Experimental oncology最新文献

The creation of a central bank of personalized information of cancer patients, including children, allowed to obtain objective data and establish continuous cancer surveillance in the child population in Ukraine. The aim of the study was to analyze the dynamics of cancer incidence (1989-2019) and mortality (1999-2019) based on the 3^rd revision of International Classification of Childhood Cancer (ICCC-3).

Materials and methods: A study cohort includes 31,537 patients aged 0-19 years at the time of diagnosis in 1989-2019, registered in Ukrainian population.

Results: The major groups of malignancies in the child population are presented by leukemia, lymphomas, central nervous system (CNS) tumors, epithelial neoplasms, bone cancer and soft tissues sarcomas. There were observed no gender differences in cancer incidence, except germ cell tumors and trophoblastic tumors, gonadal malignancies, as well as some other malignant epithelial neoplasms, with their proportion being twice higher in the female population. Our analysis showed a trend towards increase in the incidence of leukemia, CNS neoplasms, neuroblastoma, trophoblastic tumors and epithelial malignancies; decrease in the incidence of lymphomas and bone neoplasms; stabilization in the incidence of malignancies of liver and kidneys. The dynamic changes in cancer mortality in the studied cohort were observed, namely, the decrease of mortality from leukemias and lymphomas in males (but not in females), along with the increase of mortality from CNS neoplasms, neuroblastoma, soft tissues sarcomas and germ cell tumors, regardless of gender.

Conclusions: The analysis and presentation of the epidemiological data on children's malignancies implementing ICCC-3 classification for all relevant records in the National Cancer Registry of Ukraine allows for evaluating the major trends of cancer incidence and mortality in Ukrainian pediatric population, taking into account tumor morphology, topography, gender and age.

Background: Glioblastoma (GBM) is the most prevalent malignant tumor of the brain in adults with the inherent aggressive behavior and high recurrence rate. The stereotactic radiosurgery (SRS) is currently considered as one of the effective modalities for GBM treatment allowing for the improvement of survival with the acceptable toxicity level.

Aim: To assess the effects of various factors on the survival of GBM patients following SRS.

Patients and methods: We retrospectively reviewed treatment outcomes of 68 patients who received SRS for recurrent GBM treatment in 2014-2020. SRS was delivered with Trilogy linear accelerator (6 MeV). The area of recurrent tumor/continued tumor growth was irradiated. For the treatment of the primary GBM, the adjuvant radiotherapy was provided at the standard fractionated regimen with the total boost dose of 60 Gy divided to 30 fractions (Stupp's protocol) in the setting of the concomitant chemotherapy with temozolomide. 36 patients then received temozolomide as the maintenance chemotherapy. SRS for the treatment of recurrent GBM was provided at a boost dose of 20.2 Gy on average being delivered into 1-5 fractions with average single dose of 12.4 Gy. The survival was analyzed by the Kaplan-Meier method with a log-rank test used for assessing the impact of the independent predictors on the survival risks.

Results: The median overall survival (OS) was 21.7 months (95% confidence interval (CІ) 16.4-43.1), median survival after SRS was 9.3 months (95% CІ 5.6-22.7). The majority of patients (72%) were alive for at least 6 months following SRS and about half of patients (48%) survived for at least 24 months following the resection of the primary tumor. OS and survival after SRS depend significantly on the extent of the surgical resection of the primary tumor. The addition of temozolomide to radiotherapy prolongs survival in GBM patients. The relapse time affected significantly OS (p = 0.00008), but not survival after SRS. Neither OS, nor survival after SRS were affected significantly by such factors as the age of patients, the number of SRS fractions (one fraction vs several fractions), and target volume.

Conclusion: Radiosurgery improves the survival in patients with recurrent GBM. The extent of the surgical resection and adjuvant alkylating chemotherapy of the primary tumor, overall biologically effective dose and time between the primary diagnosis and SRS affect significantly the survival. The search for the more effective schedules for treating such patients requires further studies with more numerous cohorts of patients and extended follow-up.

The strategy for the treatment of gastric cancer (GC), in particular the use of the extended surgical interventions in different countries varies. The different proportion of specific molecular GC subtypes in various populations frequently is not taken into account for comparing treatment outcomes. This pilot study analyzes the association of survival of GC patients after the extended combined surgical interventions depending on the molecular subtype of the tumors. An improved survival for patients with diffuse cancer types (p53-, VEGFR⁺, HER2/neu⁺, Ki-67⁺ phenotype) was demonstrated. The authors propose their point of view on the importance of recognizing GC molecular heterogeneity.Key Words: gastric cancer, molecular classification, tumor biology.

Magnetic signals emitted by living organisms, regardless of a biological species, are important biophysical indicators. The study of these indicators is very relevant and promising for the visualization of the tumor process and the development of technologies using artificial intelligence when it comes to malignant neoplasms, particularly resistant to chemotherapy.

Aim: To measure magnetic signals from transplantable rat tumors and their counterparts resistant to cytostatics for evaluating the features of the accumulation of iron-containing nanocomposite Ferroplat.

Materials and methods: Doxorubicin (Dox)-sensitive and Dox-resistant Walker-256 carcinosarcoma and cisplatin-sensitive and cisplatin-resistant Guerin's carcinoma transplanted in female Wistar rats were studied. The magnetism of tumors, liver and heart was determined using Superconductive Quantum Interference Device (SQUID) - magnetometry in a non-contact (13 mm over the tumor) way using specially designed computer programs. In a group of the experimental animals, a ferromagnetic nanocomposite (Ferroplat) was administered as a single intravenous injection and biomagnetism was assessed in 1 h.

Results: The magnetic signals coming from Dox-resistant Walker-256 carcinosarcoma in the exponential growth phase were significantly higher in comparison with sensitive tumor. Intravenous administration of Ferroplat increased biomagnetism by at least an order of magnitude, especially in resistant tumors. At the same time, the magnetic signals of the liver and heart were within the magnetic noise.

Conclusion: The use of SQUID-magnetometry with ferromagnetic nanoparticles as a contrast agent is a promising approach for visualization of malignant neoplasms with varying sensitivity to chemotherapy.

The search for new prognostic and stratification genetic and epigenetic markers in neuroblastoma is an urgent problem in pediatric oncology. The review summarizes recent progress in studying the expression of genes involved in p53 pathway regulation in neuroblastoma. Several markers associated with recurrence risk and poor outcome are considered. Among them are MYCN amplification, high MDM2 and GSTP1 expression and homozygous mutant allele variant of GSTP1 gene A313G polymorphism. Prognostic criteria for neuroblastoma based on the analysis of miR-34a, miR-137, miR-380-5p, and miR-885-5p expression involved in regulating p53-mediated pathway are also considered. The authors' research data on the role of the above markers in regulation of this pathway in neuroblastoma are presented. The study of alterations in expression of microRNAs and genes involved in p53 pathway regulation will not only expand our understanding of the mechanisms of neuroblastoma pathogenesis but could substantiate new approaches for delineating risk groups and risk stratification of neuroblastoma patients as well as treatment optimization based on the genetic characteristics of the tumor.

Background: Leptin is an adipokine encoded by the Ob (obese) gene and predominantly produced by adipocytes. The roles of both leptin and leptin receptor (ObR) in numerous pathophysiological conditions including mammary tumor (MT) development have been reported.

Aim: To examine protein expression levels of leptin and its receptors (ObR) including the long form, ObRb, in MT tissue and mammary fat pad of a transgenic mammary cancer mouse model. Further, we investigated whether the effects of leptin on MT development are systemic or local.

Materials and methods: MMTV-TGF-α transgenic female mice were fed ad libitum from week 10 up to week 74. Protein expression levels of leptin, ObR, and ObRb were measured in the mammary tissue samples of 74-week old MMTV-TGF-α mice with and without MT (MT-positive/MT-negative) by Western blot analysis. Serum leptin levels were measured by using the mouse adipokine LINCOplex kit 96-well plate assay.

Results: Protein expression levels of ObRb were significantly lower in MT as compared to control tissue of mammary gland. In addition, protein expression levels of leptin were significantly higher in the MT tissue of MT-positive mice compared to control tissue of MT-negative mice. However, ObR protein expression levels in tissues of mice with and without MT were similar. Serum leptin levels at different ages were not significantly different between the two groups.

Conclusion: Leptin and ObRb in the mammary tissue may play a critical role in the mammary cancer development, while contribution of short ObR isoform may be less important.

Aim: To compare the dynamics of changes in the hormonal status of female rats in the setting of the FAC (5-fluorouracil, doxorubicin and cyclophosphamide) chemotherapy and after local administration of platelet-rich plasma (PRP).

Materials and methods: The study was carried out on female Wistar rats treated according to the FAC chemotherapy scheme (4 courses with a 3-week interval). The ovariotoxic effect of the FAC chemotherapy was assessed by the levels of anti-Mullerian hormone, estradiol (E2) and follicle-stimulating hormone in the proestrus phase. Three weeks after the last course of chemotherapy, 5 rats were administered with local intra- and periovarian injection of PRP (triply with a 1-week interval).

Results: The dynamics of all investigated hormonal markers of the ovarian reserve in experimental animals was characterized by a progressive decrease in anti-Mullerian hormone and E2 levels and an increase in follicle-stimulating hormone level. The dynamics of the studied parameters after the serial administration of PRP demonstrated an improvement in the hormonal status.

Conclusion: FAC chemotherapy in the experiment causes premature ovarian failure, and local administration of PRP improves the hormonal parameters of the ovarian reserve.

Background: The combination of zinc oxide (ZnO) nanoparticles (NPs) with carriers enhances the anticancer effect of nanocomposites.

Aim: To explore the mechanisms of cytotoxic action of dextran-graft-polyacrylamide (D-g-PAA/ZnO) NPs against prostate cancers cell lines in vitro.

Materials and methods: Dextran-polyacrylamide was used as a matrix for the synthesis of ZnO NPs. Prostate cancer cells LNCaP, DU-145 and PC-3 were treated with D-g-PAA/ZnO NPs. The expression of Bax, Bcl-2, p53 and Ki-67 was studied using immunocytochemical analysis. Cytomorphological changes in cells were detected after their incubation with nanocomposites for 24 h.

Results: The treatment with D-g-PAA/ZnO NPs caused the increase in the Bax and p53 and the decrease in Ki-67 and Bcl-2 expression. Morphological changes associated with apoptosis were registered: decrease in cell size, appearance of cytoplasmic vacuolation, condensation of chromatin, blebbing.

Conclusions: Treatment with D-g-PAA/ZnO nanocomposite led to the initiation of apoptotic cell death in prostate cancer cells in vitro.

Background: Salivary gland tumors are rare. Nevertheless, the accurate preoperative diagnosis of the malignant potential of the lesion is essential for appropriate patient management. The recently published Milan system for reporting salivary gland cytology (MSRSGC) is an effort to provide better communication regarding the nature of lesions to clinicians. Aim: To evaluate the diagnostic utility of fine-needle aspiration cytology (FNAC) of neoplastic salivary gland lesions and the MSRSGC applicability in risk stratification.

Materials and methods: This was a retrospective study of the cytological and histopathological correlation between neoplastic lesions of salivary gland lesions conducted over four years (August 2010 - September 2014) in two tertiary care hospitals. There were 66 cases of FNAC of salivary gland neoplasms. The sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of FNAC were analyzed. The risk of malignancy for MSRSGC was calculated.

Results: The overall diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were 93.94; 95.5; 99.8; 96.8, and 98.7%, respectively. By correlating the cytological diagnosis of benign neoplasm with histopathological diagnosis, the risk of malignancy was 0% and risk of neoplasm was 100%. For cases in the category suspicious of malignancy, risk of neoplasm was 100% and risk of malignancy was 85%.

Conclusion: The present study demonstrated that this salivary gland cytology reporting system was useful in classifying the lesions in well-delineated categories with ease. MSRSGC system of standardized reporting is helpful for guiding clinicians in appropriate management of the patient. However, many multicenter studies with large sample sizes and long-term follow-up are needed along with wide propagation of its standardized reporting format to be adopted universally.