Current medicinal chemistry最新文献

{"title":"Oxidative Stress Biomarkers in Hypertension.","authors":"Petros Fountoulakis, Islam Kourampi, Panagiotis Theofilis, Anastasios Marathonitis, Georgios Angelos Papamikroulis, Ourania Katsarou, Georgios Marinos, Evangelos Oikonomou, Gerasimos Siasos, Dimitris Tousoulis","doi":"10.2174/0109298673325682241114162014","DOIUrl":"https://doi.org/10.2174/0109298673325682241114162014","url":null,"abstract":"<p><p>Arterial hypertension is a silent and progressive disease with deleterious vascular implications on all target organs, including the heart, the brain, the kidneys, and the eyes. Oxidative stress, defined as the overproduction of Reactive Oxygen Species (ROS) over antioxidants, is capable of deteriorating not only the normal endothelial but also the cellular function with further cardiovascular implications. Xanthine oxidase activity, NADPH oxidase overexpression, and ROS production lead to hypertension and high arterial tone, culminating in end-organ damage. The inactivation of NO by superoxide reduces vasodilation and promotes peroxynitrite formation, which damages cellular components. Activation of MMPs by oxidative stress contributes to pathological neovascularization and angiogenesis. Salucin-β-induced activation of Angiotensin-II and NADPH results in vascular remodeling and fibrosis, while lipid peroxidation and PARP- 1 activation further exacerbate cellular apoptosis and vascular calcification. Moreover, to reliably assess the oxidative status an emerging number of biomarkers are under investigation. Antioxidant therapy, alongside traditional antihypertensive agents such as beta-blockers and ACE inhibitors, offers the potential to mitigate oxidative stress and its detrimental effects. Additionally, polyphenols, found in plant-based foods, show promise in managing oxidative stress in hypertensive patients although this data has not been confirmed in randomized clinical trials. Understanding the intricate relationship between oxidative stress and hypertension underscores the importance of developing comprehensive therapeutic strategies to reduce cardiovascular risk and improve patient outcomes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930970","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}

{"title":"Mechanochemical Synthesis of Diclofenac Conjugates with Glucosamine and Chitosan Exhibiting COX-2 Selective Ulcer Safe Anti-inflammatory Activity.","authors":"Sana Afzal, Mohammad Saeed Iqbal, Abdul Haleem Khan","doi":"10.2174/0109298673352652241217090558","DOIUrl":"https://doi.org/10.2174/0109298673352652241217090558","url":null,"abstract":"<p><strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs are associated with severe gastrointestinal irritation upon prolonged use, largely due to their carboxylic (-- COOH) functional group.</p><p><strong>Aim: </strong>To address this issue, we aimed to synthesize diclofenac conjugates with glucosamine and chitosan, converting the -COOH group into an amide (-CONH-) via a mechanochemical, environmentally friendly method.</p><p><strong>Method: </strong>In this study, diclofenac acid was first converted to its acid chloride using thionyl chloride under mechanochemical conditions and subsequently reacted with glucosamine base and chitosan. The resulting conjugates were evaluated for anti-inflammatory activity through the rat-paw edema test, along with ulcerogenicity, COX inhibition assays, and cardiovascular assessment.</p><p><strong>Result: </strong>The mechanochemical approach provided high yields (>90%) and resulted in conjugates that significantly reduced paw edema (62.3 ± 2.3% for diclofenac-glucosamine and 58.5 ± 1.6% for diclofenac-chitosan) compared to diclofenac sodium (49.0 ± 1.3%) after 5 h. Notably, the conjugates were ulcer-safe, as no gastric lesions were observed, unlike the multiple lesions detected in animals treated with diclofenac sodium. Both conjugates also demonstrated a high degree of COX-2 selectivity and cardiovascular safety.</p><p><strong>Conclusion: </strong>This study highlights the potential of mechanochemical synthesis for efficient amide formation, avoiding the need for hydroxyl group protection.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930969","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}

{"title":"Antimalarial Drug Discovery from Natural and Synthetic Sources.","authors":"Nik Nur Solehah Fitri Nik Mohd Azam, Shatrah Othman, Yeun-Mun Choo","doi":"10.2174/0109298673312727240527064833","DOIUrl":"10.2174/0109298673312727240527064833","url":null,"abstract":"<p><p>Malaria remains a significant global health threat despite extensive efforts aimed at its eradication. Numerous challenges persist in eliminating the disease, chief among them being the parasite's ability to mutate, resulting in drug resistance. The discovery of antimalarial drugs has relied on both phenotypic and target-based approaches. While phenotypic screening has identified promising candidates, target-based methods offer a more precise approach by leveraging chemically validated targets and computational tools. Analysis of <i>Plasmodium spp</i> . protein structures reveal druggable targets, offering opportunities for <i>in silico</i> screening. Combining compounds from natural and synthetic sources in a target-based approach accelerates the discovery of new antimalarial agents. This review explores previous breakthroughs in antimalarial drug discovery from natural products and synthetic origins, emphasizing their specific target proteins within <i>Plasmodium</i> species.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"87-110"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179159","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}

{"title":"The Role of Quercetin for the Treatment of Endometriosis and Endometrial Cancer: A Comprehensive Review.","authors":"Shahla Chaichian, Banafsheh Nikfar, Sepideh Arbabi Bidgoli, Bahram Moazzami","doi":"10.2174/0109298673269733230921092509","DOIUrl":"10.2174/0109298673269733230921092509","url":null,"abstract":"<p><p>Endometrial glands and stroma can be seen outside the uterine cavity in endometriosis, a gynecological disorder linked to estrogen dependency. Hormonal therapies, surgical excision, and non-steroidal anti-inflammatory drug therapy are among the traditional endometriosis treatments, however, various side effects limit their efficacy. Therefore, it is vital to research complementary and alternative therapeutic modalities to decrease the side effects of conventional therapies. While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. This review aims to comprehensively review quercetin's potential as a non-pharmacological treatment for endometriosis by interacting with several cellular and molecular targets.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"74-86"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49675360","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}

{"title":"Defective Mitophagy Impairs Response to Inflammatory Activation of Macrophage-Like Cells.","authors":"Alexander Nikolaevich Orekhov, Alexander Dmitrievich Zhuravlev, Andrey Yurievich Vinokurov, Nikita Gennadievich Nikiforov, Andrey Vladimirovich Omelchenko, Vasily Nikolaevich Sukhorukov, Vasily Vladimirovich Sinyov, Igor Alexandrovich Sobenin","doi":"10.2174/0109298673294643240228105957","DOIUrl":"10.2174/0109298673294643240228105957","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and aims: &lt;/strong&gt;The role of mitophagy in atherosclerosis has been extensively studied during the last few years. It was shown that mitophagy is involved in the regulation of macrophages, which are important players as immune cells in atherosclerosis development. In this study, we investigated the relationship between mitophagy and response to inflammatory stimulation of macrophage-like cells. Six cybrid cell lines with normal mitophagy, that is, increasing in response to stimulation, and 7 lines with defective mitophagy not responding to stimulation were obtained. The objective of the study was to compare the nature of the inflammatory response in normal and defective mitophagy in order to elucidate the role of mitophagy defects in inflammation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used cytoplasmic hybrids (cybrids) as cellular models, created using mitochondrial DNA from different atherosclerosis patients. Mitophagy was stimulated by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and assessed as the degree of colocalization of mitochondria with lysosomes using confocal microscopy. Western blotting methods were used for the determination of proteins involved in the exact mechanism of mitophagy. Experiments with stimulation of mitophagy show a high correlation between these two approaches (microscopy and blotting). The pro-inflammatory response of cybrids was stimulated with bacterial lipopolysaccharide (LPS). The extent of the inflammatory response was assessed by the secretion of cytokines CCL2, IL8, IL6, IL1β, and TNF measured by ELISA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Basal level of secretion of cytokines CCL2, IL8 and TNF was 1.5-2 times higher in cultures of cybrids with defective mitophagy compared to cells with normal mitophagy. This suggests a persistently elevated inflammatory response in cells with defective mitophagy, even in the absence of an inflammatory stimulus. Such cells in the tissue will constantly recruit other immune cells, which is characteristic of macrophages derived from monocytes circulating in the blood of patients with atherosclerosis. We observed significant differences in the degree and type of response to inflammatory activation in cybrids with defective mitophagy. These differences were not so much quantitative as they were dramatically qualitative. Compared with cells with normal mitophagy, in cells with defective mitophagy, the relative (to basal) secretion of IL8, IL6 and IL1b increased after the second LPS activation. This indicates a possible lack of tolerance to inflammatory activation in cells with defective mitophagy, since typically, re-activation reveals a smaller pro-inflammatory cytokine response, allowing the inflammatory process to resolve. In cells with normal mitophagy, exactly this normal (tolerant) inflammatory reaction was observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Data on the involvement of mitophagy, including defective mitophagy, in disturbances of the inflammatory re","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"111-122"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027580","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}

{"title":"Identification and Characterization of Prognostic Macrophage Subpopulations for Human Esophageal Carcinoma.","authors":"Penghui Li, Xiaohui Gao, Di Huang, Xinyu Gu","doi":"10.2174/0109298673284207240108105724","DOIUrl":"10.2174/0109298673284207240108105724","url":null,"abstract":"<p><strong>Aims: </strong>The aim of the present study was to investigate the relationship between the cellular ecosystem and the progression of esophageal carcinoma (ESCA) based on the evolution of macrophages and to analyze the potential of using macrophages as a new therapeutic approach in ESCA treatment.</p><p><strong>Background: </strong>Macrophage-based immunotherapy could be used for treating ESCA patients, but its clinical application is limited by the intra-tumor heterogeneity of macrophages.</p><p><strong>Objective: </strong>The objective of this study was to analyze the diversity, differentiation trajectory, and intercellular communication of macrophages in ESCA and its prognostic significance.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) data in the GSE154763 dataset were downloaded from Gene Expression Omnibus (GEO) to identify cell clusters and annotate cell types using the Seurat R package. The scRNA-seq profiles of macrophages were extracted, and cluster analysis was performed to identify macrophage subsets. The differentiation trajectories of macrophage subgroups were visualized employing Monocle2. Finally, ligand-receptor pairs and communication intensity among the classified subgroups were analyzed using Cell Chat.</p><p><strong>Results: </strong>A total of 8 cell types were identified between ESCA tissues and paracancer tissues. The most abundant macrophages in ESCA tissues were further divided into 5 cell clusters. Compared with the normal tissues, the proportion of HSPA6+ macrophages in ESCA tissues increased the most, and the number of ligand-receptor pairs that mediated the communication of HSPA6+ macrophages with mast cells and monocytes also increased significantly. More importantly, a high proportion of HSPA6+ macrophages was inversely correlated with the survival outcomes for ESCA patients.</p><p><strong>Conclusions: </strong>This study analyzed the diversity, distribution and differentiation trajectory of macrophages in ESCA tissues at single-cell level and classified a prognostic macrophage subtype (HSPA6+ macrophages) of ESCA, providing a theoretical basis for macrophage-targeted therapy in ESCA.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"123-135"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740609","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}

{"title":"Pro-renin Receptor (PRR) as a Target to Reduce Non-alcoholic Fatty Liver Disease Post Liver Transplantation.","authors":"Rozita Khodashahi, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand","doi":"10.2174/0109298673345528241101092336","DOIUrl":"https://doi.org/10.2174/0109298673345528241101092336","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disorders following liver transplantation. The prorenin receptor (PRR) plays a role in glucose and lipid metabolism, and the hepatic dysregulation of PRR is associated with the upregulation of several molecular pathways, such as the mammalian target of rapamycin (mTOR) and Peroxisome proliferator-activated receptor (PPAR) that promotes hepatic lipogenesis and leads to lipid accumulation in hepatocytes by upregulation of lipogenic genes. PRR inhibition leads to a reduction in the hepatic expression of sortilin-1 and low-density lipoprotein receptor (LDLR) levels and down-regulation of pyruvate dehydrogenase (PDH) and acetyl-CoA carboxylase (ACC) and reduces fatty acids synthesis in hepatocytes. In addition, β-oxidation regulatory genes are upregulated by PRR inhibition to attenuate liver lipid content and liver steatosis. This evidence suggests that targeting the dysregulated hepatic PRR may be effective in reducing liver steatosis postliver transplantation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926882","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}

{"title":"lncRNA-056298 Regulates GAP43 and Promotes Cardiac Intrinsic Autonomic Nerve Remodelling in a Canine Model of Atrial Fibrillation Induction after Ganglionated Plexus Ablation.","authors":"Shuting Bai, Ximin Wang, Yinglong Hou, Yansong Cui, Qiyuan Song, Juanjuan Du, Yujiao Zhang, Jingwen Xu","doi":"10.2174/0109298673289298240129103537","DOIUrl":"10.2174/0109298673289298240129103537","url":null,"abstract":"<p><strong>Background: </strong>Cardiac intrinsic autonomic nerve remodelling has been reported to play an important role in the recurrence of atrial fibrillation after radiofrequency ablation, which significantly affects the long-term efficacy of this procedure. lncRNAs have been shown to interact in the pathological processes underlying heart diseases. However, the roles and mechanisms of lncRNAs in cardiac intrinsic autonomic nerve remodelling during atrial fibrillation reduction after ganglionated plexus ablation remain unknown.</p><p><strong>Objective: </strong>The aim of this study was to investigate the mechanism by which lncRNA- 056298 modulates GAP43 to affect cardiac intrinsic autonomic nerve remodelling and facilitate the induction of atrial fibrillation after ganglionated plexus ablation.</p><p><strong>Methods: </strong>A canine model of right atrial ganglionated plexus ablation was established. The atrial electrophysiological characteristics and neural markers were detected before and after 6 months of ganglionated plexus ablation. High-throughput sequencing was used to screen differentially expressed lncRNAs in target atrial tissues, and lncRNA- 056298 was selected to further explore its effects and mechanisms on cardiac intrinsic autonomic nerve remodelling.</p><p><strong>Results: </strong>The induction rate of atrial fibrillation increased in dogs after ganglionated plexus ablation. Overexpression of lncRNA-056298 by lentivirus can shorten the atrial effective refractory period and increase the induction of atrial fibrillation. lncRNA- 056298 promoted cardiac intrinsic autonomic nerve remodelling via endogenous competition with cfa-miR-185 to induce transcription of its target gene GAP43, thereby affecting the induction of atrial fibrillation.</p><p><strong>Conclusion: </strong>lncRNA-056298 regulates GAP43 by sponging miR-185, which affects cardiac intrinsic autonomic nerve remodelling and mediates atrial fibrillation induction after ganglionated plexus ablation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"136-159"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650487","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}

{"title":"Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy.","authors":"Zhongfeng Cui, Chunli Liu, Hongzhi Li, Juan Wang, Guangming Li","doi":"10.2174/0109298673290101240223074545","DOIUrl":"10.2174/0109298673290101240223074545","url":null,"abstract":"<p><strong>Aims: </strong>To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma (LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic signatures contribute to the mining of novel biomarkers, which are essential for the construction of a precision medicine system for LIHC and the improvement of survival.</p><p><strong>Background: </strong>Tyrosine metabolism plays a critical role in the initiation and development of LIHC. Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature to improve the prognostic prediction of patients with LIHC.</p><p><strong>Objective: </strong>To investigate the correlation between tyrosine metabolism and progression of LIHC and to develop a tyrosine metabolism-related prognostic model.</p><p><strong>Methods: </strong>Gene expression and clinicopathological information of LIHC were obtained from The Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC) were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and other clinicopathological features.</p><p><strong>Results: </strong>Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected from the common differentially expressed genes (DEGs) between the 3 subtypes were used to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk groups. In both the training and validation sets, high-risk patients tended to have worse overall survival, less active immunotherapy response, higher immune infiltration and clinical grade, and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan-- cancer analysis also supported that the RiskScore had a strong prognostic performance in other cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of LIHC prognosis.</p><p><strong>Conclusion: </strong>Our study developed a tyrosine metabolism-related risk model that performed well in survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"160-187"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982547","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}

{"title":"Clinical Trials of High-intensity Focused Ultrasound for Cancer: Concerns Arising from Low Post-Hoc Power.","authors":"Tinghe Yu, Xinya Li","doi":"10.2174/0109298673281773240104142757","DOIUrl":"10.2174/0109298673281773240104142757","url":null,"abstract":"<p><p>Prospective controlled trials of high-intensity focused ultrasound (HIFU) for cancers were evaluated. Post-hoc power was <0.80 in 30/46 trials and in 22/38 trials with positive results, indicating low quality in most trials. Unscientific endpoints, small sample sizes, and high dropout rates led to low post-hoc power that caused inter-trial heterogeneity and overestimated the therapeutic effect. The objective response rate was not a substitute for survival time for estimating the sample size and assessing the efficacy. The present data can interpret a paradox: HIFU is considered to have slighter cytotoxicity to noncancer tissues and no radiation but is frequently combined with chemotherapy and/or radiotherapy in practice.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"2-5"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697120","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}