Leuprolide Acetate Inhibits Spinal Cord Inflammatory Response in Experimental Autoimmune Encephalomyelitis by Suppressing NF-&amp;#954;B Activation

Guzmán-Soto, Irene; Salinas, Eva; Jl, Quintanar

doi:10.1159/000438927

Cited by 16 publications

(15 citation statements)

References 43 publications

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“…As previously reported in literature, most of these factors are affected by action of ZA and LA [25,26,27,28,29,30]. In particular, a direct correlation between GM-CSF and MCP-1 decreased levels and cell invasiveness has been demonstrated [25,28].…”

Section: Discussionsupporting

confidence: 57%

Zoledronic Acid and Leuprolide Acetate Affect Du-145 Migration towards Stem Cell Conditioned Medium

Montagna

Bertolini

Mognetti

et al. 2019

GJCT

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Prostate cancer (PCa) is the most frequent genitourinary tumour and the third specific death cause, mostly because of bone metastasis. Currently, PCa is treated with GnRH analogues (leuprolide acetate-LA) and bisphosphonates (zoledronic acid-ZA) often in association. Thus, the aim of this work has been to study, in vitro, the effects of these drugs on cell line derived from PCa (DU-145). Particularly, we focused on some crucial aspects that drugs might play in tumor evolution and metastatization, by interfering with vitality, migration and interactions with bone cells. ZA cytotoxicity has been confirmed on DU-145 after 48-hours incubation at 5 μM, while LA cytotoxicity appears only after 72-hours contact at higher concentrations (100 μM). Both sub cytotoxic ZA and LA doses decreased 3D (transwell assay) PCa cell migration rate. pAkt/Akt ratio is diminished by LA and, even if less strikingly, by ZA, in agreement with the respective inhibition migration ratios. Cells underwent migration test in mesenchymal stem cells – MSC – conditioned medium (MSC-CM), which significantly increases the rate of migration (210%± 2.2; P<0.05). Addition of both ZA and LA quenched the attractive effect of conditioned medium. Our results suggest that LA and, mostly, ZA have a direct toxic effect on cancer cells. Furthermore, they inhibit cellular migration even under attractive stimuli exerted by MSC, and this might contribute to explain their effect in limiting metastatization.

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Section: Discussionsupporting

confidence: 57%

Zoledronic Acid and Leuprolide Acetate Affect Du-145 Migration towards Stem Cell Conditioned Medium

Montagna

Bertolini

Mognetti

et al. 2019

GJCT

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“…More evidence has come also from other Japanese authors who showed that GnRH analogs treatment attenuated the expression of IL-8 by reducing TNF-α-induced NF-κB activation [204]. In an interesting study about spinal cord inflammatory response, Guzman-Soto et al, found that GnRH analog—leurolide has an effect on the activation/expression levels transcription nuclear factor NF-κB and the proinflammatory cytokines like TNF-α [205]. Further research about the connections between GnRH analogs and TNF-α pathways is needed (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms

Ciebiera

Włodarczyk

Zgliczyńska

et al. 2018

IJMS

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Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. The incidence of UFs has been estimated at 25–80% depending on selected population. The pathophysiology of UFs remains poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is the main component of all pathways leading to UF tumor formation and tumor necrosis factor α (TNF-α) is believed to be one of the key factors in this field. TNF-α is a cell signaling protein involved in systemic inflammation and is one of the cytokines responsible for the acute phase reaction. This publication presents current data about the role of tumor necrosis factor α in the biology of UFs and the related symptoms. TNF-α is an extremely important cytokine associated with the biology of UFs, UF-related symptoms and complaints. Its concentration has been proven to be elevated in women with clinically symptomatic UFs. The presented data suggest the presence of an “inflammation-like” state in women with UFs where TNF-α is a potent inflammation inducer. The origin of numerous symptoms reported by women with UFs can be traced back to the TNF-α influence. Nevertheless, our knowledge on this subject remains limited and TNF-α dependent pathways in UF pathophysiology should be investigated further.

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“…In addition to the effects on the nervous system, it has been reported that GnRH and LA have a direct action on the modulation of the function of the immune system. Specifically, it has been described that GnRH and LA treatments significantly reduce the expression of proinflammatory cytokines (Guzmán-Soto et al 2016, Quintanar andGuzmán-Soto 2013). Also, in rats with acute spinal cord injury, it was found that there was a decrease in activated microglia in the spinal cord of animals that received treatment with LA (Díaz- Galindo et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Neurological improvement in patients with chronic spinal cord injury treated with leuprolide acetate, an agonist of GnRH

Quintanar¹,

Díaz-Galindo²,

Calderón-Vallejo³

et al. 2018

Acta Neurobiologiae Experimentalis

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It has been reported that gonadotropin-releasing hormone (GnRH), and its analogue leuprolide acetate (LA), have neurotrophic properties; particularly in the regeneration of injured spinal cord in animal models and in the case of a patient with spinal cord injury (SCI). The aim of this study was to establish whether treatment with LA improves sensitivity, motor activity and independence in patients with chronic SCI. Patients were treated LA once a month for six months. They were evaluated at the beginning and at the end of treatment; using a sensitivity and motor impairment scale, according to the American Spinal Injury Association (ASIA), and grade of independence scale; employing the spinal cord independence measure (SCIM). Statistical analysis showed a significant improvement in the ASIA sensory score and the SCIM score when comparing the initial versus final evaluation after six months of LA administration. Some patients showed an increase in frequency of bowel movements. Treatment with LA induces improvements in sensitivity, motor activity and independence in patients with chronic SCI. One advantage of this protocol is that it is a non-invasive method of easy and safe application, with few side effects.

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Leuprolide Acetate Inhibits Spinal Cord Inflammatory Response in Experimental Autoimmune Encephalomyelitis by Suppressing NF-κB Activation

Cited by 16 publications

References 43 publications

Zoledronic Acid and Leuprolide Acetate Affect Du-145 Migration towards Stem Cell Conditioned Medium

Zoledronic Acid and Leuprolide Acetate Affect Du-145 Migration towards Stem Cell Conditioned Medium

The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms

Neurological improvement in patients with chronic spinal cord injury treated with leuprolide acetate, an agonist of GnRH

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