Compositions containing C-substituted diindolylmethane...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C548S455000

Reexamination Certificate

active

10872928

ABSTRACT:
Disclosed are methods and compositions for the treatment of a wide array of cancers and tumors. In illustrative embodiments, diindolylmethanes, C-substituted diindolylmethanes, and analogs thereof have been described, which when administered either alone, or in combination with other anti-cancer or anti-tumorigenic compounds, provide new therapies for the treatment of cancer.

REFERENCES:
patent: 5948808 (1999-09-01), Safe
patent: WO 98/0357 (1998-11-01), None
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Chemical Abstracts, vol. 130, No. 16 (1999), Abstract No. 204767t, McDougal, A., et al. “Methyl-substituted diindolylmethanes as AhR-based antitumorigenic/antiestrogenic compounds.”
Chen, et al., “Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane,”Carcinogenesis, 19:1631-1639 (1998).
Chen, et al., “Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells,”Biochem. Parmacol. 51:1069-1076 (1996).
McDougal and Safe, “Methyl-substituted diindolylmethanes as AhR-based antitumorigenic/antiestrogenic compounds,”Organohalogen Compounds37:253-256 (1998).
McDougal, et al., “Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependant responses by symmetrical dihalosubstituted analogs of diindolylmethane,”Cancer Letts. 151:169-179 (2000).
Michaud, et al., “Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort,”J. Natl. Cancer Inst. 91:605-613 (1999).
Ramamoorthy, et al., “AhR-mediated antiestrogenicity of diindolylmethane and analogsin vivoand in vitro,”Organohalogen Compounds37:321-324 (1998).
Safe, “2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD) and related environmental antiestrogens: characterization and mechanism of action,”Endocrine Disrupters, Naz (ed.), CRC Press, Boca Raton, Florida, pp. 187-221 (1999).
McDougal, et al., “Tamoxifen-induced antitumorigenic/antiestrogenic action synergized by a selective aryl hydrocarbon receptor modulator,”Cancer Res. 61:3902-3907 (2001).
Safe, “Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Spl interactions,”Vitam. Horm. 62:231-252 (2001).
Safe, “Molecular biology of the Ah receptor and its role in carcinogenesis,”Toxicol. Lett.120:1-7 (2001).
Sanderson, et al., “2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1 and 19 in H295R human adrenocortical carcinoma cells,”Toxicol Sci. 61(1):40-48 (2001).
Chen, et al., “Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization,”Gene262:207-214 (2001).
Wormke, et al., “Estrogen and aryl hydrocarbon receptor expression and crosstalk in human Ishikawa endometrial cancer cells,”J. Steroid Biochem. Mol. Biol. 72(5):197-207 (2000).
Safe, et al., “Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms,”Toxicol. Lett. 102-103:343-7 (1998).
PCT International Search Report mailed Jul. 31, 2002, in PCT/US01/42519.

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