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Frontiers in Endocrinology 2023While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with...
PURPOSE
While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.
METHODS
The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.
RESULTS
Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [Lu]Lu-DOTA-TATE dose and peaked within 48 hours.
CONCLUSIONS
[Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Pheochromocytoma; Retrospective Studies; Prolactin; Hydrocortisone; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Follicle Stimulating Hormone; Catecholamines; Thyrotropin
PubMed: 37886645
DOI: 10.3389/fendo.2023.1275813 -
Proceedings of the National Academy of... Aug 2023Interneuron populations within the nucleus accumbens (NAc) orchestrate excitatory-inhibitory balance, undergo experience-dependent plasticity, and gate-motivated...
Interneuron populations within the nucleus accumbens (NAc) orchestrate excitatory-inhibitory balance, undergo experience-dependent plasticity, and gate-motivated behavior, all biobehavioral processes heavily modulated by endogenous cannabinoid (eCB) signaling. While eCBs are well known to regulate synaptic plasticity onto NAc medium spiny neurons and modulate NAc function at the behavioral level, how eCBs regulate NAc interneuron function is less well understood. Here, we show that eCB signaling differentially regulates glutamatergic and feedforward GABAergic transmission onto NAc somatostatin-expressing interneurons (NAc) in an input-specific manner, while simultaneously increasing postsynaptic excitability of NAc neurons, ultimately biasing toward vHPC (ventral hippocampal), and away from BLA (basolateral amygdalalar), activation of NAc neurons. We further demonstrate that NAc are activated by stress in vivo and undergo stress-dependent plasticity, evident as a global increase in intrinsic excitability and an increase in excitation-inhibition balance specifically at vHPC, but not BLA, inputs onto NAc neurons. Importantly, both forms of stress-induced plasticity are dependent on eCB signaling at cannabinoid type 1 receptors. These findings reveal eCB-dependent mechanisms that sculpt afferent input and excitability of NAc neurons and demonstrate a key role for eCB signaling in stress-induced plasticity of NAc-associated circuits.
Topics: Endocannabinoids; Nucleus Accumbens; Neurons; Somatostatin; Cannabinoids
PubMed: 37590414
DOI: 10.1073/pnas.2300585120 -
Chinese Journal of Cancer Research =... Oct 2023Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors. Radiopharmaceuticals are important components of nuclear medicine. Among the...
Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors. Radiopharmaceuticals are important components of nuclear medicine. Among the radiopharmaceuticals approved by the Food and Drug Administration (FDA), radio-tracers targeting prostate-specific membrane antigen (PSMA) and somatostatin receptor (SSTR) have held essential positions in the diagnosis and treatment of prostate cancers and neuroendocrine neoplasms, respectively. In recent years, FDA-approved serials of immune-therapy and targeted therapy drugs targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), and nectin cell adhesion molecule 4 (Nectin 4). How to screen patients suitable for these treatments and monitor the therapy? Nuclear medicine with specific radiopharmaceuticals can visualize the expression level of those targets in systemic lesions and evaluate the efficacy of treatment. In addition to radiopharmaceuticals, imaging equipment is also a key step for nuclear medicine. Advanced equipment including total-body positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI) has been developed, which contribute to the diagnosis and treatment of tumors, as well as the development of new radiopharmaceuticals. Here, we conclude most recently advances of radiopharmaceuticals in nuclear medicine, and they substantially increase the "arsenal" of clinicians for tumor therapy.
PubMed: 37969954
DOI: 10.21147/j.issn.1000-9604.2023.05.05 -
Journal of Clinical Pathology Sep 2023Epidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinases family and overexpression of EGFR has been linked to poor prognosis and cancer...
AIMS
Epidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinases family and overexpression of EGFR has been linked to poor prognosis and cancer progression. Somatostatin receptor 2 (SSTR2) is a G-protein-coupled receptor (GPCR) with diverse biological functions in humans, and it is upregulated through the NF-KB signalling pathway in nasopharyngeal carcinomas (NPC). However, no studies have examined the EGFR and SSTR2 in NPC. This study aimed to investigate whether SSTR2 is associated with EGFR and clinicopathological features in NPC.
METHODS
Bioinformatics analysis was performed to assess the correlation between EGFR and SSTR2 based on the GEO database. The expression of SSTR2 and EGFR was evaluated by immunohistochemistry (IHC) in 491 cases of NPC and 50 cases of non-cancerous nasopharyngeal epithelium.
RESULTS
The bioinformatics analysis and IHC showed a positive correlation between SSTR2 and EGFR in NPC. High expression of SSTR2 and EGFR was significantly increased in NPC patients compared with non-cancerous nasopharyngeal epithelium. High expression of SSTR2 and/or EGFR was associated with a worse outcome and a higher risk of progression. The study found that patients receiving chemoradiotherapy (CR) with high expression of SSTR2, high expression of EGFR, and high coexpression of SSTR2 and EGFR had a poorer prognosis in both progression-free survival (PFS) and overall survival (OS). Interestingly, NPC patients with high expression of SSTR2, high expression of EGFR, high coexpression of EGFR and SSTR2, and EGFR/SSTR2 anyone high expression had a better prognosis with CR combined with targeted therapy. Cox multivariate analysis identified SSTR2 and EGFR as independent poor predictors of PFS.
CONCLUSION
Our study is the first to shed light on the intricate relationship between SSTR2 and EGFR in NPC and provides new insights into the potential benefits of EGFR targeted therapy for patients with high SSTR2 expression. Additionally, SSTR2 has potential as a new biomarker for poor prognosis in NPC patients.
PubMed: 37758305
DOI: 10.1136/jcp-2023-208987 -
Theranostics 2024Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumors (NETs) has been explored for more than two decades, but there are only limited...
Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumors (NETs) has been explored for more than two decades, but there are only limited data on the treatment of NETs of unknown primary site (CUP-NETs). This study aimed to analyze the long-term outcome, efficacy, and safety of PRRT in patients with CUP-NETs. Patients with pathologically confirmed metastatic CUP-NET who received lutetium-177 (Lu) and/or yttrium-90 (Y) labeled somatostatin analogs between March 2001 and March 2019 were retrospectively reviewed; those patients were referred as cCUP-NETs (clinical CUP-NETs). Eighty-one patients had unknown primary tumors even after [Ga]Ga-SSTR and [F]FDG PET/CT and were classified as pCUP-NETs (PET CUP-NETs). Treatment response was assessed according to RECIST 1.1 and PERCIST. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis, and adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. A total of 575 PRRT cycles were administered to 156 patients (76 men and 80 women) evaluable for analysis: these patients were monitored for a median period of 92.3 mo (range, 4.0-169.1 mo). The disease control rate was 41.4% (43.4%) by RECIST and 40.2% (40.8%) by PERCIST in cCUP-NENs (pCUP-NETs). The objective response rate (ORR) with PRRT was 29.4% and 32.2% in cCUP-NENs and pCUP-NETs, respectively. The median PFS and OS for the entire cohort were 17.4 mo (95% confidence interval [95% CI], 11.4-23.4) and 67.4 mo (95% CI, 47.2-87.2) for all patients, respectively. The median OS for G3 tumors was significantly lower (15 mo) than for patients with G1 NET (85.5 mo), G2 (71.7 mo), and for patients with unknown grade (63.3 mo) NETs (P = 0.186, HR: 10.6, 95% CI: 3.87, 28.97, P = 0.09). PRRT was well tolerated by all patients. During treatment and long-term follow-up, CTCAE grade 3 and grade 4 thrombocytopenia and leukocytopenia were observed in only 3 patients (1.9%); there was no evidence of renal or hepatic toxicity. In a large cohort of patients with advanced CUP-NETs treated with PRRT in a real-world scenario and followed up to 14 years after the commencement, PRRT has demonstrated favorable and clinically significant efficacy and survival with minimal and acceptable side effects. Our results indicate that PRRT is a well-tolerated and effective treatment option for patients with metastatic CUP-NETs expressing somatostatin receptors.
Topics: Male; Humans; Female; Positron Emission Tomography Computed Tomography; Neoplasms, Unknown Primary; Retrospective Studies; Neuroendocrine Tumors; Radioisotopes; Receptors, Somatostatin; Octreotide; Organometallic Compounds
PubMed: 38164147
DOI: 10.7150/thno.88619 -
Frontiers in Endocrinology 2023The significance of neuroendocrine (NE) markers in triple-negative breast cancer (TNBC) patients has not been investigated. This study aims to clarify the incidence and...
BACKGROUND
The significance of neuroendocrine (NE) markers in triple-negative breast cancer (TNBC) patients has not been investigated. This study aims to clarify the incidence and prognostic significance of NE marker expression in TNBC, determine its association with other clinicopathological parameters, and further explore the pathological features and potential treatment options for TNBC patients expressing NE markers.
METHODS
Clinicopathological data were collected from 396 TNBC patients undergoing radical breast cancer surgery at Peking Union Medical College Hospital from January 2002 to December 2014, with a final follow-up in July 2019. Immunohistochemistry (IHC) staining was performed for NE markers including chromogranin A (CgA) and synaptophysin (Syn). For TNBC patients with positive NE marker expression, IHC staining was then performed for alpha-thalassemia/mental retardation X-linked (ATRX), O(6)-methylguanine-methyltransferase (MGMT), somatostatin receptor 2 (SSTR2), and programmed death receptor-ligand 1 (PD-L1). The chi-square or Fisher exact test was used to evaluate the correlations between NE marker expression and other parameters. Survival curves were plotted using the Kaplan-Meier (K-M) method to assess the prognostic significance of NE markers in TNBC.
RESULTS
NE marker-positive staining was observed in 7.6% (30/396) of all TNBC cases. Only 0.5% (2/396) cases had ≥ 90% neoplastic cells expressing NE markers. Positive NE marker expression was associated with negative basal-like marker expression. K-M survival analysis showed that the NE marker-positive TNBC patients had higher disease-free survival (DFS) rates than the NE marker-negative patients at the same stage. Among the 30 NE marker-positive TNBC cases, 13.3% and 26.7% showed negative IHC staining for ATRX and MGMT, respectively, while 13.3% had a 3+ score for SSTR2 IHC staining. For PD-L1 IHC staining, 13.3% of the 30 TNBC cases were higher than 10 scores in Combined Positive Score (CPS), and 10.0% were higher than 10% in Tumor Cell Proportion Score (TPS).
CONCLUSION
There was a small proportion of TNBC patients expressing NE markers. TNBC patients with positive NE marker expression had a better prognosis than the negative group at the same stage. TNBC cases with positive NE marker expression may potentially benefit from immunotherapy or somatostatin analogue treatment.
Topics: Humans; Triple Negative Breast Neoplasms; B7-H1 Antigen; Prognosis; Disease-Free Survival; Mastectomy
PubMed: 38125789
DOI: 10.3389/fendo.2023.1205631 -
Archives of Endocrinology and Metabolism May 2024Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is... (Review)
Review
Expression of somatostatin receptors in hemangioblastomas associated with von Hippel-Lindau disease as a novel diagnostic, therapeutic, and follow-up opportunity: A case report and literature review.
Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.
Topics: Humans; Hemangioblastoma; von Hippel-Lindau Disease; Receptors, Somatostatin; Male; Middle Aged; Octreotide; Cerebellar Neoplasms; Follow-Up Studies; Magnetic Resonance Imaging; Radiopharmaceuticals
PubMed: 38788146
DOI: 10.20945/2359-4292-2023-0181 -
Growth Axis , , and Genes Express and Are Affected by the Injection of Exogenous Growth Hormone in .Genes Oct 2023In this study, to explore the effect of growth hormone changes on the related genes and regulatory roles of the turtle, PCR amplification, real-time fluorescence...
In this study, to explore the effect of growth hormone changes on the related genes and regulatory roles of the turtle, PCR amplification, real-time fluorescence quantitative analysis, and enzyme cutting technology were used to clone and sequence the () gene, (), and () sequence of . The effects of human growth hormone on the mRNA expression of growth-axis-related genes , , and in different sexes were observed. The study of the gene in turtles using real-time fluorescence quantitative PCR showed that the gene was mainly expressed in the nervous system and the digestive system, with the highest expression found in the brain, while the gene and the gene were expressed in all tissues of . The gene was expressed in the brain, pituitary, liver, stomach, and intestine, with the highest expression in the brain and the lowest expression in the liver. Within 4 weeks of the injection of exogenous growth hormone, the expression level of the gene in the brain of both sexes first increased and then decreased, showing a parabolic trend, and the expression level of the experimental group was lower than that of the control group. After the injection of growth hormone (GH), the expression of the gene in the liver of both sexes showed a significant increase in the first week, decreasing to the control group level in the second week, and then gradually increasing. Finally, a significant level of difference in the expression of the gene was reached at 3 and 4 weeks. In terms of the gene, the changing trend of the expression level in the liver was the same as that of the gene. After the injection of exogenous growth hormone, although the expression of the gene increased the inhibition of the secretion of the gene by the Reeves' turtle, exogenous growth hormone could replace the synthesis of GH and , accelerating the growth of the turtle. The experiments showed that the injection of recombinant human growth hormone affects the expression of , , and genes, and promotes the growth of the Reeves' turtle.
Topics: Male; Animals; Female; Humans; Growth Hormone; Receptors, Somatotropin; Insulin-Like Growth Factor I; Human Growth Hormone; Gene Expression Regulation; Somatostatin; Turtles
PubMed: 38002975
DOI: 10.3390/genes14112032 -
Indian Pediatrics Jun 2024Congenital hyperinsulinism (CHI) is a rare condition but is a common cause of severe and persistent hypoglycemia in early life. Prompt recognition of CHI is critical to... (Review)
Review
Congenital hyperinsulinism (CHI) is a rare condition but is a common cause of severe and persistent hypoglycemia in early life. Prompt recognition of CHI is critical to prevent the impact of neuroglycopenia and consequent lifelong neurodisability. It is important to be alert to the possibility of CHI in newborn babies with recurrent hypoglycemia associated with high glucose requirements. Pediatricians are advised to mitigate the risk of hypoglycemia by early treatment with high concentration dextrose and intravenous glucagon infusions. Specific medical therapies with diazoxide and/or somatostatin receptor analogues may be commenced after the finding of detectable insulin at hypoglycemia, a biochemical characteristic of CHI. Early exploration of genetic etiology is recommended, chiefly in the search for a focal form, amenable to limited pancreatic surgery. Genetic ascertainment is also useful to understand the basis of disease, variable responses to medical therapies and escalation of conservative treatment to subtotal pancreatectomy. CHI is a heterogeneous disorder with varying natural history. Many newborns and infants with CHI have severe and complex illness features; their long-term care is best achieved through review at specialist centers.
Topics: Humans; Congenital Hyperinsulinism; Infant, Newborn; Pediatricians; Infant; Hypoglycemia
PubMed: 38584412
DOI: No ID Found -
Clinical Nuclear Medicine Nov 2023Given their neuroendocrine origin, head and neck paragangliomas (HNPGLs) can be imaged with somatostatin receptor (SSTR)-directed PET/CT. We aimed to determine whether...
BACKGROUND
Given their neuroendocrine origin, head and neck paragangliomas (HNPGLs) can be imaged with somatostatin receptor (SSTR)-directed PET/CT. We aimed to determine whether the in vivo PET signal can differentiate between varying HNPGL subtypes.
PATIENTS AND METHODS
Fourteen patients with HNPGL received pretherapeutic SSTR-PET/CTs using 68 Ga-DOTATOC. Six (42.9%) patients had a jugular paraganglioma (PGL-J), 5 (35.7%) were diagnosed with carotid paraganglioma (PGL-Cs), and the remaining 3 patients (21.4%) had PGL-C with pathogenic SDHx germline variants (PGL-C-SDH). A visual and quantitative assessment of the primary tumor on SSTR-PET was performed, including SUV max and target-to-background ratio (TBR). Quantitative values were then compared between subgroups of patients affected with different HNPGL entities.
RESULTS
On visual assessment, all primary HNPGLs could be identified on SSTR-PET/CT. Quantification of HNPGL revealed substantially elevated SUV max in PGL-J (101.7 ± 58.5) when compared with PGL-C-SDH (13.4 ± 5.6, P < 0.05), but not when compared with PGL-C (66.7 ± 27.3, P = 0.4; PGL-C vs PGL-C-SDH, P = 0.2). TBR of PGL-J (202.9 ± 82.2), however, further differentiated between PGL-C (95.7 ± 45.4, P < 0.05) and PGL-C-SDH (20.4 ± 12.2, P < 0.01; PGL-C vs PGL-C-SDH, P = 0.3). Moreover, whole-body readout revealed metastases in 2/3 (66.7%) of PGL-C-SDH patients, with a single SSTR-expressing skeletal lesion in one subject and bipulmonary lesions in the other patient.
CONCLUSIONS
In patients with HNPGL, SSTR-PET/CT identified the primary and metastatic disease and provides substantially elevated TBR, indicating excellent image contrast. PET-based quantification can also differentiate between varying HNPGL subtypes.
Topics: Humans; Positron Emission Tomography Computed Tomography; Receptors, Somatostatin; Head and Neck Neoplasms; Paraganglioma, Extra-Adrenal; Paraganglioma
PubMed: 37756444
DOI: 10.1097/RLU.0000000000004870