Endocrine-related cancer最新文献_第2页

Vemurafenib activates the sonic hedgehog pathway and promotes thyroid cancer stem cell self-renewal. Vemurafenib激活声波hedgehog通路，促进甲状腺癌症干细胞自我更新。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-27 Print Date: 2023-11-01 DOI: 10.1530/ERC-22-0392

Yurong Lu, Yuqing Zhao, Penggang Liu, Xiulong Xu

{"title":"Vemurafenib activates the sonic hedgehog pathway and promotes thyroid cancer stem cell self-renewal.","authors":"Yurong Lu, Yuqing Zhao, Penggang Liu, Xiulong Xu","doi":"10.1530/ERC-22-0392","DOIUrl":"10.1530/ERC-22-0392","url":null,"abstract":"B-Raf kinase inhibitors such as vemurafenib (PLX4032) and dabrafenib have limited therapeutic efficacy on BRAF-mutated thyroid cancer. Cancer stem cells (CSCs) play important roles in tumor recurrence, drug resistance, and metastasis. Whether CSCs play a role in dampening the antitumor activity of B-Raf kinase inhibitors remains unknown. Here, we report that vemurafenib (PLX4032) induced the expression of several stemness-related genes including Gli1, Snail, BMI1, and SOX2 in two anaplastic thyroid cancer cell lines, SW1736 and 8505C, but decreased the expression of these genes in A375 cells, a human melanoma cell line. PLX4032 promoted thyroid cancer stem cell self-renewal, as evidenced by increased numbers of aldehyde dehydrogenase-positive cells and thyrospheres. Mechanistically, PLX4032 activates the PI-3 and mitogen-activated protein kinase pathways through HER3 to cross-activate Gli1, a transcription factor of the sonic hedgehog (Shh) pathway. GANT61, a specific inhibitor of Gli1, blocked the expression of the stemness-related genes in PLX4032-treated thyroid cancer cells in vitro and in vivo in two thyroid cancer xenograft models. GANT61 treatment alone weakly inhibited SW1736 tumor growth but enhanced the antitumor activity of PLX4032 when used in combination. Our study provides mechanistic insights into how thyroid cancer poorly responds to B-Raf kinase inhibitors and suggests that targeting B-Raf and the Shh pathway in combination may overcome thyroid cancer drug resistance.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Embryonic stem cell factor FOXD3 (Genesis) defects in gastrointestinal stromal tumors. 胃肠道间质瘤中的胚胎干细胞因子FOXD3（Genesis）缺陷。

IF 4.1 2区医学

Endocrine-related cancer Pub Date : 2023-09-11 Print Date: 2023-10-01 DOI: 10.1530/ERC-23-0067

Fabio R Faucz, Anelia D Horvath, Guillaume Assié, Madson Q Almeida, Eva Szarek, Sosipatros Boikos, Anna Angelousi, Isaac Levy, Andrea G Maria, Ajay Chitnis, Cristina R Antonescu, Rainer Claus, Jérôme Bertherat, Christoph Plass, Charis Eng, Constantine A Stratakis

{"title":"Embryonic stem cell factor FOXD3 (Genesis) defects in gastrointestinal stromal tumors.","authors":"Fabio R Faucz, Anelia D Horvath, Guillaume Assié, Madson Q Almeida, Eva Szarek, Sosipatros Boikos, Anna Angelousi, Isaac Levy, Andrea G Maria, Ajay Chitnis, Cristina R Antonescu, Rainer Claus, Jérôme Bertherat, Christoph Plass, Charis Eng, Constantine A Stratakis","doi":"10.1530/ERC-23-0067","DOIUrl":"10.1530/ERC-23-0067","url":null,"abstract":"Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms, believed to originate from the interstitial cells of Cajal (ICC), often caused by overexpression of tyrosine kinase receptors (TKR) KIT or PDGFRA. Here, we present evidence that the embryonic stem cell factor FOXD3, first identified as 'Genesis' and involved in both gastrointestinal and neural crest cell development, is implicated in GIST pathogenesis; its involvement is investigated both in vitro and in zebrafish and a mouse model of FOXD3 deficiency. Samples from a total of 58 patients with wild-type GISTs were used for molecular analyses, including Sanger sequencing, comparative genomic hybridization, and methylation analysis. Immunohistochemistry and western blot evaluation were used to assess FOXD3 expression. Additionally, we conducted in vitro functional studies in tissue samples and in transfected cells to confirm the pathogenicity of the identified genetic variants. Germline partially inactivating FOXD3 sequence variants (p.R54H and p.Ala88_Gly91del) were found in patients with isolated GISTs. Chromosome 1p loss was the most frequent chromosomal abnormality identified in tumors. In vitro experiments demonstrate the impairment of FOXD3 in the presence of those variants. Animal studies showed disruption of the GI neural network and changes in the number and distribution in the ICC. FOXD3 suppresses KIT expression in human cells; its inactivation led to an increase in ICC in zebrafish, as well as mice, providing evidence for a functional link between FOXD3 defects and KIT overexpression leading to GIST formation.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 10","pages":""},"PeriodicalIF":4.1,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10564589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10560191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intratumour microbiota modulates adrenocortical cancer responsiveness to mitotane. 肿瘤内微生物群调节癌症肾上腺皮质对米托坦的反应。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-11 Print Date: 2023-10-01 DOI: 10.1530/ERC-23-0094

Giulia Cantini, Elena Niccolai, Letizia Canu, Leandro Di Gloria, Simone Baldi, Arianna Pia Propato, Laura Fei, Giulia Nannini, Soraya Puglisi, Gabriella Nesi, Matteo Ramazzotti, Amedeo Amedei, Michaela Luconi

{"title":"Intratumour microbiota modulates adrenocortical cancer responsiveness to mitotane.","authors":"Giulia Cantini, Elena Niccolai, Letizia Canu, Leandro Di Gloria, Simone Baldi, Arianna Pia Propato, Laura Fei, Giulia Nannini, Soraya Puglisi, Gabriella Nesi, Matteo Ramazzotti, Amedeo Amedei, Michaela Luconi","doi":"10.1530/ERC-23-0094","DOIUrl":"10.1530/ERC-23-0094","url":null,"abstract":"The infiltrating microbiota represents a novel cellular component of the solid tumour microenvironment that can influence tumour progression and response to therapy. Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy for which mitotane (MTT) treatment represents the first-line therapy, though its efficacy is limited to a therapeutic window level (14–20 mg/L). Novel markers able to predict those patients who would benefit from MTT therapy are urgently needed to improve patient’s management. The aim of our study was to evaluate the presence of intratumoural bacterial microbiota DNA in 26 human ACC tissues vs 9 healthy adrenals; moreover, the association between the relative bacterial composition profile, the tumour mass characteristics and MTT ability to reach high circulating levels in the early phase of treatment, were explored. We found the presence of bacterial DNA in all adrenal samples from both tumours and healthy cortex specimens, documenting significant differences in the microbial composition between malignancy and normal adrenals: in detail, the ACC tissues were characterised by a higher abundance of the Proteobacteria phylum (especially the Pseudomonas and Serratia genera). In addition, the Proteobacteria’s low abundance was negatively associated with tumour size, Ki67 and cortisol secretion. MTT levels reached higher levels at 9 months in ACC patients with high abundance of Proteobacteria, Pseudomonas and Serratia and with low abundance of Bacteroidota, Firmicutes and Streptococcus. These findings are the first indication that human ACCs are characterised by infiltrating bacteria and their specific abundance profile seems to influence the increase in circulating MTT levels at 9 months.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GH and IGF1 in cancer therapy resistance. 生长激素和IGF1在肿瘤治疗耐药中的作用。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-01 DOI: 10.1530/ERC-22-0414

Reetobrata Basu, John Kopchick

引用次数: 0

Chromosomal alterations in sporadic medullary thyroid carcinoma and correlation with outcome. 散发性甲状腺髓样癌的染色体改变及其与预后的关系。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-01 DOI: 10.1530/ERC-22-0251

Teresa Ramone, Cristina Romei, Raffaele Ciampi, Roberta Casalini, Angelo Valetto, Veronica Bertini, Francesco Raimondi, Anthony Onoja, Alessandro Prete, Antonio Matrone, Carla Gambale, Paolo Piaggi, Liborio Torregrossa, Clara Ugolini, Rossella Elisei

{"title":"Chromosomal alterations in sporadic medullary thyroid carcinoma and correlation with outcome.","authors":"Teresa Ramone, Cristina Romei, Raffaele Ciampi, Roberta Casalini, Angelo Valetto, Veronica Bertini, Francesco Raimondi, Anthony Onoja, Alessandro Prete, Antonio Matrone, Carla Gambale, Paolo Piaggi, Liborio Torregrossa, Clara Ugolini, Rossella Elisei","doi":"10.1530/ERC-22-0251","DOIUrl":"https://doi.org/10.1530/ERC-22-0251","url":null,"abstract":"Somatic copy number alterations (SCNA) involving either a whole chromosome or just one of the arms, or even smaller parts, have been described in about 88% of human tumors. This study investigated the SCNA profile in 40 well-characterized sporadic medullary thyroid carcinomas by comparative genomic hybridization array. We found that 26/40 (65%) cases had at least one SCNA. The prevalence of SCNA, and in particular of chromosome 3 and 10, was significantly higher in cases with a RET somatic mutation. Similarly, SCNA of chromosomes 3, 9, 10 and 16 were more frequent in cases with a worse outcome and an advanced disease. By the pathway enrichment analysis, we found a mutually exclusive distribution of biological pathways in metastatic, biochemically persistent and cured patients. In particular, we found gain of regions involved in the intracellular signaling and loss of regions involved in DNA repair and TP53 pathways in the group of metastatic patients. Gain of regions involved in the cell cycle and senescence were observed in patients with biochemical disease. Finally, gain of regions associated with the immune system and loss of regions involved in the apoptosis pathway were observed in cured patients suggesting a role of specific SCNA and corresponding altered pathways in the outcome of sporadic MTC.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9927676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting growth hormone in cancer: future perspectives. 靶向生长激素治疗癌症:未来展望。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-01 DOI: 10.1530/ERC-23-0033

Yue Wang, Stephen M F Jamieson, Jo K Perry

引用次数: 1

Congenital IGF-1 deficiency protects from cancer: lessons from Laron syndrome. 先天性IGF-1缺乏可以预防癌症:从Laron综合征的经验教训。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-01 DOI: 10.1530/ERC-22-0394

Zvi Laron, Haim Werner

{"title":"Congenital IGF-1 deficiency protects from cancer: lessons from Laron syndrome.","authors":"Zvi Laron, Haim Werner","doi":"10.1530/ERC-22-0394","DOIUrl":"https://doi.org/10.1530/ERC-22-0394","url":null,"abstract":"Many clinical and experimental studies have implicated the growth hormone (GH)-insulin-like growth factor (IGF-1) axis with the progression of cancer. The epidemiological finding that patients with Laron syndrome (LS), the best-characterized disease under the spectrum of congenital IGF-1 deficiencies, do not develop cancer is of major scientific and translational relevance. The evasion of LS patients from cancer emphasizes the central role of the GH-IGF-1 system in cancer biology. To identify genes that are differentially expressed in LS and that might provide a biological foundation for cancer protection, we have recently conducted genome-wide profiling of LS patients and normal controls. Analyses were performed on immortalized lymphoblastoid cell lines derived from individual patients. Bioinformatic analyses identified a series of genes that are either over- or under-represented in LS. Differential expression was demonstrated in a number of gene families, including cell cycle, metabolic control, cytokine-cytokine receptor interaction, Jak-STAT and PI3K-AKT signaling, etc. Major differences between LS and controls were also noticed in pathways associated with cell cycle distribution, apoptosis, and autophagy. The identification of novel downstream targets of the GH-IGF-1 network highlights the biological complexity of this hormonal system and sheds light on previously unrecognized mechanistic aspects associated with GH-IGF-1 action in the cancer cell.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

One hundred years after the discovery of insulin and glucagon: the history of tumors and hyperplasias that hypersecrete these hormones. 胰岛素和胰高血糖素发现一百年后:肿瘤和增生过度分泌这些激素的历史。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-01 DOI: 10.1530/ERC-23-0046

Wouter W de Herder, Gunter Klöppel

引用次数: 0

Whole-exome sequencing of rectal neuroendocrine tumors. 直肠神经内分泌肿瘤的全外显子组测序。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-09-01 DOI: 10.1530/ERC-22-0257

Yuanliang Li, Yiying Guo, Zixuan Cheng, Chao Tian, Yingying Chen, Ruao Chen, Fuhuan Yu, Yanfen Shi, Fei Su, Shuhua Zhao, Zhizheng Wang, Jie Luo, Huangying Tan

{"title":"Whole-exome sequencing of rectal neuroendocrine tumors.","authors":"Yuanliang Li, Yiying Guo, Zixuan Cheng, Chao Tian, Yingying Chen, Ruao Chen, Fuhuan Yu, Yanfen Shi, Fei Su, Shuhua Zhao, Zhizheng Wang, Jie Luo, Huangying Tan","doi":"10.1530/ERC-22-0257","DOIUrl":"https://doi.org/10.1530/ERC-22-0257","url":null,"abstract":"The genetic characteristics of rectal neuroendocrine tumors (R-NETs) were poorly understood. Depicting the genetic characteristics may provide a biological basis for prognosis prediction and novel treatment development. Tissues of 18 R-NET patients were analyzed using whole-exome sequencing. The median tumor mutation burden (TMB) and microsatellite instability (MSI) were 1.15 Muts/MB (range, 0.03-23.28) and 0.36 (range, 0.00-10.97), respectively. Genes involved in P53 signaling, PI3K-AKT signaling, DNA damage repair, WNT signaling, etc. were frequently altered. Higher TMB (P = 0.078), higher CNV (P = 0.110), somatic mutation of CCDC168 (P = 0.049), HMCN1 (P = 0.040), MYO10 (P = 0.007), and amplification of ZC3H13 (P < 0.001) were associated with shorter OS. Potentially targetable gene alterations (PTGAs) were seen in 72% of the patients. FGFR1 amplification (22%) was the most common PTGA followed by BARD1 and BRCA2 mutation (each 17%). As for gene variations associated with the efficacy of immune checkpoint blockade (ICB), FAT1 alteration (39%) and PTEN depletion (28%) were commonly observed. In conclusion, frequently altered oncogenic pathways might contribute to the development and progression of R-NETs. Gene alterations significantly associated with prognosis might be potential novel targets. Targeted therapy might be a promising strategy as targetable alterations were prevalent in R-NETs. FAT1 alteration and PTEN depletion might be the main genetic alterations influencing the response to ICB besides overall low TMB and MSI in R-NETs.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10077145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The aggressiveness of succinate dehydrogenase subunit B-deficient chromaffin cells is reduced when their bioelectrical properties are restored by glibenclamide. 当格列本脲恢复琥珀酸脱氢酶亚基B缺陷嗜铬细胞的生物电特性时，其攻击性降低。

IF 3.9 2区医学

Endocrine-related cancer Pub Date : 2023-08-25 Print Date: 2023-10-01 DOI: 10.1530/ERC-23-0167

Francesca Amore, Rachele Garella, Alice Santi, Daniele Guasti, Serena Martinelli, Letizia Canu, Daniele Bani, Jiri Neuzil, Mario Maggi, Roberta Squecco, Elena Rapizzi

{"title":"The aggressiveness of succinate dehydrogenase subunit B-deficient chromaffin cells is reduced when their bioelectrical properties are restored by glibenclamide.","authors":"Francesca Amore, Rachele Garella, Alice Santi, Daniele Guasti, Serena Martinelli, Letizia Canu, Daniele Bani, Jiri Neuzil, Mario Maggi, Roberta Squecco, Elena Rapizzi","doi":"10.1530/ERC-23-0167","DOIUrl":"10.1530/ERC-23-0167","url":null,"abstract":"Pheochromocytomas/paragangliomas (PPGLs) are neuroendocrine tumours, mostly resulting from mutations in predisposing genes. Mutations of succinate dehydrogenase (SDH) subunit B (SDHB) are associated with high probability of metastatic disease. Since bioelectrical properties and signalling in cancer are an emerging field, we investigated the metabolic, functional and electrophysiological characteristics in human succinate dehydrogenase subunit B (SDHB)-deficient pheochromocytoma cells. These cells exhibited reduced SDH function with elevated succinate-to-fumarate ratio and reduced intracellular ATP levels. The analysis of membrane passive properties revealed a more hyperpolarized membrane potential and a lower cell capacitance of SDHB-deficient cells compared to the parental ones. These bioelectrical changes were associated with reduced proliferation and adhesion capacity of SDHB-deficient cells. Only in SDHB-deficient cells, we also observed an increased amplitude of potassium currents suggesting an activation of ATP-sensitive potassium channels (KATP). Indeed, exposure of the SDHB-deficient cells to glibenclamide, a specific KATP inhibitor, or to ATP caused normalization of potassium current features and altered proliferation and adhesion. In this work, we show for the first time that reduced intracellular ATP levels in SDHB-deficient chromaffin cells impaired cell bioelectrical properties, which, in turn, are associated with an increased cell aggressiveness. Moreover, we first ever demonstrated that glibenclamide not only reduced the outward potassium currents in SDHB-deficient cells but increased their growth capacity, reduced their ability to migrate and shifted their phenotype towards one more similar to that of parental one.","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10456596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0