13-cis-Retinoic Acid Plus Interferon- 2a in Locally Advanced Squamous Cell Carcinoma of the Cervix

Lippman, Scott M.; Kavanagh, John J.; Paredes-Espinoza, Mario; Delgadillo-Madrueño, Fernando; Paredes-Casillas, Patricia; Hong, Waun Ki; Massimini, Giorgio; Holdener, E. E.; Krakoff, Irwin H.

doi:10.1093/jnci/85.6.499

Cited by 82 publications

(40 citation statements)

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“…A certain subset of the >60 types of human papilloma viruses, a family of DNA viruses, are associated with epithelial tumors (130). For example, human papilloma virus types 16 and 18 are associated with malignant cervical intraepithelial neoplasms, and the combination of IFN-a and retinoids has been found surprisingly active in this condition (145). Human papilloma virus types 6 and 11 are associated with benign condylomata acuminata and laryngeal papilloma.…”

Section: Viral Diseasesmentioning

confidence: 99%

Cytokine therapeutics: lessons from interferonalpha.

Gutterman

1994

Proc. Natl. Acad. Sci. U.S.A.

636

356

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Cytokines are soluble proteins that allow for communication between cells and the external environment.Interferon (IFN) a, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator ofgrowth and differentiation, affecting cellular communication and signal transduction pathways as well as immunological control. This review focuses on the biological and clinical activities of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-a in malignant, viral, immunological, angiogenic, inflammatory, and fibrotic diseases suggests a spectrum of interrelated pathophysiologies. The principles learned from in vivo studies will be discussed, particulady hairy cell leukemia, chronic myelogenous leukemia, certain angiogenic diseases, and hepatitis. After the surprising discovery of activity in a rare B-cell neoplasm, IFN-a emerged as a prototypic tumor suppressor protein that represses the dinhl tumorigenic phenotype in some malgancies capable of differentiation. Regulatory agencies throughout the world have approved IFN-a for treatment of 13

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Section: Viral Diseasesmentioning

confidence: 99%

Cytokine therapeutics: lessons from interferonalpha.

Gutterman

1994

Proc. Natl. Acad. Sci. U.S.A.

636

356

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“…This interest has been fueled by the finding that retinoids are natural cancer preventive agents and that administration of retinoid can be used to treat existing cancer (2,3,15). Retinoids interact with the retinoid receptors that are ligand-activated, transacting transcription factors (4,16,17).…”

mentioning

confidence: 99%

AGN193109 Is a Highly Effective Antagonist of Retinoid Action in Human Ectocervical Epithelial Cells

Agarwal

Chandraratna

Johnson

et al. 1996

Journal of Biological Chemistry

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Retinoids are important physiological agents that regulate epithelial cell differentiation and proliferation. The importance of these agents in regulating growth, development, and differentiation has led to a search for new retinoid agonists and antagonists. In the present manuscript we show that AGN193109, a retinoid analog, is an efficient antagonist of retinoid action in human cervical epithelial cells. Treatment of ECE16-1 cells with natural or synthetic retinoids reduces cytokeratin K5, K6, K14, K16, and K17 levels, increases cytokeratin K7, K8, and K19 levels, increases retinoic acid receptor-␤ (RAR␤) mRNA levels, suppresses proliferation, and alters cell morphology. Co-treatment with AGN193109 prevents these responses. Half-maximal and maximal antagonism is observed at a molar ratio of AGN193109: retinoid agonist of 1:1 and 10:1, respectively. When administered alone AGN193109 has no agonist activity. Thus, AGN193109, which binds to RAR␣, RAR␤, and RAR␥ with K d values ‫؍‬ 2, 2, and 3 nM, respectively, but is unable to bind to the retinoid X receptors, is a highly active antagonist of retinoid action in ECE16-1 cells.

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“…There are encouraging preclinical and clinical data with combined CRA and IFN in squamous carcinoma of the skin, locally advanced untreated cervical cancer, and renal cell carcinoma [17][18][19][20]. In our institution, we studied the combination of CRA, IFN and paclitaxel for patients with prostate cancer and other advanced malignancies in a phase I study and showed the clinical safety of the combination [21].…”

Section: Introductionmentioning

confidence: 99%