Conservative therapy with CIN I-II vaginal suppositories Cervicon-Dim (intermediate results of a clinical study)

CIN is most common in women of reproductive age. The current treatment standards for CIN I and/or CIN II are invasive and aggressive, which sometimes leads to a disruption of reproductive function. At the same time, long-term follow-up and non-intervention can result in further progression of the process. Therefore the search for conservative treatment of CIN I-II remains a challenging task. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel group study which showed that administration of Cervicon-DIM vaginal suppositories for 90 days at a dose of 200 mg/day or 100 mg/day is associated with improved histological condition of CIN I-II and even leads to cure.

цервикальная интраэпителиальная неоплазия, CIN I, CIN II, ВПЧ, дииндолилметан, ДИМ, Цервикон-ДИМ, клиническое исследование, cervical intraepithelial neoplasia, HPV, Diindolylmethane, DIM, Cervicon-DIM, clinical study

1. Дмитриева Г.А., Биткина О.А. Папилломавирусная инфекция. М.: Медицинская книга, 2006: 76.

2. Маянский А.Н. Патогенетическая микробиология: Руководство. Н. Новгород: Изд-во Нижегородской государственной медицинской академии, 2006: 520.

3. Апгар Б.С., Броцман Г.Л., Шпицер М. Клиническая кольпоскопия. М.: Практическая медицина, 2012: 496.

4. Маянский А.Н. Папилломавирусы человека: Возбудители доброкачественных и злокачественных неоплазий. Вопросы диагностики в педиатрии, 2010, 2 (2): 5-11.

5. Schneider J et al. Abnormal oxidative metabolism of estradiol in women with breast cancer. Proc Natl acad Sci USA, 1982, 79 (9): 3047-51.

6. Chung SH, Wiedmeyer K, Shai A et al. Requirement for estrogen receptor a in a mouse model for human papillomavirus-associated cervical cancer. Cancer Res., 2008, 68 (23): 9928-9934.

7. Morimoto Y et al. Urinary estrogen metabolites during a randomized soy trial. Nutr Cancer, 2012, 64 (2): 307-14.

8. Киселев В.И. Вирусы папилломы человека в развитии рака шейки матки. М.: ДГГ, 2004: 184.

9. Banerjee S. Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic. Banerjee S, Kong D, Wang Z. Mutat Res, 2011, 728: 47-66.

10. Zhu J, Li Y, Guan C, Chen Z. Anti-proliferative and pro-apoptotic effects of 3,3'-diindolylmethane in human cervical cancer cells. Oncol Rep, 2012, 28 (3): 1063-8.

11. Chen DZ, Qi M, Auborn KJ, Carter TH. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium.J. Nutr., 2001, 131 (12): 3294-3302.

12. Sepkovic DW, Stein J, Carlisle AD et al. Diindolylmethane inhibits cervical dysplasia, alters estrogen metabolism, and enhances immune response in the K14-HPV16 transgenic mouse model. Cancer Epidemiol. Biomarkers Prev, 2009, 18 (11), 2957-2964.

13. Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer, 2004, 50 (2): 161-7.

14. Chang, X et al. 3,3'-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis, 2005, 26 (4): 771-8.

15. Kim EJ, Shin M, Park H, Hong JE, Shin HK, Kim J et al. Oral administration of 3,3'-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.J.Nutr., 2009, 139 (12): 2373-9.

16. Semov A, Iourtchenko L, Liu LF, Li S, Xu Y, Su X et al. Diindolylmethane (DIM) selectively inhibits cancer stem cells. Biochem. Biophys. Res. Commun., 2012; 424 (1): 45-51.

17. Zeligs MA et al. US patent 6.416.793, Formulation and use of controlled-release indole alkaloids.

18. Kiselev VI. Diindolylmethane-based drug for the treatment of hyperplastic and inflammatory diseases. WO 2011/136691 A1. 2011.

19. Киселев В.И. Суппозитории вагинальные на основе 3,3'-дииндолилметана (метиндола) (RU 2318510).

20. Bell MC et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol., 2000, 78(2): 123-9.

21. Giuseppe Del Priore, Deleep Kumar Gudipudi, Nadine Montemarano, Antonella M Restivo, Jeanetta Malanowska-Stega, Alan A Arslan. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol, 2010, 116 (3): 464-7.

22. Zeligs MA, Sepkovic DW, Manrique C. Absorption-enhanced 3,3'-diindolylmethane: human use in HPV-related, benign and pre-cancerous conditions. Proc Am. Assoc. Cancer Res, 2003, 44.

23. Carter TH, Liu K, Ralph W et al. Diindolylmethane alters gene expression in human keratinocytes in vitro.J. Nutr, 2002, 132 (11): 3314-3324.

24. Savino JA, Evans JF, Rabinowitz D, Auborn KJ, Carter TH. Multiple, disparate roles for calcium signaling in apoptosis of human prostate and cervical cancer cells exposed to diindolylmethane. Mol Cancer Ther, 2006, 5 (3): 556-63.