Cold Spring Harbor perspectives in medicine最新文献

Models of High-Grade Serous Ovarian Carcinoma. 高级别浆液性卵巢癌的模型。

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-10-06 DOI: 10.1101/cshperspect.a041949

Oscar J Pundel, Benjamin G Neel

{"title":"Models of High-Grade Serous Ovarian Carcinoma.","authors":"Oscar J Pundel, Benjamin G Neel","doi":"10.1101/cshperspect.a041949","DOIUrl":"https://doi.org/10.1101/cshperspect.a041949","url":null,"abstract":"High-grade serous ovarian carcinoma (HGSC) remains an incompletely understood, highly lethal disease. Historically, a lack of fidelitous in vitro and in vivo models representing HGSC biology and therapy response has been a major barrier to progress. As we discuss below, multiple (if not most) early studies used-and some investigators continue to use-human \"ovarian cancer cell lines\" that lack key genomic/genetic features of HGSC, rendering their conclusions questionable. The frequently deployed ID8 syngeneic mouse model is similarly suspect, as it derives from ovarian surface epithelium (OSE) and is Trp53 wild-type. In contrast, most, if not all, HGSC arises in fallopian tube epithelium (FTE), and bona fide HGSC is universally TP53 mutant or silenced. Over the past 10 years, attempts have been made to rectify these historical deficiencies, including careful assessment of the genetic composition of standard ovarian cancer cell lines and the development of mouse and human organoids, genetically engineered mouse models (GEMMs), and patient-derived xenografts (PDXs). In this review, we discuss these advances, exploring their differences, strengths, and weaknesses. We also describe \"next-generation\" approaches to more faithfully model HGSC cells in the context of a more realistic tumor microenvironment.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238495","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

Genetic Predisposition to Hematologic Malignancies. 血液恶性肿瘤的遗传易感性。

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-10-01 DOI: 10.1101/cshperspect.a041585

Kayla V Hamilton, Akiko Shimamura, Jessica A Pollard

{"title":"Genetic Predisposition to Hematologic Malignancies.","authors":"Kayla V Hamilton, Akiko Shimamura, Jessica A Pollard","doi":"10.1101/cshperspect.a041585","DOIUrl":"10.1101/cshperspect.a041585","url":null,"abstract":"Hematologic malignancies (HMs) have been increasingly recognized in association with an underlying genetic predisposition syndrome (GPS) in individuals of all ages. It is critical for hematology and oncology providers to be aware of the diagnostic findings, physical examination findings, and aspects of family history that raise suspicion for an underlying GPS. Moreover, recognition of how somatic gene panel testing, frequently done at the time of HM diagnosis, may raise suspicion for an underlying germline condition based on the mutation profile reported, is prudent. With knowledge of an underlying germline condition, the chemotherapy used for a given HM may be impacted and the role of hematopoietic stem cell transplant more critically considered. Off-therapy monitoring after HM treatment is completed will also likely be impacted. In this work, we review key features of several GPSs associated with increased risks for HM while also outlining the diagnostic workup to identify GPSs and treatment considerations for affected patients. Armed with this knowledge, treating providers may evaluate the possibility of a GPS in patients with leukemia/lymphoma and modify their treatment plan accordingly.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390338","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

Cancer Metabolism: Aspirations for the Coming Decade. 癌症代谢：未来十年的愿望

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-10-01 DOI: 10.1101/cshperspect.a041555

Ralph J DeBerardinis, Karen H Vousden, Navdeep S Chandel

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 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-10-01 DOI: 10.1101/cshperspect.a041600

Lucienne Chatenoud, Kevan C Herold, Jean-François Bach, Jeffrey A Bluestone

引用次数: 0

α-Synuclein Biomarkers for Parkinson's Disease. 帕金森病α-突触核蛋白生物标志物

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041944

Alexandra Lodge, Julian Agin-Liebes

{"title":"α-Synuclein Biomarkers for Parkinson's Disease.","authors":"Alexandra Lodge, Julian Agin-Liebes","doi":"10.1101/cshperspect.a041944","DOIUrl":"https://doi.org/10.1101/cshperspect.a041944","url":null,"abstract":"α-Synuclein (α-syn) biomarkers show great promise as diagnostic tools for Parkinson's disease (PD). In recent years, a large body of evidence has validated their efficacy as diagnostic tools for PD and other synucleinopathies and has shown potential for use in patients with isolated prodromal symptoms of PD, such as rapid eye movement (REM) sleep behavior disorder and hyposmia, and further illuminates the pathophysiology of both idiopathic and genetic causes. Various detection methods have been deployed, predominantly immunohistochemistry and α-syn seed amplification assays. α-Syn has been shown to be detectable in many different tissues and biofluids in PD patients, each with benefits and limitations for practical use. α-Syn biomarker studies have shown sensitivities for diagnosis of PD and specificity against healthy controls up to 100%. However, lack of standardization of methods of detection currently limits interlaboratory validation of results. Verification of these assays could lead to more widespread inclusion of these modalities to detect α-syn into biological definitions of PD and provide frameworks for developing disease-modifying therapies. In this review, we discuss the current state of α-syn biomarkers and highlight their potential use in clinical practice and research settings, while identifying further work that is needed in this field.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124490","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

Animal Models of Parkinson's Disease. 帕金森病的动物模型。

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041644

Valina L Dawson, Ted M Dawson

{"title":"Animal Models of Parkinson's Disease.","authors":"Valina L Dawson, Ted M Dawson","doi":"10.1101/cshperspect.a041644","DOIUrl":"https://doi.org/10.1101/cshperspect.a041644","url":null,"abstract":"Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially in mice, has aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of exhibiting a broad range of phenotypes and coupled with their conserved genetic and anatomical structures provides unparalleled molecular and pathological tool to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. α-Synuclein preformed fibril (PFF) injections, which induce the aggregation of endogenous α-synuclein, remarkably recapitulate pathological processes observed in human PD. Here, we provide an overview of the generation and characterization of transgenic and knockout mice and the α-synuclein PFF models used to study PD followed by molecular insights that have been gleamed these PD mouse models.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124474","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

Parkinson's Disease, Second Edition. 帕金森病，第二版。

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041954

Serge Przedborski, Stanley Fahn

引用次数: 0

Cancer Therapies Targeting Cellular Metabolism. 针对细胞代谢的癌症疗法。

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-09-02 DOI: 10.1101/cshperspect.a041657

Benjamin Morris, Alejandro Gutierrez

{"title":"Cancer Therapies Targeting Cellular Metabolism.","authors":"Benjamin Morris, Alejandro Gutierrez","doi":"10.1101/cshperspect.a041657","DOIUrl":"10.1101/cshperspect.a041657","url":null,"abstract":"Cancer is caused by mutations that drive aberrant growth, proliferation, and invasion, thus overriding regulatory mechanisms that normally link these processes to organismal needs and cellular physiology. This imposes demands for the production of energy and biomass and for survival in microenvironments that are often nonphysiologic and nutrient-poor, which are met by rewiring of cellular metabolism. The resultant dependence of tumor cells on altered metabolism can induce sensitivity to specific metabolic perturbations that can be exploited for cancer therapy. Some cancers are caused by mutations that impart a novel function to metabolic enzymes, leading to the production of a tumor-promoting metabolite that is dispensable in normal cells, representing an ideal therapeutic target. Tumors can also exploit metabolic regulation of cellular immunity to evade antitumor immune responses, and deciphering this biology has revealed potential targets for therapeutic intervention. Here, we discuss a number of illustrative examples highlighting the therapeutic potential and the challenges of targeting metabolism for cancer therapy.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715435","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

Who Are the Space Invaders? Planetary Protection and the Role of Biological Interactions between Extraterrestrial and Terrestrial Biospheres. 谁是太空入侵者？行星保护和地外生物圈与地球生物圈之间生物相互作用的作用。

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-09-02 DOI: 10.1101/cshperspect.a041626

D E Betsy Pugel, John D Rummel

{"title":"Who Are the Space Invaders? Planetary Protection and the Role of Biological Interactions between Extraterrestrial and Terrestrial Biospheres.","authors":"D E Betsy Pugel, John D Rummel","doi":"10.1101/cshperspect.a041626","DOIUrl":"10.1101/cshperspect.a041626","url":null,"abstract":"Exploring our solar system and returning pieces of it to Earth is a central part of the existential quest to search for life beyond our home planet. Understanding the biosafety and biocontamination implications of landing on a planetary body or in bringing pieces of our solar system back to our home planet are the two themes that are central to planetary protection, a discipline that is unique to spacefaring nations. The nature of planetary protection is twofold: (1) to ensure that we minimize our own terrestrial microbial footprint on other planets and moons (planetary bodies) in our solar system (forward contamination), and (2) to ensure that we minimize the potential impact of returning samples from another planet or moon to Earth (backward contamination). The discipline of planetary protection focuses on who is the biological \"invader\" and when does their arrival indicate an \"invasion\"? The degree to which there is potential for biological or organic interactions that result in biocontamination or changes in biosafety posture is the central topic of this work.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"15 9","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945414","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

A History of Cancer Research: Cancer Cell Growth and Metabolism. 癌症研究的历史：癌细胞的生长和代谢。

IF 10.1 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2025-09-02 DOI: 10.1101/cshperspect.a035782

Joseph Lipsick

引用次数: 0