Advances in experimental medicine and biology最新文献_第4页

A Comprehensive Review of the Mechanisms and Clinical Development of Monoclonal Antibodies in Cancer Therapy. 单克隆抗体在肿瘤治疗中的作用机制及临床进展综述。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/5584_2024_838

Selen Gencsoy Eker, Gizem Inetas Yengin, Cansu Tatar, Gulperi Oktem

引用次数: 0

E-Cadherin-Mediated Cell-Cell Adhesion and Invasive Lobular Breast Cancer. e -钙粘蛋白介导的细胞粘附与浸润性小叶乳腺癌。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-70875-6_14

Esme Bullock, Valerie G Brunton

{"title":"E-Cadherin-Mediated Cell-Cell Adhesion and Invasive Lobular Breast Cancer.","authors":"Esme Bullock, Valerie G Brunton","doi":"10.1007/978-3-031-70875-6_14","DOIUrl":"10.1007/978-3-031-70875-6_14","url":null,"abstract":"E-cadherin is a transmembrane protein and central component of adherens junctions (AJs). The extracellular domain of E-cadherin forms homotypic interactions with E-cadherin on adjacent cells, facilitating the formation of cell-cell adhesions, known as AJs, between neighbouring cells. The intracellular domain of E-cadherin interacts with α-, β- and p120-catenins, linking the AJs to the actin cytoskeleton. Functional AJs maintain epithelial tissue identity and integrity. Transcriptional downregulation of E-cadherin is the first step in epithelial-to-mesenchymal transition (EMT), a process essential in development and tissue repair, which, in breast cancer, can contribute to tumour progression and metastasis. In addition, loss-of-function mutations in E-cadherin are a defining feature of invasive lobular breast cancer (also known as invasive lobular carcinoma (ILC)), the second most common histological subtype of breast cancer. ILC displays a discohesive, single-file invasive growth pattern due to the loss of functional AJs. Despite being so prevalent, until recently there has been limited ILC-focused research and historically ILC patients have often been excluded from clinical trials. Despite displaying a number of good prognostic indicators, such as low grade and high rates of estrogen receptor positivity, ILC patients tend to have similar or poorer outcomes relative to the most common subtype of breast cancer, invasive ductal carcinoma (IDC). In ILC, E-cadherin loss promotes hyperactivation of growth factor receptors, in particular insulin-like growth factor 1 receptor, anoikis resistance and synthetic lethality with ROS1 inhibition. These features introduce clinical vulnerabilities that could potentially be exploited to improve outcomes for ILC patients, for whom there are currently limited tailored treatments available.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1464 ","pages":"259-275"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A Knockin Model with the Mouse Equivalent to the c.2299delG Mutation in Usherin Exhibits Early-Onset Hearing Loss and Progressive Retinal Degeneration. 诱导因子c.2299delG突变小鼠敲入模型显示早发性听力损失和进行性视网膜变性。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_42

Lars Tebbe, Muayyad R Al-Ubaidi, Muna I Naash

{"title":"A Knockin Model with the Mouse Equivalent to the c.2299delG Mutation in Usherin Exhibits Early-Onset Hearing Loss and Progressive Retinal Degeneration.","authors":"Lars Tebbe, Muayyad R Al-Ubaidi, Muna I Naash","doi":"10.1007/978-3-031-76550-6_42","DOIUrl":"10.1007/978-3-031-76550-6_42","url":null,"abstract":"Usher syndrome (USH) is the predominant cause of inherited deaf-blindness, largely attributed to type 2A (USH2A) mutations, and particularly the prevalent c.2299delG mutation. While knockout models successfully replicated the cochlear phenotype of USH, recapitulating the retinal phenotype proved challenging. Given that patient mutations often lead to mutant protein expression rather than its absence, we developed a knockin model expressing the mouse equivalent of the c.2299delG mutation in USH2A. This model exhibited a functional decline in the retina, characterized by retinal degeneration, structural anomalies in the connecting cilium and outer segment, and mislocalization of mutant USH2A and its interacting partners ADGRV1 and whirlin. Remarkably, retinal symptoms manifested earlier than in the Ush2a-/- mice. In the cochlea, the expression of truncated USH2A resulted in congenital hearing loss and disorganized stereocilia bundles. Thus, this knockin model underscores the necessity of expressing the mutant protein to faithfully reproduce the USH phenotype, providing valuable insights into the pathology of USH.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"253-257"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse. 杆状光感受器带突触中囊泡循环的分子成分。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_54

Christin Hanke-Gogokhia, Thomas E Zapadka, Stella Finkelstein, Vadim Y Arshavsky, Jonathan B Demb

引用次数: 0

Interacting Fat1 and Dchs Planar Cell Polarity Proteins Supported by Fjx1 Serve as Heterodimeric Intercellular Bridges Crucial to Support Spermatogenesis. Fjx1支持的Fat1和Dchs平面细胞极性蛋白相互作用是支持精子发生的关键异二聚体细胞间桥梁。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-82990-1_15

Tiao Bu, Lingling Wang, Xiaolong Wu, Sheng Gao, Damin Yun, Baiping Mao, Linxi Li, Fei Sun, C Yan Cheng

{"title":"Interacting Fat1 and Dchs Planar Cell Polarity Proteins Supported by Fjx1 Serve as Heterodimeric Intercellular Bridges Crucial to Support Spermatogenesis.","authors":"Tiao Bu, Lingling Wang, Xiaolong Wu, Sheng Gao, Damin Yun, Baiping Mao, Linxi Li, Fei Sun, C Yan Cheng","doi":"10.1007/978-3-031-82990-1_15","DOIUrl":"https://doi.org/10.1007/978-3-031-82990-1_15","url":null,"abstract":"Studies of the planar cell polarity (PCP) protein complexes Fat1/Fjx1 and Dchs/Fjx1 that form heterotypic interacting bridges of Fat1-Dchs between adjacent cells to confer PCP, as noted in Drosophila, are also found in mammalian cells and tissues as orthologs, such as in Sertoli cells and condensed spermatids in the seminiferous epithelium of the testis. Recent studies have shown that these two interacting PCP protein complexes are also crucial regulators of microtubule and actin dynamics, modulating the polymerization of both microtubules and actin filaments in the testis. In this review, we provide a brief update and thought-provoking concept on the PCP core proteins and the associated downstream signaling pathways utilized by PCP proteins to confer PCP and regulation of the microtubule and actin cytoskeletons in the testis. However, we focus on recent data in the field on the Fat1/Fjx1 and Dchs/Fjx1 protein complexes, which are also heterotypic interacting protein complexes, and their functional role in modulating the microtubule and actin cytoskeletal organization. Based on these recent findings, we formulate a hypothetic model depicting the role of these two PCP protein complexes in modulating the timely \"opening\" and \"closing\" of the blood-testis barrier (BTB) formed by adjacent Sertoli cells near the base of the seminiferous epithelium. Additionally, these two PCP protein complexes also modulate cytoskeletal dynamics between Sertoli cells and condensed spermatids to support haploid spermatid transport across the seminiferous epithelium during their structural transformation through spermiogenesis, and their eventual release at spermiation during the epithelial cycle of spermatogenesis. This hypothetical model will provide a useful framework for designing functional experiments to understand the role of PCP proteins in supporting spermatogenesis.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1469 ","pages":"355-374"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Recent Advances in the Role of Non-coding RNAs in Fetal Alcohol Spectrum Disorders. 非编码rna在胎儿酒精谱系障碍中的作用研究进展

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-81908-7_7

Ariana N Pritha, Andrea A Pasmay, Shahani Noor

{"title":"Recent Advances in the Role of Non-coding RNAs in Fetal Alcohol Spectrum Disorders.","authors":"Ariana N Pritha, Andrea A Pasmay, Shahani Noor","doi":"10.1007/978-3-031-81908-7_7","DOIUrl":"10.1007/978-3-031-81908-7_7","url":null,"abstract":"Despite numerous preclinical studies modeling fetal alcohol spectrum disorder (FASD)-associated neurodevelopmental deficits to date, a comprehensive molecular landscape dictating these deficits remains poorly understood. Non-coding RNAs constitute a substantial layer of epigenetic regulation of gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Yet, little is known about the differential expression of non-coding RNAs in the context of prenatal alcohol exposure (PAE) that are mechanistically linked with FASD-related neurobehavior deficits. This chapter reviews our current knowledge from preclinical studies in non-coding RNA-mediated molecular mechanisms that may underlie FASD pathophysiology. This chapter also summarizes relevant clinical evidence and current efforts in utilizing these non-coding RNA molecules as biomarkers of PAE-associated deficits impacting central nervous system (CNS) function. Unraveling the diverse roles of various species of non-coding RNAs is critical to enhancing our comprehension of these intricate molecular pathways. Understanding these pathways would likely contribute to identifying critical molecular target(s) for developing efficient treatment strategies and prognostic and diagnostic markers fostering advancements in treating and managing FASD-related CNS dysfunction.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1473 ","pages":"129-155"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Impact of Developmental Alcohol Exposure on Sleep Physiology. 发育性酒精暴露对睡眠生理的影响。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-81908-7_6

Valentina Licheri, Jonathan L Brigman

{"title":"Impact of Developmental Alcohol Exposure on Sleep Physiology.","authors":"Valentina Licheri, Jonathan L Brigman","doi":"10.1007/978-3-031-81908-7_6","DOIUrl":"10.1007/978-3-031-81908-7_6","url":null,"abstract":"The present chapter summarizes the clinical and preclinical findings collected to date, showing the impact of developmental alcohol exposure on sleep physiology. Sleep is a complex physiological process that plays a pivotal role in maintaining overall health and well-being via its involvement in regulating physiological, cognitive, and emotional functions. Clinical studies consistently report a high prevalence of sleep disturbances in children and adolescents diagnosed with fetal alcohol spectrum disorders (FASDs), including short sleep duration, sleep anxiety, bedtime resistance, increased sleep fragmentation, and parasomnias. It is established that alcohol consumption during gestation impairs brain development, leading to structural and functional alterations that may affect sleep architecture. In addition, clinical investigations have found a significant correlation between sleep-wake cycle disruptions and cognitive impairments after developmental alcohol exposure, and sleep disturbances are increasingly recognized as a substantial problem among FASD patients. However, the molecular mechanisms underlying these disturbances are poorly understood. Surprisingly, few studies with animal models of FASDs have characterized the effect of developmental ethanol exposure on sleep physiology, and these have focused on high doses. This chapter provides an overview of the current knowledge, reports the sleep disturbances in FASD patients, and then summarizes the gap in understanding the molecular and physiological mechanisms.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1473 ","pages":"111-127"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Defects of Cortical Microcircuits Following Early Exposure to Alcohol. 早期接触酒精后的皮质微回路缺陷

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-81908-7_1

Alberto Granato

引用次数: 0

Innate Antiviral Defense of the Male Reproductive System. 男性生殖系统的先天抗病毒防御。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-82990-1_3

Jing Zhang, Yixuan Yang, Daishu Han, Fei Wang

{"title":"Innate Antiviral Defense of the Male Reproductive System.","authors":"Jing Zhang, Yixuan Yang, Daishu Han, Fei Wang","doi":"10.1007/978-3-031-82990-1_3","DOIUrl":"https://doi.org/10.1007/978-3-031-82990-1_3","url":null,"abstract":"The male reproductive system (MRS) is a complex system, considering its isolated anatomical locations and special microenvironments. The major organs of the MRS, including the testis, epididymis, seminal vesicle, and prostate, are relatively separated and have distinct immune status for protecting male germ cells from adverse immune responses and counteracting microbial infection for conducting their functions. A large spectrum of viruses has tropism for the MRS and may impair male fertility. To defend against invading viruses, the MRS has developed a local innate antiviral environment to reduce virus-impaired male fertility. All major tissue cells are well equipped with innate antiviral machinery. Both tissue-specific cells and immune cells are involved in the antiviral defense against viral infection of the MRS. Understanding the mechanisms underlying local innate antiviral responses in the MRS can aid in the development of preventive and therapeutic strategies for viral diseases. This chapter focuses on pattern recognition receptor-mediated innate antiviral responses in the major cells of the testis, epididymis, seminal vesicle, and prostate.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1469 ","pages":"49-65"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Graft Source Choice. 嫁接源选择。

4区医学

Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-84988-6_4

Sanghee Hong, Mitchell E Horwitz

{"title":"Graft Source Choice.","authors":"Sanghee Hong, Mitchell E Horwitz","doi":"10.1007/978-3-031-84988-6_4","DOIUrl":"https://doi.org/10.1007/978-3-031-84988-6_4","url":null,"abstract":"Bone marrow grafts offer a lower risk of graft-versus-host disease (GVHD) but require a surgical procedure and are associated with slower engraftment rates. Peripheral blood stem cells (PBSCs) enable faster engraftment and easier collection but have historically been associated with a higher risk of GVHD. Umbilical cord blood (UCB) grafts are readily available and carry no donor risk, with a higher tolerance for human leukocyte antigen mismatches and a lower risk of GVHD, but they are constrained by limited cell doses and slower engraftment. Recent advancements in transplant techniques-such as post-transplant cyclophosphamide to reduce GVHD rates in PBSC grafts, and cord blood expansion methods to increase the effectiveness of UCB grafts-have significantly improved transplant outcomes.Each graft source offers unique benefits and drawbacks that impact the selection process, factoring in patient age, disease type, donor availability, engraftment speed, immune recovery, GVHD risk, and logistical and financial considerations. These complexities highlight the need for a comprehensive and tailored approach to graft source selection, alongside adherence to guidelines and best practices, to optimize outcomes in allogeneic hematopoietic cell transplantation.","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1475 ","pages":"57-75"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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