Publications by authors named "Sarah Parackal"
Article Synopsis
- Diffuse midline glioma (DMG), particularly DIPG, is a fatal brain tumor with no effective treatments, but recent studies identified PIK3CA and MTOR as promising targets for therapy.
- The research demonstrates that combining the PI3K/Akt/mTOR inhibitor paxalisib with the antihyperglycemic drug metformin and the PKC inhibitor enzastaurin can enhance treatment efficacy and prolong survival in animal models.
- Advanced techniques like spatial transcriptomics and ATAC-Seq were used to evaluate the effects on tumor biology, revealing significant changes that could support a clinically relevant combination therapy for DIPG.
Article Synopsis
- Diffuse midline gliomas (DMG), particularly diffuse intrinsic pontine gliomas (DIPG), are highly lethal childhood cancers, with palliative radiotherapy offering limited survival benefits of 9-11 months.
- ONC201, a drug that targets certain pathways in cancer cells, has shown potential effectiveness against DMG, but further research is needed to understand how different genetic mutations affect its response.
- Studies indicate that DIPGs with PIK3CA mutations are more sensitive to ONC201, while those with TP53 mutations are resistant; combining ONC201 with the drug paxalisib can enhance treatment effectiveness by overcoming metabolic adaptations linked to these mutations.
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG.
View Article and Find Full Text PDFPediatric solid and central nervous system tumors are the leading cause of cancer-related death among children. Identifying new targeted therapies necessitates the use of pediatric cancer models that faithfully recapitulate the patient's disease. However, the generation and characterization of pediatric cancer models has significantly lagged behind adult cancers, underscoring the urgent need to develop pediatric-focused cell line resources.
View Article and Find Full Text PDFAtypical teratoid rhabdoid tumour (ATRT) is a rare but highly aggressive undifferentiated solid tumour arising in the central nervous system and predominantly affecting infants and young children. ATRT is exclusively characterized by the inactivation of , a member of the SWI/SNF chromatin remodelling complex that is essential for the regulation of large sets of genes required for normal development and differentiation. Histone deacetylase inhibitors (HDACi) are a promising anticancer therapy and are able to mimic the normal acetylation functions of SMARCB1 in -deficient cells and drive multilineage differentiation in extracranial rhabdoid tumours.
View Article and Find Full Text PDFAccurate assessment of chemotherapy response provides the means to terminate ineffective treatment, trial alternative drug regimens or schedules and reduce dose to minimize toxicity. Here, we have compared circulating tumor DNA (ctDNA) with carcinoembryonic antigen (CEA) for the cycle by cycle assessment of chemotherapy response in 30 patients with metastatic colorectal cancer. CtDNA (quantified using individualized digital droplet PCR (ddPCR) assays) and CEA levels were determined immediately prior to each chemotherapy cycle over time periods ranging from 42-548 days (average of 10 time points/patient).
View Article and Find Full Text PDFObjectives: To compare the Roche Cell-Free DNA Collection Tubes against the Streck Cell-Free DNA BCTs for sample stability using Cell Free DNA (cfDNA) from healthy volunteers (n = 20).
Design & Methods: Whole blood was drawn into five Roche and five Streck tubes per volunteer, stored at room temperature and processed at five different time points (Days 0, 4, 7, 10 and 14). One volunteer had blood drawn into ×10 KEDTA tubes to observe the effect of no preservation buffer on White Blood Cell (WBC) lysis.