Browsing by Author "Samardzija, Gordana (56177152500)"

Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs. © 2016 Taylor & Francis.

Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs. © 2016 Taylor & Francis.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy characterized by overproduction of immature B-lymphoblasts. B-ALL is the most common pediatric tumor and remains the leading cause of mortality in children and adolescents. Molecular and cytogenetic analyses of B-ALL revealed recurrent genetic and structural genomic alterations which are routinely applied for diagnosis, prognosis and choice of treatment regimen. The present case report describes a 4-year-old female diagnosed with B-ALL. GTG-banding at low resolution revealed an abnormal clone with 46,XX,?t(X;19)(q13;q13.3),der(9) besides normal cells. Molecular cytogenetics demonstrated a balanced translocation between chromosomes 16 and 19, and an unbalanced translocation involving chromosomes 5 and 9. A locus-specific probe additionally identified that the FUS gene in 16p11.2 was split and its 5' region was translocated to subband 19q13.33, whereas the 3' region of the FUS gene remained on the derivative chromosome 16. Overall, this complex karyotype included four different chromosomes and five break events. Further analyses, including array-comparative genomic hybridization, additionally revealed biallelic deletion of the tumor suppressor genes CDKN2A/B, and deletion of the NR3C1 and VPREB1 genes. The patient passed away under treatment due to sepsis. © 2020 Spandidos Publications. All rights reserved.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy characterized by overproduction of immature B-lymphoblasts. B-ALL is the most common pediatric tumor and remains the leading cause of mortality in children and adolescents. Molecular and cytogenetic analyses of B-ALL revealed recurrent genetic and structural genomic alterations which are routinely applied for diagnosis, prognosis and choice of treatment regimen. The present case report describes a 4-year-old female diagnosed with B-ALL. GTG-banding at low resolution revealed an abnormal clone with 46,XX,?t(X;19)(q13;q13.3),der(9) besides normal cells. Molecular cytogenetics demonstrated a balanced translocation between chromosomes 16 and 19, and an unbalanced translocation involving chromosomes 5 and 9. A locus-specific probe additionally identified that the FUS gene in 16p11.2 was split and its 5' region was translocated to subband 19q13.33, whereas the 3' region of the FUS gene remained on the derivative chromosome 16. Overall, this complex karyotype included four different chromosomes and five break events. Further analyses, including array-comparative genomic hybridization, additionally revealed biallelic deletion of the tumor suppressor genes CDKN2A/B, and deletion of the NR3C1 and VPREB1 genes. The patient passed away under treatment due to sepsis. © 2020 Spandidos Publications. All rights reserved.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with being infected with coronavirus-19 (COVID-19) is a life-threatening condition resulting from cytokine storm, increased synthesis of reactive oxygen species (ROSs), and hyperinflammation occurring in genetically predisposed children following an infection with SARS-CoV-2. Aim: The primary aims of our study were to identify changes in the activity of antioxidant enzymes in erythrocytes and total oxidative status in plasma after being treated with methylprednisolone (MP). Methods: A prospective cohort study of 67 children (56.7% male) under 18 with MIS-C being treated with MP was conducted at the Mother and Child Health Institute from January 2021 to April 2022. The impact of the therapy was assessed on the basis of the clinical condition, haematological and biochemical blood parameters, and echocardiographic findings. Results: 59.7% of patients presented cardiovascular (CV) manifestations, while myocardial dysfunction was observed in half of all patients (50.7%). A severe clinical course was observed in 22/67 patients. Children with CV involvement had a significantly higher relative concentration of B lymphocytes and lower relative concentration of NK cells than patients without CV issues (p < 0.001 and p = 0.004, respectively). Patients with severe MIS-C had a lower relative count of NK cells than those with moderate MIS-C (p = 0.015). Patients with myocardial dysfunction had a higher total oxidative plasma status (TOPS) than children without (p = 0.05), which implicates pronounced oxidative stress in the former cohort. In patients with shock, lower erythrocytes superoxide dismutase (SOD) activity was observed on admission compared to patients without shock (p = 0.04). After MP was administered, TOPS was significantly reduced, while catalase (CAT) and SOD activity increased significantly. Treatment failure (TF) was observed in 6 patients, only females (p=0.005). These patients were younger (p=0.05) and had lower CAT activity on admission (p=0.04) than patients with favorable treatment responses. In the group of patients with TF, TOPS increased after treatment (before 176.2 ± 10.3 mV, after 199.0 ± 36.7 mV). Conclusion: MP leads to rapid modulation of TOPS and increases the activity of antioxidant enzymes in erythrocytes resulting in clinical and echocardiographic improvement. Based on the observed changes in the activity of the antioxidant enzymes, we can conclude that s hydrogen peroxide is the dominant ROS in patients with MIS-C. Patients with TF showed reduced CAT activity, whereas the treatment with MP led to pronounced oxidation. This implies that low CAT activity may be a contraindication for using MP. Copyright © 2023 Krasic, Vukomanovic, Ninic, Pasic, Samardzija, Mitrovic, Cehic, Nesic and Bajcetic.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with being infected with coronavirus-19 (COVID-19) is a life-threatening condition resulting from cytokine storm, increased synthesis of reactive oxygen species (ROSs), and hyperinflammation occurring in genetically predisposed children following an infection with SARS-CoV-2. Aim: The primary aims of our study were to identify changes in the activity of antioxidant enzymes in erythrocytes and total oxidative status in plasma after being treated with methylprednisolone (MP). Methods: A prospective cohort study of 67 children (56.7% male) under 18 with MIS-C being treated with MP was conducted at the Mother and Child Health Institute from January 2021 to April 2022. The impact of the therapy was assessed on the basis of the clinical condition, haematological and biochemical blood parameters, and echocardiographic findings. Results: 59.7% of patients presented cardiovascular (CV) manifestations, while myocardial dysfunction was observed in half of all patients (50.7%). A severe clinical course was observed in 22/67 patients. Children with CV involvement had a significantly higher relative concentration of B lymphocytes and lower relative concentration of NK cells than patients without CV issues (p < 0.001 and p = 0.004, respectively). Patients with severe MIS-C had a lower relative count of NK cells than those with moderate MIS-C (p = 0.015). Patients with myocardial dysfunction had a higher total oxidative plasma status (TOPS) than children without (p = 0.05), which implicates pronounced oxidative stress in the former cohort. In patients with shock, lower erythrocytes superoxide dismutase (SOD) activity was observed on admission compared to patients without shock (p = 0.04). After MP was administered, TOPS was significantly reduced, while catalase (CAT) and SOD activity increased significantly. Treatment failure (TF) was observed in 6 patients, only females (p=0.005). These patients were younger (p=0.05) and had lower CAT activity on admission (p=0.04) than patients with favorable treatment responses. In the group of patients with TF, TOPS increased after treatment (before 176.2 ± 10.3 mV, after 199.0 ± 36.7 mV). Conclusion: MP leads to rapid modulation of TOPS and increases the activity of antioxidant enzymes in erythrocytes resulting in clinical and echocardiographic improvement. Based on the observed changes in the activity of the antioxidant enzymes, we can conclude that s hydrogen peroxide is the dominant ROS in patients with MIS-C. Patients with TF showed reduced CAT activity, whereas the treatment with MP led to pronounced oxidation. This implies that low CAT activity may be a contraindication for using MP. Copyright © 2023 Krasic, Vukomanovic, Ninic, Pasic, Samardzija, Mitrovic, Cehic, Nesic and Bajcetic.

Nijmegen breakage syndrome (NBS) is a rare primary immunodeficiency disease due to a pathogenic variant in the NBN gene causing impaired DNA repair and increased predisposition for lymphoid malignancy. By contrast, solid tumors have been rarely reported. Neuroblastoma (NB) is a rare childhood solid tumor, associated with the worse outcome if MYCN oncogene is amplified. We describe 2 young pediatric patients with NBS who developed high-risk NB. The first patient died shortly after chemotherapy was introduced. The second patient successfully received modified chemotherapy resulting in clinical remission lasting 2 years after an initial diagnosis of NB. © 2024 Wolters Kluwer Health, Inc. All rights reserved.