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Biomedical subjects

W McKeehan

Publications and source records attributed to W McKeehan.

11 recordsLinked to original sources
PubMed1994

Fibroblast growth factor receptor gene expression and immunoreactivity are elevated in human glioblastoma multiforme.

Glioblastomas were examined for abnormalities in fibroblast growth factor receptor (FGFR) expression by polymerase chain reaction and immunocytochemical analysis. Polymerase chain reaction analysis demonstrated that FGFR1 mRNA levels were significantly higher in glioblastomas than in normal brain adjacent to the tumor or in untransformed human brain. These results were consistent with immunocytochemical localization of FGFR1 protein in glioblastomas: glioblastoma cells exhibited intense FGFR1 immunoreactivity in frozen sections of tumor and low to undetectable FGFR1 immunoreactivity in adjacent normal brain or in normal white matter obtained from patients without neoplastic disease. Endothelial cells of capillaries and larger vessels within the tumor were devoid of FGFR1 immunoreactivity. All glioblastomas evaluated in the present study expressed FGFR1 mRNA and FGFR1 immunoreactivity. Examination of the FGFR1 gene by Southern blot analysis indicated that overexpression of FGFR1 mRNA in glioblastomas did not result from gene amplification. These results indicate that glioblastoma cells, in contrast to endothelial cells within the tumor, display increased levels of FGFR1. Therefore, FGFR1 signal transduction may be associated with increased autocrine growth activity of tumor cells and is probably not related to the increased endothelial cell proliferation associated with these tumors.

Base Sequence↗
PubMed1994

Inositolhexakisphosphate (InsP6): an antagonist of fibroblast growth factor receptor binding and activity.

Fibroblast growth factors (FGF), which have been implicated in tumor cell growth and angiogenesis, have biological activities that appear to be mediated by both heparinlike extracellular matrix sites and transmembrane tyrosine kinase receptor sites. In the present study, we demonstrated that inositolhexakisphosphate (InsP6) inhibits basic FGF (bFGF) binding to heparin. Our spectrofluorometric analyses demonstrated that InsP6 not only bound to bFGF, presumably within the bFGF heparin-binding domain, but also protected bFGF from degradation by trypsin. Also, InsP6 inhibited the cellular binding of bFGF and other fibroblast growth factor family members such as acidic FGF (aFGF) and K-FGF in a saturable and dose-dependent manner. Furthermore, concentrations as low as 100 microM InsP6 inhibited bFGF-induced DNA synthesis in AKR-2B fibroblasts, as well as the growth of bFGF- and K-FGF-transfected NIH/3T3 cells. Together, these results indicate that InsP6 may serve as a useful antagonist of FGF activity.

Animals↗
PubMed1992

When is intervention warranted?

A chemoprevention trial in prostate cancer would be a formidable but potentially rewarding study. The current status of knowledge of drug interactions with, biomarkers of, and even the natural history of prostate cancer is insufficient to study all levels of men at risk. Currently, the most promising group to study is group I--those men with a high probability of developing prostate cancer but who do not currently have evidence of the disease. This could be a placebo-controlled, prospective and randomized study with the endpoint being clinically-detected prostate cancer. In addition, much may be gained from short-term pilot studies of "chemo-active" agents on morphologic and other biomarkers of prostate cancer initiated immediately before surgical removal. It is hoped that such studies may provide rationale for future efforts directed at preventing progression of premalignant or early prostate cancer lesions.

Anticarcinogenic Agents↗
PubMed1988

Prostatropin and acidic FGF also support proliferation of an EGF-dependent keratinocyte cell line.

Despite the relevance of epithelial cells to the biology of cancer, considerably less is known about the capacity of specific growth factors to control the proliferation of these cells compared to information available on fibroblastic cells. Epidermal growth factor is the most widely recognized mitogen for epithelial cells. We demonstrate that prostatropin and acidic fibroblast growth factor, structurally similar molecules, are potent growth factors for the mouse keratinocyte cell line Balb/MK. This indicates that these growth factors in addition to epidermal growth factor may be of physiological relevance to epidermal cell proliferation.

Animals↗
PubMed1969

The mechanism of messenger RNA translocation through ribosomes.

The two recognized enzymatic steps involved in the extension of peptides on ribosomes of the 80S type have been studied in a highly purified transfer system derived from rabbit reticulocytes. Data presented are interpreted to reflect three ribosomal binding sites through which transfer RNA is moved in two independent enzymatic reactions each of which requires guanosine 5'-triphosphate hydrolysis. The binding enzyme facilitates translocation between the entry and acceptor ribosomal sites. Transferase II is involved in translocation between the acceptor and donor ribosomal sites. A model is proposed to account for movement of transfer RNA and messenger RNA between the ribosomal sites.

Animals↗