Journal of Neuroendocrinology最新文献

The First International Symposium on Avian Endocrinology (ISAE) was held 47 years ago at the Grand Hotel in Kolkata (Calcutta), India. Professor Asok Ghosh organized and convened the symposium, and Professor Donald S. Farner was President. The 1977 ISAE was convened at a time when neuroendocrine cascades were emerging as major pathways by which environmental events are perceived and transduced resulting in endocrine secretions that then orchestrate life history stages. Methods to measure hormone concentrations in blood and other tissues were relatively recent allowing the advance of laboratory and field investigations to explore ecological bases of endocrine control systems. The rise of evolutionary endocrinology and theory in ecological contexts followed-topics that are flourishing today. Studies on poultry continue to play central roles at ISAE meetings. In recent decades, the incorporation of genomics, transcriptomics, proteomics, epigenetics and other technologies provide us with an unprecedented array of tools to explore endocrinological processes at mechanistic levels we could never have dreamed of in 1977. The future looks to be an era of major advances in neuroendocrinology. What technologies will arise and transform our knowledge further? Artificial intelligence (AI) is emerging as a tool in avian endocrinology in at least research on endocrine disrupting chemicals. Will AI facilitate new advances and research directions across the field? The future of basic research has never been brighter than it is now. As in the past, ISAEs in the next decades will integrate new discoveries across environmental and applied biology. New challenges will doubtless appear.

Peptide receptor radionuclide therapy (PRRT) using [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate (¹⁷⁷Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2. The studies have demonstrated that four cycles of PRRT with ¹⁷⁷Lu-DOTATATE prolongs progression-free survival and preserves quality of life, in patients with grade 1 and 2 advanced GEP NET. Notably, first-line PRRT using ¹⁷⁷Lu-DOTATATE in grade 2 and 3 GEP NET patients has also shown efficacy and safety. Furthermore, PRRT can ameliorate symptoms in patients with NET-associated functioning syndromes. Although various studies have explored alternative radionuclides for PRRT, none currently meet the criteria for routine clinical implementation. Ongoing research aims to further enhance PRRT, and the results from large clinical trials comparing PRRT with other NET treatments are anticipated, potentially leading to significant modifications in NET treatment strategies and PRRT protocols. The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET.

Neuroendocrine tumors (NETs) are presented with metastases due to delayed diagnosis. We aimed to identify NET-related biomarkers from peripheral blood. The development and validation of a multi-gene NETseq ensemble classifier using peripheral blood RNA-Seq is reported. RNA-Seq was performed on peripheral blood samples from 178 NET patients and 73 healthy donors. Distinguishing gene features were identified from a learning cohort (59 PRRT-naïve GEP-NET patients and 38 healthy donors). Ensemble classifier combining the output of five machine learning algorithms viz. Random Forest (RF), Extreme Gradient Boosting (XGBOOST), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), and Logistic Regression (LR) were trained and independently validated in the evaluation cohort (n = 106). The response to PRRT was evaluated in the PRRT cohort (n = 46) and the PRRT response monitoring cohort (n = 16). The response to ¹⁷⁷Lu-DOTATATE PRRT was assessed using RECIST 1.1 criteria. The Ensemble classifier trained on 61 gene features, distinguished NET from healthy samples with 100% accuracy in the learning cohort. In an evaluation cohort, the classifier achieved 93% sensitivity (95% CI: 87.8%-98.03%) and 91.4% specificity (95% CI: 82.1%-100%) for PRRT-naïve GEP-NETs (AUROC = 95.4%). The classifier returned >87.5% sensitivity across different tumor characteristics and outperformed serum Chromogranin A sensitivity (χ² = 21.89, p = 4.161e-6). In the PRRT cohort, RECIST 1.1 responders showed significantly lower NETseq prediction scores after ¹⁷⁷Lu-DOTATATE PRRT, in comparison to the non-responders. In an independent response monitoring cohort, paired samples (before PRRT and after 2nd or 3rd cycle of PRRT) were analyzed. The NETseq prediction score significantly decreased in partial responders (p = .002) and marginally reduced in stable disease (p = .068). The NETseq ensemble classifier identified PRRT-naïve GEP-NETs with high accuracy (≥92%) and demonstrated a potential role in early treatment response monitoring in the PRRT setting. This blood-based, non-invasive, multi-analyte molecular method could be developed as a valuable adjunct to conventional methods in the detection and treatment response assessment in NET patients.

Peptide receptor radionuclide therapy (PRRT) has demonstrated immense promise as a treatment for patients with neuroendocrine tumors (NET) who have somatostatin receptor (SSTR) expression. PRRT significantly reduces tumor growth, stabilizes the disease, and prolongs survival in a significant percentage of patients with metastatic/advanced NET. It produces an important beneficial effect on the quality of life (QOL) and effectively alleviates symptoms in patients with NET. Overall, PRRT is typically well-tolerated and most of the side effects are usually transient and subside on their own. It is, however, crucial to be cognizant of the potential toxicities associated with this treatment. This awareness will enable physicians to promptly detect, effectively manage, and prevent these toxicities by identifying high-risk factors in NET patients. This review provides an in-depth overview for clinicians managing NET about the toxicity of PRRT. The toxicities are stratified into acute, subacute, and long-term based on their onset following PRRT. Potential high-risk factors in order to treat effectively and prevent these toxicities in NET patients are presented including the management strategy. This review also discusses novel insights, perspectives, and recent advancements in predicting, preventing, and managing toxicity associated with PRRT, while offering prospective future research directions to minimize clinical toxicity and maximize the therapeutic benefits of PRRT as a treatment strategy for NET patients.

The incidence and prevalence of neuroendocrine tumours (NETs) are on the rise, but to date, only complete surgical resection is curative. Among the various therapeutic options for metastatic disease, peptide receptor radionuclide therapy (PRRT), linking a radioactive moiety to an octreotide derivative, has been shown to be highly efficacious and a well-tolerated therapy, improving progression-free survival and prolonging overall survival. Nevertheless, complete responses are rare, and the current β-particle emitters have non-optimal radiobiological properties. A new generation of α-particle-emitting radionuclides is being developed, with the advantages of very high energy and a short path length. We survey the most recent developments in this field, summarising the result of currently performed studies in this potentially ground-breaking novel form of therapy for NETs.

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for both oncological and hormone control and is a widely accepted standard of care treatment for patients with neuroendocrine neoplasms (NEN). Its use is anticipated to increase significantly, and this demands accurate tools and paradigms to assess treatment response post PRRT. This article outlines the current role and future developments of anatomical, molecular imaging and biomarkers for response assessment to PRRT, highlighting the challenges and provides perspectives for the need to focus on a multimodality, multidisciplinary and individualised approach for patients with this complex heterogeneous disease.

Songbird vocal behavior, physiology, and brains-including neurogenesis-change between seasons. We examined seasonal differences in neurogenesis in three brain regions associated with vocal production and learning, HVC (letter-based proper name), robust nucleus of the arcopallium (RA), and Area X, and two brain regions associated with auditory perception, caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM). To do this, we captured wild male and female European starlings (Sturnus vulgaris) in spring and fall, collected a blood sample, and minimized time from capture to tissue collection to limit suppressive effects of captivity on neurogenesis. We quantified neurogenesis using doublecortin (DCX) immunohistochemistry, counting new neurons of three DCX cell morphologies (multipolar, fusiform, and round). We found regional differences in types of morphologies expressed, and amount of neurogenesis across regions: NCM had more fusiform cells than all other regions, and RA had more round cells than other regions. Males had more neurogenesis in HVC in fall than in spring, but there was no seasonal difference in neurogenesis in HVC of females, perhaps reflecting sexually dimorphic vocal learning demands related to repertoire size and complexity. Plasma corticosterone was higher in spring than fall and was correlated with testis volume in males, but it was not correlated with another purported measure of stress, heterophil:lymphocyte ratio (HLR), nor with neurogenesis. Our results suggest that the addition of new neurons to specific regions and circuits may serve different functions for males and females, particularly in the context of vocal production, learning, and perceptual demands across seasons.

Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high-grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow-up. Alkaline phosphatase (AP), gamma-GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p < .01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02–1.04 per unit increase (1% tumor burden; all p < .001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43–0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver-directed therapies.

Glial cells are an integral component of the nervous system, performing crucial functions that extend beyond structural support, including modulation of the immune system, tissue repair, and maintaining tissue homeostasis. Recent studies have highlighted the importance of glial cells as key mediators of stress responses across different organs. This review focuses on the roles of glial cells in peripheral tissues in health and their involvement in diseases linked to psychological stress. Populations of glia associated with psychological stress ("GAPS") emerge as a promising target cell population in our basic understanding of stress-associated pathologies, highlighting their role as mediators of the deleterious effects of psychological stress on various health conditions. Ultimately, new insights into the impact of stress on glial cell populations in the periphery may support clinical efforts aimed at improving the psychological state of patients for improved health outcomes.