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Background: Clinical trials (CTs) are research investigations in which participants receive medical treatments, interventions, or tests to assess their safety and efficacy. Each planned clinical is registered through local or national medical agencies, which may differ in the amount of administrative and legal procedures. The objective of this study was to systematically analyze the registration process for clinical trials in Bosnia and Herzegovina in comparison to other Balkan countries. Methods: The search strategy was based using two online databases: Clinicaltrials.gov (CTGR) and Cortellis Clinical Trials Intelligence (cTi). Search engines included studies until 26th April 2021 and countries were compared in terms of the number of studies, status, type, funding, clinical phases and demographic data. Results: The total number of clinical trials from Bosnia and Herzegovina recorded in the CTGR database was 219, while the cTi database comprised 254 registered studies. The total number of reported clinical trials in CTGR and cTi databases were highest in Serbia (n = 1229, n = 1438), followed by Croatia (n = 1142, n = 1300), and Slovenia (n = 801, n = 948), respectively. However, the highest number of clinical trials per capita is in Slovenia (3.85e-4 in CTGR; 4.56e-4 in cTi), followed by Croatia (2.78e-4 in CTGR; 3.17e-4 in cTi), Serbia (1.41e-4 in CTGR; 1.65e-4 in cTi), and Bosnia and Herzegovina (0.67e-4 CTGR; 0.78e-4 cTi). Conclusion: Our analysis showed that Bosnia has the lowest number of clinical trials in the Balkans. Furthermore, the registration process is complex and longer than in developed countries. Since the healthcare system has been in a transition in the past decade, clinical trials are underutilized as a tool for the improvement of patient care. The clinical trial registration process could be improved by establishing an ethical committee at the state level and by enabling a parallel submission process to ethical committees and databases.
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BACKGROUND: Bosnia and Herzegovina is among ten countries in the world with the highest mortality rate due to COVID-19. Lack of lockdown, open borders, high mortality rate, no vaccination plan, and strong domestic anti-vaccination movement present serious COVID-19 concerns in Bosnia and Herzegovina. In such circumstances, we set out to study 1) the willingness of general public to receive the vaccine, 2) factors that affect vaccine rejection, and 3) motivation for vaccine acceptance. METHODS: A cross-sectional study was conducted among 10471 adults in Bosnia and Herzegovina to assess the acceptance or rejection of participants toward COVID-19 vaccination. Using a logistic regression model, we examined the associations of sociodemographic characteristics with vaccine rejection, reasons for vaccine hesitancy, preferred vaccine manufacturer, and information sources. RESULTS: Surprisingly, only 25.7% of respondents indicated they would like to get a COVID-19 vaccine, while 74.3% of respondents were either hesitant or completely rejected vaccination. The vaccine acceptance increased with increasing age, education, and income level. Major motivation of pro-vaccination behavior was intention to achieve collective immunity (30.1%), while the leading incentive for vaccine refusal was deficiency of clinical data (30.2%). The Pfizer-BioNTech vaccine is shown to be eightfold more preferred vaccine compared to the other manufacturers. For the first time in Bosnia, vaccine acceptance among health care professionals has been reported, where only 39.4% of healthcare professionals expressed willingness to get vaccinated. CONCLUSION: With the high share of the population unwilling to vaccinate, governmental impotence in securing the vaccines supplies, combined with the lack of any lockdown measures suggests that Bosnia and Herzegovina is unlikely to put COVID-19 pandemic under control in near future.
Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 , Medication Adherence , Pandemics/prevention & control , SARS-CoV-2 , Vaccination Refusal , Adolescent , Adult , Aged , Bosnia and Herzegovina/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Female , Humans , Male , Middle AgedABSTRACT
Here we describe the major genetic and genomic aberrations found in myeloid malignancies and how those markers are used in patients' diagnosis, prognosis, and targeted treatment. In Bosnia and Herzegovina, cytogenetic and molecular diagnostics for myeloid malignancies have been established and continually improved since 2005. We report the current state of available diagnostic tools for myeloid malignancies in Bosnia and Herzegovina. Myeloid malignancies are a heterogeneous group of clonal blood diseases characterized by defects in hematopoietic stem cells and myeloid progenitors that lead to abnormal proliferation, differentiation, localization, and self-renewal. Most common myeloid malignancies include myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Molecular diagnostics of myeloid malignancies have significantly expanded in the last decade with new genetic and genomic markers for diagnosis, prognosis, and treatment. CONCLUSION: In the last decade, several new genomic markers important for patient diagnosis, prognosis, and therapy have been discovered that need to be implemented in routine molecular diagnostics not only in developed nations but also in developing nations such as Bosnia and Herzegovina.
Subject(s)
Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Myeloproliferative Disorders , Bosnia and Herzegovina , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/genetics , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , PrognosisABSTRACT
The COVID-19 pandemic has demonstrated the need for massively-parallel, cost-effective tests monitoring viral spread. Here we present SARSeq, saliva analysis by RNA sequencing, a method to detect SARS-CoV-2 and other respiratory viruses on tens of thousands of samples in parallel. SARSeq relies on next generation sequencing of multiple amplicons generated in a multiplexed RT-PCR reaction. Two-dimensional, unique dual indexing, using four indices per sample, enables unambiguous and scalable assignment of reads to individual samples. We calibrate SARSeq on SARS-CoV-2 synthetic RNA, virions, and hundreds of human samples of various types. Robustness and sensitivity were virtually identical to quantitative RT-PCR. Double-blinded benchmarking to gold standard quantitative-RT-PCR performed by human diagnostics laboratories confirms this high sensitivity. SARSeq can be used to detect Influenza A and B viruses and human rhinovirus in parallel, and can be expanded for detection of other pathogens. Thus, SARSeq is ideally suited for differential diagnostic of infections during a pandemic.
Subject(s)
Clinical Laboratory Techniques , High-Throughput Screening Assays , Respiratory Tract Infections/diagnosis , Viruses/isolation & purification , COVID-19/diagnosis , Diagnosis, Differential , High-Throughput Nucleotide Sequencing , Humans , Polymerase Chain Reaction , RNA, Viral/genetics , Respiratory Tract Infections/virology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Saliva/virology , Sensitivity and Specificity , Viral Proteins/genetics , Viruses/classification , Viruses/geneticsABSTRACT
BACKGROUND: Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and WilmsÌ tumor in children. Despite recent advancements in tumor genomics, there is limited data available regarding the genetic alterations characteristic of MA. The purpose of this study is to determine the frequency of metanephric adenoma cases exhibiting cytogenetic aberration t (9;15)(p24;q24), and to investigate the association between t (9,15) and BRAF mutation in metanephric adenoma. METHODS: This study was conducted on 28 archival formalin fixed paraffin-embedded (FFPE) specimens from patients with pathologically confirmed MA. Tissue blocks were selected for BRAF sequencing and fluorescent in situ hybridization (FISH) analysis for chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3), which was previously characterized and described in two MA cases. RESULTS: BRAFV600E mutation was identified in 62% of our cases, 9 (38%) cases were BRAFWT, and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAFWT suggesting mutual exclusivity of BRAFV600E and KANK1-NTRK3 fusion, the first such observation in the literature. CONCLUSIONS: Our data shows that BRAF mutation in MA may not be as frequent as suggested in the literature and KANK-NTRK3 fusions may account for a subset of BRAFWT cases in younger patients. FISH analysis for KANK1-NTRK3 fusion or conventional cytogenetic analysis may be warranted to establish the diagnosis of MA in morphologically and immunohistochemically ambiguous MA cases lacking BRAF mutations.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Adenoma/genetics , Cytoskeletal Proteins/genetics , Kidney Neoplasms/genetics , Mutation , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins B-raf/genetics , Receptor, trkC/genetics , Adenoma/pathology , Adolescent , Adult , Aged , Child , Chromosomes, Human, Pair 15/genetics , Chromosomes, Human, Pair 9/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Kidney Neoplasms/pathology , Male , Middle Aged , Translocation, Genetic , Young AdultABSTRACT
Cell-to-cell communication is a fundamental process in every multicellular organism. In addition to membrane-bound and released factors, the sharing of cytosolic components represents a new, poorly explored signaling route. An extraordinary example of this communication channel is the direct transport of mitochondria between cells. In this review, we discuss how intercellular mitochondrial transfer can be used by cancer cells to sustain their high metabolic requirements and promote drug resistance and describe relevant molecular players in the context of current and future cancer therapy.
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Aim To investigate quality of life and exposure to lifestyle risk factors of cancer patients in Bosnia and Herzegovina and a correlation of cancer type with lifestyle risk factors. Methods This was a cross-sectional study conducted on 200 cancer patients from the Clinical Centre of the University of Sarajevo. The respondents completed an anonymous questionnaire consisting of seven sections: basic patient information, physical activity, dietary habits including alternative medicine, tobacco use, alcohol consumption, anxiety, and comorbidities. Results A total of 150 (75%) patients were overweight with 113 (56%) of them being less physically active after the confirmed diagnosis. After the diagnosis, 79 (40%) patients ate less food, and 154 (77%) healthier; 130 (65%) reported consumption of alternative medicine and food supplements, 39 (30%) spent >1/4 of average monthly salary on these products. Majority never consumed alcohol, 135 (68%) and 101 (51%) patients reported history of tobacco use. Being obese was an independent predictor for colorectal carcinoma; being less obese was linked to a decreased risk of breast cancer diagnosis. Physical activity was linked to a decreased risk of lung cancer diagnosis. Many patients (122; 61%) reported having chronic comorbidities, mostly hypertension, while 44 (22%) patients were proven to be clinically anxious. Conclusion Our data suggest lack of public awareness of the consequences of unhealthy lifestyles. Risk factors such as alcohol consumption and tobacco use differed from other European countries. Significance of lifestyle changes after the diagnosis for reducing mortality and cancer recurrence requires further research. Prevention programs and more data are needed.
Subject(s)
Life Style , Quality of Life , Bosnia and Herzegovina/epidemiology , Cross-Sectional Studies , Humans , Neoplasm Recurrence, Local , Risk FactorsABSTRACT
Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing 3 genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (eg, DNMT3A, TET2, or IDH2), and undefined cases with low mutational burden. We established an erythroid vs myeloid transcriptome-based space in which, independently of the molecular subgroup, the majority of the AEL samples exhibited a unique mapping different from both non-M6 AML and myelodysplastic syndrome samples. Notably, >25% of AEL patients, including in the genetically undefined subgroup, showed aberrant expression of key transcriptional regulators, including SKI, ERG, and ETO2. Ectopic expression of these factors in murine erythroid progenitors blocked in vitro erythroid differentiation and led to immortalization associated with decreased chromatin accessibility at GATA1-binding sites and functional interference with GATA1 activity. In vivo models showed development of lethal erythroid, mixed erythroid/myeloid, or other malignancies depending on the cell population in which AEL-associated alterations were expressed. Collectively, our data indicate that AEL is a molecularly heterogeneous disease with an erythroid identity that results in part from the aberrant activity of key erythroid transcription factors in hematopoietic stem or progenitor cells.
Subject(s)
Leukemia, Erythroblastic, Acute/genetics , Neoplasm Proteins/physiology , Transcription Factors/physiology , Transcriptome , Adult , Animals , Cell Transformation, Neoplastic/genetics , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Dioxygenases , Erythroblasts/metabolism , Erythropoiesis/genetics , Female , GATA1 Transcription Factor/deficiency , GATA1 Transcription Factor/genetics , Gene Knock-In Techniques , Genetic Heterogeneity , Hematopoietic Stem Cells/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , Mice, Transgenic , Middle Aged , Mutation , Neoplasm Proteins/genetics , Neoplastic Stem Cells/metabolism , Proto-Oncogene Proteins/deficiency , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/physiology , RNA-Seq , Radiation Chimera , Repressor Proteins/genetics , Repressor Proteins/physiology , Transcription Factors/genetics , Transcriptional Regulator ERG/genetics , Transcriptional Regulator ERG/physiology , Exome Sequencing , Young AdultABSTRACT
The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes has provided a powerful tool for studying disease evolution. Clinical features, gene mutations, and survival over 18 years were analyzed in MPN patients. One hundred thirty-eight MPN patients were subcategorized according to MPN subtypes: essential thrombocythemia (ET, n = 41), polycythemia vera (PV, n = 56), primary myelofibrosis (PMF, n = 10), and MPN unclassified (MPN-U, n = 31). Patient characteristics included clinical parameters, overall survival (OS), and mutational status of the Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) genes. We compared hematologic and clinical features of JAK2V617F-ET vs. CALR-mutated ET vs. JAK2V617F-PV patients. JAK2V617F-patients had higher values of erythrocytes, hemoglobin, and hematocrit compared to CALR-mutated patients (p < 0.05). The mutant allele burden in JAK2V617F-PV and JAK2V617F-ET patients directly correlated with erythrocyte, hemoglobin, and hematocrit values, but it inversely correlated with platelet count. Thus, mutant allele burden was an indicator of the clinical phenotype in JAK2V617F-MPN patients. OS was not affected by the mutational status. In general, mutated JAK2, CALR, and MPL genes left specific hematological signatures.
Subject(s)
Calreticulin/genetics , Janus Kinase 2/genetics , Mutation/genetics , Myeloproliferative Disorders/genetics , Phenotype , Receptors, Thrombopoietin/genetics , Adult , Aged , Aged, 80 and over , Bosnia and Herzegovina , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myeloproliferative Disorders/mortality , Myeloproliferative Disorders/pathology , Survival RateABSTRACT
OBJECTIVES: In silico bioinformatical analysis suggested that the expression of two genes, CCL5 (C-C Motif Chemokine Receptor 5) and ep300 (Histone acetyltransferase p300), could be used as potential new biomarkers in differentiation between periapical granulomas and radicular cysts. Thus, we hypothesized that gene expression of CCL5 and ep300 in periapical lesions would classify the lesions as either granuloma or cyst. MATERIALS: Patient samples (n=122) included 46 periapical granulomas, 38 radicular cysts and 38 healthy gingival samples as controls. Real-time PCR analysis of CCL5 and ep300 transcripts was compared to SDHA (Succinate dehydrogenase complex, subunit A) as the reference. Clinical parameters (e.g., intensity of inflammation and lesion size) were measured and correlated with CCL5 and ep300 expression. ROC (Receiver operating characteristic) and logistic regression analyses were used to establish the diagnostic character of ΔCt values. RESULTS: Granulomas and radicular cysts had significantly higher expression of CCL5 and ep300 compared to controls (P<0.05). However, no differences were observed when comparing granulomas and radicular cysts. ROC analyses showed that CCL5 and ep300 have good diagnostic accuracy, but low accuracy for distinguishing between the lesions. CONCLUSIONS: This study confirmed that expression of CCL5 and ep300 is relevant for the pathogenesis of periapical inflammatory lesions but cannot be used as a distinctive marker between these lesions.
Subject(s)
Chemokine CCL5/metabolism , E1A-Associated p300 Protein/metabolism , Periapical Granuloma/diagnosis , Radicular Cyst/diagnosis , Biomarkers/metabolism , Diagnosis, Differential , Gingiva/metabolism , HumansABSTRACT
The odontogenic keratocyst (OKC) may occur at any age. However, it mostly occurs during the second and third decades of life. Compared to other odontogenic cysts, this type occurs with a frequency of 5-15%. It is more common in the mandible region and in the male sex. Histologically, odontogenic keratocysts are characterized by the presence of an external connective tissue capsule, with keratinizing lining of the epithelium consisting of 5-8 cell layers with marked palisadisation of polarized basal cells and a corrugated parakeratin layer. The objective of this study is to present cases of odontogenic keratocysts, with reference to the latest classification and dilemmas in therapeutic doctrine. This project was realized in the form of descriptive studies, specifically in a series of cases. A collection of four individual cases was found at the Department of Oral Surgery. Due to the proper approach towards diagnosis, adequate and detailed histopathological analysis, and suitable therapeutic procedures, all cases of odontogenic keratocysts were successfully treated without complications. Enucleation of OKC, with a regular follow-up, proved to be the effective therapeutic choice for the patients described in this paper. Only in the case of recurrence would we consider other therapeutic options, primarily enucleation in combination with Carnoy's solution.
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BACKGROUND: AFP serum levels are considered as diagnostic and specific for hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). AIM: This study aimed to examine the diagnostic value of AFP in the distinguishing of patients with HCC from patients with LC, and to analyse the potential correlation between AFP levels and liver disease stages. MATERIAL AND METHODS: Fifty patients with LC and fifty patients with HCC were included in this study. The majority of the patients were males, while the HBV aetiology was dominant. RESULTS: Significant differences between LC and HCC patients were detected for AST, ALT, GGT, bilirubin, AFP and AP. Patients with HCC had higher AFP values compared to LC. There was no significant correlation between the size of the tumour lesion and serum AFP levels. A positive correlation between AFP concentration and GGT activity was determined, as was the negative correlation between AFP and age of the subjects. The AFP value of 23.34 ng/m showed high sensitivity (84%) and specificity (82%). CONCLUSION: The size of the surface below the ROC curve (AUC) was 0.877 (0.80-0.95), which makes AFP a good biomarker and this diagnostic test is sufficient to separate patients with HCC and LC.
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BACKGROUND/AIMS: The best treatment for an avulsed tooth is immediate replantation. If this is not possible, a proper transport medium is required for the maintenance of viability of the periodontal ligament cells (PDL). The aim was to systematically review the efficacy of different storage media used for the survival of PDL cells of avulsed teeth in the in vitro setting. METHODS: The search strategy was based on the MeSH keywords in PubMed/MEDLINE: "Transport media for avulsed teeth," "Storage media for avulsed teeth," "Knocked out teeth," "Tooth avulsion," "Biological transport of avulsed tooth," "Cell survival of avulsed tooth," "Cell viability of avulsed tooth," "Tooth replantation," and "Periodontal ligament in avulsed teeth." The "AND" and "OR" Boolean operators were applied to combine keywords. Each study was evaluated for eight criteria, including use of human PDL, in vitro cell culture models, the number of passages, types of storage media, percentages of surviving PDL cells, pH and osmolality of storage media, and the type of test used to asses PDL viability. RESULTS: In 15 selected studies, nine storage media (HBSS, tap water, DMEM, milk, saliva, 10% and 20% propolis, Gatorade, and Viaspan) were analyzed at six time points. For storage up to 2 hours, HBSS, DMEM, milk, 10% propolis, 20% propolis, and Viaspan conserved more than 80% of PDL viability. For storage at 24 hours, Viaspan showed best cell survival at 88.4%, followed by DMEM (70.9%) and 10% propolis (68.3%). Milk and HBSS showed similar PDL survival at 24 hours (57.2% and 57.3%, respectively). CONCLUSIONS: Milk remains the most convenient, cheapest, and readily available solution in most situations while also being capable of keeping PDL cells alive. Further studies are required to evaluate the efficacy of more commonly found storage media besides milk.
Subject(s)
Organ Preservation Solutions , Periodontal Ligament/cytology , Tooth Avulsion , Cell Culture Techniques , Cell Survival , HumansABSTRACT
Since the first widespread use of depleted uranium in military in the 1991 Gulf War, the so-called "Gulf War Syndrome" has been a topic of ongoing debate. However, a low number of reliable scientific papers demonstrating the extent of possible contamination as well as its connection to the health status of residents and deployed veterans has been published. The authors of this study have therefore aimed to make a selection of data based on strict inclusion and exclusion criteria. With the goal of clarifying the extent of DU contamination after the Gulf Wars, previously published data regarding the levels of DU in the Middle East region were analyzed and presented in the form of a meta-analysis. In addition, the authors attempted to make a correlation between the DU levels and their possible effects on afflicted populations. According to results observed by comparing 234U/238U and 235U/238U isotopic activity ratios, as well as 235U/238U mass ratios in air, water, soil and food samples among the countries in the Middle East region, areas indicating contamination with DU were Al Doha, Manageesh and Um Al Kwaty in Kuwait, Al-Salman, Al-Nukhaib and Karbala in Iraq, Beirut in Lebanon and Sinai in Egypt. According to these data, no DU contamination was observed in Algeria, Israel, Afghanistan, Oman, Qatar, Iran, and Yemen. Due to the limited number of reliable data on the health status of afflicted populations, it was not possible to make a correlation between DU levels and health effects in the Middle East region.
Subject(s)
Radioactive Pollutants/analysis , Uranium/analysis , Warfare , Egypt , Environmental Exposure/analysis , Humans , Iran , Iraq , Israel , Kuwait , Lebanon , Persian Gulf Syndrome , Qatar , WeaponsABSTRACT
BACKGROUND: The usage of Artificial Neural Networks (ANNs) for genome-enabled classifications and establishing genome-phenotype correlations have been investigated more extensively over the past few years. The reason for this is that ANNs are good approximates of complex functions, so classification can be performed without the need for explicitly defined input-output model. This engineering tool can be applied for optimization of existing methods for disease/syndrome classification. Cytogenetic and molecular analyses are the most frequent tests used in prenatal diagnostic for the early detection of Turner, Klinefelter, Patau, Edwards and Down syndrome. These procedures can be lengthy, repetitive; and often employ invasive techniques so a robust automated method for classifying and reporting prenatal diagnostics would greatly help the clinicians with their routine work. METHODS: The database consisted of data collected from 2500 pregnant woman that came to the Institute of Gynecology, Infertility and Perinatology "Mehmedbasic" for routine antenatal care between January 2000 and December 2016. During first trimester all women were subject to screening test where values of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (ß-hCG) were measured. Also, fetal nuchal translucency thickness and the presence or absence of the nasal bone was observed using ultrasound. RESULTS: The architectures of linear feedforward and feedback neural networks were investigated for various training data distributions and number of neurons in hidden layer. Feedback neural network architecture out performed feedforward neural network architecture in predictive ability for all five aneuploidy prenatal syndrome classes. Feedforward neural network with 15 neurons in hidden layer achieved classification sensitivity of 92.00%. Classification sensitivity of feedback (Elman's) neural network was 99.00%. Average accuracy of feedforward neural network was 89.6% and for feedback was 98.8%. CONCLUSION: The results presented in this paper prove that an expert diagnostic system based on neural networks can be efficiently used for classification of five aneuploidy syndromes, covered with this study, based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics. Developed Expert System proved to be simple, robust, and powerful in properly classifying prenatal aneuploidy syndromes.
Subject(s)
Computational Biology/methods , Demography , Mothers , Neural Networks, Computer , Pregnancy Trimester, First/blood , Prenatal Diagnosis , Adolescent , Adult , Down Syndrome/diagnosis , Down Syndrome/diagnostic imaging , Female , Humans , Klinefelter Syndrome/diagnosis , Klinefelter Syndrome/diagnostic imaging , Male , Middle Aged , Pregnancy , Trisomy 13 Syndrome/diagnosis , Trisomy 13 Syndrome/diagnostic imaging , Trisomy 18 Syndrome/diagnosis , Trisomy 18 Syndrome/diagnostic imaging , Turner Syndrome/diagnosis , Turner Syndrome/diagnostic imaging , Ultrasonography , Young AdultABSTRACT
Renal metanephric adenoma (MA) is a rare benign tumor frequently misclassified when microscopic features alone are applied. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to MA development have been recognized. Recent data suggest that 90% of MA have BRAFV600E mutations; the genetics of the remaining 10% are unclear. To date, only one case of a chromosomal translocation, t(9;15)(p24;q24) associated with MA has been reported. However, the potential role of the KANK1 gene, which lies near the breakpoint of the short arm of chromosome 9p24, in the etiology of MA was not examined. We identified the same cytogenetic aberration utilizing molecular cytogenetic techniques in a 22-year-old female patient, and further investigated the genes involved in the translocation that might have contributed to tumorigenesis. A series of fluorescence in situ hybridization (FISH) probes identified the rearranged genes to be KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3). Mate-Pair genome sequencing validated the balanced translocation between 9p24.3 and 15q25.3, involving genes KANK1 and NTRK3, respectively. BRAFV600E mutational analysis was normal. Our findings indicate that gene fusions may be one mechanism by which functionally relevant genes are altered in the development of MA. Molecular and cytogenetic analyses have elucidated a novel genetic aberration, which helps to provide a better understanding of this genomic change and assist in diagnosis and classification of new subgroups/entities in metanephric adenomas.
Subject(s)
Adenoma/genetics , Kidney Neoplasms/genetics , Translocation, Genetic , Adaptor Proteins, Signal Transducing , Adenoma/diagnosis , Adenoma/pathology , Adult , Cytoskeletal Proteins , Diagnosis, Differential , Discoidin Domain Receptor 2/genetics , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Tumor Suppressor Proteins/geneticsABSTRACT
The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties.
Subject(s)
Environmental Pollutants/toxicity , Uranium/toxicity , Animals , Chromosome Aberrations , DNA Damage , DNA Methylation , Epigenesis, Genetic , Humans , RadioactivityABSTRACT
In recent years, contradicting data has been published on the connection between the presence of depleted uranium and an increased cancer incidence among military personnel deployed in the Balkans during the 1992-1999 wars. This has led to numerous research articles investigating possible depleted uranium contamination of the afflicted regions of the Balkan Peninsula, namely Bosnia & Herzegovina, Serbia, Kosovo and Montenegro. The aim of this study was to collect data from previously published reports investigating the levels of depleted uranium in the Balkans and to present the data in the form of a meta-analysis. This would provide a clear image of the extent of depleted uranium contamination after the Balkan conflict. In addition, we tested the hypothesis that there is a correlation between the levels of depleted uranium and the assumed depleted uranium-related health effects. Our results suggest that the majority of the examined sites contain natural uranium, while the area of Kosovo appears to be most heavily afflicted by depleted uranium pollution, followed by Bosnia & Herzegovina. Furthermore, the results indicate that it is not possible to make a valid correlation between the health effects and depleted uranium-contaminated areas. We therefore suggest a structured collaborative plan of action where long-term monitoring of the residents of depleted uranium-afflicted areas would be performed. In conclusion, while the possibility of depleted uranium toxicity in post-conflict regions appears to exist, there currently exists no definitive proof of such effects, due to insufficient studies of potentially afflicted populations, in addition to the lack of a common epidemiological approach in the reviewed literature.