Ocena efektów leczenia analogami somatostatyny nieczynnych hormonalnie gruczolaków przysadki w porównaniu z akromegalią

Zawada, Natalia Bozena; Kunert‐Radek, Jolanta; Pawlikowski, Marek; Pisarek, Hanna; Radek, Maciej

doi:10.5603/ep.a2016.0043

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…Thus, our results demonstrate for the first time that treatment with pladienolide-B inhibits cell viability/proliferation in all PitNETs subtypes tested and in AtT-20 and GH3 cell lines, which compares well with the reduction on cell viability and colony formation observed in HeLa cells [33] and with recent data from our group demonstrating that pladienolide-B reduced proliferation, migration and tumorspheres-formation in prostate cancer cells [33]. Interestingly, NFPTs were less sensitive to the effect of pladienolide-B compared to GHomas or ACTHomas, which is in line with previous observations in response to other pharmacological treatments in NFPTs [42,43,74]. Notably, pladienolide-B was also able to reduce GH secretion after 24 h of incubation, a relevant result since tumor hypersecretion is linked to most of the symptoms caused by GHomas.…”

Section: Discussionsupporting

confidence: 89%

“…Of particular interest are the results found in NFPTs, which displayed a profound downregulation of most of the components analyzed, in striking contrast with the alterations observed in functioning PitNETs (GHomas, ACTHomas, and PRLomas), wherein many components are overexpressed. In line with this, previous results have demonstrated that NFPTs typically display a distinct behavior and different expression pattern of relevant components involved in pituitary cell function, such as somatostatin receptors, in comparison with functioning PitNETs and normal tissue [42,43,44,45]. Interestingly, our results showed that the expression levels of SRSF9, SND1, U2AF1, U2AF2 and SRRM4 were able to discriminate, although not perfectly, between NFPTs and NP tissues.…”

Section: Discussionsupporting

confidence: 89%

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Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features

Vázquez-Borrego

Fuentes-Fayos

Venegas-Moreno

et al. 2019

Cancers

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Pituitary neuroendocrine tumors (PitNETs) constitute approximately 15% of all brain tumors, and most have a sporadic origin. Recent studies suggest that altered alternative splicing and, consequently, appearance of aberrant splicing variants, is a common feature of most tumor pathologies. Moreover, spliceosome is considered an attractive therapeutic target in tumor pathologies, and the inhibition of SF3B1 (e.g., using pladienolide-B) has been shown to exert antitumor effects. Therefore, we aimed to analyze the expression levels of selected splicing-machinery components in 261 PitNETs (somatotropinomas/non-functioning PitNETS/corticotropinomas/prolactinomas) and evaluated the direct effects of pladienolide-B in cell proliferation/viability/hormone secretion in human PitNETs cell cultures and pituitary cell lines (AtT-20/GH3). Results revealed a severe dysregulation of splicing-machinery components in all the PitNET subtypes compared to normal pituitaries and a unique fingerprint of splicing-machinery components that accurately discriminate between normal and tumor tissue in each PitNET subtype. Moreover, expression of specific components was associated with key clinical parameters. Interestingly, certain components were commonly dysregulated throughout all PitNET subtypes. Finally, pladienolide-B reduced cell proliferation/viability/hormone secretion in PitNET cell cultures and cell lines. Altogether, our data demonstrate a drastic dysregulation of the splicing-machinery in PitNETs that might be associated to their tumorigenesis, paving the way to explore the use of specific splicing-machinery components as novel diagnostic/prognostic and therapeutic targets in PitNETs.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features

Vázquez-Borrego

Fuentes-Fayos

Venegas-Moreno

et al. 2019

Cancers

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“…The data available on the use of SSTs ligands in gonadotroph tumors is limited [4,15]. So far, studies including usually a small number of patients and various combinations of NF-PitNETs, more or less well characterized, showed that SSTs ligands octreotide and lanreotide had limited effect on tumor shrinkage [4,[15][16][17][18]. In one of the studies showing no case of tumor shrinkage on octreotide LAR, the IHC expression of SST2 was investigated-as it was positive in only 46% of cases, the authors concluded that this may have contributed to the limited effect of octreotide [16].…”

Section: Discussionmentioning

confidence: 99%

Gonadotroph Tumors Show Subtype Differences that Might Have Implications for Therapy

Ilie

Vasiljevic

Louvet

et al. 2020

Cancers

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Gonadotroph tumors, although frequent, are poorly studied and understood, being usually included in the larger nonfunctioning pituitary neuroendocrine tumors (PitNETs) group. Moreover, in comparison to the other types of PitNETs, no established medical treatment is currently available for gonadotroph tumors. Here, we performed a retrospective study and analyzed the clinicopathological characteristics of 98 gonadotroph tumors operated in a single large pituitary center. Although being larger in men (p = 0.01), the aggressiveness of gonadotroph tumors did not appear to be sex-related. LH tumors were rare (4/98) and exclusively encountered in men. Somatostatin receptor type 5 (SST5) was absent in all analyzed tumors. The immunoreactive score (IRS) of somatostatin receptor type 2 (SST2) and of estrogen receptor alpha (ERα) was associated with the histological subtype (p = 0.01 and p = 0.02). IRS ERα correlated moderately with IRS SST2 in all (rho = 0.44, adjusted p-value = 0.0001) and in male (rho = 0.51, adjusted p-value = 0.0002) patients, and with follicle-stimulating hormone (FSH) percentage in all (rho = 0.40, adjusted p-value = 0.0005) and in female (rho = 0.58, adjusted p-value = 0.004) patients. In conclusion, gonadotroph tumors exhibit histological characteristics pinpointing the existence of several subtypes. Their heterogeneity warrants further investigations and may have to be taken into account when studying these tumors and investigating treatment options.

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“…The diagnosis is usually late, in a stage of macroadenomas, mostly with invasion of the adjacent structures. Transsphenoidal surgery is rarely curative, and tumour residue can regrow in as many as 65% of patients during long-term follow-up [22,23].…”

Section: Samplementioning

confidence: 99%

Czy istnieje różnica w jakości życia i występowaniu objawów psychiatrycznych u chorych na akromegalię i inne choroby przewlekłe?

Szczęśniak

Jawiarczyk-Przybyłowska²,

Matusiak³

et al. 2015

Endokrynologia Polska

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Ocena efektów leczenia analogami somatostatyny nieczynnych hormonalnie gruczolaków przysadki w porównaniu z akromegalią

Cited by 8 publications

References 19 publications

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features

Gonadotroph Tumors Show Subtype Differences that Might Have Implications for Therapy

Czy istnieje różnica w jakości życia i występowaniu objawów psychiatrycznych u chorych na akromegalię i inne choroby przewlekłe?

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