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Ovarian Clear Cell Carcinoma: An Endometriosis-Associated Cancer with Therapeutic Challenges. 卵巢透明细胞癌：子宫内膜异位症相关癌症的治疗难题。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041315
Ruby Yun-Ju Huang, Jimmy Jin-Che Lin
{"title":"Ovarian Clear Cell Carcinoma: An Endometriosis-Associated Cancer with Therapeutic Challenges.","authors":"Ruby Yun-Ju Huang, Jimmy Jin-Che Lin","doi":"10.1101/cshperspect.a041315","DOIUrl":"https://doi.org/10.1101/cshperspect.a041315","url":null,"abstract":"<p><p>Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer with distinct pathological features, molecular profiles, and biological functions. OCCC has high incidence rates in East Asia compared to the Western hemisphere and Europe and is associated with endometriosis. With its relative resistance to conventional treatment regimens and the worst stage-adjusted prognosis among ovarian cancer subtypes, there is an urgent need to optimize therapeutic options and to improve patient outcomes. To achieve this goal, better patient stratification strategies are required. These strategies could derive from comprehensive and in-depth multidimensional analysis of tumor heterogeneity. Understanding intertumor heterogeneity could assist us in stratifying OCCC patients based on features that are prognostic or predictive. Recent genomic, epigenomic, and transcriptomic profiling analyses allow us to provide an integrative perspective on the diverse heterogeneity in OCCC that could pave the way for novel translational research and clinical development in the future.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281435","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
Cancer Metabolism: Aspirations for the Coming Decade. 癌症代谢：未来十年的愿望
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041555
Ralph J DeBerardinis, Karen H Vousden, Navdeep S Chandel
{"title":"Cancer Metabolism: Aspirations for the Coming Decade.","authors":"Ralph J DeBerardinis, Karen H Vousden, Navdeep S Chandel","doi":"10.1101/cshperspect.a041555","DOIUrl":"10.1101/cshperspect.a041555","url":null,"abstract":"<p><p>Fueled by technological and conceptual advancements over the past two decades, research in cancer metabolism has begun to answer questions dating back to the time of Otto Warburg. But, as with most fields, new discoveries lead to new questions. This review outlines the emerging challenges that we predict will drive the next few decades of cancer metabolism research. These include developing a more realistic understanding of how metabolic activities are compartmentalized within cells, tissues, and organs; how metabolic preferences in tumors evolve during cancer progression from nascent, premalignant lesions to advanced, metastatic disease; and, most importantly, how we can best translate basic observations from preclinical models into novel therapies that benefit patients with cancer. With modern tools and an incredible amount of talent focusing on these problems, the upcoming decades should bring transformative discoveries.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281434","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
Rebalancing the Immune System to Treat Type 1 Diabetes. 重新平衡免疫系统，治疗 1 型糖尿病。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041599
Yannick D Muller, Patrick Ho, Jeffrey A Bluestone, Qizhi Tang
{"title":"Rebalancing the Immune System to Treat Type 1 Diabetes.","authors":"Yannick D Muller, Patrick Ho, Jeffrey A Bluestone, Qizhi Tang","doi":"10.1101/cshperspect.a041599","DOIUrl":"https://doi.org/10.1101/cshperspect.a041599","url":null,"abstract":"<p><p>In type 1 diabetes (T1D), the immune system mistakenly attacks the pancreatic islet β cells resulting in the loss of insulin secretion. Insulin-replacement therapy developed more than a century ago provided means to manage the symptoms of diabetes without addressing the root cause of the disease-the faulty immune system. A healthy immune system has built-in mechanisms to limit unwanted, excessive immune activation and prevents damages to self-tissues. These immune self-tolerance mechanisms are often impaired in autoimmune patients including those with T1Ds. Understanding how immune self-tolerance is broken in patients with T1D can inform the design of new curative therapies that correct the immune defects. In this paper, we will summarize the mechanisms of immune tolerance, review their relevance to T1Ds, and discuss novel therapeutic approaches to rebalance the immune system for the treatment of T1Ds.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281436","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
Technologies for Decoding Cancer Metabolism with Spatial Resolution. 以空间分辨率解码癌症代谢的技术。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041553
Walter W Chen, Michael E Pacold, David M Sabatini, Naama Kanarek
{"title":"Technologies for Decoding Cancer Metabolism with Spatial Resolution.","authors":"Walter W Chen, Michael E Pacold, David M Sabatini, Naama Kanarek","doi":"10.1101/cshperspect.a041553","DOIUrl":"https://doi.org/10.1101/cshperspect.a041553","url":null,"abstract":"<p><p>It is increasingly appreciated that cancer cells adapt their metabolic pathways to support rapid growth and proliferation as well as survival, often even under the poor nutrient conditions that characterize some tumors. Cancer cells can also rewire their metabolism to circumvent chemotherapeutics that inhibit core metabolic pathways, such as nucleotide synthesis. A critical approach to the study of cancer metabolism is metabolite profiling (metabolomics), the set of technologies, usually based on mass spectrometry, that allow for the detection and quantification of metabolites in cancer cells and their environments. Metabolomics is a burgeoning field, driven by technological innovations in mass spectrometers, as well as novel approaches to isolate cells, subcellular compartments, and rare fluids, such as the interstitial fluid of tumors. Here, we discuss three emerging metabolomic technologies: spatial metabolomics, single-cell metabolomics, and organellar metabolomics. The use of these technologies along with more established profiling methods, like single-cell transcriptomics and proteomics, is likely to underlie new discoveries and questions in cancer research.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281437","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
The Teplizumab Saga: The Challenge of Not Getting Lost in Clinical Translation. 特普利珠单抗传奇：不迷失在临床转化中的挑战。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041600
Lucienne Chatenoud, Kevan C Herold, Jean-François Bach, Jeffrey A Bluestone
{"title":"The Teplizumab Saga: The Challenge of Not Getting Lost in Clinical Translation.","authors":"Lucienne Chatenoud, Kevan C Herold, Jean-François Bach, Jeffrey A Bluestone","doi":"10.1101/cshperspect.a041600","DOIUrl":"https://doi.org/10.1101/cshperspect.a041600","url":null,"abstract":"<p><p>In November 2022, teplizumab became the first drug approved to delay the course of any autoimmune disease and to change the course of type 1 diabetes (T1D) since the discovery of insulin. The path to its approval took more than 30 years with both successes and failures along the way that would have normally led to its abandonment in other circumstances. Development of the drug was based on studies in preclinical models and parallels efforts in transplantation. From a series of innovative adaptations in response to issues related to adverse events and immunogenicity, humanized Fc receptors (FcR) nonbinding antibodies were developed with improved clinical outcomes and safety as well as new mechanisms. Importantly, as a result of these developments, teplizumab has been able to achieve efficacy over extended periods of time without global immune suppression. The approval of teplizumab represents a significant first step toward achieving escape from T1D and, in the future, reversal of the disease.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281438","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
Autoantigen-Specific Immunotherapies for the Prevention and Treatment of Type 1 Diabetes. 预防和治疗 1 型糖尿病的自身抗原特异性免疫疗法。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-16 DOI: 10.1101/cshperspect.a041598
Mark Peakman, Pere Santamaria
{"title":"Autoantigen-Specific Immunotherapies for the Prevention and Treatment of Type 1 Diabetes.","authors":"Mark Peakman, Pere Santamaria","doi":"10.1101/cshperspect.a041598","DOIUrl":"https://doi.org/10.1101/cshperspect.a041598","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is driven by an immunologically complex, diverse, and self-sustaining immune response directed against tissue autoantigens, leading to loss or dysfunction of β cells. To date, the single approved immune intervention in T1D is based on a strategy that is similar to that used in other related autoimmune diseases, namely, the attenuation of immune cell activation. As a next-generation approach that is more focused on underlying mechanisms of loss of tolerance, antigen-specific immunotherapy is designed to establish or restore bystander immunoregulation in a highly tissue- and target-specific fashion. Here, we describe the basis for this alternative approach, which could also have potential for complementarity if used in combination with more conventional immune modulators, and highlight recent advances, knowledge gaps, and next steps in clinical development.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281433","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
Imaging Approaches in Cancer Biology. 癌症生物学中的成像方法。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-03 DOI: 10.1101/cshperspect.a041349
Nirakar Rajbhandari, Emily Diaz, Marcie Kritzik, Tannishtha Reya
{"title":"Imaging Approaches in Cancer Biology.","authors":"Nirakar Rajbhandari, Emily Diaz, Marcie Kritzik, Tannishtha Reya","doi":"10.1101/cshperspect.a041349","DOIUrl":"10.1101/cshperspect.a041349","url":null,"abstract":"<p><p>A majority of cancer research is focused on defining the cellular and molecular basis of cancer cells and the signals that control oncogenic transformation; as a consequence, we know very little about the dynamic behavior of cancer cells in vivo. To begin to view and understand the mechanisms and interactions that control cancer initiation, growth, and metastatic progression and how these processes are influenced by the microenvironment and the signals derived from it, it is essential to develop strategies that allow imaging of the cancer cells in the context of the living microenvironment. Here, we discuss emerging work designed to visualize how cancer cells function within the microenvironment to discover how these interactions act coordinately to enable aberrant growth and to understand how they could be targeted to design new approaches to intercept the disease.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075798","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
History of Finding Genes and Mutations Causing Inherited Retinal Diseases. 发现导致遗传性视网膜疾病的基因和突变的历史。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-09-03 DOI: 10.1101/cshperspect.a041287
Stephen P Daiger, Lori S Sullivan, Elizabeth L Cadena, Sara J Bowne
{"title":"History of Finding Genes and Mutations Causing Inherited Retinal Diseases.","authors":"Stephen P Daiger, Lori S Sullivan, Elizabeth L Cadena, Sara J Bowne","doi":"10.1101/cshperspect.a041287","DOIUrl":"10.1101/cshperspect.a041287","url":null,"abstract":"<p><p>This is a brief history of the work by many investigators throughout the world to find genes and mutations causing inherited retinal diseases (IRDs). It largely covers 40 years, from the late-1980s through today. Perhaps the best reason to study history is to better understand the present. The \"present\" for IRDs is exceptionally complex. Mutations in hundreds of genes are known to cause IRDs; tens of thousands of disease-causing mutations have been reported; clinical consequences are highly variable, even within the same family; and genetic testing, counseling, and clinical care are highly advanced but technically challenging. The aim of this review is to account for how we have come to know and understand, at least partly, this complexity.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106182","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
The Pathogenesis of Type 1 Diabetes 1 型糖尿病的发病机制
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041623
Kevan C. Herold, Jeffrey P. Krischer
{"title":"The Pathogenesis of Type 1 Diabetes","authors":"Kevan C. Herold, Jeffrey P. Krischer","doi":"10.1101/cshperspect.a041623","DOIUrl":"https://doi.org/10.1101/cshperspect.a041623","url":null,"abstract":"Type 1 diabetes (T1D) is a chronic autoimmune disease with a metabolic outcome. Studies over the past decades, have identified the contributions of genetics, environmental factors, and disorders of innate and adaptive immunity that collectively cause β-cell killing. The risk for T1D can be genetically identified but genotypes alone do not identify factors that lead to disease progression. The incidence of T1D has been increasing in the past few decades, which may be due to reduced exposure to infections and other environmental factors that can reduce autoimmunity (hygiene hypothesis). Once initiated, the disease pathogenesis progresses through stages that have been defined on the bases of immunologic (i.e., autoantibodies) and metabolic markers (glucose tolerance). The stages only loosely capture the risk for the time to diagnosis of disease, do not directly reflect disease activity, and there may be variance in the rate of progression within stages. In a general way, the stages can be used to identify patients at risk in whom interventions may be considered to modulate progression. This was achieved with the approval of teplizumab, a humanized anti-CD3 monoclonal antibody, for delaying the diagnosis of T1D.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"44 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141935075","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
The Human Pancreas in Type 1 Diabetes: Lessons Learned from the Network of Pancreatic Organ Donors with Diabetes 1 型糖尿病患者的人体胰腺：从糖尿病胰腺器官捐赠者网络中汲取的经验教训
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041588
Irina Kusmartseva, Amanda Posgai, Mingder Yang, Richard Oram, Mark Atkinson, Alberto Pugliese, Carmella Evans-Molina
{"title":"The Human Pancreas in Type 1 Diabetes: Lessons Learned from the Network of Pancreatic Organ Donors with Diabetes","authors":"Irina Kusmartseva, Amanda Posgai, Mingder Yang, Richard Oram, Mark Atkinson, Alberto Pugliese, Carmella Evans-Molina","doi":"10.1101/cshperspect.a041588","DOIUrl":"https://doi.org/10.1101/cshperspect.a041588","url":null,"abstract":"The Network for Pancreatic Organ Donors with Diabetes (nPOD) has helped shape the contemporary understanding of type 1 diabetes (T1D) pathogenesis in humans through the procurement, distribution to scientists, and collaborative study of human pancreata and disease-related tissues from organ donors with T1D and islet autoantibody positivity. Since its inception in 2007, nPOD has collected tissues from 600 donors, and these resources have been distributed across 22 countries to more than 290 projects, resulting in nearly 350 publications. Research projects supported by nPOD span the breadth of diabetes research, including studies on T1D immunology and β-cell biology, and have uniquely unveiled abnormalities in other pancreatic cell types. In this article, we will detail the history and programmatic features of nPOD, as well as highlight key scientific findings from nPOD studies. We will present our view for the future of nPOD and discuss how the success of the program has established a precedent whereby knowledge gaps in biomedical research can be addressed through the study of human tissues.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"57 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141935074","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
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