Dose fall-off during the treatment of thoracic spine metastasis with CyberKnife stereotactic body radiation therapy (SBRT)

CyberKnife stereotactic body radiation therapy (SBRT) is becoming increasingly used for cancer treatment and, to maximize its clinical application, it is important to define the dosimetric characteristics, optimal dose and fractionation regimens. The aim of this study was to evaluate the dose fall-off in two fractionated regimens of CyberKnife SBRT during the treatment of thoracic spinal metastasis. Patients with spinal metastasis involving a vertebra and pedicle were treated with 40 Gy in 5 fractions (n = 4), and patients with spinal metastasis involving only a vertebra received 33 Gy in 3 fractions (n = 4). A new approach was used to measure absolute dose fall-off distance, relative dose fall-off distance, and the dose fall-off per unit distance along four reference directions in the axial plane. Patients treated with 33 Gy/3 fractions had a greater absolute dose fall-off distance in direction 1 (from the point with maximum dose [Dmax] towards the spinal cord) and direction 3 (the opposite of the direction 1), a greater relative dose fall-off distance in direction 3, and a lower dose fall-off per unit distance in direction 1 and 3 compared to patients treated with 40 Gy/5 fractions (all p < 0.05). Overall, the dose fall-off towards the spinal cord is rapid during the treatment of thoracic spinal metastasis with CyberKnife SBRT, which allows a higher dose of radiation to be delivered to the tumor and, at the same time, better protection of the spinal cord

Dual-Level Regulation of ACC Synthase Activity by MPK3/MPK6 Cascade and Its Downstream WRKY Transcription Factor during Ethylene Induction in Arabidopsis

Plants under pathogen attack produce high levels of ethylene, which plays important roles in plant immunity. Previously, we reported the involvement of ACS2 and ACS6, two Type I ACS isoforms, in Botrytis cinerea–induced ethylene biosynthesis and their regulation at the protein stability level by MPK3 and MPK6, two Arabidopsis pathogen-responsive mitogen-activated protein kinases (MAPKs). The residual ethylene induction in the acs2/acs6 double mutant suggests the involvement of additional ACS isoforms. It is also known that a subset of ACS genes, including ACS6, is transcriptionally induced in plants under stress or pathogen attack. However, the importance of ACS gene activation and the regulatory mechanism(s) are not clear. In this report, we demonstrate using genetic analysis that ACS7 and ACS11, two Type III ACS isoforms, and ACS8, a Type II ACS isoform, also contribute to the B. cinerea–induced ethylene production. In addition to post-translational regulation, transcriptional activation of the ACS genes also plays a critical role in sustaining high levels of ethylene induction. Interestingly, MPK3 and MPK6 not only control the stability of ACS2 and ACS6 proteins via direct protein phosphorylation but also regulate the expression of ACS2 and ACS6 genes. WRKY33, another MPK3/MPK6 substrate, is involved in the MPK3/MPK6-induced ACS2/ACS6 gene expression based on genetic analyses. Furthermore, chromatin-immunoprecipitation assay reveals the direct binding of WRKY33 to the W-boxes in the promoters of ACS2 and ACS6 genes in vivo, suggesting that WRKY33 is directly involved in the activation of ACS2 and ACS6 expression downstream of MPK3/MPK6 cascade in response to pathogen invasion. Regulation of ACS activity by MPK3/MPK6 at both transcriptional and protein stability levels plays a key role in determining the kinetics and magnitude of ethylene induction