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Role of B cells in intratumoral MBTA immunotherapy of murine pheochromocytoma model B 细胞在小鼠嗜铬细胞瘤模型瘤内 MBTA 免疫疗法中的作用
IF 7.4 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-11 DOI: 10.1016/j.beem.2024.101941
Ondrej Uher, Katerina Hadrava Vanova, Katerina Petrlakova, Rachael Labitt, Radka Lencova, Andrea Frejlachova, Juan Ye, Herui Wang, Michal Masarik, Jan Zenka, Zhengping Zhuang, Karel Pacak
Immunotherapy represents a revolutionary advancement in cancer treatment, which has traditionally focused on T cells; however, the role of B cells in cancer immunotherapy has gained interest because of their role in antigen presentation, antibody production, and cytokine release. In this study, we examined the role of B cells in previously developed intratumoral MBTA therapy (mannan-BAM, TLR ligands, and anti-CD40 antibody) in murine models of MTT pheochromocytoma. The results indicated that B cells significantly enhance the success of MBTA therapy, with wild-type mice exhibiting a lower tumor incidence and smaller tumors compared with B cell-deficient mice. Increased IL-6 and TNF-alpha levels indicated severe inflammation and a potential cytokine storm in B cell-deficient mice. Neutralization of TNF-alpha ameliorated these complications but resulted in increased tumor recurrence. The results highlight the important role of B cells in enhancing the immune response and maintaining immune homeostasis during MBTA therapy. Our findings offer new insights into improving therapeutic outcomes.
免疫疗法代表了癌症治疗的革命性进步,传统的癌症治疗主要集中在 T 细胞上;然而,由于 B 细胞在抗原呈递、抗体产生和细胞因子释放中的作用,它们在癌症免疫疗法中的作用也受到了关注。在本研究中,我们在 MTT 嗜铬细胞瘤小鼠模型中研究了 B 细胞在先前开发的瘤内 MBTA 疗法(甘露聚糖-BAM、TLR 配体和抗 CD40 抗体)中的作用。结果表明,B细胞能显著提高MBTA疗法的成功率,与B细胞缺陷小鼠相比,野生型小鼠的肿瘤发病率更低,肿瘤更小。IL-6和TNF-α水平升高表明B细胞缺陷小鼠存在严重的炎症和潜在的细胞因子风暴。中和 TNF-α 可改善这些并发症,但会导致肿瘤复发。这些结果突显了 B 细胞在 MBTA 治疗过程中增强免疫反应和维持免疫平衡的重要作用。我们的研究结果为改善治疗效果提供了新的见解。
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引用次数: 0
Recent progress in molecular classification of phaeochromocytoma and paraganglioma 嗜铬细胞瘤和副神经节瘤分子分类的最新进展
IF 7.4 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-07 DOI: 10.1016/j.beem.2024.101939
Emma Boehm, Anthony J. Gill, Roderick Clifton-Bligh, Richard W. Tothill
Phaeochromocytomas (PC) and paragangliomas (PG) are neural crest cancers with high heritability. Recent advances in molecular profiling, including multi-omics and single cell genomics has identified up to seven distinct molecular subtypes. These subtypes are defined by mutations involving hypoxia-inducible factors (HIFs), Krebs cycle, kinase and WNT signalling, but are also defined by chromaffin differentiation states. PCPG have a dominant proangiogenic microenvironment linked to HIF pathway activity and are generally considered “immune cold” tumours with a high number of macrophages. PCPG subtypes can indicate increased metastatic risk but secondary mutations in telomere maintenance genes or are required to drive the metastatic phenotype. Molecular profiling can identify molecular therapeutic (e.g. and ) and radiopharmaceutical targets while also helping to support variant pathogenicity and familial risk. Molecular profiling and subtyping of PCPG therefore confers the possibility of nuanced prognostication and individual treatment stratification but this still requires large-scale prospective validation.
辉色素细胞瘤(PC)和副神经节瘤(PG)是具有高度遗传性的神经嵴癌症。分子图谱分析(包括多组学和单细胞基因组学)的最新进展确定了多达七种不同的分子亚型。这些亚型由涉及缺氧诱导因子(HIFs)、克雷布斯循环、激酶和 WNT 信号的突变所定义,但也由嗜铬细胞分化状态所定义。PCPG 具有与 HIF 通路活性相关的主要促血管生成微环境,通常被认为是具有大量巨噬细胞的 "免疫冷 "肿瘤。PCPG 亚型可表明转移风险增加,但端粒维持基因的继发性突变或需要驱动转移表型。分子图谱分析可确定分子治疗(如和)和放射性药物靶点,同时也有助于支持变异致病性和家族风险。因此,PCPG 的分子图谱分析和亚型鉴定为细微的预后判断和个体治疗分层提供了可能,但这仍需要大规模的前瞻性验证。
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引用次数: 0
Overview of recent guidelines and consensus statements on initial screening and management of phaeochromocytoma and paraganglioma in SDHx pathogenic variant carriers and patients 关于 SDHx 致病变异携带者和患者中的嗜铬细胞瘤和副神经节瘤的初步筛查和管理的最新指南和共识声明概览
IF 7.4 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-07 DOI: 10.1016/j.beem.2024.101938
Charlotte Lussey-Lepoutre, Karel Pacak, Ashley Grossman, David Taieb, Laurence Amar
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours with a strong genetic predisposition, involving over 20 genes and with germline pathogenic variants identified in 40 % of cases. The succinate dehydrogenase () genes are the most commonly implicated in hereditary PPGLs, accounting for 20 % of cases, and present unique diagnostic and treatment challenges due to their potential for multiple, recurrent, and aggressive manifestations, often necessitating lifelong follow-up. Over the past two decades, advances in biochemical and imaging assessments, management, and follow-up protocols have significantly improved care for both adult and paediatric patients. These advances include next-generation sequencing, new biochemical tests, cluster-specific functional imaging, and improved surgical and radiotherapy techniques, such as stereotactic surgery and peptide receptor radionuclide therapy (PRRT). International consensus guidelines have been developed to standardise the management of patients with pathogenic variants, emphasising multidisciplinary approaches and frequent tumour board discussions. These guidelines, summarised below, cover recommendations for initial genetic testing, tumour screening, follow-up care, and management of patients and asymptomatic carriers.
辉铬细胞瘤和副神经节瘤(PPGLs)是一种罕见的神经内分泌肿瘤,具有很强的遗传倾向,涉及 20 多个基因,40% 的病例中发现了种系致病变体。琥珀酸脱氢酶()基因是遗传性 PPGLs 最常涉及的基因,占病例的 20%,由于其潜在的多发性、复发性和侵袭性表现,给诊断和治疗带来了独特的挑战,往往需要终生随访。在过去二十年中,生化和影像评估、管理和随访方案的进步大大改善了对成人和儿童患者的治疗。这些进步包括下一代测序、新的生化检验、集群特异性功能成像以及改进的手术和放疗技术,如立体定向手术和肽受体放射性核素治疗(PRRT)。目前已制定了国际共识指南,以规范对致病变异患者的管理,强调多学科方法和经常性的肿瘤委员会讨论。这些指南涵盖了对初始基因检测、肿瘤筛查、后续治疗以及患者和无症状携带者管理的建议,概述如下。
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引用次数: 0
The implications of hormone treatment for cancer risk, screening and treatment in transgender individuals 激素治疗对变性人患癌风险、筛查和治疗的影响。
IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.beem.2024.101909

There is evidence that gender-affirming hormone treatment (GAHT) for transgender individuals modulates their risk for specific malignancies including breast and prostate cancer, and meningiomas. However, there is insufficient data to make precise risk estimates accounting for age and inherited cancer risk. As such, screening recommendations remain broad. Even less evidence exists for best practice in the management of active or historical cancers in the transgender population. Guidance is therefore mainly extrapolated from cisgender populations but with considerations of the significant benefits of GAHT in the face of any hormonal risk. Clinical experience, the multidisciplinary team and shared decision making with the patient are vital in providing person-centred care, while further research is acquired.

有证据表明,变性人接受性别确认激素治疗(GAHT)会降低他们罹患特定恶性肿瘤(包括乳腺癌、前列腺癌和脑膜瘤)的风险。然而,目前还没有足够的数据对年龄和遗传性癌症风险做出精确的风险估计。因此,筛查建议仍然很宽泛。关于变性人中活动性癌症或历史性癌症的最佳治疗方法的证据就更少了。因此,指导意见主要是从双性恋人群中推断出来的,但考虑到在面对任何激素风险时,GAHT 的显著益处。在开展进一步研究的同时,临床经验、多学科团队以及与患者共同决策对于提供以人为本的护理至关重要。
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引用次数: 0
Testosterone-induced erythrocytosis in transgender males: Challenges arising from an increasing prevalence of metabolic syndrome and wider therapeutic indications for prescribing SGLT2 inhibitor drugs 变性男性睾酮诱发的红细胞增多症:代谢综合征发病率上升带来的挑战以及 SGLT2 抑制剂药物处方治疗适应症的扩大。
IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.beem.2024.101930
Azmi Mohammed (Endocrinologist) , Yaasir H. Mamoojee (Endocrinologist) , Richard Quinton (Endocrinologist)
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引用次数: 0
Gender-affirming hormone treatment modalities for transfemale & non-binary transfeminine individuals: A UK perspective 针对变性女性和非二元变性女性的性别确认激素治疗模式:英国视角。
IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.beem.2024.101921
Rebecca C. Sagar (Academic Clinical Lecturer and Honorary Specialist Registrar in Endocrinology) , Victoria Millson-Brown (Consultant Endocrinologist)

Gender incongruence and the number of people seeking gender affirming hormone treatment has dramatically risen in the last two decades. In the UK, transgender women and non-binary transfeminine individuals are typically treated with simultaneous suppression of endogenous testosterone production through anti-androgens and exogenous oestradiol replacement. Oestrogen replacement comes in different forms and is primarily given as transdermal (gel or patch) or oral preparations in the UK. Decisions around preparation choice are based on a combination of individual preference and/or mitigating the chance of complications based on individual risk profiles. Time frames to achieve female physical changes are largely predictable and managing expectations of individuals prior to commencing treatment is highly important. Common complications include venous thromboembolism, liver dysfunction and effects on fertility, thus individuals should be thoroughly counselled prior to commencing treatment. This article provides an overview of the management and considerations of gender-affirming hormone treatment in transgender women and non-binary transfeminine individuals.

在过去二十年里,性别不协调和寻求性别肯定激素治疗的人数急剧上升。在英国,变性女性和非二元跨性别者通常会同时接受抗雄激素抑制内源性睾酮分泌和外源性雌二醇替代治疗。雌激素替代有不同的形式,在英国主要是透皮(凝胶或贴片)或口服制剂。有关制剂选择的决定是基于个人偏好和/或根据个人风险概况降低并发症几率的综合考虑。实现女性生理变化的时间框架在很大程度上是可以预测的,因此在开始治疗前管理好个人的期望值非常重要。常见的并发症包括静脉血栓栓塞、肝功能障碍和对生育能力的影响,因此在开始治疗前应向患者提供全面的咨询。本文概述了变性女性和非二元跨性别者在接受性别确认激素治疗时的管理和注意事项。
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引用次数: 0
Metabolic and cardiovascular risks of hormone treatment for transgender individuals 变性人接受激素治疗的代谢和心血管风险。
IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.beem.2024.101907

Identifying metabolic and cardiovascular risks of gender-affirming hormone therapy (GAHT) is challenging due to other confounding variables that affect patient outcomes and the diversity of treatment regimes. Masculinising hormone therapy produces atherogenic lipid profiles, while effects on other metabolic parameters are not consistent. There is insufficient evidence to conclude if cardiovascular disease risk among transmen is increased. The effects of feminising hormone therapy on metabolic parameters do not demonstrate a consistent pattern in the available literature. However, the risk of venous thromboembolism is greater in transwomen than in cis-gender men and women with a possible increase in cardiovascular disease risk. It is recommended to discuss the potential effects of GAHT on cardiovascular health and encourage patients seeking GAHT to adopt a healthy lifestyle. Performing baseline and periodic assessments of cardiovascular risk factors would enable early identification and interventions. In high-risk individuals, the cardiovascular effects of hormonal regimes might impact the treatment decision.

由于影响患者预后的其他混杂变量以及治疗方案的多样性,确定性别确认激素疗法(GAHT)的代谢和心血管风险具有挑战性。男性化激素疗法会产生致动脉粥样硬化的血脂谱,而对其他代谢参数的影响并不一致。目前还没有足够的证据来断定变性人患心血管疾病的风险是否会增加。在现有文献中,女性化激素疗法对新陈代谢参数的影响并未显示出一致的模式。不过,变性女性罹患静脉血栓栓塞症的风险高于同性别的男性和女性,可能会增加心血管疾病风险。建议讨论变性手术对心血管健康的潜在影响,并鼓励寻求变性手术的患者采取健康的生活方式。对心血管风险因素进行基线评估和定期评估将有助于早期识别和干预。对于高危人群,激素疗法对心血管的影响可能会影响治疗决策。
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引用次数: 0
Clinical considerations and endocrinological implications in the detransition process 脱胎换骨过程中的临床考虑因素和内分泌学影响。
IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.beem.2024.101932
Laura Charlton (Clinical Lead/Consultant Clinical Psychologist) , Ruth Bond (GP with special interest in Gender Dysphoria)

Detransition, the process of reverting to one’s gender assigned at birth after a period of transition, or moving away from the original transition goal, presents unique challenges in healthcare. This paper introduces the clinical issue and provides a comprehensive overview of the ethical, psychological, legal, surgical, and endocrinological considerations involved in supporting individuals who choose to detransition. It emphasises the importance of patient-centred care, informed consent, and the need for expanded research to address the specific needs of this population. The paper highlights the complexities of endocrine management, surgical reversals, and the necessity for comprehensive support systems. Key psychotherapeutic interventions, including trauma-focused Cognitive Behavioural Therapy (CBT), Eye Movement Desensitization and Reprocessing (EMDR), and third-wave approaches like Compassion-Focused Therapy (CFT), are recommended to manage associated trauma and shame. By adopting a holistic approach, healthcare providers can better assist individuals navigating the complexities of detransition.

变性是指在过渡期后恢复到出生时的性别,或偏离最初的变性目标,这一过程给医疗保健带来了独特的挑战。本文介绍了这一临床问题,并全面概述了在为选择变性的个人提供支持时所涉及的伦理、心理、法律、外科和内分泌学方面的考虑因素。它强调了以患者为中心的护理、知情同意的重要性,以及扩大研究以满足这一人群特殊需求的必要性。论文强调了内分泌管理、手术逆转的复杂性以及综合支持系统的必要性。建议采取关键的心理治疗干预措施,包括以创伤为重点的认知行为疗法(CBT)、眼动脱敏和再处理疗法(EMDR)以及第三波疗法(如以同情为重点的疗法(CFT)),以控制相关的创伤和羞耻感。通过采用综合方法,医疗服务提供者可以更好地帮助个人应对复杂的脱离社会问题。
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引用次数: 0
Testosterone and other treatments for transgender males and non-binary trans masculine individuals 针对变性男性和非二元变性男性的睾丸激素和其他治疗方法。
IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.beem.2024.101908

Testosterone therapy is the main hormonal treatment offered in transmen to alleviate somatic gender dysphoria. Testosterone can be administered via topical or injectable preparations to achieve physical changes resulting in masculinisation and improve quality of life for the treated individuals. The aim of our paper is to outline methods for testosterone replacement, their impact on main body systems of transmen, potential associated health risks and long term follow up. Androgen use in transgender medicine is safe with appropriate endocrine guidance and monitoring. Studies with longer follow-up period, including those who may prefer low dose testosterone, interested in pregnancy or older people may further improve the management of female-to-male transgender persons.

睾酮疗法是为变性人提供的主要荷尔蒙疗法,以缓解躯体性别障碍。睾酮可通过外用或注射制剂来实现身体变化,从而实现男性化,并改善接受治疗者的生活质量。本文旨在概述睾酮替代方法、其对变性人主要身体系统的影响、潜在的相关健康风险和长期随访。在适当的内分泌指导和监测下,变性人使用雄激素是安全的。进行更长期的随访研究,包括那些可能偏好小剂量睾酮、对怀孕感兴趣或年龄较大的人,可进一步改善对女男变性者的管理。
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引用次数: 0
Transgender 变性人
IF 6.1 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 DOI: 10.1016/j.beem.2024.101933
Peter Hammond (Consultant Endocrinologist and Endocrinology Lead for the Leeds Regional Gender Identity Service)
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引用次数: 0
期刊
Best practice & research. Clinical endocrinology & metabolism
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