BACKGROUND. The International Serous Fluid Cytopathology Reporting System (TISRSFC) was proposed in 2020 to standardize cytological reports and include information on perceived risk of malignancy in reports. It is necessary to analyze the use of TISRSFC to determine the principles of rational practical implementation and possible improvement of this classification. AIMS: to assess the possibility and results of the application of TISRSFC (2020) in the cytodiagnosis of pleural effusions in the organizational technologies and resource provision of a regional oncological dispensary. MATERIALS AND METHODS. An observational, crossover, retrospective, crossover study. A comparative analysis of cytological analyzes of pleural effusion with clinical and anamnestic information, histological, immunohistochemical results of 1507 patients. The microscope slide were prepared by the traditional smear method, as well as by liquid cytology. preparations were stained by Papanicolaou and Pappenheim methods. The immunocytochemical tests were performed if necessary. RESULTS: The following cytological reports corresponding to the TISRSFC categories were formulated: non-diagnostic material (C I) - 11 (0.7%), absence of malignant tumor cells (C II) - 946 (62.8%), atypia of unknown significance (C III) - 61 (4.0%), suspicion of a malignant process (C IV) - 13 (0.9%), malignant process (C V) - 476 (31.6%). There were 37 (7.8%) cases of the primary tumor - mesothelioma, 398 (83.6%) cases of metastatic tumors, including 41 (8.6%) cases of non-epithelial tumors in category C V. Immunocytochemical tests of pleural fluid were performed in 273 (18.1%) cases. Risk of malignancy (ROM) was 9.1% (1/11) for C I; 1.2% (11/946) for C II; 59.0% (36/61) for C III; 84.6% (11/13) for C IV and 100% (476/476) for C V. Cytodiagnosis with immunocytochemistry in unclear cases is characterized by a sensitivity of 92.5%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 88.5%, and an accuracy of 96.6%.
背景。国际浆液细胞病理学报告系统（TISRSFC）于 2020 年提出，旨在规范细胞学报告，并在报告中纳入恶性肿瘤感知风险信息。有必要对 TISRSFC 的使用情况进行分析，以确定合理实用的原则，并对该分类进行可能的改进。 目的：评估 TISRSFC（2020）在胸腔积液细胞诊断中应用的可能性和结果，以及地区肿瘤医院的组织技术和资源提供情况。 材料与方法：一项观察性、交叉、回顾性研究。对 1507 名患者的胸腔积液细胞学分析结果与临床和病理资料、组织学和免疫组化结果进行比较分析。显微载玻片采用传统涂片法和液体细胞学法制备。必要时进行免疫细胞化学检测。 结果：根据 TISRSFC 分类得出了以下细胞学报告：无诊断材料（CⅠ）--11（0.7%），无恶性肿瘤细胞（CⅡ）--946（62.8%），不典型性意义不明（CⅢ）--61（4.0%），怀疑恶性过程（CⅣ）--13（0.9%），恶性过程（CⅤ）--476（31.6%）。有 37 例（7.8%）原发性肿瘤--间皮瘤，398 例（83.6%）转移性肿瘤，包括 41 例（8.6%）C V 类非上皮性肿瘤。273 例（18.1%）胸腔积液进行了免疫细胞化学检测。恶性肿瘤风险（ROM）为：C I 类 9.1%（1/11）；C II 类 1.2%（11/946）；C III 类 59.0%（36/61）；C IV 类 84.6%（11/13）；C V 类 100%（476/476）。在不明确的病例中，免疫细胞化学的细胞诊断灵敏度为 92.5%，特异性为 100%，阳性预测值为 100%，阴性预测值为 88.5%，准确率为 96.6%。
{"title":"Cytodiagnosis of pleural effusions according to The International System for Reporting Serous Fluid Cytopathology: retrospective analysis of oncological dispensary experience","authors":"O. Grigoruk","doi":"10.17816/onco546017","DOIUrl":"https://doi.org/10.17816/onco546017","url":null,"abstract":"BACKGROUND. The International Serous Fluid Cytopathology Reporting System (TISRSFC) was proposed in 2020 to standardize cytological reports and include information on perceived risk of malignancy in reports. It is necessary to analyze the use of TISRSFC to determine the principles of rational practical implementation and possible improvement of this classification. AIMS: to assess the possibility and results of the application of TISRSFC (2020) in the cytodiagnosis of pleural effusions in the organizational technologies and resource provision of a regional oncological dispensary. MATERIALS AND METHODS. An observational, crossover, retrospective, crossover study. A comparative analysis of cytological analyzes of pleural effusion with clinical and anamnestic information, histological, immunohistochemical results of 1507 patients. The microscope slide were prepared by the traditional smear method, as well as by liquid cytology. preparations were stained by Papanicolaou and Pappenheim methods. The immunocytochemical tests were performed if necessary. RESULTS: The following cytological reports corresponding to the TISRSFC categories were formulated: non-diagnostic material (C I) - 11 (0.7%), absence of malignant tumor cells (C II) - 946 (62.8%), atypia of unknown significance (C III) - 61 (4.0%), suspicion of a malignant process (C IV) - 13 (0.9%), malignant process (C V) - 476 (31.6%). There were 37 (7.8%) cases of the primary tumor - mesothelioma, 398 (83.6%) cases of metastatic tumors, including 41 (8.6%) cases of non-epithelial tumors in category C V. Immunocytochemical tests of pleural fluid were performed in 273 (18.1%) cases. Risk of malignancy (ROM) was 9.1% (1/11) for C I; 1.2% (11/946) for C II; 59.0% (36/61) for C III; 84.6% (11/13) for C IV and 100% (476/476) for C V. Cytodiagnosis with immunocytochemistry in unclear cases is characterized by a sensitivity of 92.5%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 88.5%, and an accuracy of 96.6%.","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139176626","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}
The purpose of the study: to determine the most important prognostic factors, as well as the most effective treatment option in patients with continued growth of primary low-grade gliomas of the brain. Materials and Methods: This study included 40 patients with a confirmed diagnosis of progression of low-malignant glial brain tumors, who underwent inpatient treatment at the Chelyabinsk oncology center from 2007 to 2022. The ratio of men and women: 1:1.5. The mean age was 45.6 11.5 years. Patients with grade I astrocytomas predominated (n=23), oligodendroglioma was diagnosed in 8 patients. Reoperation was performed in 11 patients as the first stage of progression treatment. In 7 cases, monochemotherapy with temozolomide was performed. Repeated radiation therapy was performed in 29 patients, of which: 9 patients received a course of combined photon-neutron therapy ; 9 people stereotactic radiation therapy was performed on the CyberKnife device; in 11 cases - external beam radiation therapy . Results: The median overall survival (OS) for all patients with continued growth of low-grade cerebral gliomas after treatment was 120 months. 1-year OS - 97.3%; 3-year-old - 86.8%; 5-year-old - 78.2%. Median OS after relapse treatment was 36 months. The median OS was higher in the age group under 50 compared to the older age group: 120 and 95 months. (p0.05). The best results of treatment were noted in patients who underwent reoperation followed by a course of radiation therapy or chemotherapy with temozolomide for 48 months. and 36 months. respectively (p0.05). When analyzing the results of treatment after a course of repeated radiation therapy in an independent variant, there were undoubted advantages in patients who underwent stereotactic radiation therapy and photon-neutron therapy for 60 months. and 34 months. (p0.05). Conclusion: Thus, the optimal approach to the treatment of patients with continued growth of primary low-grade glioma brain tumors is to perform a second operation, followed by radiation therapy or chemotherapy. The method of choice for a repeat course of radiotherapy may be photon-neutron therapy or a course of stereotactic radiation therapy. Key words: recurrent , astrocytoma, temozolomide, stereotactic radiation therapy
{"title":"Evaluation of the effectiveness of multicomponent treatment in the progression of primary low-grade brain gliomas. Own experience.","authors":"M. Sarycheva","doi":"10.17816/onco456888","DOIUrl":"https://doi.org/10.17816/onco456888","url":null,"abstract":"The purpose of the study: to determine the most important prognostic factors, as well as the most effective treatment option in patients with continued growth of primary low-grade gliomas of the brain. Materials and Methods: This study included 40 patients with a confirmed diagnosis of progression of low-malignant glial brain tumors, who underwent inpatient treatment at the Chelyabinsk oncology center from 2007 to 2022. The ratio of men and women: 1:1.5. The mean age was 45.6 11.5 years. Patients with grade I astrocytomas predominated (n=23), oligodendroglioma was diagnosed in 8 patients. Reoperation was performed in 11 patients as the first stage of progression treatment. In 7 cases, monochemotherapy with temozolomide was performed. Repeated radiation therapy was performed in 29 patients, of which: 9 patients received a course of combined photon-neutron therapy ; 9 people stereotactic radiation therapy was performed on the CyberKnife device; in 11 cases - external beam radiation therapy . Results: The median overall survival (OS) for all patients with continued growth of low-grade cerebral gliomas after treatment was 120 months. 1-year OS - 97.3%; 3-year-old - 86.8%; 5-year-old - 78.2%. Median OS after relapse treatment was 36 months. The median OS was higher in the age group under 50 compared to the older age group: 120 and 95 months. (p0.05). The best results of treatment were noted in patients who underwent reoperation followed by a course of radiation therapy or chemotherapy with temozolomide for 48 months. and 36 months. respectively (p0.05). When analyzing the results of treatment after a course of repeated radiation therapy in an independent variant, there were undoubted advantages in patients who underwent stereotactic radiation therapy and photon-neutron therapy for 60 months. and 34 months. (p0.05). Conclusion: Thus, the optimal approach to the treatment of patients with continued growth of primary low-grade glioma brain tumors is to perform a second operation, followed by radiation therapy or chemotherapy. The method of choice for a repeat course of radiotherapy may be photon-neutron therapy or a course of stereotactic radiation therapy. Key words: recurrent , astrocytoma, temozolomide, stereotactic radiation therapy","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139176500","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}
The morbidity of malignant neoplasms of respiratory organs and thorax in the remote period in the male population born from 1932 to 1949 in rural settlements of Altai Krai and traced during the first trial was evaluated. Purpose: To study the morbidity of malignant neoplasms of respiratory and thoracic organs in the remote period in the male population born in 1932-1949 and located in the zone of influence of the first test. METHODS: The cohort study was based on the examination of anonymized data and operational information on first-time detected and morphologically verified cases of malignant neoplasms from 2007 to 2016. A cohort fixed by the date of the first nuclear test of 6383 individuals was studied. The main (exposed) cohort included 2291 people and the control (unexposed) cohort included 4092 people. In the cohort, 156 cases of respiratory and thoracic malignant neoplasm were identified. Person-time incidence rate PtR, standard error (mPtR) and confidence intervals (95% CI) were calculated. The incidence of respiratory and thoracic malignant neoplasms, structure and relative risk were assessed. Statistical processing of data was performed using Microsoft Office 2016 licensed software. Results: The number of person-years spent at risk of respiratory and thoracic malignant neoplasms in the male population in the main cohort is equal to 16731 person-years, in the control cohort - 30747. The person-time incident rate (PtR) in the main cohort was 436.32 105 person-years, with an mPtR of 51.07 and confidence intervals (95% CI) of 334.18 to 538.45, while in the control cohort the PTR was 269.95 105 person-years with an mPtR of 29.63 and (95% CI) of 210.68 to 329.21, respectively. Leading localizations: bronchial and lung and laryngeal malignancies. Conclusions. We found an increased relative risk of respiratory and thoracic malignancies in the male population in the remote period (RR=1.616; (95% CI) 1.180 - 2.214), with a standard error of relative risk (s) equal to 0.160.
{"title":"MALIGNANT NEOPLASMS OF THE RESPIRATORY AND THORACIC ORGANS IN THE REMOTE PERIOD IN MALES OF ALTAI KRAI AFFECTED BY FIRST NUCLEAR TEST AT SEMIPALATINSK TEST SITE","authors":"Anton O Kovrigin, I. Kolyado","doi":"10.17816/onco568565","DOIUrl":"https://doi.org/10.17816/onco568565","url":null,"abstract":"The morbidity of malignant neoplasms of respiratory organs and thorax in the remote period in the male population born from 1932 to 1949 in rural settlements of Altai Krai and traced during the first trial was evaluated. Purpose: To study the morbidity of malignant neoplasms of respiratory and thoracic organs in the remote period in the male population born in 1932-1949 and located in the zone of influence of the first test. METHODS: The cohort study was based on the examination of anonymized data and operational information on first-time detected and morphologically verified cases of malignant neoplasms from 2007 to 2016. A cohort fixed by the date of the first nuclear test of 6383 individuals was studied. The main (exposed) cohort included 2291 people and the control (unexposed) cohort included 4092 people. In the cohort, 156 cases of respiratory and thoracic malignant neoplasm were identified. Person-time incidence rate PtR, standard error (mPtR) and confidence intervals (95% CI) were calculated. The incidence of respiratory and thoracic malignant neoplasms, structure and relative risk were assessed. Statistical processing of data was performed using Microsoft Office 2016 licensed software. Results: The number of person-years spent at risk of respiratory and thoracic malignant neoplasms in the male population in the main cohort is equal to 16731 person-years, in the control cohort - 30747. The person-time incident rate (PtR) in the main cohort was 436.32 105 person-years, with an mPtR of 51.07 and confidence intervals (95% CI) of 334.18 to 538.45, while in the control cohort the PTR was 269.95 105 person-years with an mPtR of 29.63 and (95% CI) of 210.68 to 329.21, respectively. Leading localizations: bronchial and lung and laryngeal malignancies. Conclusions. We found an increased relative risk of respiratory and thoracic malignancies in the male population in the remote period (RR=1.616; (95% CI) 1.180 - 2.214), with a standard error of relative risk (s) equal to 0.160.","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139176582","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}
Pancreatic cancer is a malignant tumor originating from the pancreatic epithelium. Despite constant efforts and intensive research, it has not yet been possible to identify risk factors that significantly affect the early diagnosis and effectiveness of pancreatic cancer treatment. In the Russian Federation in 2021, 15055 patients with pancreatic cancer were identified, of which stage III -16.9%, stage IV -58.2%. Mortality in the first year of life from the moment of diagnosis was 65.1%. A total of 1,856 patients underwent radical surgical treatment. Features of the clinical picture of prostate cancer a long latent course and similarity with the clinic of chronic pancreatitis can cause late diagnosis of the disease. In about 70% of cases, the disease is manifested by the syndrome of mechanical jaundice, which requires additional invasive methods of diagnosis and treatment. At the time of diagnosis verification, 80-85% of patients are already inoperable due to local or remote spread of the tumor process. The average life expectancy of patients with unresectable pancreatic cancer is about 6-7 months. After radical surgical treatment, the 5-year survival rate of patients with this pathology, according to the results of various authors, ranges from 0 to 30%.
{"title":"Pancreatic cancer surgery is the experience of one center.","authors":"Nikita Mikolenko","doi":"10.17816/onco584148","DOIUrl":"https://doi.org/10.17816/onco584148","url":null,"abstract":"Pancreatic cancer is a malignant tumor originating from the pancreatic epithelium. Despite constant efforts and intensive research, it has not yet been possible to identify risk factors that significantly affect the early diagnosis and effectiveness of pancreatic cancer treatment. In the Russian Federation in 2021, 15055 patients with pancreatic cancer were identified, of which stage III -16.9%, stage IV -58.2%. Mortality in the first year of life from the moment of diagnosis was 65.1%. A total of 1,856 patients underwent radical surgical treatment. Features of the clinical picture of prostate cancer a long latent course and similarity with the clinic of chronic pancreatitis can cause late diagnosis of the disease. In about 70% of cases, the disease is manifested by the syndrome of mechanical jaundice, which requires additional invasive methods of diagnosis and treatment. At the time of diagnosis verification, 80-85% of patients are already inoperable due to local or remote spread of the tumor process. The average life expectancy of patients with unresectable pancreatic cancer is about 6-7 months. After radical surgical treatment, the 5-year survival rate of patients with this pathology, according to the results of various authors, ranges from 0 to 30%.","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139176392","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}
Ilya Kislyak, Marina Pokrovskaya, Darya Zhanturina, V. Pokrovsky
Drug therapy is one of the main strategies of cancer treatment. L-asparaginase, the enzyme that hydrolyzes asparagine, has long been included in the treatment regimens for acute lymphoblastic leukemia and other hematological malignancies more than 50 years ago, but its use for the treatment of solid tumors is still extremely limited. This review analyzes experimental data on the sensitivity of cell lines and xenografts of solid tumors to L-asparaginase, examines the results of clinical trials. Among the mechanisms of the cytotoxic effect of L-asparaginase on tumor cells, such processes as depletion of aspartic and glutamic acids, influence on the internal and external pathways of apoptosis, inhibition of cellular processes through a decrease in the activity of the mTOR protein, and weakening of the expression of the telomerase gene are discussed. Separately, molecular markers are considered, which can be used to suggest the effectiveness of future therapy with L-asparaginase in solid tumors. These markers include 1) expression levels of asparagine synthetase and glutamine synthetase genes, 2) degree of methylation of the ASNS promoter region, 3) PTEN protein activity and 4) autophagy, 5) bone marrow environment of tumor cells, 6) expression of genes associated with asparaginase resistance, such as the 1 opioid receptor gene and the huntingtin-associated protein 1 gene.
{"title":"The use of L-asparaginase for the treatment of solid tumors: data from experimental studies and clinical trials","authors":"Ilya Kislyak, Marina Pokrovskaya, Darya Zhanturina, V. Pokrovsky","doi":"10.17816/onco562802","DOIUrl":"https://doi.org/10.17816/onco562802","url":null,"abstract":"Drug therapy is one of the main strategies of cancer treatment. L-asparaginase, the enzyme that hydrolyzes asparagine, has long been included in the treatment regimens for acute lymphoblastic leukemia and other hematological malignancies more than 50 years ago, but its use for the treatment of solid tumors is still extremely limited. This review analyzes experimental data on the sensitivity of cell lines and xenografts of solid tumors to L-asparaginase, examines the results of clinical trials. Among the mechanisms of the cytotoxic effect of L-asparaginase on tumor cells, such processes as depletion of aspartic and glutamic acids, influence on the internal and external pathways of apoptosis, inhibition of cellular processes through a decrease in the activity of the mTOR protein, and weakening of the expression of the telomerase gene are discussed. Separately, molecular markers are considered, which can be used to suggest the effectiveness of future therapy with L-asparaginase in solid tumors. These markers include 1) expression levels of asparagine synthetase and glutamine synthetase genes, 2) degree of methylation of the ASNS promoter region, 3) PTEN protein activity and 4) autophagy, 5) bone marrow environment of tumor cells, 6) expression of genes associated with asparaginase resistance, such as the 1 opioid receptor gene and the huntingtin-associated protein 1 gene.","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139180834","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}
BACKGROUND: New treatment methods of castration-resistant prostate cancer with radionuclide therapy are needed. New methods will optimize personalized strategy for radionuclide therapy of metastatic castrate-resistant prostate cancer using low molecular weight ligands to PSMA labeled with lutetium-177. AIMS: To define the long-term effects and effectiveness of the treatment experimental animals with PET imaging to refine the research strategy. MATERIALS AND METHODS: The study was performed in nu/nu male mice with PSMA-expressing 22Rv1 prostate cancer xenografts. PET/CT study with 18F-PSMA-1007 was used to confirm the tumor regrowth after a single therapeutic dose of [177Lu]Lu-PSMA IT. RESULTS: PET imaging with 18F-PSMA-1007 showed the possibility of prolonged 22Rv1 tumor regrowth after a single injection of 9.2 MBq [177Lu]Lu-PSMA IT, which is equivalent to minimal human therapeutic dose (28.6 MBq/kg). CONCLUSIONS: The study confirmed the short period of the observed therapeutic effect after a single injection of 9.2 MBq [177Lu]Lu-PSMA IT. The tumor regrowth in 2.5 months after the reduction of 22Rv1 xenografts to a non-palpable state was confirmed by PET/CT with 18F-PSMA-1007. These results confirm the need to study the frequency of repeated administrations of radiopharmaceuticals based on ligands to PSMA labeled with lutetium-177 to achieve a stable therapeutic effect in cases where a single dose reduction is necessary. Keywords Radiopharmaceuticals, xenograft, tumor, castration-resistant prostate cancer, 177Lu, 18F
背景：利用放射性核素疗法治疗对阉割耐药的前列腺癌需要新的治疗方法。新方法将优化使用镥177标记的PSMA低分子量配体对转移性阉割耐药前列腺癌进行放射性核素治疗的个性化策略。 目的：通过 PET 成像确定治疗实验动物的长期效果和有效性，以完善研究策略。 材料与方法：该研究以表达 PSMA 的 22Rv1 前列腺癌异种移植的 nu/nu 雄性小鼠为对象。使用 18F-PSMA-1007 进行 PET/CT 研究，以确认单剂量 [177Lu]Lu-PSMA IT 治疗后肿瘤的再生情况。 结果：18F-PSMA-1007 PET 成像显示，单次注射 9.2 MBq [177Lu]Lu-PSMA IT 后，22Rv1 肿瘤有可能延长生长，这相当于人体最小治疗剂量（28.6 MBq/kg）。 结论：研究证实，单次注射 9.2 MBq [177Lu]Lu-PSMA IT 后，观察到的治疗效果持续时间很短。PET/CT 使用 18F-PSMA-1007 证实，在 22Rv1 异种移植物缩小到不可触及状态后的 2.5 个月内，肿瘤重新生长。这些结果证实，在需要减少单次剂量的情况下，有必要研究重复施用基于PSMA配体并用镥177标记的放射性药物的频率，以达到稳定的治疗效果。 关键词 放射性药物 异种移植 肿瘤 耐阉割前列腺癌 177Lu 18F
{"title":"PRECLINICAL PET/CT OF PROLONGED TUMOR GROWTH AFTER 177LU-PSMA TREATMENT IN XENOGRAFT MODEL OF HUMAN PROSTATIC CANCER","authors":"Anna Smirnova, Olga E. Klementyeva","doi":"10.17816/onco501765","DOIUrl":"https://doi.org/10.17816/onco501765","url":null,"abstract":"BACKGROUND: New treatment methods of castration-resistant prostate cancer with radionuclide therapy are needed. New methods will optimize personalized strategy for radionuclide therapy of metastatic castrate-resistant prostate cancer using low molecular weight ligands to PSMA labeled with lutetium-177. AIMS: To define the long-term effects and effectiveness of the treatment experimental animals with PET imaging to refine the research strategy. MATERIALS AND METHODS: The study was performed in nu/nu male mice with PSMA-expressing 22Rv1 prostate cancer xenografts. PET/CT study with 18F-PSMA-1007 was used to confirm the tumor regrowth after a single therapeutic dose of [177Lu]Lu-PSMA IT. RESULTS: PET imaging with 18F-PSMA-1007 showed the possibility of prolonged 22Rv1 tumor regrowth after a single injection of 9.2 MBq [177Lu]Lu-PSMA IT, which is equivalent to minimal human therapeutic dose (28.6 MBq/kg). CONCLUSIONS: The study confirmed the short period of the observed therapeutic effect after a single injection of 9.2 MBq [177Lu]Lu-PSMA IT. The tumor regrowth in 2.5 months after the reduction of 22Rv1 xenografts to a non-palpable state was confirmed by PET/CT with 18F-PSMA-1007. These results confirm the need to study the frequency of repeated administrations of radiopharmaceuticals based on ligands to PSMA labeled with lutetium-177 to achieve a stable therapeutic effect in cases where a single dose reduction is necessary. Keywords Radiopharmaceuticals, xenograft, tumor, castration-resistant prostate cancer, 177Lu, 18F","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139181051","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}
BACKGROUND: One of the alternate ways to developing novel medication is pharmacological pairs: an enzyme and a non-toxic prodrug that, under certain conditions, release cytotoxic substances within or on the surface of the cancer cells, allowing the drug to be delivered precisely to the cancer cells. AIMS: To evaluate cytotoxic and anticancer effects of the pharmacological pair C115H methionine -lyase (C115H MGL), conjugated with daidzein (C115H MGL-Dz), and S-propyl-L-cysteine sulfoxide against different kinds of solid tumors in vitro and in vivo. MATERIALS AND METHODS: MTT-test was performed to determine the cytotoxicity of C115H MGL-Dz in the presence of S-propyl-L-cysteine sulfoxide (propiin) in vitro against human embryonic kidney (HEK-293), human placenta, breast cancer (MCF7, SKBR3, and T47D), colon cancer (HT29 and COLO205), pancreatic cancer (MIA PaCa2) and prostate cancer (DU145, and PC3) cells. The anticancer activity of the pharmacological pair C115H MGL-Dz + propiin against SKBR3, MIA PaCa2, and HT29 in vivo was investigated using subcutaneous xenografts in Balb/c nude mice. RESULTS: In comparison to dipropylthiosulfinate generated in vitro using the pharmacological pairsC115H MGL + propiin, targeted delivery of C115H MGL-Dzas a component of a pharmacological pair C115H MGL-Dz + propiin to generatedipropylthiosulfinate directly on the surface of cancercells enhances cytotoxicity in all cancercells. The study of the antitumor activity of the pharmacological pair C115H MGL-Dz + propiin in vivo revealed a suppression of tumor volume growth in xenografts SKBR3 (tumor growth inhibition (TGI) 89%, p = 0.004), MIA PaCa2 (TGI 50%, p = 0.011), and HT29 (TGI 52%, p = 0.04) vs control. CONCLUSIONS: On several cancer cells, the cytotoxicity and anticancer activity of dipropylthiosulfinate produced by the pharmacological pair C115H MGL-Dz + propiin was observed. Our findings may stimulate more study into the role of pharmacological pairsas a novel strategy to cancer treatment.
{"title":"CYTOTOXIC AND ANTICANCER ACTIVITIES OF PHARMACOLOGICAL PAIRS C115H METHIONINE GAMMA-LYASE AND S-PROPYL-L-CYSTEINE SULFOXIDE","authors":"L. Abo Qoura, V. S. Pokrovsky","doi":"10.17816/onco501727","DOIUrl":"https://doi.org/10.17816/onco501727","url":null,"abstract":"BACKGROUND: One of the alternate ways to developing novel medication is pharmacological pairs: an enzyme and a non-toxic prodrug that, under certain conditions, release cytotoxic substances within or on the surface of the cancer cells, allowing the drug to be delivered precisely to the cancer cells. AIMS: To evaluate cytotoxic and anticancer effects of the pharmacological pair C115H methionine -lyase (C115H MGL), conjugated with daidzein (C115H MGL-Dz), and S-propyl-L-cysteine sulfoxide against different kinds of solid tumors in vitro and in vivo. MATERIALS AND METHODS: MTT-test was performed to determine the cytotoxicity of C115H MGL-Dz in the presence of S-propyl-L-cysteine sulfoxide (propiin) in vitro against human embryonic kidney (HEK-293), human placenta, breast cancer (MCF7, SKBR3, and T47D), colon cancer (HT29 and COLO205), pancreatic cancer (MIA PaCa2) and prostate cancer (DU145, and PC3) cells. The anticancer activity of the pharmacological pair C115H MGL-Dz + propiin against SKBR3, MIA PaCa2, and HT29 in vivo was investigated using subcutaneous xenografts in Balb/c nude mice. RESULTS: In comparison to dipropylthiosulfinate generated in vitro using the pharmacological pairsC115H MGL + propiin, targeted delivery of C115H MGL-Dzas a component of a pharmacological pair C115H MGL-Dz + propiin to generatedipropylthiosulfinate directly on the surface of cancercells enhances cytotoxicity in all cancercells. The study of the antitumor activity of the pharmacological pair C115H MGL-Dz + propiin in vivo revealed a suppression of tumor volume growth in xenografts SKBR3 (tumor growth inhibition (TGI) 89%, p = 0.004), MIA PaCa2 (TGI 50%, p = 0.011), and HT29 (TGI 52%, p = 0.04) vs control. CONCLUSIONS: On several cancer cells, the cytotoxicity and anticancer activity of dipropylthiosulfinate produced by the pharmacological pair C115H MGL-Dz + propiin was observed. Our findings may stimulate more study into the role of pharmacological pairsas a novel strategy to cancer treatment.","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139286508","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}
I. I. Khan, A. S. Latysheva, V. A. Zolottsev, Elena A. Demidova, Tatyana S. Spirina, Saida S. Karshieva, D. Sokolova, M. N. Yakunina, A. Misharin, Marina V. Komarova, V. Pokrovsky
Abstract Background: Prostate cancer (PC) is the most frequently diagnosed type of cancer in men in developed countries. PC is dependent upon androgens and could be effectively combated by androgen deprivation therapy in such patients. Reduction of androgen synthesis can be accomplished through the inhibition of the enzyme 17
{"title":"Antiproliferative activity of the novel CYP17A1 inhibitor alsevirone","authors":"I. I. Khan, A. S. Latysheva, V. A. Zolottsev, Elena A. Demidova, Tatyana S. Spirina, Saida S. Karshieva, D. Sokolova, M. N. Yakunina, A. Misharin, Marina V. Komarova, V. Pokrovsky","doi":"10.17816/onco492271","DOIUrl":"https://doi.org/10.17816/onco492271","url":null,"abstract":"Abstract Background: Prostate cancer (PC) is the most frequently diagnosed type of cancer in men in developed countries. PC is dependent upon androgens and could be effectively combated by androgen deprivation therapy in such patients. Reduction of androgen synthesis can be accomplished through the inhibition of the enzyme 17","PeriodicalId":509207,"journal":{"name":"Russian Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139283254","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}
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