Lei Gao, Sixing Wang, Xintong Hu, Lixia Wang, Yanfeng Xi, Peng Bu, Guohai Zhao, Lili Zhao, Yongming Yang, Hongwei Zhao
{"title":"Preliminary study of apatinib combined with fluzoparib in the treatment of HRP ovarian cancer via the HR pathway.","authors":"Lei Gao, Sixing Wang, Xintong Hu, Lixia Wang, Yanfeng Xi, Peng Bu, Guohai Zhao, Lili Zhao, Yongming Yang, Hongwei Zhao","doi":"10.21037/tcr-2025-666","DOIUrl":"10.21037/tcr-2025-666","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is the gynecological malignancy with the highest mortality rate. Due to late detection and easy recurrence, the 5-year survival rate of advanced ovarian cancer patients is less than 30%. The current standard treatment for ovarian cancer includes platinum-based combination therapy. Most ovarian cancer patients achieve clinical remission; however, the short-term recurrence rate is still high. For patients with recurrent ovarian cancer, who are unwilling to receive chemotherapy or cannot tolerate chemotherapy after multiple lines of chemotherapy, \"chemotherapy-free\" treatment may be appropriate. This study aimed to investigate the preliminary mechanism of action of the antiangiogenic drug apatinib combined with poly ADP ribose polymerase (PARP) inhibitor fluzoparib as a \"chemotherapy-free\" regimen in the treatment of ovarian cancer patients with homologous recombination proficiency (HRP).</p><p><strong>Methods: </strong>The HRP cell line SKOV3 was used for the experiments. The cells were treated with apatinib, fluzoparib, and apatinib combined with fluzoparib, respectively. The cell proliferation rate and migration rate were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and scratch assays. Western blot was used to detect the expression of phosphorylated mitogen-activated protein kinase kinase (<i>p-MEK)</i>, recombination activating gene 51 (<i>RAD51)</i>, and phosphorylated histone cluster 2 H2A family member X (<i>γH2AX)</i>. Animal experiments were performed to evaluate the effects of the combined therapy on tumor growth and drug toxicity by constructing a cell-line transplanted tumor model. Western blot was used to detect the expression of <i>p-MEK</i>, <i>RAD51</i>, and <i>γH2AX</i>. Immunohistochemistry (IHC) was used to detect the expression of <i>γH2AX</i>, phosphorylated extracellular signal-regulated kinase (<i>p-ERK)</i>, and breast cancer 1 <i>(BRCA1</i>).</p><p><strong>Results: </strong><i>In vitro</i>, apatinib combined with fluzoparib significantly inhibited the growth and migration of the SKOV3 cells. Western blot showed that apatinib combined with fluzoparib induced the down-regulation of <i>p-MEK</i> and homologous recombination (HR) pathway-related protein <i>RAD51</i> expression, and increased DNA damage-related protein <i>γH2AX</i> expression in the SKOV3 cells. The animal experiment results showed that apatinib combined with fluzoparib had a better antitumor effect than single-drug therapy without obvious <i>in vivo</i> toxicity. The western blot results showed that <i>γH2AX</i> protein expression was increased, and <i>p-MEK</i> protein expression was decreased in the apatinib combined with fluzoparib group. The IHC results showed that <i>γH2AX</i> protein expression was increased and <i>p-MEK</i> protein expression was decreased in the apatinib combined with fluzoparib group.</p><p><strong>Conclusions: </strong>The combination of apatinib and ","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2470-2482"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hesen Wu, Xingyi Chen, Xiaoming Feng, Wei He, Duilio Divisi, Jimmy T Efird, José Franco, Xuemin Guo
{"title":"Efficacy of three lung cancer prediction models in diagnosing benign and malignant pulmonary nodules.","authors":"Hesen Wu, Xingyi Chen, Xiaoming Feng, Wei He, Duilio Divisi, Jimmy T Efird, José Franco, Xuemin Guo","doi":"10.21037/tcr-2025-468","DOIUrl":"10.21037/tcr-2025-468","url":null,"abstract":"<p><strong>Background: </strong>The predictive models for malignant lung nodules have been developed, but need further validation and optimization for broader clinical use. This study aimed to compare the diagnostic efficacy of the Mayo model, Peking University People's Hospital (PKUPH) model, and the lung cancer biomarker panel (LCBP) model in distinguishing between benign and malignant pulmonary nodules, providing valuable clinical research data for the early diagnosis of lung cancer.</p><p><strong>Methods: </strong>Clinical and imaging data of patients diagnosed with pulmonary nodules at Meizhou People's Hospital from March 2021 through January 2023 were collected. Data from patients with benign pulmonary nodules during the same period, who served as negative referents, were also gathered. The Mayo model, PKUPH model, and LCBP model were used to clinically validate lung cancer prediction rates. The receiver operating characteristic (ROC) curves and statistical significance comparing the areas under the curve (AUCs) for each model were evaluated.</p><p><strong>Results: </strong>A total of 428 patients were included: 160 females and 268 males. The noncancer group included 218 cases (50.93%), and the cancer group included 210 cases (49.07%). The AUC values of the three models were as follows: Mayo model, 0.783; PKUPH model, 0.726; and LCBP model, 0.759. (I) For the Mayo model, at the maximum Youden index, the concordance rate was 74.3%, the sensitivity 85.71%, the specificity 63.30%, the positive predictive value 69.23%, the negative predictive value 82.14%, the positive likelihood ratio 2.335, and the negative likelihood ratio 0.226. (II) For the PKUPH model, at the maximum Youden index, the concordance rate was 70.3%, the sensitivity 84.29%, the specificity 56.88%, the positive predictive value 65.31%, the negative predictive value 78.98%, the positive likelihood ratio 1.955, and the negative likelihood ratio 0.276. (III) For the LCBP model, at the maximum Youden index, the concordance rate was 75.0%, the sensitivity 72.38%, the specificity 77.52%, the positive predictive value 75.62%, the negative predictive value 74.45%, the positive likelihood ratio 3.220, and the negative likelihood ratio 0.356.</p><p><strong>Conclusions: </strong>All three predictive models exhibit clinical applicability, with minimal differences in diagnostic efficacy. The LCBP model outperformed both the Mayo and PKUPH models in diagnostic performance, showing greater diagnostic value for the Chinese population. However, there is still room for optimization in each model.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2410-2420"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liquid biopsy in advanced and metastatic breast cancer: translating prognostic value to clinical implementation.","authors":"Chelain R Goodman, Carlos H Barcenas","doi":"10.21037/tcr-2025-40","DOIUrl":"10.21037/tcr-2025-40","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2178-2182"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Osimertinib-chemotherapy synergy in <i>EGFR</i>-mutant NSCLC: advancing central nervous system control amidst toxicity considerations.","authors":"Rahul Kumar, Emily Miao, Luke Roy George Pike","doi":"10.21037/tcr-2024-2207","DOIUrl":"10.21037/tcr-2024-2207","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2188-2191"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiming Guan, Yu Luan, Shanshan Zhao, Meiyan Li, Francesco Girolamo, Joshua D Palmer, Qi Guan
{"title":"Single-cell RNA sequencing for characterizing the immune communication and iron metabolism roles in CD31<sup>+</sup> glioma cells.","authors":"Yiming Guan, Yu Luan, Shanshan Zhao, Meiyan Li, Francesco Girolamo, Joshua D Palmer, Qi Guan","doi":"10.21037/tcr-2025-377","DOIUrl":"10.21037/tcr-2025-377","url":null,"abstract":"<p><strong>Background: </strong>Gliomas are aggressive brain tumors marked by complex cellular interactions and significant immune cell infiltration. This study investigated the role of CD31<sup>+</sup> immune cells, specifically macrophages and T cells, in the glioma microenvironment through single-cell RNA sequencing (scRNA-seq).</p><p><strong>Methods: </strong>We employed the CellChat framework to map cell-cell communication pathways and used Monocle3 for pseudotime trajectory analysis to characterize the signaling and developmental progressions within CD31<sup>+</sup> cells. Pathways such as osteopontin (SPP1) and major histocompatibility complex class II (MHC-II) were analyzed in terms of their role in immune regulation, and we examined the expression of ferritin, an iron-binding protein, to assess its potential function in modulating CD31<sup>+</sup> cell activity.</p><p><strong>Results: </strong>Our findings highlight the expression of key pathways, including SPP1 and MHC-II, influencing immune regulation. Ferritin was found to be highly expressed in CD31<sup>+</sup> cells, suggesting a dual role in iron metabolism and immune modulation within the glioma microenvironment.</p><p><strong>Conclusions: </strong>This study clarified the distinct roles of CD31<sup>+</sup> immune cells in glioma progression and identified ferritin as a potential therapeutic target for modulating immune responses in gliomas. These findings may offer new directions in glioma research and the development of immunotherapy, which can aid in improving treatment outcomes.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2421-2439"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan Chen, Yao Rao, Weihui Liu, Qian Yang, Guirong Wu, Fudao Wu, Youshu Gao, Jie Li, Jiangping Fu
{"title":"Role of TRKC and NT-3 proteins in the progression and prognosis of colorectal cancer.","authors":"Shan Chen, Yao Rao, Weihui Liu, Qian Yang, Guirong Wu, Fudao Wu, Youshu Gao, Jie Li, Jiangping Fu","doi":"10.21037/tcr-2025-519","DOIUrl":"10.21037/tcr-2025-519","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a common tumor of the digestive system. In recent years, CRC has had the fourth highest incidence and second highest mortality rate among tumors worldwide. Therefore, it is important to identify new molecular markers, and examine their relationship with the clinicopathological features and prognosis of CRC patients. This study examined the correlation between the expression levels of the tropomyosin receptor kinase C (TRKC) and neurotrophic factor-3 (NT-3) proteins, and the clinicopathological features and prognosis of CRC patients.</p><p><strong>Methods: </strong>In total, 141 paraffin-embedded specimens from patients who had undergone radical surgical resection for CRC were analyzed. All CRC diagnoses were confirmed by pathological examination. Corresponding adjacent normal tissues served as controls. Immunohistochemical staining was employed to assess the expression of the TRKC and NT-3 proteins in both the CRC and adjacent normal tissues. A subsequent statistical analysis was conducted to explore the associations between the expression levels of these proteins, and the clinicopathological features and prognostic outcomes of CRC patients.</p><p><strong>Results: </strong>The expression level of <i>TRKC</i> was significantly higher in the CRC tissues than the adjacent normal tissues, while the expression level of <i>NT-3</i> was significantly lower in the CRC tissues than the adjacent normal tissues, and the observed differences were statistically significant (P<0.001). Notably, <i>TRKC</i> expression was significantly correlated with the tumor site (P<0.05), lymph node metastasis (P<0.05), tumor node metastasis (TNM) stage (P<0.01), serum carcinoembryonic antigen (CEA) level (P<0.01), and serum carbohydrate antigen 19-9 (CA199) level (P<0.05). The patients with positive <i>TRKC</i> had significantly shorter overall survival (OS) and progression-free survival (PFS) times than those with negative <i>TRKC</i> expression (P<0.001). Further, <i>NT-3</i> expression was significantly associated with lymph node metastasis (P<0.05), distant metastasis (P<0.05), TNM stage (P<0.05), and serum CEA level (P<0.05). The patients with positive <i>NT-3</i> expression had prolonged OS and PFS compared to those with negative <i>NT-3</i> expression (P<0.01). The Cox proportional hazards regression model revealed that <i>TRKC</i> expression had a hazard ratio (HR) of 2.679 (P<0.01), while <i>NT-3</i> expression had a HR of 0.433 (P<0.05).</p><p><strong>Conclusions: </strong>We found that the TRKC and NT-3 proteins were closely associated with the occurrence, metastasis, invasion, and tumor marker levels of CRC, and can be used as independent predictors of prognosis in patients with CRC. <i>TRKC</i> mainly indicates a poor prognosis in CRC, while <i>NT-3</i> indicates a good prognosis.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2457-2469"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artificial intelligence radiomics in the diagnosis, treatment, and prognosis of gynecological cancer: a literature review.","authors":"Gengshen Bai, Shiwen Huo, Guangcai Wang, Shijia Tian","doi":"10.21037/tcr-2025-618","DOIUrl":"10.21037/tcr-2025-618","url":null,"abstract":"<p><strong>Background and objective: </strong>Gynecological cancer is the most common cancer that affects women's quality of life and well-being. Artificial intelligence (AI) technology enables us to exploit high-dimensional imaging data for precision oncology. Tremendous progress has been made with AI radiomics in cancers such as lung and breast cancers. Herein, we performed a literature review on AI radiomics in the management of gynecological cancer.</p><p><strong>Methods: </strong>A search was performed in the databases of PubMed, Embase, and Web of Science for original articles written in English up to 10 September 2024, using the terms \"gynecological cancer\", \"cervical cancer\", \"endometrial cancer\", \"ovarian cancer\", AND \"artificial intelligence\", \"AI\", AND \"radiomics\". The included studies mainly focused on the current landscape of AI radiomics in the diagnosis, treatment, and prognosis of gynecological cancer.</p><p><strong>Key content and findings: </strong>A total of 128 studies were included, with 86 studies focusing on tumor diagnosis (n=23) and characterization (n=63), 15 on treatment response prediction, and 27 on recurrence and survival prediction. AI radiomics has shown potential value in tumor diagnosis and characterization [tumor staging, histological subtyping, lymph node metastasis (LNM), lymphovascular space invasion (LVSI), myometrial invasion (MI), and other molecular or clinicopathological factors], chemotherapy or chemoradiotherapy response evaluation, and prognosis (disease recurrence or metastasis, and survival) prediction. However, most included studies were single-center and retrospective. There was substantial heterogeneity in methodology and results reporting.</p><p><strong>Conclusions: </strong>AI radiomics has been increasingly adopted in the management of gynecological cancer. Further validation in large-scale datasets is needed before clinical translation.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2508-2532"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng He, Kelong Tao, Jian Sun, Renqi Tang, Rongyao Jin
{"title":"Association between blood metal elements and lung cancer: a cross-sectional and Mendelian randomization study.","authors":"Meng He, Kelong Tao, Jian Sun, Renqi Tang, Rongyao Jin","doi":"10.21037/tcr-24-1430","DOIUrl":"10.21037/tcr-24-1430","url":null,"abstract":"<p><strong>Background: </strong>The association between exposure to certain heavy metals and an increased risk of lung cancer has been confirmed, but the exact relationship remains uncertain. This research shed light on the association between blood metal elements and lung cancer, and examined their causal association through Mendelian randomization (MR).</p><p><strong>Methods: </strong>This study retrospectively included 48,132 participants from 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression was employed for exploring the relationship between blood metal elements (cadmium, lead, mercury, selenium, manganese, cobalt, copper, iron, and zinc) and lung cancer. Additionally, MR analysis was carried out to investigate potential causal association between blood metal elements and the progression of lung cancer.</p><p><strong>Results: </strong>A positive association was observed between cadmium and lung cancer, while a negative association was noted between iron and lung cancer when all confounders in the NHANES were fully taken into account. MR analysis further demonstrated that iron was negatively linked with lung adenocarcinoma (LUAD) in Europeans [odds ratio (OR)<sub>ivw</sub> =0.77, 95% confidence interval (CI): 0.65-0.92, P=0.004; OR<sub>weighted median</sub> =0.75, 95% CI: 0.61-0.92, P=0.006]. Sensitivity analyses confirmed the robustness and reliability of this finding (P>0.05).</p><p><strong>Conclusions: </strong>Iron is inversely related to the incidence of lung cancer, with MR analysis supporting its protective role in LUAD. These findings necessitate further validation in large-scale prospective cohort studies.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2207-2219"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Grace C Blitzer, Jacques Galipeau, Sara S McCoy, Randall J Kimple
{"title":"Still thirsting for a fix.","authors":"Grace C Blitzer, Jacques Galipeau, Sara S McCoy, Randall J Kimple","doi":"10.21037/tcr-2025-150","DOIUrl":"10.21037/tcr-2025-150","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 4","pages":"2175-2177"},"PeriodicalIF":1.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}