Growth Hormone & Igf Research最新文献

{"title":"Effects of insulin-like growth factor-I and Progranulin on a human trophoblast model","authors":"Makoto Osaka,&nbsp;Atsushi Tajima,&nbsp;Satoshi Takemori,&nbsp;Momoe Watanabe,&nbsp;Tohru Morisada,&nbsp;Shinji Tanigaki,&nbsp;Yoichi Kobayashi","doi":"10.1016/j.ghir.2025.101665","DOIUrl":"10.1016/j.ghir.2025.101665","url":null,"abstract":"<div><div>Gestational diabetes and obesity are associated with increased placental weight and fetal birth weight. Placental development is mainly promoted by trophoblast proliferation and various humoral factors. Insulin-like growth factor-1 (IGF<img>I) levels are increased in mothers with gestational diabetes, and trophoblast proliferation is promoted in a dose-dependent manner. In addition, progranulin (PGRN), an adipokine involved in obesity, plays an important role in the proliferation of trophoblast cell lines. IGF-I and PGRN independently affect placental development, but there are many unknowns regarding their interaction. In this study, we investigated the combined effects of IGF-I and PGRN on trophoblast proliferation using the human choriocarcinoma cell line JEG-3. Cell proliferation was evaluated using a cell counting method and a water-soluble tetrazolium-1 assay. Furthermore, the effect of PGRN on the intracellular signaling pathways of IGF<img>I, particularly the phosphorylation of Akt and Erk1/2, was evaluated using western blotting. IGF-I significantly increased cell proliferation in JEG-3 cells. However, the proliferative effect of a low concentration of IGF-I (100 ng/mL) was inhibited by simultaneous treatment with PGRN. Pretreatment with PGRN significantly suppressed phosphorylation of Erk1 at a low concentration of IGF-I (<em>P</em> &lt; 0.01) but had no effect on phosphorylation of Akt. PGRN may suppress IGF-I-induced trophoblast proliferation by regulating the phosphorylation of Erk1/2, especially at low concentrations of IGF<img>I. PGRN modulates the proliferative effects of IGF-I in a complex manner, dependent on the concentration and timing of exposure. These findings indicate that the placental growth factor IGF-I may be regulated by PGRN.</div><div>(245 words)</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"82 ","pages":"Article 101665"},"PeriodicalIF":1.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose optimization of PEG-rhGH therapy to improve growth outcomes of childhood-onset growth failure","authors":"Ying Wu ,&nbsp;Lai Zhang ,&nbsp;Haipeng Ma,&nbsp;Peng Wang,&nbsp;Ming Lu,&nbsp;Xinle Xv,&nbsp;Sheng Yu","doi":"10.1016/j.ghir.2025.101664","DOIUrl":"10.1016/j.ghir.2025.101664","url":null,"abstract":"<div><h3>Background</h3><div>This study evaluates the efficacy and safety of optimized PEG-rhGH dosing in pre-pubertal and pubertal children with Childhood-Onset Growth Failure due to growth hormone deficiency (GHD) or non-GHD causes.</div></div><div><h3>Methods</h3><div>This study employed a combined retrospective (<em>n</em> = 144) and prospective (n = 14) design to examine the PEG-rhGH dosing strategies' impact. A total of 158 children were enrolled in the study, of whom 130 were included in the analysis after completing a minimum of one year of follow-up. Participants were stratified into pre-pubertal and pubertal groups. PEG-rhGH therapy with dose titration was administered based on growth response and IGF-1 level. The primary goal of the study was to evaluate the effect of individualized PEG-rhGH dosing, including clinically-based target height velocity and IGF-1 titration, on height velocity in children with GHD and non-GHD small children, stratified by puberty. Outcome measures included change in height, weight, BMI, and adverse events. Data were analyzed with SPSS 25.0.</div></div><div><h3>Results</h3><div>Pre-pubertal children exhibited a significantly greater height increase compared to pubertal adolescents (9.75 cm vs. 9.01 cm, <em>p</em> = 0.0159). A dose-dependent effect on growth velocity was observed in both groups. In the pubertal group, growth velocity (GV) increased from 0.80 ± 0.20 cm/year at doses ≤0.200 mg/kg/week to 0.99 ± 0.38 cm/year at doses ≥0.220 mg/kg/week (<em>p</em> = 0.017). Similarly, in the pre-pubertal group, GV increased from 0.87 ± 0.23 cm/year at the lowest dose to 1.10 ± 0.24 cm/year at the highest dose (<em>p</em> = 0.048). These findings confirm a dose-response relationship, particularly at doses exceeding 0.200 mg/kg/week.</div></div><div><h3>Conclusions</h3><div>PEG-rhGH therapy was more effective in promoting height growth in pre-pubertal children compared to pubertal adolescents. A clear dose-dependent effect was observed in both groups, emphasizing the importance of individualized dosing for optimal growth outcomes.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"82 ","pages":"Article 101664"},"PeriodicalIF":1.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injection of lentiviral vectors expressing GH and IGF1 increases body and muscle mass in male rats","authors":"Zahra Roudbari ,&nbsp;Akram Alizadeh ,&nbsp;Mohammadreza Nassiri ,&nbsp;Ali Fallah ,&nbsp;Ali Javadmanesh","doi":"10.1016/j.ghir.2025.101663","DOIUrl":"10.1016/j.ghir.2025.101663","url":null,"abstract":"<div><div>The aim of this study was to increase growth hormone (GH1) and insulin-like growth factor-1 (IGF1) levels in rat muscle indirectly through the transduction of C2C12 cells via lentivectors and to compare their effects on muscle mass. The coding sequences of GH1, IGF1, and GH1-IGF1, linked by the 2 A self-cleaving peptide to enable polycistronic expression<strong>,</strong> were synthesized, cloned and inserted into the pCDH vector. Recombinant pseudolentiviruses containing our target genes were produced in HEK293T cells. C2C12 cells were transduced with pseudo lentiviruses and selected through resistance to puromycin antibiotics. The expression of the GH1 and IGF1 genes at the mRNA and protein levels was verified by RT–PCR and Western blotting, respectively. The recombinant pseudo lentiviruses and transduced C2C12 cells were injected into the tibialis anterior (TA), gastrocnemius and quadriceps muscle groups of eight-week-old rats. The body weights of the rats were measured weekly for eight weeks after the injection. The leg weight and histology of the muscle after eight weeks were also measured. The results revealed the expression of the GH1 and IGF1 genes at the mRNA and protein levels in C2C12 cells. An increase in both hormones, either directly or indirectly through C2C12 cells, increased the animal body weight, leg weight, and muscle fibre size after eight weeks. The direct and indirect transfer of IGF1 increased body weight, leg weight and muscle fibre size more than did the direct or indirect transfer of GH1. In the direct transfer groups, the body weight was greater than that in the indirect transfer groups after eight weeks. We demonstrated that nonpituitary secretion of GH1 mimicked some physiological effects of pituitary GH1 in a rat model. Further investigations are needed to study other possible effects of extra copy of GH1 and IGF1 genes over a longer period on other tissues.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"82 ","pages":"Article 101663"},"PeriodicalIF":1.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administration study of somapacitan, a long-acting growth hormone derivative, in horse for doping control purpose","authors":"Yoshibumi Shimizu ,&nbsp;Michiko Sugai-Bannai ,&nbsp;Haruka Tanabe ,&nbsp;Kazunobu Saito ,&nbsp;Hiroki Ito ,&nbsp;Hirotaka Tokushige ,&nbsp;Kazuhiro Kamiya ,&nbsp;Misato Hirano-Kodaira ,&nbsp;Masayuki Yamada ,&nbsp;Gary Ngai-Wa Leung","doi":"10.1016/j.ghir.2025.101662","DOIUrl":"10.1016/j.ghir.2025.101662","url":null,"abstract":"<div><div>Somapacitan is the second generation of recombinant human growth hormone (rhGH) medication that retains the pharmacological effects of rhGH but exhibits a longer duration of action due to its reversible albumin-binding in the body. In general, the use of all recombinant growth hormone (rGH) analogues is banned by the human and animal sports regulatory authorities due to their anabolic and lipolytic effects. However, little is known about the elimination kinetics and biological effects of the newly introduced long-acting rhGH, somapacitan, in horses. This paper describes the administration study of somapacitan and its elimination in horses, its correlation with plasma insulin-like growth factor-1 (IGF-1) levels, an established indicator for rGH abuse, and the evaluation of the detection capability of our recently developed liquid chromatography high-resolution mass spectrometry (LC-HRMS) method in equine plasma after extraction and trypsin digestion specifically designed for controlling the misuse or abuse of somapacitan. Three thoroughbred mares were each administered 90 mg somapacitan subcutaneously. Plasma IGF-1 concentration significantly increased in all horses after administration of somapacitan. The somapacitan-specific T10 peptide fragment that allows discriminative identification of somapacitan and rhGH was detected up to 14 days and confirmed in post-administration samples collected up to 10 days. Several shared peptide fragments between somapacitan and rhGH were also detected and confirmed in plasma samples collected 14 days post-administration, supporting the applicability of the test strategy for the analysis of authentic doping control samples in horses.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"82 ","pages":"Article 101662"},"PeriodicalIF":1.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy, safety, and outcomes of growth hormone treatment in children with idiopathic short stature","authors":"Agnès Linglart ,&nbsp;Andrew Dauber ,&nbsp;Alexander de Lima Jorge ,&nbsp;Xiaoping Luo ,&nbsp;Tsutomu Ogata ,&nbsp;Lars Sävendahl","doi":"10.1016/j.ghir.2025.101661","DOIUrl":"10.1016/j.ghir.2025.101661","url":null,"abstract":"<div><h3>Background</h3><div>Growth hormone (GH) is a treatment option in some countries for children with idiopathic short stature (ISS) given to enable them to attain height within the expected range. Currently, it is not often utilised in clinical practice. A literature review was conducted to summarise the efficacy, safety, and outcomes associated with GH treatment in children with ISS.</div></div><div><h3>Summary</h3><div>Guidelines for the diagnosis and treatment of ISS may benefit from revision to accommodate recent findings on genetic factors that influence height. Clinical trials and observational studies designed to investigate the effect of GH treatment on children with ISS have shown that it is effective in enabling them to attain height within the normal range. In some instances, height improvements are reported up to adult height. The safety of GH treatment in this patient population has also been investigated and no new safety concerns have been observed. In analyses that were designed to investigate the effect of GH on quality of life, improvements in psychosocial scores were observed, either by the patient, parent, or the treating physician.</div></div><div><h3>Key message</h3><div>GH treatment is effective in improving height outcomes and quality of life in children with ISS, with an acceptable safety profile.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"82 ","pages":"Article 101661"},"PeriodicalIF":1.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth hormone regulates deiodinase type 2 and 3 expression via GATA","authors":"Mana Mitsutani ,&nbsp;Hiromi Hano ,&nbsp;Mei Yokoyama ,&nbsp;Midori Matsushita ,&nbsp;Misa Hayashi ,&nbsp;Ichiro Yamauchi ,&nbsp;Tetsuya Tagami ,&nbsp;Kenji Moriyama","doi":"10.1016/j.ghir.2025.101659","DOIUrl":"10.1016/j.ghir.2025.101659","url":null,"abstract":"<div><h3>Objective</h3><div>Growth hormone (GH) is involved in bone and skeletal muscle growth directly or indirectly via STAT5 and/or insulin-like growth factor (IGF)-1. Thyroid hormone (TH) is essential for general cellular growth and metabolic regulation. While both GH and TH are essential for growth, their actions may partially complement each other in conditions of hormonal deficiency. For example, TH can enhance GH secretion and sensitivity, while GH is ineffective in Refetoff syndrome due to TH receptor dysfunction. However, the underlying molecular mechanism remains unclear. In this study, we investigated the molecular mechanisms underlying the complementarity between GH and TH, paying special attention to the effects of GH on the expression of both iodothyronine deiodinase (DIO) type 2 (DIO2) and type 3 (DIO3).</div></div><div><h3>Design</h3><div>The effects of growth hormone (GH) on DIOs were examined using reporter assays, chromatin immunoprecipitation, quantitative PCR, and western blotting using HEK293-derived TSA201 cells and mouse ATDC5 chondrocytes.</div></div><div><h3>Results</h3><div>GH induced the mRNA and protein expression of DIOs in ATDC5 cells via STAT5/GATA. GATAs activate the promoter activity of both DIOs. The binding sites for GATA on the <em>DIO</em> promoter were located −87 bp and − 75 bp upstream from the TSS for the <em>DIO2</em> promoter and − 6 bp upstream from the TSS for the <em>DIO3</em> promoter, respectively. GH-induced expression of DIOs in ATDC5 cells was abolished by K-7174, a GATA-specific inhibitor.</div></div><div><h3>Conclusion</h3><div>The present study demonstrates that GH regulates DIO2 and DIO3 expression via JAK/STAT5/GATAs after binding to GHR. This is the first report on the molecular mechanisms underlying GH-dependent compensation of TH action. (256 words).</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"82 ","pages":"Article 101659"},"PeriodicalIF":1.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of disease activity on cognitive and psychological outcomes in acromegaly: A prospective study","authors":"Serhat Uysal ,&nbsp;Zehra Kara ,&nbsp;Cem Sulu ,&nbsp;Serdar Sahin ,&nbsp;Ahmet Numan Demir ,&nbsp;Esra Gungormus ,&nbsp;Selin Yagci Kurtish ,&nbsp;Elif Ersoy Yilmaz ,&nbsp;Senol Turan ,&nbsp;Hande Mefkure Ozkaya ,&nbsp;Pinar Kadioglu","doi":"10.1016/j.ghir.2025.101650","DOIUrl":"10.1016/j.ghir.2025.101650","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the cognitive and psychological aspects of acromegaly and to assess how disease activity may affect these outcomes.</div></div><div><h3>Methods</h3><div>This prospective study included patients with acromegaly who consecutively admitted to Pituitary Center between June 2021 and July 2023. Cognitive functions were assessed using a series of standardized tests targeting memory, attention, executive function, verbal fluency, and visuospatial skills. Additionally, Beck Depression Inventory (BDI), Beck Anxiety Inventory, and Acromegaly Quality of Life Questionnaire (AcroQoL) assessments were conducted. These evaluations were performed preoperatively and at the 9th month postoperatively following transsphenoidal surgery (TSS) to assess the anticipated changes in neuropsychological functions based on disease activity.</div></div><div><h3>Results</h3><div>A total of 19 patients with acromegaly were included. Remission was achieved through TSS alone in 9 patients, while 10 patients required postoperative somatostatin receptor ligands. Cognitive functions (Montreal Cognitive Assessment Test) were better in the remission phase compared to the initial active disease phase (23.36 ± 3.46 vs 24.93 ± 3.73; <em>p</em> <em>=</em> 0.035). Cognitive flexibility and selective attention (Stroop Test) were impaired during the active period of the disease (17.79 ± 12.31 vs 12.29 ± 8.23; <em>p</em> <em>=</em> 0.016). Memory functions (Wechsler Memory Scale-Logical Memory Test: immediate recall, delayed recall, recognition) showed improvement from the active phase to remission (<em>p</em> <em>=</em> 0.016, <em>p</em> <em>=</em> 0.003, <em>p</em> <em>=</em> 0.008; respectively). BDI scores were significantly higher in the active phase compared to remission (7.36 ± 3.48 vs 5.43 ± 3.03; <em>p</em> <em>=</em> 0.009). Additionally, AcroQoL scores were lower during the active disease phase than in the remission phase (65.30 ± 17.75 vs 80.43 ± 13.61; <em>p</em> <em>=</em> 0.007).</div></div><div><h3>Conclusion</h3><div>Acromegaly may impair cognitive and psychological functions, which appear to improve with effective treatment.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"81 ","pages":"Article 101650"},"PeriodicalIF":1.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Pharmacodynamics, pharmacokinetics, and toxicology of Fc-growth hormone fusion protein in macaques”","authors":"Han Liu ,&nbsp;Binghuai Peng ,&nbsp;Baisong Zhou ,&nbsp;Yu Zhang ,&nbsp;Yunnan Liu ,&nbsp;Yulin Liu ,&nbsp;Ruixin Sun ,&nbsp;Zhuonan Li ,&nbsp;Qiumei Zhu ,&nbsp;Lu Yu ,&nbsp;Ruili Fu ,&nbsp;Qiong Wang ,&nbsp;Jinghui Liu ,&nbsp;Chunying Pang","doi":"10.1016/j.ghir.2025.101649","DOIUrl":"10.1016/j.ghir.2025.101649","url":null,"abstract":"","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"81 ","pages":"Article 101649"},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamics, pharmacokinetics, and toxicology of Fc-growth hormone fusion protein in macaques","authors":"Han Liu,&nbsp;Binghuai Peng,&nbsp;Baisong Zhou,&nbsp;Yu Zhang,&nbsp;Yunnan Liu,&nbsp;Yulin Liu,&nbsp;Ruixin Sun,&nbsp;Zhuonan Li,&nbsp;Qiumei Zhu,&nbsp;Lu Yu,&nbsp;Ruili Fu,&nbsp;Qiong Wang,&nbsp;Jinghui Liu,&nbsp;Chunying Pang","doi":"10.1016/j.ghir.2025.101648","DOIUrl":"10.1016/j.ghir.2025.101648","url":null,"abstract":"<div><h3>Purpose</h3><div>Growth hormone (GH) therapy for GH deficiency is used to treat multiple conditions. However, the short half-life of GH necessitates frequent dosing, which limits patient adherence. Fc fusion proteins, created by binding an active peptide to the Fc portion of IgG, are known to prolong the plasma half-life of the peptide. Pharmacodynamics and pharmacokinetics of Fc-GH in rats have been reported; however, studies in primate models are lacking. Therefore, in this study, we aimed to investigate the pharmacodynamics, pharmacokinetics, and toxicology of Fc-GH in rhesus and crab-eating macaques.</div></div><div><h3>Methods</h3><div>In rhesus macaques, Fc-GH was injected subcutaneously at 0.8, 1.6, and 3.2 mg/kg and intravenously at 1.6 mg/kg. The 1.6 mg/kg subcutaneous dose was administered five times, once every 7 days; other doses were administered as single injections for pharmacodynamic and pharmacokinetic assessments. In crab-eating macaques, potential toxicity was evaluated after single subcutaneous injections at 30, 45, and 62.5 mg/kg and repeated injections at 3, 10, and 30 mg/kg once every 7 days, followed by an 8-week recovery.</div></div><div><h3>Results</h3><div>No adverse events were observed following Fc-GH administrations. Fc-GH achieved C_max slowly after subcutaneous administration and rapidly after intravenous administration, with plasma levels being maintained over time. In rhesus macaques, the half-life increased dose-dependently: 23.72 ± 2.17 h (0.8 mg/kg), 49.44 ± 14.77 h (1.6 mg/kg), and 76.07 ± 13.19 h (3.2 mg/kg). After five injections of 1.6 mg/kg, the half-life of Fc-GH was 60.42 ± 18.29 h. Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels significantly increased and remained elevated for 28–42 days after Fc-GH injections. In crab-eating macaques, no Fc-GH accumulation was observed. The maximum tolerated single subcutaneous dose was 62.5 mg/kg; no adverse effects were observed at 30 mg/kg during repeated administration over 29 injections with an 8-week recovery.</div></div><div><h3>Conclusions</h3><div>Fc-GH demonstrated favorable pharmacokinetics and pharmacodynamics in macaques, significantly extending the half-life and enhancing IGF-1 and IGFBP-3 levels without adverse effects. These findings suggest Fc-GH as a promising long-acting GH therapy that could improve patient adherence.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"81 ","pages":"Article 101648"},"PeriodicalIF":1.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Picropodophyllotoxin alters EMT in neuroblastoma via inhibition of surface receptors IFG1R and ALK","authors":"Poonam Bhagriya ,&nbsp;Afridi Shaikh ,&nbsp;Hetal Roy","doi":"10.1016/j.ghir.2025.101638","DOIUrl":"10.1016/j.ghir.2025.101638","url":null,"abstract":"<div><div>Neuroblastoma (NB) is a type of paediatric cancer that originates from embryonic sympathoadrenal cells. Despite its paediatric origin, NB is mostly treated with strategy of non-small cell lung cancer like adults due to lack of specific therapeutic approach. To improve treatment outcome for NB patients, developing drugs that specifically target the genetic mutations or molecular pathways involved in neuroblastoma is necessary. Overexpression of the insulin-like growth factor 1 receptor (IGF1R) has been linked to various malignancies, including paediatric cancers. We hypothesized that inhibiting IGF1R with ALK (NB specific mutation) by phytochemical compound could effectively treat NB while avoiding undesirable cytotoxic effects. We evaluated the efficacy of Picropodophyllotoxin (PPP) as IGF1R inhibitor, for treatment of NB. The IC₅₀ value of PPP on SH-SY5Y, NB cells after 24 h of treatment was found to be 0.501 μM. Molecular docking studies revealed that PPP had a binding score of −7.5 kcal/mol with IGF1R and − 8.8 kcal/mol with ALK. This suggests that PPP not only binds to and inhibits IGF1R but also has a strong affinity for ALK. Gene expression studies, densitometric analysis, scratch assays, and AO/EtBr differential staining were used to evaluate the efficacy of PPP in NB cells. Transcript expression and densitometric analysis revealed that PPP could downregulate IGF1R and ALK in NB cells. Downregulation of <em>SNAIL</em>, a mesenchymal marker, and upregulation of <em>E-cadherin</em>, an epithelial marker, indicated a mesenchymal to epithelial transition in NB cells, suggesting that PPP treatment inhibited NB cell migration and proliferation. This was further supported by scratch assay results in our study. Furthermore, gene expression analysis of <em>p53</em>, <em>BAX</em> and <em>BCL2</em> indicated that PPP induces apoptosis in NB cells. AO/EtBr differential staining revealed apoptotic phenomena in NB cells after 24 h of PPP treatment. Although further research is needed to explore the receptor targeting approach using PPP for IGF1R and ALK inhibition.</div></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"80 ","pages":"Article 101638"},"PeriodicalIF":1.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}