Статьи журнала - Сибирский онкологический журнал
Все статьи: 3757
Статья обзорная
Тамоксифен является препаратом выбора при эндокринотерапии гормоноположительного рака молочной железы у женщин в репродуктивном периоде. Метаболическая активность тамоксифена в организме определяется активностью фермента CYP2D6, кодируемого одноименным геном: под действием фермента тамоксифен переходит в метаболически активную форму - эндоксифен. Фармакогенетическое тестирование гена CYP2D6 у пациентов с гормоноположительным раком молочной железы поможет прогнозировать эффективность терапии и оценить риск развития побочных эффектов в целях улучшения отдаленных результатов лечения.
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Carcinogenicity of malathion and estrogen in an experimental rat mammary gland model
Статья научная
Breast cancer is considered a major and common health problem in both developing and developed countries. The etiology of breast cancer, the most frequent malignancy diagnosed in women in the western world, has remained unidentified. Chemicals as the organophosphorous pesticide malathion have been used to control a wide range of sucking and chewing pests of field crops, and are involved in the etiology of breast cancers. The association between breast cancer initiation and prolonged exposure to estrogen suggests that this hormone may also have an etiologic role in such a process. However, the key factors behind the initiation of breast cancer remain to be elucidated. The effect of environmental substances, such as malathion and estrogen was analyzed in an experimental rat mammary gland model. Different cytoplasmic proteins are key in the transformation of a normal cell to a malignant tumor cell and among these are the Ras super family and Ras homologous A (Rho-A). both types of proteins were greater in animals treated with malathion than those with estrogens. E-Cadherins constitute a large family of cell surface proteins. results showed greater expression of E-Cadherin and vimentin than c-Ha-ras and Rho-A in rats treated by estrogens. In breast cancer, analysis using immunohistochemical markers is an essential component of routine pathological examinations, and plays an important role in the management of the disease by providing diagnostic and prognostic strategies. the aim of the present study was to identify markers that can be used as a prognostic tool for breast cancer patients.
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Introduction. Proteins associated with cellular motility are known to play an important role in invasion and metastasis of cancer, however there is no evidence of their association with the development of malignant tumors including endometrial cancer (EC). The aim of the present study was to investigate the levels of actin-binding proteins, p45-Ser-p-catenin, and calpain activity in endometrial hyperplasia and in EC. Material and Methods. Total calpain activity, p45-Ser p-catenin, Arp3, gelsolin, cofillin and thymosin p-4 levels were evaluated in 43 postmenopausal patients with stage i-ii endometrioid EC and 40 endometrial hyperplasia patients. Flow cytometry and Western blotting were used for expression determination of p45 Ser p-catenin and actin-biding proteins. Total calpain activity was estimated by fluorimetric method. Results. Levels of cofilin-1, thymosin p-4 and calpain activity were higher in cancer tissues than in endometrial hyperplasia. Cofilin-1 and thymosin p-4 levels were associated with the depth of myometrial invasion. The thymosin p-4 expression was correlated with the presence of tumor cervical invasion. Revealed correlations between the actin-binding proteins, p45-Ser-p-catenin and total calpain activity in endometrial hyperplasia tissue, but not in the tissue of cancer, is evidence of the involvement of these proteases in regulation of cell migration in endometrial hyperplasia. Levels of thymosin p-4, cofilin and total calpain activity are independent cancer risk factors in patients with endometrial hyperplasia. Conclusion. The level of actin-binding proteins as well as the total calpain activity were enhanced in endometrium carcinoma tissues compared to endometrial hyperplasia. The levels of thymosinp-4, cofilin and total calpain activity in endometrial hyperplasia tissues are associated with a hyperplasia transition to cancer and may be considered as predictive biomarkers.
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Changes in blood monocyte functional profile in breast cancer
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The purpose of the study was to identify functional features of circulation monocytes in patients with non-metastatic breast cancer. Material and Methods. The study cohort consisted of 10 breast cancer patients treated at Tomsk Cancer Research institute. 7 healthy female volunteers were enrolled as a control group. CD14+16-, CD14+16+ and CD14-16+ monocytes subsets were obtained from blood by sorting. Whole transcriptome profiling was provided in monocytes from patients and healthy females. Macrophages were differentiated from the obtained monocytes under in vitro conditions. The ability of conditioned media obtained from macrophages to influence apoptosis and proliferation of MDA-MB 231 cell line was evaluated. Results. Transcriptomic profiling revealed significant changes in monocytes of breast cancer patients. CD14+16- subset showed higher expression of transporters ABCA1 and ABCG1; chemokines CCR1, CRRL2, CXCR4; maturation and differentiation factors Mafb and Jun; endocytosis mediating factors CD163 and Siglec1; proteases and tetrasponins ADAM9, CD151, CD82, and growth factor HBEGF in patient group. Macrophages derived from monocytes of breast cancer patients produced factors that supported proliferation of the MDA-MB 231 cell line, which was not observed for monocytes from healthy volunteers. Conclusion. Thus, breast carcinoma has a systemic effect on peripheral blood monocytes, programming them to differentiate into macrophages with tumor supporting capacity.
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Chemoradiation therapy for localized colorectal cancer: a view from the outside
Статья научная
Background. Colorectal cancer is among the most lethal and prevalent malignances in the world. The management of localized colorectal cancer is highly debated. Surgical resection of the rectum, such as total mesenteric excision (TME) is usually associated with significant morbidity and mortality. The integration of various chemotherapy options into the standard treatment of localized rectal cancer could potentially enhance the tumor control with a subsequent reduction in the frequency of recurrence, thus improving overall and disease-free survival. Moreover, there are categories of patients for whom surgical treatment is contraindicated and chemotherapy will be more useful for them. Although rectal cancer is predominantly a disease of older patients, current guidelines do not incorporate optimal treatment recommendations for elderly patients with comorbidities; therefore this issue remains a matter of debate. Aim. We aimed to consider alternative approaches to the treatment of localized rectal cancer and the management of selected patients with this diagnosis. Material and Methods. We searched for publications in the Pubmed, eLibrary databases and up-to-date information on the basis of world cancer associations. Conclusions. Comparison of surgery with concurrent chemoradiotherapy for localized rectal cancer showed that in some cases neoadjuvant therapy can be useful and successful, acting as an ideal alternative. However, this approach may be suitable for selected patients who meet certain criteria. In addition, a follow-up care after treatment should include a specific range of diagnostic imaging tests.
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Chitinase-like proteins as promising markers in cancer patients
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In the present review we collected the main studies regarding the role of chitinase-like proteins (CLPs), belonging to the family of Glyco_18 domain-containing proteins, in different cancers. In humans, 3 chitinaselike proteins have been identified: YKL-40 (CHI3L1), YKL-39 (CHI3L2) and stabilin-1-interacting chitinase-like protein (SI-CLP). CLPs are produced by several types of cells and combine the properties of cytokines and growth factors. The high levels of CLPs were identified in the circulation of the patients with inflammatory diseases and various types of tumors. We highlighted the main known functions of CLPs in normal and pathological conditions, their contribution to metastasis development, angiogenesis, invasion and other processes in cancer, the correlation of the levels of CLPs with tumour progression. Our data also contribute to the understanding of question how CLP could be useful for cancer patient benefit.
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Clinical relevance of CYP2D6 genetics for tamoxifen response in breast cancer
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Статья научная
Introduction. In accordance with UICC and AJCC 8th edition TNM classifications, there is a strong evidence for division of oropharyngeal squamous cell carcinoma (OPSCC) into 2 molecular subtypes by HPV-status with distinct prognosis depending on biological differences. Such a division leads to differences in staging OPSCC and in future it will lead to implementation of preventive measures and new therapeutic strategies against HPV-positive cancer. Aim of the study: to assess the clinical and prognostic significance of the combination of P16, a surrogate marker for HPV-positivity, and high proliferative activity in patients with oropharyngeal carcinoma. Material and Methods. Immunohistochemical (ICH) analysis with monoclonal antibodies specific for P16 and Ki67 proteins was used to detect expression patterns in the formalin-fixed, paraffin-embedded tumor samples obtained from 104 patients with squamous cell carcinoma of the tongue and oropharynx, treated at Oncological Dispencery № 1 in Krasnodar from 2011 to 2016. HPV-positive status was determined if more than 70 % of tumor cells had moderate or strong nuclear and cytoplasmic P16-staining. High index of proliferative activity (PA) was detected if more than 50 % tumor cells expressed Ki67 nuclear antigen. Results. P16-positivie status was associated with tonsillar cancer (р=0.002), female gender (р=0.015), age 70 % with high PA demonstrated correlation with tonsillar cancer (р50 % and clinicopathologid parameters and overall survival confirms the biological features of HPV-associated cancer. The evaluation of this IHC-complex can increase the diagnostic accuracy of IHC-analysis of HPV-status and predict the prognosis of patients with OPSCC.
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Clostridium difficile ассоциированная диарея
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В обзоре литературы по антибиотикоассоциированной диарее показана значимость C. difficile и вырабатываемых ею токсинов А и В. Рассмотрены вопросы, касающиеся эпидемиологии, клинической симптоматики, возможных осложнений этого заболевания, диагностики, а также рациональные подходы к терапии. Антибиотикоассоциированная диарея является серьезным заболеванием и требует тщательных и взвешенных подходов к назначению лечения. Опасность внутрибольничных вспышек этого заболевания с учетом старения населения и массивного использования антибактериальных препаратов в России и других странах делает эту проблему более актуальной.
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Introduction. Colon and rectal cancer (CC, RC) are different entities from a clinical and tumor biological point of view. Up to now, both, CC and RC, are synonymously called “Colorectal Cancer” (CRC). With our experience in basic and clinical research and routine work in this field we now have come to the opinion, that the term “CRC” should definitely be questioned, and if justified, be abandoned. materials/methods. We analyzed the actual available data from the literature and our own results from the Ulm based study group FOgT to proof or reject our hypothesis. results. The following evident differences were recognized: Anatomically, the risk to develop RC is 4× higher than for CC. Molecular changes in carcinogenesis in CC are different from RC. Physical activity helps to prevent CC, not RC. Pathologically there are differences between RC and CC. In addition, there are also major clinical differences between CC and RC, such as in surgical topography and- procedures, multimodal treatment (MMT) approaches (RC in MMT is less sensitive to chemotherapy than CC), and prognostic factors for the spontaneous course and for success of MMT (e.g. TS or DPD). discussion. CC´sand RC´s definitely are different in parameters of causal and formal carcinogenesis, effectivity of primary prevention by physical activity, conventional and molecular pathology.According to our findings we can demand from the preclinical point of view that CC and RC are two different tumor entities in terms of various representative biological characteristics.CC and RC are also differing substantially in many clinical features, as outlined in a separate paper from our group. Conclusion. “CRC” should no longer be used in basic and clinical research and other fields of cancer classification as a single disease entity. CC is not the same as RC. CC might even be divided into right and left CC.
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Comparative analysis of the exosomal cargo of the estrogen-resistant breast cancer cells
Статья научная
The exosomes involvement in the pathogenesis of tumors is based on their property to incorporate into the recipient cells resulting in the both genomic and epigenomic changes. Earlier we have shown that exosomes from different types of estrogen-independent breast cancer cells (MCF-7/T developed by long-term tamoxifen treatment, and MCF-7/M) developed by metformin treatment were able to transfer resistance to the parent MCF-7 cells. To elucidate the common features of the both types of resistant exosomes, the proteome and microRNA cargo of the control and both types of the resistant exosomes were analyzed. Totally, more than 400 proteins were identified in the exosome samples. Of these proteins, only two proteins, DMbT1 (Deleted in Malignant brain Tumors 1) and THbS1 (Thrombospondin-1), were commonly expressed in the both resistant exosomes (less than 5% from total DEPs) demonstrating the unique protein composition of each type of the resistant exosomes. The comparative analysis of the miRNA differentially expressed in the both MCF-7/T and MCF-7/M resistant exosomes revealed 180 up-regulated and 202 down-regulated miRNAs. Among them, 4 up-regulated and 8 down-regulated miRNAs were associated with progression of hormonal resistance of breast tumors. The bioinformatical analysis of 4 up-regulated exosomal miRNAs revealed 2 miRNAs, mir101and mir-181b, which up-regulated PI3K signaling supporting the key role of PI3K/Akt in the development of the resistant phenotype of breast cancer cells.
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Curcumin as an anti-proliferative agent in breast cancer through RASSF1A, BAX, and CASPASE-3 protein
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Background. Curcumin is a polyphenol that has pharmacological activity that can inhibit tumor cell growth and induce apoptosis through various mechanisms. However, the specific mechanism of curcumin cytotoxicity remains controversial because of many anti- and pro-apoptotic signaling pathways in various cell types. This study aims to examine the relationship among curcumin on RASSF1A, Bax protein levels, and caspase-3 activity in supporting the apoptotic mechanism in CSA03 breast cancer cells. Material and Methods. Curcumin administration to cancer cells is based on differences in dosage with 24-hour incubation. Cytotoxicity after curcumin administration was determined using MTS. RASSF1A and Bax protein levels were tested through ELiSA. Caspase-3 activity was used to determine apoptosis and was tested using flow cytometry. Results. The results indicated that curcumin had a cytotoxicity effect of 40.85 |jg/mL. At concentrations of 40 |jg/mL and 50 jg/mL, curcumin increases levels of protein RASSF1A (A = 26.53% and 47.35%, respectively), Bax (A = 48.79% and 386.15%), and caspase-3 (A = 1,678.51% and 1,871.889%) significantly. Conclusions. Curcumin exhibits anti-proliferative activity and apoptotic (Caspase-3) effects through activation of RASSF1A and Bax.
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CАР1 - сывороточный маркер ранней диагностики рака гортани и гортаноглотки
Статья научная
Плоскоклеточный рак головы и шеи (ПРГШ) часто характеризуется бессимптомным течением и плохим прогнозом. Для потенциально злокачественных эпителиальных дисплазий на данный момент не существует точных критериев, способных предсказать их переход в рак. Цель исследования - оценка возможности использования определения аденилил циклаза ассоциированного протеина 1 (САР1) в сыворотке крови для формирования групп онкологического риска больных хроническими гиперпластическими процессами гортани и гортаноглотки, ассоциированными с диспластическими изменениями вэпителии. Материал и методы. Исследовалась сыворотка крови 45 больных ПРГШ (T1-4N0-3M0), 12 человек с хроническими воспалительными заболеваниями гортани и гортаноглотки (ХГЛ) и 15 здоровых волонтеров. Анализ сыворотки крови проводили с помощью ИФА набора CAP1 ELISA kit (Cusabio) на микропланшетном ИФА ридере Anthos Reader 2020 (Biochrom). Результаты. Анализ содержания САР1 всыворотке крови больных всех представленных групп показал различия в зависимости от стадии патологического процесса. Сывороточный уровень САР1 на 75 % был значимо выше у больных ПРГШ со стадией заболевания Т1N0M0 по сравнению с группой больных ХГЛ с дисплазией II-III степени. Было отмечено значимое различие в группах здоровых лиц и больных ХГЛ. В группе больных ПРГШ с регионарными метастазами содержание САР1 в сыворотке крови было выше в 2 раза (р≤0,01), чем у больных без метастазов в регионарные лимфоузлы. Заключение. Результаты исследования показали принципиальную возможность использования определения содержания САР1 для дифференциальной диагностики больных ХГЛ и раком гортани, а также для ранней диагностики ПРГШ и перспективность для разработки нового метода прогноза течения заболевания.
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Cлучай дифференциальной диагностики опухоли и острого воспаления желчного пузыря при МСКТ
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Статья научная
Целью исследования явилось изучение структурно-функционального состояния пристеночного слизистого слоя и полостного секрета оставшейся части желудка у 64 больных после субтотальной дистальной резекции по поводу рака в раннем послеоперационном периоде и влияния эндоскопической лазеротерапии (44 пациента) и медикаментозного лечения (20 человек) на коррекцию выявленных нарушений. Выявлено, что в ранние сроки после проведенного лечения произошло достоверное изменение состава как структурных, так и внеструктурных гликопротеинов, парциального состава отдельных моносахаров в обеих группах. Был сделан вывод о том, что лазерное лечение по сравнению с медикаментозной терапией оказывает более серьезное влияние на биосинтез полимеризованных гликопротеинов и приближает их состав к нормальным показателям.
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Статья научная
Цель исследования - оценить особенности взаимосвязи атипичных/гибридных форм EpCAM+CD45+ клеток в асцитической жидкости у больных новообразованиями яичников с уровнем онкомаркеров СА125, HE4 и степенью злокачественности опухоли. Материал и методы. В клиническое исследование NCT04817501 включены 48 больных с впервые диагностированными новообразованиями яичников, из которых 42 пациентки с впервые диагностированным раком яичников Ic-IV стадии по FIGO, а также 6 женщин с пограничными новообразованиями яичников (ПОЯ), в возрасте от 36 до 76 лет. Материалом для исследования служили образцы асцитической жидкости и венозной стабилизированной крови. Наличие атипичных/гибридных форм EpCAM+CD45+ клеток в асцитической жидкости определяли методом многоцветной проточной цитометрии. Уровень онкомаркеров СА125 и HE4 в сыворотке крови определяли методом ИФА. Результаты. Количество EpCAM+CD45+ клеток в асцитической жидкости больных серозной карциномой яичников составило 1,02 (0,30; 2,68) клеток/мкл, при этом в группе больных Low-grade серозной карциномы яичников (LGSC) их уровень составил 0,55 (0,03; 4,51) клеток/мкл, а в группе High-grade (HGSC) - 1,36 (0,41; 2,68) клеток/мкл. Показано, что количество EpCAM+CD45+ клеток в асцитической жидкости у больных с новообразованиями яичников имеет прямую корреляционную связь с уровнем CA125 и HE4 в сыворотке крови (R=0,60; р function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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Early and long-term outcomes of liver resections: a single specialized center experience
Статья научная
The purpose of the study was to evaluate the outcomes of a series of liver resections performed in a single regional specialized cancer center. Material and Methods. Eighty-nine patients underwent liver and/ or extrahepatic bile duct resections in the Penza Regional Oncology Hospital over the 8-year study period. Malignancies were observed in 81 patients. Extended liver resections (4 segments or more) were performed in 58 (65.2 %) cases. Results. Postsurgical morbidity and mortality rates were 31.5 % (28 of 89) and 6.7 % (6 of 89), respectively. Six of 10 patients with primary liver carcinomas were alive without evidence of disease progression at a follow-up time ranged from 1.0 to 76.7 months. Adjuvant chemotherapy (ACT) was the only predictor (HR=0.40; 95 % CI 0.16-0.98) of overall survival in patients with metastatic colorectal cancer (mCRC). The median survival time after liver resections for mCRC with or without ACT was 54.5 (95 % CI: 14.5-94.5) vs 21.8 months (95 % CI: 14.2-29.4), respectively. In mCRC patients with ACT, the 5-year overall survival rate was 44.8 ± 12.9 %. Conclusion. Primary hepatobiliary carcinomas and colorectal cancer liver metastases are the most common reasons for liver resections. A series of liver resections in a low-volume hospital is feasible with the achievement of good outcomes.
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Efficacy of overnight intubation in oral oncological surgeries a retrospective study
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Objective. In the post-operative period of maxillofacial oncological operations, tracheostomy is the most commonly used method for securing the airway. These untoward complications made practitioners choose alternative modalities like submental intubation, but literature support on alternatives to tracheostomy for oral oncologic cases is limited. The aim of this observational study is to ascertain whether the use of overnight intubation is a safer and cost-effective practice and if it can be considered an alternative to tracheostomy. material and methods. 30 patients, 23 males and 7 females in the age group of 34-80 years who underwent treatment for head and neck cancer with major intraoral resection and a unilateral or bilateral neck dissection were included in the study. The following variables were recorded: age, sex, site of tumour, type of neck dissection, use of mandibulotomy/ mandibulectomy, type of reconstruction, duration of stay in ICU, mean hospital stay and Mallampati classification. Postoperative complications, associated with the airway, if any, were recorded simultaneously. results. None of the 30 patients required re-intubation nor did they develop any respiratory distress post extubation. conclusion. The purpose of this study is to raise the conscience of every surgeon to cogitate his/her choice of procedure for his/her patients and advocate the use of overnight intubation, as it is a virtuous alternative to tracheostomy.
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Статья научная
The purpose of the study was to analyze the ability of five antitumor drugs from the pharmaceutical group of protein kinase inhibitors (gefitinib, imatinib, pazopanib, ponatinib and enzastaurin) to reactivate the expression of the epigenetically silenced GFP in HeLa TI cells, and to estimate the effect of epigenetically active drugs on: 1) acetylation and methylation of histones H3 and H4; 2) integral DNA methylation; 3) activity of HAT and HDAC1 enzymes; 4) expression levels of the genes encoding epigenetic regulation enzymes (DNMT1, DNMT3A, DNMT3B; SIRT1, HDAC1; SETD1A, SETD1B, SUV420H1, SUV420H2, SUV39H1, SUV39H2). Material and Methods. The epigenetic activity of antitumor drugs was determined using the HeLa TI test system, a population of HeLa cells with the retroviral vector containing the epigenetically silenced GFP. The level of integral DNA methylation was analyzed using MspI/HpaII methyl-sensitive restriction analysis. Histone modifications were analyzed by Western blotting with antibodies to acetylated and methylated histones H3 and H4. The total activity of HAT enzymes was analyzed using Histone Acetyltransferase Activity Assay Kit. Expression of the epigenetic enzyme genes was analyzed using real-time quantitative RT-PCR. Results. It was shown that only the enzyme inhibitor Cp protein kinase enzastaurin had the ability to reactivate the expression of epigenetically silenced GFP in the HeLa TI cells. We showed that under the action of enzastaurin, the level of integral DNA methylation and expression of DNMT3A and DNMT3B DNA methyltransferase genes decreased. It was also found that enzastaurin reduced the expression levels of histone deacetylases HDAC1 and SIRT1, but did not affect the activity and expression levels of histone acetylases, the level of histone methylation (H3K4me3, H3K9me3, H3K27me3, H4K20me3), and the level of expression of the histone methyltransferases (SUV39H1, SUV39H2, SUV420H1, SUV420H2, SETD1A и SETD1B). Conclusion. The data obtained are important for clarifying the mechanisms of action of 5 protein kinase inhibitors, in particular with respect to enzastaurin, the protein kinase Cp inhibitor, for which the ability to reactivate epigenetically silent genes due to the effect on DNA methylation and histone acetylation was demonstrated.
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