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Personalized tumor-informed circulating tumor DNA monitoring for early detection of recurrence in postoperative pancreatic cancer. 个性化肿瘤信息循环肿瘤DNA监测对胰腺癌术后复发的早期发现。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-22 eCollection Date: 2026-01-01 DOI: 10.3389/fonc.2026.1745466
Jingjing Chen, Lu Zou, Xinyuan Bai, Fan Tong, Jiayao Ni, Haochen Tang, Yaru Liu, Xiang Kong, Jiani Yin, Fufeng Wang, Huizi Sha, Fanyan Meng, Juan Du

Background: Up to 80% of patients with resected pancreatic cancer experience recurrence within 2 years. We evaluated the feasibility and accuracy of a personalized, tumor-informed circulating tumor DNA (ctDNA) test for the early detection of recurrence risk during long-term postoperative surveillance.

Methods: We recruited 43 patients with pancreatic cancer who underwent curative surgical resections. A personalized panel was developed to detect ctDNA in plasma based on whole-exome mutation information derived from tumor tissues. A total of 139 plasma samples were analyzed to assess recurrence risk and the efficacy of adjuvant therapy.

Results: A personalized ctDNA monitoring panel was successfully customized in 35 of 43 cases. Sixteen patients relapsed within a median of 15.7 months (range: 5.4-30.0 months) postsurgery. For the 11 patients with positive ctDNA, the median lead time from initial ctDNA positivity to radiological relapse was 4.59 months (range: 0.88-15.61). After completion of adjuvant chemotherapy (ACT), 94.3% (33/35) of patients contributed 52.5% (73/139) of the ctDNA testing samples. These samples exhibited an elevated rate of ctDNA detection (48.5%, 16/33) compared to samples obtained prior to and during the commencement of ACT, with a negative predictive value of 82.4% (14/17) and a positive predictive value of 75.0% (12/16). The presence of ctDNA was significantly correlated with shorter disease-free survival and overall survival.

Conclusions: Long-term dynamic ctDNA monitoring after pancreatic cancer resection, particularly following the completion of ACT, is predictive of recurrence risk. The proactive implementation of ctDNA monitoring after ACT in patients with resectable pancreatic cancer has important implications for clinical practice.

背景:高达80%的胰腺癌切除患者在2年内复发。我们评估了一种个性化的、肿瘤知情的循环肿瘤DNA (ctDNA)检测在术后长期监测中早期发现复发风险的可行性和准确性。方法:我们招募了43例行根治性手术切除的胰腺癌患者。基于来自肿瘤组织的全外显子组突变信息,开发了一种用于检测血浆中ctDNA的个性化面板。共分析139份血浆样本,以评估复发风险和辅助治疗的效果。结果:43例患者中35例成功定制了个性化的ctDNA监测面板。16例患者术后中位复发15.7个月(范围:5.4-30.0个月)。对于11例ctDNA阳性患者,从初始ctDNA阳性到放射学复发的中位提前时间为4.59个月(范围:0.88-15.61)。辅助化疗(ACT)完成后,94.3%(33/35)的患者贡献了52.5%(73/139)的ctDNA检测样本。与ACT开始前和开始期间获得的样本相比,这些样本的ctDNA检出率升高(48.5%,16/33),阴性预测值为82.4%(14/17),阳性预测值为75.0%(12/16)。ctDNA的存在与较短的无病生存期和总生存期显著相关。结论:胰腺癌切除术后,特别是完成ACT手术后,长期动态ctDNA监测可预测复发风险。可切除胰腺癌患者行ACT后积极实施ctDNA监测对临床实践具有重要意义。
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引用次数: 0
Efficacy and safety of traditional Chinese medicine as an adjuvant to postoperative chemotherapy in colorectal cancer: a meta-analysis. 中药辅助结直肠癌术后化疗的疗效和安全性:一项荟萃分析。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fonc.2025.1700525
Qinsi He, Xiaodan Chen, Haotian Zeng, Xinyu Gao, Zhi Zheng, Jun Rao, Qun Wen, Xuchao Yu, Jiquan Zeng

Objective: To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) for postoperative adjuvant chemotherapy for colorectal cancer.

Methods: CNKI, VIP, Wanfang, CBM, PubMed, and Web of Science were searched for the randomized controlled trials (RCT) of TCM participating in postoperative adjuvant chemotherapy for colorectal cancer. The search period was from January 1, 2018 to December 31, 2024. Cochrane bias risk assessment tool was used to evaluate the quality of included studies, and RevMan5.4 was used for meta-analysis.

Results: A total of 41 randomized controlled trials involving 2918 patients with colorectal cancer was ultimately included. The results demonstrated that the combination of TCM with chemotherapy was superior to chemotherapy alone in several aspects. These included the objective response rate (ORR), improvement of TCM-related symptoms, levels of tumor markers CEA and CA199, immune function indicators (CD3+, CD4+, CD4+/CD8+, NK cells), and quality of life as measured by the KPS score. Additionally, the combination therapy reduced CD8+ levels and mitigated abnormal laboratory indicators caused by chemotherapy, such as leukopenia, thrombocytopenia, decreased hemoglobin, and abnormal liver and kidney function. Furthermore, it alleviated chemotherapy-related adverse effects (AEs), including nausea, vomiting, and peripheral nerve toxicity.

Conclusions: TCM may be associated with improvements in quality of life and reduce chemotherapy side effects in postoperative colorectal cancer patients, though large-scale rigorous trials are needed to confirm efficacy and safety.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42025635900.

目的:系统评价中药在结直肠癌术后辅助化疗中的疗效和安全性。方法:检索中国知网(CNKI)、维普网(VIP)、万方网(Wanfang)、中国中医药网(CBM)、PubMed网(PubMed)、Web of Science网,检索中医药参与结直肠癌术后辅助化疗的随机对照试验(RCT)。搜索期为2018年1月1日至2024年12月31日。采用Cochrane偏倚风险评估工具评价纳入研究的质量,采用RevMan5.4进行meta分析。结果:最终纳入41项随机对照试验,涉及2918例结直肠癌患者。结果表明,中药联合化疗在多个方面优于单纯化疗。这些指标包括客观缓解率(ORR)、中医相关症状的改善、肿瘤标志物CEA和CA199水平、免疫功能指标(CD3+、CD4+、CD4+/CD8+、NK细胞)和KPS评分测量的生活质量。此外,联合治疗降低了CD8+水平,减轻了化疗引起的异常实验室指标,如白细胞减少、血小板减少、血红蛋白降低和肝肾功能异常。此外,它还减轻了化疗相关的不良反应(ae),包括恶心、呕吐和周围神经毒性。结论:中药可能与改善结直肠癌术后患者的生活质量和减少化疗副作用有关,但需要大规模严格的试验来证实其有效性和安全性。系统综述注册:https://www.crd.york.ac.uk/prospero/,标识符CRD42025635900。
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引用次数: 0
Comparative analysis of gastric cancer risk attribution (1990-2021) and 2050 burden projection in China, Japan, and South Korea: an age-period-cohort modeling approach based on the Global Burden of Disease 2021 study. 中国、日本和韩国胃癌风险归因(1990-2021)和2050年负担预测的比较分析:基于2021年全球疾病负担研究的年龄-时期队列建模方法
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/fonc.2025.1680684
Tao Jiang, Liming Tan, Kehang Dai
<p><strong>Background: </strong>Gastric cancer (GC) is the fifth most common cancer and fourth leading cause of cancer-related death globally, with a particularly high burden in East Asia. Significant differences exist among China, Japan, and South Korea in terms of risk factor exposure, screening practices, and demographic shifts, yet existing research lacks cross-national comparisons of long-term trends and quantitative analyses of policy effectiveness; this study aims to systematically analyze the spatiotemporal evolution of GC burden in these three countries from 1990 to 2050 by integrating the Global Burden of Disease (GBD) 2021 database with the Bayesian Age-Period-Cohort (BAPC) model to provide evidence for Asia-Pacific prevention and control strategies.</p><p><strong>Methods: </strong>We extracted data on key GC epidemiological indicators-including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years rate (ASDR)-as well as relevant risk factor data from 1990 to 2021 using the GBD 2021 database. An enhanced Age-Period-Cohort (APC) analytical framework was adopted, and log-linear models were constructed to quantify the independent impacts of age, period, and cohort effects on GC burden. The population attributable fraction (PAF) method was applied to estimate the proportion of DALYs attributable to modifiable risk factors such as smoking and high-sodium diets. For trend projection (2022-2050), the BAPC model was utilized, forming a comprehensive analytical chain that spanned data extraction, effect decomposition, and future burden forecasting.</p><p><strong>Results: </strong>From 1990 to 2021, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years rate (ASDR) of GC declined significantly across China, Japan, and South Korea. The absolute burden trends differed among the three countries: new GC cases in China increased from 300,000 in 1990 to 612,000 in 2021, with annual deaths reaching 445,000; Japan and South Korea had 9% and 7% reductions in new cases, respectively, along with substantial declines in mortality. Risk attribution analysis showed that smoking was the primary factor associated with GC burden among males in China, while high-sodium diets were the dominant associated factor in Japan and South Korea. South Korean women aged 20-49 had a higher incidence rate than their male peers (relative risk [RR] = 1.23). Decomposition analysis identified adults aged ≥65 years as the main burden group: this age group contributed 60%-70% of ASIR and ASMR in China, 55%-65% in Japan, and 50%-60% in South Korea. After 2000, the contribution of period effects to ASMR continued to decrease across the three countries. Later birth cohorts (post-1970) had significantly reduced GC risk: compared with pre-1950 cohorts, post-1970 cohorts in China had a 20% lower ASIR (reflected in a 16% lower risk amon
背景:胃癌(GC)是全球第五大常见癌症和第四大癌症相关死亡原因,在东亚负担特别高。中国、日本和韩国在风险因素暴露、筛查做法和人口变化方面存在显著差异,但现有研究缺乏长期趋势的跨国比较和政策有效性的定量分析;本研究旨在通过整合全球疾病负担(GBD) 2021数据库和贝叶斯年龄-时期-队列(BAPC)模型,系统分析1990 - 2050年这三个国家GC负担的时空演变,为亚太地区的预防和控制策略提供依据。方法:我们使用GBD 2021数据库提取1990 - 2021年主要GC流行病学指标数据,包括年龄标准化发病率(ASIR)、年龄标准化死亡率(ASMR)和年龄标准化残疾调整生命年率(ASDR)以及相关危险因素数据。采用增强型年龄-时期-队列(age - period - cohort, APC)分析框架,构建对数线性模型,量化年龄、时期和队列效应对GC负担的独立影响。采用人口归因分数(PAF)方法估计可改变的危险因素(如吸烟和高钠饮食)导致的DALYs比例。趋势预测(2022-2050)采用BAPC模型,形成了从数据提取、效应分解到未来负担预测的综合分析链。结果:从1990年到2021年,中国、日本和韩国的GC的年龄标准化发病率(ASIR)、年龄标准化死亡率(ASMR)和年龄标准化残疾调整生命年率(ASDR)显著下降。三个国家的绝对负担趋势不同:中国的胃癌新发病例从1990年的30万例增加到2021年的61.2万例,年死亡人数达到44.5万人;日本和韩国的新发病例分别减少了9%和7%,死亡率也大幅下降。风险归因分析显示,吸烟是中国男性胃癌负担的主要影响因素,而高钠饮食是日本和韩国男性胃癌负担的主要影响因素。韩国20-49岁女性的发病率高于同龄男性(相对危险度[RR] = 1.23)。分解分析发现,年龄≥65岁的成年人是主要负担群体:该年龄组在中国占ASIR和ASMR的60%-70%,在日本占55%-65%,在韩国占50%-60%。2000年以后,三个国家的时期效应对ASMR的贡献持续下降。较晚出生的队列(1970年后)显著降低了GC风险:与1950年前的队列相比,中国1970年后队列的ASIR降低了20%(反映在30-34岁年龄组的风险降低了16%),韩国1970年后队列的ASIR降低了30%(表现为50-54岁年龄组的风险降低了58%)。到2050年的预测表明,三国的ASIR和ASMR将继续下降,中国的ASIR≈17/100,000和ASMR≈8/100,000,日本和韩国的ASIR≈8-9/100,000。受人口老龄化、吸烟和高钠饮食的持续影响,中国的绝对胃癌负担仍将高于日本和韩国。结论:本研究发现,1990 - 2021年,中国、日本和韩国胃癌的ASIR、ASMR和ASDR呈明显下降趋势,但绝对疾病负担存在差异。中国由于人口众多和老龄化迅速,负担仍然沉重,而日本和韩国通过有效的筛查取得了实质性进展。风险归因分析显示,吸烟是中国的主要风险因素,而高盐饮食对日本和韩国的影响更大。预测表明,到2050年,这三个国家的疾病负担将继续下降。
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引用次数: 0
Case Report: Mammary Paget's disease with multifocal microinvasive carcinoma and extensive lymph node metastasis: therapeutic challenges and insights from a case of stage pT1mic pN3c cM0. 病例报告:乳腺Paget病合并多灶性微创癌和广泛淋巴结转移:pT1mic期pN3c cM0病例的治疗挑战和见解。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/fonc.2025.1727016
YiFan Luo, ZhiYu Liu, Jing Luo

Background: Mammary Paget's Disease (MPD) is a rare subtype of breast cancer, accounting for 1%-4% of all breast cancers. Controversy remains regarding whether sentinel lymph node biopsy (SLNB) is necessary for MPD patients undergoing breast-conserving surgery (BCS) when imaging studies fail to detect deep invasive carcinoma, and this controversy lacks support from specific case evidence.

Case summary: A patient presented with "recurrent left nipple fissure for 3 years and eczematous changes for 3 months." Preoperative biopsy at another hospital confirmed MPD; imaging showed no deep mass. Postoperative pathology revealed left breast MPD associated with multifocal microinvasive carcinoma, accompanied by metastases to left axillary lymph nodes (6/8), left subclavian lymph nodes (2/3), and left supraclavicular lymph nodes (1/3). The pathological stage was pT1mic pN3c cM0. No recurrence was observed 6 months after adjuvant therapy with the TCbHP regimen plus capecitabine consolidation therapy.

Conclusion: Although no definite mass was identified on breast magnetic resonance imaging (MRI) in this case, SLNB and subsequent pathology confirmed extensive lymph node metastasis (pN3c). Omission of SLNB could have led to understaging and compromised treatment decision-making. This single case may suggest that SLNB holds significant staging value for MPD patients with no obvious breast mass on imaging. It provides hypothesis-generating, practical evidence for addressing this controversial clinical issue, warranting further investigation in larger cohorts.

背景:乳腺佩吉特病(breast Paget's Disease, MPD)是一种罕见的乳腺癌亚型,占所有乳腺癌的1%-4%。当影像学检查未能发现深部浸润性癌时,对于行保乳手术(BCS)的MPD患者是否需要前哨淋巴结活检(SLNB)仍有争议,且缺乏具体病例证据的支持。病例总结:1例患者表现为“复发性左乳头裂3年,湿疹变化3个月”。术前在另一家医院活检证实MPD;影像学未见深部肿块。术后病理显示左乳MPD合并多灶性微创癌,伴左侧腋窝淋巴结(6/8)、左侧锁骨下淋巴结(2/3)、左侧锁骨上淋巴结(1/3)转移。病理分期为pT1mic - pN3c - cM0。辅助治疗TCbHP方案加卡培他滨巩固治疗后6个月未见复发。结论:虽然该病例在乳房磁共振成像(MRI)上未发现明确肿块,但SLNB和随后的病理证实了广泛的淋巴结转移(pN3c)。遗漏SLNB可能导致分期不足和治疗决策受损。该病例提示SLNB对影像学上无明显乳腺肿块的MPD患者具有重要的分期价值。它为解决这一有争议的临床问题提供了假设生成的实际证据,保证在更大的队列中进一步调查。
{"title":"Case Report: Mammary Paget's disease with multifocal microinvasive carcinoma and extensive lymph node metastasis: therapeutic challenges and insights from a case of stage pT1mic pN3c cM0.","authors":"YiFan Luo, ZhiYu Liu, Jing Luo","doi":"10.3389/fonc.2025.1727016","DOIUrl":"10.3389/fonc.2025.1727016","url":null,"abstract":"<p><strong>Background: </strong>Mammary Paget's Disease (MPD) is a rare subtype of breast cancer, accounting for 1%-4% of all breast cancers. Controversy remains regarding whether sentinel lymph node biopsy (SLNB) is necessary for MPD patients undergoing breast-conserving surgery (BCS) when imaging studies fail to detect deep invasive carcinoma, and this controversy lacks support from specific case evidence.</p><p><strong>Case summary: </strong>A patient presented with \"recurrent left nipple fissure for 3 years and eczematous changes for 3 months.\" Preoperative biopsy at another hospital confirmed MPD; imaging showed no deep mass. Postoperative pathology revealed left breast MPD associated with multifocal microinvasive carcinoma, accompanied by metastases to left axillary lymph nodes (6/8), left subclavian lymph nodes (2/3), and left supraclavicular lymph nodes (1/3). The pathological stage was pT1mic pN3c cM0. No recurrence was observed 6 months after adjuvant therapy with the TCbHP regimen plus capecitabine consolidation therapy.</p><p><strong>Conclusion: </strong>Although no definite mass was identified on breast magnetic resonance imaging (MRI) in this case, SLNB and subsequent pathology confirmed extensive lymph node metastasis (pN3c). Omission of SLNB could have led to understaging and compromised treatment decision-making. This single case may suggest that SLNB holds significant staging value for MPD patients with no obvious breast mass on imaging. It provides hypothesis-generating, practical evidence for addressing this controversial clinical issue, warranting further investigation in larger cohorts.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"15 ","pages":"1727016"},"PeriodicalIF":3.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124378","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
The modified Glasgow prognostic score serves as a robust predictor of unplanned readmission and 1-year mortality in lung cancer patients receiving immune checkpoint inhibitors. 改良的格拉斯哥预后评分可作为接受免疫检查点抑制剂的肺癌患者意外再入院和1年死亡率的可靠预测因子。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/fonc.2025.1698848
Fengwang Xue, Ruoqing Lu, Cailian Wang, Qilian Xiong, Ying Liu, Shengmin Guo, Bo Deng

Background: The modified Glasgow Prognostic Score (mGPS), which reflects the degree of systemic inflammation and nutritional status, is associated with prognosis in various common malignancies. However, its association with 30-day unplanned readmission and 1-year mortality in stage III-IV lung cancer (LC) patients remains unvalidated. This study aimed to evaluate the prognostic value of mGPS in stage III-IV LC patients receiving immune checkpoint inhibitors (ICIs).

Methods: In this retrospective study, 209 patients diagnosed with stage III-IV LC who underwent ICI therapy between January 2023 and May 2024 were included. Patients were stratified based on mGPS scores into three risk categories: low-risk (0 points), intermediate-risk (1 point), and high-risk (2 points). Kaplan-Meier analyses, multivariate Cox proportional hazard regression, and subgroup analyses were employed to assess primary outcomes.

Results: Among the enrolled patients, the rates of 30-day unplanned readmission and 1-year mortality were 35.4% (74/209) and 11.0% (23/209), respectively. Kaplan-Meier analysis indicated significantly elevated cumulative incidences of 30-day unplanned readmission and 1-year mortality in the high-risk group relative to intermediate- and low-risk groups (log-rank p < 0.001). Adjusted multivariable Cox regression revealed that each 1-point increase in mGPS conferred a 72% higher risk of 30-day unplanned readmission (HR 1.72, 95%CI 1.25-2.38, p = 0.001) and a 117% higher risk of 1-year mortality (HR 2.17, 95%CI 1.15-4.10, p = 0.017). Additionally, compared with low-risk patients, those in the high-risk group experienced a 198% increase in the risk of 30-day unplanned readmission (HR 2.98, 95% CI 1.56-5.69, p = 0.001) and a 366% increase in 1-year mortality risk (HR 4.66, 95% CI 1.33-16.35, p = 0.017). Trend tests confirmed that the risk of adverse outcomes rose steadily with increasing mGPS risk category. Subgroup analyses demonstrated that the prognostic effect of mGPS was consistent across age, TNM stage, metastatic status, and nutritional condition (p for interaction > 0.05).

Conclusion: Higher mGPS scores significantly correlate with elevated risks of both 30-day unplanned readmission and 1-year mortality among LC patients receiving ICI therapy. Routine mGPS monitoring may warrants further evaluation in prospective multicenter validation studies to inform prophylactic interventions.

背景:改良的格拉斯哥预后评分(mGPS)反映了全身炎症程度和营养状况,与各种常见恶性肿瘤的预后相关。然而,其与III-IV期肺癌(LC)患者30天非计划再入院和1年死亡率的关联仍未得到证实。本研究旨在评估mGPS在接受免疫检查点抑制剂(ICIs)治疗的III-IV期LC患者中的预后价值。方法:在这项回顾性研究中,209例诊断为III-IV期LC的患者在2023年1月至2024年5月期间接受了ICI治疗。根据mGPS评分将患者分为低危(0分)、中危(1分)、高危(2分)三个风险类别。采用Kaplan-Meier分析、多变量Cox比例风险回归和亚组分析评估主要结局。结果:入选患者30天非计划再入院率为35.4%(74/209),1年内死亡率为11.0%(23/209)。Kaplan-Meier分析显示,相对于中危组和低危组,高危组30天非计划再入院的累计发生率和1年死亡率显著升高(log-rank p < 0.001)。调整后的多变量Cox回归显示,mGPS每增加1个点,30天意外再入院的风险增加72% (HR 1.72, 95%CI 1.25-2.38, p = 0.001), 1年死亡率增加117% (HR 2.17, 95%CI 1.15-4.10, p = 0.017)。此外,与低风险患者相比,高风险组患者30天意外再入院风险增加198% (HR 2.98, 95% CI 1.56-5.69, p = 0.001), 1年死亡风险增加366% (HR 4.66, 95% CI 1.33-16.35, p = 0.017)。趋势试验证实,不良后果的风险随着mGPS风险类别的增加而稳步上升。亚组分析表明,mGPS对预后的影响在年龄、TNM分期、转移状态和营养状况之间是一致的(p为相互作用0.05)。结论:在接受ICI治疗的LC患者中,较高的mGPS评分与30天非计划再入院和1年死亡率升高的风险显著相关。常规mGPS监测可能需要在前瞻性多中心验证研究中进一步评估,以告知预防性干预措施。
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引用次数: 0
Recent advances in non-alcoholic steatohepatitis-associated hepatocellular carcinoma: immune cells, metabolic dysregulation, and therapeutic strategies. 非酒精性脂肪性肝炎相关肝细胞癌的最新进展:免疫细胞、代谢失调和治疗策略
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/fonc.2025.1744299
Lisi Liu, Xun Duan, Baozhao Ju

Non-alcoholic steatohepatitis (NASH), the inflammatory progression of non-alcoholic fatty liver disease (NAFLD), is a leading cause of hepatocellular carcinoma (HCC) amid rising obesity and metabolic syndrome. This review elucidates the immunometabolic interplay driving NASH-HCC pathogenesis. Immune cells, including Kupffer cells, monocyte-derived macrophages, and T-cell subsets, orchestrate chronic inflammation and fibrosis via cytokine cascades (TNF-α, IL-1β, TGF-β1) and polarization shifts. Metabolic dysregulation-including insulin resistance, lipid accumulation, and oxidative stress-exacerbates hepatocyte injury, disrupts the balance between apoptosis and compensatory proliferation, and promotes immune evasion through pathways such as β-catenin/TNFRSF19 signaling and hypoxia-inducible factor 1-alpha (HIF-1α). Gut-liver axis alterations further amplify inflammation. Therapeutic advances include immunotherapies (PD-1 inhibitors combined with anti-angiogenics), metabolic regulators (PPARα/FXR agonists, GLP-1RAs), and lifestyle interventions, though NASH-HCC shows reduced immunotherapy efficacy due to unique immunosuppressive microenvironments. Future directions emphasize novel immune targets (MDSCs, SLAMF1), metabolic reprogramming, and microbiota modulation for precision therapies. Integrating multimodal approaches holds promise for halting NASH-to-HCC progression and improving outcomes.

非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病(NAFLD)的炎症进展,在肥胖和代谢综合征增加的情况下,是肝细胞癌(HCC)的主要原因。本文综述了免疫代谢相互作用驱动NASH-HCC发病机制。免疫细胞,包括库普弗细胞、单核细胞来源的巨噬细胞和t细胞亚群,通过细胞因子级联反应(TNF-α、IL-1β、TGF-β1)和极化转移来协调慢性炎症和纤维化。代谢失调——包括胰岛素抵抗、脂质积累和氧化应激——加剧了肝细胞损伤,破坏了细胞凋亡和代偿性增殖之间的平衡,并通过β-catenin/TNFRSF19信号传导和缺氧诱导因子1- α (HIF-1α)等途径促进免疫逃避。肠肝轴的改变进一步放大了炎症。治疗进展包括免疫疗法(PD-1抑制剂联合抗血管生成)、代谢调节剂(PPARα/FXR激动剂、GLP-1RAs)和生活方式干预,尽管NASH-HCC由于独特的免疫抑制微环境而显示出免疫治疗效果降低。未来的方向强调新的免疫靶点(MDSCs, SLAMF1),代谢重编程和精确治疗的微生物群调节。整合多模式方法有望阻止nash向hcc发展并改善预后。
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引用次数: 0
ALK-positive inflammatory myofibroblastic tumor in the pelvis of a child: a case report and literature review. 儿童骨盆alk阳性炎性肌纤维母细胞瘤1例报告并文献复习。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2026-01-01 DOI: 10.3389/fonc.2026.1729014
Lei Yang, Zhiheng Yan

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that primarily affects children and young adults. While typically found in the lungs, liver, and gastrointestinal tract, pelvic involvement is recognized but occurs less frequently than intra-abdominal IMT, particularly in pediatric patients. Here we report a case of a 2-year-old boy who presented with a brief history of vomiting and decreased appetite. Imaging revealed a cystic-solid mass in the pelvis with progressive enhancement of the solid component, leading to suspicion of a vascular soft tissue neoplasm. Surgical exploration identified a free-floating mass within the abdominal cavity supported by a long vascular pedicle originating from the splenic hilum, an atypical anatomical finding that added complexity to preoperative diagnosis. Complete surgical resection was performed, and postoperative examination was conducted. Histopathological analysis confirmed IMT, and fluorescence in situ hybridization (FISH) detected ALK gene rearrangement, which supported diagnostic confirmation of IMT in this case rather than guiding therapeutic intervention. The patient recovered uneventfully following surgery, with no evidence of recurrence during follow-up. This case supports considering IMT in pediatric pelvic masses and reinforces that complete surgical resection remains the primary treatment. Although ALK gene rearrangement was not associated with therapeutic intervention in the present case, its identification remains diagnostically relevant and may provide important insights into management decisions in selected clinical scenarios, such as recurrence or unresectable disease.

炎症性肌纤维母细胞瘤(IMT)是一种罕见的肿瘤,主要影响儿童和年轻人。虽然通常在肺、肝脏和胃肠道中发现,但盆腔的累及是公认的,但比腹腔内IMT发生的频率要低,特别是在儿科患者中。在这里我们报告一个2岁的男孩谁提出了一个简短的呕吐史和食欲下降。影像学显示骨盆内有囊性实性肿块,实性成分逐渐增强,怀疑为血管性软组织肿瘤。手术探查发现腹腔内有一个自由漂浮的肿块,由源自脾门的长血管蒂支撑,这一非典型解剖发现增加了术前诊断的复杂性。手术全部切除,术后复查。组织病理学分析证实了IMT,荧光原位杂交(FISH)检测到ALK基因重排,这支持了本病例IMT的诊断确认,而不是指导治疗干预。患者术后恢复平稳,随访期间无复发迹象。本病例支持在小儿盆腔肿块中考虑IMT,并强调完全手术切除仍然是主要治疗方法。虽然在本病例中ALK基因重排与治疗干预无关,但其鉴定仍然具有诊断相关性,并可能为选定的临床情况(如复发或不可切除的疾病)的管理决策提供重要见解。
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引用次数: 0
Roles of E3 ubiquitin ligases and deubiquitinating enzymes in renal cell carcinoma. E3泛素连接酶和去泛素化酶在肾细胞癌中的作用。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/fonc.2025.1628710
Minshu Jiang, Wenxia Si, Sien Huang, Sha Qu, Minghui Zhang, Yi Quan

Ubiquitination is an important post-translational modification of proteins that precisely regulates protein stability and function through the coordinated actions of E3 ubiquitin ligases (E3s) and deubiquitinases (DUBs), participating in biological processes including protein degradation and signal transduction. In recent years, the role of ubiquitination modification in the carcinogenesis, progression, and treatment of renal cell carcinoma (RCC) has garnered increasing attention. This review summarizes the structural classifications of key enzymes in the ubiquitination process-E3s and DUBs-and to discuss their specific molecular mechanisms in RCC. Finally, we discuss the targeted therapeutic strategies focusing on these key ubiquitination-modifying enzymes in RCC.

泛素化是一种重要的蛋白质翻译后修饰,通过E3泛素连接酶(E3 - ubiquitin ligases, E3s)和去泛素酶(deubiquitinases, DUBs)的协同作用,精确调节蛋白质的稳定性和功能,参与蛋白质降解和信号转导等生物学过程。近年来,泛素化修饰在肾细胞癌(RCC)的发生、进展和治疗中的作用越来越受到关注。本文综述了泛素化过程中关键酶e3s和dub的结构分类,并讨论了它们在RCC中的具体分子机制。最后,我们讨论了针对这些关键泛素化修饰酶的RCC靶向治疗策略。
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引用次数: 0
Solitary plasmacytoma of the tibia: literature review and case report. 胫骨孤立性浆细胞瘤:文献复习及病例报告。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2026-01-01 DOI: 10.3389/fonc.2026.1503479
Xianwen Hu, Dandan Li, Xiao Hu, Shun Li, Pan Wang

Solitary plasmacytoma (SP) is seldom encountered. It can affect any bone in the body, but is more common in the spine, especially in the thoracic region, while SP in the tibia is relatively rare. Herein, we report the case of a 34-year-old woman who visited our hospital with right calf pain for over a month. The X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) revealed a tumor growing along the longitudinal axis of her right tibia, which was suspected to be malignant. The patient subsequently underwent a puncture biopsy, and the pathological results revealed a plasma cell myeloma. To further evaluate the extent of tumor involvement, the patient underwent single-phase technetium-99 labeled methylene diphosphonate (99mTc-MDP) single photon emission computed tomography (SPECT) whole-body bone imaging, and the results showed no significant radioactive concentration in the entire body except for the right proximal tibia. Based on these imaging features and pathological results, the patient was diagnosed with SP. We summarized the clinical features and imaging findings of tibial SP based on our case and the published literature The results showed that SP is more likely to occur in young people. Its imaging has a certain specificity, which is characterized by a uniform low - density shadow growing along the longitudinal axis, without a sclerotic rim, and increased radioactive uptake on whole - body bone imaging. MRI showed long signals on T1 and T2, with significant enhancement on contrast-enhanced scans, but rarely breaking through the bone cortex to form soft tissue masses. The current study suggests that a thorough understanding of the clinical and imaging characteristics of the tibial SP can increase the likelihood of obtaining an accurate diagnosis before surgery.

孤立性浆细胞瘤(SP)是罕见的。它可以影响身体的任何骨骼,但更常见于脊柱,特别是在胸部区域,而胫骨的SP相对罕见。在此,我们报告一位34岁的女性因右小腿疼痛一个多月来我院就诊的病例。x线、计算机断层扫描(CT)和磁共振成像(MRI)显示沿右胫骨纵轴生长的肿瘤,怀疑是恶性的。患者随后接受穿刺活检,病理结果显示为浆细胞骨髓瘤。为进一步评估肿瘤累及程度,患者行了单相锝-99标记二膦酸亚甲基(99mTc-MDP)单光子发射计算机断层扫描(SPECT)全身骨显像,结果显示除右侧胫骨近端外,全身无明显放射性浓度。基于这些影像学表现和病理结果,我们诊断患者为胫骨SP。我们结合我们的病例和已发表的文献,总结了胫骨SP的临床特征和影像学表现,结果表明SP更易发生在年轻人身上。其成像具有一定的特异性,表现为沿纵轴呈均匀低密度影生长,无硬化边缘,全身骨成像放射性摄取增高。MRI显示T1和T2长信号,增强扫描明显增强,但很少突破骨皮质形成软组织肿块。目前的研究表明,深入了解胫骨SP的临床和影像学特征可以增加在手术前获得准确诊断的可能性。
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引用次数: 0
Challenging the extended phenotype: HRD-negative salivary gland carcinoma in a BRCA1 founder-variant carrier, case report and literature review. 挑战扩展表型:BRCA1创始人变异携带者的hrd阴性唾液腺癌,病例报告和文献综述。
IF 3.5 3区 医学 Q2 ONCOLOGY Pub Date : 2026-01-21 eCollection Date: 2025-01-01 DOI: 10.3389/fonc.2025.1692001
William Torres, Elizabeth Vargas, Diego-Felipe Ballen, Sandra M Tapiero-Rodriguez, Enrique Cadena, Rafael Parra-Medina, Julian C Riaño-Moreno

Background: Pathogenic BRCA1 variants are established in hereditary breast and ovarian cancer (HBOC) and associated with pancreatic, prostate, and gastric cancers. Salivary gland tumors (SGTs) have been reported in BRCA1/2 carriers and suggested as part of an extended HBOC phenotype based on epidemiological associations. However, functional evidence is lacking, and homologous recombination deficiency (HRD)-the hallmark of BRCA-driven cancers-has not been systematically assessed in BRCA1-associated SGTs.

Case presentation: We report a Colombian family segregating the BRCA1 c.3331_3334delCAAG (p.Gln1111Asnfs*5) founder variant with phenotypic variability across four generations: gastric (31%), breast (37.5%), colorectal (19%), and thyroid cancers (12.5%). The proband, a 61-year-old woman, developed high-grade mucoepidermoid carcinoma of the parotid gland. Germline testing confirmed the familial BRCA1 variant. Tumor profiling revealed the same BRCA1 variant (VAF 56%) plus a pathogenic TP53 mutation (c.730G>T, p.Gly244Cys; VAF 32%), without BRCA1 loss of heterozygosity. HRD testing using shallow whole genome sequencing showed preserved homologous recombination function (Genomic Instability Score: 0.01, LGA: 11.40, LPC: 0), all below HRD-positive thresholds.

Conclusion: This represents the first SGT in a BRCA1 carrier evaluated with HRD testing. The absence of HRD argues against BRCA1-driven tumorigenesis despite clear familial segregation. These findings challenge the presumed causal relationship between BRCA1 variants and SGT development. Clinical implications are direct: SGTs in BRCA1 carriers should not be assumed eligible for PARP inhibitor therapy without HRD confirmation, and enhanced surveillance appears unwarranted. This case underscores that co-occurrence does not establish causation and highlights the critical importance of functional validation before expanding hereditary cancer spectra.

背景:致病性BRCA1变异已在遗传性乳腺癌和卵巢癌(HBOC)中确立,并与胰腺癌、前列腺癌和胃癌相关。据报道,在BRCA1/2携带者中有唾液腺肿瘤(sgt),并根据流行病学相关性认为这是扩展HBOC表型的一部分。然而,功能证据缺乏,同源重组缺陷(HRD)- brca驱动癌症的标志-尚未在brca1相关sgt中系统评估。病例介绍:我们报道了一个哥伦比亚家族分离出BRCA1 c.3331_3334delCAAG (p.Gln1111Asnfs*5)始祖变异,其表型变异跨越四代:胃癌(31%)、乳腺癌(37.5%)、结直肠癌(19%)和甲状腺癌(12.5%)。先证者为61岁女性,患腮腺高级别粘液表皮样癌。生殖系检测证实了家族性BRCA1变异。肿瘤分析显示相同的BRCA1变异(VAF 56%)加上致病性TP53突变(c.730G>T, p.Gly244Cys; VAF 32%),没有BRCA1杂合性缺失。采用浅全基因组测序的HRD检测显示,同源重组功能得以保留(基因组不稳定性评分:0.01,LGA: 11.40, LPC: 0),均低于HRD阳性阈值。结论:这是BRCA1携带者HRD检测中首次出现SGT。尽管存在明显的家族分离,但HRD的缺失反对brca1驱动的肿瘤发生。这些发现挑战了BRCA1变异与SGT发展之间假定的因果关系。临床意义是直接的:在没有HRD确认的情况下,BRCA1携带者的sgt不应该被认为有资格接受PARP抑制剂治疗,加强监测似乎是没有根据的。该病例强调了共发生不能建立因果关系,并强调了在扩大遗传性癌症谱之前进行功能验证的重要性。
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引用次数: 0
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Frontiers in Oncology
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