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Integrating Salivary Biomarkers CST4 and miR-223 With Health-Related Factors for Gastric Cancer Detection and Risk Assessment. 唾液生物标志物CST4和miR-223与胃癌检测和风险评估相关因素的整合
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-09-19 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251375898
Maryam Koopaie, Saba Manafi, Soheila Manifar, Shima Younespour, Sajad Kolahdooz, Mahdi Karimipour Pareshkooh

Background: Gastric cancer remains a leading cause of cancer-related death. Early detection is crucial, but effective non-invasive screening methods are lacking. This study investigates the diagnostic potential of salivary Cystatin S (CST4) and MicroRNA-223 (miR-223) biomarkers, integrated with health-related factors for early gastric cancer detection.

Methods: Forty-five patients with gastric cancer and 45 healthy controls participated in this case-control study. Saliva samples were collected and analyzed for CST4 and miR-223 levels. Demographic data and health-related factors, including hot drink consumption, gastric ulcer history, Helicobacter pylori infection, body mass index (BMI), DMFT (Dental Decay, Missing, and Filled Teeth), and salty food intake, were also collected through a standardized questionnaire. Salivary CST4 levels were determined using enzyme-linked immunosorbent assay (ELISA), and miR-223 levels were quantified using real-time polymerase chain reaction (PCR). Statistical analyses, encompassing multiple logistic regression, were conducted to evaluate the diagnostic efficacy of the biomarkers alongside health-related parameters.

Results: Significant differences in salivary CST4 and miR-223 levels were observed between gastric cancer patients and healthy controls (P < 0.001). Combining salivary biomarkers and health-related factors yielded high accuracy, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89 for the model using CST4 and miR-223. Multiple logistic regression analysis identified several health-related factors, including gastric ulcer history and Helicobacter pylori infection, as significant predictors of gastric cancer risk. The inclusion of health factors, along with biomarkers, enhanced early detection's sensitivity and specificity.

Conclusions: The study highlights the potential of salivary biomarkers CST4 and miR-223 as non-invasive tools for early gastric cancer detection. Integrating these biomarkers with health-related factors, such as gastric ulcer history and Helicobacter pylori infection, enhances the risk assessment and diagnostic accuracy for gastric cancer.

背景:胃癌仍然是癌症相关死亡的主要原因。早期检测至关重要,但缺乏有效的非侵入性筛查方法。本研究探讨了唾液胱抑素S (CST4)和MicroRNA-223 (miR-223)生物标志物结合与健康相关因素在早期胃癌检测中的诊断潜力。方法:45例胃癌患者和45例健康对照者进行病例-对照研究。收集唾液样本并分析CST4和miR-223水平。人口统计数据和健康相关因素,包括热饮消费、胃溃疡史、幽门螺杆菌感染、体重指数(BMI)、蛀牙、缺牙和补牙、含盐食物摄入等,也通过标准化问卷收集。采用酶联免疫吸附法(ELISA)测定唾液CST4水平,采用实时聚合酶链反应(PCR)测定miR-223水平。统计分析包括多元逻辑回归,以评估生物标志物与健康相关参数的诊断效果。结果:胃癌患者与健康对照组唾液CST4和miR-223水平存在显著差异(P miR-223。多元logistic回归分析发现,胃溃疡病史和幽门螺杆菌感染等与健康相关的因素是胃癌风险的重要预测因素。将健康因素与生物标志物结合起来,提高了早期检测的敏感性和特异性。结论:该研究强调了唾液生物标志物CST4和miR-223作为早期胃癌检测的非侵入性工具的潜力。将这些生物标志物与胃溃疡病史和幽门螺杆菌感染等与健康相关的因素相结合,可以提高胃癌的风险评估和诊断准确性。
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引用次数: 0
A Partially Randomized Diagnostic Trial of OCT-EUS Integration: Enhancing Surgical Margin Delineation and Lymph Node Dissection in Oncological Resection. 一项OCT-EUS整合的部分随机诊断试验:在肿瘤切除中增强手术边界划定和淋巴结清扫。
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-09-12 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251363829
Yutao Wang, Lu Zhao, Jiahao Zhao, Xuanyu Wei, Daorong Wang, Jun Liu, Linjie Hu, Bing Xu, Jun Ji, Jiayi Zhang, Chaowu Chen, Dong Tang

Background: Accurate intraoperative navigation remains challenging in gastrointestinal tumor surgery. This study aims to explore the potential of optical coherence tomography (OCT) and endoscopic ultrasonography (EUS) in enhancing the accuracy of intraoperative navigation.

Methods: This single-center diagnostic study was conducted at Northern Jiangsu People's Hospital from August to December 2024. This study is part of a prospective study, and more patients will be recruited in the future. The normal tissues, tumor tissues, vascular tissues, adipose tissues and lymph nodes of 12 patients with gastrointestinal tumors were collected for OCT and EUS scanning, and the image differences were compared. In addition, 43 lymph node specimens from 18 randomly selected patients were scanned by OCT and EUS, and pathological reports were used as the baseline. The results of OCT and EUS were compared retrospectively.

Results: There are notable differences between OCT and EUS imaging. EUS can capture images of the entire tissue layer, making it more effective than OCT in assessing tumor invasion depth. Conversely, OCT serves as an "optical biopsy," providing higher precision in the early stages of lesions. Our further research indicates that the combined application of these modalities holds significant potential. In a double-blind evaluation of 43 lymph nodes from 18 randomly selected patients, OCT demonstrated a sensitivity of 81.25%, specificity of 88.89%, and a positive predictive value (PPV) of 81.25%. In comparison, EUS showed a sensitivity of 87.50%, specificity of 85.19%, and a PPV of 77.78%. The combined use of OCT and EUS achieved a sensitivity of 93.75%, specificity of 92.59%, and a PPV of 88.24%.

Conclusions: The combined use of OCT and EUS can enhance sensitivity and specificity, thereby improving the accuracy of intraoperative navigation.

Trial registration: Chinese Clinical Trial Registry (No. ChiCTR2400088875); Registered 28 August 2024, first patient enrolled 20 September 2024.

背景:准确的术中导航在胃肠道肿瘤手术中仍然具有挑战性。本研究旨在探讨光学相干断层扫描(OCT)和超声内镜(EUS)在提高术中导航准确性方面的潜力。方法:本研究于2024年8月- 12月在苏北人民医院进行。本研究为前瞻性研究的一部分,未来将招募更多的患者。收集12例胃肠道肿瘤患者的正常组织、肿瘤组织、血管组织、脂肪组织和淋巴结进行OCT和EUS扫描,比较图像差异。另外,随机选取18例患者43份淋巴结标本进行OCT和EUS扫描,并以病理报告为基线。回顾性比较OCT和EUS检查结果。结果:OCT影像与EUS影像有显著差异。EUS可以捕获整个组织层的图像,在评估肿瘤侵袭深度方面比OCT更有效。相反,OCT作为“光学活检”,在病变的早期阶段提供更高的精度。我们进一步的研究表明,这些模式的联合应用具有巨大的潜力。在随机选择18例患者的43个淋巴结的双盲评估中,OCT的敏感性为81.25%,特异性为88.89%,阳性预测值(PPV)为81.25%。而EUS的敏感性为87.50%,特异性为85.19%,PPV为77.78%。OCT和EUS联合使用的灵敏度为93.75%,特异性为92.59%,PPV为88.24%。结论:OCT与EUS联合应用可提高术中导航的敏感性和特异性,从而提高术中导航的准确性。试验注册:中国临床试验注册中心ChiCTR2400088875);2024年8月28日注册,2024年9月20日首例患者入组。
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引用次数: 0
Immature Granulocytes and Nivolumab Outcomes in Stage IV Non-Small Cell Lung Cancer: Insights by Tumor Subtype. 未成熟粒细胞和纳武单抗在IV期非小细胞肺癌中的预后:肿瘤亚型的见解
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251371094
Mustafa Ersoy

Background: In non-small cell lung cancer (NSCLC) treatment, immunotherapy has become the standard therapy when platinum-based chemotherapy is ineffective, in the absence of a targetable mutation. However, a significant proportion of patients do not benefit from this treatment, underscoring the critical need for predictive biomarkers. This study aims to investigate the potential predictive role of immature granulocytes in response to nivolumab treatment, which can be used as a second-line therapy independent of programmed death ligand 1 (PDL-1) expression and other markers. Furthermore, the study seeks to determine whether there is a difference in the treatment response of immature granulocytes between the 2 main subtypes of NSCLC: lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD).

Methods: This retrospective study enrolled 50 patients with NSCLC who underwent treatment at the Kütahya Health Sciences University Evliya Çelebi Education and Research Hospital and Kütahya City Hospital between January 2021 and January 2025. The study examined the difference between patients' baseline immature granulocyte levels and their initial response to treatment, as assessed by positron emission tomography-computed tomography.

Results: The study found a statistically significant association between higher baseline immature granulocyte levels and poorer treatment response. Subgroup analysis by lung cancer subtype revealed that the difference was more prominent in the LUSCs group.

Conclusion: Immature granulocytes may predict response to nivolumab treatment in NSCLC patients, particularly in the LUSCs subgroup. Based on the findings of this study, immature granulocytes and other neutrophil-dependent inflammatory markers could serve as potential predictors of immunotherapy response and provide insights into the mechanisms of immunotherapy resistance, warranting further investigation. Our study may also encourage future research to look for separate markers for LUSCs and LUADs, given the continued critical need for predictive markers in this field.

背景:在非小细胞肺癌(NSCLC)的治疗中,当铂基化疗无效时,免疫治疗已成为标准治疗,缺乏靶向突变。然而,很大一部分患者并没有从这种治疗中获益,这凸显了对预测性生物标志物的迫切需求。本研究旨在探讨未成熟粒细胞对纳武单抗治疗反应的潜在预测作用,纳武单抗可作为独立于程序性死亡配体1 (PDL-1)表达和其他标志物的二线治疗。此外,本研究旨在确定两种主要NSCLC亚型:肺鳞状细胞癌(LUSC)和肺腺癌(LUAD)之间未成熟粒细胞的治疗反应是否存在差异。方法:这项回顾性研究纳入了50例非小细胞肺癌患者,这些患者于2021年1月至2025年1月在k塔哈亚健康科学大学Evliya Çelebi教育与研究医院和k塔哈亚市医院接受治疗。该研究检查了患者基线未成熟粒细胞水平与他们对治疗的初始反应之间的差异,通过正电子发射断层扫描-计算机断层扫描进行评估。结果:研究发现,基线未成熟粒细胞水平较高与治疗反应较差之间存在统计学意义上的关联。按肺癌亚型进行的亚组分析显示,LUSCs组的差异更为显著。结论:未成熟粒细胞可以预测NSCLC患者对纳武单抗治疗的反应,特别是在LUSCs亚组中。基于本研究的发现,未成熟粒细胞和其他嗜中性粒细胞依赖的炎症标志物可以作为免疫治疗反应的潜在预测因子,并为免疫治疗耐药的机制提供见解,值得进一步研究。鉴于该领域对预测标记物的持续需求,我们的研究也可能鼓励未来的研究寻找LUSCs和luad的单独标记物。
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引用次数: 0
Frontiers in Systemic Therapy for Unresectable or Metastatic Adrenocortical Carcinoma: Harnessing Novel Therapeutic Approaches. 不可切除或转移性肾上腺皮质癌的系统治疗前沿:利用新的治疗方法。
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-08-29 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251364042
Adam E Singer, Nikhita Kathuria-Prakash, David Shabsovich, Lizette Garcia, Leland Damron, Allan J Pantuck, Alexandra Drakaki

Adrenocortical carcinoma is a rare, aggressive endocrine malignancy with limited effective systemic therapy options and an overall poor prognosis for unresectable or metastatic disease. Chemotherapy and mitotane are the traditional systemic therapies of choice. More recently, as drug development in oncology has shifted away from chemotherapy, a host of therapeutic approaches targeting novel mechanisms of action has been studied in adrenocortical carcinoma. This review summarizes all nonchemotherapeutic approaches that have been and/or are currently being tested in clinical trials for the treatment of unresectable or metastatic adrenocortical carcinoma.

肾上腺皮质癌是一种罕见的侵袭性内分泌恶性肿瘤,有效的全身治疗选择有限,不可切除或转移性疾病的整体预后较差。化疗和米托坦是传统的全身疗法的选择。最近,随着肿瘤药物开发从化疗转向化疗,许多针对肾上腺皮质癌的新作用机制的治疗方法已被研究。本综述总结了所有已经和/或目前正在临床试验中用于治疗不可切除或转移性肾上腺皮质癌的非化疗方法。
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引用次数: 0
Efficacy and Safety of First-Line Chemotherapy-Based Combination Therapy for Patients With Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis. 一线化疗联合治疗广泛期小细胞肺癌的疗效和安全性:系统评价和网络荟萃分析
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-08-28 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251364320
Qingfang Zhao, Xiaomin Liu, Minghua Yu, Jinglong Chen

Background: Multiple first-line chemotherapy-based combination regimens are available for patients with extensive-stage small cell lung cancer (ES-SCLC), however, direct head-to-head comparisons remain limited. This network meta-analysis (NMA) aimed to indirectly compare the efficacy and safety of various first-line combination therapies. Methods: A comprehensive literature search was conducted across electronic databases and academic conference proceedings to identify eligible randomized controlled trials (RCTs). Bayesian network meta-analysis and systematic review were performed on the selected studies. Primary outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), along with adverse events of grade ⩾ 3 (grade ⩾ 3 AEs) and subgroup analyses. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022360249). Results: The analysis included 12 randomized trials encompassing 5840 patients and 14 treatment regimens. The combination of benmelstobart, anlotinib and chemotherapy showed the most significant improvement in PFS (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.26-0.41) and OS (HR = 0.61, 95% CI = 0.47-0.79) compared with chemotherapy alone. This regimen ranked highest for PFS (Bayesian ranking probability 99%) and OS (39%). However, it was also associated with a higher risk of Grade ⩾ 3 AEs (HR = 2.01, 95% CI = 1.09-3.73). In patients with baseline liver metastases, this regimen provided the greatest PFS benefit (99%), whereas serplulimab plus chemotherapy offered the best OS (53%). Conversely, for patients with baseline brain metastases, combination therapy failed to demonstrate a significant survival benefit. Conclusions: For treatment-naïve ES-SCLC patients, benmelstobart plus anlotinib plus chemotherapy yielded the most favorable outcomes in terms of PFS, OS and ORR, but a less favorable safety profile. These findings support its use as a potent therapeutic option in few patient populations.

背景:广泛期小细胞肺癌(ES-SCLC)患者可使用多种基于一线化疗的联合方案,然而,直接的头对头比较仍然有限。该网络荟萃分析(NMA)旨在间接比较各种一线联合治疗的疗效和安全性。方法:通过电子数据库和学术会议记录进行全面的文献检索,以确定符合条件的随机对照试验(rct)。对入选研究进行贝叶斯网络meta分析和系统评价。主要结局包括总生存期(OS)、无进展生存期(PFS)和客观反应率(ORR),以及小于或等于3级的不良事件(小于或等于3级ae)和亚组分析。该研究方案已在国际前瞻性系统评价注册(PROSPERO: CRD42022360249)注册。结果:该分析包括12项随机试验,包括5840例患者和14种治疗方案。与单独化疗相比,本美司巴特、安洛替尼联合化疗对PFS(风险比[HR] = 0.33, 95%可信区间[CI] = 0.26-0.41)和OS (HR = 0.61, 95% CI = 0.47-0.79)的改善最为显著。该方案在PFS(贝叶斯排名概率99%)和OS(39%)方面排名最高。然而,它也与等级大于或等于3 ae的高风险相关(HR = 2.01, 95% CI = 1.09-3.73)。在基线肝转移患者中,该方案提供了最大的PFS获益(99%),而serplulimab +化疗提供了最好的OS(53%)。相反,对于基线脑转移的患者,联合治疗未能显示出显著的生存益处。结论:对于treatment-naïve ES-SCLC患者,benmelstobart + anlotinib +化疗在PFS、OS和ORR方面产生了最有利的结果,但安全性较差。这些发现支持它在少数患者群体中作为一种有效的治疗选择。
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引用次数: 0
Discordance in Immunohistochemistry Results in Breast Pathologies: Effect of Chemotherapy, Specimen Characteristics, or Pathology Center? 乳腺病理免疫组化结果不一致:化疗、标本特征还是病理中心的影响?
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-08-20 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251367498
Mustafa Ersoy

Background: Immunohistochemical results are of vital importance in the classification of patients with breast cancer into subgroups and in treatment decision-making at every stage. However, differences can occur in biopsy results obtained from the same patient. In our study, we aimed to investigate the importance of pathological examination, which is a possible reason for the differences in patients' immunohistochemistry results.

Methods: For this purpose, patients were divided into 3 groups. The differences in estrogen receptor, progesterone receptor, HER2, and Ki-67 were examined between the following groups: patients who received neoadjuvant chemotherapy and then underwent surgery (41 patients), patients who underwent surgery without chemotherapy (50 patients), and the same specimen from a different center and our center (21 patients).

Results: The pathological discordance rates were 34.1% in the neoadjuvant chemotherapy group, 28% in the surgery without chemotherapy group, and 38.1% in the comparison between our institution and an external center, with no statistically significant difference across the 3 groups (P = .667). When examining the changes within each group, statistically significant differences were found in HER2 (P = .002) for the tru-cut biopsy surgery group and Ki-67 (P = .025) for the group comparing our center to an external center.

Conclusions: As a result, it was considered that one of the important reasons for the immunohistochemical differences in breast biopsies, which is a known fact, is the evaluating center and pathologist.

背景:免疫组化结果对乳腺癌患者亚组的划分和各阶段的治疗决策具有重要意义。然而,同一患者的活检结果可能存在差异。在我们的研究中,我们旨在探讨病理检查的重要性,这可能是导致患者免疫组织化学结果差异的原因。方法:将患者分为3组。我们检测了以下组患者雌激素受体、孕激素受体、HER2、Ki-67的差异:接受新辅助化疗后手术的患者(41例),手术不化疗的患者(50例),来自不同中心和我中心的同一标本(21例)。结果:新辅助化疗组病理不一致率为34.1%,手术不化疗组为28%,我院与外部中心比较病理不一致率为38.1%,三组比较差异无统计学意义(P = .667)。当检查各组内的变化时,发现真切活检手术组的HER2 (P = 0.002)和我们中心与外部中心比较组的Ki-67 (P = 0.025)具有统计学意义。结论:因此,我们认为乳腺活检免疫组化差异的重要原因之一是评估中心和病理学家,这是一个众所周知的事实。
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引用次数: 0
NAT2: A Novel Target in Intrahepatic Cholangiocarcinoma and its Role in Modulating Tumor Behavior. NAT2:肝内胆管癌的新靶点及其在调节肿瘤行为中的作用
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-08-17 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251360481
Xiyun Chen, Guang Yang, Cheng Lou, Yulong Dong, Zhengang Yuan

Background: Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer typically diagnosed at advanced stages, limiting treatment options and reducing survival rates. Targeted therapy presents a promising strategy to improve outcomes. This study aims to identify novel molecular biomarkers influencing ICC development and explore their roles in tumor progression.

Methods: Data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed using weighted gene co-expression network analysis (WGCNA) to identify genes related to tumor metastasis and recurrence. Survival analysis and gene set enrichment analysis (GSEA) assessed the relationship between gene expression and survival, as well as associated signaling pathways. Cellular experiments, including small interfering RNA (siRNA) knockdown, cell viability assays, Transwell migration assays, and flow cytometry, were performed.

Results: The Kaplan-Meier analysis showed that ICC patients with high N-acetyltransferase 2 (NAT2) expression had significantly shorter survival times than those with low expression (P < .001). Gene set enrichment analysis revealed enrichment of MYC and MTORC1 pathways, linked to tumor proliferation, and E2F and G2M pathways, which regulate the cell cycle, in high NAT2 expression samples (P < .01). The NAT2 knockdown reduced RBE cell proliferation (P < .001) and increased late apoptosis (P < .001). Immunofluorescence analysis showed increased Bax and Caspase-3 expression and decreased BCL-2 expression (P < .05), supporting NAT2's role in regulating ICC cell apoptosis.

Conclusion: NAT2, a novel therapeutic target, holds significant potential to improve the prognosis of ICC patients.

背景:肝内胆管癌(ICC)是一种原发性肝癌,通常在晚期诊断,限制了治疗选择并降低了生存率。靶向治疗是一种改善预后的有希望的策略。本研究旨在发现影响ICC发展的新型分子生物标志物,并探讨其在肿瘤进展中的作用。方法:采用加权基因共表达网络分析(WGCNA)对来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的数据进行分析,找出与肿瘤转移和复发相关的基因。生存分析和基因集富集分析(GSEA)评估基因表达与生存的关系,以及相关的信号通路。进行细胞实验,包括小干扰RNA (siRNA)敲除、细胞活力测定、Transwell迁移测定和流式细胞术。结果:Kaplan-Meier分析显示,n-乙酰转移酶2 (NAT2)高表达的ICC患者的生存时间明显短于低表达的ICC患者(P P P P P P P)。结论:NAT2是一种新的治疗靶点,具有显著改善ICC患者预后的潜力。
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引用次数: 0
Application of Cord Blood-Derived Exosomes in Tumor Prevention and Treatment. 脐带血来源外泌体在肿瘤防治中的应用。
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-08-10 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251365360
Chen Huang, Yongsheng Li, Baozhong Zhang, Yukuan Tang, Yuyang Huang, Wei Wei

The eradication of tumors remains a critical and challenging issue in medical research. Exosomes (EXOs) derived from various sources have garnered increasing attention in the field of tumor therapy. Among these, cord blood (CB)-derived EXOs may offer unique advantages in combating tumors due to the distinctive properties of CB. This narrative review examines the current application status of CB-derived EXOs in tumor prevention and treatment: in the context of tumor treatment, it focuses on their direct therapeutic application and their use as drug carriers; regarding tumor prevention, it explores their application in cancer vaccines. In addition, it also reviews the specific components of CB from which these EXOs are derived, their particle sizes, characteristic proteins, and the types of tumors to which they have been primarily applied for prevention and treatment. In conclusion, we believe that CB-derived EXOs hold substantial potential for effective tumor prevention and treatment and are likely to emerge as a prominent area of research in the future.

肿瘤的根除仍然是医学研究中的一个关键和具有挑战性的问题。来源多样的外泌体(EXOs)在肿瘤治疗领域受到越来越多的关注。其中,由于脐带血(CB)的独特特性,脐带血衍生的exo可能在对抗肿瘤方面具有独特的优势。本文综述了cb衍生exo在肿瘤防治中的应用现状:在肿瘤治疗方面,重点介绍了cb衍生exo的直接治疗应用和作为药物载体的应用;在肿瘤预防方面,探讨了它们在肿瘤疫苗中的应用。此外,本文还综述了衍生这些exo的CB的特定成分、它们的颗粒大小、特征蛋白以及它们主要用于预防和治疗的肿瘤类型。总之,我们相信cb衍生的exo具有有效预防和治疗肿瘤的巨大潜力,并可能成为未来研究的一个突出领域。
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引用次数: 0
Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer. 嘌呤核苷磷酸化酶(PNP)作为侵袭性膀胱癌的生物标志物和治疗靶点。
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-08-10 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251359145
Yanfei Chen, Peiyi Xian, Jianming Lu, Le Zhang, Chao Cai, Weide Zhong

Background: This study investigates the potential of purine nucleoside phosphorylase (PNP) as a biomarker and therapeutic target in muscle-invasive bladder cancer (MIBC). We aimed to explore PNP's expression, prognostic value, and role in metabolic pathways, along with its association with gene mutations.

Methods: We conducted multi-omics analyses using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases to evaluate PNP expression across MIBC samples and its prognostic impact through Kaplan-Meier and Cox regression analyses. Functional enrichment and gene set variation analysis (GSVA) were performed to identify PNP-related pathways. In addition, in vitro siRNA knockdown experiments were carried out to assess PNP's influence on MIBC cell proliferation.

Results: Our findings revealed that PNP is significantly overexpressed in MIBC tissues and serves as an independent prognostic factor, correlating with poor clinical outcomes across multiple cohorts (TCGA: hazard ratio [HR] > 1.3, P < .05; GSE48075: HR > 1.5, P = .07; GSE169455: HR > 2.8, P < .001). Functional enrichment analysis identified PNP's involvement in various metabolic pathways. Furthermore, we observed a high frequency of RB1 mutations in the PNP-high expression group. Based on this observation, we hypothesize that patients harboring RB1 mutations may benefit from PNP-targeted therapy. In vitro experiments demonstrated that PNP knockdown significantly reduces MIBC cell proliferation.

Conclusion: This study underscores PNP's role as a promising biomarker and therapeutic target in MIBC.

背景:本研究探讨了嘌呤核苷磷酸化酶(PNP)作为肌肉浸润性膀胱癌(MIBC)的生物标志物和治疗靶点的潜力。我们的目的是探讨PNP的表达、预后价值、在代谢途径中的作用,以及它与基因突变的关系。方法:利用来自癌症基因组图谱(TCGA)、基因表达图谱(GEO)等公共数据库的数据进行多组学分析,通过Kaplan-Meier和Cox回归分析评估PNP在MIBC样本中的表达及其对预后的影响。通过功能富集和基因集变异分析(GSVA)鉴定pnp相关通路。此外,我们还进行了体外siRNA敲低实验,以评估PNP对MIBC细胞增殖的影响。结果:我们的研究结果显示,PNP在MIBC组织中显著过表达,并作为一个独立的预后因素,与多个队列的不良临床结果相关(TCGA:风险比[HR] > 1.3, p1.5, P = .07;结论:该研究强调了PNP作为MIBC中有前景的生物标志物和治疗靶点的作用。
{"title":"Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer.","authors":"Yanfei Chen, Peiyi Xian, Jianming Lu, Le Zhang, Chao Cai, Weide Zhong","doi":"10.1177/11795549251359145","DOIUrl":"10.1177/11795549251359145","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the potential of purine nucleoside phosphorylase (PNP) as a biomarker and therapeutic target in muscle-invasive bladder cancer (MIBC). We aimed to explore PNP's expression, prognostic value, and role in metabolic pathways, along with its association with gene mutations.</p><p><strong>Methods: </strong>We conducted multi-omics analyses using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases to evaluate PNP expression across MIBC samples and its prognostic impact through Kaplan-Meier and Cox regression analyses. Functional enrichment and gene set variation analysis (GSVA) were performed to identify PNP-related pathways. In addition, <i>in vitro</i> siRNA knockdown experiments were carried out to assess PNP's influence on MIBC cell proliferation.</p><p><strong>Results: </strong>Our findings revealed that PNP is significantly overexpressed in MIBC tissues and serves as an independent prognostic factor, correlating with poor clinical outcomes across multiple cohorts (TCGA: hazard ratio [HR] > 1.3, <i>P</i> < .05; GSE48075: HR > 1.5, <i>P</i> = .07; GSE169455: HR > 2.8, <i>P</i> < .001). Functional enrichment analysis identified PNP's involvement in various metabolic pathways. Furthermore, we observed a high frequency of RB1 mutations in the PNP-high expression group. Based on this observation, we hypothesize that patients harboring RB1 mutations may benefit from PNP-targeted therapy. In vitro experiments demonstrated that PNP knockdown significantly reduces MIBC cell proliferation.</p><p><strong>Conclusion: </strong>This study underscores PNP's role as a promising biomarker and therapeutic target in MIBC.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251359145"},"PeriodicalIF":1.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838306","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}
引用次数: 0
The Prognostic Value of B12/CRP Ratio (BCR) in Patients Diagnosed With Solid Cancer. B12/CRP比值(BCR)在实体癌诊断中的预后价值
IF 1.9 4区 医学 Q3 ONCOLOGY Pub Date : 2025-08-10 eCollection Date: 2025-01-01 DOI: 10.1177/11795549251360891
Merve Keskinkilic, Elif Cetin Basaran, Tugba Yavuzsen

Background: This study aimed to determine the prognostic effect of the serum vitamin B12 level/CRP ratio (BCR) on patients diagnosed with solid cancer.

Methods: Patients >18 years diagnosed with solid cancer were included in the study, the data of the patients were retrospectively examined, and the cut-off values for BCR were determined using receiver operating characteristic (ROC) analysis. Accordingly, grouping was performed, appropriate statistical analyses were performed, and P < .05 was accepted as the significance limit value.

Results: The median age of the 344 patients included in the study was found to be 60.9 (range: 27-88) years. Around 56.6% (n = 174) of the patients had nondistant metastatic group and 49.4% (n = 170) had metastatic group. The median follow-up period of the patients was found to be 46.8 (range: 4-63) months. In the metastatic group, mortality was statistically significantly 2.1 times higher in those with a BCR cut-off value <3.5 (95% confidence interval [CI]; 1.4-3.2, P < .001). In the nonmetastatic group, mortality was statistically significantly twice higher in those with a BCR cut-off value <3.8 (95% CI; 1.4-3.3, P < .001). In addition, mortality was statistically significantly higher in high-risk patients in the nonmetastatic group (63.8% (n = 188) vs 45.5% (n = 156) (P < .001). The mOS period for patients in the high-risk group was 42.8 ± 1.4 (95% CI: 40.1-45.5) months, the mOS period for patients in the low-risk group was 51.5 ± 1.3 (95% CI: 49.0-54.0) months, and the mOS period for the entire group was 46.8 ± 1.0 (95% CI: 44.8-48.7) months (P < .001).

Conclusıons: In conclusion, our study has shown that BCR, which has not been reported in the literature to date, is one of the cheapest and easily accessible inflammation markers that can determine prognosis in cancer patients.

背景:本研究旨在确定血清维生素B12水平/CRP比值(BCR)对确诊实体癌患者预后的影响。方法:选取年龄在bb0 ~ 18岁确诊为实体癌的患者,对患者资料进行回顾性分析,采用受试者工作特征(receiver operating characteristic, ROC)分析确定BCR的临界值。结果:纳入研究的344例患者中位年龄为60.9岁(范围:27-88岁)。非远处转移组占56.6% (n = 174),转移组占49.4% (n = 170)。患者的中位随访时间为46.8个月(范围4-63个月)。在转移组中,BCR临界值P P P P P Conclusıons的死亡率具有统计学意义,高出2.1倍:总之,我们的研究表明,迄今为止尚未在文献中报道的BCR是最便宜且易于获取的炎症标志物之一,可以确定癌症患者的预后。
{"title":"The Prognostic Value of B12/CRP Ratio (BCR) in Patients Diagnosed With Solid Cancer.","authors":"Merve Keskinkilic, Elif Cetin Basaran, Tugba Yavuzsen","doi":"10.1177/11795549251360891","DOIUrl":"10.1177/11795549251360891","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to determine the prognostic effect of the serum vitamin B12 level/CRP ratio (BCR) on patients diagnosed with solid cancer.</p><p><strong>Methods: </strong>Patients >18 years diagnosed with solid cancer were included in the study, the data of the patients were retrospectively examined, and the cut-off values for BCR were determined using receiver operating characteristic (ROC) analysis. Accordingly, grouping was performed, appropriate statistical analyses were performed, and <i>P</i> < .05 was accepted as the significance limit value.</p><p><strong>Results: </strong>The median age of the 344 patients included in the study was found to be 60.9 (range: 27-88) years. Around 56.6% (n = 174) of the patients had nondistant metastatic group and 49.4% (n = 170) had metastatic group. The median follow-up period of the patients was found to be 46.8 (range: 4-63) months. In the metastatic group, mortality was statistically significantly 2.1 times higher in those with a BCR cut-off value <3.5 (95% confidence interval [CI]; 1.4-3.2, <i>P</i> < .001). In the nonmetastatic group, mortality was statistically significantly twice higher in those with a BCR cut-off value <3.8 (95% CI; 1.4-3.3, <i>P</i> < .001). In addition, mortality was statistically significantly higher in high-risk patients in the nonmetastatic group (63.8% (n = 188) vs 45.5% (n = 156) (<i>P</i> < .001). The mOS period for patients in the high-risk group was 42.8 ± 1.4 (95% CI: 40.1-45.5) months, the mOS period for patients in the low-risk group was 51.5 ± 1.3 (95% CI: 49.0-54.0) months, and the mOS period for the entire group was 46.8 ± 1.0 (95% CI: 44.8-48.7) months (<i>P</i> < .001).</p><p><strong>Conclusıons: </strong>In conclusion, our study has shown that BCR, which has not been reported in the literature to date, is one of the cheapest and easily accessible inflammation markers that can determine prognosis in cancer patients.</p>","PeriodicalId":48591,"journal":{"name":"Clinical Medicine Insights-Oncology","volume":"19 ","pages":"11795549251360891"},"PeriodicalIF":1.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838307","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}
引用次数: 0
期刊
Clinical Medicine Insights-Oncology
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