American journal of cancer research最新文献

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Tumor Treating Fields enhance chemotherapy efficacy by increasing cellular drug uptake and retention in mesothelioma cells.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/ODWL5634
Rosy Amodeo, Lavinia Morosi, Marina Meroni, Ezia Bello, Sara Timo, Roberta Frapolli, Maurizio D'Incalci, Monica Lupi
{"title":"Tumor Treating Fields enhance chemotherapy efficacy by increasing cellular drug uptake and retention in mesothelioma cells.","authors":"Rosy Amodeo, Lavinia Morosi, Marina Meroni, Ezia Bello, Sara Timo, Roberta Frapolli, Maurizio D'Incalci, Monica Lupi","doi":"10.62347/ODWL5634","DOIUrl":"10.62347/ODWL5634","url":null,"abstract":"<p><p>Tumor Treating Fields (TTFields) applied with standard chemotherapy have been approved for the first-line treatment of unresectable pleural mesothelioma (PM), an aggressive malignancy with limited effective therapy options. In this study, we demonstrated that the simultaneous exposure to TTFields and doxorubicin or vinorelbine enhanced treatment efficacy in patient-derived PM cells by increasing intracellular drug concentrations. This was achieved by modulating several genes that encode transport proteins, such as the downregulation of P-glycoprotein (P-gp). Using specific, sensitive and quantitative analytical techniques, we observed a more than 70% increase in intracellular concentrations of doxorubicin and vinorelbine in samples treated with TTFields, and a greater than 50% increase in drug uptake in cells exposed to TTFields and pemetrexed. This result indicates that the increased drug concentration observed in TTFields treated cells is significant not only for drugs that are P-gp substrates but also suggests that TTFields could potentially affect other efflux pumps. However, the co-exposure to the drug and TTFields was critical to increasing intracellular drug levels, highlighting the necessity of concurrent use with drugs to enhance the antiproliferative effects of treatment. The <i>in vitro</i> findings were further corroborated by <i>in vivo</i> pharmacokinetic experiments in mice subcutaneously injected with epithelioid PM tumors. Indeed, a 30% increase in intratumor concentrations was observed when vinorelbine was administered with TTFields. Our findings suggest that TTFields could be a well-tolerated approach for enhancing intratumoral drug levels and potentially achieving a more significant therapeutic impact on PM treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"271-285"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412861","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}
引用次数: 0
Factors influencing serum hCG negativization timing in gestational trophoblastic neoplasia.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/HFRL7722
Saie Zhu, Limeng Cai, Yuting Wang, Wanting Huang, Jiaojiao Jin, Haoyu Wang, Jianhua Qian
{"title":"Factors influencing serum hCG negativization timing in gestational trophoblastic neoplasia.","authors":"Saie Zhu, Limeng Cai, Yuting Wang, Wanting Huang, Jiaojiao Jin, Haoyu Wang, Jianhua Qian","doi":"10.62347/HFRL7722","DOIUrl":"10.62347/HFRL7722","url":null,"abstract":"<p><p>Gestational trophoblastic neoplasia (GTN) refers to malignant diseases originating from placental trophoblast cells. Despite high complete remission rates with standard treatments, the adverse effects of chemotherapy, variation in treatment regimens, and the psychological impact on patients significantly influence the prognosis. This study aims to identify factors influencing the time to serum human chorionic gonadotropin (hCG) negativization, thereby contributing to the optimization of patient management strategies. We conducted a retrospective analysis of 206 patients diagnosed with invasive mole and gestational choriocarcinoma treated at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to May 2022. Patients- and treatment-related risk factors were collected. We evaluated 33 variables potentially related to the duration of serum hCG negativization with statistically significant variables from univariate analyses subsequently included in multivariate Cox regression analysis. Through univariate analysis, we identified 11 significant predictors that related with hCG negativization, including body mass index (BMI), age at menarche, number of miscarriages, prior pregnancy status, time since prior pregnancy, maximum tumor diameter, maximum lung tumor diameter, alkaline phosphatase levels, pre-chemotherapy hCG levels, initial chemotherapy regimen, and whether hysterectomy was performed. Cox regression analysis highlighted that increased BMI was associated with a shorter time to hCG negativization (HR=1.730, P=0.001). In contrast, higher pre-treatment hCG levels, longer time since the last pregnancy, and undergoing hysterectomy were associated with prolonged hCG conversion times. In conclusion, this study underscores the importance of individual factors such as BMI, pre-treatment hCG levels, and surgical interventions in determining the duration of hCG negativization in GTN patients. These findings suggest that tailored treatment strategies considering these factors could enhance treatment efficacy and patient outcomes. Increased awareness and careful consideration of these factors should be integral to pre-treatment planning and patient counseling.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"331-347"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413077","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}
引用次数: 0
Tumor-treating fields and concurrent cisplatin: an in vitro demonstration of efficacy in triple-negative breast cancer.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/LXJH5896
Austin R Smothers, Mya E Beasley, Hunter S Warren, Olivia G Kegel, W Jeffery Edenfield, John J O'Connell, Brian W Booth
{"title":"Tumor-treating fields and concurrent cisplatin: an <i>in vitro</i> demonstration of efficacy in triple-negative breast cancer.","authors":"Austin R Smothers, Mya E Beasley, Hunter S Warren, Olivia G Kegel, W Jeffery Edenfield, John J O'Connell, Brian W Booth","doi":"10.62347/LXJH5896","DOIUrl":"10.62347/LXJH5896","url":null,"abstract":"<p><p>Chemotherapy is commonly used to treat patients with triple-negative breast cancer. Combinations of platinum-based chemotherapies have demonstrated higher rates of pathologic complete responses of triple-negative breast cancer compared to combinations without platinum-based chemotherapies. However, there is a significant increase in general toxicity with the addition of platinum-based regimens. Some groups have investigated using tumor-treating fields as an alternative treatment method for triple-negative breast cancer, and chemosensitization by tumor-treating fields has been observed <i>in vitro</i>. With the goal of minimizing the toxicities associated with platinum-based chemotherapy, we investigated anti-mitotic effects of concurrent tumor-treating fields and cisplatin treatment to show that the addition of tumor-treating fields further inhibited cell growth in triple-negative breast cancer. We show that combining cisplatin with tumor-treating fields induces higher levels of apoptosis within triple-negative breast cancer cells as opposed to normal epithelial cells and the combination has a more immediate mechanism of cell death than either monotherapy. We also demonstrate that, when combined with tumor-treating fields, a lower dose of chemotherapy can be used to achieve the same efficacy of triple-negative breast cancer cell death as higher doses of individual therapy.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"322-330"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412863","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}
引用次数: 0
Triptolide induces immunogenic cell death in cervical cancer cells via ER stress and redox modulation.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/XNVR3799
Ziwen Zheng, Yamei Chen, Chao Wang, Ling Li, Buzhen Tan
{"title":"Triptolide induces immunogenic cell death in cervical cancer cells via ER stress and redox modulation.","authors":"Ziwen Zheng, Yamei Chen, Chao Wang, Ling Li, Buzhen Tan","doi":"10.62347/XNVR3799","DOIUrl":"10.62347/XNVR3799","url":null,"abstract":"<p><p>Cervical cancer remains a significant global health burden, particularly in developing countries, despite advances in screening and prevention. Novel therapeutic strategies are urgently needed to improve outcomes for patients with advanced or metastatic disease. Triptolide (TL), a key component of the Chinese herb Tripterygium wilfordii, has shown potent anticancer effects in various malignancies. In this study, we investigated the anticancer effects of TL on cervical cancer cells in vitro and in vivo, focusing on its ability to induce immunogenic cell death (ICD). TL exhibited potent cytotoxicity, inhibited proliferation, induced apoptosis, and suppressed tumor growth in cervical cancer models. Mechanistically, TL induced ICD in cervical cancer cells, as evidenced by the calreticulin (CRT) exposure on the cell surface and the release of HMGB1 and ATP. TL-induced CRT exposure was mediated by endoplasmic reticulum (ER) stress, as demonstrated by the upregulation of ATF3 and the activation of oxidative stress and immune pathways. Oral administration of TL significantly inhibited tumor growth in a cervical cancer xenograft model, without overt toxicities. These findings highlight the potential of TL as a novel immunotherapeutic agent for cervical cancer and warrant further investigation into its clinical translation. The combination of TL with immune checkpoint inhibitors or other immunotherapies may provide a promising strategy to enhance the efficacy of cervical cancer treatment while minimizing adverse effects.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"69-83"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412859","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}
引用次数: 0
Development and validation of a nomogram model for predicting lymph node metastasis in early non-small-cell lung cancer.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/JBKV3746
Hao Xie, Chao Wang, Lin Ma, Qiang Zhang
{"title":"Development and validation of a nomogram model for predicting lymph node metastasis in early non-small-cell lung cancer.","authors":"Hao Xie, Chao Wang, Lin Ma, Qiang Zhang","doi":"10.62347/JBKV3746","DOIUrl":"10.62347/JBKV3746","url":null,"abstract":"<p><p>This study aimed to identify risk factors associated with lymph node metastasis (LNM) in early non-small-cell lung cancer (eNSCLC) patients and to develop a nomogram model for individualized LNM risk assessment. A retrospective analysis was conducted using clinical data from 1013 eNSCLC patients treated at Beijing Jishuitan Hospital between January 2019 and June 2024. Patients were divided into a training group (668 patients), a validation group (345 patients), and an external group (112 patients). Multivariate logistic regression analysis was performed to identify independent risk factors for LNM. The factors identified were integrated into a nomogram model, and its predictive performance was assessed using the area under the receiver operating characteristic curve (AUC). Independent risk factors for LNM included age, tumor size, degree of differentiation, and CYFRA21-1 levels (all P<0.05). The nomogram demonstrated strong predictive performance with AUC values of 0.828, 0.751, and 0.789 in the training, validation, and external groups, respectively. Calibration curves showed good agreement between predicted and observed probabilities, and decision curve analysis confirmed the model's clinical utility. The developed nomogram is an effective tool for predicting LNM risk in eNSCLC patients. It may help optimize individualized treatment strategies, potentially improving patient outcomes.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"299-310"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413062","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}
引用次数: 0
Effects of 131I and TSH suppression therapy on METTL3, METTL14 levels and recurrence in thyroid cancer.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/THJB4749
Li-Guo Yang, Zhi-Gang Yang, Jun Zhang, Yi-Li Fu
{"title":"Effects of <sup>131</sup>I and TSH suppression therapy on METTL3, METTL14 levels and recurrence in thyroid cancer.","authors":"Li-Guo Yang, Zhi-Gang Yang, Jun Zhang, Yi-Li Fu","doi":"10.62347/THJB4749","DOIUrl":"10.62347/THJB4749","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the changes in the expression levels of METTL3 and METTL14 in patients with differentiated thyroid cancer (DTC) and their association with thyroid function indicators, as well as to explore the potential value of these genes in predicting the risk of DTC recurrence.</p><p><strong>Methods: </strong>This cohort study included 189 DTC patients treated at Shidong Hospital between April 2016 and February 2021. Patients were divided into an experimental group, which received combined radioactive iodine (<sup>131</sup>I) therapy and thyroid-stimulating hormone (TSH) suppression therapy (n = 119), and a control group, which received only TSH suppression therapy (n = 70). Messenger RNA (mRNA) expression levels of METTL3 and METTL14 in patients' serum were measured before and six months after treatment using quantitative real-time polymerase chain reaction (qRT-PCR). Thyroid function indicators, including free triiodothyronine (FT3), free thyroxine (FT4), TSH, and thyroglobulin (Tg), were assessed using electrochemiluminescence immunoassay. Disease-free survival (DFS) was analyzed using Cox regression analysis, and data visualization was performed with the ggplot2 package in R.</p><p><strong>Results: </strong>Both METTL3 and METTL14 expression levels significantly decreased after treatment in both the experimental and control groups (P < 0.001). Regarding thyroid function indicators, FT3 and FT4 levels significantly increased, while TSH and Tg levels significantly decreased post-treatment (P < 0.001). Lower post-treatment expression levels of METTL3 and METTL14 were significantly associated with a higher risk of recurrence. Cox regression analysis further indicated that post-treatment METTL3, METTL14, TSH, and Tg levels were independent predictors of DFS (P < 0.05).</p><p><strong>Conclusion: </strong>Low expression levels of METTL3 and METTL14 are closely associated with malignant progression and an increased risk of recurrence in DTC. Patients receiving combined <sup>131</sup>I and TSH suppression therapy demonstrated longer DFS. These findings suggest that METTL3 and METTL14 could serve as potential biomarkers for prognosis evaluation in DTC patients.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"42-58"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413065","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}
引用次数: 0
Impact of real-time contrast-enhanced ultrasound on thyroid function in microwave ablation treatment of thyroid tumors.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/OIUD6634
Chao Chen, Yangyang Zhang, Qianqian Liu, Meiding Wang, Su Mou, Jun Luo, Guo Zhou
{"title":"Impact of real-time contrast-enhanced ultrasound on thyroid function in microwave ablation treatment of thyroid tumors.","authors":"Chao Chen, Yangyang Zhang, Qianqian Liu, Meiding Wang, Su Mou, Jun Luo, Guo Zhou","doi":"10.62347/OIUD6634","DOIUrl":"10.62347/OIUD6634","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the impact of contrast-enhanced ultrasound on the efficacy of microwave ablation in the treatment of benign thyroid tumors, as well as its effect on thyroid function, to assess its application value.</p><p><strong>Methods: </strong>We retrospectively analyzed data from 60 patients with benign thyroid nodules treated at Sichuan Provincial People's Hospital from January 2021 to December 2021. All patients underwent microwave ablation. Based on the intraoperative assessment of the ablation effect, they were divided into a contrast-enhanced ultrasound group (n=34) and a conventional ultrasound group (n=26). Postoperatively, the treatment outcomes were classified into complete ablation or the presence of residual nodules. We also assessed the recurrence rate one year after treatment, along with inflammatory factors, stress response indicators, and effects on thyroid function.</p><p><strong>Results: </strong>The complete ablation rate for thyroid nodules in the contrast-enhanced ultrasound group was significantly higher than that in the conventional ultrasound group (P<0.05). Intraoperative measurements revealed lower ablated nodule volumes, bleeding volumes, and in situ replacement rates in the contrast-enhanced ultrasound group, with statistically significant differences (P<0.05). Preoperative thyroid function hormone indicators, inflammatory factors and stress response indicators did not significantly differ between the two groups. Postoperatively, both groups had lower levels of free triiodothyronine (FT3) and free thyroxine (FT4), along with higher levels of thyroid-stimulating hormone (TSH), white blood cells (WBC), serum C-reactive protein (CRP), interleukin-6 (IL-6), norepinephrine (NE), epinephrine (E), and cortisol (Cor) compared to preoperative levels. However, the contrast-enhanced ultrasound group demonstrated higher FT3 and FT4 levels and lower WBC, serum CRP, IL-6, NE, E, Cor and TSH levels than the conventional ultrasound group, with statistically significant differences (all P<0.05). No statistically significant differences in complication rates were observed between the two groups.</p><p><strong>Conclusion: </strong>Contrast-enhanced ultrasound in microwave ablation for benign thyroid nodules can improve the complete ablation rate, reduce recurrence, and have a minimal impact on thyroid function, without increasing complication rates. It is recommended for clinical use.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"32-41"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413153","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}
引用次数: 0
Mechanism analysis and targeted therapy of IDH gene mutation in glioma.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/NSXC2205
Xingyuan Ma, Chao Sun, Xiao Ding, Jiaqi Xu, Yuhang Zhang, Tingzhen Deng, Yatao Wang, Haijun Yang, Ruiwen Ding, Haotian Li, Dawen Wang, Maohua Zheng
{"title":"Mechanism analysis and targeted therapy of IDH gene mutation in glioma.","authors":"Xingyuan Ma, Chao Sun, Xiao Ding, Jiaqi Xu, Yuhang Zhang, Tingzhen Deng, Yatao Wang, Haijun Yang, Ruiwen Ding, Haotian Li, Dawen Wang, Maohua Zheng","doi":"10.62347/NSXC2205","DOIUrl":"10.62347/NSXC2205","url":null,"abstract":"<p><p>Isocitrate dehydrogenase (IDH) is a pivotal enzyme responsible for catalyzing the oxidative decarboxylation of isocitrate into α-ketoglutarate (α-KG). This enzyme serves as a crucial regulator in the tricarboxylic acid cycle (TCA cycle), acting as a rate-limiting step. Its role extends beyond mere metabolic function, influencing cellular homeostasis and overall cell function. In the past decade, prominent research in cancer genetics has revealed that genes responsible for encoding isocitrate dehydrogenase are commonly mutated across various human malignancies. Significant research in the field has shown that these mutations are commonly found in diseases like glioma, acute myeloid leukemia (AML), cholangiocarcinoma (CCA), chondrosarcoma, and thyroid cancer (TC). As research on IDH progresses, deeper insights into the biological effects of IDH mutations have been gained, unveiling their potential role in tumorigenesis. In addition, IDH mutants' unique activities creates new pathways in tumor metabolism, gene rearrangement, and therapeutic resistance. Currently, innovative molecular targeting strategies for genes bearing mutations in IDH have been devised to enhance the therapeutic efficacy against cancers harboring IDH mutations. These methods represent a promising avenue for improving treatment outcomes in IDH-mutated malignancies. This article mainly summarizes the related research on glioma caused by IDH mutation, and focuses on the biological characteristics and transformation of IDH.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"248-270"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412760","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}
引用次数: 0
NFATC2 target gene signature correlates with immune checkpoint blockade resistance in melanoma.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/EYML2689
Bashir Lawal, Yue Wang, Parisa Lotfinejad, Renu Sharma, Chuang Yang, Anusha Annasamudram, Xiao-Song Wang
{"title":"NFATC2 target gene signature correlates with immune checkpoint blockade resistance in melanoma.","authors":"Bashir Lawal, Yue Wang, Parisa Lotfinejad, Renu Sharma, Chuang Yang, Anusha Annasamudram, Xiao-Song Wang","doi":"10.62347/EYML2689","DOIUrl":"10.62347/EYML2689","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs), such as anti-PD-1 and anti-CTLA-4, have significantly advanced melanoma treatment by reactivating the immune system to target cancer cells. However, a substantial portion of patients do not respond or develop resistance, highlighting the need for more effective predictive biomarkers. Dysregulation of transcriptional programs has been implicated in cancer progression and immune evasion, with transcription factors (TFs) playing a crucial role. In this study, we investigated transcriptional gene signatures (TGSs) for their potential to predict ICI resistance in melanoma by analyzing two independent clinical trial datasets. Among the identified TFs, NFATC2 (Nuclear Factor of Activated T Cells 2) was observed to be a promising marker for resistance to anti-PD-1 therapy. NFATC2, a regulator of T cell activation, may be co-opted by melanoma cells to evade immune surveillance. Our analysis indicated that elevated NFATC2 TGS scores were associated with ICI resistance and poorer survival outcomes across multiple melanoma cohorts. Validation in independent datasets further suggested NFATC2's potential predictive value, particularly in patients without liver metastasis or with prior anti-CTLA-4 therapy. Elevated NFATC2 TGS scores also correlated with reduced immune cell infiltration, specifically of CD8+ T cells, increased markers of T cell exhaustion, and higher tumor purity. These findings support NFATC2 TGS as a candidate biomarker for stratifying melanoma patients and potentially informing ICI therapy response. Further research into NFATC2-associated immune evasion mechanisms may offer insights for overcoming resistance to immunotherapy.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"311-321"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412768","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}
引用次数: 0
Establishment and validation of a prognostic risk early-warning model for retinoblastoma based on XGBoost.
IF 3.6 3区 医学
American journal of cancer research Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.62347/WHUQ1208
Feng Wang, Jian Wang
{"title":"Establishment and validation of a prognostic risk early-warning model for retinoblastoma based on XGBoost.","authors":"Feng Wang, Jian Wang","doi":"10.62347/WHUQ1208","DOIUrl":"10.62347/WHUQ1208","url":null,"abstract":"<p><p>Retinoblastoma (RB) is the most common intraocular malignancy in children, and early detection and treatment are crucial for improving patient outcomes. Conventional treatments, such as enucleation and radiotherapy, have limitations in fully addressing prognosis. This study aimed to establish and validate an early-warning prognostic model for RB based on the XGBoost algorithm to improve the prediction accuracy of the 5-year survival rate in children. A retrospective analysis was conducted on 320 children with RB treated at Changzhi People's Hospital between February 2012 and April 2019. The patients were randomly divided into a training group (n=224) and a validation group (n=96). Clinical data, including age, gender, tumor characteristics, and tumor marker levels, were collected. Prognostic factors were analyzed using XGBoost and Cox regression models, and model performance was evaluated using various statistical methods. No significant differences were observed in baseline data between the two sets (P>0.05). Cox regression analysis identified tumor diameter (P=0.032), IIRC stage (P<0.001), and NSE (P=0.016) as independent prognostic factors. The XGBoost model achieved an area under the curve (AUC) of 0.951 in the training group, significantly higher than the Cox model (P=0.001), while in the validation group, the XGBoost model's AUC was 0.902, with no significant difference compared to the Cox model (P=0.117). The XGBoost model demonstrated high accuracy and clinical utility in predicting the 5-year survival of children with RB. Decision curve analysis (DCA) and calibration curves further confirmed that the XGBoost model offers higher clinical net benefits and superior calibration ability across various thresholds.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"99-112"},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413074","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}
引用次数: 0
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