Octreotide reduces hepatic, renal and breast cystic volume in autosomal-dominant polycystic kidney disease

Peces, R; Cuesta-López, Emilio; Peces, Carlos; Pérez-Dueñas, Virginia; Vega-Cabrera, Cristina; Selgas, Rafael

doi:10.1007/s11255-010-9748-1

Cited by 12 publications

(9 citation statements)

References 12 publications

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“…For example, the mammalian target of rapamycin (mTOR) inhibitor rapamycin was thought to be a powerful drug for treating ADPKD, but it has not been effective (5,14,23). In recent reports, tolvaptan and octreotide have shown therapeutic effects in ADKPD, and both drugs target intracellular cAMP accumulation (4,7,12,16,18,24). In our study, ABCC3 was remarkably downregulated in polycystic kidney cells, and restoring ABCC3 decreased cell proliferation by reducing intracellular cAMP content.…”

Section: Discussionmentioning

confidence: 53%

Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney

Chang

Park

Woo

et al. 2015

American Journal of Physiology-Renal Physiology

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Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal proliferation of renal tubular epithelial cells, resulting in the loss of renal function. Despite identification of the genes responsible for ADPKD, few effective drugs are currently available for the disease. Thus finding additional effective drug targets is necessary. The functions of multidrug- resistance-associated protein 3 (MRP3) have been reported only in the field of drug resistance, and the renal functions of MRP3 are mostly unknown. In this study, we found that MRP3 was significantly downregulated in kidneys of human patients with ADPKD and polycystic kidney disease (PKD) mouse models. Our results suggest that downregulated MRP3 stimulated renal epithelial cell proliferation through the B-Raf/MEK/ERK signaling pathway. In contrast, we found that restoring MRP3 reduced cell proliferation and cystogenesis in vitro. These results suggest that the renal function of MRP3 is related to renal cell proliferation and cyst formation and that restoring MRP3 may be an effective therapeutic approach for PKD.

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Section: Discussionmentioning

confidence: 53%

Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney

Chang

Park

Woo

et al. 2015

American Journal of Physiology-Renal Physiology

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“…2,5,16,17,24 To date, the lowering of cAMP in cystic cholangiocytes by agonists of somatostatin receptors is the only available pharmacologic treatment for patients with symptomatic liver disease. 2,5,7,8 The efficacy of two synthetic somatostatin analogues, octreotide and pasireotide, has been previously evaluated by us in preclinical trials, and our data demonstrate that pasireotide is more effective than octreotide in suppressing hepatorenal cystogenesis. 16,17 Furthermore, we recently examined the synergistic effects of pasireotide and hydroxychloroquine on disease progression in PCK rats.…”

Section: Discussionmentioning

confidence: 61%

Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease

Pisarello

Masyuk

Gradilone

et al. 2018

The American Journal of Pathology

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Hepatic cystogenesis in polycystic liver disease (PLD) is associated with abnormalities in multiple cellular processes, including elevated cAMP and overexpression of histone deacetylase 6 (HDAC6). Disease progression in polycystic kidney (PCK) rats (an animal model of PLD) is attenuated by inhibition of either cAMP production or HDAC6. Therefore, we hypothesized that concurrent targeting of HDAC6 and cAMP would synergistically reduce cyst growth. Changes in hepatorenal cystogenesis were examined in PCK rats treated with a pan-HDAC inhibitor, panobinostat; three specific HDAC6 inhibitors, ACY-1215, ACY-738, and ACY-241; and a combination of ACY-1215 and the somatostatin receptor analogue, pasireotide. We also assessed effects of ACY-1215 and pasireotide alone and in combination on cell proliferation, cAMP production, and expression of acetylated α-tubulin in vitro in cultured cholangiocytes and the length of primary cilia and the frequency of ciliated cholangiocytes in vivo in PCK rats. Panobinostat and all three HDAC6 inhibitors decreased hepatorenal cystogenesis in PCK rats. ACY-1215 was more effective than other HDAC inhibitors and was chosen for combinational treatment. ACY-1215 + pasireotide combination synergistically reduced cyst growth and increased length of primary cilia in PCK rats. In cultured cystic cholangiocytes, ACY-1215 + pasireotide combination concurrently decreased cell proliferation and inhibited cAMP levels. These data suggest that the combination of drugs that inhibit HDAC6 and cAMP may be an effective therapy for PLD.

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“…Recent clinical trials have found SST agonists to be efficacious in ameliorating the growth of liver in ADPKD / PLD (polycystic liver disease) [60][61][62][63]. Data thus far has clearly found Octreotide to be safe and effective in treating polycystic liver disease.…”

Section: Human Trialsmentioning

confidence: 99%

Novel Therapies for Polycystic Kidney Disease

Gattone¹,

Bacallao²

2011

J Genet Syndr Gene Ther

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Octreotide reduces hepatic, renal and breast cystic volume in autosomal-dominant polycystic kidney disease

Cited by 12 publications

References 12 publications

Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney

Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney

Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease

Novel Therapies for Polycystic Kidney Disease

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