15 research outputs found
Psychological features of personal development of younger adolescents in the process of leisure activities
The article presents the results of analysis of younger adolescents’ psychological characteristics and provides a description of a comprehensive program created in order to ensure effective personal development of children in this age group in the process of carrying out leisure activities. To test the program, a sample was formed consisting of 60 adolescents studying at Municipal Budgetary General Education Institution “School No. 134” in Nizhny Novgorod. The results of the study indicate significant changes among all criteria analyzed for the experimental and the control groups. The scientific significance of the data obtained lies in the expansion of the idea of younger adolescents’ personal qualities’ multidimensionality and the opportunity provided to study the phenomenon in more detail. Indicators obtained during the course of the study can be used to organise extracurricular activities for adolescents, hold seminars and personal development trainings as well as develop methodological manuals on personality psychology
Наследственные злокачественные опухоли яичника
Background. Hereditary genetic mutations are a significant risk factor for malignant transformation of cells and cancer development. Hereditary genetic mutations account for 15 to 25 % of all ovarian carcinomas. Purpose of the study: to summarize data on hereditary ovarian malignancies, namely: genetic defects, features of the clinical course, treatment options, and disease prevention. Material and methods. A systemic search was undertaken using PubMed, Medline, Cochrane Library databases for publications from 1999 to 2021. Results. The review describes the main genetic defects and hereditary cancer syndromes predisposing to the development of hereditary malignant ovarian tumors. The features of the clinical course and response to drug therapy have been presented. This article summarizes clinical guidelines of the professional communities (National Comprehensive Cancer Network (NCCN), American Society Of Clinical Oncology (ASCO), The U.S. Preventive Services Task Force, and European Society For Medical Oncology (ESMO). These guidelines contain early detection strategies and approaches to prevent the development of cancers in mutation carriers. Conclusion. Detection of hereditary cancer syndromes is important for patients and their families. Recognizing hereditary predisposition to cancer is important to allow timely surveillance and preventative interventions for both patients and family members.Введение. Наследственные дефекты генов – достоверный фактор риска злокачественной трансформации клеток и развития онкологических заболеваний. На долю наследственных форм приходится 15–25 % всех случаев карцином яичника. Цель исследования – обобщить имеющиеся данные о наследственных злокачественных опухолях яичников: ассоциированных генетических дефектах, особенностях клинического течения, лечения и профилактических мероприятий. Материал и методы. Поиск литературных источников выполнялся в базах PubMed, Medline, Cochrane Library, включались публикации с 1999 по 2021 г. Результаты. Описаны основные генетические дефекты и ассоциированные с ними опухолевые синдромы, предрасполагающие к развитию наследственных злокачественных опухолей яичника. Представлены особенности клинического течения и чувствительность к лекарственной терапии. Обобщены рекомендации профессиональных сообществ: Национальной онкологической сети США (National Comprehensive Cancer Network, NCCN), Американского общества клинической онкологии (American Society Of Clinical Oncology, ASCO), Рабочей группы по профилактике заболеваний в США (The U.S. Preventive Services Task Force), Европейского общества медицинской онкологии (European Society For Medical Oncology, ESMO), направленные на раннее выявление новообразований, и представлен комплекс профилактических мер для предотвращения развития злокачественных опухолей яичника у носителей герминальных мутаций. Заключение. Выявление наследственных опухолевых синдромов имеет важное значение для пациентов и их семей. Своевременное определение предрасположенности к развитию злокачественных опухолей позволяет оптимизировать программы скрининга и профилактики онкологических заболеваний
The prognostic significance of the omental chemotherapy response score in hereditary ovarian tumors after neoadjuvant chemotherapy
The study was aimed to evaluate histopathological tumor response of omental metastases in BRCA1-associated and sporadic ovarian tumors after platinum-based neoadjuvant chemotherapy (nACT). We selected patients with histologically confirmed ovarian high-grade serous carcinoma who were treated with nACT followed by optimal debulking. Forty patients (14 BRCA1-associated cancers and 26 sporadic cases) meeting the criteria mentioned above were enrolled in the pathological examination. Clinical data (platinum-free interval, PFI) were collected through database review. Good regress [score 3] was observed in 4 out of 16 (25%) BRCA1-associated carcinomas and in one of 24 (4%) sporadic cancers (p = 0.14, Fisher's exact test). PFI was associated with the degree of response (minimal regress – median PFI 3.62 months, moderate regress – median 8.17 months, good regress - 21.28 months, p = 0.026, Kruskal-Wallis test). The omental response score predicted platinum-free interval in BRCA1-associated tumors (score 2+3 vs. 1; median PFI, 18.6 vs. 2.9 months; p = 0.04, Mann–Whitney U test). Histopathological tumor response of omental metastasis in BRCA1-associated and sporadic ovarian tumors after platinum-based neoadjuvant chemotherapy predicts PFI.Целью данного исследования стало сравнение выраженности патоморфологического регресса метастазов в большой сальник BRCA1-ассоциированных и спорадических опухолей яичника в ответ на платиносодержащую неоадъювантную химиотерапию (НАХТ). В исследование включены 40 пациенток (16 больных с мутацией BRCA1 и 24 «спорадических» случаев) в соответствии с следующими критериями: серозный гистотип опухоли высокой степени злокачественности, платиносодержащая НАХТ, оптимальная циторедуктивная операция (ОЦО), известная длительность бесплатинового интервала (БПИ). При оценке гистопатологического регресса метастазов в большой сальник в группе BRCA1-ассоциированного рака яичника РЯ частота выраженных регрессов [3 балла] составила 4/16 (25%), в группе спорадических опухолей – 1/24 (4%) (p = 0,14, точный критерий Фишера). Продолжительность БПИ достоверно зависела от степени регресса (при минимальном регрессе медиана составила 3,62 мес., при умеренном – 8,17 мес., при выраженном – 21,28 мес.; p = 0,026, тест краскела-Уоллиса). В группе носителей мутаций BRCA1 наблюдалось различие в продолжительности БПИ между случаями с умеренным и выраженным регрессом и случаями с минимальным регрессом (медианы 18,6 мес. vs. 2,9 мес., соответственно; p = 0,04, критерий Манна-Уитни). Степень выраженности патоморфологического регресса метастазов в большой сальник BRCA1-ассоциированных и спорадических опухолей яичника в ответ на НАХТ после ОЦО коррелирует с продолжительностью БПИ
ОПЫТ ИСПОЛЬЗОВАНИЯ ЛУЧЕВОЙ ТЕРАПИИ ПРИ BRCA-ПОЗИТИВНОМ РАКЕ ЯИЧНИКОВ
Cancer cells with the loss of BRCA 1 or BRCA 2 function are unable to repair DNA double-strand breaks and demonstrate the increased sensitivity to various DNA-damaging agents. We aimed to describe successful treatment outcomes in two patients with BRCA1-associated ovarian cancer, who showed a complete clinical response to radiotherapy in combination with platinum-based chemotherapy. The progression-free survival was 11 months in one case and 8 months in another case.Клетки опухоли с нарушенной функцией генов BRCA 1/2 не способны восстанавливать разрывы двойной цепи ДНК и демонстрируют повышенную чувствительность к различным ДНК-повреждающим агентам. Представлен опыт успешного лечения двух больных распространенным раком яичников, носительниц мутации в гене BRCA1, которые получали лучевую терапию c химиотерапией препаратами платины. В результате лечения был зафиксирован полный клинический ответ. Период до прогрессирования в первом случае составил 11 мес, во втором – 8 мес
High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients
<p>Abstract</p> <p>Background</p> <p>A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk.</p> <p>Methods</p> <p>The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed.</p> <p>Results</p> <p>BRCA1 5382insC allele was detected in 28/290 (9.7%) OC cases from the North-West and 11/64 (17.2%) OC patients from the South of Russia. In addition, 4 BRCA1 185delAG, 2 BRCA1 4153delA, 1 BRCA2 6174delT, 2 CHEK2 1100delC and 1 NBS1 657del5 mutation were detected. 1 patient from Krasnodar was heterozygous for both BRCA1 5382insC and NBS1 657del5 variants.</p> <p>Conclusion</p> <p>Founder BRCA1 mutations, especially BRCA1 5382insC variant, are responsible for substantial share of OC morbidity in Russia, therefore DNA testing has to be considered for every OC patient of Russian origin. Taken together with literature data, this study does not support the contribution of CHEK2 in OC risk, while the role of NBS1 heterozygosity may require further clarification.</p
КЛИНИКО-МОРФОЛОГИЧЕСКИЕ ОСОБЕННОСТИ НАСЛЕДСТВЕННОГО РАКА ЯИЧНИКА
Germ-line mutations in BRCA1 and BRCA2 genes are the most established risk factors for hereditary breast and ovarian cancers. The purpose of the study was to analyze BRCA1/2 testing in ovarian cancer patients. Materials and methods. We analyzed 222 patients with ovarian cancer (OC) who underwent genetic testing. Results. Recurrent Slavic mutations in these genes were detected in 60/222 (27%) patients.104 patients lacked any clinical signs of hereditary form of the disease, however BRCA1/2 genetic defects were identified among 11 (11%) of these women. BRCA1/2-associated carcinomas were characterized by more advanced stage at diagnosis and predominance of high-grade serous histological tumor subtype. Conclusion. These results emphasize the need for BRCA1/2 testing for all patients with OC. BRCA1/2-associated carcinomas have clinical and pathological cgaracteristics, which should be considered while planning therapy. Наследственные мутации в генах BRCA1 и BRCA2 являются наиболее известными и изученными факторами риска карцином молочной железы и яичника. Цель исследования – анализ опыта BRCA1/2- тестирования больных раком яичника. Материал и методы. Проанализированы данные 222 больных раком яичника (РЯ), направленных на генетическое тестирование. Результаты. Генетический дефект в генах BRCA1/2 был выявлен у 60 (27 %) из 222 пациенток. В группе женщин без клинических признаков наследственной формы заболевания генетические дефекты BRCA1/2 были обнаружены у 11 (11 %) из 104 пациенток. BRCA1/2-ассоциированные карциномы характеризовались более поздней стадией заболевания и преобладанием низкодифференцированного серозного гистологического типа опухоли. Заключение. BRCA1/2-ассоциированные опухоли составляют значимую часть злокачественных новообразований яичника, что обусловливает целесообразность генетического тестирования для всех пациенток с РЯ. BRCA1/2-ассоциированные карциномы имеют клинические и морфологические особенности, которые необходимо учитывать при планировании терапии.
Clinical features of BRCA-positive ovarian cancer
It has been recently proved that cells with impaired BRCA1function demonstrate high sensitivity to platinum-containing derivatives because they are not able to eliminate DNA disorders caused by these agents. Early studies showed that BRCA carriers had better odds of surviving ovarian cancer than do women without these mutations. The purpose of the study was to evaluate clinical significance of BRCA1 mutation carriage in response to chemotherapy as well as to life span in patients with advanced ovarian cancer. Treatment outcomes of 21 patients with advanced ovarian cancer with inherited BRCA1gene mutation, who were treated from January 2000 to January 2008, were analyzed. The control group consisted of 42 (1:2) cases with advanced non-inherited ovarian cancer matched by stage, histological type, age and the extent of primary cytoreductive surgery. All BRCA-positive patients responded to neoadjuvant platinum-containing chemotherapy. In non-inherited ovarian cancer patients, complete response was observed in 36 % (8/8 (100 %) vs 9/25 (36 %); OR 14,8; 95 % CI 1,78–100; p=0,002). In comparison with the control group patients, BRCA-positive patients had higher rates of complete response to the first-line platinum-containing chemotherapy (81 % vs 33,4 %; OR 8,50; 95 % СI 2,52–34,89; p=0,001) and to the second-line chemotherapy (62 % vs 21,4 %; OR 5,96; 95 % СI 1,76–22,50; p=0,004). After the third line chemotherapy, BRCA-positive patients had a tendency to better results (18,8 % vs 5,6 %; p=0,233). A statistically significant improvement in the median relapse-free survival time was observed in patients with BRCA1mutations after the first-line chemotherapy as compared to that observed in the control group patients (20,05 vs 7,21 months; p=0,005). Life span in BRCA-positive patients was significantly longer than in patients with non-inherited ovarian cancer (medium 9,3 years vs 3,4 years; p=0,001)
RADIOTHERAPY IN MANAGEMENT OF BRCA-POSITIVE OVARIAN CANCER
Cancer cells with the loss of BRCA 1 or BRCA 2 function are unable to repair DNA double-strand breaks and demonstrate the increased sensitivity to various DNA-damaging agents. We aimed to describe successful treatment outcomes in two patients with BRCA1-associated ovarian cancer, who showed a complete clinical response to radiotherapy in combination with platinum-based chemotherapy. The progression-free survival was 11 months in one case and 8 months in another case
Efficacy of dose-intensive platinum-containing neoadjuvant chemotherapy in the combination treatment for locally advanced cervical cancer
Objective: to assess the efficacy of dose-intensive platinum-containing neoadjuvant chemotherapy in patients with FIGO stage IB2–IIB locally advanced cervical cancer.Materials and methods. We evaluated the efficacy and toxicity of 3 cycles of intravenous dose-intensive neoadjuvant chemotherapy with either AP regimen (cisplatin 75 mg/m2 and doxorubicin 35 mg/m2) or TP regimen (cisplatin 60 mg/m2 and paclitaxel 60 mg/m2).Results. The study included 105 patients (75 in the AP group and 30 in the TP group) aged between 27 and 63 years (mean age 44 years) with primary verified cervical cancer (T1–2B0–2Nx–0M0). Surgery was performed in 66 patients (88 %) from the AP group and 24 patients (80 %) from the TP group. Six patients (8 %) receiving AP regimen and 1 patient (3.3 %) receiving TP regimen developed disease progression. Four women (2.8 %) from the AP group developed relapses, whereas none of the patients from the TP group had relapses. Dose-intensive chemotherapy did not cause any significant complications at both chemotherapeutic and surgical stages. Our findings suggest that dose-intensive neoadjuvant chemotherapy is an effective method with an objective response rate of 84 % (63 cases) and 56.7 % (17 cases) in groups AP and TP respectively. Fifty-nine patients (78.7 %) receiving AP regimen had pathological response; of them, 7 participants (9.4 %) demonstrated pathological complete response (ypCR). In the TP group, 19 patients (63.3 %) had pathological response and 4 patients (13.4 %) had pathological complete response. Median follow-up time was 16.7 months (range: 3–29 months) in the AP group and 9.1 months (range: 2.8–12.7 months) in the TP group.Conclusion. Dose-intensive neoadjuvant chemotherapy can be considered as an alternative to standard treatment of locally advanced cervical cancer; however, further studies are needed due to the small sample size in this study