Drug prioritization identifies panobinostat as a tailored treatment element for patients with metastatic hepatoblastoma.

Background: Patients with metastatic hepatoblastoma are treated with severely toxic first-line chemotherapies in combination with surgery. Yet, inadequate response of lung metastases to neo-adjuvant chemotherapy still compromises patient outcomes making new treatment strategies, tailored to more efficient lung clearance, mandatory.

Methods: We harnessed a comprehensive patient-derived xenograft platform and a variety of in vitro and in vivo assays to establish the preclinical and biological rationale for a new drug for patients with metastatic hepatoblastoma.

Hepatoblastoma Relapse-Findings from the German HB99 Trial and the German Liver Tumor Registry.

Survival rates for HB patients have improved; however, outcomes for patients who relapse remain poor. A retrospective review of information gathered for the HB99 study and the German Liver Tumor Registry identified 25 relapse patients (6.9%, 25/362).

Targeting G9a/DNMT1 methyltransferase activity impedes IGF2-mediated survival in hepatoblastoma.

Background: As the variable clinical outcome of patients with hepatoblastoma (HB) cannot be explained by genetics alone, the identification of drugs with the potential to effectively reverse epigenetic alterations is a promising approach to overcome poor therapy response. The gene ubiquitin like with PHD and ring finger domains 1 (UHRF1) represents an encouraging epigenetic target due to its regulatory function in both DNA methylation and histone modifications and its clinical relevance in HB.

Methods: Patient-derived xenograft in vitro and in vivo models were used to study drug response.

Establishing a three-dimensional scaffold model of hepatoblastoma.

Emerging technologies such as three-dimensional (3D) cell culture and the generation of biological matrices offer exciting new possibilities in disease modelling and tumour therapy. The paucity of laboratory models for hepatoblastoma (HB), the most prevalent malignant liver tumour in children, has hampered the identification of new treatment options for HB patients. We aimed to establish a reliable 3D testing platform using liver-derived scaffolds and HB cell lines that reflect the heterogeneous biology of the disease so as to allow reproducible preclinical research and drug testing.

Impact of BCL-2 Expression on Course of Disease in Neuroblastoma.

Objective:  The antiapoptotic BCL-2 protein has implications for maturation and differentiation of neural tissue and acts as a strong modulator of carcinogenesis in different tumors. Recent research focuses not only on its benefit as a prognostic factor, but also as a potential therapeutic target. The role of BCL-2 in neuroblastoma, the most common extracranial solid tumor in childhood, remains controversial.

Computational drug prediction in hepatoblastoma by integrating pan-cancer transcriptomics with pharmacological response.

Background And Aims: Hepatoblastoma (HB) is the predominant form of pediatric liver cancer, though it remains exceptionally rare. While treatment outcomes for children with HB have improved, patients with advanced tumors face limited therapeutic choices. Additionally, survivors often suffer from long-term adverse effects due to treatment, including ototoxicity, cardiotoxicity, delayed growth, and secondary tumors.

Genetic Disruption of Cilia-Associated Signaling Pathways in Patients with VACTERL Association.

VACTERL association is a rare malformation complex consisting of vertebral defects, anorectal malformation, cardiovascular defects, tracheoesophageal fistulae with esophageal atresia, renal malformation, and limb anomalies. According to current knowledge, VACTERL is based on a multifactorial pathogenesis including genomic alterations. This study aimed to improve the understanding of the genetic mechanisms in the development of VACTERL by investigating the genetic background with a focus on signaling pathways and cilia function.

Targeting the Unwindosome by Mebendazole Is a Vulnerability of Chemoresistant Hepatoblastoma.

Resistance to conventional chemotherapy remains a huge challenge in the clinical management of hepatoblastoma, the most common liver tumor in childhood. By integrating the gene expression data of hepatoblastoma patients into the perturbation prediction tool Connectivity Map, we identified the clinical widely used anthelmintic mebendazole as a drug to circumvent chemoresistance in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner.

The Neurokinin-1 Receptor Is a Target in Pediatric Rhabdoid Tumors.

Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/ substance P complex plays an important role in cancer and proved to be a promising target.

Genetic Evidence for Congenital Vascular Disorders in Patients with VACTERL Association.

Introduction:  The VACTERL association is a rare malformation complex, showing at least three anomalies of the following organ systems: vertebra, anorectum, heart and vessels, trachea and esophagus, genitourinary tract, and limbs. In addition to a multifactorial event, congenital vascular disorders are also discussed as triggers for the VACTERL association. The aim of this study was to determine whether there is a genetic background for vascular disorders triggering VACTERL association.

Total Psoas Muscle Area as a Marker for Sarcopenia Is Related to Outcome in Children With Neuroblastoma.

Sarcopenia describes a generalized loss of skeletal muscle mass, strength, or function. Determined by measuring the total psoas muscle area (tPMA) on cross-sectional imaging, sarcopenia is an independent marker for poor post-surgical outcomes in adults and children. Children with cancer are at high risk for sarcopenia due to immobility, chemotherapy, and cachexia.

Marginal adaptation of CAD-CAM and heat-pressed lithium disilicate crowns: A systematic review and meta-analysis.

Statement Of Problem: Lithium disilicate crowns can be manufactured by computer-aided design and computer-aided manufacturing (CAD-CAM) or with the heat-pressed technique. The outcome of studies comparing the effect of the manufacturing method on the marginal adaptation of these crowns is not clear.

Purpose: The purpose of this systematic review and meta-analysis was to investigate the effect of the CAD-CAM system and pressing technique on the marginal adaptation of lithium disilicate crowns.

Erratum: Wagner, A.E., et al. SP8 Promotes an Aggressive Phenotype in Hepatoblastoma via FGF8 Activation. 2020, , 2294.

Two contributors' names were missing in the original version of the authorship of the paper [...

Sarcopenia is a prognostic outcome marker in children with high-risk hepatoblastoma.

Background: Children with hepatoblastoma (HB) are at risk of sarcopenia due to immobility, chemotherapy, and malnutrition. We hypothesized that children with HB have a low preoperative total psoas muscle area (tPMA), reflecting sarcopenia, which negatively impacts outcome.

Procedure: Retrospective study of children (1-10 years) with hepatoblastoma treated at a large university children's hospital from 2009 to 2018.

A combined clinical and biological risk classification improves prediction of outcome in hepatoblastoma patients.

Aim: Stratification of hepatoblastoma (HB) patients is based on clinical and imaging characteristics obtained at the time of diagnosis. We aim to integrate biomarkers into a tool that accurately predicts survival of HB patients.

Methods: We retrospectively analysed 174 HB patients for the presence of four biomarkers and explored their prognostic potential by correlating with overall survival (OS) and event-free survival (EFS).

SP8 Promotes an Aggressive Phenotype in Hepatoblastoma via FGF8 Activation.

Hepatoblastoma (HB) is the most common malignant liver tumor in childhood and it generally has a good prognosis. However, if associated with aggressive metastatic disease, outcome is still poor. The molecular mechanisms leading to metastatic spread in HB patients are still unknown.

High expression of IGF2-derived intronic miR-483 predicts outcome in hepatoblastoma.

Background: The role of microRNAs (miRs) as biomarkers to predict outcome in hepatoblastoma (HB), the most common malignant liver tumor in childhood, has still to be determined. Recently, the so-called four-miR signature has been described to efficiently stratify HB patients according to their prognosis.

Objective: We examined the recently described four-miR signature for its clinical relevance in an independent validation cohort of HB patients and tried to optimize its predictive value by analyzing four additional miRs involved in HB biology.

Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications.

Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB.

Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations.

Background: Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic and epigenetic alterations in the WNT/β-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of β-catenin mutations and gene expression changes of several WNT antagonists.

Lymphatic Leakage after Surgery for Neuroblastoma: A Rare Complication?

Introduction:  Neuroblastoma is the most common extracranial solid tumor in infancy. It is responsible for around 15% of all oncological deaths during childhood. Due to its retroperitoneal location, neuroblastoma is invasively growing directly in and around the lymphatic duct.

Vessel adherent growth represents a major challenge in the surgical resection of neuroblastoma and Is associated with adverse outcome.

Purpose: Neuroblastoma (NB) is the most common extracranial, solid tumor in childhood, with a peak incidence in children under 6 years of age. Due to its variable course of disease, which ranges from spontaneous regression to metastatic spread, NB still represents a significant therapeutic challenge. Strikingly, a certain number of NBs intraoperatively show vessel adhesion and/or infiltrative growth, which is often not visible in pre-operative imaging.

Speech Recognition Evaluation of a State-Of-The-Art Smartglass in the Use Case Pediatric Resuscitation.

Emergencies involving children are rare events. Due to the associated lack of routine and special features in pediatric resuscitation, it is prone to errors and the results are unsatisfactory. One way of tackling this problem is to use assistance services.

Activation of Hedgehog Signaling in Aggressive Hepatic Hemangioma in Newborns and Infants.

Background/aim: Hepatic hemangiomas (HH) can show an aggressive course with significant complications. Prognostic markers that identify an aggressive course are entirely absent. Since we have showed that Hedgehog signaling is overexpressed in aggressive hemangiomas of the skin.

Targeting excessive MYCN expression using MLN8237 and JQ1 impairs the growth of hepatoblastoma cells.

Hepatoblastoma (HB) is the most common liver tumor in children under the age of 3 years worldwide. While many patients achieve good outcomes with surgical resection and conventional chemotherapy, there is still a high‑risk population that exhibits a poor treatment response and unfavorable prognosis, which warrants the search for novel treatment options. In recent years, it has become clear that genetic events alone are not sufficient to explain the aggressive phenotype of this embryonal malignancy.

Author Correction: The landscape of genomic alterations across childhood cancers.

In this Article, author Benedikt Brors was erroneously associated with affiliation number '8' (Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee, USA); the author's two other affiliations (affiliations '3' and '7', both at the German Cancer Research Center (DKFZ)) were correct. This has been corrected online.