Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2006-01-17
2006-01-17
Henley, III, Raymond J. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S681000
Reexamination Certificate
active
06987127
ABSTRACT:
Malignant melanoma cells spontaneously generate reactive oxygen species (ROS) that promote constitutive activation of the transcription factor nuclear factor-kB (NF-kB). Although antioxidants and inhibitors of NAD(P)H oxidases significantly reduce constitutive NF-kB activation and suppress cell proliferation, the nature of the enzyme responsible for ROS production in melanoma cells has not been determined. To address this issue, we now have characterized the source of ROS production in melanoma cells. ROS are generated by isolated, cytosol-free melanoma plasma membranes, with inhibition by NAD(P)H oxidase inhibitors. The p22phox, gp91phoxand p67phoxcomponents of the human phagocyte NAD(P)H oxidase, and the 91phoxhomolog NOX4were demon-strated in melanomas by RT-PCR and sequencing, and protein product for both p22phoxand gp91phoxwere detected in cell membranes by immunoassay. Normal human epidermal melanocytes expressed only p22phoxand NOX4. Melanoma proliferation was reduced by NAD(P)H oxidase inhibitors and by transfection of antisense but not sense oligonucleotides for p22phoxand NOX4. Also, the flavoprotein inhibitor diphenylene iodonium inhibited constitutive DNA binding of nuclear protein to the NF-kB and cyclic-AMP response element consensus oligonucleotides, without affecting DNA binding activity to AP-1 or OCT-1.
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Alston & Bird LLP
Charlotte-Mecklenburg Hospital Authority
Henley III Raymond J.
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