Al's Comment:
I am a big fan of Optune, and think almost all GBM patients should be on it. It is the best treatment currently available, but it is not good enough by itself. We need to find what to add to it so that it works for everyone. This article presents one such combination. There are hundreds of other combinations that also need to be tested and the only way we are going to find the best combination is for us to track the outcomes of every patient who uses Optune. We are now tracking patients in our virtual trial project. Go to virtualtrials.com and click on virtual trial to learn about it and join. It is free - but you need to commit to posting update monthly for as long as needed. All brain tumor patients should be participating, but especially if you are considering Optune.
Posted on: 12/03/2018
Int J Mol Sci. 2018 Nov 21;19(11). pii: E3684. doi: 10.3390/ijms19113684.
Functional Biological Activity of Sorafenib as a Tumor-Treating Field Sensitizer for Glioblastoma Therapy.
Jo Y1,2, Kim EH3, Sai S4, Kim JS5, Cho JM6, Kim H7, Baek JH8, Kim JY9, Hwang SG10, Yoon M11.
Author information:
1. Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. unyjjo@gmail.com.
2. Department of Bio-Convergence Engineering, Korea University, Seoul 02842, Korea. unyjjo@gmail.com.
3. Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. eunhokim8@gmail.com.
4. Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Chiba 263-0024, Japan. sai.sei@qst.go.jp.
5. Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. kjs@kirams.re.kr.
6. Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. chojaemin09@naver.com.
7. Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. hyeongi@kirams.re.kr.
8. Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. jihan918@kirams.re.kr.
9. Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. wjdduql@hanmail.net.
10. Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea. sgh63@kcch.re.kr.
11. Department of Bio-Convergence Engineering, Korea University, Seoul 02842, Korea. radioyoon@korea.ac.kr.
Abstract
Glioblastoma, the most common primary brain tumor in adults, is an incurable malignancy with poor short-term survival and is typically treated with radiotherapy along with temozolomide. While the development of tumor-treating fields (TTFields), electric fields with alternating low and intermediate intensity has facilitated glioblastoma treatment, clinical outcomes of TTFields are reportedly inconsistent. However, combinatorial administration of chemotherapy with TTFields has proven effective for glioblastoma patients. Sorafenib, an anti-proliferative and apoptogenic agent, is used as first-line treatment for glioblastoma. This study aimed to investigate the effect of sorafenib on TTFields-induced anti-tumor and anti-angiogenesis responses in glioblastoma cells in vitro and in vivo. Sorafenib sensitized glioblastoma cells to TTFields, as evident from significantly decreased post-TTFields cell viability (p < 0.05), and combinatorial treatment with sorafenib and TTFields accelerated apoptosis via reactive oxygen species (ROS) generation, as evident from Poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, use of sorafenib plus TTFields increased autophagy, as evident from LC3 upregulation and autophagic vacuole formation. Cell cycle markers accumulated, and cells underwent a G2/M arrest, with an increased G0/G1 cell ratio. In addition, the combinatorial treatment significantly inhibited tumor cell motility and invasiveness, and angiogenesis. Our results suggest that combination therapy with sorafenib and TTFields is slightly better than each individual therapy and could potentially be used to treat glioblastoma in clinic, which requires further studies.
PMID: 30469352
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