BXL628, A Novel Vitamin D3 Analog Arrests Prostate Growth in Patients with Benign Prostatic Hyperplasia: A Randomized Clinical Trial

Colli, Enrico; Rigatti, Patrìzio; Montorsi, Francesco; Artibani, Walter; Petta, S; Mondaini, Nicola; Scarpa, R.M.; Usai, Paolo; Olivieri, Lorenza; Maggi, Mario

doi:10.1016/j.eururo.2005.08.014

Cited by 88 publications

(71 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Results in Fig. 5A demonstrate that lymph node cells from NOD mice immunized with PSBP [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] and treated with vehicle respond vigorously to the peptide, as determined by IFN-␥ production, whereas the response is significantly reduced in lymph node cells from Elocalcitol-treated NOD mice. A significant inhibition induced by Elocalcitol treatment is also observed following restimulation of lymph node cells from PSBP 21-40 -primed mice with purified native PSBP, indicating its capacity to inhibit T cell responses to naturally processed autoantigen epitopes (Fig.…”

Section: Elocalcitol Treatment Inhibits Cd4 ϩ T Cell Responses To An mentioning

confidence: 99%

“…In the present study, we have examined the capacity of Elocalcitol (BXL-628), a VDR agonist tested preclinically (20) and clinically (21) for the treatment of benign prostatic hyperplasia (BPH), to treat autoimmune prostatitis in the NOD mouse, a strain genetically prone to develop different organ-specific autoimmune diseases, including type 1 diabetes, thyroiditis, sialilitis, oophoritis, adrenalitis, and orchitis (22). The male NOD mouse is susceptible to induction of experimental autoimmune prostatitis (EAP) by injection of mouse prostate homogenate in complete Freund's adjuvant.…”

Section: Treatment Of Experimental Autoimmune Prostatitis In Nonobesementioning

confidence: 99%

“…Using 20-mers overlapping by 10 amino acid residues covering the entire PSBP sequence, we have recently identified PSBP [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] as an immunodominant, naturally processed epitope presented by I-A g7 to NOD CD4 ϩ T cells, able to induce autoimmune prostatitis in NOD mice (G. Penna et al, manuscript in preparation). To determine the capacity of Elocalcitol to inhibit T cell responses to prostate autoantigens, NOD mice have been immunized with PSBP [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] peptide and treated with vehicle or Elocalcitol for 9 days. Results in Fig.…”

Section: Elocalcitol Treatment Inhibits Cd4 ϩ T Cell Responses To An mentioning

confidence: 99%

“…5B). To assess the capacity of Elocalcitol to inhibit CD4 ϩ T cell responses in the target organ, pooled prostate-infiltrating CD4 ϩ T cells from PSBP 21-40 -primed NOD mice treated for 4 wk with vehicle or with Elocalcitol were cultured with splenic Thy 1.2-negative APCs from vehicle-treated NOD mice in the presence of 1 M PSBP [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] peptide. Results in Fig.…”

Section: Elocalcitol Treatment Inhibits Cd4 ϩ T Cell Responses To An mentioning

confidence: 99%

“…To detect Ag-specific responses, popliteal lymph node cells or spleen cells from vehicle or Elocalcitol-treated mice were cultured for the indicated time in flat-bottom 96-well plates (Costar) with the indicated concentrations of PSBP or PSBP [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] peptide. Cultures of lymph node cells were performed in synthetic HL-1 medium (Ventrex Laboratories), supplemented with 2 mM L-glutamine and 50 g/ml gentamicin (Sigma-Aldrich), whereas spleen cells and prostate-infiltrating CD4 ϩ cells were cultured in round-bottom 96-well plates in RPMI 1640 (Invitrogen Life Technologies) supplemented with 10% heat-inactivated FCS (Serono), 50 M 2-ME, 2 mM L-glutamine, and 50 g/ml gentamicin (Sigma-Aldrich).…”

Section: Cell Culturesmentioning

confidence: 99%

See 4 more Smart Citations

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

Penna

Amuchastegui

Cossetti

et al. 2006

The Journal of Immunology

119

View full text Add to dashboard Cite

On the basis of on the marked inhibitory activity of the vitamin D receptor agonist Elocalcitol on basal and growth factor-induced proliferation of human prostate cells and on its potent anti-inflammatory properties, we have tested its capacity to treat experimental autoimmune prostatitis (EAP) induced by injection of prostate homogenate-CFA in nonobese diabetic (NOD) mice. Administration of Elocalcitol, at normocalcemic doses, for 2 wk in already established EAP significantly inhibits the intraprostatic cell infiltrate, leading to a profound reduction in the number of CD4+ and CD8+ T cells, B cells, macrophages, dendritic cells, and I-Ag7-positive cells. Immunohistological analysis demonstrates reduced cell proliferation and increased apoptosis of resident and infiltrating cells. Significantly decreased production of the proinflammatory cytokines IFN-γ and IL-17 is observed in prostate-draining lymph node T cells from Elocalcitol-treated NOD mice stimulated by TCR ligation. In addition, Elocalcitol treatment reduces IFN-γ production by prostate-infiltrating CD4+ T cells and draining lymph node T cells specific for an immunodominant peptide naturally processed from prostate steroid-binding protein, a prostate-specific autoantigen. Finally, CD4+ splenic T cells from Elocalcitol-treated NOD mice show decreased ability, upon adoptive transfer into NOD.SCID recipients, to induce autoimmune prostatitis, paralleled by a reduced capacity to produce IFN-γ in response to prostate steroid-binding protein. The results indicate that Elocalcitol is able to interfere with key pathogenic events in already established EAP in the NOD mouse. These data show a novel indication for vitamin D receptor agonists and indicate that treatment with Elocalcitol may inhibit the intraprostatic inflammatory response in chronic prostatitis/chronic pelvic pain syndrome patients.

show abstract

Section: Elocalcitol Treatment Inhibits Cd4 ϩ T Cell Responses To An mentioning

confidence: 99%

Section: Treatment Of Experimental Autoimmune Prostatitis In Nonobesementioning

confidence: 99%

Section: Elocalcitol Treatment Inhibits Cd4 ϩ T Cell Responses To An mentioning

confidence: 99%

Section: Elocalcitol Treatment Inhibits Cd4 ϩ T Cell Responses To An mentioning

confidence: 99%

Section: Cell Culturesmentioning

confidence: 99%

See 3 more Smart Citations

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

Penna

Amuchastegui

Cossetti

et al. 2006

The Journal of Immunology

119

View full text Add to dashboard Cite

show abstract

LUTS treatment: Future treatment options

2007

View full text Add to dashboard Cite

Lower urinary tract symptoms (LUTS) are commonly divided into storage, voiding, and postmicturition symptoms, and may occur in both men and women. Male LUTS have historically been linked to benign prostatic hyperplasia (BPH), but are not necessarily prostate related. The focus of treatment for LUTS has thus shifted from the prostate to the bladder and other extraprostatic sites. LUTS include symptoms of the overactive bladder (OAB), which are often associated with detrusor overactivity. Treatment for LUTS suggestive of BPH has traditionally involved the use of alpha(1)-adrenoceptor (AR) antagonists; 5alpha-reductase inhibitors; and phytotherapy-however, several new therapeutic principles have shown promise. Selective beta(3)-adrenoceptor agonists and antimuscarinics are potentially useful agents for treating LUTS, particularly for storage symptoms secondary to outflow obstruction. Other agents of potential or actual importance are antagonists of P2X(3) receptors, botulinum toxin type A, endothelin (ET)-converting enzyme inhibitors, and drugs acting at vanilloid, angiotensin, and vitamin D(3) receptor sites. Drugs interfering with the nitric oxide/cGMP-cAMP pathway, Rho-kinase and COX inhibitors, as well as drugs targeting receptors and mechanisms within the CNS, are also of interest and deserving of further study for the treatment of LUTS.

show abstract

BXL‐628, a vitamin D receptor agonist effective in benign prostatic hyperplasia treatment, prevents RhoA activation and inhibits RhoA/Rho kinase signaling in rat and human bladder

Morelli¹,

Vignozzi²,

Filippi

et al. 2006

The Prostate

Self Cite

112

View full text Add to dashboard Cite

show abstract

BXL628, A Novel Vitamin D3 Analog Arrests Prostate Growth in Patients with Benign Prostatic Hyperplasia: A Randomized Clinical Trial

Cited by 88 publications

References 13 publications

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

LUTS treatment: Future treatment options

BXL‐628, a vitamin D receptor agonist effective in benign prostatic hyperplasia treatment, prevents RhoA activation and inhibits RhoA/Rho kinase signaling in rat and human bladder

Contact Info

Product

Resources

About