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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
Oncogenic Control of Metabolism 代谢的致癌控制
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-02 DOI: 10.1101/cshperspect.a041531
Natalya N. Pavlova, Craig B. Thompson
{"title":"Oncogenic Control of Metabolism","authors":"Natalya N. Pavlova, Craig B. Thompson","doi":"10.1101/cshperspect.a041531","DOIUrl":"https://doi.org/10.1101/cshperspect.a041531","url":null,"abstract":"A cell committed to proliferation must reshape its metabolism to enable robust yet balanced production of building blocks for the assembly of proteins, lipids, nucleic acids, and other macromolecules, from which two functional daughter cells can be produced. The metabolic remodeling associated with proliferation is orchestrated by a number of pro-proliferative signaling nodes, which include phosphatidylinositol-3 kinase (PI3K), the RAS family of small GTPases, and transcription factor <em>c-myc</em>. In metazoan cells, these signals are activated in a paracrine manner via growth factor–mediated activation of receptor (or receptor-associated) tyrosine kinases. Such stimuli are limited in duration and therefore allow the metabolism of target cells to return to the resting state once the proliferation demands have been satisfied. Cancer cells acquire activating genetic alterations within common pro-proliferative signaling nodes. These alterations lock cellular nutrient uptake and utilization into a perpetual progrowth state, leading to the aberrant accumulation and spread of cancer cells.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"95 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579089","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
Osteosarcoma through the Lens of Bone Development, Signaling, and Microenvironment 从骨骼发育、信号传导和微环境的角度看骨肉瘤
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-02 DOI: 10.1101/cshperspect.a041635
Elizabeth P. Young, Amanda E. Marinoff, Eunice Lopez-Fuentes, E. Alejandro Sweet-Cordero
{"title":"Osteosarcoma through the Lens of Bone Development, Signaling, and Microenvironment","authors":"Elizabeth P. Young, Amanda E. Marinoff, Eunice Lopez-Fuentes, E. Alejandro Sweet-Cordero","doi":"10.1101/cshperspect.a041635","DOIUrl":"https://doi.org/10.1101/cshperspect.a041635","url":null,"abstract":"In this work, we review the multifaceted connections between osteosarcoma (OS) biology and normal bone development. We summarize and critically analyze existing research, highlighting key areas that merit further exploration. The review addresses several topics in OS biology and their interplay with normal bone development processes, including OS cell of origin, genomics, tumor microenvironment, and metastasis. We examine the potential cellular origins of OS and how their roles in normal bone growth may contribute to OS pathogenesis. We survey the genomic landscape of OS, highlighting the developmental roles of genes frequently altered in OS. We then discuss the OS microenvironment, emphasizing the transformation of the bone niche in OS to facilitate tumor growth and metastasis. The role of stromal and immune cells is examined, including their impact on tumor progression and therapeutic response. We further provide insights into potential development-informed opportunities for novel therapeutic strategies.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"33 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579458","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
Retinal Disorders 视网膜疾病
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-02 DOI: 10.1101/cshperspect.a041728
José-Alain Sahel, Eyal Banin, Jean Bennett, Jacque L. Duncan, Botond Roska
{"title":"Retinal Disorders","authors":"José-Alain Sahel, Eyal Banin, Jean Bennett, Jacque L. Duncan, Botond Roska","doi":"10.1101/cshperspect.a041728","DOIUrl":"https://doi.org/10.1101/cshperspect.a041728","url":null,"abstract":"Retinal disorders caused by genetic or environmental factors cause severe visual impairment and often result in blindness. The past ten years have seen rapid progress in our understanding of the biological basis of these conditions, as well as significant advances towards gene and cell-based therapies. Regulatory challenges remain, but there is reason to hope that creative approaches will lead to safe and effective breakthrough treatments for these conditions in the near future.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"43 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579287","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
Geroscience and Its Promise 老年科学及其前景
IF 5.4 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2024-04-02 DOI: 10.1101/cshperspect.a041725
S. Jay Olshansky, James L. Kirkland
{"title":"Geroscience and Its Promise","authors":"S. Jay Olshansky, James L. Kirkland","doi":"10.1101/cshperspect.a041725","DOIUrl":"https://doi.org/10.1101/cshperspect.a041725","url":null,"abstract":"Why we age and whether our lifespan can be extended have intrigued scientists for centuries. Meanwhile public health advances mean humanity is having to confront the realities of an aging and increasingly frail population. The nascent field of geroscience offers hope that healthspan not just lifespan can be extended. It has spawned a vibrant scientific community that includes researchers studying fundamental biology, translational approaches, economics, and research funding. The knowledge gained from work in this area has the potential to influence the lives of most people alive today.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"31 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579274","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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