Pasireotide as Maintenance Treatment With Monthly Deep Intramuscular Injection in SSTR2/3/5-Expressing Synovial Sarcoma and Desmoplastic Small Round Cell Tumor

PAMSARC is a non-commercial interventional Phase 2 clinical trial of academic research institutions, with its primary goal being to improve medical treatment of fusion driven Desmoplastic small round cell tumor (DSRCT) and Synovial sarcoma (SySa) in young adults and adolsecents with male predominance.
Current management of DSRCT and SySa includes chemotherapy, radiation and aggressive cytoreductive surgery. Despite advances in multimodal therapy, outcomes remain poor with frequent disease recurrence and very limited options for patients with advanced disease.
Selected somatostatin receptor (SSTR) family members, i.e., SSTR2, SSTR3 and SSTR5, are frequently overexpressed in DSRCT and SySa, providing the rationale for treatment with somatostatin analogues (SSA).
Pasireotide is a SSA with high affinity for SSTR1, -2, -3, and -5 and is approved for the treatment of Cushing's disease and acromegaly and has also shown activity in other cancers. In patients with advanced stage DSRCT and SySa, conventional chemotherapeutic approaches frequently lead to disease response, however, the duration of progression-free time after chemotherapy is short. The targeted approach with pasireotide after initial intensive multimodal treatment may have the potential to significantly improve outcome.

开始日期2024-09-01

申办/合作机构

University Hospital Heidelberg

NL-OMON57054 / SuspendedN/AIIT

*Managing pasireotide-associated hyperglycaemia in acromegaly with eucaloric very-low carbohydrate ketogenic diet versus diabetes medication: a multicentre, randomized, open-label proof-of-concept study* - PasiAcroKeto

开始日期2024-07-01

申办/合作机构-

CTIS2023-505791-30-01 / Recruiting

A multicentric, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of COLIRIOBCN070660 administered topically in patients with moderately severe to severe non-proliferative diabetic retinopathy - RETISOM

开始日期2024-05-08

申办/合作机构-

100 项与 SSTR5 x SSTR1 x SSTR3 x SSTR2 相关的临床结果

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100 项与 SSTR5 x SSTR1 x SSTR3 x SSTR2 相关的转化医学

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0 项与 SSTR5 x SSTR1 x SSTR3 x SSTR2 相关的专利（医药）

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110

项与 SSTR5 x SSTR1 x SSTR3 x SSTR2 相关的文献（医药）

2024-07-01·Veterinary Medicine and Science

Expression of somatostatin receptors in canine and feline meningioma

Article

作者: Gradner, Gabriele ; Wolfram, Michael ; Oevermann, Anna ; Tichy, Alexander ; Wolfesberger, Birgitt ; Immler, Martin ; Walter, Ingrid

AbstractObjectivesThe standard treatment for canine and feline meningiomas includes radiotherapy, surgical excision or combined therapy. However, new therapeutic approaches are required due to the possible recurrence or progression of meningiomas despite initial therapy. Adjunctive therapy with synthetic long‐acting somatostatin (SST) analogues has been described in humans with SST‐expressing tumours. The expression of SST receptors (SSTRs) by feline meningiomas is currently unknown, and there are little data about canine meningiomas. We hypothesized that SSTR is expressed by canine and feline meningiomas ().MethodsSeven canines and 11 felines with histologically confirmed meningiomas underwent STTR screening. RNA expressions of SSTR1, SSTR2, SSTR3 and SSTR5 (canine) and SSTR1–SSTR 5 (feline) in fresh frozen and formalin‐fixed and paraffin‐embedded (FFPE) samples were investigated using real‐time (RT)‐qPCR. The expression of SSTR1 and SSTR2 in FFPE samples was evaluated using immunohistochemistry (IHC). The specificity of applied antibodies for canine and feline species was confirmed by western blotting.ResultsIn canine meningiomas (n = 7), RNA expression of SSTR1, SSTR2 and SSTR5 was detected in all samples; SSTR3 RNA expression was detected in only 33% of samples. In feline meningiomas (n = 12), RNA expression of SSTR1, SSTR4, SSTR5 and SSTR2 was detected in 91%, 46%, 46% and 36% of samples, respectively; SSTR3 was not expressed. Overall, the detection rate was lower in FFPE samples. IHC revealed the expression of SSTR1 and SSTR2 in all samples from both species. However, it is important to exercise caution when interpreting IHC results due to the presence of diffuse background staining.ConclusionsSSTRs are widely expressed in canine and feline meningiomas, thereby encouraging further studies investigating SSTR expression to conduct trials about the effect of adjunctive therapy with long‐acting SST‐analogues.

2024-05-01·General and Comparative Endocrinology

Loss of function in somatostatin receptor 5 has no impact on the growth of medaka fish due to compensation by the other paralogs

Article

作者: Delgadin, T H ; Boan, A F ; Fernandino, J I ; Canosa, L F

Somatic growth in vertebrates is regulated endocrinologically by the somatotropic axis, headed by the growth hormone (GH) and the insulin growth factor-I (IGF-I). Somatostatin (Sst), a peptide hormone synthesized in the hypothalamus, modulates GH actions through its receptors (Sstr). Four Sstr subtypes (Sstr 1-3 and 5) have been identified in teleosts. However, little is known about whether they have a specific function or tissue expression. The aim of this study was to determine the role of sstr2 and sstr5 in the growth of the medaka (Oryzias latipes). The assessed expression pattern across diverse tissues highlighted greater prevalence of sstr1 and sstr3 in brain, intestine and muscle than in pituitary or liver. The expression of sstr2 was high in all the tissues tested, while sstr5 was predominantly expressed in the pituitary gland. A CRISPR/Cas9 sstr5 mutant with loss of function (sstr5^-/-) was produced. Assessment of sstr5^-/- indicated no significant difference with the wild type regarding growth parameters such as standard length, body depth, or peduncle depth. Furthermore, the functional loss of sstr5 had no impact on the response to a nutritional challenge. The fact that several sstr subtypes were upregulated in different tissues in sstr5^-/- medaka suggests that in the mutant fish, there may be a compensatory effect on the different tissues, predominantly by sstr1 in the liver, brain and pituitary, with sstr2 being upregulated in pituitary and liver, and sstr3 only presenting differential expression in the brain. Analysis of the sstr subtype and the sstr5^-/- fish showed that sstr5 was not the only somatostatin receptor responsible for Sst-mediated Gh regulation.

2024-04-01·Journal of Neurosurgery

Correlation between tumor invasion and somatostatin receptor subtypes in acromegaly

Article

作者: Zhu, Dimin ; Zhu, Yonghong ; Yang, Jia ; Wang, Haijun ; Chen, Jinping ; Mao, Zhigang ; Yao, Shun ; Akter, Farhana ; Chen, Wenli ; Zeng, Ailiang ; Zhang, Shaolin

OBJECTIVEThe low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs.METHODSA total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0–2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor–1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion.RESULTSCompared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm3 vs 3.50 ± 4.02 cm3, p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = −0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001).CONCLUSIONSTumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.