Embryonal Malignancy Research Articles

Primary Adrenal Neuroblastoma in an Adult: A Rare Case Report

ABSTRACT Neuroblastoma (NB), an embryonal malignancy originating from neural crest cells, is predominantly a pediatric disease, making adult cases exceedingly rare. This case report documents the presentation and diagnostic process of a 23-year-old female diagnosed with adrenal NB, a condition scarcely encountered in adults. The patient presented with abdominal pain and a palpable mass. Imaging through computed tomography scan revealed a large necrotic mass in the left adrenal region. Ultrasound-guided fine-needle aspiration cytology (FNAC) showed round cells with scant cytoplasm and characteristic nuclear features, suggesting a round cell tumor, potentially NB. Surgical excision confirmed the diagnosis of poorly differentiated NB with low mitotic-karyorrhectic index. Adult NB, with an incidence of 1 in 10 million per year, has a notably worse prognosis compared to pediatric cases. The literature lacks consensus on optimal treatment protocols for adult patients, though a multimodal approach including surgery, chemotherapy, and possibly radioactive iodine therapy is often employed. This case underscores the utility of FNAC in preliminary diagnosis and highlights the clinical challenges posed by adult NB, emphasizing the need for more comprehensive studies to develop standardized treatment guidelines.

Update on surveillance for Wilms tumor and hepatoblastoma in Beckwith-Wiedemann Syndrome and other predisposition syndromes.

Wilms tumors are commonly associated with predisposition syndromes many, but not all, of which include overgrowth. Several of these syndromes also include a risk of other embryonal malignancies - particularly hepatoblastoma. Guidelines for surveillance in this population were published in 2017 and recently members of the AACR Pediatric Cancer Working Group met to update those guidelines with a review of more recently published evidence and risk estimates. This perspective serves to update pediatric oncologists, geneticists, radiologists, counselors and other healthcare professionals on revised diagnostic criteria, review previously published surveillance guidelines and harmonize updated surveillance recommendations in the North American and Australian context for patients with overgrowth syndromes and other syndromes associated with Wilms tumor predisposition.

High Parathyroid Hormone Rather than Low Vitamin D Is Associated with Reduced Event-Free Survival in Childhood Cancer.

Vitamin D deficiency is linked to poor cancer outcomes but the impact of its consequence, elevated parathyroid hormone (PTH), remains understudied. PTH receptor activation influences cancer progression in vitro, yet the effect of elevated PTH on pediatric cancer survival is unexamined. This retrospective study examines associations between PTH, 25-OH vitamin D (25OHD), and event-free survival (EFS) and overall survival (OS) in patients with pediatric cancer. Laboratory data from 4,349 patients (0-18 years) at a tertiary pediatric cancer unit were analyzed for the highest PTH and lowest 25OHD levels at diagnosis and the following 5 years. Data on relapse, secondary malignancies, and mortality were stratified by PTH levels above/below the cohort median (47 pg/mL) and 25OHD levels ≤30 nmol/L. EFS and OS were analyzed and hazard ratios (HR) were calculated for the entire cohort and six cancer subgroups. PTH and 25OHD values were available for 1,286 patients (731 male). Higher PTH associated with inferior EFS in primary malignant brain tumors [HR, 1.80 (1.19-2.72)], embryonal malignancies [HR, 2.20 (1.1-4.43)], and lymphatic malignancies [HR 1.98 (1.05-3.72)]. Vitamin D deficiency associated with inferior EFS in embryonal malignancies [HR 2.41 (1.24-4.68)]. In a multivariate Cox model, only higher PTH remained significant for inferior EFS. Elevated PTH may indicate adverse outcomes in certain pediatric cancers. This study identifies elevated parathyroid hormone as a potential marker for poor outcomes in patients with pediatric cancer, emphasizing the need for adequate vitamin D and calcium management.

Beckwith-Wiedemann Syndrome: deciphering the genetic and clinical complexity - A case report with literature review

Beckwith-Wiedemann syndrome (BWS) is a rare and heterogeneous genetic condition characterized by overgrowth, organomegaly, and increased vulnerability to embryonal tumors. This review investigates the complex genetic and epigenetic pathways underlying Beckwith-Wiedemann syndrome, focusing on the 11p15.5 region on chromosome 11. Abnormalities in the 11p15.5 area, such as imprinting control region dysregulation and CDKN1C gene mutations, contribute to disrupted growth regulation. This content also provides an overview of the incidence and pathophysiology of this syndrome. Clinical manifestations include macrosomia, macroglossia, and abdominal wall abnormalities. The increased risk of embryonal malignancies, such as Wilms tumor and hepatoblastoma, emphasises the importance of diligent medical observation. Early diagnosis through genetic testing is crucial for tailored management and genetic counseling. This detailed discussion of Beckwith-Wiedemann syndrome sheds light on the molecular complexities of the condition, emphasizing the significance of genetic testing, early detection, and multidisciplinary management for affected infants.

Craniofacial malignant tumors, their extensions, and surgical strategy for their treatment

Purpose: To identify extension routes of craniofacial malignancies and formulate a surgical treatment plan based thereupon. Material and Methods: We retrospectively reviewed the medical records of 253 patients with craniofacial malignancies who underwent surgical treatment at the Romodanov Neurosurgery Institute from 2002 through 2022. Of the 253 patients, 112 had a primary tumor, and 141, a secondary tumor. Preoperative Karnofsky performance scores ranged from 50 to 70 points. Patients underwent neurological and ophthalmological status assessment, as per routine protocols. Results: Epithelial malignancies were the most common (53.7%), whereas anaplastic meningioma and embryonal malignancies were rather uncommon (1.2% and 0.4%, respectively) craniofacial malignancies. The presence of certain clinical symptoms was associated primarily with tumor origin and extension. A high rate of general brain and rhinological symptoms in our study sample was caused by a high percentage of intracranial and paranasal sinus tumors. Craniofacial malignancies most commonly originate from the midline (particularly, anterior midline skull base). Ethmoidal labyrinth was the most common site of origin (45.0%), followed by a sphenoid sinus (12.2%), pterygopalatine and infratemporal fossae (9.9%), whereas the cavernous sinus and olfactory fossa were the least common sites of origin (0.4% and 1.2%, respectively). Craniofacial tumors extended most commonly intracranially (transdurally, epidurally, via adhesion to the dura mater, and/or cavernous sinus growth) or intraorbitally. Anterior craniofacial resection (bifrontal craniotomy with combined with either lateral rhinotomy or supraorbital advancement; or a subcranial approach) was the most common surgical treatment. Postoperative cerebrospinal fluid rhinorrhea and infectious complications (meningitis and meningoencephalitis) were the most frequent complications. The overall postoperative mortality rate was 2.0%. Conclusion: First, compared to the transcranial and facial approaches, the craniofacial resection is advantageous in terms of the radicality of tumor excision. Second, the subcranial approach is preferable to the bifrontal approach in the presence of marked extracranial tumor component, whereas the transbasal Derome approach is effective in the presence of marked extracranial and/or intracranial tumor components. Finally, both the orbitozygomatic and infratemporal approaches allow for the radicality of excision of lateral skull base malignancies, but the latter approach is associated with a lower rate of complications.

Critical Appraisal of Paediatric Embryonal Cancers Treated with Image-guided Intensity-modulated Proton Therapy

AimTo carry out a comprehensive critical appraisal of image-guided intensity-modulated proton therapy practice for craniospinal irradiation (CSI). Materials and methodsAn image-guided intensity-modulated proton therapy database of 45 consecutive paediatric patients with central nervous system embryonal malignancies treated between January 2019 and April 2022 were critically appraised for demography, diagnosis, treatment planning strategy and treatment delivery accuracy. ResultsMost patients (median age: 7.5 years; male:female ratio: 34:11) had medulloblastoma (56%), followed by recurrent ependymoma (19%), pinealoblastoma (5%), germ cell (5%) and others (15%). The dose to the planning target volume-craniospinal (PTV-CS; length 39.06–79.59 cm) varied from 21 to 35 GyRBE, whereas the combined median dose to craniospinal and boost was 54 GyRBE. In all patients, the 95% isodose line covered the cribriform plate completely and optic nerves mostly, with a median V95% of 100% and 82.96%, keeping Dmax to the lens <3.9 GyRBE. In skeletally immature patients (88.38%), the anterior vertebral body was completely covered in 18.18% and underdosed in 70.15% of the cases, resulting in a median Dmean of 10.11 GyRBE to the oesophagus. Lateral spine coverage was maintained on the edges of the vertebral body in 52.2%, whereas it extended beyond in 48.8%. The median V98% for clinical target volumes and V95% for PTVs of the brain, spine and craniospinal were >97%, with excellent conformity (0.89) and homogeneity (0.07) indices for PTV-CS. All neurological organs at risk received a median Dmax ranging from 36 to 44 GyRBE from the combined CSI and boost regimens. Analysis of patient-specific quality assurance results revealed that 545 (97.67%) planar dosage verification had gamma (3% at 3 mm) values >95%. The online patient set-up verification showed translational and rotational deviation within 2 mm and 0.5° in 88–94% and 97% of the cases. Systematic and random error were within 0.90 mm and 1.71 mm in translation and 0.1° and 0.2° in rotation. ConclusionA change in practice pattern was observed. The findings from our comprehensive critical appraisal add to the growing library of CSI practice and may serve as a reference for inter-institutional comparison.

Interplay: The Essential Role between INSM1 and N-Myc in Aggressive Neuroblastoma.

Simple SummaryNeuroblastoma (NB) is a cancer that starts in certain very early forms of nerve cells of the sympathetic nervous system, most often found in an embryo or fetus. Symptoms may include bone pain, an abdominal mass, frequent urination, limping, anemia, spinal cord weakness, or bruising of the eye area. N-Myc is a key driver of high-risk NB. An elevated expression of N-Myc often predicts a poorer prognosis, in both time to tumor progression and overall survival rate. We discovered a transcription factor, insulinoma-associated-1 (INSM1), as the downstream target gene of N-Myc. INSM1 has emerged as a novel NB biomarker that plays a critical role in facilitating NB tumor cell development. Both N-Myc and INSM1 demonstrate high clinical relevance to NB. Therefore, further understanding the association of INSM1 and N-Myc functions in aggressive NB should be beneficial for future NB treatment.An aggressive form of neuroblastoma (NB), a malignant childhood cancer derived from granule neuron precursors and sympathoadrenal lineage, frequently comprises MYCN amplification/elevated N-Myc expression, which contributes to the development of neural crest-derived embryonal malignancy. N-Myc is an oncogenic driver in NB. Persistent N-Myc expression during the maturation of SA precursor cells can cause blockage of the apoptosis and induce abnormal proliferation, resulting in NB development. An insulinoma-associated-1 (INSM1) zinc-finger transcription factor has emerged as an NB biomarker that plays a critical role in facilitating tumor cell growth and transformation. INSM1 plays an essential role in sympathoadrenal cell differentiation. N-Myc activates endogenous INSM1 through an E2-box of the INSM1 proximal promoter, whereas INSM1 enhances N-Myc stability via RAC-α-serine/threonine protein kinase (AKT) phosphorylation in NB. The ectopic expression of INSM1 stimulates NB tumor growth in contrast to the knockdown of INSM1 that inhibits NB cell proliferation. The clinical pathological result and bioinformatics analysis show that INSM1 is a strong diagnostic and a prognostic biomarker for the evaluation of NB progression. The INSM1/N-Myc expression shows high clinical relevance in NB. Therefore, targeting the INSM1/N-Myc-associated signaling axis should be a feasible approach to identifying new drugs for the suppression of NB tumor growth.

Fetal Disseminated Malignant Rhabdoid Tumor.

Fetal Disseminated Malignant Rhabdoid Tumor.

Superiority of 11 C-Choline PET/CT in the Delineation of a Rare Intracranial Diffuse Embryonic Tumor.

Intracranial diffuse embryonal tumor in the adult is rare. We report a young woman with a diffuse embryonal malignancy in the saddle area, which was depicted well by 11 C-choline PET/CT, superior to 18 F-FDG PET/CT and contrast-enhanced MRI. Under the guiding of 11 C-choline PET/CT, the biopsy was successfully performed and the diagnosis was established. This case highlights that 11 C-chione PET/CT may be useful to diagnose and delineate the intracranial diffuse embryonic tumors.

Therapeutic Targeting of the Anaplastic Lymphoma Kinase (ALK) in Neuroblastoma-A Comprehensive Update.

Neuroblastoma (NBL) is an embryonic malignancy of the sympathetic nervous system and mostly affects children under the age of five. NBL is highly heterogeneous and ranges from spontaneously regressing to highly aggressive disease. One of the risk factors for poor prognosis are aberrations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), which is involved in the normal development and function of the nervous system. ALK mutations lead to constitutive activation of ALK and its downstream signalling pathways, thus driving tumorigenesis. A wide range of steric ALK inhibitors has been synthesized, and several of these inhibitors are already in clinical use. Major challenges are acquired drug resistance to steric inhibitors and pathway evasion strategies of cancer cells upon targeted therapy. This review will give a comprehensive overview on ALK inhibitors in clinical use in high-risk NBL and on the potential and limitations of novel inhibitors. Because combinatory treatment regimens are probably less likely to induce drug resistance, a special focus will be on the combination of ALK inhibitors with drugs that either target downstream signalling pathways or that affect the survival and proliferation of cancer cells in general.

Proteomics identify nuclear export as a targetable pathway in neuroblastoma: Comment on “XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IκB”

Neuroblastoma (NBL) is an embryonal malignancy of childhood with poor outcomes for patient with high-risk disease. Multimodal treatment approaches have improved outcomes but at the cost of significant toxicity, and there is no durable therapeutic approach for relapsed disease. As NBL has no singular oncogenic driver, targeted therapeutic options have been limited. Galinski et al report the results of a proteomic screen of neuroblastomas and identify the nuclear export protein XPO1 as a protein that is preferentially expressed and located in neuroblast nuclei. XPO1 overexpression is associated with nuclear export of IκB and increased NF-κB activity, both of which can be abrogated in NBL cell lines with the XPO1 inhibitor Selinexor with or without the proteasome inhibitor bortezomib. This work highlights new strategies for therapeutic target identification and the novel identification of nuclear export as a targetable oncogenic pathway across malignancies.

Expression of p53 is significantly associated with recurrence-free survival and overall survival in pleuropulmonary blastoma (PPB): a report from the International Pleuropulmonary Blastoma/DICER1 Registry.

Pleuropulmonary blastoma (PPB) is a primary embryonal malignancy of childhood that is characterized by distinct morphologic types: type Ir (regressed), type I (cystic), type II (cystic and solid), and type III (solid). Prognosis varies by PPB type. Most cases are associated with a germline pathogenic mutation in DICER1; however, there is limited data on the factor(s) at a cellular level that drive progression from type I to type III. In this study, we evaluated the expression of p53 and its prognostic implications. A total of 143 PPB cases were included in the study with the following distribution in PPB types: Ir (14%), I (23%), II (32%), and III (31%). P53 expression by immunohistochemistry (IHC) was recorded as four groups: 0%, 1-25%, 26-75%, and 76-100%. All type I PPBs showed 0-25% p53 expression compared to the higher p53 expression (>25%) in type III PPB (p < 0.0001), to support the argument that p53 has a role in tumor progression. In addition, type Ir with the architectural hallmarks of type I PPB, but lacking the primitive cell population, has negligible p53 expression. High p53 expression (staining observed in >25% of the tumor cells) was significantly associated with age over 1 year (p = 0.0033), neoadjuvant therapy (p = 0.0009), positive resection margin (p = 0.0008) and anaplasia (p < 0.0001). P53 expression was significantly associated with recurrence-free survival (p < 0.0001) and overall survival (p = 0.0350), with higher p53 expression associated with worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphologic types compared to p53 expression groups (p = 0.647). TP53 sequence was performed in 16 cases; the most common variant identified was a missense variant (12 cases), and in one case a frameshift truncating variant was noted. Based on these findings, we recommend performing p53 IHC in all newly diagnosed cases of types II and III PPB to further aid in risk stratification.

Single-cell atlas of developing murine adrenal gland reveals relation of Schwann cell precursor signature to neuroblastoma phenotype

Neuroblastoma is the most common extracranial solid tumor and accounts for ∼10% of pediatric cancer-related deaths. The exact cell of origin has yet to be elucidated, but it is generally accepted that neuroblastoma derives from the neural crest and should thus be considered an embryonal malignancy. About 50% of primary neuroblastoma tumors arise in the adrenal gland. Here, we present an atlas of the developing mouse adrenal gland at a single-cell level. Five main cell cluster groups (medulla, cortex, endothelial, stroma, and immune) make up the mouse adrenal gland during fetal development. The medulla group, which is of neural crest origin, is further divided into seven clusters. Of interest is the Schwann cell precursor ("SCP") and the "neuroblast" cluster, a highly cycling cluster that shares markers with sympathoblasts. The signature of the medullary SCP cluster differentiates neuroblastoma patients based on disease phenotype: The SCP signature score anticorrelates with ALK and MYCN expression, two indicators of poor prognosis. Furthermore, a high SCP signature score is associated with better overall survival rates. This study provides an insight into the developing adrenal gland and introduces the SCP gene signature as being of interest for further research in understanding neuroblastoma phenotype.

Verteporfin induces apoptosis and reduces the stem cell-like properties in Neuroblastoma tumour-initiating cells through inhibition of the YAP/TAZ pathway

Neuroblastoma is an embryonal malignancy of early childhood arising from the embryonic sympatho-adrenal lineage of the neural crest. About half of all cases are currently classified as high-risk of disease recurrence, with an overall survival rate of less than 40% at 5 years despite intensive therapy. Recent studies on matched primary tumours and at the relapse revealed downregulation of genes transcriptionally silenced by YAP as significant association with neuroblastoma relapse. Here, we evaluated the pharmacological targeting of YAP/TAZ with the YAP/TAZ-TEAD inhibitor Verteporfin (VP) in Tumour Initiating Cells (TICs) derived from High-Risk Neuroblastoma patients. VP treatment suppresses YAP/TAZ expression, induces apoptosis and causes the re-organization of the cytoskeleton reducing cells migration and clonogenic ability. Moreover, VP reduces the percentage of side population cells and ABC transporters involved in drug resistance, and the percentage of stem cell subpopulations CD133+ and CD44+ of TICs. Finally, we demonstrated that VP sensitizes TICs to the standard drugs used for neuroblastoma therapy etoposide and cis-platin opening the way to use VP as drug repositioning candidate for recurrent neuroblastoma.

An unusual cause of peritoneal ascitis: An isolated bilateral neuroblastom

Neuroblastoma (NB) is the most common extracranial solid tumor of infancy. It is an embryonal malignancy of the sympathetic nervous system arising from neuroblasts (pluripotent sympathetic cells). Most patients present with signs and symptoms related to tumor growth, although small tumors have been detected due to the common use of prenatal ultrasonography. Large abdominal tumors often result in increased abdominal girth and other local symptoms. Peritoneal ascites involvement is rare, we report the case a 6-month-old female child with an isolated huge ascitis and pleural effusion unresponsive to treatment.

Neuroblastoma patient-derived cultures are enriched for a mesenchymal gene signature and reflect individual drug response.

Ex vivo evaluation of personalized models can facilitate individualized treatment selection for patients, and advance the discovery of novel therapeutic options. However, for embryonal malignancies, representative primary cultures have been difficult to establish. We developed patient‐derived cell cultures (PDCs) from chemo‐naïve and post–treatment neuroblastoma tumors in a consistent and efficient manner, and characterized their in vitro growth dynamics, histomorphology, gene expression, and functional chemo‐response. From 34 neuroblastoma tumors, 22 engrafted in vitro to generate 31 individual PDC lines, with higher engraftment seen with metastatic tumors. PDCs displayed characteristic immunohistochemical staining patterns of PHOX2B, TH, and GD2 synthase. Concordance of MYCN amplification, 1p and 11q deletion between PDCs and patient tumors was 83.3%, 72.7%, and 80.0% respectively. PDCs displayed a predominantly mesenchymal‐type gene expression signature and showed upregulation of pro‐angiogenic factors that were similarly enriched in culture medium and paired patient serum samples. When tested with standard‐of‐care cytotoxics at human C max‐equivalent concentrations, MYCN‐amplified and non‐MYCN‐amplified PDCs showed a differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients’ responses, and correlated with gene signatures of chemosensitivity. In this translational proof‐of‐concept study, early‐phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated the individual molecular and phenotypic profile of patient tumors, and highlighted their potential as a platform for individualized ex vivo drug‐response testing.

Infant cancers in France: Incidence and survival (2000–2014)

BackgroundOn average 185 children are diagnosed each year in France with a cancer in their first year of life, representing 11 % of cancers diagnosed in children less than 15 years. MethodsA retrospective population-based observational study was conducted between 2000 and 2014 of all infants with a diagnosis of cancer using the National Registry of Childhood Cancers Database. ResultsOut of 2760 cases of primary cancers in infancy, there were mainly neuroblastomas 30.1 %), central nervous system (CNS) tumors (16.1 %), leukemias (15.3 %), retinoblastomas (11.6 %), and Wilms tumors (6.9 %). Embryonal malignancies accounted for 55.2 % of cases. Most diagnoses showed a male excess, particularly for malignant gonadal germ-cell tumors (GCT) with a 17.5 sex-ratio. The annual incidence rate, 242.9 per million infants overall, was stable over the study period for all types of cancer. Most deaths occurred within the first month of life (70.8 % of deaths). The 5-year overall survival (5-y OS) was 81.0 % (95 %CI, 79.4–82.4) with large contrasts between diagnoses. The best 5-y OS (>85 %) were observed for retinoblastomas, carcinomas, nephroblastomas, GCT, neuroblastomas, and hepatoblastomas. Conversely, the lowest 5-y OS (<65 %) were observed for acute myeloid leukemias, CNS tumors, and lymphoid leukemias. We observed no substantial change over time (80.5 % [95 %CI, 77.7–82.9] in 2000–2004 and 82.6 % [95 %CI, 80.0–84.9] in 2010–2014) for all cancers combined. The same result has been found whatever the diagnostic group. ConclusionOur results contribute to better understand these tumors by quantifying their impact on the French population and assessing the burden of some devastating infant cancers.

Primary cerebral neuroblastoma in young adult

Neuroblastoma is an embryonal malignancy of the sympathetic nervous system arising from pluripotent sympathetic cells (neuroblasts). It is the most common extracranial solid tumor in infants. Although it can arise anywhere along sympathetic chain, it is extremely unusual for neuroblastoma to present as intracranial lesion and that too in a young adult. Here, we describe a 24-year-old male presented with complaints of headache and retro-orbital pain. Magnetic resonance imaging (MRI) of the brain revealed a left occipital lobe mass lesion. He underwent left parieto-occipital craniotomy and near-total excision. Postoperative MRI showed minimal residual lesion. Initial histopathological examination was reported as a malignant round cell tumor. However, block and slide review with immunohistochemistry markers was suggestive of neuroblastoma. He received adjuvant radiation of 50.4 Gy in 28 fractions, followed by eight cycles of adjuvant chemotherapy with lomustine and cisplatin. At 3-year follow-up, MRI showed post-operative gliosis in left parietal lobe with no evidence of recurrence.

4-Hydroxychalcone Induces Cell Death via Oxidative Stress in MYCN-Amplified Human Neuroblastoma Cells.

Neuroblastoma is an embryonal malignancy that arises from cells of sympathoadrenal lineage during the development of the nervous system. It is the most common pediatric extracranial solid tumor and is responsible for 15% of childhood deaths from cancer. Fifty percent of cases are diagnosed as high-risk metastatic disease with a low overall 5-year survival rate. More than half of patients experience disease recurrence that can be refractory to treatment. Amplification of the MYCN gene is an important prognostic indicator that is associated with rapid disease progression and a poor prognosis, highlighting the need for new therapeutic approaches. In recent years, there has been an increasing focus on identifying anticancer properties of naturally occurring chalcones, which are secondary metabolites with variable phenolic structures. Here, we report that 4-hydroxychalcone is a potent cytotoxin for MYCN-amplified IMR-32 and SK-N-BE (2) neuroblastoma cells, when compared to non-MYCN-amplified SH-SY5Y neuroblastoma cells and to the non-neuroblastoma human embryonic kidney cell line, HEK293t. Moreover, 4-hydroxychalcone treatment significantly decreased cellular levels of the antioxidant glutathione and increased cellular reactive oxygen species. In addition, 4-hydroxychalcone treatment led to impairments in mitochondrial respiratory function, compared to controls. In support of this, the cytotoxic effect of 4-hydroxychalcone was prevented by co-treatment with either the antioxidant N-acetyl-L-cysteine, a pharmacological inhibitor of oxidative stress-induced cell death (IM-54) or the mitochondrial reactive oxygen species scavenger, Mito-TEMPO. When combined with the anticancer drugs cisplatin or doxorubicin, 4-hydroxychalcone led to greater reductions in cell viability than was induced by either anti-cancer agent alone. In summary, this study identifies a cytotoxic effect of 4-hydroxychalcone in MYCN-amplified human neuroblastoma cells, which rationalizes its further study in the development of new therapies for pediatric neuroblastoma.

Minimally invasive surgery to treat embryonal tumors of childhood.

Minimally invasive surgery (MIS) to resect primary and metastatic pediatric embryonal tumors offers the potential for reduced postoperative morbidity with smaller wounds, less pain, fewer surgical site infections, decreased blood loss, shorter hospital stays, and less disruption to treatment regimens. However, significant controversy surrounds the question of whether a high-fidelity oncologic resection of childhood embryonal tumors with gross total resection, negative margins, and appropriate lymph node sampling can be achieved through MIS. This review outlines the diverse applications of MIS to treat definitively pediatric embryonal malignancies, including this approach to metastatic deposits. It outlines specific patient populations and presentations that may be particularly amenable to the minimally invasive approach. This work further summarizes the current evidence supporting the efficacy of MIS to accomplish a definitive, oncologic resection without compromising relapse-free or overall survival. Finally, the review offers technical considerations to consider in order to achieve a safe and complete resection.