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Combined modality treatment of early breast cancer. Literature review 早期乳腺癌的综合治疗。文献综述
Q4 Medicine Pub Date : 2024-01-05 DOI: 10.21294/1814-4861-2023-22-6-172-178
F. Akhmetzyanov, R. F. Akhmetzyanova, L. E. Ankhimova, E. S. Gorshkova, A. V. Karamanyan
The object of the study was to conduct a systematic literature review on combined modality treatment for early-stage breast cancer using postoperative and intraoperative radiation therapy, and consider new treatment approaches for early breast cancer.Material and Methods. The search for sources relevant to the review topic was carried out in the Medline, Cochrane Library, and Elibrary systems. A total of 905 studies on combination treatments for early breast cancer were identified, of which 43 were included in the review.Results. Data analysis showed that the rate of local relapses in early breast cancer was lower in patients who underwent breast-conserving surgery in combination with adjuvant radiation therapy than in patients without adjuvant radiation therapy. Research is ongoing on radiotherapy deintensification using intraoperative radiation therapy for patients at low risk of recurrence. Ongoing clinical trials support the omission of radiotherapy after breast-conserving surgery for elderly women with hormone receptor-positive early-stage breast cancer, who receive adjuvant endocrine therapy. Understanding the characteristics of the tumor process will allow us to personalize the treatment of patients with early breast cancer, reduce the risk of local relapses, and avoid unnecessary treatment-related complications.Conclusion. To improve survival in breast cancer patients is only possible by maximizing the tumor control. The effectiveness of adjuvant radiation therapy, which is an integral component in the combined modality treatment of early breast cancer, has been proven. However, third-generation studies discuss the feasibility of identifying a low-risk group of patients with a favorable clinical prognosis, who receive adequate endocrine therapy, and additional radiation do not provide a significant survival benefit.
本研究的目的是对早期乳腺癌术后和术中放射治疗联合模式进行系统性文献综述,并考虑早期乳腺癌的新治疗方法。在 Medline、Cochrane 图书馆和 Elibrary 系统中搜索与综述主题相关的资料。共找到 905 项关于早期乳腺癌综合治疗的研究,其中 43 项纳入综述。数据分析显示,接受保乳手术联合辅助放疗的早期乳腺癌患者局部复发率低于未接受辅助放疗的患者。针对低复发风险患者的术中放疗减量研究正在进行中。正在进行的临床试验支持对接受内分泌辅助治疗的激素受体阳性早期乳腺癌老年妇女在保乳手术后不进行放疗。了解肿瘤过程的特点将使我们能够对早期乳腺癌患者进行个性化治疗,降低局部复发的风险,避免不必要的治疗相关并发症。只有最大限度地控制肿瘤,才能提高乳腺癌患者的生存率。辅助放疗是早期乳腺癌综合治疗中不可或缺的组成部分,其有效性已得到证实。然而,第三代研究探讨了确定临床预后良好的低危患者群体的可行性,这些患者接受了充分的内分泌治疗,但额外的放射治疗并不能为患者带来显著的生存获益。
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引用次数: 0
Association of integrin expression in tumor tissue with hematogenic metastasis of breast cancer 肿瘤组织中整合素的表达与乳腺癌血行转移的关系
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-103-110
M. Zavyalova, G. A. Kuznetsov, E. Grigoryeva, L. Tashireva, D. Pismenny, V. Perelmuter
Background. Distant hematogenous metastasis is the leading cause of tumor-related death from breast cancer. To prevent metastasis, prognostic markers for predicting the risk and location of hematogenous metastases are required. In this regard, it is of great importance to study the expression of integrins involved in the most important processes that determine the progression of cancer.The objective of the study was to investigate the association of integrin expression in tumor tissue with hematogenous metastasis of patients with breast cancer.Material and Methods. The study included 72 patients (average age – 51 ± 12 years) with stage T1–4N0–3M0–1 unspecifed invasive ductal breast carcinoma, with all molecular biological subtypes (luminal A, luminal B, HER2-positive and triple negative). The biopsy material was examined before the start of antitumor treatment. Expression of integrins in tumor cells was assessed by immunohistochemical methods. Antibodies CD61 (integrin β3, Invitrogen, USA), CD104 (integrin β4, Invitrogen, USA), CD51 (integrin αV, Invitrogen, USA) were used.Results. In patients with hematogenous metastases, cytoplasmic rather than cytoplasmic/membrane colocalization, CD61 expression was more often detected (p=0.036). Cytoplasmic and membrane colocalization of CD104 was more frequently detected in brain metastases compared to lung (p=0.026) and bone (p=0.036) metastases. Expression of CD51 integrin was more often associated with lung metastases than with bone metastases (p=0.045).Conclusion. The frequency and localization of hematogenous metastases in breast cancer patients are associated with the presence and localization of CD61, CD104 and CD51 expression in the tumor cell.
背景。远处血行转移是乳腺癌肿瘤相关死亡的主要原因。为了防止转移,需要有预后标志物来预测血行转移的风险和位置。在这方面,研究参与决定癌症进展的最重要过程的整合素的表达具有重要意义。本研究的目的是调查整合素在肿瘤组织中的表达与乳腺癌患者血行转移的关系。研究对象包括72名T1-4N0-3M0-1期未明确分期的浸润性导管乳腺癌患者(平均年龄-51±12岁),均为分子生物学亚型(管腔A型、管腔B型、HER2阳性和三阴性)。活检材料在抗肿瘤治疗开始前进行检查。肿瘤细胞中整合素的表达通过免疫组化方法进行评估。使用的抗体为CD61(整合素β3,美国Invitrogen公司)、CD104(整合素β4,美国Invitrogen公司)、CD51(整合素αV,美国Invitrogen公司)。在血行转移的患者中,CD61的表达更常被检测到是细胞质而非细胞质/膜共聚焦(p=0.036)。与肺转移(p=0.026)和骨转移(p=0.036)相比,脑转移更常检测到 CD104 的细胞质和细胞膜共定位。与骨转移相比,CD51整合素的表达更常与肺转移相关(p=0.045)。乳腺癌患者血行转移的频率和定位与肿瘤细胞中 CD61、CD104 和 CD51 表达的存在和定位有关。
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引用次数: 0
Relationship between the cytokine profle of supernatants of invasive breast carcinoma and its molecular and histopathological characteristics 浸润性乳腺癌上清液中的细胞因子概况与其分子和组织病理学特征之间的关系
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-92-102
A. Autenshlyus, S. Arkhipov, E. Mikhaylova, V. Arkhipova, N. Varaksin
The aim of the study was to analyze the correlation between the cytokine profile of supernatants of invasive breast carcinoma of a nonspecific type (IBC-NST) samples, histopathological and molecular genetic parameters of IBC-NST, expression of the CD34 as a marker of angiogenesis and metastasis to regional lymph nodes (RLN).Material and Methods. The production of 14 cytokines in IBC-NST biopsy samples from 28 patients aged 37–60 years was studied. The concentration of cytokines in the supernatants of biopsies (CCSB) was determined (in pg/ml) using enzyme immunoassay (ELISA). The expression of CD34 and markers of IBC-NST molecular subtypes (HER2/neu, ER, PR, Ki67) in IBC-NST biopsy samples was evaluated by immunohistochemical method. The relative content of tumor cells of different differentiation grade in the IBC- NST samples was evaluated by histopathological analysis.Results. The assessment of CCSB showed statistically significant differences in IFN-γ, G-CSF, IL-2, IL-10 and MCP-1 between patients of group I (with metastases in RLNs) and group II (without metastases in RLNs). In group I, the correlations between histopathological parameters (Her2/neu, CD34 and Ki67 expressions, % of mitoses and poorly-differentiated cancer cells) and CCSB (MCP-1, IL-18) were revealed. In group II, the correlations between CCSB (IL-2, VEGF-A, G-CSF, IL-1Ra) and histopathological parameters, such as expression of Her2/neu, CD34, PR, % of mitoses and well-differentiated cancer cells, were revealed. The ROC analysis showed that the presence or absence of metastases in RLNs can be predicted on the basis of CD34 expression levels and concentrations of IL-10, G-CSF, and MCP-1 in supernatants of IBC-NST biopsy samples. The quality of the model for stratifying patients into groups with and without RLN metastases, based on the assessment of the concentration of MCP-1 in the supernatants of IBC-NST biopsies, reached maximum values (AUC=1.000) with relatively high CD34 expression.Conclusion. The analysis of the data obtained showed that the assessment of CD34 expression and production of cytokines in IBC-NST biopsies is important for predicting the presence or absence of metastases in RLNs.
该研究旨在分析非特异性浸润性乳腺癌(IBC-NST)样本上清液中细胞因子谱、IBC-NST的组织病理学和分子遗传学参数、作为血管生成和区域淋巴结(RLN)转移标志物的CD34的表达之间的相关性。研究了 28 名 37-60 岁 IBC-NST 患者活检样本中 14 种细胞因子的产生情况。使用酶联免疫吸附法(ELISA)测定活检上清液(CCSB)中细胞因子的浓度(以 pg/ml 为单位)。免疫组化法评估了 IBC-NST 活检样本中 CD34 和 IBC-NST 分子亚型标记物(HER2/neu、ER、PR、Ki67)的表达。组织病理学分析评估了 IBC-NST 样本中不同分化等级肿瘤细胞的相对含量。CCSB评估结果显示,I组(RLN有转移)和II组(RLN无转移)患者的IFN-γ、G-CSF、IL-2、IL-10和MCP-1差异有统计学意义。在 I 组中,组织病理学参数(Her2/neu、CD34 和 Ki67 表达、有丝分裂和低分化癌细胞百分比)与 CCSB(MCP-1、IL-18)之间存在相关性。在第二组中,CCSB(IL-2、VEGF-A、G-CSF、IL-1Ra)与组织病理学参数(如 Her2/neu、CD34、PR、有丝分裂百分比和分化良好的癌细胞的表达)之间的相关性显现出来。ROC分析表明,根据CD34的表达水平以及IBC-NST活检样本上清液中IL-10、G-CSF和MCP-1的浓度,可以预测RLN中是否存在转移。根据对 IBC-NST 活检样本上清液中 MCP-1 浓度的评估,将患者分为有和无 RLN 转移组的模型质量在 CD34 表达相对较高时达到了最大值(AUC=1.000)。对所获数据的分析表明,评估 IBC-NST 活检组织中 CD34 的表达和细胞因子的产生对于预测 RLN 是否存在转移非常重要。
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引用次数: 0
Virtual surgical planning in soft tissue reconstruction for oral cancer 口腔癌软组织重建中的虚拟手术规划
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-121-129
K. Amiraliyev, C. Rahimov, N. Amiraliyev, I. Farzaliyev
Introduction. Reconstruction of soft tissue defects after radical surgeries in cancer patients is important for early surgical rehabilitation and improving quality of life. Our study presents technologies for virtual surgical planning (VSP) of soft tissue defect reconstruction in patients with squamous cell carcinoma of the oral cavity.Case presentation. We described VSP in a report of a 54-year-old patient with locally advanced buccal mucosa cancer after extensive radical resection and reported the results. VSP was used to construct a 3D model from CT images, which was used to accurately assess the margin of radical surgical resection, as well as to develop individually based reconstruction of soft tissue defects. Next, we reported a series of cases of patients with oral cancer of various locations, who, after radical surgery, underwent reconstruction with using of VSP (n=7) or conventional reconstruction (n=10). A comparative analysis of intra and postoperative results was carried out.Results. In a patient with locally advanced left buccal mucosa cancer, reconstruction of the postoperative defect was successful without local complications after reconstruction. Good functional and aesthetic results were obtained. The patient was observed for 2 years without signs of disease. A comparative assessment of the results of the main and control groups showed that patients in the VSP group had a shorter operation time and postoperative hospital stay, as well as fewer and milder postoperative local complications in comparison with the control group.Conclusion. Our results showed the effectiveness of using 3D technology in reconstructive surgery of soft tissue defects after radical surgery for oral SCC. This technology has significantly reduced operative time, hospital stay, and improved flap utilization. This method has great potential for wider application and provides greater benefits with further improvement of technology.
简介癌症患者根治术后软组织缺损的重建对于早期手术康复和提高生活质量非常重要。我们的研究介绍了口腔鳞状细胞癌患者软组织缺损重建的虚拟手术规划(VSP)技术。我们在一名 54 岁的局部晚期口腔黏膜癌患者的广泛根治性切除术后的报告中描述了 VSP,并报告了结果。VSP 被用于根据 CT 图像构建三维模型,该模型被用于准确评估根治性手术切除的边缘,以及对软组织缺损进行基于个体的重建。接下来,我们报告了一系列不同部位口腔癌患者的病例,这些患者在接受根治性手术后,使用 VSP 重建(7 例)或传统重建(10 例)。对术中和术后结果进行了对比分析。在一名局部晚期左侧口腔粘膜癌患者身上,术后缺损的重建非常成功,重建后没有出现局部并发症。获得了良好的功能和美学效果。对患者进行了两年的观察,未发现任何疾病迹象。对主要组和对照组结果的比较评估显示,与对照组相比,VSP 组患者的手术时间和术后住院时间更短,术后局部并发症更少、更轻。我们的研究结果表明,在口腔 SCC 根治术后的软组织缺损重建手术中使用 3D 技术非常有效。这项技术大大缩短了手术时间和住院时间,并提高了皮瓣的利用率。随着技术的进一步改进,这种方法具有更广泛的应用潜力,并能带来更大的益处。
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引用次数: 0
Impact of molecular genetic profle of meningiomas on the clinical course and recurrence using combined modality treatment 脑膜瘤的分子遗传学特征对采用联合模式治疗的临床过程和复发的影响
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-138-152
G. Sergeev, A. S. Gaytan, M. A. Travin, A. B. Ponomarev, M. A. Afonina, I. A. Savitskaya, F. Yakhya, A. Krivoshapkin
Introduction. Meningioma is one of the most common central nervous system tumors, accounting for 39.7 % of all primary brain tumors. The tumor originates from arachnoid meningothelial cells and is characterized by a wide range of histological types classified into 15 subtypes. The histological classification of meningiomas allows us to predict meningioma behavior and the risk of disease recurrence, as well as to define treatment strategies. However, clinical outcomes in histological subgroups of patients are often inconsistent with the histological grade of malignancy. Thus, a more reliable method is needed both to determine the histological subtype of the tumor and to predict the clinical course of the disease with the potential for targeted treatment.The purpose of the study was to summarize the available data on the effect of results of the genomic and proteomic tumor analysis on carcinogenesis with the relationship between the mutational changes and noninvasive diagnosis, treatment and the course of the disease.Material and Methods. Literature search was carried out in the PubMed, Elibrary system, publications were included mainly from 2010 to 2023. with the identification of articles by the keyword “genetic analysis of meningiomas” and synonyms. 550 articles were found, of which 55 were used to write a literature review.Conclusion. The study of the molecular genetic profile of meningiomas will improve the classification and establish a correlation with MRI data, the course of the disease and prognosis.
简介脑膜瘤是最常见的中枢神经系统肿瘤之一,占所有原发性脑肿瘤的 39.7%。该肿瘤起源于蛛网膜脑膜上皮细胞,组织学类型多种多样,可分为 15 个亚型。脑膜瘤的组织学分类使我们能够预测脑膜瘤的行为和疾病复发的风险,并确定治疗策略。然而,组织学亚组患者的临床结果往往与恶性肿瘤的组织学分级不一致。因此,需要一种更可靠的方法,既能确定肿瘤的组织学亚型,又能预测疾病的临床过程,并有可能进行有针对性的治疗。本研究的目的是总结肿瘤基因组和蛋白质组分析结果对癌变影响的现有数据,以及突变变化与非侵入性诊断、治疗和疾病过程之间的关系。在 PubMed 和 Elibrary 系统中进行文献检索,主要包括 2010 年至 2023 年期间的出版物,通过关键词 "脑膜瘤的基因分析 "和同义词识别文章。共找到 550 篇文章,其中 55 篇用于撰写文献综述。对脑膜瘤分子遗传特征的研究将改进分类,并建立与核磁共振成像数据、病程和预后的相关性。
{"title":"Impact of molecular genetic profle of meningiomas on the clinical course and recurrence using combined modality treatment","authors":"G. Sergeev, A. S. Gaytan, M. A. Travin, A. B. Ponomarev, M. A. Afonina, I. A. Savitskaya, F. Yakhya, A. Krivoshapkin","doi":"10.21294/1814-4861-2023-22-6-138-152","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-6-138-152","url":null,"abstract":"Introduction. Meningioma is one of the most common central nervous system tumors, accounting for 39.7 % of all primary brain tumors. The tumor originates from arachnoid meningothelial cells and is characterized by a wide range of histological types classified into 15 subtypes. The histological classification of meningiomas allows us to predict meningioma behavior and the risk of disease recurrence, as well as to define treatment strategies. However, clinical outcomes in histological subgroups of patients are often inconsistent with the histological grade of malignancy. Thus, a more reliable method is needed both to determine the histological subtype of the tumor and to predict the clinical course of the disease with the potential for targeted treatment.The purpose of the study was to summarize the available data on the effect of results of the genomic and proteomic tumor analysis on carcinogenesis with the relationship between the mutational changes and noninvasive diagnosis, treatment and the course of the disease.Material and Methods. Literature search was carried out in the PubMed, Elibrary system, publications were included mainly from 2010 to 2023. with the identification of articles by the keyword “genetic analysis of meningiomas” and synonyms. 550 articles were found, of which 55 were used to write a literature review.Conclusion. The study of the molecular genetic profile of meningiomas will improve the classification and establish a correlation with MRI data, the course of the disease and prognosis.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139389172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of E-cadherin and β-catenin in head and neck squamous cell carcinoma E 黏附因子和β-catenin在头颈部鳞状细胞癌中的作用
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-130-137
A. A. Petrova, S. Samoylova, L. V. Magomedkerimova, S. A. Parts, I. V. Reshetov
Aim of the study: to present and summarize current data on the prognostic value of E-cadherin and β-catenin markers for head and neck squamous cell carcinoma, as well as to substantiate the potential benefit from implementing research results into clinical practice within the framework of a personalized approach to the treatment of head and neck squamous cell carcinoma.Material and Methods. We performed a literature search and review in Pubmed, Scopus, Google Scholar and RSCI databases regarding the association of the level of E-cadherin and β-catenin markers with disease prognosis, aggressiveness of tumor behavior and response to treatment.Results. Detailed information on the functions and mechanisms of E-cadherin and β-catenin proteins were presented and pathogenetic pathways involved in epithelial-mesenchymal transition were described. The results of studies on the association of β-catenin and E-cadherin expression levels with the prognosis of head and neck squamous cell carcinoma are collected and summarized. High expression levels of β-catenin and E-cadherin are associated with lymph node metastasis, poor prognosis and poor response to treatment.Conclusion. The expression levels of β-catenin and E-cadherin correlate with tumor invasion and lymph node metastasis, thus suggesting that β-catenin and E-cadherin can be used as potential markers of prognosis and treatment response in patients with head and neck squamous cell carcinoma. Further studies are needed to evaluate the co-expression of E-cadherin, β-catenin and other squamous cell carcinoma-associated markers, their impact on prognosis and treatment response, as well as their prognostic value.
研究目的:介绍和总结有关头颈部鳞状细胞癌E-cadherin和β-catenin标记物预后价值的现有数据,并证实在头颈部鳞状细胞癌个性化治疗方法框架内将研究成果应用于临床实践的潜在益处。我们在Pubmed、Scopus、Google Scholar和RSCI数据库中对E-cadherin和β-catenin标记物水平与疾病预后、肿瘤行为的侵袭性和治疗反应的相关性进行了文献检索和综述。详细介绍了E-cadherin和β-catenin蛋白的功能和机制,并描述了上皮-间质转化过程中的致病途径。收集并总结了β-catenin和E-cadherin表达水平与头颈部鳞状细胞癌预后相关性的研究结果。结论:β-catenin和E-cadherin的高表达水平与淋巴结转移、预后不良和治疗反应差有关。β-catenin和E-cadherin的表达水平与肿瘤侵袭和淋巴结转移相关,因此提示β-catenin和E-cadherin可作为头颈部鳞状细胞癌患者预后和治疗反应的潜在标志物。还需要进一步的研究来评估E-cadherin、β-catenin和其他鳞状细胞癌相关标记物的共同表达、它们对预后和治疗反应的影响及其预后价值。
{"title":"Role of E-cadherin and β-catenin in head and neck squamous cell carcinoma","authors":"A. A. Petrova, S. Samoylova, L. V. Magomedkerimova, S. A. Parts, I. V. Reshetov","doi":"10.21294/1814-4861-2023-22-6-130-137","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-6-130-137","url":null,"abstract":"Aim of the study: to present and summarize current data on the prognostic value of E-cadherin and β-catenin markers for head and neck squamous cell carcinoma, as well as to substantiate the potential benefit from implementing research results into clinical practice within the framework of a personalized approach to the treatment of head and neck squamous cell carcinoma.Material and Methods. We performed a literature search and review in Pubmed, Scopus, Google Scholar and RSCI databases regarding the association of the level of E-cadherin and β-catenin markers with disease prognosis, aggressiveness of tumor behavior and response to treatment.Results. Detailed information on the functions and mechanisms of E-cadherin and β-catenin proteins were presented and pathogenetic pathways involved in epithelial-mesenchymal transition were described. The results of studies on the association of β-catenin and E-cadherin expression levels with the prognosis of head and neck squamous cell carcinoma are collected and summarized. High expression levels of β-catenin and E-cadherin are associated with lymph node metastasis, poor prognosis and poor response to treatment.Conclusion. The expression levels of β-catenin and E-cadherin correlate with tumor invasion and lymph node metastasis, thus suggesting that β-catenin and E-cadherin can be used as potential markers of prognosis and treatment response in patients with head and neck squamous cell carcinoma. Further studies are needed to evaluate the co-expression of E-cadherin, β-catenin and other squamous cell carcinoma-associated markers, their impact on prognosis and treatment response, as well as their prognostic value.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Variability of the mitochondrial genome in young Yakut patients with breast cancer 雅库特年轻乳腺癌患者线粒体基因组的变异性
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-74-82
D. Tikhonov, A. Egorov, M. Golubenko, A. Molokov, V. Belyavskaya, P. Gervas, N. Skryabin
Background. The Sakha (Yakutia) population, the indigenous population of Siberia living in Yakutia, has one of the lowest rates of breast cancer (BC) incidence worldwide. The low BC incidence among the indigenous population of Yakutia has been reported by several authors, but to date the reasons for this phenomenon have not been fully elucidated. It should be noted that the study of factors that reduce the risk of BC is important for its prevention. In several studies, no hereditary BC was found in the Yakuts, and no pathogenic variants of the BRCA1/2 genes associated with hereditary syndromes of breast and ovarian cancers were found. In this regard, we decided to shift the focus to studying the mitochondrial genome of Sakha BC patients using the sequencing method.The purpose of the study was to identify BC-associated mitochondrial genome variants in Sakha patients.Material and Methods. The study included 14 Sakha patients diagnosed with BC. The median age of the patients was 49 years. DNA isolation was performed using phenol-chloroform extraction. DNA libraries were prepared using the Nextera Flex kit (Illumina, USA).Whole-genome sequencing of the mitochondrial genome was performed on a MiSeq instrument (Illuminа, USA). in the Shared Use Centre of the Research Institute of Medical Genetics, Tomsk National Research Centre of the Russian Academy of Sciences. The results obtained in BC patients were compared with those of control subjects.Results. In Sakha women with BC, 159 mitochondrial genome variants that differed from the human mitochondrial DNA (mtDNA) reference sequence (rCRS) were identified. Likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were shown to be associated with BC. For the first time, variants predisposing to BC (m.10398A>G; m.14783T>C; m.15043G>A; m.15301G>A) were identified. A distinctive feature of the mitochondrial genome of populations with a low BC incidence is a high level of mtDNA variants with changes in the length of the polycytosine region in the D310 locus.Conclusion. For the first time, mtDNA variants with changes in the length of the polycytosine tract in the D310 locus and likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were identified in Sakha BC women. The data obtained indicate that further studies on the role of the identified mtDNA variants in the development of BC using a larger sample of Sakha patients are required.
背景。萨哈(雅库特)人是居住在雅库特的西伯利亚土著居民,是全世界乳腺癌(BC)发病率最低的人群之一。雅库特原住民乳腺癌发病率低的情况已有多位学者报道,但迄今为止,造成这一现象的原因尚未完全阐明。应该指出的是,研究降低 BC 风险的因素对于预防 BC 非常重要。在多项研究中,没有发现雅库特人有遗传性 BC,也没有发现与乳腺癌和卵巢癌遗传综合征相关的 BRCA1/2 基因的致病变体。有鉴于此,我们决定将研究重点转向使用测序方法研究萨哈族 BC 患者的线粒体基因组。研究包括 14 名被确诊为 BC 的萨哈族患者。患者的中位年龄为 49 岁。DNA分离采用苯酚-氯仿提取法。线粒体基因组的全基因组测序在俄罗斯科学院托木斯克国家研究中心医学遗传学研究所共享中心的 MiSeq 仪器(Illuminа,美国)上进行。将 BC 患者的结果与对照组的结果进行了比较。结果发现,在萨哈女性 BC 患者中,有 159 个线粒体基因组变异与人类线粒体 DNA(mtDNA)参考序列(rCRS)不同。结果表明,MT-ND1 基因的 m.3736G>A 和 MT-CO1 基因的 m.7279T>C 可能与 BC 有关。首次发现了易导致 BC 的变体(m.10398A>G;m.14783T>C;m.15043G>A;m.15301G>A)。BC发病率低的人群线粒体基因组的一个显著特点是,D310位点多胞嘧啶区长度发生变化的mtDNA变异水平较高。在萨哈族 BC 妇女中首次发现了 D310 位点多胞嘧啶区长度变化的 mtDNA 变异以及 MT-ND1 基因 m.3736G>A 和 MT-CO1 基因 m.7279T>C 的可能致病变异。获得的数据表明,需要使用更多的萨哈病人样本,进一步研究已确定的 mtDNA 变异在 BC 发病中的作用。
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引用次数: 0
The use of xenogenic testicular antigens for induction of antitumor reactions 利用异种睾丸抗原诱导抗肿瘤反应
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-111-120
G. Seledtsova, A. B. Dorzhieva, I. P. Ivanova, V. Seledtsov
Testicular antigens (TAGs) are normally expressed only by cells of testicular and placental tissues. Human immune system is tolerant to TAG, but if the integrity of the testicular membranes is disrupted, these antigens, entering the bloodstream, induce autoimmune reactions for eliminating them from the body. In malignancy, TAGs begin to be expressed by tumor cells of the liver, breast, pancreas, intestine, and lung. Immunological recognition of these AGs leads to autoimmune reactions against these AGs, i.e. antitumor reactions in the body. We used xenogenic TAGs derived from ram testis to increase TAG immunogenicity. The use of ram TAGs is justified by the fact that TAGs are evolutionarily conserved molecules and there is a high degree of homology between human and animal TAGs.The purpose of the study was to evaluate the lifespan of tumor-bearing mice and parameters of cellular immunity in various options for immunizing mice with ram TAGs.Material and Methods. C57BL/6 mice were used. The efficacy of therapeutic or prophylactic vaccination with xenogenic TAGs was studied by changing lifespan of B16 and LLC tumor-bearing mice. Formation of immune responses was evaluated by proliferative ability of splenocytes to respond to vaccination and control AGs and by their production of IFN-gamma and IL-10.Results. In the LLC carcinoma model with a preventive vaccination option, the lifespan of mice with syngeneic vaccination did not differ from the tumor control; the lifespan of mice with xenogeneic vaccination increased by 60%. In therapeutic vaccination option, no significant differences in lifespan of vaccinated mice were found. A significant increase in the proliferative activity of splenocytes in response to tumor AGs was found in both LLC- and B16 tumor-bearing mice previously vaccinated with xenogenic TAGs. The increased IFN-gamma production by splenocytes was observed in B16 and LLC tumorbearing mice with xenogeneic vaccination. The IFN-gamma production by splenocytes in tumor-bearing mice with syngeneic vaccination was not increased. A significant decrease in IL-10 production was noted in mice with xenogeneic vaccination.
睾丸抗原(TAG)通常只由睾丸和胎盘组织细胞表达。人体免疫系统对 TAG 具有耐受性,但如果睾丸膜的完整性遭到破坏,这些抗原进入血液后就会诱发自身免疫反应,将其排出体外。在恶性肿瘤中,肝脏、乳腺、胰腺、肠道和肺部的肿瘤细胞开始表达 TAG。对这些 AGs 的免疫识别会导致针对这些 AGs 的自身免疫反应,即体内的抗肿瘤反应。我们使用来自公羊睾丸的异种 TAG 来增加 TAG 的免疫原性。使用公羊 TAGs 的理由是 TAGs 是进化上保守的分子,而且人类和动物的 TAGs 之间存在高度的同源性。本研究的目的是评估肿瘤小鼠的寿命以及用公羊 TAGs 免疫小鼠的各种方案中细胞免疫的参数。使用 C57BL/6 小鼠。通过改变 B16 和 LLC 肿瘤小鼠的寿命来研究异种 TAG 治疗性或预防性接种的效果。通过脾细胞对疫苗和对照 AGs 的增殖反应能力以及它们产生的 IFN-gamma 和 IL-10 来评估免疫反应的形成。在LLC癌模型中,选择预防性疫苗接种的小鼠寿命与肿瘤对照组没有差异;选择异种接种的小鼠寿命延长了60%。在治疗性疫苗接种方案中,接种小鼠的寿命没有发现显著差异。曾接种异种TAGs的LLC和B16肿瘤小鼠脾细胞对肿瘤AGs的增殖活性都有明显增加。在接种异种疫苗的 B16 和 LLC 肿瘤小鼠中观察到脾脏细胞产生的 IFN-gamma 增加。而接种了合成疫苗的肿瘤小鼠脾脏细胞产生的 IFN-gamma 没有增加。在接种异种疫苗的小鼠中,IL-10的产生明显减少。
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引用次数: 0
BRCA1/2 mutation spectrum in Armenian patients with breast and ovarian cancers 亚美尼亚乳腺癌和卵巢癌患者的 BRCA1/2 基因突变谱
Q4 Medicine Pub Date : 2024-01-03 DOI: 10.21294/1814-4861-2023-22-6-83-91
Y. Belysheva, E. K. Bakaeva, A. Venina, A. Romanko, G. Raskin, A. Sokolenko, E. N. Suspitsin, A. A. Avetisyan, S. Orlov, E. N. Imyanitov
The aim of the study was to compare the spectra of pathogenic BRCA1 and BRCA2 variants in patients with hereditary breast cancer (BC) and ovarian cancer (OC) from two groups of ethnic Armenians: Yerevan and cities of southern Russia.Material and Methods. 106 BC patients from the V.A. Fanardjian National Centre of Oncology (Yerevan, Republic of Armenia) and 117 BC and OC patients of Armenian origin who were referred to the Petrov National Medical Centre of Oncology (St. Petersburg, Russia) from several cancer centers of Russia (Krasnodar, Sochi, Pyatigorsk) were included into the study. The coding sequences of BRCA1 and BRCA2 genes were analyzed by the method of targeted high-throughput sequencing.Results. Pathogenic variants of BCRA1 and BCRA2 genes were detected in 16/106 (BRCA1: n=9, BRCA2: n=7; 15%) BC patients from Yerevan. The only recurrent mutation was the BRCA1 nonsense variant c.5444G>A [W1815X], accounting for 44% of all pathogenic alleles identified. In patients of Armenian origin from Russia, pathogenic BRCA1/2 variants were detected in 16/117 (14%) individuals (BRCA1: n=6, BRCA2: n=10). The proportion of samples with mutations was 13% in the group of BC patients and 19% in the group of OC patients. 75% of pathogenic alleles were represented by five recurrent mutations: BRCA1 c.2649_2650insGGCA, BRCA2 c.2808_2808_2811delACAA, BRCA1 c.4065_4068delTCAA, BRCA2 c.9027delT and BRCA2 c.8437G>T [G2813X]. The independent origin of the pathogenic BRCA2 c.2808_2808_2811delACAA variant in Armenian and non-Armenian patients was shown.Conclusion. A significant difference in the spectrum of BRCA1/2 mutations between Armenian patients from Yerevan and patients from southern regions of Russia was found. This should be taken into account when developing diagnostic programs.
该研究旨在比较两个亚美尼亚族群体中遗传性乳腺癌(BC)和卵巢癌(OC)患者的致病性 BRCA1 和 BRCA2 变体谱:材料与方法。研究对象包括来自 V.A. Fanardjian 国家肿瘤中心(亚美尼亚共和国埃里温)的 106 名 BC 患者,以及从俄罗斯多个癌症中心(克拉斯诺达尔、索契、皮亚季戈尔斯克)转诊至彼得罗夫国家肿瘤医疗中心(俄罗斯圣彼得堡)的 117 名 BC 和 OC 亚美尼亚裔患者。研究采用靶向高通量测序法分析了 BRCA1 和 BRCA2 基因的编码序列。在埃里温的 16/106 例(BRCA1:9 例,BRCA2:7 例;15%)BC 患者中检测到 BCRA1 和 BCRA2 基因的致病变异。唯一反复出现的变异是 BRCA1 无义变异 c.5444G>A [W1815X],占所有已发现致病等位基因的 44%。在来自俄罗斯的亚美尼亚裔患者中,有16/117人(14%)检测到致病性BRCA1/2变异(BRCA1:6人,BRCA2:10人)。在 BC 患者组中,出现变异的样本比例为 13%,在 OC 患者组中为 19%。75%的致病等位基因由五个复发性突变代表:BRCA1 c.2649_2650insGGCA、BRCA2 c.2808_2808_2811delACAA、BRCA1 c.4065_4068delTCAA、BRCA2 c.9027delT和BRCA2 c.8437G>T [G2813X]。结果表明,在亚美尼亚和非亚美尼亚患者中,致病的 BRCA2 c.2808_2808_2811delACAA 变异具有独立的来源。来自埃里温的亚美尼亚患者与来自俄罗斯南部地区的患者在 BRCA1/2 基因突变谱方面存在明显差异。在制定诊断方案时应考虑到这一点。
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引用次数: 0
Changes in left ventricular systolic and diastolic function after chemotherapy for breast cancer with doxorubicin 乳腺癌多柔比星化疗后左心室收缩和舒张功能的变化
Q4 Medicine Pub Date : 2024-01-02 DOI: 10.21294/1814-4861-2023-22-6-64-73
I. A. Karput, V. A. Snezhitskii, M. Kurbat, V. A. Gorustovich, Yu. I. Karpovich, A. Y. Rubinskii, T. A. Smirnova, A. Babenka
Introduction. Detection of the cardiotoxic effect during chemotherapy (CT) for malignant neoplasms is one of the most important tasks of a practicing physician. Purpose: to study changes in left ventricular systolic and diastolic function using echocardiography (EchoCG) during chemotherapy with doxorubicin in patients with primary breast cancer (BC) and to identify potential markers of early cardiotoxicity (CT).Material and Methods. The study included 100 patients with a confirmed diagnosis of breast cancer who were treated at the health care institution “Grodno University Clinic” (Grodno, Belarus).Results. In the study sample, a number of EchoCG parameters were measured before and after chemotherapy in 100 patients with breast cancer. Depending on the choice of the threshold level of relative reduction in global longitudinal strain (GLS) in %, different median values were recorded in the subgroups with and without CT (before and after chemotherapy). Data are presented on the difference in the relative dynamics of EchoCG indicators in % between the subgroups with CT and without CT, which shows how large the differences between the subgroups are in % after the end of chemotherapy. Against the background of the absence of statistically significant differences, trends towards an increase or decrease in indicators were recorded, which can characterize them as potential CT markers.Conclusion. We hypothesize that indexed end-systolic volume, indexed end-diastolic volume, early diastolic peak velocity of lateral mitral annulus motion may be considered as potential CT markers in the subclinical stage along with GLS; if it is impossible to measure a relative decrease in GLS, these indicators collectively may indicate the development of a CT effect at the subclinical stage. When diagnosing a relative decrease in the GLS index by less than 15 %, but by more than 10 %, we propose to consider the indexed end-systolic volume index as a marker of the early CT effect if its increase after the end of chemotherapy is recorded by 10 % or more, respectively.
简介在恶性肿瘤化疗(CT)期间检测心脏毒性效应是执业医生最重要的任务之一。目的:使用超声心动图(EchoCG)研究原发性乳腺癌(BC)患者在接受多柔比星化疗期间左心室收缩和舒张功能的变化,并确定早期心脏毒性(CT)的潜在标志物。研究对象包括在医疗机构 "格罗德诺大学诊所"(白俄罗斯格罗德诺)接受治疗的100名确诊为乳腺癌的患者。在研究样本中,对 100 名乳腺癌患者化疗前后的一系列 EchoCG 参数进行了测量。根据全纵向应变(GLS)相对减少百分比临界值的选择,在有 CT 和无 CT 的分组(化疗前和化疗后)中记录了不同的中值。数据显示了有 CT 和无 CT 亚组之间 EchoCG 指标的相对动态差异(%),说明了化疗结束后亚组之间的差异(%)有多大。在没有显著统计学差异的背景下,我们记录了指标增减的趋势,这可以将它们描述为潜在的CT标志物。我们假设,在亚临床阶段,收缩末期容积指数、舒张末期容积指数、二尖瓣环侧向运动的舒张早期峰值速度可与GLS一起被视为潜在的CT标志物;如果无法测量GLS的相对下降,这些指标可共同表明亚临床阶段CT效应的发展。在诊断 GLS 指数相对下降小于 15%但大于 10%时,如果化疗结束后收缩末期容积指数增加 10%或更多,我们建议将其作为早期 CT 效应的标志物。
{"title":"Changes in left ventricular systolic and diastolic function after chemotherapy for breast cancer with doxorubicin","authors":"I. A. Karput, V. A. Snezhitskii, M. Kurbat, V. A. Gorustovich, Yu. I. Karpovich, A. Y. Rubinskii, T. A. Smirnova, A. Babenka","doi":"10.21294/1814-4861-2023-22-6-64-73","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-6-64-73","url":null,"abstract":"Introduction. Detection of the cardiotoxic effect during chemotherapy (CT) for malignant neoplasms is one of the most important tasks of a practicing physician. Purpose: to study changes in left ventricular systolic and diastolic function using echocardiography (EchoCG) during chemotherapy with doxorubicin in patients with primary breast cancer (BC) and to identify potential markers of early cardiotoxicity (CT).Material and Methods. The study included 100 patients with a confirmed diagnosis of breast cancer who were treated at the health care institution “Grodno University Clinic” (Grodno, Belarus).Results. In the study sample, a number of EchoCG parameters were measured before and after chemotherapy in 100 patients with breast cancer. Depending on the choice of the threshold level of relative reduction in global longitudinal strain (GLS) in %, different median values were recorded in the subgroups with and without CT (before and after chemotherapy). Data are presented on the difference in the relative dynamics of EchoCG indicators in % between the subgroups with CT and without CT, which shows how large the differences between the subgroups are in % after the end of chemotherapy. Against the background of the absence of statistically significant differences, trends towards an increase or decrease in indicators were recorded, which can characterize them as potential CT markers.Conclusion. We hypothesize that indexed end-systolic volume, indexed end-diastolic volume, early diastolic peak velocity of lateral mitral annulus motion may be considered as potential CT markers in the subclinical stage along with GLS; if it is impossible to measure a relative decrease in GLS, these indicators collectively may indicate the development of a CT effect at the subclinical stage. When diagnosing a relative decrease in the GLS index by less than 15 %, but by more than 10 %, we propose to consider the indexed end-systolic volume index as a marker of the early CT effect if its increase after the end of chemotherapy is recorded by 10 % or more, respectively.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139390492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Siberian journal of oncology
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