PHOX2B (Paired Like Homeobox 2B)

Our findings reveal that PHOX2B positively regulates PHOX2B-AS1 expression and that inhibiting the antisense transcript reduces PHOX2B protein levels. Together, these results provide strong evidence for the existence of a gene antisense to PHOX2B and highlight a strict correlation and reciprocal regulation between PHOX2B and PHOX2B-AS1.

Despite this scientific and clinical progress, the high cost of developing CAR T cells through the traditional biopharma pathway is limiting late-stage clinical development, necessitating the creation of new business models to commercialize CAR T cells for these small markets. CAR T cells hold great promise for improving outcomes for pediatric patients with cancer, but substantial additional research and clinical development is needed if this promise is to be realized for children afflicted with cancer.

PB infiltration is associated with EFS and OS at diagnosis; it is also significantly associated with survival outcomes of patients with ≥10% BM infiltration at diagnosis. During follow-up, neuroblastoma mRNA detection in PB can be of added value, when BM analysis is not possible.

Thus, the half-maximal inhibitory concentration was measured and cisplatin treatment assay was carried out...Finally, we demonstrated that DLX5 which was transcriptionally activated by MYCN, promoted growth, metastasis and chemoresistance of neuroblastoma through enhanced AKT phosphorylation. The findings in our study provided new insight for progression and chemoresistance of neuroblastoma.

In an additional PPGL, widespread SOX2 expression in PHOX2B+ tumor cells supports this hypothesis. Finally, DLK1-NOTCH signaling was predicted as a central regulator of chromaffin-sustentacular communication, suggesting DLK1 fine-tunes chromaffin regeneration via NOTCH inhibition and may represent a therapeutic target in PPGL.

we demonstrate that the missense c.428A>G variant, reported by us and others in a set of CCHS + HSCR cases but never associated with NB, not only causes the amino acid change p.Q143R change but also disrupts the intron 2 splice donor site, producing an aberrant mRNA transcript and likely a hypomorphic, dysfunctional protein. We, therefore, propose that in the presence of splicing defects of PHOX2B, a loss-of-function mechanism may underlie CCHS + HSCR and potentially explain the absence of neural-crest-derived tumors.

While most TESLA-revealed CaRE-gene relationships involved neuroblastoma-related regulatory elements, we found many CaREs and target connections normally active only in other tissues. This highlights the power of TESLA-seq to reveal gene regulatory networks, including edges active outside of a given experimental system.

NKX2.2, CD99, and SOX17 showed CS ≥4 in 7%, 0%, and 3% of tumors, respectively. Overall, we found that in the appropriate clinicopathologic context, utilizing a panel of SOX2, OCT3/4 (to exclude embryonal carcinoma), AE1/AE3, NKX2.2, CD99, and SOX17 could be helpful in the diagnosis of ENT; many other traditional diagnostic biomarkers show limited utility.

EwS and ECs show a certain degree of molecular similarity, and the original description of EwS as an endothelioma of bone should still be considered as a possibility. We discuss our data in the light of the little work that exists on the innervation and lymphatic supply of bone.

To assess lipid dynamics during treatment, we monitored patients at multiple time points and observed decreasing TC, TG, LDL-C, TC/HDL-C, and TG/HDL-C levels, alongside increasing HDL-C, suggesting treatment-induced improvement in lipid metabolism. In patients with disease progression or relapse, lipid levels (TC, LDL-C, HDL-C) were significantly elevated at the time of the event compared to post-chemotherapy levels.In summary, dysregulation of serum lipids is common in NB and lipid profiles are closely linked to NB progression and may serve as potential biomarkers for prognosis and treatment monitoring.

Therefore, we propose that alternative nomenclature "gangliocytoid neuroendocrine neoplasm" or "composite gangliocytoid neuroendocrine neoplasm" be considered. The relative lack of pathogenic mutations raises the possibility that these tumors might harbor epigenetic drivers.

Moreover, PF-9363 plus retinoids increases GD2 expression, rendering neuroblastoma cells more sensitive to anti-GD2 immunotherapy. Overall, our studies demonstrate that KAT6A/B inhibition increases the effectiveness of retinoids and GD2-targeted immunotherapy in neuroblastoma.