Publications by authors named "R Firestein"
Uterine fibroids (UFs) are the most common non-cutaneous tumors in women worldwide. UFs arise from genetic alterations in myometrial stem cells (MM SCs) that trigger their transformation into tumor initiating cells (UF SCs). Mutations in the RNA polymerase II Mediator subunit MED12 are dominant drivers of UFs, accounting for 70% of these clinically significant lesions.
View Article and Find Full Text PDFPrimary central nervous system tumors are the most frequent solid tumors in children, accounting for over 40% of all childhood brain tumor deaths, specifically high-grade gliomas. Compared with pediatric low-grade gliomas (pLGGs), pediatric high-grade gliomas (pHGGs) have an abysmal survival rate. The WHO CNS classification identifies four subtypes of pHGGs, including Grade 4 Diffuse midline glioma H3K27-altered, Grade 4 Diffuse hemispheric gliomas H3-G34-mutant, Grade 4 pediatric-type high-grade glioma H3-wildtype and IDH-wildtype, and infant-type hemispheric gliomas.
View Article and Find Full Text PDFPediatric high-grade gliomas (pHGG) are malignant and usually fatal central nervous system (CNS) WHO Grade 4 tumors. The majority of pHGG consist of diffuse midline gliomas (DMG), H3.3 or H3.
View Article and Find Full Text PDFArticle 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.