Clinical and translational discovery最新文献

{"title":"Targeting mutated KRAS in the first-line therapy","authors":"Hideaki Ijichi","doi":"10.1002/ctd2.291","DOIUrl":"https://doi.org/10.1002/ctd2.291","url":null,"abstract":"<p>KRAS is one of the most frequently mutated oncogenes in cancer.<span>¹</span> Codon 12, 13 and 61 mutations are frequently observed as the hot spot mutations in various cancers. Normally, KRAS protein functions as a molecular switch downstream of cell surface receptors, such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor, etc., shuttling GTP-bound active state and GDP-bound inactive state, which turns on and off the growth factors’ signals that activate MAPK, PI3K/AKT/mTOR and other signalling pathways fundamental for cell proliferation, differentiation and survival. The oncogenic mutations lock the KRAS at the active state, resulting in contributing to tumorigenesis. Genetically engineered mouse models containing tissue-specific Kras codon 12 mutation have developed clinically relevant cancers in the corresponding tissues, which indicates the central driver role of KRAS mutation in cancer formation and progression.<span>2</span></p><p>Therefore, targeting the mutated KRAS is considered an ideal therapeutic strategy in the KRAS-mutated cancers. Especially, KRAS codon 12 mutation is detected in 90% of pancreatic cancer,<span>1</span> which suggests the tumour addiction to the mutated KRAS in the most deadly cancer with a 5-year survival of still around 10%. However, KRAS has been undruggable for more than 40 years, because of its relatively smooth protein structure and lack of approachable binding pocket.<span>1</span></p><p>Recently, KRAS G12C-specific covalent inhibitors, sotorasib and adagrasib, that lock KRAS to a GDP-bound inactive state, were developed and clinically approved for the treatment of cancers with KRAS G12C mutation,<span>3</span><b>^,</b><span>4</span> with significant therapeutic efficacy, especially in non-small cell lung cancer (NSCLC). It was a breakthrough in the field: Now, KRAS is druggable. Following them, other KRAS G12C inhibitors, as well as inhibitors specific for other KRAS mutations, have been on the line of development with growing expectations in the improvement of clinical practice.</p><p>Subsequent to the success of the KRAS G12C inhibitor, acquired resistance to the inhibitor has become a clinical problem and the underlying mechanisms have been explored.<span>5</span> Compared to NSCLC, colorectal cancer with KRAS G12C mutation showed a limited objective response to the KRAS G12C inhibitors, indicating resistance to the therapy. To overcome the resistance, combinatorial therapeutics have been investigated with the KRAS G12C inhibitors. Recently, a couple of studies demonstrated the feasibility and possible efficacy of the combination of the KRAS G12C inhibitors with EGFR inhibitors in advanced colorectal cancer.<span>6</span><b>^-</b><span>8</span> Among them, the CodeBreaK 300, a phase 3, multicenter, open-label, randomized trial (NCT05198934) showed that a KRAS G12C-specific inhibitor sotorasib, in combination with EGFR inhibitor panitumu","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of immune microenvironment on musculoskeletal health","authors":"Ren Xu","doi":"10.1002/ctd2.290","DOIUrl":"https://doi.org/10.1002/ctd2.290","url":null,"abstract":"<p>Understanding the interplay between immune cells and the bone marrow microenvironment is crucial for elucidating age-related musculoskeletal changes. In this commentary manuscript, we summarized that studies have shown that proinflammatory immune cells in the bone marrow, such as macrophages and neutrophils, can inhibit bone formation by secreting grancalcin. Research on skeletal stem cells (SSCs) in aged mice reveals a shift towards pro-inflammatory gene expression, affecting their osteogenic potential, while another study maps age-related changes in cranial SSC niches, emphasizing the role of the CXCL12–CXCR4 axis in stem cell-immune cell communication, Additionally, the immune system influences hematopoietic stem cells (HSCs); Niche ageing and accumulation of mutations with age lead to HSC exhaustion and a bias towards myeloid differentiation, with toll-like receptors playing a key role in maintaining hematopoiesis and bone metabolism balance.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling a novel cellular stress response mechanism to photodamage","authors":"Naibedya Dutta,&nbsp;Gilberto Garcia,&nbsp;Ryo Higuchi-Sanabria","doi":"10.1002/ctd2.286","DOIUrl":"https://doi.org/10.1002/ctd2.286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Ultraviolet (UV) radiation, a component of sunlight, holds both advantageous anddetrimental effects on human health. While shorter wavelengths of UV radiationaid in melanin and vitamin D synthesis, longer wavelengths pose risks like skincancer and premature aging due to DNA damage. To combat such stress, cellsemploy various mechanisms, including the heat shock response (HSR). Activation of this response involves a highly regulated transcriptional processorchestrated by heat shock factors (HSFs). While HSF1 has been observed as a keytranscription factor for HSR, other HSFs are also found to be associated withdiverse cellular functions, including stress responses. Here, we discuss arecent study by Feng et al., published in <i>Clinical and Translational Medicine</i>, shedding light on the novel function of HSF4 in regulating inflammation and senescence following UV exposure. The researchers observed acomplex of HSF4 and the cofactor COIL (Coilin) at R-loops–aberrant DNA-RNAhybrid structures arising from UV-induced DNA damage in human skin cells. Inthe study, they proposed the HSF4-COIL complex at R-loops as a potential therapeutic target to mitigate UV-induced skin damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140333104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new metabolic signature to predict melanoma recurrence","authors":"Ngan K. Vu,&nbsp;Rachel J. Perry","doi":"10.1002/ctd2.288","DOIUrl":"https://doi.org/10.1002/ctd2.288","url":null,"abstract":"<p>Melanoma is one of the most prevalent cancers in the United States, accounting for 5% of all new cancer cases, and has been increasing worldwide.<span>¹</span> Melanoma arises from the malignant proliferation of melanocytes, cells that produce melanin that provides skin pigmentation. The high metastatic potential of melanoma drastically affects the prognosis of patients diagnosed at later stages. In particular, 50%–75% of melanoma cases metastasize to the brain, accounting for 54% of all melanoma-related deaths.<span>^{2, 3}</span> It is thus critical to diagnose melanoma at earlier stages to limit metastasis and more widespread invasion, allowing for complete surgical removal of the tumour.</p><p>While excision of early-stage melanoma results in a favourable prognosis, recurrence can occur in many of these patients, being responsible for a large proportion of melanoma-related deaths. The mechanisms underlying melanoma recurrence remain incompletely understood. Recent evidence points toward the critical influence of the tumour microenvironment (TME) on melanoma recurrence. The TME is composed of the extracellular matrix, immune cells, mesenchymal cells, and blood vessels that surround the tumour cells, communicating their behaviour and response to treatment. Dissecting the melanoma TME therefore may give rise to diagnostic markers and mechanistic insights into its recurrence patterns, opening avenues for the development of targeted therapies that can lower the risk of melanoma recurrence.</p><p>Recent development in artificial intelligence (AI)-driven histopathology introduces important tools that can be leveraged to investigate the spatial organization and molecular markers in the TME. The application of AI technology has been proven to objectively and consistently produce valuable clinical information that provides molecular markers and predicts cancer outcomes. The utilization of AI in cancer histopathology is not just limited to its predictive and prognostic usage. This technology can be used to profile and map tumour immune cell networks and dissect molecular pathways within the TME, revealing critical mechanistic insights into response to treatments, recurrence patterns, and metastatic potential.</p><p>In a recent study, Szadai et al.<span>⁴</span> employed AI-powered histopathology and spatial proteomics to explore and compare the tumour cells and TME interplay between recurrent and non-recurrent primary melanoma samples. This AI-driven methodology proved to be effective in distinguishing normal tissue from stromal and tumour regions across both groups. Notably, these authors integrated laser-microdissection technology and quantitative proteomic analysis with digital pathology readouts. This unique approach produced critical spatial proteomics data that sheds light on the molecular interplay between mitochondrial functions and immune response in the tumour and stromal components of recurrent melanoma.</p><p","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140297254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial omics accelerate the study of cancer-associated fibroblasts in non-small lung cancer","authors":"Haozhen Liu,&nbsp;Jixian Liu,&nbsp;Chao Chen","doi":"10.1002/ctd2.285","DOIUrl":"https://doi.org/10.1002/ctd2.285","url":null,"abstract":"<p>Tumour microenvironment (TME) is one of the important factors associated with cancer progression. TME is a multicellular system composed of fibroblasts, endothelial and immune cells, distributed in the extracellular matrix (ECM), and closely interacts with tumour cells to promote the occurrence and development of cancers. In TME, secreted products of various immune and non-immune cell types, such as cytokines and chemokines, as well as metabolites, hypoxia, angiogenesis and ECM remodelling drive chronic inflammation.<span>¹</span> Recent studies have shown that cancer-associated fibroblasts (CAFs) are important regulators of anti-tumour immune response. CAFs can reshape TME by secreting a variety of cytokines, thereby promoting immune escape. Therefore, targeting CAFs may improve the effectiveness of immunotherapy.<span>^{2, 3}</span> For example, NOX4 inhibitors can reverse the formation of CAFs, thereby restoring anti-tumor immunotherapy efficacy.<span>³</span> However, due to the high heterogeneity of the CAF population, its origin and function remain unclear, and the lack of understanding of these issues greatly limits the clinical transformation of CAFs.<span>⁴</span></p><p>The development of single-cell transcriptome sequencing (scRNA-seq) has brought fundamental advances in cancer research. The subpopulations and functions of CAFs in non-small-cell lung cancer (NSCLC) have been described in several studies using scRNA-seq.<span>^5-7</span> However, due to the loss of spatial information, most studies limited their research focus to immune cells in tumours. The emergence of spatial omics technology has made up for the shortcomings of single-cell sequencing, using spatial transcriptome technologies, it is expected to characterize the molecular characteristics and immune regulatory functions of CAFs in cancer.</p><p>In a recent study by Xu et al., a subpopulation of CAFs, <i>POSTN</i>⁺ CAFs were found to have a close localization with <i>SPP1</i>⁺ macrophages, and correlated with exhausted phenotypes and lower infiltration of T cells in NSCLC.<span>⁸</span> Initially, the study identified diverse fibroblast subpopulations in NSCLC through the integration of fibroblasts in the Peking cohort (<i>N</i> = 1986) with fibroblasts in Samsung cohort<span>⁶</span> (<i>N</i> = 3499) and Tongji cohort<span>⁷</span> (<i>N</i> = 4497). Several iCAF subpopulations (clusters C01_CCL11, C05_IGF1 and C06_CCL2), adventitial fibroblasts (C03_PI16), alveolar fibroblasts (C04_COL13A1), as well as myCAF subgroups (C02_POSTN, C07_MKI67 and C09_MYH11) were identified. Specifically, they found that <i>POSTN</i>⁺ CAFs (C02_POSTN) were enriched in tumour/metastatic samples compared to normal samples. Gene Set Variation Analysis was performed and <i>POSTN</i>⁺ CAFs showed activities in several pro-invasive pathways such as “angiogenesis” and","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140135375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of telocytes dominated cell–cell communication in fibroproliferative acute respiratory distress syndrome","authors":"Yonghua Zheng,&nbsp;Songshan Cai,&nbsp;Zongfeng Zhao,&nbsp;Xiangdong Wang,&nbsp;Lihua Dai,&nbsp;Dongli Song","doi":"10.1002/ctd2.277","DOIUrl":"https://doi.org/10.1002/ctd2.277","url":null,"abstract":"<p>Telocytes (TCs) are a new type of interstitial cell identified in multiple tissues of mammals, including the human lung, and mediate homocellular or heterocellular cell-cell communication. Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure and combined with direct and indirect lung injury, which is induced by pneumonia, sepsis, burns, etc. Pulmonary fibrosis is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium and gets more and more attention as a well-recognized sequela of ARDS or mechanical ventilation. However, the existing intervention measures could not prevent the progression of pulmonary fibrosis. Although the protective effect of TCs in acute lung injury had been demonstrated in both cellular and animal models in previous studies by our or other researchers, the roles of TCs mediated cell-cell communication in fibroproliferative ARDS is unclear. This review is aimed at integrating our understanding of TC-mediated cell–cell communication in lung diseases with pulmonary fibrosis after ARDS.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomedicine: a frontier of the breast cancer treatment","authors":"Swarup Sonar,&nbsp;Sidhanti Nyahatkar,&nbsp;Ketki Kalele,&nbsp;Manab Deb Adhikari","doi":"10.1002/ctd2.281","DOIUrl":"https://doi.org/10.1002/ctd2.281","url":null,"abstract":"<p>Cancer is an unsolved health crisis that affects a large number of world's population.<span>¹</span> Breast cancer is the most challenging problem in the current time and this cancer affects a huge female population every year.<span>²</span> Several factors are involved in breast cancer such as age, genetic mutation, obesity, food habits, family history, etc. In this situation, we need an affordable, effective, and efficient theranostics approach. This global crisis is addressed via nanomedicine, which is an applied domain of nanotechnology (it is related to cancer diagnosis, sensor, and therapeutics development based on nanomaterials and nanotechnology).<span>³</span> Nanoparticles based nanomedicine has dynamic application in cancer diagnostic tools development,  therapeutic approach development, and several biological molecules transports.<span>⁴</span> It is also an effective and specific drug transport vehicle for breast cancer.<span>⁴</span> The purpose of nanomedicine is to develop a strong immune response (cellular and humoral immune response together) against cancer. Nanovaccine (majorly based on nanoparticle modification for cellular transport) is more stable, biocompatible, and less toxic.<span>^{5, 6}</span> Immune response developmentary antigen protein-loaded particles are developed Treg (regulatory T-cells) cells mediated immune response.<span>⁷</span> Nanomedicine becomes a promising solution for breast cancer. Nanomaterial size, surface charges, and chemical composition play principleroles in therapeutic release, cytotoxicity, and drug-uptake phenomena.<span>⁸</span> The scientific investigation currently highlights that during cancer development and progression, extracellular vesicles (EVs) play a regulatory role in cancer.<span>⁹</span> This type of invention introduces a new member of nanomedicine, called EVs. In breast cancer, exosomes (a subpopulation of EVs) regulate several stages of cancer development (cancer cell proliferation, angiogenesis, immune cells suppression, metastasis, and drug and therapeutic-resistance development).<span>^10-13</span> Exosomes cargo molecules are significantly influenced by breast cancer development.<span>¹⁰</span> Blood-circulated exosomes carry signature breast cancer biomarkers (diagnostic and prognostic biomarkers).<span>^{10, 13}</span> In breast cancer, the most challenging part of early diagnosis. Exosomes-based liquid biopsy is the most efficient approach for screening cancer compared to tissue biopsy.<span>¹⁴</span> The current development of nanomedicine indicates that single exosome profiling, exosome barcoding, exosome sensor, and multi-omic approaches are leading frontier combating for breast cancer.<span>^{15, 16}</span> Plant-source exosomes (tea leaf exosomes) based nanomedicine also (tea leaf exosomes) show breast cancer healing ac","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the biological effects of socioeconomic adversity in cancer","authors":"David Füller","doi":"10.1002/ctd2.284","DOIUrl":"https://doi.org/10.1002/ctd2.284","url":null,"abstract":"<p>Numerous studies have demonstrated socioeconomic differences in cancer incidence and outcomes, including shorter cancer survival times in patients with lower educational attainment and income, which represent important indicators of lower socioeconomic status (SES). The hypothesis proposing that disparities in cancer outcomes and mortality linked to the social determinants of health (SDoH) can be accounted for by higher risk factor prevalences or the interrelation of various SDoH has been contradicted by current evidence and previous studies have introduced potential biological mechanisms of the SDoH which are summarised by the term ‘biology of socioeconomic adversity’. Socioeconomic inequalities in cancer risk and outcomes cannot be entirely attributed to differences in clinical, behavioural, and environmental risk factors in current clinical research. Hence, it is crucial to investigate various factors, including specific biomarkers and pathophysiological pathways affected by the SDoH.</p><p>For more than 30 years, numerous studies have demonstrated socioeconomic differences in cancer incidence and survival.<span>^1-3</span> In the first place, it was found that shorter survival times in solid cancers and lymphoma are associated with lower income and education levels, two important indicators of lower SES, and it was noted that this effect could not be accounted for by the stage of disease at initial presentation and that this association persisted after statistically adjusting for all known prognostic factors.<span>⁴</span> Today, socioeconomic inequalities in cancer survival rates still persist in clinical trials despite access to protocol-directed care,<span>⁵</span> implying that optimal equitable healthcare cannot resolve inequalities in outcomes. For these reasons, a multiplex approach to this global health problem is necessary.</p><p>The hypothesis proposing that disparities in premature and cancer mortality linked to the SDoH can be accounted for by higher risk factor prevalences, like smoking, as well as by the interrelation of various SDoH, such as low income and living in adverse neighbourhood physical and social environments which aggregate within an individual, thereby amplifying health effects, holds significant appeal. However, it has been estimated that only about half of the association between area-level SES, which includes factors such as income, education, and occupation at the neighbourhood level, and cancer mortality risk can be explained by higher rates of individual-level risk factors including smoking, diet, physical activity, participation in cancer screening programs, and obesity.<span>⁶</span> Even more, current evidence contradicts the idea that differences in cancer-associated mortality based on educational attainment, an often used indicator of individual-level SES and a key SDoH, can be attributed to differences in conventional cancer risk factors or the interrelation","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140096698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omic approaches for biomarker discovery in Moyamoya disease","authors":"Laura Gatti,&nbsp;Anna Bersano,&nbsp;Gemma Gorla,&nbsp;Giuliana Pollaci,&nbsp;Tatiana Carrozzini,&nbsp;Antonella Potenza","doi":"10.1002/ctd2.270","DOIUrl":"https://doi.org/10.1002/ctd2.270","url":null,"abstract":"<p>Moyamoya disease (MMD) is a rare cerebrovascular condition characterized by a chronic and progressive narrowing of the terminal portion of the bilateral internal carotid arteries, causing the formation of an abnormal vascular network. These compensatory brain vessels often prove insufficient, leading MMD patients to severe ischemic or hemorrhagic clinical manifestations. Surgical treatment, mainly based on direct and indirect revascularization, represents the preferred procedure for MMD patients until now, for improving cerebral hemodynamics and decreasing the pathological collateral network development. The specific mechanism underlying both the progressive arterial wall thickening and the spontaneous angiogenesis of the defective moyamoya vessels remains poorly understood. Moreover, the lack of reliable animal or cellular pre-clinical models and the heterogeneous data on MMD pathophysiology have hampered the clinical validation of powerful biomarkers, as well as the development of tailored therapeutic options.</p><p>The previous investigations aimed at biomarker discovery mainly addressed patients’ peripheral blood samples, which may not reflect the real pathological changes of MMD cerebral vessels. On the other hand, prior interesting studies involving cerebral artery specimens (e.g. middle cerebral artery [MCA]) were performed through RNA microarray techniques, which have several limitations as compared to high-throughput RNA sequencing (RNA-seq). As an example, the long noncoding RNA profile of MMD patients’ MCA provided data regarding antibacterial response, T-cell receptor signalling pathway and cytokine production.<span>¹</span> Interestingly, Xu et al. carried out an RNA-seq analysis of MMD patients’ MCA, as compared to atherosclerosis-associated intracranial artery stenosis/occlusion. The authors identified several differential expressed genes mainly involved in extracellular matrix organization and mitochondrial function, thus highlighting novel insights into disease pathogenesis.<span>²</span></p><p>Since the challenging sampling of cerebral artery specimens for transcriptomic studies, other ultrasensitive techniques were recently carried out for molecular profiling of circulating biomarkers from cerebrospinal fluid (CSF) or blood. The study by Ota et al. through a next-generation sequencing (NGS) approach demonstrated that specific changes occurred in the expression levels of extracellular vesicle-derived microRNAs (miRNAs), extracted from intracranial CSF of MMD patients when compared to controls.<span>³</span> The authors suggested that MMD has a specific regulatory mechanism for angiogenesis, different from that found in other ischemic disorders. Proteomic approaches towards MMD patients’ circulating fluids have already been reported. Tandem mass tag (TMT)-labelled proteome analysis was performed on serum-derived exosomes, extracted from pure ischemic or hemorrhagic MMD patients and healthy cont","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140063727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sculpting nursing resilience: Transforming lives, nurturing ethics in chimeric antigen receptor T-cell therapy","authors":"Pranay Bende","doi":"10.1002/ctd2.283","DOIUrl":"https://doi.org/10.1002/ctd2.283","url":null,"abstract":"<p>Revolutionizing cancer care, chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy anticancer treatment that uses genetically modified T-cells to combat cancer. Nurses have a key role in fostering resilience in patients and caregivers undergoing this therapy, and in navigating ethical and legal issues and safeguarding their rights and interests. Unlike haematological malignancies, solid tumours have more diverse and heterogeneous tumour-associated antigens (TAAs), which can lead to off-target toxicity or antigen escape.<span>¹</span></p><p>Resilience enables the adversity to rebound from stress and trauma even amid faced with uncertainties risks and side effects including cytokine release syndrome, hypogammaglobulinemia, neurotoxicity, infection, prolonged cytopenias, and organ damage, and can lead to life-threatening in some cases (See Figure 1).</p><p>Mr. Bende contributed to preparing and collecting original literature and figures and writing and editing the manuscript.</p><p>The author declares no conflict of interest.</p><p>Not applicable.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140063734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}