Влияние новой фармацевтической композиции, содержащей эпигаллокатехин-3-Галлат, на метилирование генов-онкосупрессоров у пациенток с цервикальной интраэпителиальной неоплазией

Purpose: to develop preventive measures and reasonable therapy of pathological processes in the cervix uteri based on detection of methylation of tumor suppressor genes and groups at high-risk of cancer among patients of reproductive age with benign and premalignant cervical processes. Effectiveness of complex pathogenetic treatment of the cervix uteri has been evaluated in 127 women of reproductive age with benign and premalignant cervical processes before and after the combined treatment with a pharmaceutical composition containing active substance epigallocatechin-3-gallate (EGCG). Shown that pharmaceutical composition containing EGCG contributes demethylation of the tumor suppressor genes that confirm powerful oncoprotector action in treating precancerous lesions. One year after the complex combined therapy (including surgery) with pharmaceutical composition containing EGCG, recurrent cervical pathological processes have not been detected in patients with benign lesions, CIN I and CIN II.Целью исследования была разработка патогенетически обоснованного направления терапии и профилактики патологических процессов шейки матки с учетом выявления метилирования генов-супрессоров опухолевого роста и формирования групп повышенного онкологического риска у больных с доброкачественными и предраковыми процессами шейки матки в репродуктивном возрасте. Была оценена патогенетическая эффективность комплексной терапии шейки матки у 127 пациенток репродуктивного возраста с доброкачественными и предраковыми процессами шейки матки до и после комбинированного лечения с применением фармакологической композиции, содержащей в качестве действующего вещества эпигаллокатехин-3-галлат (EGCG). Показано, что применение фармакологической композиции, содержащей в качестве действующего вещества EGCG, способствует деметилированию генов-супрессоров опухолевого роста, что характеризует его в качестве эффективного онкопротектора при предраковых процессах шейки матки. Спустя год после комплексной и комбинированной терапии (в том числе хирургического лечения при наличии показаний к операции) с применением фармакологической композиции, содержащей в качестве действующего вещества EGCG, ни в одном случае не наблюдалось рецидивирования патологического процесса шейки матки у больных с доброкачественными процессами, CINI и CINII

Preclinical antitumor activity of the diindolylmethane formulation in xenograft mouse model of prostate cancer

Aim: Preclinical study of the specific anticancer pharmacological activity of the formulation containing active substance 3,3ʹ-diindolylmethane (DIM), cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E), in vivo in a xenograft animal model of LNCaP. Materials and Methods: The DIM, cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E) formulation was intragastrically administered to BALB/c-nude (nu/nu) mice during 33 days post inoculation at the dose of 133 mg/kg/day. Antitumor activity of the test drug was estimated by the rate of tumor growth inhibition (T/C% — treated versus control), dividing the tumor volumes from treatment groups with the control groups. Results: Statistically significant tumor xenograft regressions have been shown in group which received the DIM, cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E) on the 37th day of observation post inoculation. The highest antitumor activity was achieved on the 39th day (T/C = 16,8%). Therapeutic effect lasts for 6 days after the end of therapy period. Conclusion: Our findings demonstrate inhibitory effect of the formulation on tumor development in the xenograft animal model due to the tumor growth rate reduction. Key Words: 3,3´-diindolylmethane, bioavailability, anticancer activity, xenograft model, LNCaP cell line, preclinical studies

Preclinical antitumor activity of the diindolylmethane formulation in xenograft mouse model of prostate cancer

Aim: Preclinical study of the specific anticancer pharmacological activity of the formulation containing active substance 3,3′-diindolylmethane (DIM), cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E), in vivo in a xenograft animal model of LNCaP. Materials and Methods: The DIM, cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E) formulation was intragastrically administered to BALB/c-nude (nu/nu) mice during 33 days post inoculation at the dose of 133 mg/kg/day. Antitumor activity of the test drug was estimated by the rate of tumor growth inhibition (T/C% - treated versus control), dividing the tumor volumes from treatment groups with the control groups. Results: Statistically significant tumor xenograft regressions have been shown in group which received the DIM, cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E) on the 37th day of observation post inoculation. The highest antitumor activity was achieved on the 39th day (T/C = 16,8%). Therapeutic effect lasts for 6 days after the end of therapy period. Conclusion: Our findings demonstrate inhibitory effect of the formulation on tumor development in the xenograft animal model due to the tumor growth rate reduction. Copyright © Experimental Oncology, 2014

A new promising way of maintenance therapy in advanced ovarian cancer: a comparative clinical study

Background: There is an urgent need for more novel and efficacious therapeutic agents and strategies for the treatment of ovarian cancer - one of the most formidable female malignancies. These approaches should be based on comprehensive understanding of the pathobiology of this cancer and focused on decreasing its recurrence and metastasis. The aim of this study was to evaluate the efficacy of five-year maintenance therapy with indole-3-carbinol (I3C) as well as I3C and epigallocatechin-3-gallate (EGCG) conducted before, during, and after combined treatment compared with combined treatment alone in advanced ovarian cancer. Methods: Patients with stage III-IV serous ovarian cancer were assigned to receive combined treatment plus I3C (arm 1), combined treatment plus I3C and EGCG (arm 2), combined treatment plus I3C and EGCG plus long-term platinum-taxane chemotherapy (arm 3), combined treatment alone without neoadjuvant platinum-taxane chemotherapy (control arm 4), and combined treatment alone (control arm 5). Combined treatment included neoadjuvant platinum-taxane chemotherapy, surgery, and adjuvant platinum-taxane chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and rate of patients with recurrent ovarian cancer with ascites after combined treatment. Results: After five years of follow-up, maintenance therapy dramatically prolonged PFS and OS compared to control. Median OS was 60.0 months (95% CI: 58.0-60.0 months) in arm 1, 60.0 months (95% CI: 60.0-60.0 months) in arms 2 and 3 while 46.0 months (95% CI: 28.0-60.0 months) in arm 4, and 44.0 months (95% CI: 33.0-58.0 months) in arm 5. Median PFS was 39.5 months (95% CI: 28.0-49.0 months) in arm 1, 42.5 months (95% CI: 38.0-49.0 months) in arm 2, 48.5 months (95% CI: 39.0-53.0 months) in arm 3, 24.5 months (95% CI: 14.0-34.0 months) in arm 4, 22.0 months (95% CI: 15.0-26.0 months) in arm 5. The rate of patients with recurrent ovarian cancer with ascites after combined treatment was significantly less in maintenance therapy arms compared to control. Conclusions: Long-term usage of I3C and EGCG may represent a new promising way of maintenance therapy in advanced ovarian cancer patients, which achieved better treatment outcomes

Preclinical antitumor activity of the diindolylmethane formulation in xenograft mouse model of prostate cancer

Aim: Preclinical study of the specific anticancer pharmacological activity of the formulation containing active substance 3,3′-diindolylmethane (DIM), cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E), in vivo in a xenograft animal model of LNCaP. Materials and Methods: The DIM, cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E) formulation was intragastrically administered to BALB/c-nude (nu/nu) mice during 33 days post inoculation at the dose of 133 mg/kg/day. Antitumor activity of the test drug was estimated by the rate of tumor growth inhibition (T/C% - treated versus control), dividing the tumor volumes from treatment groups with the control groups. Results: Statistically significant tumor xenograft regressions have been shown in group which received the DIM, cod liver oil, polysorbate 80 and α-tocopherol acetate (vitamin E) on the 37th day of observation post inoculation. The highest antitumor activity was achieved on the 39th day (T/C = 16,8%). Therapeutic effect lasts for 6 days after the end of therapy period. Conclusion: Our findings demonstrate inhibitory effect of the formulation on tumor development in the xenograft animal model due to the tumor growth rate reduction. Copyright © Experimental Oncology, 2014

A new promising way of maintenance therapy in advanced ovarian cancer: a comparative clinical study

Background: There is an urgent need for more novel and efficacious therapeutic agents and strategies for the treatment of ovarian cancer - one of the most formidable female malignancies. These approaches should be based on comprehensive understanding of the pathobiology of this cancer and focused on decreasing its recurrence and metastasis. The aim of this study was to evaluate the efficacy of five-year maintenance therapy with indole-3-carbinol (I3C) as well as I3C and epigallocatechin-3-gallate (EGCG) conducted before, during, and after combined treatment compared with combined treatment alone in advanced ovarian cancer. Methods: Patients with stage III-IV serous ovarian cancer were assigned to receive combined treatment plus I3C (arm 1), combined treatment plus I3C and EGCG (arm 2), combined treatment plus I3C and EGCG plus long-term platinum-taxane chemotherapy (arm 3), combined treatment alone without neoadjuvant platinum-taxane chemotherapy (control arm 4), and combined treatment alone (control arm 5). Combined treatment included neoadjuvant platinum-taxane chemotherapy, surgery, and adjuvant platinum-taxane chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and rate of patients with recurrent ovarian cancer with ascites after combined treatment. Results: After five years of follow-up, maintenance therapy dramatically prolonged PFS and OS compared to control. Median OS was 60.0 months (95% CI: 58.0-60.0 months) in arm 1, 60.0 months (95% CI: 60.0-60.0 months) in arms 2 and 3 while 46.0 months (95% CI: 28.0-60.0 months) in arm 4, and 44.0 months (95% CI: 33.0-58.0 months) in arm 5. Median PFS was 39.5 months (95% CI: 28.0-49.0 months) in arm 1, 42.5 months (95% CI: 38.0-49.0 months) in arm 2, 48.5 months (95% CI: 39.0-53.0 months) in arm 3, 24.5 months (95% CI: 14.0-34.0 months) in arm 4, 22.0 months (95% CI: 15.0-26.0 months) in arm 5. The rate of patients with recurrent ovarian cancer with ascites after combined treatment was significantly less in maintenance therapy arms compared to control. Conclusions: Long-term usage of I3C and EGCG may represent a new promising way of maintenance therapy in advanced ovarian cancer patients, which achieved better treatment outcomes

Investigation of the efficacy and safety of a diindolylmethane-based drug in patients with cervical intraepithelial neoplasia grades 1-2 (CIN 1-2)

Objective. To investigate the efficacy and safety of the vaginal suppositories Cervicon-DIM (diindolylmethane) in patients with histologically confirmed neoplastic processes of the cervix uteri - cervical intraepithelial neoplasia grades 1-2 (CIN 1-2). Subject and methods. The randomized study enrolled 160 patients aged 18 to 45 years; the follow-up period was 3 months. The investigators analyzed clinical and laboratory data and evaluated the efficacy and safety of treatment with Cervicon-DIM versus placebo. Results. Cervicon-DIM was shown to contribute to the elimination of human papillomavirus infection and to the regression of mild and moderate neoplastic processes of the cervix uteri (CIN 1-2). Conclusion. It is appropriate to prescribe Cervicon-DIM as one suppository (100 mg) twice daily for 3 months to patients with human papillomavirus infection and those with CIN 1-2. © 2018, Bionika Media Ltd. All rights reserved