American journal of cancer research最新文献

{"title":"TRIM68 regulates ubiquitinated degradation of Rabex-5 and plays a role in progression of breast cancer through Rab5-Rac1.","authors":"Lei Qiao, Chao Dong, Wenlei Jia, Binlin Ma","doi":"10.62347/IFAH5271","DOIUrl":"10.62347/IFAH5271","url":null,"abstract":"<p><p>TRIM family proteins are widely involved in tumorigenesis and progression, while TIRM68 is less explored in breast cancer. The expression of TRIM68 in breast cancer was explored in two public databases (GEPIA and UALCAN), and the survival was tested on Kaplan-Meier plotter database. The expression of TRIM68 in local breast cancer and corresponding para-carcinoma tissues were determined using qRT-PCR and immunohistochemistry. The gain- and loss-of function of TRIM68 were carried in breast cancer cells by knockdown or overexpression, the migration and invasion of breast cancer cells were examined by trasnwell, epithelial-mesenchymal transition (EMT) was determined by western blot, cell morphology was observed under light microscope. The activation of Rab5-Rac1 was determined using GST-pull down assay. The ubiquitination of Rabex-5 was determined using in vitro ubiquitination assay. The lower expression of TRIM68 in breast cancer tissues compared to the non-tumor tissues, both in public data and our local clinic samples. Also, lower TRIM68 expression was in breast cancer cells. TRIM68 overexpression impaired, but TRIM68 knockdown facilitated the migration, invasion and EMT in breast cancer cells. TRIM68 regulates the activation of Rab5-Rac1 signaling, and Rabex-5 was identified to be mediated by TRIM68 in a ubiquitination-dependent degradation manner. Furthermore, Rabex-5 knockdown completely abrogated the pro-tumor effects of TRIM68 knockdown in breast cancer cells. Our study first uncovered the crucial role of TRIM68 in malignant behaviors of breast cancer cells, through Rabex-5-mediated Rac5 activation, and shed new light on the development of the diagnostic and therapeutic strategies of breast cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2636-2650"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468175","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":"Reactive oxygen species-dependent regulation of hypoxia-inducible factor 1α/C-X-C motif chemokine receptor 4 signaling promotes ozone-induced cancer metastasis.","authors":"Che-Hsin Lee, Chun-Sheng Chuang, Po-Yen Chiu, Pei-Hsuan Chen, Li-Hsien Wu, Ming-Der Huang, Chia C Wang","doi":"10.62347/DKDS6537","DOIUrl":"10.62347/DKDS6537","url":null,"abstract":"<p><p>Air pollutants, including vehicle emissions and photochemical smog such as ozone, have become a significant health concern in most industrialized nations. Inhaling ozone has repeatedly been linked to increased lung inflammation, immune responses, and cancer development, ultimately speeding up lung cancer metastasis and leading to higher death rates. However, the direct connection between ozone exposure and tumor cell migration has not yet been definitively established. This study aims to investigate the effects of ozone exposure on cancer spread and its underlying mechanisms, focusing on the hypoxia-inducible factor 1α (HIF-1α)/C-X-C motif chemokine receptor 4 (CXCR4) pathway, which influences cancer cell migration and epithelial-mesenchymal transition (EMT). Using B16F10 melanoma and LL2 Lewis lung carcinoma cells, we examined how 1 ppm ozone exposure affects reactive oxygen species (ROS) production and its subsequent impact on the HIF-1α/CXCR4 pathway. Our results show a significant increase in HIF-1α/CXCR4 expression and EMT-related proteins after ozone exposure. Additionally, the use of arbutin, a known ROS scavenger, significantly reduced HIF-1α/CXCR4 levels and cell migration, confirming the role of ROS in ozone-induced metastasis. In summary, our research suggests that ozone promotes cancer spread by activating the HIF-1α/CXCR4 signaling pathway, highlighting an environmental factor that could facilitate cancer progression.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2534-2547"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468359","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":"Association between perioperative opioid consumption and postoperative outcomes in lung cancer surgery: evidence from a retrospective study with inflammatory and immune biomarker analysis [Retraction].","authors":"","doi":"10.62347/KTLF9693","DOIUrl":"https://doi.org/10.62347/KTLF9693","url":null,"abstract":"<p><p>[This retracts the article on p. 866 in vol. 16, PMID: 42004068.].</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2679"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468270","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":"LAMP5 as a novel prognostic biomarker linked to the tumor immune microenvironment in esophageal squamous cell carcinoma.","authors":"Gaoyan Wang, Zhijie Li, Jia Liang, Lei Liu, Yan Zhao, Supeng Shen","doi":"10.62347/WWRY9690","DOIUrl":"10.62347/WWRY9690","url":null,"abstract":"<p><strong>Background: </strong>Identifying reliable prognostic biomarkers and elucidating their cellular origins in the tumor microenvironment (TME) is crucial for improving esophageal squamous cell carcinoma (ESCC) management.</p><p><strong>Methods: </strong>Differentially expressed genes were identified from GSE53624 and GSE32424 datasets. LASSO-Cox regression generated a prognostic risk signature, and a nomogram was built for overall survival prediction. CIBERSORT assessed immune infiltration. Experimental validation included qPCR, immunohistochemistry, and functional assays in cell lines and clinical specimens (n = 65). Lysosomal-associated membrane protein 5 (LAMP5)-modified ESCC cells were co-cultured with CD8⁺ T cells to assess activation and viability. A mouse subcutaneous tumor model was used for <i>in vivo</i> validation.</p><p><strong>Results: </strong>A four-gene prognostic signature was established; LAMP5 demonstrated the strongest independent prognostic value (area under the curve = 0.773). LAMP5-associated genes were enriched in immune-related pathways. Overexpression of LAMP5 promoted malignant behavior, inhibited ESCC cell apoptosis, and suppressed CD8⁺ T cell activation. High LAMP5 expression correlated with advanced TNM stage, poor prognosis, and lymph node metastasis. <i>In vivo</i>, LAMP5 overexpression inhibited CD8⁺ T cell activation and promoted tumor growth.</p><p><strong>Conclusion: </strong>LAMP5 is associated with immune responses in the TME and acts as a promising novel biomarker for ESCC. Its overexpression inhibits CD8⁺ T cell activation and drives malignant progression.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2433-2457"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468432","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 of immune checkpoint inhibitors plus chemotherapy versus chemotherapy-based control in cervical cancer: a meta-analysis.","authors":"Jing Wang, Fei Lin, Xiuxiu Chen","doi":"10.62347/KTTH2223","DOIUrl":"10.62347/KTTH2223","url":null,"abstract":"<p><strong>Objective: </strong>Although chemotherapy is standard for cervical cancer, the added clinical benefit of immune checkpoint inhibitors compared with chemotherapy-based control strategies remains unclear. This meta-analysis aimed to systematically evaluate the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy versus chemotherapy-based control regimens in patients with cervical cancer, synthesizing evidence across randomized and non-randomized studies to inform clinical decision-making and future research.</p><p><strong>Methods: </strong>We systematically searched for eligible comparative studies evaluating immune checkpoint inhibitors combined with chemotherapy versus chemotherapy-based control regimens in patients with cervical cancer. The primary outcomes were progression-free survival (PFS) and overall survival (OS), while secondary outcomes included treatment response, adverse events, subgroup effects, and publication bias. Hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using standard meta-analytic methods, and study quality was assessed using the Cochrane risk-of-bias framework.</p><p><strong>Results: </strong>Compared with chemotherapy-based control strategies, neoadjuvant immune checkpoint inhibitors plus chemotherapy significantly improved progression-free survival (HR, 0.60; 95% CI, 0.47-0.72) and overall survival (HR, 0.64; 95% CI, 0.55-0.73). Improvements in OS and PFS were generally consistent across most predefined subgroups, including age, ECOG performance status, race, chemotherapy backbone, disease status, and prior chemoradiotherapy exposure. In contrast, the addition of immunotherapy did not significantly increase the incidence of overall adverse events (RR, 1.02; 95% CI, 0.94-1.10) or decreased white blood cell count (RR, 0.88; 95% CI, 0.63-1.23). For response outcomes, complete response showed a borderline improvement (RR, 1.17; 95% CI, 0.99-1.37), stable disease was significantly reduced (RR, 0.73; 95% CI, 0.59-0.91), whereas partial response, objective response rate, and disease control rate were not significantly different between groups. Funnel-plot assessment suggested no major publication bias, although a moderate risk of small-study effects could not be excluded.</p><p><strong>Conclusion: </strong>Immune checkpoint inhibitors combined with chemotherapy appear superior to chemotherapy-based control regimens for cervical cancer, demonstrating significant improvements in progression-free and overall survival, along with indications of deeper tumor response.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2131-2147"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468396","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 safety analysis of a novel BTK inhibitor in patients with mantle cell lymphoma harboring TP53 mutations.","authors":"Min Liu, Yannong Ding, Hui Lan","doi":"10.62347/RDKL6452","DOIUrl":"10.62347/RDKL6452","url":null,"abstract":"<p><strong>Objective: </strong>To rigorously evaluate the efficacy and safety of a novel Bruton tyrosine kinase inhibitor (BTKi), alone or in combination with venetoclax, in patients with TP53-mutated mantle cell lymphoma (MCL), focusing on survival outcomes, depth of response, minimal residual disease (MRD), clearance, and treatment-emergent toxicities.</p><p><strong>Methods: </strong>We conducted a retrospective, observational cohort study of consecutive adults with TP53-mutated MCL treated with BTKi-based regimens between January 2022 and December 2025. Patients were assigned to BTKi monotherapy (ibrutinib or acalabrutinib; n = 108) or BTKi plus venetoclax (n = 112). Clinical, pathological, and genomic data were recorded using standardized electronic case-report forms. Responses were assessed according to contemporary MCL criteria, and recurrence/progression-free survival (RFS/PFS) and overall survival (OS) were calculated from predefined time points.</p><p><strong>Results: </strong>Combined treatment significantly prolonged median RFS from 11 to 34 months (HR for recurrence or death 0.42, 95% CI 0.29-0.61; P<0.001), and median OS from 20 to 50 months (HR 0.44, 95% CI 0.31-0.63; P<0.001). Overall response rates were higher with BTKi-based combination therapy (76.8% vs. 58.3%; P = 0.001), with comparable rates of complete response. In multivariable models, BTKi-based combination therapy remained independently associated with longer PFS (HR 0.187, 95% CI 0.079-0.442; P<0.001).</p><p><strong>Conclusion: </strong>In patients with TP53-mutated MCL, BTKi-based combination therapy confers clinically meaningful and durable improvements in RFS and OS, with higher overall response rates than monotherapy and acceptable toxicity profiles.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2481-2492"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468245","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":"Various machine learning prediction models for short-term postoperative prognosis of colorectal cancer based on intraoperative hypothermia.","authors":"Yanfang Ma, Wei Lu, Dong Guo","doi":"10.62347/JESM9471","DOIUrl":"10.62347/JESM9471","url":null,"abstract":"<p><p>This retrospective study aimed to investigate inadvertent intraoperative hypothermia (IIH) in patients undergoing laparoscopic radical resection for colorectal cancer (CRC) and to compare predictive models for short-term prognosis. Among 296 CRC patients (January 2022 to June 2024), univariate and multivariate logistic regression identified independent risk factors. Based on these, five models (nomogram, neural network, decision tree, random forest, gradient boosting machine) were constructed and evaluated using ROC, calibration curves, decision curves, and confusion matrices, with an additional 102 patients (July 2024 to July 2025) for clinical validation. Of the 296 patients, 72 (24.32%) had poor short-term prognosis, and 102 (34.46%) experienced IIH. Restricted cubic spline analysis showed IIH duration >55 minutes significantly increased poor prognosis risk. IIH was an independent risk factor (OR=4.498, P<0.001), remaining significant after adjusting for tumor location, TNM stage, and CEA (OR=4.245, P<0.001). Rectal tumor location, TNM stage III, and CEA ≥5 ng/mL were also risk factors. Except for the decision tree, the four other models showed good predictive performance in both sets. In the independent validation (102 cases), prediction accuracies were 83.33%, 78.43%, 78.43%, 77.45%, and 75.49%, respectively. In conclusion, IIH is an independent risk factor for poor short-term prognosis after laparoscopic CRC resection, with significantly increased risk when duration exceeds 55 minutes. Logistic regression, neural network, random forest, and gradient boosting machine all demonstrate excellent predictive performance.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2170-2188"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468288","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":"Vitamin B1 suppresses liver cancer growth and restores tumor microcirculation.","authors":"Qin Wang, Si-Qi Li, Xue-Ting Liu, Ai-Ling Li, Bing-Wei Li, Hong-Wei Li, Rui-Juan Xiu, Jian-Qun Han, Xiao-Yan Zhang","doi":"10.62347/CEGI5848","DOIUrl":"10.62347/CEGI5848","url":null,"abstract":"<p><p>Inadequate perfusion and hypoxia constitute the primary characteristics of tumor vasculature and drive malignant progression. Strategies aiming at alleviating hypoxia and enhancing blood perfusion may potentiate chemotherapy and immunotherapy, thereby restraining tumor growth. Vitamin B1 (VitB1), an essential coenzyme for multiple metabolic enzymes, plays a crucial role in cellular energy metabolism and in maintaining the balance between glycolysis and the tricarboxylic acid cycle. However, whether the tumor-suppressive effects of VitB1 are associated with modulation of tumor microcirculation remains unclear. This study aimed to evaluate the anti-tumor effects of VitB1 and to investigate the potential relationship with microcirculatory changes in liver cancer. VitB1 inhibited tumor-cell proliferation <i>in vitro</i>, indicating a potential direct effect on tumor cells. <i>In vivo</i>, VitB1 suppressed liver cancer growth in a dose-dependent manner. High- and medium-dose VitB1 treatment increased microvascular blood perfusion and flow velocity assessed using a laser Doppler flowmetry (LDF) system and decreased tumor microvessel density, without affecting tumor microvascular red blood cell concentration. Moreover, high- and medium-dose VitB1 significantly increased the amplitudes of the neurogenic and endothelial oscillatory components of blood perfusion and flow velocity. These findings suggest that the anti-tumor effects of VitB1 may involve the modulation of neurogenic and endothelial activity, which is associated with improved tumor microhemodynamics. Further studies are needed to elucidate the precise mechanisms and the interplay between direct tumor cell effects and microcirculatory changes.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2548-2561"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468314","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":"Unc-51 like kinase 3 induces reticulophagy by mediating the GLI1/CAMK2B signaling pathway to promote the malignant progression of prostate cancer.","authors":"Qin-Quan Wang, Chen Sun, Jin-Hua Wu, Dong-Dong Yu, Hui-Liang Zhou","doi":"10.62347/OTBP6619","DOIUrl":"10.62347/OTBP6619","url":null,"abstract":"<p><p>Recent studies have found that the reticulophagy pathway is able to clear excess endoplasmic reticulum to protect cells from endoplasmic reticulum stress-induced damage. The role of reticulophagy in prostate cancer is still unknown. Key genes of reticulophagy were studied. Subsequently, the ULK3 and CAMK2B mRNA levels were confirmed. ULK3 and CAMK2B expression were elevated in prostate cancer tissues. The silencing of ULK3 inhibited prostate cancer cell vitality. The overexpression of ULK3 had the opposite effect. ULK3 was able to enhance the CAMK2B protein expression by promoting the entry of GLI1 into the nucleus, thereby upregulating the level of reticulophagy. Knockdown of CAMK2B could inhibit reticulophagy induced by ULK3. Further experiments showed that ULK3 phosphorylated GLI1, promoted its nuclear entry and binding to the CAMK2B promoter to enhance CAMK2B expression. Down-regulation of ULK3 inhibited the growth of prostate cancer vitality in vivo. This study confirmed that ULK3 promoted the prostate cancer by upregulating GLI1/CAMK2B-induced reticulophagy.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2109-2130"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468225","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":"Erratum: ATG10 overexpression is related to the dismal prognosis and promotes the growth and migration of hepatocellular carcinoma cells via cyclin B1/CDK1 and CDK2.","authors":"Feng Li, Kai Li, Dan Li, Wei Zhang, Kong-Wu Yang, Di Ke, Qiang Guo, Rong-Shu Shi","doi":"10.62347/RFYI1135","DOIUrl":"https://doi.org/10.62347/RFYI1135","url":null,"abstract":"<p><p>[This corrects the article on p. 1188 in vol. 13, PMID: 37168332.].</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2675-2676"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468379","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}