scholarly journals Substance P-Saporin for Bone Cancer Pain in Dogs

2013 ◽  
Vol 119 (5) ◽  
pp. 999-1000 ◽  
Author(s):  
Ken-ichiro Hayashida
2013 ◽  
Vol 119 (5) ◽  
pp. 1178-1185 ◽  
Author(s):  
Dorothy Cimino Brown ◽  
Kimberly Agnello

Abstract Background: Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor–bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs. Methods: In a single-blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard-of-care analgesic therapy alone (control, n = 35) or intrathecal SP-SAP (20–60 µg) in addition to standard-of-care analgesic therapy (n = 35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death. Results: Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly, more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization than dogs that were treated with SP-SAP (24%; P < 0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (P < 0.01). Conclusion: Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.


Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.


IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S386
Author(s):  
Huizhu Liu ◽  
Xuejing Lü ◽  
Ning Lü ◽  
Yuqiu Zhang

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