The authors describe the use of stereoscopic short-range magnetic resonance (MR) angiography to diagnose whether and by what means the brainstem is compressed in a case of facial spasm. The MR images were obtained on a 1.5-tesla imaging system with three-dimensional time-of-flight pulse sequence (repetition time 39 msec, echo time 9 msec). Six-source MR images, in which the internal acoustic meatuses were described, were processed using a maximum-intensity projection technique to reconstruct the MR angiograms. The internal acoustic meatuses, the posterior fossa, and the nearby arteries are shown on a single MR angiogram. When two MR angiograms with projection angles 10 degrees apart are placed side by side and observed through polarized glasses, a stereoscopic view of the compressing artery can easily be seen.
Objective
Despite the development of newly developed drugs, most multiple myeloma (MM) patients with high‐risk cytogenetic abnormalities such as t(4;14) or del17p relapse at anin early stage of their clinical course. We previously reported that a natural product,komaroviquinone (KQN), isolated from the perennial semi‐shrub
Dracocephalum komarovi
, i.e., komaroviquinone (KQN) and its derivative GTN024 induced the apoptosis of MM cells by producing reactive oxygen species (ROS), but both exhibited significant hematological toxicity. Aim of this study is to clarify anti‐tumor activity, safety and pharmacokinetics of GTN057, an optimization compound of KQN in vivo.
Methods
ICR/SCID xenograft model of KMS11, a t(4;14) translocation‐positive MM cell line, was used for in vivo study. Mice pharmacokinetics of GTN057 and the degradation products were analyzed by LC‐MS/MS.
Results
Herein, our in vitro experiments revealed that GTN057 is much less toxic to normal hematopoietic cells, induced the apoptosis of both MM cell lines andpatient samples, including those with high‐risk cytogenetic changes. A xenograft model of a high‐risk MM cell line demonstrated that GTN057 significantly delayed the tumor growth with no apparent hematological or systemic toxicities in vivo. The pathological examination of GTN057‐treated tumors in vivoshowed revealed apoptosis of MM cells and anti‐angiogenesis. In addition to the production of ROS, GTN057 inhibited the downstream signaling of c‐MET, a receptor tyrosine kinase a receptor forand hepatocyte growth factor (HGF) receptor. Thus, GTN057 is less toxic and is able tomay be a candidate drug for treating MM patients, via multifunctional mechanisms. We have also extensively studied the pharmacologyical analysis of GTN057. The metabolites of GTN057, (e.g.,such as GTN054), may also have anti‐tumorantitumor activity.
Conclusion
Natural products or and their derivatives can could be good sources of antineoplastic drugs even for high‐risk cancer.
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