American journal of cancer research最新文献

{"title":"Multidisciplinary collaborative approach to cardiopulmonary rehabilitation in cancer patients with intensive care unit-acquired weakness: a clinical efficacy and safety analysis.","authors":"Ming Yao, Li Zhang, Meng Ai, Haiyan Chen, Lu Zhang, Yanshun Wei, Dandan Wang, Yajie Jia","doi":"10.62347/UVQC5990","DOIUrl":"10.62347/UVQC5990","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the efficacy and safety of a multidisciplinary team (MDT)-based cardiopulmonary rehabilitation model in patients with intensive care unit-acquired weakness (ICU-AW).</p><p><strong>Methods: </strong>Between January 2020 and June 2023, 80 ICU patients were enrolled: 40 received standard cardiopulmonary rehabilitation (control group), and 40 underwent MDT-based rehabilitation (observation group). Outcome measures included ICU-AW incidence, muscle strength Medical Research Council (MRC) scores, upper/lower limb strength, Barthel Index Sequential Organ Failure Assessment (SOFA) Acute Physiology and Chronic Health Evaluation (APACHE) II scores, duration of ICU and hospital stay, mechanical ventilation time, complications, and patient satisfaction. Predictive variables for ICU-AW were also analyzed.</p><p><strong>Results: </strong>On days 4 and 7 post-intervention, ICU-AW incidence was significantly lower in the observation group (both P < 0.05). MRC scores, limb muscle strength, Barthel Index, and satisfaction were significantly higher in the observation group (all P < 0.05), while SOFA, APACHE II scores, ICU stay, hospital stay, and ventilation duration were significantly lower (all P < 0.05). SOFA scores declined from day 5, with lower values in the observation group (<i>P</i> < 0.05). The risk of ICU-AW in the observation group was a significant reduction in risk than in the control group (OR = 0.067, 95% CI: 0.005-0.606, P = 0.017). No significant differences in complications were observed (P > 0.05).</p><p><strong>Conclusions: </strong>MDT-based cardiopulmonary rehabilitation significantly improves muscle strength, functional status, and patient satisfaction, while reducing ICU-AW incidence, ICU and hospital stay, and ventilation duration. These findings support its broader clinical application in ICU-AW management.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2427-2438"},"PeriodicalIF":3.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of LRRC15-SCG5 in ECM protein binding as a prognostic signature for urothelial carcinoma.","authors":"Shao-Wei Dong, Chih-Heng Chen, Kai-Yi Tzou, Su-Wei Hu, Chia-Chang Wu, Chien Hsiu Li","doi":"10.62347/ABZG4705","DOIUrl":"10.62347/ABZG4705","url":null,"abstract":"<p><p>Membrane-bound LRRC15 facilitates communication with adjacent cells by interacting with extracellular molecules, yet its role in urothelial carcinoma remains undefined. A systematic analysis of clinicopathological transcriptome profiles of urothelial carcinoma patients reveals that dysregulated levels of LRRC15 are associated with tumor malignancy features and poor prognosis. A clinically based molecular simulation model highlights potential mechanisms whereby LRRC15 mediates urothelial carcinoma cell motility and growth, primarily through the extracellular matrix organization pathway. Further molecular interaction mapping identifies SCG5 as a novel molecule linking to LRRC15 via protein-protein interactions, positively correlating with advanced pathological features and worse prognosis in urothelial carcinoma patients. Kaplan-Meier plotter results indicate that the LRRC15/SCG5 axis can serve as a prognostic marker for low survival rates in both non-muscle invasive and muscle-invasive bladder cancer. Molecules affected by the LRRC15/SCG5 axis in bladder cancer and upper tract urothelial carcinoma contribute to signatures of poor prognosis in urothelial carcinoma. These findings support targeting the LRRC15/SCG5 axis as a potential therapeutic strategy to intervene in urothelial carcinoma progression.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2301-2318"},"PeriodicalIF":3.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a predictive model for cancer therapy-related cardiac dysfunction in breast cancer patients using echocardiographic indicators.","authors":"Shan Hui, Junyi Yu, Yuanyuan Tang","doi":"10.62347/WPUW2205","DOIUrl":"10.62347/WPUW2205","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop and validate a predictive model for cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients undergoing chemotherapy, targeted therapy, or immunotherapy.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 506 patients treated at Hunan Provincial People's Hospital (2018-2023).</p><p><strong>Results: </strong>Clinical and imaging biomarkers, including NT-proBNP (P < 0.001), left ventricular ejection fraction (LVEF; P = 0.003), and left atrial diameter (LA; P = 0.012), were evaluated. Lasso-Cox regression identified eight significant predictors (all P < 0.05), which were incorporated into a nomogram. The model exhibited excellent discrimination in both the training (AUC 0.82, 95% CI 0.78-0.86) and validation cohorts (AUC 0.79, 95% CI 0.74-0.83). Time-dependent ROC curves demonstrated consistent predictive accuracy at 4 weeks (AUC 0.80, P < 0.001), 8 weeks (AUC 0.81, P < 0.001), and 12 weeks (AUC 0.79, P = 0.002). Calibration curves indicated good agreement (Hosmer-Lemeshow test P = 0.34), and decision curve analysis confirmed the model's clinical utility (net benefit > 15% across threshold probabilities).</p><p><strong>Conclusion: </strong>This validated tool facilitates early CTRCD risk stratification (C-index 0.80, P < 0.001), supporting personalized monitoring of cardiotoxicity.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2243-2258"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and toxicity of PD-1 inhibitor combined with induction chemotherapy for locally advanced laryngeal and hypopharyngeal cancers.","authors":"Tingting Zhao, Wan Liu, Rong Yan, Yanjie Ma, Xudong Wang, Minghui Wei","doi":"10.62347/HVRH6856","DOIUrl":"10.62347/HVRH6856","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy, toxicity, and voice rehabilitation outcomes of PD-1 inhibitors combined with induction chemotherapy (PCIC) compared to induction chemotherapy (IC) alone.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 250 patients with stage III/IVA squamous cell carcinoma of the larynx/hypopharynx treated between June 2021 and December 2023. After 1:1 propensity score matching, 216 patients (108 per group) were analyzed. Both groups received platinum-based induction chemotherapy, with the PCIC group receiving an additional PD-1 inhibitor, toripalimab. Efficacy was evaluated based on response rates and survival outcomes, while toxicity profiles and voice rehabilitation were assessed.</p><p><strong>Results: </strong>The PCIC group had significantly higher complete remission rates (81.48% vs. 65.74%; P = 0.021) and improved 1-year overall survival (62.96% vs. 49.07%; P = 0.040). The incidence of neutropenia and nausea was higher in the PCIC group (P < 0.05). Voice quality assessments showed worse objective vocal grade but better patient-perceived vocal quality in the PCIC group (both P < 0.05).</p><p><strong>Conclusion: </strong>The combination of PD-1 inhibitors with induction chemotherapy improve remission rates and survival in patients with locally advanced laryngeal and hypopharyngeal cancers. However, increased toxicity and voice rehabilitation challenges highlight the need for comprehensive patient support during treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2193-2207"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of immediate intravesical therapy on non-muscle invasive bladder cancer with risk factors analysis for recurrence.","authors":"Bo Liu, Shide Gong, Yongwei Chen, Bangming Xiao, Junlin Wang, Xinbo Sun","doi":"10.62347/DNBH6092","DOIUrl":"10.62347/DNBH6092","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of immediate intravesical therapy (IIT) on recurrence rates in non-muscle invasive bladder cancer (NMIBC) patients and to explore the potential protective role of vitamin supplementation.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 216 NMIBC patients treated between April 2019 and March 2023. Patients were categorized into two groups: IIT group (n = 154) and no-IIT group (n = 62). Inclusion criteria included pathologically confirmed NMIBC, initial transurethral resection of bladder tumor (TURBT), and a minimum follow-up of one year. Patients who underwent radical cystectomy, had other malignancies, or suffered from severe comorbid conditions were excluded. Recurrence within one year post-treatment was used to stratify patients into recurrence and non-recurrence groups. Statistical analyses were performed to identify factors significantly associated with recurrence. Logistic regression and receiver operating characteristic curve analyses were employed to evaluate predictive performance.</p><p><strong>Results: </strong>The recurrence rate was significantly lower in the IIT group (33.12%) compared to the no-IIT group (95.16%, P < 0.001). IIT significantly reduced the risk of recurrence (P < 0.001). Among vitamin supplements, only vitamin K3 demonstrated a significant association with recurrence (P = 0.010). Logistic regression confirmed IIT as an independent protective factor (OR = 0.026, P < 0.001). The area under the curve (AUC) for individual predictors ranged from 0.587 to 0.754, while the combined model achieved an AUC of 0.877, indicating strong predictive performance.</p><p><strong>Conclusion: </strong>IIT and self-supplementation with vitamin K3 are associated with a reduced risk of NMIBC recurrence. These findings suggest that adjunctive strategies alongside standard transurethral resection of bladder tumor may enhance patient outcomes. Further prospective studies are warranted to confirm these associations and support their integration into clinical practice.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2275-2284"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher hospital frailty risk score is predictive of 90-day readmission after minimally invasive colorectal cancer surgery: a national readmission database analysis.","authors":"Hsin-Pao Chen, Chih-I Chen, Ling-Chiao Song, Yu-Chun Lin, Yi-Kai Kao, Pin-Chun Chen, Chia-Hung Chen, Kuang-Wen Liu","doi":"10.62347/GQFR4339","DOIUrl":"10.62347/GQFR4339","url":null,"abstract":"<p><p>Minimally invasive procedures are common in colorectal cancer (CRC) surgeries, but the impact of frailty on postoperative outcomes is unclear. This study aimed to assess how frailty status affects postoperative outcomes after minimally invasive CRC surgery. This study examined the impact of frailty on postoperative outcomes following minimally invasive colorectal cancer (CRC) surgery. Using data from the 2016-2020 U.S. National Readmission Database, the study included patients aged ≥ 60 years who underwent first-time minimally invasive (laparoscopic or robotic) CRC resection during hospitalization. Patients were categorized into low, intermediate, and high frailty risk groups based on the Hospital Frailty Risk Score (HFRS). Outcomes assessed included 90-day readmissions, in-hospital mortality, and complications. The analysis of 6,417 patients revealed that intermediate frailty was associated with higher in-hospital mortality (OR = 2.01), and high frailty had an even greater risk (OR = 3.83). Frailty also showed a dose-response relationship with complications, with the odds of complications being significantly higher in both intermediate (OR = 4.59) and high frailty groups (OR = 37.12). Only the high frailty group had an elevated risk of 90-day readmission (OR = 1.27). Certain subgroups, such as patients aged < 80, without diabetes or chronic kidney disease, with rectal tumors, and those undergoing robotic surgery, were particularly affected by frailty in terms of in-hospital mortality. The study highlights that higher frailty, as measured by the HFRS, is a strong predictor of adverse postoperative outcomes and early readmission in older patients undergoing minimally invasive CRC surgery, with especially notable effects in certain subgroups, possibly due to the greater surgical complexity or physiological burden in these groups.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2208-2221"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of immune-related adverse events and analysis of risk factors in older and younger rectal cancer patients receiving immunotherapy.","authors":"Jie Liao, Haiwen Ye, Jian Wang, Fei Liu, Hongjia Zhu, Guowei Xie, Junjiang Pan","doi":"10.62347/QLFX5040","DOIUrl":"10.62347/QLFX5040","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has transformed rectal cancer treatment but poses risks of immune-related adverse events (irAEs), particularly in elderly patients who exhibit immunosenescence and inflammaging. This study compares the incidence and severity of irAEs in elderly and young rectal cancer patients receiving immunotherapy and identifies predictive biomarkers for these events.</p><p><strong>Methods: </strong>We retrospectively analyzed 405 rectal cancer patients treated with immunotherapy from January 2015 to December 2023. Patients were categorized into younger (< 60 years) and older (≥ 60 years) groups. Incidence and severity of irAEs were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) standards. Blood samples were analyzed for hematological and immunological markers.</p><p><strong>Results: </strong>The older group displayed a significantly higher incidence of irAEs at 48.65% compared to 32.11% in the younger group (<i>P</i> = 0.003). Severity varied, with 69.72% of younger patients experiencing irAEs of grade ≤ 2 versus 51.69% in the older group (<i>P</i> = 0.001). Notably, higher absolute lymphocyte count (ALC), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were associated with increased irAEs (<i>P</i> = 0.002, <i>P</i> = 0.001, <i>P</i> = 0.007, respectively). The multivariate analysis identified ALC, IL-6, CRP, B and T Lymphocyte Attenuator, Human Granulocyte-macrophage Colony Stimulating Factor, Programmed Death-1 and Programmed Death-Ligand 1 as significant predictors of irAEs, with ALC showing an odds ratio (OR) of 9.700 (<i>P</i> = 0.001) and IL-6 an OR of 58.961 (<i>P</i> < 0.001). Furthermore, the platelet-to-lymphocyte ratio (PLR) inversely correlated with irAEs (<i>P</i> = 0.013).</p><p><strong>Conclusion: </strong>Older rectal cancer patients receiving immunotherapy were at increased risk for both greater incidence and severity of irAEs. Specific biomarkers, such as ALC and IL-6, were associated with a heightened risk of these events.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2153-2169"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of lipid metabolism-related marker genes in colorectal cancer.","authors":"Bo Gao, Jitao Hu, Hao Wu, Baokun Li","doi":"10.62347/EGUX7327","DOIUrl":"10.62347/EGUX7327","url":null,"abstract":"<p><strong>Objective: </strong>To identify lipid metabolism associated biomarkers in colorectal cancer (CRC).</p><p><strong>Methods: </strong>To refine our list of candidate genes, we utilized the Molecular Complex Detection (MCODE) plug-in within Cytoscape software and performed protein-protein interaction (PPI) network analysis to extract hub genes centrally located within the networks, which potentially possess important regulatory functions. Hub gene-associated miRNAs and transcription factors (TFs) were analyzed using miRNet. Immunohistochemical staining was employed to verify the expression levels of hub genes in clinical CRC tissues. Concurrently, cellular experiments were designed to explore the functional roles of the hub gene DHCR7 at the cellular level, providing scientific evidence for the precision treatment of CRC.</p><p><strong>Results: </strong>A total of 9008 differentially expressed genes (DEGs) were identified between CRC and control samples. Gene Set Enrichment Analysis (GSEA) revealed that these DEGs were mainly enriched in biological processes such as myogenesis, adipogenesis, oxidative phosphorylation, and fatty acid metabolism. Using Weighted Gene Co-expression Network Analysis (WGCNA), we found that the pink and yellow modules were most significantly associated with CRC. Cytoscape analysis identified six hub genes (DHCR7, FABP4, FASN, FAXDC2, PTGIS, SLC27A6). Their diagnostic performance was verified in the external GSE23878 dataset. Clinical studies showed a downregulation trend in the expression of FAXDC2 and PTGIS in CRC tissue samples, while FASN and DHCR7 were up-regulated in colon cancer tissues. However, the expression trend of FABP4 was inconsistent with previous bioinformatics predictions. Further cellular experimental results demonstrated that DHCR7 knockdown significantly inhibited CRC cell proliferation and induced apoptosis, which strongly supported the previous bioinformatics analysis.</p><p><strong>Conclusion: </strong>Our research successfully identified six hub genes in CRC through a series of rigorous analyses and experimental validations. These findings provide important molecular basis for further investigation into the pathogenesis and progression of CRC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2022-2040"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrast-enhanced MRI and CT in evaluating treatment response for recurrent endometrial cancer: a retrospective case-control study.","authors":"Yan Chen, Xueling Wang","doi":"10.62347/TUED9082","DOIUrl":"10.62347/TUED9082","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the diagnostic performance of contrast-enhanced magnetic resonance imaging (CE-MRI) and computed tomography (CT) in evaluating treatment response for recurrent endometrial cancer (EC), and to assess the added value of integrating imaging findings with biomarker data.</p><p><strong>Methods: </strong>This retrospective case-control study included 217 patients with recurrent EC treated between January 2020 and December 2023. Patients were divided into response (n = 102) and non-response (n = 115) based on Response Evaluation Criteria in Solid Tumors (RECIST) (1.1). An internal validation cohort (n = 142) and an external cohort (n = 168) were also analyzed. Preoperative CE-MRI and CT scans were reviewed by experienced radiologists. Biomarker positivity rates - including estrogen receptor (ER), progesterone receptor (PR), cancer antigen 125 (CA125), cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and ovarian cancer-related protein 1 (OVX1), were assessed. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate diagnostic performance, and an integrated model combining imaging and biomarkers was developed.</p><p><strong>Results: </strong>CE-MRI achieved an AUC of 0.864, sensitivity of 78.3%, and specificity of 86.3%, while CT showed an AUC of 0.854, sensitivity of 81.2%, and specificity of 83.4%. The integrated model improved performance with an AUC of 0.889, sensitivity of 94.3%, and specificity of 81.2%. Internal and external validation models yielded AUCs of 0.859 and 0.918, respectively.</p><p><strong>Conclusions: </strong>Both CE-MRI and CT are effective in assessing treatment response, with CE-MRI offering slightly superior specificity. Integration of imaging and biomarker data significantly enhances diagnostic accuracy, supporting its potential in optimizing individualized treatment strategies for recurrent EC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2077-2096"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitope-guided selection of CXCR4-targeting antibodies using AlphaFold3 for GPCR modulation and cancer therapy.","authors":"Srimathi Venkataraman, Yi-Chuan Li, Zi-Wei Hung, Yu-Chieh Hsu, Zhuo Yang, Tsung-I Tsai, Mien-Chie Hung, Kyung Ho Han, Chih-Wei Lin","doi":"10.62347/DJMA8500","DOIUrl":"10.62347/DJMA8500","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) play important roles by transmitting signals when they bind to specific ligands in human. Dysregulation of the GPCRs has been associated to metabolic diseases, inflammatory and cancers, and making them key targets for therapeutic intervention. The structural characterization of GPCR-ligand interactions remains challenging due to the difficulty in obtaining complex structures. In this study, we chose CXC chemokine receptor 4 (CXCR4), a member of the GPCR family, as the receptor and employed AlphaFold3 to predict the interaction sites between ligands and GPCRs. The results show that the extracellular loop 2 (ECL2) region is crucial for CXCL12-CXCR4 interactions. Using this epitope-guided approach, we selected antibodies from a combinatorial library that bind to CXCR4 and block CXCL12 signaling. Two antibodies, C5 and F4, were found to inhibit CXCL12 signaling in reporter cell lines. Furthermore, these antibodies also exhibited antibody-dependent cellular cytotoxicity against the acute T cell leukemia cell line and the B cell lymphoma cell line. This approach provides a promising way to develop effective antibodies for treating CXCR4-expressed cancer cells, as well as for other diseases linked to GPCR dysfunction.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 5","pages":"2127-2139"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}