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
{"title":"Role of B cells in intratumoral MBTA immunotherapy of murine pheochromocytoma model","authors":"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","doi":"10.1016/j.beem.2024.101941","DOIUrl":"https://doi.org/10.1016/j.beem.2024.101941","url":null,"abstract":"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.","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma Boehm, Anthony J. Gill, Roderick Clifton-Bligh, Richard W. Tothill
{"title":"Recent progress in molecular classification of phaeochromocytoma and paraganglioma","authors":"Emma Boehm, Anthony J. Gill, Roderick Clifton-Bligh, Richard W. Tothill","doi":"10.1016/j.beem.2024.101939","DOIUrl":"https://doi.org/10.1016/j.beem.2024.101939","url":null,"abstract":"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.","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Lussey-Lepoutre, Karel Pacak, Ashley Grossman, David Taieb, Laurence Amar
{"title":"Overview of recent guidelines and consensus statements on initial screening and management of phaeochromocytoma and paraganglioma in SDHx pathogenic variant carriers and patients","authors":"Charlotte Lussey-Lepoutre, Karel Pacak, Ashley Grossman, David Taieb, Laurence Amar","doi":"10.1016/j.beem.2024.101938","DOIUrl":"https://doi.org/10.1016/j.beem.2024.101938","url":null,"abstract":"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.","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The implications of hormone treatment for cancer risk, screening and treatment in transgender individuals","authors":"","doi":"10.1016/j.beem.2024.101909","DOIUrl":"10.1016/j.beem.2024.101909","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521690X24000630/pdfft?md5=09689fa866d8624d81d0b944eca73533&pid=1-s2.0-S1521690X24000630-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Testosterone-induced erythrocytosis in transgender males: Challenges arising from an increasing prevalence of metabolic syndrome and wider therapeutic indications for prescribing SGLT2 inhibitor drugs","authors":"","doi":"10.1016/j.beem.2024.101930","DOIUrl":"10.1016/j.beem.2024.101930","url":null,"abstract":"","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gender-affirming hormone treatment modalities for transfemale & non-binary transfeminine individuals: A UK perspective","authors":"","doi":"10.1016/j.beem.2024.101921","DOIUrl":"10.1016/j.beem.2024.101921","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521690X24000757/pdfft?md5=54468a8b1e776408fb77978d3bcbacc2&pid=1-s2.0-S1521690X24000757-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic and cardiovascular risks of hormone treatment for transgender individuals","authors":"","doi":"10.1016/j.beem.2024.101907","DOIUrl":"10.1016/j.beem.2024.101907","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521690X24000617/pdfft?md5=b527309d0293b6e0c81e36d80cdd71af&pid=1-s2.0-S1521690X24000617-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical considerations and endocrinological implications in the detransition process","authors":"","doi":"10.1016/j.beem.2024.101932","DOIUrl":"10.1016/j.beem.2024.101932","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Testosterone and other treatments for transgender males and non-binary trans masculine individuals","authors":"","doi":"10.1016/j.beem.2024.101908","DOIUrl":"10.1016/j.beem.2024.101908","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521690X24000629/pdfft?md5=43ca672c6325d1ba65e54f70fda44f3a&pid=1-s2.0-S1521690X24000629-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}