Tumor Of Childhood Research Articles

Diagnóstico clínico de hemangiomatose neonatal disseminada: um relato de caso

Hemangioma is the most common vascular tumor of childhood. It may present as multiple cutaneous hemangiomas on rare occasions, with or without visceral involvement. The condition of lesions restricted to the skin is called benign neonatal hemangiomatosis, and in the case of visceral lesions associated with cutaneous lesions, the denomination is disseminated or diffuse neonatal hemangiomatosis (DNH). For the diagnosis of DNH, three criteria must be met: onset in the neonatal period, involvement of three or more organs, and absence of malignancy in hemangiomas. ASAS, a full-term, vaginally delivered newborn, weight: 3560g, length: 52cm, head circumference: 35cm, APGAR: 9/9. Maternal history of syphilis during pregnancy - mother adequately treated in pregnancy. At birth, she presented with purpuric lesions of variable size on the chest, limbs, feet, and hands, which discolored under digital pressure; larger lesions with relief, not scaly. He developed severe heart failure and was admitted to the Neonatal Intensive Care Unit (NICU) in a secondary hospital in the Federal District. Imaging tests were performed: Computed tomography of the skull, thorax, and total abdomen, which revealed the presence of a possible hemangioma in the left frontal lobe, telangiectasias in the lungs, and multiple hepatic hemangiomas. He had a clinical diagnosis of DNH. The case described corroborates the fact that knowledge about the disease is relevant, as early diagnosis can lead to more accurate approaches that may reduce morbidity and mortality from the disease.

The Role of Natural Extracts in the Management of Infantile Hemangiomas and Vascular Tumors.

Hemangiomas are vascular tumors resulting from the proliferation of endothelial-like cells; they are the most common childhood tumors, affecting approximately 5-10% of newborns and infants. Besides hemangiomas, which are definitely benign tumors despite their overgrowth potential, there are other vascular tumors like hemangioendotheliomas, which may display intermediate characteristics between benign hemangiomas and highly malignant angiosarcomas. Standard therapy may be constricted by serious adverse effects, high cost, or traumatic influence. Diet is a major resource for health preservation, disease prevention, and treatment. The therapeutic property of edible berries, marine products, or medicinal plants have long been known and used in traditional medicine; a plant-based nutrition can prevent the development and progression of diseases associated with extensive neo-vascularization. The purpose of our review is to highlight those natural treatments that hemangioma and vascular tumor patients can receive in the future, both for their benefit and that of their families. We performed the review according to the Preferred Reporting Items for Systematic Reviews and Metanalysis Statement. We used the Web of Science, PubMed, and EMBASE engines for the study, and searched for the association of hemangioma with naturopathic treatment/plant extract/plants in published articles. We found that natural extracts from plants and fruits are cost-effective and safe treatments for hemangiomas and vascular tumors, as well as for other forms of cancer. In any case, more in vitro and in vivo studies are needed to confirm the proposed signaling pathways in tumors and validate the improvement parameters after natural products administration. The era of molecularly targeted therapy and personalized medicine is approaching and naturally occurring substances are very useful tools for tumor treatment and prevention. Plant extract substances have strong specificity and pertinence, are non- toxic and have few side effects, and may become an emerging cancer treatment.

Pattern of Childhood malignant tumours in Umuahia South East Nigeria

Introduction: Cancers in children should be incorporated as one of the childhood killer diseases in developing countries.
 Aim: The aim of this study is to evaluate the demographic and pathologic characteristics of childhood tumours in Umuahia. South East Nigeria
 Methodology: The Operative records, histology request and report forms were studied and the clinico-pathologic information were retrieved and analysed using SPSS version 20.0
 Results: A total of 50 cases of malignant diseases of children were clinically diagnosed and histologically confirmed. The mean age of the patients were 8 years with age range of 1 to 17 years. The male to female ratio was 1:1. The peak age of incidence falls in the 1-5 age groups which accounted for 40%. Wilm’s tumour was the commonest 25, Rhabdomyosarcoma 10 cases, Neuroblastoma 5cases, Oesteosarcoma 5cases, Teratomas 5 cases.
 Conclusion: childhood cancer is increasing in our environment. However, late presentation, ignorance, poverty leads to poor outcome.

COMPARISON OF LIMB SALVAGE WITH MEGA PROSTHESIS VERSUS AUTO GRAFT RECONSTRUCTION AFTER CRYOTHERAPY IN LIMB SARCOMA PATIENTS

Osteosarcoma is the most common primary malignant bone tumor, with children and adolescents being the most at-risk population. It accounts for 2% of all childhood tumors. The main goal of this study was to compare the use of limb salvage with mega prosthesis versus auto graft reconstruction after cryotherapy in patients with limb sarcoma. This retrospective study was conducted at Liaquat College of Medicine and Dentistry Darul Sehat Hospital Karachi from June 2023 to August 2023. The data was collected with the permission of the hospital's ethical committee. A standard uniform management protocol was adopted for each case. All patients were skeletally immature, with the predicted overall growth of less than 3 cm calculated using the Multiplier method. The data was collected from 45 patients with a mean age of 13.8±4.6 years. The predominant type of tumor was Osteosarcoma (77.14%) followed by Ewing Sarcoma and Chondrosarcoma. Five patients required a more extended hospital stay after mega prosthesis as compared to the other group. It is concluded that patients with limb sarcomas treated with Mega prosthesis had better functional outcomes than those treated with autograft reconstruction after cryotherapy.

Commentary: Disseminated Adult Wilms Tumour in Pregnancy- Leveraging Multidisciplinary Care in a Low Resource Setting

Adult Wilms tumor is a rare occurrence with limited examples cited in literature. It is predominantly a childhood tumor occurring between the average ages of 2 to 3 years but can occur up to age 8 years and for unknown reasons it affects more African children than Caucasians [1,2].

Клінічне спостереження тератоми головного мозку новонародженого

A congenital brain tumor is a tumor detected before birth or during the first two months of life. The frequency of congenital brain tumors is extremely low - 0.34 per 1 million newborns, and no more than 1.5% of all neoplasms of the central nervous system in children, but the rapid growth of the tumor and the destruction of normal brain tissue give them a fatal prognosis. Purpose - to expand knowledge on the possibilities of antenatal diagnosis and the features of the management of the early neonatal period of congenital mіalformations based on the clinical observation of fetal brain teratoma. An overview of literature sources is provided on the prevalence of pathology, histological structure (teratomas, neuroepithelial and mesenchymal tumors), features of the clinical course that distinguish them from childhood tumors - mainly supratentorial localization, lack of growth restriction due to the mobility of the bones of the skull, prognosis and tactics of pregnancy and childbirth . Ultrasound examination is the main method of diagnosis of brain tumors, which are visualized in the form of a solid or cystic calcified formation or not, and manifestations of hypervascularization can also be absent or present. The features of the structure and development of the teratoma, which contains cells of all 3 germ layers and has properties of rapid destructive growth, are also described. Hydrocephalus accompanying congenital brain tumors can be caused both by compression of the ventricular system and intracranial hemorrhages. Thanks to modern diagnostic capabilities, most cases are detected in terms of possible termination of pregnancy, in the case of childbirth with such a pathology, in 60% of cases, a cesarean section is used. The given clinical case shows the possibilities of antenatal diagnosis of a brain tumor and even clearly establishing the depth of the lesion, at the same time as the lack of treatment options. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Bilateral pheochromocytoma in patients with von Hippel–Lindau syndrome: clinical and molecular genetic features

Bilateral adrenal pheochromocytoma (PCС) is extremely rare in children, with major predisposing factors being multiple endocrine neoplasia type 2 and von Hippel–Lindau syndrome. In case of bilateral PCC with underlying von Hippel–Lindau syndrome, organ-preserving surgery is preferred in view of the low malignant potential of such neoplasms. We aimed to study clinical and molecular genetic features of patients with bilateral adrenal PCCs treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. The study included 20 patients with paraganglioma (PGL)/PCC (PPGL) who had received treatment (n = 17) or outpatient care (n = 3) at the Center over the period from 2012 to 2023. Bilateral adrenal PCC was diagnosed in 4 (20%) patients. In all these cases, the diagnosis was confirmed by histology. Molecular genetic testing was carried out at the Laboratory of Molecular Biology at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation in order to search for germline pathogenic variants in PCC/PGL susceptibility genes. The median age of the four patients with bilateral adrenal PCC was 9.5 years (range 4.5–14.6 years). All the patients were male. In one patient, synchronous bilateral PCC/PGL was observed. In 100% of the cases, arterial hypertension was diagnosed at the onset of the primary disease and was treated with alpha-blockers as part of preparation for surgery. According to the results of a 24-hour urine biochemistry test, all the patients had at least a 4-fold increase above the upper limit of normal for normetanephrine levels. Molecular genetic testing using the multiplex ligation-dependent probe amplification method revealed a pathogenic germline variant in exon 3 of the VHL gene in all the children (4/4). Hereditary PPGL was proven in 2/4 (50%) patients. In all the cases, R0/R1 resection was achieved. Organ-sparing surgery on one/two adrenal glands was performed in 3/4 cases. One out of four (25%) patients developed a local relapse 18.4 months after diagnosis. The overall survival rate in this group was 100%, with a median follow-up time of 8.1 months (range 0.8–50.2 months). Bilateral adrenal PCC is a very rare childhood tumor. A medical genetic consultation is necessary to identify tumor predisposition syndromes. A multidisciplinary team discussion of a surgical strategy is recommended, with organ-sparing surgery on one or two adrenal glands being the treatment of choice that should be carried out at centers specializing in pediatric surgical oncology. Here, we report a rare clinical case of bilateral retroperitoneal PCC/PGL in a patient with von Hippel-Lindau syndrome. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment.

Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

Inhibition of Survivin Homodimerization Decreases Neuroblastoma Cell Growth.

Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been tested in adult cancers and inhibitors of survivin homodimerization are emerging. We compared genetic inhibition of survivin transcription with the inhibition of survivin homodimerization by S12 and LQZ-7I, chosen from a larger panel of survivin dimerization inhibitors with activity against NB cells. Mice hemizygous for Birc5 were crossed with NB-prone TH-MYCN mice to generate Birc5+/-/MYCNtg/+ mice. The marked decrease of survivin transcription in these mice did not suffice to attenuate the aggressiveness of NB, even when tumors were transplanted into wild-type mice to assure that immune cell function was not compromised by the lack of survivin. In contrast, viability, clonogenicity and anchorage-independent growth of NB cells were markedly decreased by S12. S12 administered systemically to mice with subcutaneous NB xenotransplants decreased intratumoral hemorrhage, albeit not tumor growth. LQZ-7I, which directly targets the survivin dimerization interface, was efficacious in controlling NB cell growth in vitro at markedly lower concentrations compared to S12. LQZ-7I abrogated viability, clonogenicity and anchorage-independent growth, associated with massively distorted mitotic spindle formation. In vivo, LQZ-7I effectively reduced tumor size and cell proliferation of NB cells in CAM assays without apparent toxicity to the developing chick embryo. Collectively, these findings show that inhibiting survivin homodimerization with LQZ-7I holds promise for the treatment of NB and merits further investigation.

The dual HDAC and PI3K inhibitor, CUDC‑907, inhibits tumor growth and stem‑like properties by suppressing PTX3 in neuroblastoma.

Neuroblastoma (NB) is one of the common solid tumors in childhood and poses a threat to the lives of children. Patients with advanced‑stage or recurrent NB have a poor prognosis. CUDC‑907, as a novel dual‑target inhibitor of histone deacetylase (HDAC) and phosphatidylinositol‑3‑kinase (PI3K), has been proven to play an antitumor role in several types of tumors. However, the exact role of CUDC‑907 in NB remains unclear. In the present study, invivo and invitro assays were performed to investigate the anti‑NB activity of CUDC‑907. Pentraxin 3 (PTX3) small interfering RNA (siRNA) and PTX3 overexpression plasmid were transfected into cells to define the underlying mechanisms of CUDC‑907. Tumor tissues and clinical information were collected and immunohistochemistry (IHC) was conducted to analyze the association between the expression of HDAC1, HDAC2, HDAC3 and CD44, and the prognosis of patients with NB. The results indicated that CUDC‑907 significantly inhibited the proliferation and migration, and induced the apoptosis of NB cells, downregulating the expression level of MYCN, and suppressing the PI3K/AKT and MAPK/ERK pathways. Furthermore, CUDC‑907 suppressed the stem‑like properties of NB cells by inhibiting PTX3, a ligand and upstream protein of CD44. IHC revealed that the high expression of HDAC1, 2, 3 and CD44 was associated with a poor prognosis of patients with NB. On the whole, these findings indicate that CUDC‑907 may be developed into a possible therapeutic approach for patients with NB.

Atenolol oral comparado con propranolol oral para hemangioma infantil

Introduction Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its β-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic β-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. Methods We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. Conclusion The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).

Differentiated neuroblastoma cells remain epigenetically poised for de-differentiation to an immature state.

Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for a significant share of childhood cancer deaths. Prior studies utilizing RNA sequencing of bulk tumor populations showed two predominant cell states characterized by high and low expression of neuronal genes. Although cells respond to treatment by altering their gene expression, it is unclear whether this reflects shifting balances of distinct subpopulations or plasticity of individual cells. Using mouse and human neuroblastoma cell lines lacking MYCN amplification, we show that the antigen CD49b (also known as ITGA2) distinguishes these subpopulations. CD49b expression marked proliferative cells with an immature gene expression program, whereas CD49b-negative cells expressed differentiated neuronal marker genes and were non-cycling. Sorted populations spontaneously switched between CD49b expression states in culture, and CD49b-negative cells could generate rapidly growing, CD49b-positive tumors in mice. Although treatment with the chemotherapy drug doxorubicin selectively killed CD49b-positive cells in culture, the CD49b-positive population recovered when treatment was withdrawn. We profiled histone 3 (H3) lysine 27 acetylation (H3K27ac) to identify enhancers and super enhancers that were specifically active in each population and found that CD49b-negative cells maintained the priming H3 lysine 4 methylation (H3K4me1) mark at elements that were active in cells with high expression of CD49b. Improper maintenance of primed enhancer elements might thus underlie cellular plasticity in neuroblastoma, representing potential therapeutic targets for this lethal tumor.

Specificities of childhood tumours and the paediatric oncology service in the context of decentralisation

Tumors in children have peculiarities of natural development, diagnosis and clinical features, morphological structure, age, sex, pre-selection, etc. In the structure of oncopediting morbidity prevail hemoblasts 58-60%, brain tumors 17- 18%, kidney 7-7.5%, bone 5.0-5.5%, soft tissue sarcomas 4.0-4.5%, thyroid gland tumors 0.8-1.0%, reproductive organs1.0-1.2%, liver - 1.0%, others - 2.5-3.0% [15, 16, 23].Tumors in children occupy the second place in the structure of mortality of children up to 18 years of age. A special place goes to Eving’s sarcoma, Wilms’ tumor, embryonal rhabdomyosarcoma and others [21].The oncology service also has its own particular managerial features, such as having certain criteria and facilities, centres specialising in paediatric oncology, specialists, technical devices, diagnostic and treatment technologies, medical equipment and generic and effective drugs. The service must have onco-pediatric specialists in every region of the Republic of Moldova - north, centre, south and south-east. Interdisciplinary cooperation is needed with family medicine, local specialists and tertiary specialists, as well as with the families of these children, local administrative bodies and the voluntary sector. There is a need for an infrastructure for the paediatric oncology advisory service and interdependence with the Oncology Institute, rehabilitation centres, continuing education centres in hospital and palliative care, and social services.

Diagnostic problems in pediatrics on the example of a clinical case of neuroblastoma

Neuroblastoma (NB) is a malignant extracranial solid tumor of childhood. The peak incidence occurs in the first year of life. In 50% of cases, the disease already has signs of metastasis at the time of diagnosis. The clinical picture in neuroblastoma is varied; the symptoms are not specific and depend on the localization. The diagnosis is confirmed by histological examination of the biopsy of the primary tumor and metastasis. A specific method for the topical diagnosis of neuroblastoma is 123I-labeled metaiodobenzylguanidine scintigraphy, which makes it possible to detect the primary tumor, the presence of regional and distant metastases. Combinations of high-dose chemotherapy and transplantation of autologous stem cells and differentiating agents, as well as immunotherapy with anti-GD2 monoclonal antibodies, can increase the life expectancy of patients.

MODL-39. ELUCIDATING THE TRANSCRIPTOMIC LANDSCAPE OF METASTATIC PEDIATRIC MEDULLOBLASTOMA

Abstract Medulloblastoma (MB) is a highly aggressive and the most common brain tumor in childhood. MB presents a high intertumoral heterogeneity, with at least four molecular subgroups (SHH, WNT, Group 3, and Group 4) identified. MB can metastasize to the leptomeningeal space, known as Leptomeningeal Disease (LMD) and its presence is a universal predictor of poor outcome among MB patients. Metastatic MB is predominantly found in the MB Group 3 type. Although LMD represents a main clinical challenge, its molecular mechanisms remain poorly characterized. Recent research has shown that primary and MB metastasis diverge dramatically. Our work has focused on establishing therapy naïve Group 3 Patient-Derived Xenografts that faithfully replicate the nature of primary and metastatic Medulloblastoma with the aim to perform comparative genomic and transcriptomic analyses between these models to identify genetic drivers/pathways that sustain metastatic MB or leptomeningeal disease. Our results show various signaling pathways enriched across LMD models, such as protein secretion and oxidative phosphorylation. We also have identified differentially expressed genes, where sets of genes have shown to be present in more than one PDX model, such as members of the Solute Carriers family (SLC44A3 and SLC17A9) and FCGBP. Retrieval of short variants from RNAseq data has not revealed thus far mutations enriched in LMD, suggesting these changes could be attributed to epigenetic disruption rather than genetic changes. In conclusion, our results support the notion that primary and LMD are transcriptionally different, with various enriched pathways and sets of DEG among LMD Group 3 PDX models. These findings are in progress for functional validation. Work is currently being done to profile the epigenome of LMD by correlating transcriptomic data with active chromatin markers such as H3K27ac and H3K4me1. Through these approaches, we aim to elucidate the genetic dependencies of metastatic Medulloblastoma that will help for targeted therapies.

Social participation of school-aged survivors of pediatric brain tumors: A daily diary report.

Difficulties with social functioning are common among survivors of pediatric brain tumors. Social participation is an understudied measure of social functioning that is associated with emotional health across the lifespan. This paper uses a diary method to assess the social participation of survivors of pediatric brain tumors in middle childhood. Survivors of pediatric brain tumors (N=47; age 10.6±1.4years; 51.1% male, 89.4% White) who were 5.3 (SD=2.4, range: 2-9.9) years post therapy completed a daily diary assessment of social interaction (5-7days) and an objective measure of facial affect recognition. The participant's caregiver completed the NIH Toolbox Emotion Measures and a background information questionnaire. Overall, frequency and quality of reported social interactions were low for survivors, with a large subset of survivors (n=16, 34%) endorsing fewer than 10 social interactions over the course of a typical school week, and almost half of parents (48.9%) reporting that their child participates in zero social activities outside of school during a typical week. Participants engaged in more positive social participation exhibited stronger social skills (facial affect recognition (F(2,44) =4.85, p<.05). School-aged survivors of pediatric brain tumors seemed to be infrequently engaged in social participation and quality interaction with peers. More specifically, the interactions most commonly reported on the diary assessment are not indicative of friendship development and maintenance. Survivors of pediatric brain tumors would likely benefit from interventions designed to increase quality time spent with peers.

S-100 and MATH-1 Protein Expressions Can Be Useful for the Prediction of Clinical Outcome in Neuroblastoma Patients.

Neuroblastoma (NB) is the most frequent extracranial solid tumor of childhood, remarkable for its broad spectrum of clinical behavior. This diversity in behavior correlates closely with defined clinical and biological features and combinations of prognostic variables are used for risk-group assignment. S-100 proteins have roles in differentiation and were shown to be frequently dysregulated in NB. MATH-1 protein plays role in neuronal cell differentiation through development. However, up to date, there are no studies evaluating the relationship between MATH-1 and NB. Grb2-associated binding (Gab) proteins have roles in the regulation of cell growth and differentiation. Gab1 was reported to be related to poor survival of high-risk NB patients. The aim of this study was to investigate the relationship between differentiation-related S-100, MATH-1, and Gab1 proteins and risk group and/or stages of NB. A significant relation was found between S-100 and early stages of NB. This study also revealed a significant association between MATH-1 and low-risk groups. S-100 and MATH-1 were also shown to provide survival advantages among stages and risk groups. The findings of this study support the assumption that S-100 and MATH-1 can be potential prognostic biomarkers for staging and risk-group assignment of NB patients. These proteins can be useful tools for clinicians to guide through treatment options, especially for the evaluation of tumor differentiation.

Reduced Anticancer Potency of Carboplatin in the Presence of Sialic Acid in SH-SY5Y Cells

Background: Neuroblastoma (NB) is the most common solid childhood tumor with aggressive behavior and a high mortality rate. Multiple therapeutic approaches have been developed and applied to treat neuroblastoma, but resistance to therapies is inevitable, leading to treatment failure and cancer relapse. Therefore, perceiving the mechanisms of reduced drug sensitivity seems appropriate and promising in NB treatment to determine synergistic effects strategies like combination therapy. Objectives: The present study aimed to investigate the modulation effect of the therapeutic efficacy of carboplatin (a chemotherapeutic agent) by co-administration of sialic acid (an alpha-keto acid sugar with a 9-carbon backbone located at the outermost end of N-linked and O-linked carbohydrate chains and in lipid-associated glycoconjugates showing aberrant expression in tumor cells caused tumor-genesis) in NB cells. Methods: In the present study, the effects of sialic acid, carboplatin, and Sia-Carbo (sialic acid in combination with carboplatin) were evaluated on viability and apoptosis using the determination of EC50 and IC50. Also, the capability of metastasis and apoptosis were assessed using real-time PCR. Moreover, the expression of MRP-1 encoded by ABCC1 (as a target for therapeutic suppression in high-risk neuroblastoma) was studied in different treatment groups. Conclusions: Regarding IC50 increasing carboplatin in the presence of sialic acid, the results showed that sialic acid treatment significantly modulated carboplatin's effect on cell apoptosis and induced ABCC1 expression. These findings show that sialic acid metabolic engineering can be a good approach to neuroblastoma therapy. It was suggested that targeting aberrant sialylation in combination with carboplatin exerts more profound apoptotic and anticancer effects on the neuroblastoma SH-SY5Y cell line than carboplatin monotherapy.

Characterisation of Aberrant Metabolic Pathways in Hepatoblastoma Using Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS).

Hepatoblastoma (HB) is a rare childhood tumour with an evolving molecular landscape. We present the first comprehensive metabolomic analysis using untargeted and targeted liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS) of paired tumour and non-tumour surgical samples in HB patients (n = 8 pairs). This study demonstrates that the metabolomic landscape of HB is distinct from that of non-tumour (NT) liver tissue, with 35 differentially abundant metabolites mapping onto pathways such as fatty acid transport, glycolysis, the tricarboxylic acid (TCA) cycle, branched-chain amino acid degradation and glutathione synthesis. Targeted metabolomics demonstrated reduced short-chain acylcarnitines and a relative accumulation of branched-chain amino acids. Medium- and long-chain acylcarnitines in HB were similar to those in NT. The metabolomic changes reported are consistent with previously reported transcriptomic data from tumour and non-tumour samples (49 out of 54 targets) as well as metabolomic data obtained using other techniques. Gene set enrichment analysis (GSEA) from RNAseq data (n = 32 paired HB and NT samples) demonstrated a downregulation of the carnitine metabolome and immunohistochemistry showed a reduction in CPT1a (n = 15 pairs), which transports fatty acids into the mitochondria, suggesting a lack of utilisation of long-chain fatty acids in HB. Thus, our findings suggest a reduced metabolic flux in HB which is corroborated at the gene expression and protein levels. Further work could yield novel insights and new therapeutic targets.

An Observational Case-Control Study on Parental Age and Childhood Renal Tumors.

Despite excellent outcomes, many open questions remain about Wilms tumor (WT). Influences and risk factors for tumorigenesis, as well as tumor aggressiveness and recurrence, are not fully understood. Parental age plays a role in various childhood diseases and is also discussed as a risk factor for childhood cancer. We analyzed both maternal and paternal age at birth as risk factors for the occurrence of Wilms and non-Wilms tumors in children and investigated whether older maternal or paternal age is associated with a higher tumor incidence. During 1990 and 2019 we collected data from 3991 patients from the multicenter studies SIOP9/GPO, SIOP 93-01/GPOH, and SIOP 2001/GPOH, of whom maternal and paternal age was available in 2277 cases. Data from the Federal Statistical Office containing live births in Germany from 1990-2019 served as a comparative database. For maternal age at birth, the control data yielded 22,451,412 cases and for paternal age yielded 19,046,314 cases. Comparing maternal and paternal ages of the study patients with those of the control data, we confirmed that higher parental age is not correlated with the incidence of renal tumors in childhood. Mean ages of fathers and mothers in patients and the control cohort increased between 1991 and 2019 (fathers: 30.28 vs. 34.04; mothers: 27.68 vs. 29.79 in the patient group and 31.29 vs. 34.23 and 28.88 vs. 32.67 in the control group, respectively) without higher numbers of patients with kidney cancer over time. No influence was found for the subtype of cancer nor for syndromes. In addition, overall survival of patients is independent of the year of diagnosis and the age of the parents but depends on histology type and stage in WT.