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{"title":"A hybrid epithelial/mesenchymal state in head and neck cancer: A biomarker for survival with differential prognosis by self-reported race.","authors":"Angela L Mazul, Thomas F Barrett, Graham Colditz, Anuraag S Parikh, Salma Ramadan, Jose P Zevallos, Jason T Rich, R Alex Harbison, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Itay Tirosh, Sidharth V Puram","doi":"10.1016/j.medj.2024.05.014","DOIUrl":"10.1016/j.medj.2024.05.014","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is the 6^th leading cause of cancer-related mortality, with racial disparities amplifying the challenges in treatment. Although the relationship between hybrid epithelial/mesenchymal (E/M) states and tumor progression is of interest, no studies have characterized the clinical relevance of hybrid E/M states in head and neck cancer outcomes among self-reported racial cohorts.</p><p><strong>Methods: </strong>Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas. We utilized our previously collected single-cell profiles to generate inferred malignant profiles and then scored these for hybrid E/M. We then conducted a survival analysis on overall and disease-free survival among self-reported Black and White Americans.</p><p><strong>Findings: </strong>The hybrid E/M state was differentially associated with head and neck cancer survival by self-reported race and ethnicity, with a stronger association in non-Hispanic Black patients. Black patients with a high hybrid E/M score had a higher risk of death or recurrence (hazard ratio [HR]: 4.18 [95% confidence interval (CI): 2.06, 8.49]) than White patients with a high hybrid E/M score (HR: 1.58 [95% CI: 1.11, 2.26]).</p><p><strong>Conclusion: </strong>Our results suggest a complex interplay of social structure, racism, and genetic diversity. We implore researchers to consider the social and biological context contributing to disparities.</p><p><strong>Funding: </strong>A.L.M. received support from the National Institute of Minority Health and Health Disparities (K01MD013897 [principal investigator (PI), A.L.M.]). S.V.P. received support from the National Institute of Dental and Craniofacial Research (R01DE032865 [PI, S.V.P.] and R01DE032371 [PI, S.V.P.]).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432984","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":"Exploiting the potential of dupilumab in the treatment of eosinophilic COPD.","authors":"Maria Gabriella Matera, Mario Cazzola","doi":"10.1016/j.medj.2024.05.011","DOIUrl":"10.1016/j.medj.2024.05.011","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) often involves type 1 (T1) inflammation, but 40% of patients have T2 inflammation, which worsens outcomes. Dupilumab, targeting interleukin (IL)-4 and IL-13, shows promise in phase 3 trials. The new NOTUS trial¹ showed effectiveness in reducing exacerbations and improving lung function. However, its predominantly white population limits generalizability. Future research should include diverse populations and assess different therapies combined with dupilumab to improve outcomes.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer research is not correlated with driver gene mutation burdens.","authors":"Gaurav Mendiratta, David Liarakos, Melinda Tong, Satoko Ito, Eugene Ke, George Goshua, Edward C Stites","doi":"10.1016/j.medj.2024.05.013","DOIUrl":"10.1016/j.medj.2024.05.013","url":null,"abstract":"<p><strong>Background: </strong>Cancer research is pursued with the goal of positively impacting patients with cancer. Decisions regarding how to allocate research funds reflect a complex balancing of priorities and factors. Even though these are subjective decisions, they should be made with consideration of all available objective facts. An accurate estimate of the affected cancer patient population by mutation is one variable that has only recently become available to inform funding decisions.</p><p><strong>Methods: </strong>We compared the overall incident burden of mutations within each cancer-associated gene with two measures of cancer research efforts: research grant funding amounts and numbers of academic manuscripts. We ask to what degree the aggregate set of cancer research efforts reflects the relative burdens of the different cancer genetic drivers. We thoroughly investigate the design of our queries to ensure that the presented results are robust and conclusions are well justified.</p><p><strong>Findings: </strong>We find cancer research is generally not correlated with the relative burden of mutation within the different genetic drivers of cancer.</p><p><strong>Conclusions: </strong>We suggest that cancer research would benefit from incorporating, among other factors, an epidemiologically informed mutation-estimate baseline into a larger framework for funding and research allocation decisions.</p><p><strong>Funding: </strong>This work was supported in part by the National Institutes of Health (NIH) P30CA014195 and NIH DP2AT011327.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the power of nanomedicine: Cell membrane-derived biomimetic cancer nanovaccines for cancer treatment.","authors":"Guo Zhao, Shuhang Wang, Guangjun Nie, Ning Li","doi":"10.1016/j.medj.2024.03.012","DOIUrl":"10.1016/j.medj.2024.03.012","url":null,"abstract":"<p><p>Over the past decades, nanomedicine researchers have dedicated their efforts to developing nanoscale platforms capable of more precisely delivering drug payloads to attack tumors. Cancer nanovaccines are exhibiting a distinctive capability in inducing tumor-specific antitumor responses. Nevertheless, there remain numerous challenges that must be addressed for cancer nanovaccines to evoke sufficient therapeutic effects. Cell membrane-derived nanovaccines are an emerging class of cancer vaccines that comprise a synthetic nanoscale core camouflaged by naturally derived cell membranes. The specific cell membrane has a biomimetic nanoformulation with several distinctive abilities, such as immune evasion, enhanced biocompatibility, and tumor targeting, typically associated with a source cell. Here, we discuss the advancements of cell membrane-derived nanovaccines and how these vaccines are used for cancer therapeutics. Translational endeavors are currently in progress, and additional research is also necessary to effectively address crucial areas of demand, thereby facilitating the future successful translation of these emerging vaccine platforms.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse repurposing: Potential utility of cancer drugs in nonmalignant illnesses.","authors":"Mina Nikanjam, Kaitlyn Wells, Shumei Kato, Jacob J Adashek, Shanna Block, Razelle Kurzrock","doi":"10.1016/j.medj.2024.04.008","DOIUrl":"10.1016/j.medj.2024.04.008","url":null,"abstract":"<p><p>Growth and immune process dysregulation can result in both cancer and nonmalignant disease (hereditary or acquired, with and without predisposition to malignancy). Moreover, perhaps unexpectedly, many nonmalignant illnesses harbor genomic alterations indistinguishable from druggable oncogenic drivers. Therefore, targeted compounds used successfully to treat cancer may have therapeutic potential for nonmalignant conditions harboring the same target. MEK, PI3K/AKT/mTOR, fibroblast growth factor receptor (FGFR), and NRG1/ERBB pathway genes have all been implicated in both cancer and noncancerous conditions, and several cognate antagonists, as well as Bruton's tyrosine kinase inhibitors, JAK inhibitors, and CD20-directed antibodies, have established or theoretical therapeutic potential to bridge cancer and benign diseases. Intriguingly, pharmacologically tractable cancer drivers characterize a wide spectrum of disorders without malignant potential, including but not limited to Alzheimer's disease and a variety of other neurodegenerative conditions, rheumatoid arthritis, achondroplastic dwarfism, and endometriosis. Expanded repositioning of oncology agents in order to benefit benign but serious medical illnesses is warranted.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946152","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":"Two cardiac myosin inhibitors in the treatment of obstructive hypertrophic cardiomyopathy.","authors":"Milind Y Desai, Eugene Braunwald","doi":"10.1016/j.medj.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.medj.2024.06.001","url":null,"abstract":"<p><p>A key area of therapeutic progress in obstructive hypertrophic cardiomyopathy revolves around the emergence of cardiac myosin inhibitors, of which mavacamten and aficamten represent the first and second molecules. We summarize the key research evidence, including many similarities and potential differences between various clinical trials studying these molecules.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MARIPOSA-2: Is the treatment worse than the disease?","authors":"Alexandria T M Lee, Sai-Hong Ignatius Ou","doi":"10.1016/j.medj.2024.05.005","DOIUrl":"10.1016/j.medj.2024.05.005","url":null,"abstract":"","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":17.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T therapy and targeted treatments: Emerging combination strategies in solid tumors.","authors":"Jiahao Liu, Xiaofei Jiao, Ding Ma, Yong Fang, Qinglei Gao","doi":"10.1016/j.medj.2024.03.001","DOIUrl":"10.1016/j.medj.2024.03.001","url":null,"abstract":"<p><p>CAR-T cell therapies hold great potential in achieving long-term remission in patients suffering from malignancies. However, their efficacy in treating solid tumors is impeded by challenges such as limited infiltration, compromised cancer recognition, decreased cytotoxicity, heightened exhaustion, absence of memory phenotypes, and inevitable toxicity. To surmount these obstacles, researchers are exploring innovative strategies, including the integration of CAR-T cells with targeted inhibitors. The combination of CAR-T therapies with specific targeted drugs has shown promise in enhancing CAR-T cell infiltration into tumor sites, boosting their tumor recognition capabilities, strengthening their cytotoxicity, alleviating exhaustion, promoting the development of a memory phenotype, and reducing toxicity. By harnessing the synergistic potential, a wider range of patients with solid tumors may potentially experience favorable outcomes. To summarize the current combined strategies of CAR-T therapies and targeted therapies, outline the potential mechanisms, and provide insights for future studies, we conducted this review by collecting existing experimental and clinical evidence.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.","authors":"Shanghao Liu, Xiaohan Chen, Xuanwei Jiang, Xiaochun Yin, Ginenus Fekadu, Chuan Liu, Yan He, Huihui Chen, Wenjing Ni, Ruiying Wang, Qing-Lei Zeng, Yuping Chen, Ling Yang, Ruihua Shi, Sheng-Hong Ju, Jie Shen, Jingli Gao, Linhua Zhao, Wai-Kit Ming, Victor W Zhong, Gao-Jun Teng, Xiaolong Qi","doi":"10.1016/j.medj.2024.03.003","DOIUrl":"10.1016/j.medj.2024.03.003","url":null,"abstract":"<p><strong>Background: </strong>Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population.</p><p><strong>Methods: </strong>The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD).</p><p><strong>Findings: </strong>Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY.</p><p><strong>Conclusions: </strong>The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population.</p><p><strong>Funding: </strong>The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":17.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enfortumab vedotin and pembrolizumab combination as a relevant game changer in urothelial carcinoma: What is left behind?","authors":"Joaquim Bellmunt, Rosa Nadal","doi":"10.1016/j.medj.2024.04.006","DOIUrl":"https://doi.org/10.1016/j.medj.2024.04.006","url":null,"abstract":"<p><p>The EV-302 study¹ marks a pivotal leap in the management of advanced urothelial carcinoma, setting a new benchmark for frontline therapy. Enfortumab vedotin plus pembrolizumab is the first combination therapy that has ever outperformed standard chemotherapy. The degree of benefit and the reported safety profile should make this combination a first-choice option for most patients with advanced-stage urothelial carcinoma.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":17.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}