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Cold Spring Harbor perspectives in medicine最新文献

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Toward a Unified Theory of Why Young People Develop Cancer 构建年轻人罹患癌症的统一理论
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041658
Alex Kentsis
{"title":"Toward a Unified Theory of Why Young People Develop Cancer","authors":"Alex Kentsis","doi":"10.1101/cshperspect.a041658","DOIUrl":"https://doi.org/10.1101/cshperspect.a041658","url":null,"abstract":"Epidemiologic and genetic studies have now defined specific patterns of incidence and distinct molecular features of cancers in young versus aging people. Here, I review a general framework for the causes of cancer in children and young adults by relating somatic genetic mosaicism and developmental tissue mutagenesis. This framework suggests how aging-associated cancers such as carcinomas, glioblastomas, and myelodysplastic leukemias are causally distinct from cancers that predominantly affect children and young adults, including lymphoblastic and myeloid leukemias, sarcomas, neuroblastomas, medulloblastomas, and other developmental cancers. I discuss the oncogenic activities of known developmental mutators RAG1/2, AID, and PGBD5, and describe strategies needed to define missing developmental causes of young-onset cancers. Thus, a precise understanding of the mechanisms of tissue-specific somatic mosaicism, developmental mutators, and their control by human genetic variation and environmental exposures is needed for improved strategies for cancer screening, prevention, and treatment.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"10 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835164","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
New Paradigms in the Clinical Management of Li–Fraumeni Syndrome 李-弗劳米尼综合征临床治疗新范例
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041584
Camilla Giovino, Vallijah Subasri, Frank Telfer, David Malkin
{"title":"New Paradigms in the Clinical Management of Li–Fraumeni Syndrome","authors":"Camilla Giovino, Vallijah Subasri, Frank Telfer, David Malkin","doi":"10.1101/cshperspect.a041584","DOIUrl":"https://doi.org/10.1101/cshperspect.a041584","url":null,"abstract":"Approximately 8.5%–16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant—a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li–Fraumeni syndrome (LFS), associated with germline variants in the <em>TP53</em> tumor suppressor gene, and a &gt;90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning–based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"52 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835165","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
Breast Cancer 乳腺癌
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041729
Jane E. Visvader, Jeffrey M. Rosen, Samuel Aparicio
{"title":"Breast Cancer","authors":"Jane E. Visvader, Jeffrey M. Rosen, Samuel Aparicio","doi":"10.1101/cshperspect.a041729","DOIUrl":"https://doi.org/10.1101/cshperspect.a041729","url":null,"abstract":"Breast cancer kills hundreds of thousands of people every year. Rapid progress over the past two decades has increased our understanding of the genetic and environmental risk factors for disease. It has also shed light on drivers of tumor progression and the molecular landscape underpinning tumor heterogeneity, as well as the role of the microenvironment and the immune system. These strides forward should lead to more effective and tailored therapies for early- and late-stage patients.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"37 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835237","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
Mechanics of Lymphatic Pumping and Lymphatic Function 淋巴泵送和淋巴功能的机理
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041171
Mohammad S. Razavi, Lance L. Munn, Timothy P. Padera
{"title":"Mechanics of Lymphatic Pumping and Lymphatic Function","authors":"Mohammad S. Razavi, Lance L. Munn, Timothy P. Padera","doi":"10.1101/cshperspect.a041171","DOIUrl":"https://doi.org/10.1101/cshperspect.a041171","url":null,"abstract":"The lymphatic system plays a crucial role in maintaining tissue fluid balance, immune surveillance, and the transport of lipids and macromolecules. Lymph is absorbed by initial lymphatics and then driven through lymph nodes and to the blood circulation by the contraction of collecting lymphatic vessels. Intraluminal valves in collecting lymphatic vessels ensure the unidirectional flow of lymph centrally. The lymphatic muscle cells that invest in collecting lymphatic vessels impart energy to propel lymph against hydrostatic pressure gradients and gravity. A variety of mechanical and biochemical stimuli modulate the contractile activity of lymphatic vessels. This review focuses on the recent advances in our understanding of the mechanisms involved in regulating and collecting lymphatic vessel pumping in normal tissues and the association between lymphatic pumping, infection, inflammatory disease states, and lymphedema.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"3 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835382","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
Breakdown and Repair of Peripheral Immune Tolerance in Type 1 Diabetes 1 型糖尿病患者外周免疫耐受的破坏与修复
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041596
Gerald T. Nepom
{"title":"Breakdown and Repair of Peripheral Immune Tolerance in Type 1 Diabetes","authors":"Gerald T. Nepom","doi":"10.1101/cshperspect.a041596","DOIUrl":"https://doi.org/10.1101/cshperspect.a041596","url":null,"abstract":"Failures in peripheral immune tolerance mechanisms create a permissive environment for autoimmune diabetes initiation and disease progression. Biomarker analyses provide tools that allow recognition of this loss of tolerance, reflecting a serial acquisition of pathogenic characteristics causally linked to islet β-cell dysfunction and death. Autoimmune effector cell activation and expansion, ineffective immune regulation, and tissue response to injury during active disease each represent challenges to homeostasis; however, they also represent targets for therapeutic intervention, with the potential for restoration of tolerance. Limited success in recent clinical trials demonstrates that tolerance in type 1 diabetes (T1D) is achievable, but currently occurs in few subjects and is not durable in most. Combining therapeutic agents to rebuild multiple immune components to restore tolerance, particularly addressing both effector and regulatory T-cell dysfunction, is needed.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"43 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835544","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
Vascular Organization: Lessons from Development and Disease 血管组织：发育与疾病的启示
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041160
Steve Spurgin, Ondine Cleaver
{"title":"Vascular Organization: Lessons from Development and Disease","authors":"Steve Spurgin, Ondine Cleaver","doi":"10.1101/cshperspect.a041160","DOIUrl":"https://doi.org/10.1101/cshperspect.a041160","url":null,"abstract":"Organ formation requires tight coordination with vascular growth. Intricate networks of blood vessels course through all organs and tissues and are composed of both endothelial cells (ECs) and associated mural cells. Despite decades of research into the biology of blood vessel formation and homeostasis, little is known about how the vasculature ensures its properly coordinated growth and intimate development with the cells of different organs. Even more mystifying is how a highly dynamic endothelium quiesces to differentiate into mature vessels, and how disruption of this mature quiescence results in pathological conditions. Interestingly, both intra- and interorgan vascular architecture hold critical importance to the maintenance of blood vessels, as the rate of flow and supply of supportive angiogenic factors can be altered with deleterious effects. In this article, we review the basic mechanisms of blood vessel formation and maintenance with an emphasis on organ-specific vascular development, and we examine the case of transient pulmonary arteriovenous malformations as a case study of vascular homeostatic mechanisms.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"16 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835371","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
Mitochondria and Cancer 线粒体与癌症
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041534
Timothy C. Kenny, Kıvanç Birsoy
{"title":"Mitochondria and Cancer","authors":"Timothy C. Kenny, Kıvanç Birsoy","doi":"10.1101/cshperspect.a041534","DOIUrl":"https://doi.org/10.1101/cshperspect.a041534","url":null,"abstract":"Mitochondria are semiautonomous organelles with diverse metabolic and cellular functions including anabolism and energy production through oxidative phosphorylation. Following the pioneering observations of Otto Warburg nearly a century ago, an immense body of work has examined the role of mitochondria in cancer pathogenesis and progression. Here, we summarize the current state of the field, which has coalesced around the position that functional mitochondria are required for cancer cell proliferation. In this review, we discuss how mitochondria influence tumorigenesis by impacting anabolism, intracellular signaling, and the tumor microenvironment. Consistent with their critical functions in tumor formation, mitochondria have become an attractive target for cancer therapy. We provide a comprehensive update on the numerous therapeutic modalities targeting the mitochondria of cancer cells making their way through clinical trials.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"12 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835381","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
Diet and Cancer Metabolism 饮食与癌症代谢
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-15 DOI: 10.1101/cshperspect.a041549
Jason W. Locasale, Marcus D. Goncalves, Maira Di Tano, Guillermo Burgos-Barragan
{"title":"Diet and Cancer Metabolism","authors":"Jason W. Locasale, Marcus D. Goncalves, Maira Di Tano, Guillermo Burgos-Barragan","doi":"10.1101/cshperspect.a041549","DOIUrl":"https://doi.org/10.1101/cshperspect.a041549","url":null,"abstract":"Diet and exercise are modifiable lifestyle factors known to have a major influence on metabolism. Clinical practice addresses diseases of altered metabolism such as diabetes or hypertension by altering these factors. Despite enormous public interest, there are limited defined diet and exercise regimens for cancer patients. Nevertheless, the molecular basis of cancer has converged over the past 15 years on an essential role for altered metabolism in cancer. However, our understanding of the molecular mechanisms that underlie the impact of diet and exercise on cancer metabolism is in its very early stages. In this work, we propose conceptual frameworks for understanding the consequences of diet and exercise on cancer cell metabolism and tumor biology and also highlight recent developments. By advancing our mechanistic understanding, we also discuss actionable ways that such interventions could eventually reach the mainstay of both medical oncology and cancer control and prevention.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"160 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579281","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
Harnessing Antitumor Immunity in Ovarian Cancer 利用卵巢癌的抗肿瘤免疫力
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-15 DOI: 10.1101/cshperspect.a041336
Katherine C. Kurnit, Kunle Odunsi
{"title":"Harnessing Antitumor Immunity in Ovarian Cancer","authors":"Katherine C. Kurnit, Kunle Odunsi","doi":"10.1101/cshperspect.a041336","DOIUrl":"https://doi.org/10.1101/cshperspect.a041336","url":null,"abstract":"Despite progress in other tumor types, immunotherapy is not yet part of the standard of care treatment for high-grade serous ovarian cancer patients. Although tumor infiltration by T cells is frequently observed in patients with ovarian cancer, clinical responses to immunotherapy remain low. Mechanisms for immune resistance in ovarian cancer have been explored and may provide insight into future approaches to improve response to immunotherapy agents. In this review, we discuss what is known about the immune landscape in ovarian cancer, review the available data for immunotherapy-based strategies in these patients, and provide possible future directions.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"12 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579459","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
Prostanoids Regulate Angiogenesis and Lymphangiogenesis in Pathological Conditions 前列腺素调节病理情况下的血管生成和淋巴管生成
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-02 DOI: 10.1101/cshperspect.a041182
Masataka Majima, Yasuhiro Matsuda, Shin-Ichi Watanabe, Yasuaki Ohtaki, Kanako Hosono, Yoshiya Ito, Hideki Amano
{"title":"Prostanoids Regulate Angiogenesis and Lymphangiogenesis in Pathological Conditions","authors":"Masataka Majima, Yasuhiro Matsuda, Shin-Ichi Watanabe, Yasuaki Ohtaki, Kanako Hosono, Yoshiya Ito, Hideki Amano","doi":"10.1101/cshperspect.a041182","DOIUrl":"https://doi.org/10.1101/cshperspect.a041182","url":null,"abstract":"Angiogenesis, the formation of new blood vessels from the preexistent microvasculature, is an essential component of wound repair and tumor growth. Nonsteroidal anti-inflammatory drugs that suppress prostanoid biosynthesis are known to suppress the incidence and progression of malignancies including colorectal cancers, and also to delay the wound healing. However, the precise mechanisms are not fully elucidated. Accumulated results obtained from prostanoid receptor knockout mice indicate that a prostaglandin E-type receptor signaling EP<sub>3</sub> in the host microenvironment is critical in tumor angiogenesis inducing vascular endothelial growth factor A (VEGF-A). Further, lymphangiogenesis was also enhanced by EP signaling via VEGF-C/D inductions in pathological settings. These indicate the importance of EP receptor to facilitate angiogenesis and lymphangiogenesis in vivo. Prostanoids act beyond their commonly understood activities in smooth muscle contraction and vasoactivity, both of which are quick responses elicited within several seconds on stimulations. Prostanoid receptor signaling will be a potential therapeutic target for disease conditions related to angiogenesis and lymphangiogenesis.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"51 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579277","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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