HPV-associated cervical cancer: Current status and prospects

Every year, 570,000 new cases of cervical cancer (CC) are diagnosed in the world, and 311,000 people die from this disease. CC is the fourth most common type of cancer and therefore the fourth leading cause of cancer death in women worldwide. Numerous data on the occurrence and development of cervical cancer indicate an association in most cases (up to 90 %) with human papillomaviruses (HPV) of high carcinogenic risk (HCR).CC prevention strategies are based on screening, and deaths from this oncopathology can be prevented through vaccination and treatment with early detection of the disease.In this review, much attention is paid to current issues of detection and prevention of HPV-associated pathologies, and cervical cancer in particular, aiming to summarize and analyze the latest international literature data on this issue. As a result of this study, it was shown that for countries implementing the National program of vaccination against HPV of high carcinogenic risk, a decrease in the incidence of both cervical pathologies of varying severity and other cancers associated with the HPV carriage was registered.While effective implementation of actual experience and future advances in human papillomavirus vaccine prophylaxis may make it possible for all countries to move to the high levels of vaccination coverage required to eliminate HPV-associated pathologies, the results also suggest that the path to complete cervical cancer elimination as a global public health problem can be extremely difficult due to a number of existing limitations

Search for potential gastric cancer markers using miRNA databases and gene expression analysis

Aim: The aim of this study was to identify genes that are differentially expressed in gastric tumors and to analyze the association of their expression level with tumor clinicopathologic features. Methods: In the present research, we used bioinformatic-driven search to identify miRNA that are down-regulated in gastric tumors and to find their potential targets. Then, the expression levels of some of the target mRNAs were investigated using reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: As a result of the bioinformatics analysis, fifteen genes were found to be potentially differentially expressed between the tumors and normal gastric tissue. Five of them were chosen for the further analysis (WNT4, FGF12, EFEMP1, CTGF, and HSPG2) due to their important role in cell proliferation and differentiation. Expression levels of these genes were evaluated in our collection of frozen tissue samples of gastric tumor and paired normal stomach epithelia. Increased FGF12 expression was observed in diffuse type of gastric cancer while WNT4 mRNA was found to be down-regulated in intestinal type of gastric cancer. Besides, CTGF gene overexpression was revealed in diffuse type of stomach cancer in comparison with that in intestinal type. Up-regulation of CTGF was also associated with lymph node metastasis. Conclusions: The findings show its expedient to perform further investigations in order to clarify diagnostic and prognostic value of CTGF, FGF12, and WNT4’s in stomach cancer as well as the role of these genes in carcinogenesis

Composite implants coated with biodegradable polymers prevent stimulating tumor progression

In this experiment we studied oncologic safety of model implants created using the solution blow spinning method with the use of the PURASORB PL-38 polylactic acid polymer and organic mineral filler which was obtained via laser ablation of a solid target made of dibasic calcium phosphate dihydrate. For this purpose the implant was introduced into the area of Wistar rats’ iliums, and on day 17 after the surgery the Walker sarcoma was transplanted into the area of the implant. We evaluated the implant’s influence on the primary tumor growth, hematogenous and lymphogenous metastasis of the Walker sarcoma. In comparison with sham operated animals the implant group demonstrated significant inhibition of hematogenous metastasis on day 34 after the surgery. The metastasis inhibition index (MII) equaled 94% and the metastases growth inhibition index (MGII) equaled 83%. The metastasis frequency of the Walker sarcoma in para aortic lymph nodes in the implant group was not statistically different from the control frequency; there was also no influence of the implant on the primary tumor growth noted. In case of the Walker sarcoma transplantation into the calf and the palmar pad of the ipsilateral limb to the one with the implant in the ilium, we could not note any attraction of tumor cells to the implant area, i.e. stimulation of the Walker sarcoma relapse by the implant. Thus, the research concluded that the studied implant meets the requirements of oncologic safety

Composite implants coated with biodegradable polymers prevent stimulating tumor progression

In this experiment we studied oncologic safety of model implants created using the solution blow spinning method with the use of the PURASORB PL-38 polylactic acid polymer and organic mineral filler which was obtained via laser ablation of a solid target made of dibasic calcium phosphate dihydrate. For this purpose the implant was introduced into the area of Wistar rats’ iliums, and on day 17 after the surgery the Walker sarcoma was transplanted into the area of the implant. We evaluated the implant’s influence on the primary tumor growth, hematogenous and lymphogenous metastasis of the Walker sarcoma. In comparison with sham operated animals the implant group demonstrated significant inhibition of hematogenous metastasis on day 34 after the surgery. The metastasis inhibition index (MII) equaled 94% and the metastases growth inhibition index (MGII) equaled 83%. The metastasis frequency of the Walker sarcoma in para aortic lymph nodes in the implant group was not statistically different from the control frequency; there was also no influence of the implant on the primary tumor growth noted. In case of the Walker sarcoma transplantation into the calf and the palmar pad of the ipsilateral limb to the one with the implant in the ilium, we could not note any attraction of tumor cells to the implant area, i.e. stimulation of the Walker sarcoma relapse by the implant. Thus, the research concluded that the studied implant meets the requirements of oncologic safety

ПОТЕРЯ ГЕТЕРОЗИГОТНОСТИ ЛОКУСОВ ГЕНОВ BRCA1 И BRCA2 В ОПУХОЛИ МОЛОЧНОЙ ЖЕЛЕЗЫ

One of the factors of variability of malignant neoplasms is the loss of heterozygosity (LOH). The biological meaning of LOH, in relation to carcinogenesis, is associated with the inactivation of heterozygous loci of pathogenetically significant genes. Thus, the aim of this work was to study BRCA1/2 LOH in breast tumors.Material and Methods. The study included 122 patients with stage IIAIIIC breast cancer. DNA was isolated from 122 biopsy samples of tumor tissue using the QIAamp DNA mini Kit (Qiagen, Germany). To assess the status of LOH, microarray analysis was performed on high-density DNA chips from Affymetrix CytoScanTM HD Array. To process the results of microchipping, we used the Chromosome Analysis Suite 3.3 program (Affymetrix, USA).Results. The loss of heterozygosity in the BRCA1 gene was found to be associated with response to NAC. It was shown that in 59 patients LOH in the BRCA1gene was associated with an objective response to treatment (p=0.005). The presence of LOH in the studied genes was associated with a favorable prognosis. The 5-year non-metastatic survival rates were 75 % and 100 % in patients with LOH in the BRCA1 and BRCA2 genes, respectively (log-rank test: p=0.003 and p=0.05, respectively).Conclusion. The phenomenon of LOH in the BRCA1/2 genes was shown to be associated with response to NACT. BRCA1/2. Further studies are needed to evaluate the frequency of BRCA1/2 LOH after NAC for choosing and changing treatment tactics. Одним из факторов вариабельности злокачественных новообразований является потеря гетерозиготности (LOH – loss of heterozygosity). Предполагается, что биологический смысл LOH применительно к канцерогенезу связан с инактивацией гетерозиготных локусов патогенетически значимых генов.Целью исследования явилось исследование потери гетерозиготности генов BRCA1/2 в опухоли молочной железы.Материал и методы. В исследование были включены 122 больных раком молочной железы IIA–IIIC стадии. ДНК выделяли из 122 биопсийных образцов опухолевой ткани с помощью набора QIAamp DNA mini Kit (Qiagen, Germany). Для оценки статуса LOH проведен микроматричный анализ на ДНК-чипах высокой плотности фирмы Affymetrix CytoScanTM HD Array. Для обработки результатов микрочипирования использовали программу «Chromosome Analysis Suite 3.3» (Affymetrix, USA).Результаты. В результате проведенного исследования было установлено, что наличие потери гетерозиготности в гене BRCA1 сопряжено с ответом на неоадъювантную химиотерапию. Показано, что у 59 больных наличие LOH в гене BRCA1 сопряжено с объективным ответом на лечение (p=0,005). Наличие потери гетерозиготности в изучаемых генах сопряжено с благоприятным прогнозом. Показатель 5-летней безметастатической выживаемости у пациентов с потерей гетерозиготности для гена BRCA1 составляет 75 % (log-rank test p=0,003), для гена BRCA2 все пациенты имели 100 % безметастатическую выживаемость, log-rank test p=0,05.Заключение. Показано, что потеря гетерозиготности в генах BRCA1/2 связана с эффективностью неоадъювантной химиотерапии, а также является независимым прогностическим фактором. С учетом полученных результатов можно предположить, что инактивация BRCA1/2 должна коррелировать с чувствительностью к терапии на основе платины, что, несомненно, делает дальнейшее изучение данного вопроса актуальным.

Полнотранскриптомный анализ опухоли молочной железы в процессе неоадъювантной химиотерапии: связь с ответом на предоперационную химиотерапию

Introduction. Treatment of breast cancer often includes systemic neoadjuvant chemotherapy. The frequency of complete morphological response varies significantly depending on the molecular subtype of tumor. However, even in triple negative breast cancer, which is considered the most sensitive, it does not exceed 50 %. Therefore, the search for new genetic predictors of tumor response to preoperative treatment, as well as the assessment of tumor changes during neoadjuvant chemotherapy are highly relevant.Objective – to perform whole-transcriptome analysis of breast cancer during neoadjuvant chemotherapy depending on tumor response to preoperative treatment.Materials and methods. This study included 39 patients with luminal B HER2-positive (human epidermal growth factor receptor 2) breast cancer who received 6 to 8 cycles of neoadjuvant chemotherapy. We performed whole-transcriptome analysis of paired biopsy and surgical specimens using the Clariom™ S Assay, human (Affymetrix, USA).Results. We observed significant differences in the pretreatment expression of 166 genes (13 were up-regulated and 153 were down-regulated) between patients with objective response to therapy and those without it. Comparison of preand post-treatment expression profiles demonstrated 680 differentially expressed genes in patients with complete and partial response and 3240 differentially expressed genes in patients with stable or progressive disease. Venn diagram showed that patients with and without objective response to neoadjuvant chemotherapy shared 105 differentially expressed genes.Conclusion. We performed primary screening of genes in breast tumors before therapy and identified genes whose pretreatment expression differed significantly between patients with objective response to neoadjuvant chemotherapy and those without it. Further validation of these genes in an independent sample will allow the development of a genetic panel to evaluate the response to neoadjuvant chemotherapy. Assessment of changes in the expression of tumor genes during treatment depending on patient’s response to therapy can be useful for further development of a panel of genes, which will enable the evaluation of clinical response to chemotherapy, as well as identification of key cellular processes that change the activity of genes during therapy.Введение. Лечение рака молочной железы во многих случаях включает системную химиотерапию в неоадъювантном режиме. Согласно данным литературы частота полного морфологического ответа опухоли значительно варьирует в зависимости от ее молекулярного подтипа, однако даже при самом чувствительном, трижды негативном подтипе она не превышает 50 %. в связи с этим актуальны поиск генетических предикторов ответа опухоли на предоперационное лечение и оценка изменений, которые происходят в опухоли в процессе неоадъювантной химиотерапии.Цель исследования – проведение полнотранскриптомного анализа опухоли молочной железы в ходе неоадъювантной химиотерапии в зависимости от ответа на предоперационное лечение.Материалы и методы. В исследование включены 39 пациентов с раком молочной железы люминального в HER2-позитивного подтипа (human epidermal growth factor receptor 2, рецептор эпидермального фактора роста, тип 2), получавшие 6–8 курсов неоадъювантной химиотерапии. Были исследованы парные образцы биопсийного и операционного материала. Полнотранскриптомный микроматричный анализ проводился с использованием платформы Clariom™ S Assay, human (Affymetrix, США).Результаты. При сравнении экспрессионного профиля пациентов с наличием и отсутствием объективного ответа на лечение до проведения неоадъювантной химиотерапии было выявлено 166 дифференциально экспрессирующихся генов (13 up-regulated, 153 down-regulated). При сравнении экспрессионного профиля до и после лечения у больных с полной и частичной регрессией выявлено 680 дифференциально экспрессирующихся генов, а у больных со стабилизацией или прогрессированием – 3240 этих генов. С помощью построения диаграммы венна было показано, что 105 дифференциально экспрессирующихся генов являются общими для пациентов с наличием/отсутствием объективного ответа на неоадъювантную химиотерапию до и после лечения.Заключение. Был проведен первичный скрининг генов в опухоли молочной железы до лечения. Выявлены гены, экспрессия которых до терапии статистически значимо различалась у больных с объективным ответом на неоадъювантную химиотерапию и его отсутствием. Дальнейшая валидация данных генов на независимой выборке даст возможность разработать генетическую панель для определения ответа на неоадъювантную химиотерапию. Оценка изменения экспрессии опухолевых генов в ходе лечения у больных в зависимости от ответа на эту терапию может быть полезна для разработки в дальнейшем панели генов, выявление изменений которых позволит судить о клиническом ответе опухоли на химиотерапию, а также выделить ключевые клеточные процессы, меняющие активность генов в процессе терапии

Полнотранскриптомный анализ опухоли молочной железы в процессе неоадъювантной химиотерапии: связь с ответом на предоперационную химиотерапию. Дополнительный материал

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