Furthermore, the survival benefit with PD was also present when PD was administered in conjunction with RT. Our results demonstrate the first therapeutic DMH4 regimen that provides an improved survival benefit relative to RT alone in preclinical trials for BSG. As our BSG model is a pediatric model, our results suggest that PD-0332991 should be evaluated in clinical trials for CYM 50260 children with Ink4a-ARF deficient gliomas including DIPGs. While Ink4a-ARF deletion at the genomic level is rare in DIPGs, there is evidence that Ink4a protein expression is lost through other mechanisms. DIPGs that lose Ink4a protein expression through other mechanisms may also respond well to PD. In addition, as secondary gliomas in children have a high frequency of Ink4a-ARF loss and PDGFR�� amplifications, PD-0332991 may be particularly suitable for this population. Our results are consistent with recent publications in several preclinical glioma models and other tumor types such as malignant rhabdoid tumors noting that Ink4a-ARF loss is a biomarker for response to PD-0332991. Interestingly, potential synergy between PD-0332991 and RT has been noted in adult glioma xenograft studies as well, although in those studies PD-0332991 was either given concurrently with RT or prior to RT. In summary, our results in genetically engineered mouse models of BSG suggest that PD-0332991 may be efficacious in the treatment of pediatric gliomas that have Ink4a-ARF loss. While the PDGF-B; p53 deficient BSG model was relatively resistant to PD, evaluating PD in both models allowed us to recognize that Ink4a-ARF loss is a biomarker for therapeutic response to PD. Our results support the notion that DIPG is a heterogeneous disease and a biopsy at diagnosis is necessary to guide which therapeutic agents will be most efficacious. By evaluating DIPG biopsy tissue for Rb and Ink4a protein expression, patients that are most likely to benefit from PD can be identified. It is worth noting that there may be other biomarkers for response such as amplification of D-type cyclins, CDK4 or CDK6 amplifications- all of which are present in DIPGs and other pediatric high-grade gliomas. Lastly, with the recent identification of histone mutations in pediatric gliomas and particularly in DIPGs, future studies from our laboratory will determine how histone mutations influence response to PD-0332991. However, regardless of the potential for high growth rates, there can be limitations on chytrid proliferation. An important stage in the chytrid life cycle is the free-swimming zoospore whose task is to find the correct host before the zoospore��s limited internal nutrient stores are depleted. Gerphagnon et al. utilized another filamentous cyanobacteria, Anabaena macrospora, to identify the stages of infection. Once attached, the zoospore injects its contents into the cell and a prosporangium is formed.