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Pasireotide-a novel somatostatin receptor ligand after 20 years of use.

ABSTRACT: Pasireotide, a novel multireceptor-targeted somatostatin receptor ligand (SRL) is characterized by a higher affinity to somatostatin receptor type 5 than type 2, unlike first-generation SRLs. Because of the broader binding profile, pasireotide has been suggested to have a greater clinical efficacy in acromegaly than first-generation SRLs and to be efficacious in Cushing's disease. The consequence of this binding profile is the increased blood glucose level in some patients. This results from the inhibition of both insulin secretion and the incretin effect and only a modest suppression of glucagon. A monthly intramuscular formulation of long-acting release pasireotide has been approved for both acromegaly and Cushing's disease treatment. This review presents data on the efficacy and safety of pasireotide treatment mostly in patients with acromegaly and Cushing's disease. Moreover, other possible therapeutic applications of pasireotide are mentioned.

SUBMITTER: Bolanowski M

PROVIDER: S-EPMC9156514 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Pasireotide-a novel somatostatin receptor ligand after 20 years of use.

Bolanowski Marek M Kałużny Marcin M Witek Przemysław P Jawiarczyk-Przybyłowska Aleksandra A

Reviews in endocrine & metabolic disorders 20220124 3

Pasireotide, a novel multireceptor-targeted somatostatin receptor ligand (SRL) is characterized by a higher affinity to somatostatin receptor type 5 than type 2, unlike first-generation SRLs. Because of the broader binding profile, pasireotide has been suggested to have a greater clinical efficacy in acromegaly than first-generation SRLs and to be efficacious in Cushing's disease. The consequence of this binding profile is the increased blood glucose level in some patients. This results from the ...[more]

PMID: 35067849

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Project description:Prostate cancer (PC) is one of the most frequently diagnosed cancers and a leading cause of cancer-related deaths in Western society. Current PC therapies prevalently target the functions of androgen receptor (AR) and may only be effective within short time periods, beyond which the majority of PC patients progress to castration-resistant PC (CRPC) and metastatic disease. The role of estradiol/estradiol receptor (ER) axis in prostate transformation and PC progression is well established. Further, considerable efforts have been made to investigate the mechanism by which somatostatin (SST) and somatostatin receptors (SSTRs) influence PC growth and progression. A number of therapeutic strategies, such as the combination of SST analogs with other drugs, show, indeed, strong promise. However, the effect of the combined treatment of SST analogs and estradiol on proliferation, epithelial mesenchyme transition (EMT) and migration of normal- and cancer-derived prostate cells has not been investigated so far. We now report that estradiol plays anti-proliferative and pro-apoptotic effect in non-transformed EPN prostate cells, which express both ERα and ERβ. A weak apoptotic effect is observed in transformed CPEC cells that only express low levels of ERβ. Estradiol increases, mainly through ERα activation, the expression of SSTRs in EPN, but not CPEC cells. As such, the hormone enhances the anti-proliferative effect of the SST analog, pasireotide in EPN, but not CPEC cells. Estradiol does not induce EMT and the motility of EPN cells, while it promotes EMT and migration of CPEC cells. Addition of pasireotide does not significantly modify these responses. Altogether, our results suggest that pasireotide may be used, alone or in combination with other drugs, to limit the growth of prostate proliferative diseases, provided that both ER isoforms (α and β) are present. Further investigations are needed to better define the cross talk between estrogens and SSTRs as well as its role in PC.

Project description:BackgroundCanada was one of the first countries to regulate the medical use of cannabis. However, literature on Canada's medical cannabis program is limited.MethodsWe use administrative data from the medical cannabis program, and licensed cannabis vendor catalog data to describe a) the participation of patients, physicians, and cannabis vendors in the program from its inception in 1999 to 2021, and b) trends in medical cannabis consumption, prices and potency. We also use national surveys conducted over the last several decades to estimate trends in regular cannabis use (medical or otherwise) and how it changed during the medical cannabis access regimes.ResultsIn 2001, the Canadian government granted access to those with physician-documented evidence of a severe health problem that could not be managed using conventional therapies. Most patients accessed cannabis grown under a personal production license. By 2013, authorized daily cannabis dosages were very high. In 2014, the government, concerned over illegal diversion, required that cannabis be purchased from a licensed commercial grower; personal production was banned. Physicians were given responsibility for authorizing patient access. To fill the regulatory void, the physician regulatory bodies in Canada imposed their own prescribing restrictions. After these changes, the number of physicians who were willing to support patient cannabis use markedly decline but the number of patients participating in the program sharply increased. Medical cannabis use varied by province-rates were generally lower in provinces with stricter regulations on physician cannabis prescribing. Most varieties of cannabis oil available for sale are now high in CBD and low in THC. Dry cannabis varieties, conversely, tend to be high in THC and low in CBD. Inflation adjusted prices of most varieties of medical cannabis have declined over time. We find that rates of daily cannabis use (medical or otherwise) increased markedly after the 2014 policy regime. The fraction of Canadians using cannabis daily increased again after the 2018 legalization of recreational cannabis; at the same time, participation in the medical access program declined.ConclusionThe implications for patient health outcomes of changes in the medical cannabis program and legalization of recreational use remains an important area for future research.

Project description:BackgroundMorbidity after pancreatectomy is commonly due to leakage of exocrine secretions resulting in abscess or pancreatic fistula (PF). Previously, we authored a double-blind randomized controlled trial demonstrating that perioperative pasireotide administration lowers abscess or PF formation by >50%. Accordingly, we adopted pasireotide use as standard practice after pancreatectomy in October 2014 and hypothesized a similar PF/abscess rate reduction would be observed.Study designA prospectively maintained database was queried for all patients who underwent pancreatectomy between October 2014 and July 2017. Pasireotide was administered preoperatively and twice daily for 7 days postoperatively or until discharge. The primary end point was clinically relevant PF/abscess requiring procedural intervention, identical to the earlier trial outcomes. Logistic regression was used to compare outcomes with the placebo arm of the earlier randomized trial and to control known PF risk factors.ResultsDuring the 34-month study period, 652 patients underwent pancreatectomy (211 distal pancreatectomy, 441 pancreaticoduodenectomy). Compared with the historical placebo group (n = 148), the observational group had an increased prevalence of higher American Society of Anesthesiologists scores (69% vs 54%; p < 0.001) and high-risk cases (small duct and soft gland, 47% vs 36%; p = 0.030). The primary end point occurred in 13.3% of patients receiving pasireotide vs 20.9% in the placebo arm of the earlier trial trial (odds ratio 0.58; 95% CI 0.37 to 0.92; p = 0.020). Biliary leakage was lower in those receiving pasireotide (0.6% vs 3.4%; p = 0.014), and other morbidity was unchanged. No subpopulation was identified more likely to benefit from pasireotide.ConclusionsAt our center, adoption of pasireotide has allowed us to achieve a clinically significant abscess or pancreatic leak rate of 13.3%, approximating the effect observed in the randomized trial of pasireotide during routine surgical practice.

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Pasireotide-a novel somatostatin receptor ligand after 20 years of use.

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Pasireotide-a novel somatostatin receptor ligand after 20 years of use.

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