Impact of TGFB1 Leu10Pro polymorphism on acute radiotherapy-induced toxicity in prostate cancer patients

Background: Radiotherapy (RT)-induced acute toxicity associated with bladder and bowel injury has great impact the quality of life for prostate cancer (PCa) patients. TGFB1 is a key proinflammatory and profibrotic cytokine, but its role in acute toxicity is still unclear. TGFB1 T>C transition at codon 10 results in leucine to proline substitution and increased TGFB1 protein levels. The aim of this study was to examine impact of TGFB1 Leu10Pro (rs1800470) polymorphism on RT-induced acute toxicity in PCa patients. Patients and methods: Eighty two patients who had a localized or locally advanced PCa were treated with radical (72 Gy)(n=47) or postoperative/salvage (66 Gy)(n=35) RT without previous hormonal therapy. TGFB1 Leu10Pro was determined by PCR-RFLP analysis on DNA from PBMC. The differences in the distribution of genotypes for dominant, recessive, codominant and overdominant genetic model between patients with or without acute genitourinary (GU) or gastrointestinal (GI) toxicity as well as different grade of toxicity were tested by χ2 and Fisher’s exact test. P values ≤0.05 were considered statistically significant. Results: Heterozygote PCa patients had lower rate of acute GU and GI toxicity then homozygotes (LeuLeu, LeuPro, ProPro were: 100%, 90.7%, 100% for GU and 92.0%, 88.4%, 100%, respectively for GI). The frequency of toxicity grade ≥2 were higher in LeuPro then both homozygote carriers (41% vs. 28.2% for GU and 26.3% vs. 21.6% for GI acute toxicity). The differences were not statistically significant. Conclusion: The present study did not establish impact of TGFB1 Leu10Pro polymorphism on RT-induced acute toxicity in PCa patients.5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5, Virtual event, December 3, Belgrade, 2021

Association between TGFB1 C-509T polymorphism and acute toxicity after radiotherapy for prostate cancer

Background: Radiotherapy (RT) for prostate cancer (PCa) is associated with a spectrum of side effects (toxicity) in the surrounding normal tissues. TGFB1 is a key cytokine associated with inflammation and fibrosis, but its role in acute toxicity is unclear. The presence of T allele at −509 bp of the promoter region of TGFB1 gene is related to higher concentrations of TGFB1 than C allele. We aimed to investigate association between C-509T polymorphism (rs1800469) and RT-induced acute toxicity. Patients and methods: Eighty six patients who had a localized or locally advanced PCa were treated with radical (72 Gy)(n=49) or postoperative/salvage (66 Gy)(n=37) RT without previous hormonal therapy. TGFB1 C-509T was determined by PCR-RFLP analysis on DNA from PBMC. The differences in the distribution of genotypes between patients with or without acute genitourinary (GU) or gastrointestinal (GI) toxicity were tested by χ2 and Fisher’s exact test. P values ≤0.05 were considered statistically significant. The genotype-specific associations with toxicity were estimated as odds ratios (OR) with 95% confidence intervals (CIs) for dominant, recessive, codominant and overdominant genetic model. Results: Heterozygote carriers of TGFB1 C-509T had statistically significant lower rate of acute GU and GI toxicity then homozygotes (CC plus TT) (p=0.048; p=0.047). Additionally, the OR indicated lower risk for acute toxicity development in heterozygote than homozygote patients (OR (95%CI) were: 0.12 (0.01- 1.11) for GU and 0.19 (0.03- 1.02) for GI). Conclusion: The obtained data indicate that CT genotype of TGFB1 C-509T could be potential biomarkers of lower risk for acute RT-induced toxicity.5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5, Virtual event, December 3, Belgrade, 2021

Can miRNA expression patterns predict radiotoxicity in patients with glioblastoma?

Background: Standard treatment of the glioblastoma patients is implemented with Stupp’s protocol since 2005, but 2-years survival of the patients are still at low percentage. Even with implementation of modern radiotherapy techniques, acute radiotoxicity is still observed in these patients. Micro RNAs (miRNAs) expression patterns are introduced in recent years as factors that might predict survival in patients with glioblastoma, as well as cancer treatment related side effects. Material and methods: The data used in this review were conducted from research papers in PUBMED/MEDLINE databases with a special focus on role of miRNAs in cancer and with emphasis on brain tumors correlated to acute radiotoxicity. Results: Inflammation due to oxidative stress via free radicals is one of the mechanisms of radiation injury of irradiated cells and may correlate with toxicity. MiRNAs expression in prostate cancer patients may predict acute radiotoxicity, while miRNAs expression levels that could predict radiation toxicity in glioblastoma are still under investigation. However, it has been shown that miRNA levels like miR-16, miR 21, miR-19a and miR-22 are increased after radiation in glioma, while levels of miR-107, miR-181a are decreased. Conclusion: Recent studies have shown that miRNAs may have role as potent indicator of radiotoxicity in cancer patients. To date, there is no available data about acute brain radiotoxicity and its correlation with expression levels of mRNAs in patients with GB. There is a emerge need for further investigation on role of radioresponsive miRNAs in glioblastoma patients with acute radiotoxicity.5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5, Virtual event, December 3, Belgrade, 2021

Total number of cattle in the Republic of Serbia after an outbreak of Lumpy Skin Disease

Numerous studies conducted worldwide indicate a tendency towards a continuous decline in number of cattle. Appropriate measures should be taken to prevent the reduction of the number of cattle and to increase the concentration of animals per farm. In this regard, the objective of this study was to analyze the total number of cattle after an outbreak of Lumpy Skin Disease (LSD) in the Republic of Serbia. Due to the occurrence of this highly dangerous infectious disease in the Balkans and Eastern Europe, emergency and preventive vaccination was performed in infected and vulnerable areas in the Republic of Serbia. To prevent the spread of LSD, competent authorities banned public gatherings of cattle at fairs, exhibitions, livestock markets and purchase places, which resulted in economic losses for certain farmers. This disease is believed to have impacted the total number of cattle slaughtered and the number of deaths, as well as the import and export of live cattle, animal products and by-products of animal origin. The comparison between indices for the number of cattle shows a decline in the total number of cattle in the analyzed period across statistical territorial units. Results on the total number of cattle can be used, among other things, to create new and more complex questions arising from current and future farming problems

Total Number of Cattle in the Republic of Serbia after an Outbreak of Lumpy Skin Disease

Numerous studies conducted worldwide indicate a tendency towards a continuous decline in number of cattle. Appropriate measures should be taken to prevent the reduction of the number of cattle and to increase the concentration of animals per farm. In this regard, the objective of this study was to analyze the total number of cattle after an outbreak of Lumpy Skin Disease (LSD) in the Republic of Serbia. Due to the occurrence of this highly dangerous infectious disease in the Balkans and Eastern Europe, emergency and preventive vaccination was performed in infected and vulnerable areas in the Republic of Serbia. To prevent the spread of LSD, competent authorities banned public gatherings of cattle at fairs, exhibitions, livestock markets and purchase places, which resulted in economic losses for certain farmers. This disease is believed to have impacted the total number of cattle slaughtered and the number of deaths, as well as the import and export of live cattle, animal products and by-products of animal origin. The comparison between indices for the number of cattle shows a decline in the total number of cattle in the analyzed period across statistical territorial units. Results on the total number of cattle can be used, among other things, to create new and more complex questions arising from current and future farming problems

Defining breed standards and breeding goals for domestic donkey

Domestic donkey is a transboundary breed present in many Balkan countries. According to the Law on Animal Production, in many Balkan countries, for every breed of domestic animals it is necessary to create a separate breeding programme. Based on the results of a study evaluating the main morphological, reproductive and functional traits in 47 domestic donkeys in Macedonia during 2017 and 2018, current standards and breeding goals were defined for the next national breeding programme of this breed. According to the fact that the domestic donkey is a metapopulation and transboundary breed in almost all Balkan countries, it is a good recommendation to create a regional breeding programme with flexible standards and breeding goals for this relative of horses for all Balkan countries together

Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors

Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an “in-house” gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine

Association of polymorphisms in TGFB1, XRCC1, XRCC3 genes and CD8 T-lymphocyte apoptosis with adverse effect of radiotherapy for prostate cancer

The genetic background of each person might affect the severity of radiotherapy (RT)-induced normal tissue toxicity. The aim of study was to evaluate the influence of TGFB1 C-509T and Leu10Pro, XRCC1 Arg280His and XRCC3 Thr241Met polymorphisms as well as the level of radiation-induced CD8 T-lymphocyte apoptosis (RILA) on adverse effects of RT for prostate cancer (PCa). The study included 88 patients with localized or locally advanced PCa who were treated with RT. The polymorphisms were determined by PCR–RFLP analysis on DNA from peripheral blood mononuclear cells. RILA values were measured by flow cytometry. We found that CT genotype of TGFB1 C-509T could be protective biomarker for acute genitourinary (GU) and gastrointestinal (GI) radiotoxicity, while Thr variant of XRCC3 Thr241Met could predict the risk for acute GU radiotoxicity. Correlation between RILA values and toxicity was not detected. Univariate logistic regression analysis showed that Gleason score and risk group were risk factors for late GU, while for late GI radiotoxicity it was diabetes mellitus type 2. However, in multivariate model those were not proven to be significant and independent risk factors. Identification of assays combination predicting individual radiosensitivity is a crucial step towards personalized RT approach

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide

A personalized approach to chemoradiation is important in reducing its potential side effects and identifying a group of patients prone to toxicity. MicroRNAs have been shown to have a predictive potential for radiotoxicity. The goal of the study was to test if levels of miRNA in peripheral blood mononuclear cells of glioblastoma patients are associated with toxicity and to identify the peak time point for toxicity. MicroRNA-10b/21/34a levels were measured in 43 patients with and without toxicity, at baseline, at the 15th, and at the 30th fraction by Real-Time quantitative Polymerase Chain Reaction. MicroRNA-10b/21 levels increased with toxicity grade (p = 0.014; p = 0.013); miR-21/34a levels were significantly different between patients with and without toxicity at the 15th fraction (p = 0.030; p = 0.045), while miR-34a levels significantly changed during treatment (p < 0.001). All three miRNAs showed a significantly high positive correlation with one another. MiR-34a might be considered as a predictive factor for toxicity due to its changes during treatment, and differences between the groups with and without toxicity; miR-10b might be used to predict toxicity; miR-10b/21 might be used for predicting the grade of toxicity in GB patients