Endocrine-related cancer最新文献_第5页

ob/ob obese mice promote tumorigenesis of endometrial cancer associated with Pten deficiency. 肥胖小鼠促进与Pten缺乏相关的子宫内膜癌的肿瘤发生。

Endocrine-related cancer Pub Date : 2025-03-27 Print Date: 2025-05-01 DOI: 10.1530/ERC-24-0228

Keun Cheon Kim, Amanda Hull, Eric Johannsen, Mark I Hunter, Tae Hoon Kim, Jae-Wook Jeong

{"title":"ob/ob obese mice promote tumorigenesis of endometrial cancer associated with Pten deficiency.","authors":"Keun Cheon Kim, Amanda Hull, Eric Johannsen, Mark I Hunter, Tae Hoon Kim, Jae-Wook Jeong","doi":"10.1530/ERC-24-0228","DOIUrl":"10.1530/ERC-24-0228","url":null,"abstract":"Obesity refers to the condition of being overweight due to abnormal fat accumulation and is highly associated with the development of various cancers. Endometrial cancer is the most diagnosed gynecologic cancer. Obesity is a strong risk factor for endometrial cancer. However, the etiological and pathophysiological effects of obesity on endometrial cancer have not been fully understood. To determine the effect of obesity on tumorigenesis in endometrial cancer, we examined the effect of obesity on tumorigenesis using genetically engineered mouse models, including an obesity model (ob/ob), an endometrial cancer model (Pgrcre/+Ptenf/f ; Ptend/d ), and an endometrial cancer with obesity model (Pgrcre/+Ptenf/fob/ob; Ptend/dob/ob). Histopathological analysis was performed on the uteri of the three groups during tumorigenesis. From 1.5 months of age, the body and uterine weight of Ptend/dob/ob mice were significantly higher than those of the Ptend/d mice. Ptend/dob/ob mice had higher tumor grade with myometrial invasion at 1.5 and 2 months than Ptend/d mice. The levels of phospho-histone H3, a proliferation marker and phospho-STAT3 were significantly increased in the endometrial cancer of Ptend/dob/ob mice compared to Ptend/d mice. Our results suggest that obesity accelerates the progression of endometrial cancer associated with Pten mutation.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CCL2 expression predicts clinical outcomes and regulates E-cadherin and angiogenesis in pituitary tumours. CCL2 的表达可预测临床结果，并调节垂体瘤中的 E-粘连蛋白和血管生成。

Endocrine-related cancer Pub Date : 2025-03-24 Print Date: 2025-05-01 DOI: 10.1530/ERC-24-0293

Ana Luísa Silva, Sayka Barry, Mariana Lopes-Pinto, Rita Joaquim, Catarina Miranda, Fábio Reis, Micaella Miranda, Paulo Matos, Oniz Suleyman, Tiago Oliveira, Dolores López-Presa, Gonçalo Borrecho, Francisco Tortosa, Claúdia C Faria, Márta Korbonits, Pedro Marques

{"title":"CCL2 expression predicts clinical outcomes and regulates E-cadherin and angiogenesis in pituitary tumours.","authors":"Ana Luísa Silva, Sayka Barry, Mariana Lopes-Pinto, Rita Joaquim, Catarina Miranda, Fábio Reis, Micaella Miranda, Paulo Matos, Oniz Suleyman, Tiago Oliveira, Dolores López-Presa, Gonçalo Borrecho, Francisco Tortosa, Claúdia C Faria, Márta Korbonits, Pedro Marques","doi":"10.1530/ERC-24-0293","DOIUrl":"10.1530/ERC-24-0293","url":null,"abstract":"The crosstalk between tumour cells and microenvironment components in pituitary neuroendocrine tumours (PitNETs), including chemokines, may impact tumour behaviour and clinical outcomes. CCL2 was previously identified as a key chemokine in PitNETs, but its role remains unknown. We aimed to study the role of CCL2 in defining the phenotype and clinical outcomes of PitNETs and in regulating macrophage chemotaxis, epithelial-to-mesenchymal transition (EMT) and angiogenesis. We studied CCL2 and E-cadherin expression, macrophages (CD68 and CD163) and vessels (CD31) in samples from 86 PitNET patients. Higher CCL2 mRNA expression was found in patients who required multimodal and multiple treatments and had active disease at the last follow-up. Higher CCL2 immunoreactivity was observed in patients with larger PitNETs. Among somatotroph tumours, CCL2 mRNA expression correlated with serum IGF-1 at the last follow-up. CCL2 mRNA expression levels correlated negatively with CDH1 expression and with E-cadherin complete membranous staining. In vitro, CCL2 downregulated E-cadherin expression in GH3 cells but did not affect cell morphology or migration. CCL2 expression correlated with the number of vessels, vessel perimeter and vessel area in PitNETs but not with PitNET-infiltrating macrophages. Our data suggest that CCL2 may lead to (or is at least a predictive marker of) poorer clinical outcomes and more difficult-to-treat PitNETs, potentially through its regulatory effects on different tumour-related mechanisms beyond immune cell chemotaxis, including in the activation of the EMT pathway and modulation of angiogenesis in PitNETs. Further studies are needed to corroborate our findings and to validate CCL2 as a potential predictive marker and therapeutic target in PitNETs.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589108","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

Clinical, genetic, radiological characteristics and management of mediastinal paragangliomas: a literature review and case series. 纵隔副神经节瘤的临床、遗传、放射学特征和治疗：文献回顾和病例系列。

Endocrine-related cancer Pub Date : 2025-03-24 Print Date: 2025-05-01 DOI: 10.1530/ERC-24-0279

Mark Quinn, Yasmine Kemkem, Gemma White, Phil Touska, Dimitra Christodoulou, Audrey Jacques, Louise Breen, Barbara McGowan, Mamta Joshi, Fahim Ul Hassan, Karen Harrison-Phipps, Johnathan G Hubbard, Rupert Obholzer, Louise Izatt, Paul Carroll, Anand Velusamy

{"title":"Clinical, genetic, radiological characteristics and management of mediastinal paragangliomas: a literature review and case series.","authors":"Mark Quinn, Yasmine Kemkem, Gemma White, Phil Touska, Dimitra Christodoulou, Audrey Jacques, Louise Breen, Barbara McGowan, Mamta Joshi, Fahim Ul Hassan, Karen Harrison-Phipps, Johnathan G Hubbard, Rupert Obholzer, Louise Izatt, Paul Carroll, Anand Velusamy","doi":"10.1530/ERC-24-0279","DOIUrl":"10.1530/ERC-24-0279","url":null,"abstract":"Paragangliomas (PGLs) are neuroendocrine tumours (NETs) that arise from neural crest-derived cells. Up to 40% of cases occur due to the presence of a pathogenic germline variant (PGV) in a known gene. Mediastinal PGLs are rare but are being diagnosed with increasing frequency. Treatment generally involves surgery but is complicated in mediastinal PGLs due to their anatomy. Here, we will perform a literature review and discuss our experience with 18 such cases. Cases were identified via the Guy's and St Thomas' NHS Foundation Trust NET multidisciplinary team database. Tumours ranged in size from 0.6 × 0.6 to 6.8 × 4.9 cm. 72.2% were associated with a PGV of SDHB or SDHD. 22.2% developed metastatic disease, but it was only possible to attribute 50% of these to a mediastinal primary. 68Ga-DOTATATE PET CT demonstrated 100% sensitivity. The literature review identified 233 cases. A PGV was reported in 81% of cases, with metastatic disease in approximately 39.2%. It was not possible to confirm that all cases of metastatic disease were secondary to a mediastinal primary. Our experience confirms the high rate of mediastinal PGLs arising in the presence of a PGV. The lower rate of metastatic disease in our cohort (11.1%) likely represents earlier diagnosis thanks to the application of screening protocols and the increased sensitivity of 68Ga-DOTATATE PET CT. With this increased sensitivity, we have diagnosed small mediastinal PGLs that were not evident on alternative imaging modalities. In the absence of growth or catecholamine secretion, the need to intervene on these is unclear.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased cancer risk in a cohort of patients with acromegaly in Israel. 以色列肢端肥大症患者的癌症风险增加。

Endocrine-related cancer Pub Date : 2025-03-24 Print Date: 2025-05-01 DOI: 10.1530/ERC-24-0087

Hadar Duskin-Bitan, Alon Perez, Doron Netzer, Arnon D Cohen, Doron Comaneshter, Tanya Beckenstein, Shlomit Yaron, Zaina Adnan, Yaron Rudman, Hiba Masri Iraqi, Ilan Shimon

{"title":"Increased cancer risk in a cohort of patients with acromegaly in Israel.","authors":"Hadar Duskin-Bitan, Alon Perez, Doron Netzer, Arnon D Cohen, Doron Comaneshter, Tanya Beckenstein, Shlomit Yaron, Zaina Adnan, Yaron Rudman, Hiba Masri Iraqi, Ilan Shimon","doi":"10.1530/ERC-24-0087","DOIUrl":"10.1530/ERC-24-0087","url":null,"abstract":"The association between acromegaly and cancer had been assessed mainly in population studies with inconsistent results. The objective of this study was to investigate the risk of cancer in a large cohort of patients with acromegaly compared with matched controls. The comprehensive computerized database of the largest healthcare provider organization in Israel was searched for patients diagnosed with acromegaly in 2000-2021. All diagnoses were qualitatively validated. Patients were individually matched 1:5 with a control group for age, sex and socioeconomic status. Clinical and outcome data were collected from medical files. The final cohort consisted of 470 patients (54% male) with acromegaly and 2,330 control subjects. The mean age at diagnosis was 53 years, and the mean duration of follow-up after diagnosis was 10.4 years. The prevalence of solid malignancies was 21.3% in the acromegaly group and 14.8% in the control group (OR 1.6, 95% CI 1.2-2.0). Patients with acromegaly had a higher rate of thyroid cancer (2.8 vs 0.6%; OR 5.1, CI 2.3-11.0) and a tendency for a higher risk of colorectal cancer (3.6 vs 2.8%; OR 1.3, CI 0.7-2.2), prostate cancer (2.8 vs 1.7%; OR 1.6, CI 0.8-3.1) and renal cancer (1.5 vs 0.8%; OR 1.8, CI 0.8-4.4), but not hematological malignancies. They also had a higher mortality rate (21.3 vs 15.7%; OR 1.5, CI 1.1-1.9). In conclusion, the higher prevalence of malignant solid tumors in patients with acromegaly compared with control subjects suggests that periodic screening for early detection of solid cancers may be considered in this patient population.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588679","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

Mannose enhances anti-tumor effect of PLX4032 in anaplastic thyroid cancer. 甘露糖增强PLX4032对间变性甲状腺癌的抗肿瘤作用。

Endocrine-related cancer Pub Date : 2025-03-24 Print Date: 2025-05-01 DOI: 10.1530/ERC-24-0209

Zhuolin Li, Liumei Song, Yuanxing Yang, Yang Zhao, Sharui Ma

{"title":"Mannose enhances anti-tumor effect of PLX4032 in anaplastic thyroid cancer.","authors":"Zhuolin Li, Liumei Song, Yuanxing Yang, Yang Zhao, Sharui Ma","doi":"10.1530/ERC-24-0209","DOIUrl":"10.1530/ERC-24-0209","url":null,"abstract":"Anaplastic thyroid cancer represents the most aggressive form of thyroid cancer and harbors BRAF mutations in over 40% of cases. Vemurafenib (PLX4032), a BRAF kinase inhibitor, shows promise in BRAFV600E-positive advanced thyroid cancer but may promote resistance in anaplastic cases. This study investigates whether mannose, known to selectively inhibit thyroid cancer, enhances PLX4032 efficacy. To evaluate whether mannose could enhance the response of anaplastic thyroid cancer cells to vemurafenib, we employed several in vitro assays, including MTT, colony formation, flow cytometry, migration and invasion assays. In addition, we performed in vivo assays using mouse models with subcutaneous xenografts. Our findings demonstrated that vemurafenib and mannose synergistically inhibit anaplastic thyroid cancer cell proliferation. The combined treatment significantly impeded anaplastic thyroid cancer cell migration and invasion while promoting apoptosis. In vivo studies corroborated these observations. The underlying mechanism by which mannose potentiates the antitumor effects of vemurafenib was explored using the Seahorse XFe96 Analyzer to measure glycolysis parameters and Western blotting to assess the expression of associated proteins. Mechanistically, vemurafenib reduced the expression of ZIP10, which in turn decreased the enzyme activity of phosphomannose isomerase. This suppression of ZIP10 enhanced mannose-mediated inhibition of glycolysis and thus its antitumor effect, as confirmed by rescue experiments with ZIP10 overexpression. The resulting decrease in glycolysis led to lower ATP levels, which are essential for the phosphorylation of ERK and AKT. Therefore, the combination of vemurafenib and mannose inhibited the levels of pERK and pAKT, thereby improving the effectiveness of PLX4032 in treating anaplastic thyroid cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenotype of pheochromocytoma and paraganglioma by germline mutation: a Korean multicenter study. 由种系突变引起的嗜铬细胞瘤和副神经节瘤的表型：一项韩国多中心研究。

Endocrine-related cancer Pub Date : 2025-03-20 Print Date: 2025-05-01 DOI: 10.1530/ERC-24-0269

Min Jeong Park, Seung Shin Park, Bon Hyang Lee, Jin Sun Jang, Won Woong Kim, Su Jin Kim, Yu-Mi Lee, Kyu Eun Lee, Tae-Yon Sung, Moon-Woo Seong, Woochang Lee, Jung-Min Koh, Jung Hee Kim, Seung Hun Lee

{"title":"Phenotype of pheochromocytoma and paraganglioma by germline mutation: a Korean multicenter study.","authors":"Min Jeong Park, Seung Shin Park, Bon Hyang Lee, Jin Sun Jang, Won Woong Kim, Su Jin Kim, Yu-Mi Lee, Kyu Eun Lee, Tae-Yon Sung, Moon-Woo Seong, Woochang Lee, Jung-Min Koh, Jung Hee Kim, Seung Hun Lee","doi":"10.1530/ERC-24-0269","DOIUrl":"10.1530/ERC-24-0269","url":null,"abstract":"Recent advances in genetic testing have challenged the traditional genotype-phenotype correlation in pheochromocytomas and paragangliomas (PPGL). We aimed to characterize the genotype-phenotype correlations in PPGL in a large Korean cohort and compare our findings with those from other countries. We retrospectively analyzed 627 patients with PPGL from two centers who underwent genetic testing for germline pathogenic variants (PVs) from 2000 to 2023 to examine the prevalence of clusters and their correlation with specific phenotypes. Moreover, we systematically reviewed 44 studies that investigated the frequency of germline PVs based on geographical differences. Germline PVs were identified in 29.7% of patients (n = 186). The prevalence of cluster 1A, 1B and 2 PVs was 10.6% (n = 67), 8.0% (n = 50) and 11.1% (n = 69), respectively. Cluster 1 patients were presented with more aggressive features, including younger age at diagnosis (39 years), higher rates of extra-adrenal (44.4%), and metastatic (27.8%) tumors, than did the wild-type and cluster 2 groups (P < 0.001). Cluster 1A patients had significantly higher metastasis rates than cluster 1B patients (38.8 vs 12.5%; P < 0.001). The cluster 2 group showed a high recurrence risk but rarely developed metastases. The cluster 1-to-cluster 2 ratio among Koreans (1.7) was lower than that among Europeans (2.9) and North Americans (3.3). This study underscores the genetic and clinical heterogeneity of PPGL among Korean patients based on genetic clusters and highlights geographic variations in PVs. These findings have significant implications for risk stratification, surveillance and management strategies for patients with PPGL.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588686","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

Transforming thyroid cancer management: the impact of neoadjuvant therapy. 甲状腺癌治疗的变革：新辅助治疗的影响。

Endocrine-related cancer Pub Date : 2025-03-08 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0185

Inés Califano, Gregory Randolph, Fabián Pitoia

{"title":"Transforming thyroid cancer management: the impact of neoadjuvant therapy.","authors":"Inés Califano, Gregory Randolph, Fabián Pitoia","doi":"10.1530/ERC-24-0185","DOIUrl":"10.1530/ERC-24-0185","url":null,"abstract":"Neoadjuvant therapy has an emerging role in the management of locally advanced thyroid cancer. Recent developments in systemic therapies, particularly with the introduction of multikinase inhibitors and selective inhibitors, have demonstrated promising results. The objective of this review is to delve into the implications of these developments and their potential impact on the management of advanced thyroid cancers, which initially present as borderline resectable or unresectable. For differentiated thyroid cancer and poorly differentiated thyroid cancer, agents such as lenvatinib have shown substantial tumor reduction, facilitating surgical resection. Similarly, for medullary thyroid cancer, selpercatinib have exhibited interesting response rates, enhancing the feasibility of surgery with reduced morbidity in limited clinical case series of patients with RET mutations. In BRAF mutant ATC, the combination of BRAF and MEK inhibitors has significantly improved treatment protocols, providing a pathway to surgical intervention and significantly improving survival rates. The addition of immune checkpoint inhibitors to these regimens showed further extension of survival and reduced recurrence rates in retrospective studies that still need confirmation. Despite these preliminary favorable results, neoadjuvant therapies are not without challenges. The risk of adverse events, particularly related to the inhibition of the VEGF pathway, necessitates careful patient selection and management. The variability in tumor responses and the potential for serious complications underscore the need for continued research to refine these approaches in this difficult patient population.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443050","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

Divergent PTEN-p53 interaction upon DNA damage in a human thyroid organoid model with germline PTEN mutations. 不同PTEN-p53相互作用对生殖系PTEN突变的人甲状腺类器官模型DNA损伤的影响

Endocrine-related cancer Pub Date : 2025-03-08 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0216

Juan Andres Venegas, Omer Enes Onur, Shin Chung Kang, Masahiro Hitomi, Charis Eng

{"title":"Divergent PTEN-p53 interaction upon DNA damage in a human thyroid organoid model with germline PTEN mutations.","authors":"Juan Andres Venegas, Omer Enes Onur, Shin Chung Kang, Masahiro Hitomi, Charis Eng","doi":"10.1530/ERC-24-0216","DOIUrl":"10.1530/ERC-24-0216","url":null,"abstract":"Germline mutations in the tumor suppressor phosphatase and tensin homolog (PTEN) cause PTEN hamartoma tumor syndrome (PHTS). PHTS is characterized by an elevated lifetime risk of differentiated thyroid cancer (DTC), 30 times higher than the general population. However, only 1 in 3 PHTS patients develop DTC, and it remains unknown whether specific PTEN variants are associated with an increased risk of DTC. PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway, a frequently affected pathway in sporadic DTC. PTEN also acts as a guardian of the genome by interacting with other tumor suppressors. Here, we report how ionizing radiation, an environmental tumorigenic contributor, modifies the DNA damage response based on the type of germline PTEN variants. We hypothesized that certain PTEN variants associated with DTC create a pro-oncogenic molecular signature upon radiation-induced DNA damage. DTC-associated (PTEN M134R ) or DTC-non-associated (PTEN G132D ) germline PTEN mutant alleles were introduced into a human induced pluripotent cell (hiPSC) line derived from a healthy donor utilizing CRISPR-Cas9 gene editing technology. We determined radiation-induced transcriptomic changes in functional thyroid organoids induced from wild-type and both heterozygous PTEN mutant hiPSCs. Both bulk and single-cell RNA sequencing data indicated that radiation upregulated the p53 network more potently in the thyroid organoids with PTEN WT/G132D than those with PTEN WT/M134R , which could be mediated by AKT-dependent MDM2 inactivation and PTEN-p53 physical interaction. Our data suggest that the lack of p53 pathway activation through PTEN-p53 network interactions explains why PTEN M134R is a DTC-susceptible variant.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolically active brown adipose tissue in PPGL: an observational cohort study. PPGL中代谢活跃的棕色脂肪组织：一项观察性队列研究。

Endocrine-related cancer Pub Date : 2025-03-07 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0200

Eduard Oštarijaš, Michael C Onyema, Zoulikha Zair, David R Taylor, Fannie Lajeunesse-Trempe, Saira Reynolds, Nicola Mulholland, Ben Corcoran, Mohamed Halim, Eftychia E Drakou, Ashley B Grossman, Royce P Vincent, Simon J B Aylwin, Georgios K Dimitriadis, Silvija Canecki-Varžić

{"title":"Metabolically active brown adipose tissue in PPGL: an observational cohort study.","authors":"Eduard Oštarijaš, Michael C Onyema, Zoulikha Zair, David R Taylor, Fannie Lajeunesse-Trempe, Saira Reynolds, Nicola Mulholland, Ben Corcoran, Mohamed Halim, Eftychia E Drakou, Ashley B Grossman, Royce P Vincent, Simon J B Aylwin, Georgios K Dimitriadis, Silvija Canecki-Varžić","doi":"10.1530/ERC-24-0200","DOIUrl":"10.1530/ERC-24-0200","url":null,"abstract":"Brown adipose tissue (BAT) activity, identifiable through fluorodeoxyglucose positron emission tomography (FDG-PET), has gained interest due to its potential link with metabolic disorders and tumour pathophysiology. This study aims to explore the activation of BAT in patients with phaeochromocytoma/paraganglioma (PPGL) and its clinical relevance. This retrospective observational study, conducted in a large academic centre in London, reviewed FDG-PET images of 62 confirmed PPGL patients, collected between 2013 and 2021. We assessed patient demographics, biochemistry, radiological features, mutational status and outcomes, focussing on activated BAT detection. Of the 62 patients, 13% demonstrated active brown adipose tissue (aBAT) on FDG-PET imaging. Histopathological confirmation of BAT from one patient was used to validate BAT activation observed during imaging. Multivariate analysis indicated that elevated plasma normetanephrine concentrations were directly proportional to aBAT presence, suggesting their strong association with BAT activation. Despite identifying aBAT, no significant differences were found in BMI, sex, age or mutational status between aBAT-positive and aBAT-negative groups. Kaplan-Meier survival plots assessing overall and progression-free survival did not reach statistical significance. This study underscores the complex interaction between catecholamine excess and BAT activation in patients with PPGLs. The findings suggest that aBAT activity might be an indicator of severe catecholamine excess (especially normetanephrine), potentially influencing patient outcomes. Our study adds to the limited pool of knowledge and offers novel insights into BAT activation in patients with PPGLs, highlighting its potential link with metabolic derangements and patient outcomes.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discordant risk factors between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinoma. 胰腺神经内分泌肿瘤与胰腺导管腺癌不一致的危险因素。

Endocrine-related cancer Pub Date : 2025-03-01 Print Date: 2025-04-01 DOI: 10.1530/ERC-24-0142

Shruti Chandra, Thorvardur R Halfdanarson, Erin E Carlson, Kari G Rabe, Amit Mahipal, Shounak Majumder, William R Bamlet, Masayasu Horibe, Sri Harsha Tella, Omair Shariq, Ryan M Carr, Sean P Cleary, Ann L Oberg, Samuel O Antwi

{"title":"Discordant risk factors between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinoma.","authors":"Shruti Chandra, Thorvardur R Halfdanarson, Erin E Carlson, Kari G Rabe, Amit Mahipal, Shounak Majumder, William R Bamlet, Masayasu Horibe, Sri Harsha Tella, Omair Shariq, Ryan M Carr, Sean P Cleary, Ann L Oberg, Samuel O Antwi","doi":"10.1530/ERC-24-0142","DOIUrl":"10.1530/ERC-24-0142","url":null,"abstract":"Pancreatic neuroendocrine neoplasm (panNEN) is a rare malignancy and the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma (PDAC), but its etiology is poorly understood. We investigated whether the risk factors of panNEN are concordant with those known for PDAC. We performed the largest case-control study to date on panNENs, comprising 927 sporadic nonfunctional panNEN cases and 1807 frequency-matched controls, using data from the Mayo Clinic Biospecimen Resource for Pancreas Research. We assessed associations for obesity, first-degree family history of pancreatic cancer, cigarette smoking, overall type II diabetes mellitus (T2DM), new-onset T2DM (<1 year before panNEN diagnosis), longstanding T2DM (≥5 years), alcohol intake and aspirin use. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). Our results show that overall T2DM (OR = 1.71, 95% CI: 1.37-2.14) and new-onset T2DM (OR = 2.65, 95% CI: 1.92-3.69) are associated with higher odds of panNEN, but not longstanding T2DM (OR = 1.29, 95% CI: 0.94-1.75). A non-significant elevated odds of panNEN was observed among participants with a positive family history of pancreatic cancer (OR = 1.44, 95% CI: 0.96-2.14). Alcohol use was inversely related to panNEN (OR = 0.52, 95% CI: 0.42-0.66, ever-vs-never). No association was observed for smoking, obesity or aspirin use. These findings indicate that overall T2DM and new-onset T2DM are associated with higher odds of panNEN. Unlike PDAC, alcohol use was inversely related to panNEN, and we found no associations for cigarette smoking, obesity or aspirin use. These results indicate differences in the risk factor profiles of panNEN and PDAC.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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