卷 22, 编号 1 (2017)
- 年: 2017
- 文章: 8
- URL: https://journal-vniispk.ru/1028-9984/issue/view/2393
Articles
THE ROLE OF ALPHA-FETOPROTEIN RECEPTOR IN THE DELIVERY OF TARGETED PREPARATIONS IN ONCOLOGY
摘要
There was executed the analysis of thematic literature during from 1956 to 2015 devoted to receptors to fetal proteins, including to alpha-fetoprotein (AFP) known in medicine as oncomarker and used by malignant cells for the organization of tumoral homeostasis. As protein carrier, AFP similar to albumin takes of vitally important molecules in a space «hydrophobic pocket» and moves inside a cell, but as the cancer-embryonal antigen (CEA) - determines the existence of a malignant tumor, but not the type of a neoplasm. On the bounding of AFP with teratogen and their internalization and delivery in an embryo there is based the development of ways of «address» delivery of substances into a cell. This is realized by means of receptor mediated endocytosis via specific membranous receptors to AFP (ReCAF) with high selectivity concerning malignant cells of various genesis. Up to 90% of all malignant cells of the human and tumor models for human and mammalians express AFP receptors, including rather recently opened stem tumor cells - the most probable source of metastasing. AFP production and expression of receptors is selectively raised in malignant tumors of patients and human tumor models. The hyperproduction of AFP and hyperexpression of ReCAF are related to the histologic type of tumor model and are characteristic for embrional cell tumors and hepatoblastomas with initially low drug sensitivity or with the resistance. When choosing the model it is necessary to consider that in different types of tumor cells ReCAF have specific features in cultivation which are not pronounced in conditions of an animal organism. More differentiated tumors are characterized by the larger level of the AFP production and a hyperexpression of ReCAF. The use of subcutaneous tumor xenografts signal for AFP localizations with the hyperexpression of receptors, allows to reveal mostly evidentially the effectiveness of the therapeutic system at the preclinical level. Address delivery of therapeutic systems created on the basis of AFP or its fragments is capable of causing the change of their pharmacological properties. The therapeutic prize is possible due to the induction of process of apoptosis via the mitochondrial pathway, but at the same time the fall in the cytotoxic capacity of system is possible.
Russian Journal of Oncology. 2017;22(1):4-14
4-14
THE BRAF MUTATION V600E IN PAPILLARY THYROID CANCER, CLINICAL-MORPHOLOGICALPARALLELES AND PROGNOSIS
摘要
On the material of the 67 cases of papillary thyroid cancer (PTC) authors executed the study of the interrelationship between the BRAF mutation V600E and the forecast, biomolecular and morphological characteristics of the disease. There was implemented the analysis of samples for the presence of 7 KRAS gene mutations, 4 mutations of the PIK3CA gene, mutation BRAF V600E with the revealing of the interrelationship between such biomolecular markers for proliferation and apoptosis as Ki-67, p53, Bcl2. Also there was performed chromogenic hybridization (CISH method) in situ to study the status of the HER2 gene. There was determined the interrelationship between BRAF mutation V600E and clinical indices of prognosis: tumor sizes, capsule invasion, presence of metastases in regional lymph nodes. In addition, there was evaluated the interrelationship between BRAF mutation V600E and 10-years survival rate. No mutation were identified in KRAS, PI3K genes. BRAF mutation V600E was identified in 50 cases (75%). The frequency of V600E in women accounted of 75 ± 6.4%, in men - 67 ± 27.1%. In patients with the presence of V600E the size of a node was slightly less than in the absence of mutations and in 76% of cases did not reach the average value of 1.8 cm. Invasion into the capsule was identified in 35 ± 12.7% cases with a positive BRAF mutation V600E status and in 56 ± 8.4% - in cases with a negative status. Metastases in regional lymph nodes occurred in 36 ± 11.6% in patients with V600E and in 47 ± 18.9% of cases without this mutation. There was obtained the interrelationship between V600E and Ki-67: the average level of the proliferative activity in the presence of the given mutation was 4.4 ± 0.6%, in the absence - 9.4 ± 3.9%. No interrelationship was obtained between V600E and other biomolecular parameters or this interrelationship was tendentious in character. In terms of 10-years survival the groups with or without V600E statistically did not differ. Based on the data, it was possible to say about the absence of the negative impact of V600E on the prognosis in PTC patients
Russian Journal of Oncology. 2017;22(1):15-20
15-20
INTRATUMORAL STROMAL MAST CELLS IN RENAL CELL CARCINOMA: CLINICAL AND MORPHOLOGICAL COMPARISONS
摘要
In the work there was investigated the prognostic value of the counting of intratumoral stromal mast cells (MC) in renal cell carcinoma. Tissue samples were obtained intraoperatively from 63 patients with renal cell carcinoma. The average age of patients accounted for 58.2 ± 12 years. There were observed 34 (54%) men and 29 (46%) women. There were revealed correlation relationships between the density of distribution of mast cells in tumor and the clinical stage of the disease (r = 0.69; p = 0.0001), tumor nodule size (r = 0.58; p = 0.0001), the presence of regional and distant metastases (r = 0.48; p = 0.0001), tumor grade according to the criteria of Fuhrman (r = 0.89; p = 0.001), and postoperative survival of patients (r = 0.40; p = 0.001). There was found no interrelationship between the number of MC in tumor with the gender (r = -0.03; p = 0.8), age (r = -0.15; p= 0.25), and the histological type of tumor (r = 0.16; p = 0.19). The gain in the number of intratumoral stromal MC in carcinoma can be considered as a predictor of the possible appearance of metastases. The high amount of MC in tumor has been shown to correlate with a poor prognosis of the patients with renal cell carcinoma.
Russian Journal of Oncology. 2017;22(1):21-24
21-24
POSSIBILITIES OF THE CORRECTION OF ENDOGENOUS INTOXICATION DURING CHEMOTHERAPY IN GYNECOLOGICAL CANCER PATIENTS
摘要
Introduction. The application of efferent therapy (extracorporeal therapy) now becomes relevant due to the individual intolerance to various drugs, side effects of a great many of drugs, which is especially important when treating onco-gynecological pathology, often accompanied by the development of endogenous intoxication. The purpose of the study is the evaluation of the state of the system of endotoxemia in gynecological cancer patients under treatment by certain types of chemotherapy with the use of extracorporeal approaches. Material and Methods. In the blood of 86 ovarian cancer patients under a neoadjuvant intraperitoneal chemotherapy conducted on protein concentrate of ascitic fluid and neoadjuvant chemotherapy with prior plasma exchange, as well as in 16 patients with cervical cancer at chemoimmunotherapy on autologous blood there were investigated indices of endogenous intoxication, reflecting the level of endotoxins and functional state of albumin. Results. Intraperitoneal chemotherapy on ascites protein concentrate obtained with the use of filtration detoxification was established to have a considerably lower toxicity as compared with the standard procedure of intraperitoneal chemotherapy. Chemotherapy conducted on autologous media with the inclusion of ronkoleukine and reaferon eliminates the toxic effects of cytostatic agents by the restoration of the functional activity of the albumin molecule. Application of plasmapheresis before neoadjuvant polychemotherapy declines the exertion in the endotoxemia system in gynecological cancer patients. Conclusion. The use of extracorporeal methods of the therapy and body fluids as a medium for cytostatics allows to decline the level of endogenous intoxication in patients with gynecological cancer.
Russian Journal of Oncology. 2017;22(1):25-31
25-31
IMMEDIATE AND REMOTE RESULTS OF PALLIATIVE SURGERY IN PATIENTS WITH METASTATIC COLORECTAL CANCER
摘要
The significance of the study is associated with the high level of the morbidity rate of colorectal cancer, generous amount of patients with the 4th stage and the necessity of the research of palliative surgical treatment. A retrospective analysis of 364 cases with metastatic colorectal cancer included 58 patients with palliative colon resection and 306 patients with bypass anastomosis and unloading stoma. Evaluated parameters are the frequency of postoperative complications, postoperative mortality rate, median survival and one-year survival. In the group of palliative resections the frequency of postoperative complications and postoperative mortality rate were 32.7% and 20.6%, in the group of symptomatic operations the same results were 12.1% and 8.8%. Median survival, one-year survival in the group of palliative resections are longer than in the group of symptomatic operations - 10.0 and 5.1 months, 37.0% and 18.3%, respectively (p < 0.05). However, after stratification of studied subgroups according to the sign of the presence or absence of post-operative chemotherapy the survival were shown to be higher in patients with chemotherapy and hardly depended on fact of the removal of the primary tumor. To our opinion the high rate of postoperative complications and the postoperative mortality rate after palliative resections of the colon can be corrected by more precise determination of indications to their performance in emergency surgery. The improvement in survival indices is associated with the execution of postoperative adjuvant chemotherapy.
Russian Journal of Oncology. 2017;22(1):32-38
32-38
THE ROLE OF GENES RAD50 AND SMARCA5 IN REGULATION OF SENSITIVITY TO CISPLATIN IN TUMOR CELLS OF OVARIAN, HEAD AND NECK CANCER
摘要
Aim of the study. To assess the role of genes RAD50 and SMARCA5 in regulation of sensitivity to cisplatin and other anticancer DNA damaging drugs (5-fluorouracil, olaparib), to assess the role of these genes in the response to the DNA damage in ovarian cancer (OVCAR-8) and head and neck cancer cell lines (SCC61, SCC25). Material and Methods. We used small interfering RNAs (siRNAs) (Qiagen,Germany) to deplete either RAD50 and SMARCA5 or control genes and under basal and DNA damaging drug-treatment conditions, we assessed cell viability with the use of Cell Titer Blue reagent (Promega,USA) with following spectrophotometry. To assess the role of genes in response to DNA damage, analysis of phospho-H2AX focus formation was performed by means of using immunofluorescence microscopy. Results. We demonstrated the role of RAD50 and SMARCA5 in regulation of survival and sensitivity of ovarian cancer (OVCAR-8), head and neck cancer cell lines (SCC61, SCC25) to cisplatin and other DNA damaging drugs (5-fluorouracil, olaparib). Our data suggest the role of SMARCA5 in regulation of baseline histone H2AX protein phosphorylation in the absence of DNA damage. Conclusion. Our findings characterize genes RAD50 and SMARCA5 as promising therapeutic targets and predictive markers for response to cisplatin and other DNA damaging drugs in patients with ovarian cancer and squamous cell carcinoma of head and neck.
Russian Journal of Oncology. 2017;22(1):39-43
39-43
FEATURES OF THE ORGANIZATION OF ANTICANCER MEASURES IN TERRITORIES WITH LOW POPULATION DENSITY ON THE EXAMPLE OF THE TOMSK REGION
摘要
The poor performance of rural health in remote from the center territories of the Tomsk region, determined the need for the optimization of cancer control measures. In 2013-2015 in the oncology service of the Tomsk region there were occurred structural and qualitative changes: there was formed a three-level system of the provision of specialized health care. For workers of the first level of health care system - feldsher obstetric units (FOUs) there were approved methodical approaches to the organization and implementation of screening for external location cancer, the formation of cancer risk groups for further examination; routing and observation of cases with risk factors, precancerous and background processes; documenting of the execution of the examination for cancer; routing and tactics for the observation of cancer patients. There are introduced motivational measures for the improvement of the quality of the work of medical staff. There are actively practiced mobile forms of the activity, with taking into account seasonality, the state of the transport accessibility (the use of mobile mammographs based on KAMAZ chassis, the regional project «The floating clinic», curation of districts by oncologists). There was introduced the mechanism of «individual road map», including telemedical technologies for distance observation of patient documents (the number of unnecessary visits of rural residents decreased by 30%). There were founded primary oncological units (POU), their base is enhanced by the diagnostic equipment, which reduced the number of underexamined patients by 47.5%. There was created the network of primary cytological laboratories completed with microscopes with digital processing and transmission of images over the Internet, there were performed more than 20,000 telemedical consultations, resulting in 70 diagnosed cases of cervical cancer for 2 years. The execution of POU-based courses of drug antitumor therapy increased the number of patients received the treatment at site of residing by 2.2 times. There was organized beneficiary drug coverage, including drugs for the treatment of chronic pain. Thanks to the work of POUs in the new status there were increased both the coverage of the population by cancer preventive examinations and indices of detection rates of precancerous diseases and chronic external localization diseases as in men as well in women.
Russian Journal of Oncology. 2017;22(1):44-50
44-50
THE PLACE OF SURGERY IN MODERN TREATMENT OF SKIN MELANOMA
摘要
Recent breakthroughs in the treatment of melanoma are associated with the systemic therapy by drugs of new classes, however, the place of surgery remains to be the main in the management of both localized and widespread melanoma. In this literature review, there are systematized the modern concepts of local excision of the primary tumor, the value of biopsy of sentinel lymph node and possibilities of surgical treatment of distant metastases of melanoma.
Russian Journal of Oncology. 2017;22(1):51-56
51-56