Nox4 knockdown or Tempol treatment suppressed tumor ROS and tumor growth in cycling hypoxia-treated mice and control mice. Recently, it has been shown that endogenous ROS play an important role in angiogenesis and tumor growth. Many cancer cells show increased levels of ROS via genetic alternations or growth factors. The increased ROS could modulate signaling pathways and transcription factors for tumor initiation and progression. Here, we highlighted how the tumor microenvironment, cycling hypoxia, increased tumor cell ROS via Nox4 and further promoted tumor growth in GBM. Blockage of ROS production via Nox4 shRNA or Tempol treatment inhibits endogenous tumor microenvironment or exogenous cycling hypoxia-mediated tumor growth, suggesting that ROS play crucial roles in the promotion of tumor growth induced by cycling hypoxia. Although it is possible that other ROS-mediated signaling pathways are involved, we report here that ROS play important roles in cycling hypoxia-mediated HIF-1activation and further promote tumor progression in GBM. This information may be useful to understanding new mechanisms of tumor microenvironment-promoted tumorigenesis and to develop new therapeutic strategies by targeting ROS signaling in human GBM. The penicillin-binding proteins (PBPs) are conserved proteins which play a critical role in building the cell wall in several bacterial pathogens by catalyzing the biosynthesis of peptidoglycan. Indeed, inhibition of PBPs produces an imbalance in cell wall metabolism resulting in growth arrest or lysis. Publications Using Abomle Fedratinib b-lactam antibiotics covalently link PBPs and therefore act as suicide inhibitors of PBPs. Acquisition of PBPs with low affinity for the b-lactams is a mean of antibiotic resistance, in addition to a decreased permeability of the outermembrane, antibiotic export, or degradation by b-lactamases. Neisseria meningitidis, a Gram-negative human pathogenic bacterium, infects asymptomatically the nasopharynx of about 10% of the population worldwide.