Endocrine-related cancer最新文献

Real-world effectiveness of darolutamide in metastatic castration-resistant prostate cancer. darolutamide在转移性去势抵抗性前列腺癌中的实际疗效。

Endocrine-related cancer Pub Date : 2025-05-29 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0188

Alyssa Liang, Shuchi Gulati, Quillan Huang, Heidi Dowst, Aedric Lim, Neda Zarrin-Khameh, Guilherme Godoy, Attiya B Noor, Patricia Castro, Michael E Scheurer, Mamta Parikh, Primo N Lara, Susan Hilsenbeck, Martha Mims, Nicholas Mitsiades

{"title":"Real-world effectiveness of darolutamide in metastatic castration-resistant prostate cancer.","authors":"Alyssa Liang, Shuchi Gulati, Quillan Huang, Heidi Dowst, Aedric Lim, Neda Zarrin-Khameh, Guilherme Godoy, Attiya B Noor, Patricia Castro, Michael E Scheurer, Mamta Parikh, Primo N Lara, Susan Hilsenbeck, Martha Mims, Nicholas Mitsiades","doi":"10.1530/ERC-24-0188","DOIUrl":"10.1530/ERC-24-0188","url":null,"abstract":"Darolutamide is a second-generation androgen receptor (AR) antagonist (2GARA) with established benefit in treating patients with non-metastatic castration-resistant prostate cancer (M0-CRPC) and metastatic castration-sensitive prostate cancer. Its real-world effectiveness in the treatment of patients with metastatic (M1) CRPC, including those who have progressed on CYP17 inhibitors (CYP17Is) or other 2GARAs (enzalutamide/apalutamide), is not well-described. We assessed the real-world effectiveness of darolutamide in a racially diverse cohort of 44 M1-CRPC and 11 M0-CRPC patients and collected data on baseline and emerging AR mutations in circulating tumor DNA (ctDNA) in these patients. The median progression-free survival (PFS) was 2.15 months for M1-CRPC and 21.16 months for M0-CRPC patients. In the M1-CRPC cohort, the median PFS was longer in those who had only received prior CYP17Is compared to 2GARA-resistant patients (2.43 vs 1.61 months; P = 0.03). Darolutamide suppressed serum PSA levels by >50% in 5/44 M1-CRPC patients (11.4%), all previously 2GARA-naïve. M1-CRPC patients resistant only to CYP17Is had improved mean best percent PSA changes from baseline compared to 2GARA-resistant patients (4.68 vs 42.34%; P = 0.047). PFS was not significantly different between African-American and non-African-American patients, or between patients with and without AR mutations at baseline. AR mutations emerging or increasing in allele fraction in ctDNA upon darolutamide treatment included H875Y, H100Q, D891H, T878A, L702H, L329W, N767Y and AR copy number gain. In summary, darolutamide may provide some benefit in CYP17I-refractory M1-CRPC patients, even in the presence of AR mutations. Resistance to other 2GARAs may significantly decrease benefit from darolutamide.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and safety of RET-kinase inhibitors in RET-altered thyroid cancers: a systematic review and single-arm meta-analysis. ret激酶抑制剂治疗ret改变的甲状腺癌的疗效和安全性：一项系统评价和单臂荟萃分析

Endocrine-related cancer Pub Date : 2025-05-29 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0219

Israt Jahan Riya, Ifrat Jahan Piya, Jonathan N Priantti, Cha Len Lee, Lina Barman, Almunthir Altobi

{"title":"Efficacy and safety of RET-kinase inhibitors in RET-altered thyroid cancers: a systematic review and single-arm meta-analysis.","authors":"Israt Jahan Riya, Ifrat Jahan Piya, Jonathan N Priantti, Cha Len Lee, Lina Barman, Almunthir Altobi","doi":"10.1530/ERC-24-0219","DOIUrl":"10.1530/ERC-24-0219","url":null,"abstract":"The RET proto-oncogene, which encodes a receptor tyrosine kinase, is an important factor in the pathogenesis of medullary and papillary thyroid cancers. Selpercatinib and pralsetinib, both specific RET-kinase inhibitors, are the only FDA-approved drugs for treating RET-altered thyroid cancer. We wanted to evaluate the safety and efficacy of selpercatinib and pralsetinib in RET-altered thyroid cancers. We searched the PubMed, Embase, Cochrane, and Clinicaltrials.gov databases for randomized controlled trials and observational studies published up to March 30, 2024, and included those that reported any of the desired endpoints. The primary endpoints were 1-year progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Quantitative analyses were performed using the R programming language. We included four studies with 560 patients, 510 with RET-mutant and 50 with RET-fusion thyroid cancer. The 1-year PFS was 84% (95% CI, 79-88, I 2 = 43%), ORR was 69% (95% CI, 65-73, I 2 = 0) and DCR was 93% (95% CI, 89-96, I 2 = 44%). Some important grade ≥3 adverse events were hypertension (16%; 95% CI, 11-22; I 2 = 43%), diarrhea (3%; 95% CI, 2-5; I 2 = 0), increased ALT (11%; 95% CI, 8-14; I 2 = 0) and increased AST (6%; 95% CI, 4-10; I 2 = 0). In conclusion, these findings suggest that selpercatinib and pralsetinib are efficacious and safe for use in patients with RET-altered thyroid cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential activity of specific inhibitors of transcription regulating cyclin-dependent kinases in thyroid cancer cells. 甲状腺癌细胞中调节周期蛋白依赖性激酶的特异性转录抑制剂的差异活性。

Endocrine-related cancer Pub Date : 2025-05-29 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0124

Neel Rajan, Tilak Khanal, Amy Adik, Anisley Valenciaga, Akanksha Nigam, Sandya Liyanarachchi, Matthew D Ringel

{"title":"Differential activity of specific inhibitors of transcription regulating cyclin-dependent kinases in thyroid cancer cells.","authors":"Neel Rajan, Tilak Khanal, Amy Adik, Anisley Valenciaga, Akanksha Nigam, Sandya Liyanarachchi, Matthew D Ringel","doi":"10.1530/ERC-24-0124","DOIUrl":"10.1530/ERC-24-0124","url":null,"abstract":"'Superenhanced' transcription of oncogenes by aberrant looping of upstream enhancer elements to transcriptional regulatory regions is a mechanism of oncogene overexpression. Non-selective cyclin-dependent kinase inhibitors (CDKi) that target transcriptionally regulatory CDKs, including CDK7, 9, 12 and 13, reduce mRNA levels of super-enhanced oncogenes and have activity against thyroid cancer cells. We hypothesized that more specific inhibitors of CDKs would have differential activities in thyroid cancer cells and may be suitable for further studies. We selected thyroid cancer cell lines with a variety of genetic drivers for initial screening studies with CDK7/12/13 (THZ1) and CDK9 (AZD4573) inhibitors. IC50 values ranged from 5 to 100 nM for THZ1 for all cell lines and six of eight cell lines for AZD4573, with inhibition of RNAPII phosphorylation and evidence of reduced cell migration. Four thyroid cancer cell lines with common driver mutations, including 8505C (BRAFV600E), BCPAP (BRAFV600E), TPC1 (RET fusion) and FTC133 (PTEN null), were selected for detailed studies with more specific inhibitors. In these cells, the CDK 12/13 inhibitor (SR-4835) and AZD4573 were more effective than the specific CDK7 inhibitor YKL-5-124 at reducing cell survival, migration and proliferation, and at inducing apoptosis. Treatment with SR-4835 was the most potent, induced DNA damage and resulted in cyclin K loss. Combined reduction in CDK12/13 levels with siRNA reduced RNAPII phosphorylation. These data suggest that specific inhibitors of CDK12/13 may be particularly active in thyroid cancer cell lines; further studies evaluating their efficacy are warranted in thyroid cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vivo and in vitro analysis of functional effects of the SDHD H50R variant. sddd H50R变异的体内外功能效应分析。

Endocrine-related cancer Pub Date : 2025-05-14 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0337

Shivam Priya, Karthik Chakravarthy, Edward Ziegler, Xavier Vesco, Krista La Perle, Xiaoli Zhang, Lawrence S Kirschner

{"title":"In vivo and in vitro analysis of functional effects of the SDHD H50R variant.","authors":"Shivam Priya, Karthik Chakravarthy, Edward Ziegler, Xavier Vesco, Krista La Perle, Xiaoli Zhang, Lawrence S Kirschner","doi":"10.1530/ERC-24-0337","DOIUrl":"10.1530/ERC-24-0337","url":null,"abstract":"Germline mutations in the four genes (SDHA, SDHB, SDHC and SDHD) encoding the succinate dehydrogenase (SDH) holoenzyme are known to predispose towards the development of tumor including pheochromocytomas/paragangliomas (PPGLs), gastrointestinal stromal tumors (GISTs), clear cell renal cancers (RCC) and possibly others. Mutations in these genes have also been described in patients with Cowden syndrome, which includes tumors of the breast, brain and thyroid gland. Although nonsense mutations are clearly pathogenic, the functional consequences of many missense mutations are unclear. It has previously been reported that the missense mutations SDHDG12S and SDHDH50R predispose to thyroid and breast cancers, although this characterization has been disputed. To address this question, we developed mouse models to test tumorigenicity of these variants. The reference mouse genome codes for a serine at residue 12 in Sdhd, so this variant was not pursued further. To assess the role of SDHDH50R (H50R), we generated a knock-in mouse allele for this variant and studied its effects in vivo as well as in vitro in mouse embryonic fibroblasts. Unlike null alleles for Sdhd, the H50R allele did not produce embryonic lethality when homozygous. There was no statistically significant difference in survival or tumor formation in homozygous or heterozygous animals compared to littermate controls. In vitro studies similarly failed to detect significant differences in proliferation, colony formation or metabolic function. Based on our analysis of this allele's function both in vivo and in vitro, we conclude that the SDHDH50R allele is most likely a non-pathogenic polymorphism.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of multikinase inhibitors in reshaping the treatment of advanced gastroenteropancreatic neuroendocrine tumors. 多激酶抑制剂对晚期胃肠胰神经内分泌肿瘤治疗的影响。

Endocrine-related cancer Pub Date : 2025-05-01 DOI: 10.1530/ERC-25-0052

Alexander R Siebenhüner, Julie Refardt, Guillaume P Nicolas, Reto Kaderli, Martin Walter, Aurel Perren, Emanuel Christ

{"title":"Impact of multikinase inhibitors in reshaping the treatment of advanced gastroenteropancreatic neuroendocrine tumors.","authors":"Alexander R Siebenhüner, Julie Refardt, Guillaume P Nicolas, Reto Kaderli, Martin Walter, Aurel Perren, Emanuel Christ","doi":"10.1530/ERC-25-0052","DOIUrl":"https://doi.org/10.1530/ERC-25-0052","url":null,"abstract":"Neuroendocrine tumors (NETs) pose a considerable challenge due to their increasing incidence and frequently late-stage diagnosis. The arrival of multikinase inhibitors (MKIs) into clinical practice has brought notable progress in the management of advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This review aims at exploring the impact of MKIs in reshaping the treatment landscape for advanced GEP-NETs. Current approaches in managing advanced GEP-NETs are discussed, including somatostatin analogs, surgery, peptide receptor radionuclide therapy (PRRT), and approved systemic treatments such as everolimus or sunitinib. The limitations and challenges faced in treating these tumors remain significant. Here we review the clinical evidence supporting the use of everolimus as a targeted therapy, which has demonstrated improved progression-free survival (PFS), as well as the need for alternative therapies. Discussions focus on the clinical effectiveness and the emerging role of both established and novel MKIs in the treatment of GEP-NETs, including recent evidence from the CABINET trial and other emerging agents such as surufatinib, axitinib, pazopanib, and lenvatinib. We explore the clinical evidence that showcases sunitinib's and other MKIs' effectiveness in prolonging PFS compared to placebo in advanced GEP-NETs. Recently, MKIs have shown to have a significant impact for treatment of advanced GEP-NETs. There remain several unmet needs that must be addressed, particularly regarding optimal treatment sequencing and the development of predictive biomarkers. Ongoing research and the use of current and emerging MKIs hold great potential to advance the treatment landscape for advanced GEP-NETs significantly.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrin-fibronectin interaction is a pivotal biological and clinical determinant in papillary thyroid carcinoma. 整合素-纤维连接蛋白相互作用是甲状腺乳头状癌的关键生物学和临床决定因素。

Endocrine-related cancer Pub Date : 2025-05-01 DOI: 10.1530/ERC-25-0101

Domenico Rocco, Anna Tortora, Vincenzo Marotta, Aline Maria Machado, Heloisa Sobreiro Selistre-de-Araujo, Mario Vitale

{"title":"Integrin-fibronectin interaction is a pivotal biological and clinical determinant in papillary thyroid carcinoma.","authors":"Domenico Rocco, Anna Tortora, Vincenzo Marotta, Aline Maria Machado, Heloisa Sobreiro Selistre-de-Araujo, Mario Vitale","doi":"10.1530/ERC-25-0101","DOIUrl":"10.1530/ERC-25-0101","url":null,"abstract":"Integrins influence tumor growth, metastasis, and angiogenesis, making them potential targets for therapeutic intervention. In this study, we analysed the TCGA mRNA-seq dataset to assess the expression levels of fibronectin (FN1) and associated integrin subunits, evaluating their relationship with clinical features in papillary thyroid cancer (PTC). These findings were further validated in a cell model. FN1 mRNA levels in BRAFV600E-positive PTC were 80-fold compared to normal thyroid tissue (NT), whereas PTC with RAS mutations exhibited FN1 levels similar to NT. ITGAV, encoding the αv integrin subunit, which pairs with β3 to form a receptor for FN, was also overexpressed in PTC. Elevated FN1 expression, and to a lesser extent ITGAV, correlated positively with lymph node metastasis, advanced cancer stages, extrathyroidal extension, and poorer prognoses. Patients in the highest quartile of FN1 expression had increased risk of disease recurrence (OR=7.277, 95% CI: 2.019 - 26.191, p < 0.0024). A non-tumoral thyroid cell line and two PTC cell lines were used as models to validate the mRNA-seq results. The proliferation and migration of a FN1 knock-out PTC cell mutant were significantly reduced and proliferation was restored upon the addition of soluble FN. DisBa-01, a recombinant RGD-disintegrin derived from Bothrops alternatus snake venom, that acts as an antagonist to the FN/αvβ3 interaction, inhibited PTC cell proliferation and migration. These results demonstrate that FN expression is a hallmark of aggressiveness in PTC. FN/αvβ3 interaction plays a pivotal role in PTC, suggesting that the FN/αvβ3 signalling is a potential therapeutic target for disintegrins or other molecules with similar action.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peptide receptor radionuclide therapy in malignant insulinoma. 肽受体放射性核素治疗恶性胰岛素瘤。

Endocrine-related cancer Pub Date : 2025-05-01 DOI: 10.1530/ERC-25-0018

David A Pattison, Grace Kong, Timothy Akhurst, Matthew Burge, Cherie Chiang, Michael S Hofman, Te-Jui Hung, Amanda Love, Michael Michael, Satomi Okano, Aravind S Ravi Kumar, Nirupa Sachithanandan, David Wyld, Rodney J Hicks

{"title":"Peptide receptor radionuclide therapy in malignant insulinoma.","authors":"David A Pattison, Grace Kong, Timothy Akhurst, Matthew Burge, Cherie Chiang, Michael S Hofman, Te-Jui Hung, Amanda Love, Michael Michael, Satomi Okano, Aravind S Ravi Kumar, Nirupa Sachithanandan, David Wyld, Rodney J Hicks","doi":"10.1530/ERC-25-0018","DOIUrl":"10.1530/ERC-25-0018","url":null,"abstract":"Management of malignant insulinoma (MI) presents dual management challenges of hypoglycaemia and tumour control. This study aims to analyse long-term outcomes of PRRT for treatment of MI. We retrospectively reviewed consecutive patients with MI treated with [177Lu]Lu-DOTATATE (LuTATE) at two Australian NET centres between 2004-2022. Follow-up for hypoglycaemia, molecular imaging, radiologic and biochemical responses, treatment-related side-effects, progression free- and overall-survival were assessed. Of 15 patients (7 female; median age 60, range 26-82) treated for intractable hypoglycaemia WHO Grade (G) was known in 12 patients (3 G1, 6 G2 and 3 G3). PRRT was administered median 7 cycles (range 1-15) with median cumulative activity 42GBq (range 4-117GBq) and radiosensitizing chemotherapy in 9/15 (60%). Resolution of hypoglycaemia was observed in 14/15 (93%) patients after median 2.5 months (range 0.2-23.5) but recurred in 7/14 cases after median 17.7 months (range 7.6-48.3). Patients with recurrent hypoglycaemia had longer time to hypoglycaemia resolution (median 3.0 vs 0.5 months), were more likely G3 (57% vs 0%) and experienced higher mortality (86% vs 29%). In all 7 cases, PRRT re-treatment was successful. Duration of hypoglycaemia remission was median 23.8 months (range 9.2-101). Median progression free- and overall-survival was 17.9 months (95% CI, 8.5-43.2) and 50.1 months (95% CI, 23.0-ND) respectively. Side-effects included G3/4 myelosupression in 4/15 patients, and hypoglycaemia flare (hospitalisation >48 hours) in 7/15 patients. PRRT provides durable hypoglycaemic and oncologic disease control of MI with manageable toxicity including hypoglycaemia flare requiring multidisciplinary care.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Familial Mahvash disease with metastatic pancreatic NET and MEN1 mutations. 家族性Mahvash病伴转移性胰腺NET和MEN1突变。

Endocrine-related cancer Pub Date : 2025-05-01 DOI: 10.1530/ERC-25-0087

Jelka Kuiper, Wouter W de Herder, Yassine Ben Brahim, Marie-Louise F Van Velthuysen, Lodewijk A A Brosens, Richard A Feelders, Janneke G Langendonk, Ronald van Marion, Esther Korpershoek, Gunter Klöppel, Anja Wagner, Johannes Hofland

{"title":"Familial Mahvash disease with metastatic pancreatic NET and MEN1 mutations.","authors":"Jelka Kuiper, Wouter W de Herder, Yassine Ben Brahim, Marie-Louise F Van Velthuysen, Lodewijk A A Brosens, Richard A Feelders, Janneke G Langendonk, Ronald van Marion, Esther Korpershoek, Gunter Klöppel, Anja Wagner, Johannes Hofland","doi":"10.1530/ERC-25-0087","DOIUrl":"10.1530/ERC-25-0087","url":null,"abstract":"Homozygous pathogenic glucagon receptor (GCGR) mutations cause a syndrome with pancreatic glucagon cell hyperplasia and neoplasia (GCHN) and hyperglucagonemia without a glucagonoma syndrome named Mahvash disease. The disease follows an autosomal recessive course and is an exceptionally rare hereditary pancreatic neuroendocrine tumour (panNET) syndrome, with only seven cases documented in the literature. The study aims to elucidate the genotype-phenotype correlation in Mahvash disease and panNET development. Clinical features, molecular profile, pancreatic pathology, and follow-up were studied in detail in six of the 11 family members. The patients' medical records were reviewed up until November 2024. Eight family members were positive for the likely pathogenic GCGR c.455C<T(p.Ser152Phe) germline variant. Three of the family members were homozygous for the GCGR germline variant. Two homozygous patients showed GCHN in pancreatic resection samples, with one of whom exhibiting lymphogenic and hepatic metastases. Three patients each had a glucagon-positive tumour with distinct somatic mutations in the MEN1 gene. One family member, heterozygous for the GCGR variant, presented with three small panNET, with the one biopsied lesion showing glucagon immunoreactivity. We report the first study of a single family with multiple members presenting with GCNH, caused by a novel germline GCGR variant. We are also presenting the first patient with liver metastases in GCHN and another patient with multiple small panNET heterozygous for the novel GCGR gene variant. Our observations highlight the malignant potential for GCHN and suggest that somatic MEN1 mutations may play a role in the development of glucagon-positive panNET from glucagon cell hyperplasia.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxygen regulates proliferation and phenotype in the RS0 SDH-deficient pheochromocytoma cell line. 氧调节RS0 sdh缺陷嗜铬细胞瘤细胞系的增殖和表型。

Endocrine-related cancer Pub Date : 2025-05-01 DOI: 10.1530/ERC-25-0022

James F Powers, Brent Cochran, James D Baleja, Inna Lomakin, Xue Zhang, Annette Shepard-Barry, Arthur S Tischler

{"title":"Oxygen regulates proliferation and phenotype in the RS0 SDH-deficient pheochromocytoma cell line.","authors":"James F Powers, Brent Cochran, James D Baleja, Inna Lomakin, Xue Zhang, Annette Shepard-Barry, Arthur S Tischler","doi":"10.1530/ERC-25-0022","DOIUrl":"https://doi.org/10.1530/ERC-25-0022","url":null,"abstract":"The RS0 cell line is a rat-derived pheochromocytoma line developed as a model to study pheochromocytoma/paraganglioma caused by hereditary mutations of the SDHB gene. Previous studies demonstrated that xenografts of the RS0 parent tumor replicate characteristics of their human counterparts, including loss of SDHB and upregulation of genes in hypoxia signaling pathways activated by EPAS1/HIF2A. Establishment of the cell line required a low O2 concentration, as cell proliferation was arrested in a traditional cell culture atmosphere of 20% O2. The present study profiled effects of 20% versus 5% O2 and EPAS1/HIF2A inhibitors on RS0 cell phenotype and tested how RS0 cells cultured under these influences compare to their parent xenografts and normal rat adrenal medulla. O2 concentration in cell cultures influences almost every aspect of the cells' biology, most obviously proliferation but also ultrastructure, transcriptome, metabolism and endocrine function. The cells most closely resemble their xenografts when maintained in a low O2 environment but some differences between the cells in vivo and in vitro are not fully explained. Genes downregulated in high O2 are predominantly associated with the cell cycle while those upregulated in low O2 include stemness and neuronal progenitor markers that may have contributed to establishment of the cell line, as well as drug targets expressed in human pheochromocytoma/paraganglioma. Some effects of high O2 are mimicked by EPAS1/HIF2A inhibitors currently considered for treatment of metastatic Sdh-deficient PPGL while others may be HIF-independent. The cytostatic effect of EPAS1/HIF2A inhibitors is reversible, suggesting possible limits to their usefulness as monotherapies.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FAM64A contributes to ovarian cancer proliferation and metastasis by suppressing TWIST1 ubiquitination degradation. FAM64A通过抑制TWIST1泛素化降解参与卵巢癌的增殖和转移。

Endocrine-related cancer Pub Date : 2025-05-01 DOI: 10.1530/ERC-24-0048

Juan Zhao, Ting Yang, Sijuan Tian, Meili Pei, Minyi Zhao, Li Wang, Xiaofeng Yang

{"title":"FAM64A contributes to ovarian cancer proliferation and metastasis by suppressing TWIST1 ubiquitination degradation.","authors":"Juan Zhao, Ting Yang, Sijuan Tian, Meili Pei, Minyi Zhao, Li Wang, Xiaofeng Yang","doi":"10.1530/ERC-24-0048","DOIUrl":"10.1530/ERC-24-0048","url":null,"abstract":"Ovarian cancer is among the most common cancers among gynecological malignancies. FAM64A is associated with various cancer progressions, but its function and mechanism in ovarian cancer remain unclear. We analyzed and examined the expression of FAM64A in ovarian cancer cells and tissues. The proliferation, migration, and invasion were assessed by knocking down and overexpressing FAM64A in A2780 and SKOV3 cells, respectively. Bioinformatics combined with molecular experiments validated the molecular mechanism of FAM64A. The xenograft tumor model and lung metastasis model were created to explore the impact of FAM64A on tumor growth and metastasis of the nude mice. To evaluate the relative signaling molecule expression, immunohistochemistry (IHC) and Western blot assays were conducted. FAM64A was up-regulated in ovarian cancer tissues and cells and demonstrated to promote the proliferation, migration, and invasion of A2780 and SKOV3 cells in vitro. Bioinformatics and western blot assay indicated that FAM64A could regulate EMT-related transcription factor TWIST1 by suppressing TWIST1 ubiquitination and degradation via the E3 ubiquitin ligase STUB1. Moreover, the Knockdown of FAM64A inhibited tumor growth of xenograft tumor mice and lung metastasis in vivo. FAM64A exerts its oncogene function via regulating TWIST1 ubiquitination and degradation, indicating that FAM64A may provide a promising therapeutic target for the treatment of ovarian cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0