Ovarian cancer is the seventh most common cancer in women worldwide and the leading cause of gynecological malignant diseases-related deaths in women. The most significant risk factor for ovarian cancer is an inherited genetic mutation in one of two genes: breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2). The germline mutation c.5266dupC (also known as 5382insC or 5385insC) is the most common mutation among Slavic patients with breast and/or ovarian cancer. Missense mutation c.181T > G (also known as 300T > G or p.C61G) is regarded as the founder change in many Central European countries. We screened 306 ovarian cancer patients diagnosed at different ages by mutagenically separated polymerase chain reaction (PCR) and real-time PCR. A total of 25 BRCA1 mutations were detected (18 cases of 5382insC and 7 cases of 300 T > G). The frequency of the BRCA1 5382insC mutation is similar in breast and ovarian cancer patients from Ukraine, but the frequency of 300T > G was estimated in Ukraine at first time.
Aim: To study antitumor activity of triptorelin — agonist of gonadotropin-releasing hormone and exemestane — inhibitor of aromatase in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant transplantable ascites ova rian tumor (OT); to assess tumor response to treatment and VEGF expression in tumor cells under different combinations of cytostatic and hormonal drugs. Materials and Methods: 36 female Wistar rats, which underwent intraperitoneal transplantation of ascites OT (5×106 cells per animal), have been involved in the study. Rats were distributed into 4 groups (9 rats in each group): group 1 — animals, which received combination of cisplatin and triptorelin; group 2 — rats treated with combination of cisplatin and exemestane; group 3 — animals, which were administered with combination of cisplatin, triptorelin and exemestane; group 4 — rats, which received combination of triptorelin and exemestane. Histological study with assessment of treatment pathomorphosis in OT and immunohistochemical study have been carried out to analyze VEGF expression in OT cells. Survival of animals has been evaluated. Results: Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly higher rates of treatment pathomorphosis (10.1 ± 0.1% and 16.2 ± 0.3%, respectively) and antiangiogenic activity in OT (21.4 ± 1.4% and 15.0 ± 1.3%, respectively), as well as the highest survival of animals (100.0 and 85.7%, respectively) as compared with the same in rats treated in regimen of monotherapy with cisplatin, triptorelin, exemestane or by combination of hormonal drugs. Among animals treated by combination of cytostatic drug with triptorelin, two were cured (22.2%), and among rats, which received cisplatin and exemestane, one animal (11.1%) was cured. Conclusions: Triptorelin and exemestane increase antitumor activity of cisplatin in respect to the transplantable malignant ascites OT and significantly increase survival of animals, especially when triptorelin and cisplatin are used in combination.
Abstract:The objective of this study is to investigate hormonal receptor status of MOT (malignant ovarian tumor) and to evaluate its clinical and prognostic significance. Retrospective analysis of the case reports of 284 patients with MOT of different histogenesis, stages I-IV, and immunohistochemical study of paraffin-embedded tissues were performed. Hormonal receptor status of tumors with different morphology genesis was studied and hormonal receptor phenotype of serous OC (ovarian cancer) was determined. The analysis of correlation between the expression of steroid hormone receptors (receptors to estrogens (ER), progesterone (PR) and testosterone (TR)) in ovarian tumors, histological type of tumors and clinical morphological parameters were performed. Overall and relapse-free survival rates of the patients with serous OC depending on the hormonal receptor phenotype of the tumor were assessed. Presence of positive expression of steroid hormone receptors in serous OC (ER-66.4%, PR-63.4%, TR-53.0%), mucinous OC (ER-88.0%, PR-84.0%, TR-60.0%) and in sex cord stromal tumors (ER-74.1%, PR and TR-77.8%) is proved by correlation of all steroid receptors expression with morphology type of ovarian tumors (ER -r = 0.4; PR -r = 0.4; TR -r = 0.3; р < 0.05). Direct correlation between hormonal receptor phenotype of serous OC and the age period of the patients was established (r = 0.5; р = 0.002): postmenopausal women patients reported the most increased frequency of serous OC with positive hormonal receptor tumor phenotypes (52.4%), in particular during their late post-menopausal period (39.0%). Significantly low overall survival among the patients with positive hormonal receptor phenotype of serous OC was recorded (29.5 ± 3.4%) in comparison with the same score in the patients with negative phenotype of tumors (44.5 ± 3.7%) (р < 0.05). Multifactor analysis of Cox-regression model has defined that positive hormonal receptor phenotype of serous OC increases the risk of disease relapse (HR 1.4; 95.0% CI 1.1-1.7), significantly decreases overall survival rates in the patients (HR 1.4; 95.0% CI 1.1-1.8). Positive hormonal receptor status of MOT is an independent factor of unfavorable clinical progress of tumor process which can be regarded as the criterion for development of the methods of hormonal therapy application in complex treatment of the patients, and demands further large-scale multi-center studies in that direction.
The objective: to study and systematize the main clinical variants of CIN 3 with the spread of atypical epithelium to the vaults and walls of the vagina; to develop complex approaches to the treatment of patients with CIN 3 with the spread of atypical epithelium to the vaults and walls of the vagina with neoadjuvant therapy and surgical treatment; to study the therapeutic effectiveness of the use of a2b-interferon in the form of vaginal suppositories and Tyloron in the complex treatment of patients with CIN 3 with the spread of abnormal epithelium to the vaults and walls of the vagina during the first stage of complex drug treatment. Patients and methods. A survey of 62 patients with histologically verified CIN 3 with the spread of atypical epithelium to the vaults and walls of the vagina was carried out. At the stage of neoadjuvant etiotropic therapy, the patients were randomized into two groups. 31 patients were included in the main group (A), 31 patients were included in the control group (B). In group A, patients with neoadjuvant were given б2b-interferon at 500 000 IU in the form of vaginal suppositories twice a day for 14 days and a Tyloron 1 tablet 125 mg once a day in a day No.10. In group B, the standard therapy is intended for patients – an a2b-interferon of 500 000 IU in the form of vaginal suppositories twice a day for 14 days. The surgical stage of treatment was carried out in accordance with the clinical and histological diagnosis and the variant of the process spread to the walls of the vagina. Diathermoconization of the cervix and combined vaginal trachelectomy type A with resection of the upper third of the vagina were performed. Results. Three clinical variants of CIN 3 with spreading to the vaults and walls of the vagina were established. The first clinical variant – CIN 3 is localized to ectocervix, CIN 1–2 (IHC p16 negative) is localized on the vaults and walls of the vagina. The second clinical variant – CIN 3 is localized on ectocervix and extends to the vault and walls of the vagina. The third clinical variant – CIN 3 is localized on ectocervix and multicentric dissemination of CIN 3 – on vaults and walls of the vagina. The choice of an integrated treatment program with a surgical component depends on the clinical option. Conclusions. 1. Three clinical variants of CIN 3 with spreading to the vault and walls of the vagina have been established. Half the patients had the first clinical variant. 2. The main colposcopic signs of CIN 3 with spreading to the vaults and walls of the vagina: dense acetic-white epithelium, coarse mosaic, a sign of the internal border. 3. In 3 weeks after the course of treatment with neoadjuvant therapy in combination of Тyloron with a2b-interferon in the form of vaginal suppositories, it is possible to achieve from 85 to 100.0% positive dynamics, whereas in the traditional method of treatment, from 41 to 75%, which is statistically significant less (p<0.01). 4. The study showed that there is a relatively strong statistically significant association of neoadjuvant therapy using a combination of Tyloron with interferon-a2b suppositories in the complex treatment of CIN3 with spreading to the vault and vaginal walls compared to conventional therapy (c21=10.64; j=0.41; p<0.01). After three weeks, the positive dynamics in the main group (A) significantly increased (RR=1.6; 95% CI: 1.2–2.2; p<0.01). Key words: CIN 3, vaginal vault, vagina, trachelectomy, treatment.
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