Seminars in oncology最新文献_第4页

Overexpression of CAD in stomach adenocarcinoma tissues and its clinical significance CAD在胃腺癌组织中的过表达及其临床意义

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-08-11 DOI: 10.1016/j.seminoncol.2025.152396

Siyi Wang , Hang Xing , Meiting Long , Min Zhou , Zhe Wang , Bingchen Hou , Steven Mo , Di Na , Shanshan Bu

Stomach adenocarcinoma (STAD) is one of the deadliest malignant tumors worldwide. Carbamoyl-phosphate synthetase 2 (CAD) expression is essential for categorizing and detecting STAD initiation and development. We explored the differential expression of genes (DEGs) affected by CAD overexpression and subsequently revealed the classification module of CAD-based scoring sets using weighted gene co-expression network analysis (WGCNA). Subsequently, enrichment analysis of biological functions and signaling pathways in clinically significant modules was conducted. We constructed a CAD-based clinical scoring model using univariate and multivariate Cox regression analyses. In addition, by using immune cell infiltration analysis, we investigated the interaction between CAD-based score and the immune microenvironment, identified upstream regulatory factors, including RNA binding proteins (RBPs), that affect the transcription of the STAD-related CAD-based score, and explored potential drug targets. We identified 4,977 abnormal regulatory genes related to CAD in STAD, among which the module genes most related to CAD were significantly enriched in cancer-related signaling pathways, such as VEGF, MAPK and TGF-beta signaling pathway. The CAD-based scores, T and N were identified as independent prognostic factors for STAD patients. We also found that under the influence of high expression of CAD, the infiltration level of most immune cells is lower, such as CD4 T cells and Tfh, and CAD has an inhibitory effect on the infiltration of certain immune cells. Notably, the potential drug targets PDHB and NDUFB6 are upstream regulatory factors in STAD. This study explored the role of highly expressed CAD-related genes in STAD and explored the tumorigenesis and progression of this disease. This research identified potential diagnostic and prognostic drug targets and provided new insights into the molecular mechanisms of STAD.

胃腺癌（STAD）是世界上最致命的恶性肿瘤之一。氨甲酰磷酸合成酶2 （CAD）的表达对于STAD的发生和发展的分类和检测至关重要。我们探索了受CAD过表达影响的基因（deg）的差异表达，随后使用加权基因共表达网络分析（WGCNA）揭示了基于CAD的评分集的分类模块。随后，对临床重要模块的生物学功能和信号通路进行富集分析。我们使用单变量和多变量Cox回归分析构建了基于cad的临床评分模型。此外，通过免疫细胞浸润分析，我们研究了基于cad的评分与免疫微环境之间的相互作用，确定了上游调控因子，包括RNA结合蛋白（rbp），影响stad相关的基于cad的评分的转录，并探索了潜在的药物靶点。我们在STAD中发现了4977个与CAD相关的异常调控基因，其中与CAD最相关的模块基因在肿瘤相关信号通路中显著富集，如VEGF、MAPK和tgf - β信号通路。基于cad的评分、T和N被确定为STAD患者的独立预后因素。我们还发现，在CAD高表达的影响下，大多数免疫细胞的浸润水平降低，如CD4 T细胞和Tfh， CAD对某些免疫细胞的浸润有抑制作用。值得注意的是，潜在的药物靶点PDHB和NDUFB6是STAD的上游调控因子。本研究探讨了高表达的cad相关基因在STAD中的作用，并探讨了该疾病的肿瘤发生和进展。本研究确定了潜在的诊断和预后药物靶点，并为STAD的分子机制提供了新的见解。

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引用次数: 0

Psoas muscle depletion correlates with poor prognosis and compromised immunity in resectable gastric cancer: A multicenter study 腰肌耗竭与可切除胃癌预后不良和免疫功能低下相关：一项多中心研究

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-08-11 DOI: 10.1016/j.seminoncol.2025.152400

Hao Zhou , Li Zhong , Zihan Jin , Xun Hou , Haiyun Tang , Shibin Yang , Yulong He , Wu Song , Changhua Zhang , Zhewei Wei

Sarcopenia, assessed by the psoas muscle index (PMI), is characterized with the loss of skeletal muscle mass and strength, and has gained growing attentions in the field of cancers. However, its role in gastric cancer (GC), especially in patients received gastrectomy, remains underexplored. This multicenter retrospective study examined 439 patients with resectable GC to assess the prognostic significance of sarcopenia, measured by PMI and PMI change rate (PMICR), while also exploring potential links with tumor immunity. Kaplan–Meier analysis revealed that low PMICR was significantly associated with worse survival outcomes in all patient cohorts. Further multivariate Cox analysis identified PMICR (hazard ratio: 2.80, 95% CI: 1.73–4.56), but not baseline PMI—as an independent predictor of overall survival. Immunologically, low PMICR patients exhibited decreased tertiary lymphoid structure density and reduced tumor-infiltrating lymphocytes (CD3+ T cells and CD20+ B cells). The developed nomogram incorporating PMICR showed superior prognostic performance versus TNM stage, with concordance indices of 0.821 (95% CI: 0.789–0.853), 0.800 (95% CI: 0.753–0.847), and 0.816 (95% CI: 0.743–0.889) for training, internal validation, and external validation cohorts, respectively. These results suggested that PMICR, as a measure of sarcopenia, more accurately predicted survival outcomes and might be associated with immune status in resectable GC patients. Moreover, the newly developed nomogram demonstrated high accuracy in predicting prognosis.

以腰肌指数（PMI）评估的骨骼肌减少症以骨骼肌质量和力量的减少为特征，在癌症领域受到越来越多的关注。然而，其在胃癌（GC）中的作用，特别是在接受胃切除术的患者中，仍未得到充分探讨。这项多中心回顾性研究检查了439例可切除的胃癌患者，通过PMI和PMI变化率（PMICR）来评估肌肉减少症的预后意义，同时也探索了与肿瘤免疫的潜在联系。Kaplan-Meier分析显示，在所有患者队列中，低PMICR与较差的生存结果显著相关。进一步的多变量Cox分析确定PMICR（风险比：2.80,95% CI: 1.73-4.56）是总生存期的独立预测因子，但不是基线pmi。在免疫学上，低PMICR患者表现出三级淋巴结构密度降低和肿瘤浸润淋巴细胞（CD3+ T细胞和CD20+ B细胞）减少。与TNM分期相比，纳入PMICR的nomogram显示出更好的预后表现，训练组、内部验证组和外部验证组的一致性指数分别为0.821 （95% CI: 0.789-0.853）、0.800 （95% CI: 0.753-0.847）和0.816 （95% CI: 0.743-0.889）。这些结果表明，PMICR作为肌肉减少症的一种测量方法，更准确地预测了可切除胃癌患者的生存结果，并可能与免疫状态相关。此外，新开发的nomogram预测预后的准确度较高。

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引用次数: 0

Antibody treatments for digestive cancers: Past, present, and future 消化系统癌症的抗体治疗：过去，现在和未来

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-08-06 DOI: 10.1016/j.seminoncol.2025.152369

Ikrame Dadi , Thibault Mazard , Lena-Marie Schmitt , Tommy Chastel , Andrei Turtoi , Marie-Alix Poul , Sophie Pattingre

Gastrointestinal (GI) malignancies accounted for more than one in four cancer cases (4.8 million cases) in 2020. Among these, around 37% were colorectal followed by gastric (21%) and liver cancers (18%). Notably, GI cancers are responsible for nearly one-third of cancer-related mortality (3.4 million deaths worldwide). For decades, treatment relied primarily on conventional cytotoxic chemotherapies, which target rapidly dividing malignant cells but also cause significant harm to healthy tissue. Recent biotechnological advances enhanced our understanding of cancer biology, leading to the identification of specific molecular alterations and the development of new drugs, known as "targeted therapies." These therapies include two major categories: small molecule kinase inhibitors (SMKIs), which inhibit dysregulated intracellular kinases, and monoclonal antibodies (mAbs), able to interfere with extracellular ligands, membrane receptors, or membrane-bound proteins.

This review aims to summarize recent advancements in the treatment of GI cancers using mAbs. We provide an overview of clinically approved mAbs in GI cancers, detailing their targets, mechanisms of action, and limitations. We differentiate between mAbs that directly target cancer cells and those that act on the tumor microenvironment (TME). Additionally, we discuss developments and technological optimizations used to improve the efficacy and specificity of these therapies.

2020年，胃肠道（GI）恶性肿瘤占癌症病例的四分之一以上（480万例）。其中，约37%为结直肠癌，其次是胃癌（21%）和肝癌（18%）。值得注意的是，胃肠道癌症造成了近三分之一的癌症相关死亡（全世界340万人死亡）。几十年来，治疗主要依赖于传统的细胞毒性化疗，这种疗法针对快速分裂的恶性细胞，但也会对健康组织造成重大伤害。最近的生物技术进步增强了我们对癌症生物学的理解，导致了特定分子变化的识别和新药的开发，被称为“靶向治疗”。这些疗法包括两大类：抑制细胞内失调激酶的小分子激酶抑制剂（SMKIs）和能够干扰细胞外配体、膜受体或膜结合蛋白的单克隆抗体（mab）。本文综述了利用单克隆抗体治疗胃肠道肿瘤的最新进展。我们提供临床批准的单克隆抗体在胃肠道癌症的概述，详细说明他们的目标，作用机制和局限性。我们区分直接靶向癌细胞的单克隆抗体和作用于肿瘤微环境（TME）的单克隆抗体。此外，我们还讨论了用于提高这些疗法的疗效和特异性的发展和技术优化。

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引用次数: 0

Lactylation in radiosensitivity regulation: Mechanistic insights and recent advances 放射敏感性调节中的乳酸化：机制见解和最新进展

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-26 DOI: 10.1016/j.seminoncol.2025.152394

Caiqiang Zhu , Meng Tian , Xiaoke Di , Jin Liu , Huanhuan Chen , Lu Xu , Ying Liu , Xinchen Sun , Zhaoyue Zhang

Lactylation, as a novel post-translational modification, has gained a lot of attention in the biomedical field in recent years. Lactylation is not only related to cellular metabolism but also increasingly prominent in the tumor microenvironment, particularly in regulating radiation sensitivity. This review aims to explore the potential connection between lactylation modification and the regulation of radiation sensitivity. Current research shows that lactylation might be crucial in how tumor cells respond to radiotherapy by influencing energy metabolism, gene expression, and cell signaling. However, despite preliminary studies revealing the association between lactylation and radiation sensitivity, the understanding of its specific mechanisms remains insufficient, necessitating more systematic research to elucidate this process. Therefore, by analyzing the biological basis of lactylation modification, its role in tumor metabolism, and its relationship with radiotherapy, we summarize the importance and application prospects of lactylation in tumor treatment, providing direction for future research.

乳酸化修饰作为一种新型的翻译后修饰，近年来在生物医学领域受到了广泛的关注。乳酸化不仅与细胞代谢有关，而且在肿瘤微环境中也越来越突出，特别是在调节辐射敏感性方面。本文旨在探讨乳酸化修饰与辐射敏感性调节之间的潜在联系。目前的研究表明，乳酸化可能在肿瘤细胞如何通过影响能量代谢、基因表达和细胞信号传导来对放疗做出反应中起着至关重要的作用。然而，尽管初步研究揭示了乳酸化与辐射敏感性之间的联系，但对其具体机制的了解仍然不足，需要更系统的研究来阐明这一过程。因此，我们通过分析乳酸化修饰的生物学基础、其在肿瘤代谢中的作用以及与放疗的关系，总结了乳酸化修饰在肿瘤治疗中的重要性及应用前景，为今后的研究提供方向。

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引用次数: 0

Germline mutations in B-cell non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) and patient outcomes b细胞非霍奇金淋巴瘤相关噬血细胞淋巴组织细胞增多症（LA-HLH）的种系突变和患者预后

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-22 DOI: 10.1016/j.seminoncol.2025.152388

Xing Zhong , Xinyu Zhu , Xiaoxia Ma , Lili Zhou , Xiu Luo , Ping Li , Yi Ding , Jianfei Fu , Jiaqi Bo , Muye Yang , Aibin Liang , Yu Zeng , Bing Xiu

Lymphoma-associated hemophagocytic lymphohistiocytosis/syndrome (LA-HLH/LAHS) represents the most prevalent form of malignancy-associated HLH and is associated with an exceptionally poor prognosis. Emerging evidence implicates germline mutations as potential contributors to hematologic abnormalities, suggesting a genetic predisposition in affected individuals.

We conducted whole-exome sequencing (WES) on a cohort of 12 LA-HLH patients, with detailed analysis of 3 representative cases exhibiting coexisting genetic disorders. These cases were comprehensively evaluated for their clinical management strategies and therapeutic outcomes.

Our study revealed that gene mutations were detected in 6 patients (6/12), including 2 had somatic mutations, 3 had germline mutations, and 1 had both somatic and germline mutations. Among the 4 patients harbored germline mutations, 3 were diagnosed with concurrent genetic disease. Most patients (11/12) responded to immunochemotherapy for a short time and then progressed or relapsed, even after autologous hematopoietic stem cell transplantation (ASCT). Interestingly, two patients received CAR-T-cell therapy and achieved extremely good responses. One patient received CD19 CAR-T-cell infusion and had a PFS of 26 months. The other patient received double CAR-T infusions and has remained in complete remission for more than 2 years (until now).

This study proposes that LA-HLH may constitute a novel genetic subtype of lymphoma. Systematic genetic sequencing should be prioritized to guide precision treatment approaches in selected cases, including immunotherapies such as CAR-T-cell therapy. These insights redefine our understanding of LA-HLH pathogenesis and clinical intervention strategies.

淋巴瘤相关的噬血细胞淋巴组织细胞增多症/综合征（LA-HLH/LAHS）是恶性肿瘤相关的HLH最常见的形式，并伴有异常差的预后。新出现的证据暗示种系突变是血液学异常的潜在贡献者，表明受影响个体的遗传易感性。我们对12例LA-HLH患者进行了全外显子组测序（WES），并详细分析了3例具有代表性的共存遗传疾病病例。对这些病例的临床管理策略和治疗结果进行综合评估。我们的研究发现6例（6/12）患者检测到基因突变，其中2例为体细胞突变，3例为种系突变，1例为体细胞和种系突变。在4例种系突变患者中，3例诊断为并发遗传病。大多数患者（11/12）对免疫化疗有短期反应，然后进展或复发，即使在自体造血干细胞移植（ASCT）后也是如此。有趣的是，两名患者接受了car - t细胞治疗，并取得了非常好的疗效。一名患者接受了CD19 car - t细胞输注，PFS为26个月。另一位患者接受了两次CAR-T输注，并保持完全缓解超过2年（至今）。本研究提示LA-HLH可能构成一种新的遗传淋巴瘤亚型。应该优先考虑系统的基因测序，以指导特定病例的精确治疗方法，包括免疫疗法，如car - t细胞疗法。这些见解重新定义了我们对LA-HLH发病机制和临床干预策略的理解。

{"title":"Germline mutations in B-cell non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) and patient outcomes","authors":"Xing Zhong , Xinyu Zhu , Xiaoxia Ma , Lili Zhou , Xiu Luo , Ping Li , Yi Ding , Jianfei Fu , Jiaqi Bo , Muye Yang , Aibin Liang , Yu Zeng , Bing Xiu","doi":"10.1016/j.seminoncol.2025.152388","DOIUrl":"10.1016/j.seminoncol.2025.152388","url":null,"abstract":"<div><div>Lymphoma-associated hemophagocytic lymphohistiocytosis/syndrome (LA-HLH/LAHS) represents the most prevalent form of malignancy-associated HLH and is associated with an exceptionally poor prognosis. Emerging evidence implicates germline mutations as potential contributors to hematologic abnormalities, suggesting a genetic predisposition in affected individuals.</div><div>We conducted whole-exome sequencing (WES) on a cohort of 12 LA-HLH patients, with detailed analysis of 3 representative cases exhibiting coexisting genetic disorders. These cases were comprehensively evaluated for their clinical management strategies and therapeutic outcomes.</div><div>Our study revealed that gene mutations were detected in 6 patients (6/12), including 2 had somatic mutations, 3 had germline mutations, and 1 had both somatic and germline mutations. Among the 4 patients harbored germline mutations, 3 were diagnosed with concurrent genetic disease. Most patients (11/12) responded to immunochemotherapy for a short time and then progressed or relapsed, even after autologous hematopoietic stem cell transplantation (ASCT). Interestingly, two patients received CAR-T-cell therapy and achieved extremely good responses. One patient received CD19 CAR-T-cell infusion and had a PFS of 26 months. The other patient received double CAR-T infusions and has remained in complete remission for more than 2 years (until now).</div><div>This study proposes that LA-HLH may constitute a novel genetic subtype of lymphoma. Systematic genetic sequencing should be prioritized to guide precision treatment approaches in selected cases, including immunotherapies such as CAR-T-cell therapy. These insights redefine our understanding of LA-HLH pathogenesis and clinical intervention strategies.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 5","pages":"Article 152388"},"PeriodicalIF":3.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the prognostic value and immunotherapeutic strategy of aggrephagy in melanoma: Integrating single-cell sequencing and machine learning 解读黑色素瘤的预后价值和免疫治疗策略：整合单细胞测序和机器学习

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-21 DOI: 10.1016/j.seminoncol.2025.152371

Zihao Li , Jiaheng Xie , Liqun Li , Yucang He , Wanying Chen , Hao Dai , Songyun Zhao

This study aimed to investigate the role of aggrephagy in cutaneous melanoma (CM) and explore its potential as a biomarker for prognosis and therapeutic targeting. We utilized single-cell sequencing technology and machine learning algorithms to analyze melanoma transcriptome data from the TCGA database and validated our findings using 3 independent datasets from the GEO database. By employing enrichment scoring in single-cell sequencing, we identified characteristic expression patterns of different cell types involved in aggrephagy and constructed an aggrephagy-related signature (ARS). We further evaluated the association of ARS with clinical features, immune cell infiltration, tumor mutational load (TMB), and immune checkpoint gene expression. Additionally, we conducted in vivo experiments by knocking down TPX2, the most critical oncogene in ARS, using shRNA and assessed its effects on tumor proliferation and T-cell growth via subcutaneous tumor formation assays and flow cytometry in mice. The ARS demonstrated robust prognostic predictive power across multiple datasets, with higher ARS scores associated with poorer overall survival (OS) and lower levels of immune cell infiltration. Patients with low ARS scores were more likely to benefit from immune checkpoint inhibitor therapies, while those with high scores exhibited increased sensitivity to 2 common chemotherapeutic agents. Compared to published melanoma prognostic models, our ARS showed higher accuracy and stability. The construction of an ARS-related nomogram further facilitated more accurate clinical decision-making. In vivo experiments confirmed that TPX2 knockdown inhibited tumor proliferation and enhanced T-cell growth, highlighting its critical role in CM progression. Our study highlights the complex functions of the aggrephagy-related signature in cutaneous melanoma, underscoring its potential as a therapeutic target and a valuable tool for prognostic assessment.

本研究旨在探讨聚集性在皮肤黑色素瘤（CM）中的作用，并探讨其作为预后和治疗靶向的生物标志物的潜力。我们利用单细胞测序技术和机器学习算法分析来自TCGA数据库的黑色素瘤转录组数据，并使用来自GEO数据库的3个独立数据集验证我们的发现。通过在单细胞测序中使用富集评分，我们确定了不同细胞类型参与聚合的特征表达模式，并构建了聚合相关特征（ARS）。我们进一步评估了ARS与临床特征、免疫细胞浸润、肿瘤突变负荷（TMB）和免疫检查点基因表达的关系。此外，我们利用shRNA进行了体内实验，通过敲除ARS中最关键的致癌基因TPX2，并通过小鼠皮下肿瘤形成实验和流式细胞术评估了其对肿瘤增殖和t细胞生长的影响。ARS在多个数据集中显示出强大的预后预测能力，较高的ARS评分与较差的总生存率（OS）和较低的免疫细胞浸润水平相关。ARS评分低的患者更有可能受益于免疫检查点抑制剂治疗，而评分高的患者对两种常见化疗药物的敏感性增加。与已发表的黑色素瘤预后模型相比，我们的ARS显示出更高的准确性和稳定性。构建与急性呼吸道综合征相关的nomogram图，进一步提高了临床决策的准确性。体内实验证实，TPX2敲低抑制肿瘤增殖，增强t细胞生长，突出其在CM进展中的关键作用。我们的研究强调了皮肤黑色素瘤中聚集相关特征的复杂功能，强调了其作为治疗靶点和预后评估的有价值工具的潜力。

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引用次数: 0

Prostate cancer in Türkiye: Trend analysis of incidence and mortality rates 日本前列腺癌：发病率和死亡率的趋势分析

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-19 DOI: 10.1016/j.seminoncol.2025.152391

Guven Turan , Merve Turan , Yasemin Basbinar , Hulya Ellidokuz

Prostate cancer is a significant global health concern, with substantial regional variations in incidence and mortality rates. In Türkiye, it's the second most common cancer and fourth leading cause of cancer-related deaths among men. This study aims to analyze trends in prostate cancer incidence and mortality rates in Türkiye. Prostate cancer trends in Türkiye is analyzed by using data of incidence from Türkiye Cancer Statistics Reports and mortality from TurkStat. Trends in incidence and mortality rates were analyzed using Joinpoint regression, evaluating average annual percentage changes and annual percentage change (APC). From 2004 to 2018, age-standardized prostate cancer incidence rate increased from 24.9 to 40.3 per 100,000, with the highest in aged 75 and older. The Annual Average Percentage Change (AAPC) was 2.6%[CI, 1.1 to 4.3] overall, with specific rates of 2.3% [CI, 0.5 to 3.5] in the 50–54 and −1.9% [CI, −3.7 to −0.1] in the 80–84 age group. The APC was 9.2% [CI, 3.6 to 24.8] from 2004 to 2008. From 2016–2018, APCs in 50–54 and 60–64 age groups are 13.4% [CI, 3.6 to 20.4] and 13.7% [CI, 0.4 to 23.6], respectively. Mortality rate ranged from 7.3 to 9.2 per 100,000 from 2009 to 2022, with a 4.9% [CI, 2.1 to 11.6] increase in 2009–2014 and a 1.9%–1.9%[CI, 4.4 to −0.6] decrease in 2014–2022. The incidence rate of prostate cancer in Türkiye increased until 2008, but then stabilised with the rates rising at the age of 50–54 and decreasing at the age of 80–84 years. Mortality rates initially increased but declined in the last 8 years. Further research is needed to explore factors influencing these trends.

前列腺癌是一个重大的全球健康问题，在发病率和死亡率方面存在很大的区域差异。在日本，它是第二大常见癌症，也是男性癌症相关死亡的第四大原因。本研究旨在分析日本前列腺癌发病率和死亡率的趋势。通过使用来自 rkiye癌症统计报告的发病率数据和来自TurkStat的死亡率数据，分析了 rkiye癌症统计报告的前列腺癌趋势。采用关节点回归分析发病率和死亡率的趋势，评估年平均百分比变化和年百分比变化（APC）。从2004年到2018年，年龄标准化前列腺癌发病率从24.9 / 10万上升到40.3 / 10万，其中75岁及以上人群发病率最高。总体而言，年平均百分比变化（AAPC）为2.6%[CI， 1.1至4.3]，50-54岁年龄组的具体比率为2.3% [CI， 0.5至3.5]，80-84岁年龄组的具体比率为- 1.9% [CI, - 3.7至- 0.1]。2004 - 2008年APC为9.2% [CI, 3.6 ~ 24.8]。2016-2018年，50-54岁和60-64岁年龄组的apc分别为13.4% [CI, 3.6 - 20.4]和13.7% [CI, 0.4 - 23.6]。2009年至2022年，死亡率为每10万人7.3至9.2人，2009 - 2014年上升4.9% [CI， 2.1至11.6]，2014-2022年下降1.9%-1.9% [CI， 4.4至- 0.6]。日本人前列腺癌的发病率在2008年之前一直在上升，但随后趋于稳定，在50-54岁时发病率上升，在80-84岁时发病率下降。死亡率最初有所上升，但在过去8年中有所下降。需要进一步的研究来探索影响这些趋势的因素。

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引用次数: 0

Clinical efficacy and security analysis of DEB-TACE combined with trans arterial infusion of carrelizumab in the therapy of advanced liver cancer DEB-TACE联合经动脉输注卡瑞珠单抗治疗晚期肝癌的临床疗效及安全性分析

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-17 DOI: 10.1016/j.seminoncol.2025.152393

Yang Chen, Xinxin Zang, Xiaoxuan Zhang, Songyan Zhang

To explore the clinical efficacy and security analysis of DEB-TACE combined with carrelizumab in the therapy of advanced liver cancer. This study was prospectively designed. Using a random number table method, 96 patients with advanced liver cancer hospitalized from August 2022 to August 2023 were divided into the DT group (DEB-TACE treatment, n = 48) and the DT-C group (on the basis of the DT group, receiving carrelizumab infusion via hepatic artery, n = 48). The changes of therapeutic effect, serum tumor markers, T lymphocyte subsets, overall survival (OS) and progression-free survival (PFS) and the adverse effect were observed. The ORR and DCR of the DT-C group were higher than that of the DT group (P < 0.05). After 1 month of treatment, CD3⁺, CD4⁺ and CD4⁺/CD8⁺ were increased and the DT-C group was higher than the DT group (P < 0.001). The CD8+ decreased after 1 month of treatment, and the CD8+ in the DT-C group was significantly lower than that in the DT group (P < 0.001). AFP and PIVKA-II decreased after 1 month of treatment, and the DT-C group was lower than the DT group (P < 0.001). The overall survival (OS) (2-year survival rate 33.33%) and progression-free survival (PFS) (2-year survival rate 18.75%) of the DT-C group were higher than those of the DT group (P < 0.05). There was no difference in the adverse reaction incidence (P > 0.05). DEB-TACE combined with trans arterial infusion of carrelizumab is safe and effective in the treatment of advanced liver cancer. Compared with DEB-TACE alone, this combination therapy results in higher CD3+, CD4+, and CD4+/CD8+ levels, as well as reduced CD8+, AFP, and PIVKA-II levels.

探讨DEB-TACE联合卡瑞珠单抗治疗晚期肝癌的临床疗效及安全性分析。本研究采用前瞻性设计。采用随机数字表法，将2022年8月至2023年8月住院的96例晚期肝癌患者分为DT组（DEB-TACE治疗，n = 48）和DT- c组（在DT组的基础上，经肝动脉输注卡瑞珠单抗，n = 48）。观察两组治疗效果、血清肿瘤标志物、T淋巴细胞亚群、总生存期（OS）、无进展生存期（PFS）及不良反应的变化。DT- c组的ORR和DCR均高于DT组（P <； 0.05）。治疗1个月后CD3+、CD4+、CD4+/CD8+均升高，且DT- c组高于DT组（P <； 0.001）。治疗1个月后CD8+下降，DT- c组CD8+明显低于DT组（P <； 0.001）。治疗1个月后，AFP和PIVKA-II降低，DT- c组低于DT组（P <； 0.001）。DT- c组总生存率（OS）（2年生存率33.33%）和无进展生存率（PFS）（2年生存率18.75%）均高于DT组（P <； 0.05）。两组不良反应发生率比较差异无统计学意义（P >； 0.05）。DEB-TACE联合经动脉输注卡瑞珠单抗治疗晚期肝癌安全有效。与单独使用DEB-TACE相比，这种联合治疗导致CD3+、CD4+和CD4+/CD8+水平升高，CD8+、AFP和PIVKA-II水平降低。

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引用次数: 0

Metabolic reprogramming: The driving force behind cancer drug resistance 代谢重编程：癌症耐药性背后的驱动力

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-16 DOI: 10.1016/j.seminoncol.2025.152392

Amr Ali Mohamed Abdelgawwad El-Sehrawy , Chou-Yi Hsu , Ali G. Alkhathami , Muktesh Chandra , Tina Saeed Basunduwah , H. Malathi , Jitendra Narayan Senapati , Apurav Gautam , Mundher Kadhem , Hatif Abdulrazaq Yasin

Metabolic reprogramming enables stress adaptation of cancer cells to treatment and is a primary causative force of drug resistance. Dysregulation of glucose, amino acid, and lipid metabolism supplies energy, biosynthetic precursors, and redox balance, promoting survival in the treated tumor. These processes are coordinated by oncogenic signaling, loss of tumor suppressors, and regulatory non-coding RNAs, which promote cancer stemness, immune evasion, and resistance to apoptosis. This review examines the mechanisms by which central metabolic pathways, particularly glycolysis, glutamine metabolism, and fatty acid synthesis, are altered to facilitate drug resistance in various types of cancer. Additionally, we report on novel therapeutic approaches that exploit such metabolic weaknesses to prevent therapy resistance and enhance clinical outcomes. Future directions emphasize the need for advanced metabolic profiling to personalize treatment approaches and the clinical translation of promising preclinical findings to overcome this significant obstacle in cancer therapy.

代谢重编程使癌细胞能够适应治疗的压力，是耐药性的主要致病力。葡萄糖、氨基酸和脂质代谢失调提供能量、生物合成前体和氧化还原平衡，促进治疗肿瘤的生存。这些过程是由致癌信号、肿瘤抑制因子的缺失和调节非编码rna协调的，这些非编码rna促进癌症的发生、免疫逃避和对细胞凋亡的抵抗。这篇综述探讨了中枢代谢途径，特别是糖酵解、谷氨酰胺代谢和脂肪酸合成被改变以促进各种类型癌症耐药的机制。此外，我们报告了利用这种代谢弱点来预防治疗耐药性和提高临床结果的新治疗方法。未来的方向强调需要先进的代谢分析来个性化治疗方法和临床前研究结果的临床转化，以克服癌症治疗中的这一重大障碍。

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引用次数: 0

From tissue architecture to clinical insights: Spatial transcriptomics in solid tumor studies 从组织结构到临床洞察：实体肿瘤研究中的空间转录组学

IF 3 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-07-14 DOI: 10.1016/j.seminoncol.2025.152389

Arpit Sharma , Shruti S. Raut , Alok Shukla , Shivani Gupta , Abha Mishra , Amit Singh

Cancer is a highly heterogeneous disease, and its diagnosis, prognosis, and therapeutic responsiveness depend not only on genetic alterations but also on the intricate organization of cells within the tumor microenvironment (TME). Spatial transcriptomics—a suite of techniques that preserves the spatial context of gene expression in intact tissue—has revolutionized our ability to decipher tumor architecture and intercellular communication. This review provides an in‐depth analysis of recent advancements in spatial transcriptomics technologies and their applications in solid tumor research. We first describe the evolution of spatial transcriptomics from early in situ hybridization methods to state‐of‐the‐art imaging‐ and sequencing‐based platforms. Next, we discuss how spatially resolved transcriptomics is transforming cancer research by revealing the molecular landscapes of tumor cores, invasive edges, and immunological niches. The integration of spatial transcriptomics with single‐cell multiomics and advanced computational algorithms is leading to the identification of novel prognostic and predictive biomarkers. Despite tremendous progress, challenges remain in terms of technical resolution, data processing, sample preparation, and clinical standardization. Finally, we highlight emerging trends—including three-dimensional (3D) spatial profiling, multimodal integration, and the use of artificial intelligence and Deep learning—to envision a future in which spatial transcriptomics will serve as a pivotal tool for precision oncology. Together, these developments promise to refine cancer biomarker studies and ultimately improve patient outcomes.

癌症是一种高度异质性的疾病，其诊断、预后和治疗反应不仅取决于遗传改变，还取决于肿瘤微环境（TME）内细胞的复杂组织。空间转录组学——一套保留完整组织中基因表达空间背景的技术——已经彻底改变了我们破译肿瘤结构和细胞间通讯的能力。本文综述了空间转录组学技术的最新进展及其在实体肿瘤研究中的应用。我们首先描述了空间转录组学的演变，从早期的原位杂交方法到最先进的成像和测序平台。接下来，我们将讨论空间解析转录组学如何通过揭示肿瘤核心、侵袭边缘和免疫生态位的分子景观来改变癌症研究。空间转录组学与单细胞多组学和先进的计算算法的整合正在导致新的预后和预测性生物标志物的鉴定。尽管取得了巨大的进步，但在技术解决、数据处理、样品制备和临床标准化方面仍然存在挑战。最后，我们强调了新兴趋势-包括三维（3D）空间分析，多模式集成以及人工智能和深度学习的使用-设想空间转录组学将作为精确肿瘤学的关键工具的未来。总之，这些进展有望改进癌症生物标志物研究，并最终改善患者的治疗效果。

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引用次数: 0