Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats

Lu, Chengqiang; Chou, An‐Kuo; Wu, Chin-Shan; Yang, Chih‐Hsun; Chen, J. T.; Wu, Ping; Lin, Sheng; Muhammad, R.; Yang, Lin-Cheng

doi:10.1038/sj.gt.3301774

Cited by 37 publications

(19 citation statements)

References 22 publications

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“…Betaendorphins, as endogenous opioids, have a potent analgesic action [22]. Moreover, beta-endorphins and other opioids were found to cause peripheral analgesia when the precursor molecules CRF and POMC were expressed at peripherally inflamed sites [14,23,24]. In addition, POMC and CRF mRNA expression has been shown in human skin [25,26].…”

Section: Discussionmentioning

confidence: 99%

GaAlAs (830 nm) low‐level laser enhances peripheral endogenous opioid analgesia in rats

et al. 2007

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Section: Discussionmentioning

confidence: 99%

GaAlAs (830 nm) low‐level laser enhances peripheral endogenous opioid analgesia in rats

et al. 2007

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“…Previous studies indicated that transplantation of encapsulated tumor cells secreting opioid peptides such as ␤-EP or enkephalin provided antinociceptive effect (Gonzalez-Navarro et al, 1987;Wu et al, 1994;Saitoh et al, 1995). In addition, recent evidence indicates that POMC gene delivery in muscle or kidney alleviates formalin-induced pain (Lu et al, 2002) or bladder pain (Chuang et al, 2003). Hence, ␤-EP production in the peripheral tissues via POMC gene delivery may exert antinociceptive function.…”

Section: Discussionmentioning

confidence: 99%

“…POMC neuropeptides such as ␣-MSH and ␤-EP have been identified in various non-neuronal cells, including memory T cells, macrophages, and melanocytes (Schauer et al, 1994;Cabot et al, 1997;Raffin-Sanson et al, 2003). In addition, POMC gene delivery in muscle or bladder by gene gun approach alleviates pain via local generation of ␤-EP (Lu et al, 2002;Chuang et al, 2003), indicating that POMC could be processed in the peripheral tissues to elicit antinociceptive effect.…”

mentioning

confidence: 99%

Gene Transfer of Pro-opiomelanocortin Prohormone Suppressed the Growth and Metastasis of Melanoma: Involvement of α-Melanocyte-Stimulating Hormone-Mediated Inhibition of the Nuclear Factor κB/Cyclooxygenase-2 Pathway

Liu

Liu²,

Lin³

et al. 2005

Mol Pharmacol

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Pro-opiomelanocortin (POMC) is a prohormone of various neuropeptides, including corticotropin, ␣-melanocyte-stimulating hormone (␣-MSH), and ␤-endorphin (␤-EP). POMC neuropeptides are potent inflammation inhibitors and immunosuppressants and may exert opposite influences during tumorigenesis. However, the role of POMC expression in carcinogenesis remains elusive. We evaluated the antineoplastic potential of POMC gene delivery in a syngenic B16-F10 melanoma model. Adenovirus-mediated POMC gene delivery in B16-F10 cells increased the release of POMC neuropeptides in cultured media, which differentially regulated the secretion of pro-and anti-inflammatory cytokines in lymphocytes. POMC gene transfer significantly reduced the anchorage-independent growth of melanoma cells. Moreover, pre-or post-treatment with POMC gene delivery effectively retarded the melanoma growth in mice. Intravenous injection of POMC-transduced B16-F10 cells resulted in reduced foci formation in lung by 60 to 70% of control. The reduced metastasis of POMC-transduced B16-F10 cells could be attributed to their attenuated migratory and adhesive capabilities. POMC gene delivery reduced the cyclooxygenase-2 (COX-2) expression and prostaglandin (PG) E 2 synthesis in melanoma cells and tumor tissues. In addition, application of NS-398, a selective COX-2 inhibitor, mimicked the antineoplastic functions of POMC gene transfer in melanoma. The POMC-mediated COX-2 down-regulation was correlated with its inhibition of nuclear factor B (NFB) activities. Exogenous supply of ␣-MSH inhibited NFB activities, whereas application of the ␣-MSH antagonist growth hormone-releasing peptide-6 (GHRP-6) abolished the POMC-induced inhibition of NFB activities and melanoma growth in mice. In summary, POMC gene delivery suppresses melanoma via ␣-MSH-induced inhibition of NFB/COX-2 pathway, thereby constituting a novel therapy for melanoma.POMC is a multifunctional polycistronic gene located on human chromosome 2p23.3. POMC is a 31 kDa prohormone that is processed into various neuropeptides, including corticotropin, melanotropins (␣-, ␤-, and ␥-MSH), lipotropins, and ␤-endorphin (␤-EP) (Solomon, 1999;Catania et al., 2004b). POMC peptides possess pleiotropic functions including pigmentation, adrenocortical function, regulation of energy stores, the immune system, and the central and peripheral

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“…Preclinical studies of chronic pain have used several gene therapy vectors (Cope et al, 2006). Adenoviral, AAV, and HSV vectors have been used to deliver therapeutic genes including β-endorphin (Finegold et al, 1999), proopiomelanocortin (Lu et al, 2002), interleukin 2 (IL-2) (Yao et al, 2003), proenkephalin-A (Braz et al, 2001), IL-10 (Milligan et al, 2005a;Milligan et al, 2005b), glial-derived growth factor (Hao et al, 2003) and neurotrophin-3 (Pradat et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

Immunological thresholds in neurological gene therapy: highly efficient elimination of transduced cells might be related to the specific formation of immunological synapses between T cells and virus-infected brain cells

et al. 2006

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First-generation adenovirus can be engineered with powerful promoters to drive expression of therapeutic transgenes. Numerous clinical trials for glioblastoma multiforme using first generation adenoviral vectors have either been performed or are ongoing, including an ongoing, Phase III, multicenter trial in Europe and Israel (Ark Therapeutics, Inc.). Although in the absence of antiadenovirus immune responses expression in the brain lasts 6-18 months, systemic infection with adenovirus induces immune responses that inhibit dramatically therapeutic transgene expression from first generation adenoviral vectors, thus, potentially compromising therapeutic efficacy. Here, we show evidence of an immunization threshold for the dose that generates an immune response strong enough to eliminate transgene expression from the CNS. For the systemic immunization to eliminate transgene expression from the brain, ≥1 × 10 7 infectious units (iu) of adenovirus need to be used as immunogen. Furthermore, this immune response eliminates >90% of transgene expression from 1 × 10 7 -1 × 10³ iu of vector injected into the striatum 60 days earlier. Importantly, elimination of transgene expression is independent of the nature of the promoter that drives transgene expression and is accompanied by brain infiltration of CD8 + T cells and macrophages. In conclusion, once the threshold for systemic immunization (i.e. 1 × 10 7 iu) is crossed, the immune response eliminates transgene expression by >90% even from brains that receive as little as 1000 iu of adenoviral vectors, independently of the type of promoter that drives expression.

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Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats

Cited by 37 publications

References 22 publications

GaAlAs (830 nm) low‐level laser enhances peripheral endogenous opioid analgesia in rats

GaAlAs (830 nm) low‐level laser enhances peripheral endogenous opioid analgesia in rats

Gene Transfer of Pro-opiomelanocortin Prohormone Suppressed the Growth and Metastasis of Melanoma: Involvement of α-Melanocyte-Stimulating Hormone-Mediated Inhibition of the Nuclear Factor κB/Cyclooxygenase-2 Pathway

Immunological thresholds in neurological gene therapy: highly efficient elimination of transduced cells might be related to the specific formation of immunological synapses between T cells and virus-infected brain cells

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