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Notably, Dr. Lotan’s group later demonstrated that retinoids, e.g., all-trans retinoic acid (ATRA), inhibited the growth of head and neck squamous cell carcinoma cells in vitro, and suppressed the squamous differentiation of head and neck cancers.Citation6-Citation8 These findings as well as prior data from other groups would, in part, pave the way for retinoids to be implemented clinically in chemoprevention trials of human carcinomas. 13-cis retinoic acid (isotretinoin) was shown by Hong and colleagues to prevent the development of second primary tumors in head and neck cancer patients following local therapy.Citation9 In addition, Dr. Lotan et al. later demonstrated that expression of retinoic acid receptor-β (RARβ) was lost in premalignant head and neck lesions and was restored following treatment with isotretinoin suggesting that this nuclear receptor mediates the response to retinoids and may be a useful intermediate biologic marker in trials of these agents for the prevention of oral carcinogenesis.Citation10 At MD Anderson Cancer Center, Dr. Lotan extensively studied the biological signaling mechanisms and antitumor effects of natural retinoids, synthetic retinoid derivatives and retinoid-related molecules (RRMs) as well as their relevance to the chemoprevention and therapy of aerodigestive tract cancers. Dr. Lotan’s laboratory was among the first to demonstrate that synthetic retinoids exhibit their antitumor effects in a retinoid receptor-independent fashion through upregulation of reactive oxygen species (ROS) as a prerequisite for apoptosis inductionCitation11,Citation12 as well as through other signaling mechanisms that in part implicate mitochondrial permeability and respiration.Citation13,Citation14 More recently and up to his retirement, most of Dr. Lotan’s research focused on the retinoid-regulated gene, GPRC5A, and its role in lung cancer development following the report by his group that mice with knockout of both alleles of this G-protein coupled receptor developed lung adenomas and adenocarcinomas.Citation15 Scientifically and according to internal institutional publications (Division of Cancer Medicine Messages), it is remarked that during Dr. Lotan’s career, he has written over 300 peer-reviewed papers, 120 reviews and 60 book chapters. Additionally, it has been estimated that the manuscripts and books he wrote, co-wrote or edited have been cited 14,965 times.
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JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTEno. 22 (2007): 1668.0-1682
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTEno. 21 (2007): 1603.0-1612
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