Endocrine-related cancer最新文献_第2页

Cellular mechanisms of RET receptor dysfunction in multiple endocrine neoplasia 2. 多发性内分泌肿瘤中 RET 受体功能障碍的细胞机制 2.

Endocrine-related cancer Pub Date : 2024-12-13 Print Date: 2025-01-01 DOI: 10.1530/ERC-24-0187

Timothy J Walker, Lois M Mulligan

{"title":"Cellular mechanisms of RET receptor dysfunction in multiple endocrine neoplasia 2.","authors":"Timothy J Walker, Lois M Mulligan","doi":"10.1530/ERC-24-0187","DOIUrl":"10.1530/ERC-24-0187","url":null,"abstract":"Graphical abstract: Abstract: Rearranged during transfection (RET) is a developmentally important receptor tyrosine kinase that has been identified as an oncogenic driver in a number of cancers. Activating RET point mutations gives rise to the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2), characterized by medullary thyroid carcinoma. There are two MEN2 subtypes, MEN2A and MEN2B, that differ in tumour aggressiveness and the associated constellation of other disease features, which are caused by distinct patterns of RET amino acid substitution mutations. MEN2A-RET mutations affecting extracellular cysteine residues promote ligand-independent dimerization and constitutive RET activity, while MEN2B is caused by a single amino acid change in the tyrosine kinase domain of RET, releasing autoinhibition and producing a more active MEN2B-RET kinase that can promote signalling as monomers or dimers in the absence of a ligand. These mutations cause intrinsic biochemical changes in the RET structure and activation but also trigger extrinsic effects that alter RET cellular location, interactions and mechanisms of downregulation that can prolong or mislocate RET activity, changing or enhancing functional outcomes. Furthermore, changes in specific combinations of RET-mediated effects associated with different mutations give rise to the distinct MEN2 disease phenotypes. Here, we discuss the current understanding of the intrinsic and extrinsic characteristics of RET MEN2A cysteine and MEN2B mutants and how these contribute to transforming cellular processes and to the differences in tumour progression and disease aggressiveness.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515228","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

Mechanisms of RET-mediated signal transduction. RET 介导的信号转导机制。

Endocrine-related cancer Pub Date : 2024-12-13 Print Date: 2025-01-01 DOI: 10.1530/ERC-24-0131

Francesca Carlomagno, Marialuisa Moccia, Giorgia Federico, Massimo Santoro

引用次数: 0

ERRATUM: The role of oestrogen receptor α in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2. ERRATUM：雌激素受体α在人类甲状腺癌中的作用：核心调节蛋白和酪氨酸激酶受体HER2的贡献。

Endocrine-related cancer Pub Date : 2024-11-25 DOI: 10.1530/ERC-09-0216e

Dara O Kavanagh, Marie McIlroy, Eddie Myers, Fiona Bane, Thomas B Crotty, E McDermott, Arnold D Hill, Leonie S Young

引用次数: 0

AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma. AGO2 蛋白：作为肾上腺皮质癌新型生物标志物的 miRNA 通路中的一个关键酶。

Endocrine-related cancer Pub Date : 2024-11-20 Print Date: 2024-12-01 DOI: 10.1530/ERC-24-0061

Anila Hashmi, Alexander Papachristos, Stan Sidhu, Gyorgy Hutvagner

{"title":"AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma.","authors":"Anila Hashmi, Alexander Papachristos, Stan Sidhu, Gyorgy Hutvagner","doi":"10.1530/ERC-24-0061","DOIUrl":"10.1530/ERC-24-0061","url":null,"abstract":"Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy characterized by diagnostic challenges, high recurrence rates, and poor prognosis. This study explored the role of miRNA processing genes in ACC and their potential role as diagnostic and prognostic biomarkers. We analyzed the mRNA expression levels of miRNA machinery components (DROSHA, DGCR8, XPO5, RAN, DICER, TARBP2, and AGO2) utilizing mRNA-Seq data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) projects. Additionally, protein levels were quantified in tissue samples from the Kolling Institute of Medical Research's tumor bank. Our results demonstrated that among all miRNA processing components, AGO2 exhibited significant overexpression in ACC compared to the normal adrenal cortex and benign adrenal adenoma (P < 0.001). Kaplan-Meier survival analysis indicated that higher AGO2 expression correlated with significantly worse overall survival in ACC patients (HR: 7.07, P < 0.001). Among 32 cancer types in TCGA, the prognostic significance of AGO2 was most prominent in ACC. This study is the first to report AGO2's potential as a diagnostic and prognostic biomarker in ACC, emphasizing its significance in ACC pathogenesis and potential application as a non-invasive liquid biopsy biomarker.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484030","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

Impact of age on genomic alterations and the tumor immune microenvironment in papillary thyroid cancer. 年龄对甲状腺乳头状癌基因组改变和肿瘤免疫微环境的影响

Endocrine-related cancer Pub Date : 2024-11-04 Print Date: 2024-12-01 DOI: 10.1530/ERC-23-0341

Dominique D Liddy, Zhongyue Zhang, Kalyanee Shirlekar, Zhongping He, Kelly M Herremans, Song Han, Jason O Brant, Francis D Moore, Steven J Hughes, Aditya S Shirali

{"title":"Impact of age on genomic alterations and the tumor immune microenvironment in papillary thyroid cancer.","authors":"Dominique D Liddy, Zhongyue Zhang, Kalyanee Shirlekar, Zhongping He, Kelly M Herremans, Song Han, Jason O Brant, Francis D Moore, Steven J Hughes, Aditya S Shirali","doi":"10.1530/ERC-23-0341","DOIUrl":"10.1530/ERC-23-0341","url":null,"abstract":"Differentiated thyroid cancer in older adults has been linked to alterations in the mutational landscape and tumor immune cell infiltration that create a tumor-permissive microenvironment. We sought to determine the impact of age on genomic alterations and immune cell composition in papillary thyroid cancer (PTC). Genomic alterations, immune cell composition, and clinical data were obtained using The Cancer Genome Atlas and computational immunogenomic analyses. Disease severity was recoded into three groups: Group A (T1-2N0M0), Group B (T1-3N1a-1bM0), and Group C (T4NxMx or TxNxM1). Histopathologic subtypes included conventional, follicular-variant, and tall cell variant PTC. Spearman's rank correlation, ANOVA, t-test, and multivariable linear regression were performed. A total of 470 PTC samples were retrieved from the TCGA portal with genomic alteration and immune cell composition data. TERT promoter alterations were more common in patients aged ≥65 years (26% vs 4%, P < 0.0001). Tumor mutational burden increased with increasing age (r = 0.463, P < 0.0001). Increasing age was associated with decreased CD8+ T cells (r = -0.15, P = 0.01) using CIBERSORT and decreased B cells (r = -0.13), CD8+ T cells (r = -0.19), and neutrophils (r = -0.14, P < 0.05) using TIMER. Multivariate regression found that increasing age was independently associated with increased resting NK cells and resting dendritic cells, and decreased naïve B cells and CD8+ T cells (P < 0.05). PTC tumors of older adults are characterized by increased TERT promoter alterations, increased tumor mutational burden, and a decreased cytotoxic CD8+ T cells and increased resting dendritic cell immune infiltrate. Further studies are needed to determine if these changes in immune cell infiltrate are associated with compromised outcomes.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309472","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

Evaluating the prognostic potential of circulating cell-free DNA in advanced thyroid cancer. 评估晚期甲状腺癌循环游离 DNA 的预后潜力

Endocrine-related cancer Pub Date : 2024-11-01 DOI: 10.1530/ERC-24-0227

Ayanthi Wijewardene, Roderick J Clifton-Bligh, Bin Wang, Catherine Luxford, Bruce G Robinson, Martyn Bullock, Matti Gild

{"title":"Evaluating the prognostic potential of circulating cell-free DNA in advanced thyroid cancer.","authors":"Ayanthi Wijewardene, Roderick J Clifton-Bligh, Bin Wang, Catherine Luxford, Bruce G Robinson, Martyn Bullock, Matti Gild","doi":"10.1530/ERC-24-0227","DOIUrl":"https://doi.org/10.1530/ERC-24-0227","url":null,"abstract":"Liquid biopsies are a minimally invasive approach to obtain biomarkers including cell free DNA (cfDNA) from peripheral blood. Our study evaluated the utility of cfDNA in advanced thyroid cancers. Patients aged >18 years with metastatic medullary thyroid cancer (MTC), poorly differentiated thyroid cancer (PDTC), or anaplastic thyroid cancer (ATC) were enrolled in this prospective study between 2020 and 2024. As part of standard care, sequencing of germline and tumoral DNA was conducted, and patients with germline mutations were excluded from the study. Whole blood samples were collected in Streck cell-free DNA BCT tubes, cfDNA was extracted from plasma using the EZ1and2 ccfDNA kit and EZ2 Connect. The extracted cfDNA was then sequenced across 50 key cancer-related genes using the Oncomine Precision Assay (OPA) panel on an Ion Torrent Genexus Integrated Sequencer. Forty patients were included; 27 MTC, 2 ATC and 11 PDTC. Tumoral mutations were detected in 36 of the included patients (90%): cfDNA detected mutations in 18/36 patients (13 MTC, 1 ATC, 4 PDTC (50%). Sensitivity of cfDNA was 86% (6/7) pre TKI therapy, and reduced to 54% on therapy (13/24), suggestive of lack of tumor-derived DNA shedding with strong on-target treatment efficacy. Median cfDNA concentration was higher in samples with a detected mutation than those without, 11.91 ng/ml vs 5.81 ng/ml respectively. While an increasing cfDNA was associated with worse progression free survival (p < 0.01). cfDNA is a novel biomarker with potential to monitor disease progression in patients with advanced thyroid cancers.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741786","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

RETRACTION: Improvement of chemotherapeutic drug efficacy by endoplasmic reticulum stress. 返回：通过内质网应激提高化疗药物的疗效。

Endocrine-related cancer Pub Date : 2024-10-18 Print Date: 2024-11-01 DOI: 10.1530/ERC-15-0019r

Chrysovalantou Mihailidou, Ioulia Chatzistamou, Athanasios G Papavassiliou, Hippokratis Kiaris

引用次数: 0

Nutrition, GH/IGF-1 signaling, and cancer. 营养、GH/IGF-I 信号传导与癌症。

Endocrine-related cancer Pub Date : 2024-10-07 Print Date: 2024-11-01 DOI: 10.1530/ERC-23-0048

Maura Fanti, Valter D Longo

{"title":"Nutrition, GH/IGF-1 signaling, and cancer.","authors":"Maura Fanti, Valter D Longo","doi":"10.1530/ERC-23-0048","DOIUrl":"10.1530/ERC-23-0048","url":null,"abstract":"Cancer is the second leading cause of death in the United States and among the most prevalent diseases globally, with an incidence expected to grow because of smoking, pollution, poor dietary habits, obesity, and the rise in the older population. Given their ability to reduce risk factors, albeit with varying efficacy, nutrition and fasting could help prevent cancer and other age-related disorders. Calorie restriction (CR), various forms of intermittent fasting (IF) or periodic fasting (PF), and fasting-mimicking diets (FMDs) have been shown to improve health span, increase lifespan, and prevent or postpone cancer in rodents. The effects of specific diets and fasting regimens on aging and cancer appear to be mediated in part by the reduction in the activity of the growth hormone (GH)/insulin-like-growth-factor-I (IGF-1) axis. Nevertheless, recent data indicate that the alternation of low and normal levels of these hormones and factors may be ideal for optimizing longevity and function. Here, we review the role of nutrition, CR, and fasting/FMD on cancer, focusing on the hypothesis that the modulation of GH, IGF-1, and insulin signaling partly mediates the effect of these dietary interventions on cancer prevention.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019949","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

Management of advanced high grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): comprehensive review of the current literature. 晚期高级别胃肠胰神经内分泌肿瘤（GEP-NENs）的治疗：现有文献综述。

Endocrine-related cancer Pub Date : 2024-09-21 Print Date: 2024-10-01 DOI: 10.1530/ERC-24-0025

A Mohamed, M Trybula, S L Asa, T R Halfdanarson, M B Sonbol

{"title":"Management of advanced high grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): comprehensive review of the current literature.","authors":"A Mohamed, M Trybula, S L Asa, T R Halfdanarson, M B Sonbol","doi":"10.1530/ERC-24-0025","DOIUrl":"10.1530/ERC-24-0025","url":null,"abstract":"The classification and management of neuroendocrine neoplasms (NENs) arising in the tubular gastrointestinal (GI) tract and pancreas have significantly evolved over the last decades. In the latest WHO classification published in 2022, NENs are separated regardless of their primary origin into two main groups: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The substantial changes in the grading system changed the definition of grade 3 to include high-grade well-differentiated NETs (G3-NETs), and poorly differentiated NECs (-NECs). Although these two subgroups are considered high grades with Ki-67 >20%, they have different genomic profiles, prognosis, and clinical behavior, which critically influence their treatment strategies. The available clinical trial data to guide therapy of these high-grade subgroups are extremely limited, which impacts their management. In this review, we will summarize the current advances in the multidisciplinary approach for the management of high-grade gastroenteropancreatic NENs (GEP-NENs) including G3-NETs and NECs.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918391","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

Endocrine-related cancer Pub Date : 2024-09-21 Print Date: 2024-10-01 DOI: 10.1530/ERC-24-0111

Adam I Kaplan, Trisha Dwight, Catherine Luxford, Diana E Benn, Roderick J Clifton-Bligh

{"title":"SDHA-related phaeochromocytoma and paraganglioma: review and clinical management.","authors":"Adam I Kaplan, Trisha Dwight, Catherine Luxford, Diana E Benn, Roderick J Clifton-Bligh","doi":"10.1530/ERC-24-0111","DOIUrl":"10.1530/ERC-24-0111","url":null,"abstract":"Phaeochromocytomas and paragangliomas (collectively termed PPGL) are rare yet highly heritable neuroendocrine tumours, with over one-third of cases associated with germline pathogenic variants (PVs) in numerous genes. PVs in the succinate dehydrogenase subunit-A gene (SDHA) were initially implicated in hereditary PPGL in 2010, and SDHA has since become an important susceptibility gene accounting for up to 2.8% of cases. However, it remains poorly understood, particularly regarding the clinical nature of SDHA PPGL, rates of recurrence and metastasis, and the nature of metastatic disease. We present a narrative review of SDHA-related PPGL, covering pathophysiology, relevance to current clinical practice, and considerations for clinical genetics. We analyse a pool of 107 previously reported cases of SDHA-associated PPGL to highlight the spectrum of SDHA-related PPGL. Our analysis demonstrates that SDHA PPGL occurs across a wide age range (11-81 years) and affects men and women equally. SDHA PPGL typically presents as single tumours (91%), usually occurring in the head and neck (46%) or abdomen (43%, including 15% with phaeochromocytomas). Metastatic disease was reported in 25.5% of cases, with bone (82%) and lymph nodes (71%) being the most common sites of metastasis, often identified many years after the initial diagnosis. A family history of SDHA-related neoplasia was rare, reported in only 4% of cases. Understanding the clinical nature and risks associated with SDHA PVs is essential for facilitating the optimal management of patients and their families.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918392","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