Metabolic effects of gender-affirming hormone therapy
Related Articles
Consensus on the key characteristics of metabolism disruptors
Metabolism-disrupting agents (MDAs) are chemical, infectious or physical agents that increase the risk of metabolic disorders. Examples include pharmaceuticals, such as antidepressants, and environmental agents, such as bisphenol A. Various types of studies can provide evidence to identify MDAs, yet a systematic method is needed to integrate these data to help to identify such hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we developed 12 KCs of MDAs based on our knowledge of processes underlying metabolic diseases and the effects of their causal agents: (1) alters function of the endocrine pancreas; (2) impairs function of adipose tissue; (3) alters nervous system control of metabolic function; (4) promotes insulin resistance; (5) disrupts metabolic signalling pathways; (6) alters development and fate of metabolic cell types; (7) alters energy homeostasis; (8) causes inappropriate nutrient handling and partitioning; (9) promotes chronic inflammation and immune dysregulation in metabolic tissues; (10) disrupts gastrointestinal tract function; (11) induces cellular stress pathways; and (12) disrupts circadian rhythms. In this Consensus Statement, we present the logic that revealed the KCs of MDAs and highlight evidence that supports the identification of KCs. We use chemical, infectious and physical agents as examples to illustrate how the KCs can be used to organize and use mechanistic data to help to identify MDAs.
Exploring metabolic reprogramming in esophageal cancer: the role of key enzymes in glucose, amino acid, and nucleotide pathways and targeted therapies
Esophageal cancer (EC) is one of the most common malignancies worldwide with the character of poor prognosis and high mortality. Despite significant advancements have been achieved in elucidating the molecular mechanisms of EC, for example, in the discovery of new biomarkers and metabolic pathways, effective treatment options for patients with advanced EC are still limited. Metabolic heterogeneity in EC is a critical factor contributing to poor clinical outcomes. This heterogeneity arises from the complex interplay between the tumor microenvironment and genetic factors of tumor cells, which drives significant metabolic alterations in EC, a process known as metabolic reprogramming. Understanding the mechanisms of metabolic reprogramming is essential for developing new antitumor therapies and improving treatment outcomes. Targeting the distinct metabolic alterations in EC could enable more precise and effective therapies. In this review, we explore the complex metabolic changes in glucose, amino acid, and nucleotide metabolism during the progression of EC, and how these changes drive unique nutritional demands in cancer cells. We also evaluate potential therapies targeting key metabolic enzymes and their clinical applicability. Our work will contribute to enhancing knowledge of metabolic reprogramming in EC and provide new insights and approaches for the clinical treatment of EC.
What makes a man unmanly? The global concept of ‘unmanliness’
This paper presents the findings of a multi-national study that led to the development of a new analytical framework in masculinity research—the Global Concept of ‘Unmanliness’ (GCU). Drawing on three key theories—hegemonic masculinity, precarious manhood and masculinity threat, and emasculation—we conducted an innovative study across 15 countries (selected from an initial pool of 62) to examine cultural perceptions of ‘unmanliness.’ Participants provided open-ended responses to identify traits and behaviors considered unmanly within their cultural contexts. By analyzing common themes expressed by young men, we propose the Global Concept of ‘Unmanliness’ as a framework for understanding how societies define and enforce masculinity norms. Furthermore, comparing these findings with the Global Gender Gap Index (GGGI) revealed a key distinction in how ‘unmanliness’ is characterized across different levels of gender emancipation. In countries with high GGGI rankings (e.g., Norway, Ireland, Germany), ‘unmanliness’ is more often associated with physical traits and behaviors linked to femininity (e.g., clothing, makeup). Conversely, in countries with low GGGI rankings (e.g., Pakistan, Morocco, Nigeria), it is more commonly defined by acts such as violence against women. Our study highlights how cultural and structural gender dynamics shape the boundaries of masculinity and offers a new lens for cross-cultural research on gender norms.
The guided fire from within: intratumoral administration of mRNA-based vaccines to mobilize memory immunity and direct immune responses against pathogen to target solid tumors
We investigated a novel cancer immunotherapy strategy that effectively suppresses tumor growth in multiple solid tumor models and significantly extends the lifespan of tumor-bearing mice by introducing pathogen antigens into tumors via mRNA-lipid nanoparticles. The pre-existing immunity against the pathogen antigen can significantly enhance the efficacy of this approach. In mice previously immunized with BNT162b2, an mRNA-based COVID-19 vaccine encoding the spike protein of the SARS-CoV-2 virus, intratumoral injections of the same vaccine efficiently tagged the tumor cells with mRNA-expressed spike protein. This action rapidly mobilized the pre-existing memory immunity against SARS-CoV-2 to kill the cancer cells displaying the spike protein, while concurrently reprogramming the tumor microenvironment (TME) by attracting immune cells. The partial elimination of tumor cells in a normalized TME further triggered extensive tumor antigen-specific T cell responses through antigen spreading, eventually resulting in potent and systemic tumor-targeting immune responses. Moreover, combining BNT162b2 treatment with anti-PD-L1 therapy yielded a more substantial therapeutic impact, even in “cold tumor” types that are typically less responsive to treatment. Given that the majority of the global population has acquired memory immunity against various pathogens through infection or vaccination, we believe that, in addition to utilizing the widely held immune memory against SARS-CoV-2 via COVID-19 vaccine, mRNA vaccines against other pathogens, such as Hepatitis B Virus (HBV), Common Human Coronaviruses (HCoVs), and the influenza virus, could be rapidly transitioned into clinical use and holds great promise in treating different types of cancer. The extensive selection of pathogen antigens expands therapeutic opportunities and may also overcome potential drug resistance.
International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma
T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies. The International Myeloma Working Group conveyed panel of experts to review patient and disease-related factors affecting efficacy and safety of immunotherapy, summarize existing information on sequencing therapy and provide a series of core recommendations.
Responses