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New method of modified chemoradiotherapy for cancer of the upper and middle ampullary rectum 改良放化疗治疗上、中壶腹直肠癌的新方法
Pub Date : 2023-04-13 DOI: 10.37748/2686-9039-2023-4-2-6
Y. Gevorkyan, N. Soldatkina, M. N. Chernyak, M. Gusareva, O. Bondarenko, E. Dzhenkova, A. Dashkov, V. E. Kolesnikov, D. Petrov, R. E. Tolmakh, D. A. Savchenko
The last decade is characterized by significant progress in the treatment of rectal cancer (reduction in the number of relapses to 5–6 % with the use of prolonged radiation therapy) before surgery. The greatest success has been achieved in the treatment of cancer of the lower ampulla of the rectum, when it is possible to develop a complete clinical response of the rectal tumor to chemoradiotherapy. Nevertheless, the requirement issues to improve the results of treatment of cancer of the upper and middle ampullar rectum with an increase in the survival of patients remain. Which makes it relevant to develop new methods, that increase the effectiveness of the treatment of rectal cancer.The method of modified chemoradiotherapy for cancer of the upper ampulla of the rectum was developed in our study. The method is as follows: at the first stage, one day before the start of radiation therapy, the patient undergoes superselective catheterization of the superior rectal artery through the radial or femoral artery, followed by regional administration of radiomodifying chemotherapy drugs: cisplatin 50 mg and fluorouracil 500 mg. In one day, patients begin to undergo a course of conformal remote large- fraction radiation therapy to the primary focus and metastasis pathways for 5 sessions with a single focal dose of 5 Gy to a total focal dose of 25 Gy using a low-energy linear accelerator. During the entire course of radiation therapy, fluorouracil 500 mg is administered daily intravenously for 30 minutes in 30 minutes before the session. Surgical intervention with the sampling of material for research is carried out 6–8 weeks after the radiation therapy is completed. To assess the effectiveness of the modified chemoradiotherapy, the stage of tumor regression was determined according to the RECIST scale, and the level of therapeutic pathomorphology of the tumor according to Dworak was determined during a morphological study of the rectal tumor removed during the operation.The developed method of modified chemoradiotherapy makes it possible to achieve regression of the rectal tumor in a short time, reduce the time and increase the effectiveness of treatment. The method of modified chemoradiotherapy is intended for patients with cancer of the upper and middle ampullar rectum T3-4N0-2M0, for whom radiation therapy is indicated as the first stage of treatment, after which resection of the rectum is performed in a standard volume.
过去十年的特点是手术前直肠癌治疗取得了重大进展(使用长期放射治疗将复发率降低至5 - 6%)。直肠下壶腹癌的治疗取得了最大的成功,此时直肠肿瘤对放化疗有了完全的临床反应。然而,提高上壶腹和中壶腹直肠癌的治疗效果,提高患者的生存率仍然是需要解决的问题。这就需要开发新的方法,提高直肠癌治疗的有效性。本研究提出改良放化疗治疗直肠上壶腹癌的方法。方法如下:第一阶段,放疗开始前1天,患者经桡动脉或股动脉超选择性置管直肠上动脉,局部给予化疗药物顺铂50 mg、氟尿嘧啶500 mg。在一天内,患者开始接受一个疗程的适形远程大剂量放射治疗,以主要病灶和转移途径为5个疗程,单局剂量为5 Gy至总局剂量为25 Gy,使用低能线性加速器。在整个放射治疗过程中,在放射治疗前30分钟内每日静脉注射氟尿嘧啶500毫克,持续30分钟。在放射治疗完成后6-8周进行手术干预,并取样研究材料。为了评估改良放化疗的有效性,根据RECIST量表确定肿瘤消退的分期,并根据Dworak对术中切除的直肠肿瘤进行形态学研究,确定肿瘤的治疗病理形态学水平。所开发的改良放化疗方法可以在短时间内实现直肠肿瘤的消退,减少了治疗时间,提高了治疗效果。改良放化疗方法适用于壶腹上、中端直肠癌T3-4N0-2M0患者,第一阶段采用放疗,然后在标准体积内行直肠切除术。
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引用次数: 0
Monograph review by Kit O. I., Shaposhnikov A. V. "General carcinogenesis. Exogenous tumorogenic effects" Kit O. I. Shaposhnikov A. V.的专著综述。“一般的致癌作用。外源性致瘤效应”
Pub Date : 2023-03-04 DOI: 10.37748/2686-9039-2023-4-1-9
A. Abrosimov
The second part of a three-component work on gen- eral carcinogenesis has been published. The first part (2021) deploys modern theories, models of general carcinogenesis: mutation theory, models of genomic instability, Darwinian and non-genotoxic models, and also explains the roles of inflammation, immunological devi- ations and tumor microenvironment in carcinogenesis.
关于一般癌变的三部分工作的第二部分已经发表。第一部分(2021年)部署了现代理论,一般癌变模型:突变理论,基因组不稳定性模型,达尔文和非基因毒性模型,并解释了炎症,免疫偏差和肿瘤微环境在癌变中的作用。
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引用次数: 0
Major and minor populations of lymphocytes: local features in different stages of colon cancer 淋巴细胞的主要和次要群体:不同阶段结肠癌的局部特征
Pub Date : 2023-02-01 DOI: 10.37748/10.37748/2686-9039-2023-4-1-4
A. B. Sagakyants, E. Dzhenkova, E. Mirzoyan, I. Novikova, E. Zlatnik, E. Bondarenko, A. Shaposhnikov, A. Maslov, O. Y. Kaymakchi, Y. Przhedetskiy, A. N. Shevchenko
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引用次数: 0
Dynamic assessment of intraperitoneal aerosol chemotherapy under pressure impact on peritoneal carcinomatosis in ovarian cancer (immediate results) 压力作用下腹腔雾化化疗治疗卵巢癌腹膜癌的动态评价(即时结果)
Pub Date : 2023-02-01 DOI: 10.37748/2686-9039-2023-4-1-5
A. Dzasokhov, A. Kostin, V. Astashov, M. Andreev, A. V. Turiev, A. Uskov
Purpose of the study. Dynamic assessment of the direct impact of pressurized intraperitoneal aerosol chemotherapy (PIPAC) on peritoneal carcinomatosis in ovarian cancer.Patients and methods. The study involved 164 people with visually detectable and morphologically verified ovarian cancer with peritoneal carcinomatosis of the peritoneum (IIIb-IIIc stages of ovarian cancer). All patients underwent combined treatment of ovarian cancer, which included primary cytoreduction and 6 courses of сhemotherapy according to the TC scheme. In the main group, the standard treatment was supplemented with 3 sessions of PIPAC. Statistical processing was carried out by analyzing the exact criterion of the Wilcoxon-Mann-Whitney sums, the distribution of patients in groups by age and peritoneal lesion was estimated. It was found that the distribution of the analyzed parameters was random. The distribution in the groups by stages of the disease was homogeneous, which is justified by the use of the Barnard criterion. The dynamics of the parameters of the study was evaluated by the methods of basic statistics. Used software packages: MedCals, Statistica.Results. The results obtained demonstrate a distinct positive dynamics in the group of patients receiving PIPAC in addition to standard treatment of newly diagnosed ovarian cancer: a significant decrease in the peritoneal cancer index, therapeutic pathomorphosis in peritoneal samples during treatment, reduction of ascites.Conclusion. The team of authors managed to establish that PIPAC simultaneously with standard combined treatment for newly diagnosed ovarian cancer with peritoneal carcinomatosis makes it possible to achieve a dynamic regression effect of peritoneal carcinomatosis of the peritoneum, morphological regression of carcinomatosis and complete resorption of ascites in the vast majority of treated patients. The revealed therapeutic effect was prolonged and persistent with an objective assessment 6 months after the end of treatment.
研究目的:腹腔加压雾化化疗(PIPAC)对卵巢癌腹膜癌变直接影响的动态评价。患者和方法。该研究涉及164名视觉可检测和形态学证实的卵巢癌伴腹膜癌(IIIb-IIIc期卵巢癌)的患者。所有患者均接受卵巢癌联合治疗,包括原发性细胞减少和6个疗程的血液治疗。主组在标准治疗的基础上加用3次PIPAC。通过分析Wilcoxon-Mann-Whitney和的精确标准进行统计处理,估计患者按年龄和腹膜病变分组的分布。结果表明,分析参数的分布是随机的。按疾病阶段分组的分布是均匀的,使用巴纳德标准证明了这一点。采用基础统计学方法对研究参数的动态进行评价。使用的软件包:MedCals、statistical、results。结果表明,在新诊断的卵巢癌的标准治疗之外,接受PIPAC的患者组有明显的积极动态:腹膜癌指数显著降低,治疗期间腹膜样品的治疗性病理形态,腹水减少。作者团队成功地建立了PIPAC与新诊断的卵巢癌合并腹膜癌的标准联合治疗的同时,可以在绝大多数接受治疗的患者中实现腹膜腹膜癌的动态消退、癌变的形态消退和腹水的完全吸收。治疗结束后6个月客观评价显示疗效持久。
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引用次数: 0
Optimal management of long-term air leakage after lung resections for cancer 肺癌肺切除术后长期漏气的最佳处理
Pub Date : 2023-02-01 DOI: 10.37748/2686-9039-2023-4-1-8
K. D. Iozefi, D. Kharagezov, Y. Lazutin, O. Stateshny, A. Milakin, I. Leyman, T. Ayrapetova, V. N. Vitkovskaya, M. A. Gappoeva, E. Mirzoyan, M. A. Khomidov, A. N. Shevchenko, S. Dimitriadi
Lung resection is the main diagnostic and therapeutic surgical intervention in terms of lung cancer management. Air leak through pleural drains often occurs after lung resections due to damage to the pulmonary parenchyma. Therefore, proper drainage of the pleural cavity is very important for the successful outcome of the operation. The installation of a single pleural drainage after anatomical resection, the refusal to use vacuum aspiration and the earliest possible removal of drains contribute to the rapid activation of patients in the postoperative period. Prolonged air leakage (PAL) after lung resection, on average, develops in 15 % of lung cancer patients, remaining one of the most common complications adversely affecting the rehabilitation of patients and leading to delayed discharge from the hospital. The incidence of empyema with prolonged air leakage is 10.4 % with air discharge for more than 7 days compared to 1 % with air leaks less than or equal to 7 days. PAL requires prolonged drainage of the pleural cavity, which increases postoperative pain, causing shallow breathing, difficulty coughing leads to an increased risk of pneumonia, decreased mobility is accompanied by a high risk of thromboembolic complications. In addition, the treatment of complications is associated with the need to perform additional invasive interventions such as chemical or mechanical pleurodesis. Prolonged air leakage is associated with an increase in hospital mortality. Patients with an air leak have a 3.4 times greater risk of death than patients without it. Active tactics in relation to PAL include preoperative prediction of a high risk of complications, intraoperative measures to prevent air leak from the lung parenchyma and postoperative treatment to reduce the duration of PAL. The urgency of the problem is due to the fact that prolonged air leakage in patients with lung cancer after organ-preserving operations is associated with an increased risk of infectious complications due to the need for prolonged drainage of the pleural cavity. In this review, the main attention is paid to two components of postoperative management of PAL: diagnosis with an accurate assessment of the intensity of air leak and treatment of alveolar-pleural fistulas.
肺切除术是肺癌治疗的主要手术手段。肺切除术后,由于肺实质损伤,常发生胸膜漏气。因此,胸膜腔的正确引流对手术的成功与否至关重要。解剖切除后安装单一胸腔引流管,拒绝真空抽吸,尽早拔除引流管,有助于术后患者快速激活。平均15%的肺癌患者在肺切除术后出现长时间漏气(PAL),这仍然是影响患者康复并导致延迟出院的最常见并发症之一。漏气持续时间超过7天的脓气肿发生率为10.4%,而漏气少于或等于7天的脓气肿发生率为1%。PAL需要长时间胸腔引流,这增加了术后疼痛,引起呼吸浅,咳嗽困难导致肺炎的风险增加,活动能力下降伴有血栓栓塞并发症的高风险。此外,并发症的治疗需要进行额外的侵入性干预,如化学或机械胸膜穿刺术。长时间的空气泄漏与医院死亡率的增加有关。漏气患者的死亡风险是没有漏气患者的3.4倍。与PAL相关的积极策略包括术前对并发症高风险的预测,术中防止肺实质漏气的措施以及术后减少PAL持续时间的治疗。问题的紧迫性在于,肺癌患者在器官保存手术后,由于需要长时间的胸腔引流,漏气时间延长,感染并发症的风险增加。在这篇综述中,主要关注PAL术后管理的两个组成部分:准确评估漏气强度的诊断和肺泡胸膜瘘的治疗。
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引用次数: 0
Molecular features of malignant gastric tumors 胃恶性肿瘤的分子特征
Pub Date : 2023-02-01 DOI: 10.37748/2686-9039-2023-4-1-7
Yuriy A. Gevorkyan, A. Dashkov, N. Soldatkina, V. E. Kolesnikov, N. Timoshkina, D. S. Krutilin, О. К. Bondarenko
Gastric cancer is one of the most widespread cancers and makes a significant contribution to the global mortality rate from malignant neoplasms. The late onset of clinical symptoms is the main reason why the disease is often diagnosed at an advanced stage, and this limits the available therapeutic approaches. Despite the fact, that extensive studies have been carried out to identify the mechanisms and markers of the development and progression of the disease, their results are currently not fully included in clinical practice. As a consequence, only marginal improvement in long-term survival has been achieved and patient prognosis remains poor. Understanding the molecular genetic features of gastric malignant tumors can provide insight into their pathogenesis, help identify new biomarkers for prognosis and diagnosis, and identify new therapeutic targets. In recent decades, advances in high throughput sequencing technologies have improved understanding of the molecular genetic aspects of gastric cancer. This review considers molecular level changes, including information on tumor suppressor genes, oncogenes, cell cycle and apoptosis regulators, cell adhesion molecules, loss of heterozygosity, micro-satellite instability and epigenetic aberrations (change in methylation level and modification of histones). The review is also devoted to the molecular aspects of pathogenesis – changes in the signaling pathways involved in the gastric cancer development; the classification of sporadic and hereditary gastric cancer at the molecular genetic level is considered. The characteristics and classification of GC presented in this review at the genetic and epigenetic levels confirms that this disease is heterogeneous. These data can be used both to develop and test potential markers and new targeted therapeutic approaches.
胃癌是最普遍的癌症之一,在全球恶性肿瘤死亡率中占有重要地位。临床症状的晚发是该病常常在晚期诊断的主要原因,这限制了可用的治疗方法。尽管已经开展了广泛的研究,以确定该疾病发生和进展的机制和标志物,但其结果目前尚未完全纳入临床实践。其结果是,长期生存仅取得了微小的改善,患者预后仍然很差。了解胃恶性肿瘤的分子遗传特征,有助于深入了解其发病机制,有助于发现新的预后和诊断生物标志物,并确定新的治疗靶点。近几十年来,高通量测序技术的进步提高了对胃癌分子遗传学方面的认识。本文综述了分子水平的变化,包括肿瘤抑制基因、癌基因、细胞周期和凋亡调节因子、细胞粘附分子、杂合性丧失、微卫星不稳定性和表观遗传畸变(甲基化水平和组蛋白修饰的变化)的信息。本文还从分子层面探讨了胃癌的发病机制——参与胃癌发展的信号通路的变化;本文从分子遗传学的角度对散发性胃癌和遗传性胃癌进行了分类。本文在遗传和表观遗传水平上介绍了胃癌的特点和分类,证实了该病的异质性。这些数据可用于开发和测试潜在的标记物和新的靶向治疗方法。
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引用次数: 1
Influence of induced diabetes mellitus on hormonal profile of Lewis lung carcinoma in BALB/c Nude mice 诱导糖尿病对BALB/c裸小鼠Lewis肺癌激素谱的影响
Pub Date : 2023-02-01 DOI: 10.37748/2686-9039-2023-4-1-2
E. Frantsiyants, V. Bandovkina, I. Kaplieva, A. Shikhlyarova, E. Surikova, I. Neskubina, Y. Pogorelova, L. Trepitaki, N. Cheryarina
Purpose of the study. The assessment of diabetes mellitus (DM) effect on levels of sex hormones in tumor and peritumoral tissues in BALB/c Nude mice with Lewis lung carcinoma (LLC).Materials and methods. The study included 42 male and female BALB/c Nude mice aged 8–9 weeks weighing 21–22 g. Alloxan-induced DM was reproduced in mice of the main group, and then LLC was transplanted. Levels of estrone (E1), estradiol (E2), testosterone (T), progesterone (P4) and prolactin (PRL), as well as steroid hormone receptors: estrogens (REα, REβ), androgens (RA), and progesterone (RP4) were measured by RIA and ELISA in samples of tumor and peritumoral tissues. Animals with LLC without DM were used as controls. The statistical analysis was performed using the Statistica 10 program; differences were considered significant at p < 0.05.Results. DM in males was reproduced only after a double injection of alloxan, and was characterized by lower blood glucose levels compared to females. The growth of LLC in animals with alloxan-induced DM was possible only in female BALB/c Nude mice; in BALB/c Nude males, the tumor could not be transplanted either independently or in combination with DM. Females in the main group showed greater average tumor volumes throughout the experiment and reduced survival, compared to the control group. Tumor samples from females with LLC+DM were more saturated with sex steroids, but depleted in steroid hormone receptors, which probably contributed to the ability to avoid the body's regulatory signals.Conclusion. The growth of LLC in presence of induced DM was sex-dependent, since the tumor could not be transplanted to male mice. DM affected the levels of sex steroids and their receptors tumor tissues in female BALB/c Nude mice.
研究目的:糖尿病(DM)对Lewis肺癌BALB/c裸鼠肿瘤及瘤周组织性激素水平的影响材料和方法。研究对象为8-9周龄雄性和雌性BALB/c裸鼠42只,体重21-22 g。主组小鼠复制四氧嘧啶诱导的DM,然后移植LLC。采用RIA和ELISA法检测肿瘤及瘤周组织中雌激素(E1)、雌二醇(E2)、睾酮(T)、孕酮(P4)、催乳素(PRL)及甾体激素受体雌激素(REα、REβ)、雄激素(RA)、孕酮(RP4)水平。无糖尿病的LLC动物作为对照。使用Statistica 10程序进行统计分析;p < 0.05认为差异有统计学意义。男性糖尿病患者仅在两次注射四氧嘧啶后才会出现,其特征是血糖水平低于女性。在四氧嘧啶诱导的DM动物中,LLC仅在雌性BALB/c裸鼠中生长;在BALB/c裸男性中,肿瘤既不能单独移植,也不能与DM合并移植。与对照组相比,主组女性在整个实验过程中平均肿瘤体积更大,生存时间更短。患有LLC+DM的女性肿瘤样本中性类固醇含量更高,但类固醇激素受体含量较低,这可能是避免机体调节信号的原因。在诱导DM存在的情况下,LLC的生长是性别依赖的,因为肿瘤不能移植到雄性小鼠身上。DM影响雌性BALB/c裸鼠性类固醇及其受体肿瘤组织的水平。
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引用次数: 1
Indices of insulin-like growth factors family in the lung tissue of patients with non-small cell lung cancer after COVID-19 of various severity 不同严重程度非小细胞肺癌患者新冠肺炎后肺组织胰岛素样生长因子家族指标
Pub Date : 2023-02-01 DOI: 10.37748/2686-9039-2023-4-1-3
O. Kit, E. Frantsiyants, D. Kharagezov, V. Bandovkina, N. Cheryarina, Y. Pogorelova, Y. Lazutin, A. Milakin, I. Leyman, O. Stateshny
Purpose of the study. An analysis of levels of IGF and their carrying proteins in lung tissues of cancer patients depending on the severity of the previous COVID-19 infection.Patients and methods. The study included 60 patients with histologically verified non-small cell lung cancer (NSCLC) T1–3NхM0 receiving treatment at the Thoracic Department, National Medical Research Centre for Oncology, in 2020–2021. The control group included 30 NSCLC patients after asymptomatic or mild COVID-19 disease (15 males and 15 females); the main group included 30 (15 men and 15 women) patients after severe or moderate to severe COVID-19 infection. The mean age of patients was 59.11 ± 2.89 years; no significant differences were noted between the control and main groups. All participants gave their informed consent prior to the study approved by the Ethics Committee of National Medical Research Centre for Oncology. Qualitative assessment of IGF-I, IGF-II and IGFBP-1,2,3 levels in the tissues of the tumor, peritumoral area and resection line were measured by ELISA (Mediagnost, Germany). The statistical analysis was performed in the Statistica 10 program, the differences were considered statistically significant at p < 0.05.Results. Regardless of the gender, levels of IGF-I and IGF-II in tumor and resection line samples in patients of the main group were higher than in the control group on average by 1.5–2.2 times, and IGFBP-1 in the tumor was lower by 1.3 times in men and by 5 times in women. The ratio of IGF and IGFBP-1-3 in patients of the control group in perifocal tissues changed towards the parameters in the tumor tissue. IGF/IGFBP-1-3 in men of the main group were lower or did not differ from the indices in the intact tissue, while in women they increased, similarly to the tumor tissue.Conclusion. An increase in the ratio of IGF and carrier proteins in the tumor tissue of patients in the main group indicated an excessive accumulation of IGF in it, which may contribute to more aggressive growth of malignant tumors. The most pronounced disorders in the system of insulin-like growth factors were found in the tissues of the tumor and intact lung of patients with previous severe and moderate to severe COVID-19.
研究目的:根据先前感染COVID-19的严重程度对癌症患者肺组织中IGF及其携带蛋白水平的分析。患者和方法。该研究包括60例组织学证实的非小细胞肺癌(NSCLC) T1-3NхM0患者,于2020-2021年在国家肿瘤医学研究中心胸外科接受治疗。对照组包括30例无症状或轻度COVID-19疾病后的非小细胞肺癌患者(男15例,女15例);主要组为重度或中重度感染后患者30例(男15例,女15例)。患者平均年龄59.11±2.89岁;对照组和主要组之间无显著差异。所有参与者在研究前均获得国家肿瘤医学研究中心伦理委员会批准的知情同意。采用ELISA法(Mediagnost,德国)定性评价肿瘤组织、肿瘤周围区域和切除线上的IGF-I、IGF-II和IGFBP-1、2、3水平。统计学分析在Statistica 10程序中进行,p < 0.05认为差异有统计学意义。不论性别,主组患者肿瘤和切除线样本中IGF-I和IGF-II水平平均较对照组高1.5-2.2倍,肿瘤中IGFBP-1水平男性低1.3倍,女性低5倍。对照组患者局周组织中IGF和IGFBP-1-3的比值向肿瘤组织中的参数变化。主组男性IGF/IGFBP-1-3与正常组织指数较低或无差异,而女性IGF/IGFBP-1-3与肿瘤组织指数相似,呈升高趋势。主组患者肿瘤组织中IGF与载体蛋白比值升高,表明IGF在肿瘤组织中过度积累,可能导致恶性肿瘤更加侵袭性生长。胰岛素样生长因子系统紊乱最明显的是既往重型和中重度COVID-19患者的肿瘤组织和完整肺。
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引用次数: 0
Immunohistochemical assessment of possible anticancer effect mechanisms of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)- 5,6,7-trichloro-1,3-tropolone in PDX models of lung cancer 2-(6,8-二甲基-5-硝基-4-氯喹啉-2-基)- 5,6,7-三氯-1,3-tropolone对肺癌PDX模型可能的抗癌作用机制的免疫组化评价
Pub Date : 2023-02-01 DOI: 10.37748/2686-9039-2023-4-1-1
E. F. Komarova, E. Lukbanova, E. Dzhenkova, A. Goncharova, E. Zaikina, S. Gurova, A. V. Galina, L. K. Kurbanova, M. V. Mindar, D. Khodakova, M. S. Gusareva, M. Zinkovich
Purpose of the study. Evaluation of the expression of immunohistochemical tumor markers Ki-67, b-catenin, Bcl-2, P53, connexin 32 and connexin 43 when using 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone in mice with xenographs of squamous cell lung cancer.Materials and methods. Subcutaneous PDX models of human squamous cell lung cancer were created in immunodeficient BALB/c Nude mice. A fragment of the patient’s tumor (3 × 3 × 3 mm) was implanted subcutaneously in the right thigh of a previously anesthetized mouse. 200 μl of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone was administered orally using a probe in 12 doses once every 3 days. All animals were divided into groups depending on the tropolone doses: experimental groups 2–5 with doses of 0.0055, 0.055, 0.55 and 2.75 mg/g, respectively. The control group received 1 % starch gel which was tropolone carrier. The animals were euthanized 36 days after the start of the substance administration, and the tumor tissue was isolated and prepared for the IHC study according to the standard protocol. IHC reactions were performed using antibodies for Ki-67, b-catenin, Bcl-2, P53, connexin 32 and connexin 43.Results. Higher tropolone doses were associated with decreased expression of Ki-67, b-catenin, and the Bcl-2 protein, but increased expression of the P53 protein. The dosage of tropolone and expression of connexin 43 were directly proportional.Conclusion. Immunohistochemical analysis of expression of proteins in PDX models of human squamous cell lung cancer when using 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7-trichloro-1,3-tropolone showed the changes indicating its antitumor efficacy and suggesting a possible mechanism of action based on the activation of apoptosis.
研究目的:2-(6,8-二甲基-5-硝基-4-氯喹啉-2-基)-5,6,7-三氯-1,3-tropolone对鳞状细胞肺癌小鼠免疫组化肿瘤标志物Ki-67、b-catenin、Bcl-2、P53、连接蛋白32、连接蛋白43表达的影响材料和方法。在免疫缺陷BALB/c裸鼠中建立人鳞状细胞肺癌皮下PDX模型。将患者肿瘤碎片(3 × 3 × 3 mm)皮下植入先前麻醉的小鼠右大腿。用探针口服2-(6,8-二甲基-5-硝基-4-氯喹啉-2-基)-5,6,7-三氯-1,3-tropolone 200 μl,共12次,每3 d 1次。所有动物根据tropolone剂量分为实验组2-5组,剂量分别为0.0055、0.055、0.55和2.75 mg/g。对照组给予1%淀粉凝胶作为tropolone载体。在给药36天后对动物实施安乐死,并根据标准方案分离肿瘤组织,准备进行免疫组化研究。采用Ki-67、b-连环蛋白、Bcl-2、P53、连接蛋白32和连接蛋白43抗体进行免疫组化反应。高剂量的tropolone与Ki-67、b-catenin和Bcl-2蛋白表达降低相关,但与P53蛋白表达升高相关。tropolone的用量与connexin 43的表达成正比。免疫组化分析2-(6,8-二甲基-5-硝基-4-氯喹啉-2-基)-5,6,7-三氯-1,3-tropolone对人鳞状细胞肺癌PDX模型中蛋白表达的影响表明其抗肿瘤作用的变化,并提示其可能基于激活细胞凋亡的作用机制。
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引用次数: 0
Modern approaches to glioblastoma therapy 胶质母细胞瘤的现代治疗方法
Pub Date : 2023-02-01 DOI: 10.37748/2686-9039-2023-4-1-6
N. S. Kuznetsova, S. Gurova, A. Goncharova, E. Zaikina, M. Gusareva, M. Zinkovich
Glioblastoma (GBM) is the most malignant and the most common primary tumor of the central nervous system. During the last several years GBM has been classified and managed according to the World Health Organization (WHO) criteria which subdivide it into primary and secondary GBM. As it is suggested, GBM originates from glial cells and has a diffuse growth pattern, but its etiology and pathophysiology are poorly investigated up to date. Its rapid progression and anatomical location in the brain often limits the effectiveness of therapeutic interventions. Despite all scientific and technological advances, GBM remains an incurable disease with a median survival of approximately 18 months. Standard treatment options involving maximal safe resection of the tumor followed with radiotherapy and chemotherapy do not provide satisfactory Results.Better understanding of the molecular pathology of GBM and its associated signaling pathways has opened up possibilities for new treatments for newly diagnosed and relapsing tumors. A multitargeted therapeutic approach using compounds capable of inhibiting more than one specific molecular target is a promising alternative to conventional therapies.Currently, specialists study such innovative treatment options as small molecule inhibitors aimed at signaling pathway disruptions, immunotherapy, including checkpoint inhibitors, oncolytic vaccines, CAR T-cell therapy, and drug delivery systems. In terms of an innovative approach, the elaboration of targeted drug delivery systems is of particular interest, since this strategy looks the most promising due to its ability to increase the bioavailability and effectiveness of both standard and newly tested agents. This review discusses results of preclinical and clinical studies of innovative therapeutic approaches, their advantages and disadvantages. An interdisciplinary approach is expected to be able to combine the results of cutting-edge research in this area and to provide novel promising therapeutic strategies for patients with GBM.
胶质母细胞瘤(GBM)是最恶性和最常见的原发性中枢神经系统肿瘤。在过去几年中,根据世界卫生组织(世卫组织)将其细分为原发性和继发性GBM的标准对GBM进行了分类和管理。目前认为,GBM起源于神经胶质细胞,具有弥漫性生长模式,但其病因和病理生理研究尚不充分。它在大脑中的快速进展和解剖位置往往限制了治疗干预的有效性。尽管科技进步,GBM仍然是一种无法治愈的疾病,中位生存期约为18个月。标准的治疗方案包括最大限度的安全切除肿瘤,然后是放疗和化疗,并没有提供令人满意的结果。更好地了解GBM的分子病理学及其相关的信号通路,为新诊断和复发肿瘤的新治疗开辟了可能性。使用能够抑制多个特定分子靶点的化合物的多靶点治疗方法是传统治疗的有希望的替代方法。目前,专家们正在研究诸如针对信号通路中断的小分子抑制剂、免疫疗法(包括检查点抑制剂)、溶瘤疫苗、CAR - t细胞疗法和药物输送系统等创新治疗方案。就创新方法而言,拟定靶向给药系统特别令人感兴趣,因为这种策略看起来最有希望,因为它能够提高标准药物和新测试药物的生物利用度和有效性。本文综述了创新治疗方法的临床前和临床研究结果及其优缺点。跨学科的方法有望结合这一领域的前沿研究成果,并为GBM患者提供新的有希望的治疗策略。
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South Russian Journal of Cancer
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