of ALDH3A1 in cornea contribute to maintenance of a stable an d transparent corneal structure. Alkali burn is a common damage to the corneal surface, which produces an alkaline hydrolysis of matrix proteins and induces an inflammatory reaction. Our study was intended to detect changes in ALDH3A1 expression after corneal alkaline burn. METHODS: To address this issue we employed RTQ-PCR to monitor the transcriptional change of ALDH3A1 after alkali burn. We used zymography to test enzyme activity changes of ALDH3A1 in the alkali burn cornea; And SDS-PAGE and mass spectrometry technology were used to verify protein content changes and to identify ALDH3A1 protein. RESULTS: Using zymography, ALDH3A1 enzymic activity was observed to decrease immediately after corneal alkali burn and the levels recovered following healing. Proteins extracted from alkali burned corneas, when run on SDS-PAGE, showed the same sized band (about 54 kDa, which is the molecular weight of ALDH3A1) but in much smaller quantity, compared to normal corneas. This result was further verified by mass spectrometry fingerprinting of the in-gel lysis product. An immediate decrease of ALDH3A1 transcription after alkali burning of the cornea was also found using RTQ-PCR. This level of transcription was gradually restored during healing. CONCLUSIONS: Alkali burn of the corneal surface caused a rapid decrease of ALDH3A1 in the corneal at both the RNA and protein levels, which leads to the loses of the protective component of the corneal surface and makes it vulnerable to further damage. The ALDH3A1 level in the cornea gradually recovered during the healing process. Use of an anti-oxidation reagent as a treatment ingredient for alkali burn of the corneal surface could compensate for the decrease of anti-oxidation protection potential caused by ALDH3A1 loss.

Aldehyde Dehydrogenase↗

PubMed2004

Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis.

BACKGROUND: Metastatic disease is a major adverse prognostic factor in breast carcinoma. Lymph node metastases often represent the first step in the metastatic process. METHODS: To gain insight into the molecular events that underlie breast carcinoma metastasis, the authors compared gene expression profiles, obtained by cDNA microarray analysis, of nine matched primary tumors and metastases after screening for enrichment of tumor cells. Statistical analysis identified genes that are expressed at elevated or decreased levels in metastases relative to the corresponding primary tumors. Multidimensional scaling analysis indicated that in terms of expression levels, primary tumors were tightly clustered, whereas metastases exhibited a greater spread; this finding points to the more heterogeneous nature of metastases. Among the differentially expressed entities were the invasion- and tissue modeling-related genes IGFBP5, fibronectin, and MMP2; the cell cycle regulatory gene cyclin D1; other genes, such as enolase 2; and an expressed sequence tag similar to angiopoietin 1. To validate and extend these initial findings, the authors constructed a tissue microarray consisting of 100 primary malignancies paired with their lymph node metastases. Antibodies for the IGFBP-5, fibronectin, MMP-2, cyclin D1, and MDM-2 proteins were used to stain tissue array sections. RESULTS: Consistent with microarray data, statistically significant overexpression of IGFBP-5, down-regulation of cyclin D1, and unchanged MDM-2 levels were observed in metastatic tumor cells. Nonetheless, although fibronectin and MMP2 mRNA expression levels were decreased in many metastasis specimens, expression levels of the corresponding proteins in the extracellular matrix were elevated in most metastases. Decreased expression of fibronectin and MMP2 in lymph node metastases was further confirmed by real-time polymerase chain reaction assays performed on five additional specimen pairs. CONCLUSIONS: The results of the current study suggest that extracellular matrix protein expression and nuclear gene expression are associated via a negative-feedback regulatory mechanism. Therefore, gene expression profiling and tissue array validation should be combined to elucidate molecular events associated with the metastatic process.

Breast Neoplasms↗