Cancer Medicine最新文献_第3页

Radiomic prediction for durable response to high-dose methotrexate-based chemotherapy in primary central nervous system lymphoma 原发性中枢神经系统淋巴瘤患者对基于甲氨蝶呤的大剂量化疗的持久反应的放射学预测

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-10 DOI: 10.1002/cam4.70182

Haoyi Li, Mingming Xiong, Ming Li, Caixia Sun, Dao Zheng, Leilei Yuan, Qian Chen, Song Lin, Zhenyu Liu, Xiaohui Ren

Background

The rarity of primary central nervous system lymphoma (PCNSL) and treatment heterogeneity contributes to a lack of prognostic models for evaluating posttreatment remission. This study aimed to develop and validate radiomic-based models to predict the durable response (DR) to high-dose methotrexate (HD-MTX)-based chemotherapy in PCNSL patients.

Methods

A total of 159 patients pathologically diagnosed with PCNSL between 2011 and 2021 across two institutions were enrolled. According to the NCCN guidelines, the DR was defined as the remission lasting ≥1 year after receiving HD-MTX-based chemotherapy. For each patient, a total of 1218 radiomic features were extracted from prebiopsy T1 contrast-enhanced MR images. Multiple machine-learning algorithms were utilized for feature selection and classification to build a radiomic signature. The radiomic-clinical integrated models were developed using the random forest method. Model performance was externally validated to verify its clinical utility.

Results

A total of 105 PCNSL patients were enrolled after excluding 54 cases with ineligibility. The training and validation cohorts comprised 76 and 29 individuals, respectively. Among them, 65 patients achieved DR. The radiomic signature, consisting of 8 selected features, demonstrated strong predictive performance, with area under the curves of 0.994 in training cohort and 0.913 in validation cohort. This signature was independently associated with the DR in both cohorts. Both the radiomic signature and integrated models significantly outperformed the clinical models in two cohorts. Decision curve analysis underscored the clinical utility of the established models.

Conclusions

This radiomic signature and integrated models have the potential to accurately predict the DR to HD-MTX-based chemotherapy in PCNSL patients, providing valuable therapeutic insights.

背景原发性中枢神经系统淋巴瘤（PCNSL）的罕见性和治疗的异质性导致缺乏评估治疗后缓解的预后模型。本研究旨在开发和验证基于放射组学的模型，以预测 PCNSL 患者对基于高剂量甲氨蝶呤（HD-MTX）化疗的持久反应（DR）。方法两家机构共招募了159名2011年至2021年间病理诊断为PCNSL的患者。根据NCCN指南，DR定义为接受HD-MTX化疗后缓解时间≥1年。从每位患者的活检前 T1 对比增强 MR 图像中提取了共 1218 个放射学特征。利用多种机器学习算法进行特征选择和分类，以建立放射学特征。放射学-临床综合模型是利用随机森林方法开发的。对模型的性能进行了外部验证，以验证其临床实用性。结果在排除 54 例不符合条件的病例后，共有 105 例 PCNSL 患者被纳入研究。训练组和验证组分别有 76 人和 29 人。其中，65 名患者获得了 DR。由 8 个选定特征组成的放射学特征表现出很强的预测能力，训练组的曲线下面积为 0.994，验证组的曲线下面积为 0.913。该特征与两个队列中的 DR 均有独立关联。在两个队列中，放射特征和综合模型的表现均明显优于临床模型。决策曲线分析强调了已建立模型的临床实用性。结论该放射学特征和综合模型有可能准确预测 PCNSL 患者对基于 HD-MTX 化疗的 DR 的反应，提供有价值的治疗见解。

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引用次数: 0

Immune-dysregulation harnessing in myeloid neoplasms 利用免疫调节治疗骨髓性肿瘤

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-10 DOI: 10.1002/cam4.70152

Mohammad Jafar Sharifi, Ling Xu, Nahid Nasiri, Mehnoosh Ashja-Arvan, Hadis Soleimanzadeh, Mazdak Ganjalikhani-Hakemi

Myeloid malignancies arise in bone marrow microenvironments and shape these microenvironments in favor of malignant development. Immune suppression is one of the most important stages in myeloid leukemia progression. Leukemic clone expansion and immune dysregulation occur simultaneously in bone marrow microenvironments. Complex interactions emerge between normal immune system elements and leukemic clones in the bone marrow. In recent years, researchers have identified several of these pathological interactions. For instance, recent works shows that the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), from bone marrow stromal cells contributes to immune dysregulation and the selective proliferation of JAK2V617F+ clones in myeloproliferative neoplasms. Moreover, inflammasome activation and sterile inflammation result in inflamed microenvironments and the development of myelodysplastic syndromes. Additional immune dysregulations, such as exhaustion of T and NK cells, an increase in regulatory T cells, and impairments in antigen presentation are common findings in myeloid malignancies. In this review, we discuss the role of altered bone marrow microenvironments in the induction of immune dysregulations that accompany myeloid malignancies. We also consider both current and novel therapeutic strategies to restore normal immune system function in the context of myeloid malignancies.

髓系恶性肿瘤在骨髓微环境中产生，并塑造有利于恶性发展的微环境。免疫抑制是髓系白血病发展过程中最重要的阶段之一。在骨髓微环境中，白血病克隆扩增和免疫失调同时发生。骨髓中的正常免疫系统元素和白血病克隆之间出现了复杂的相互作用。近年来，研究人员发现了其中几种病理相互作用。例如，最近的研究表明，骨髓基质细胞分泌肿瘤坏死因子-α（TNF-α）等炎性细胞因子，导致骨髓增殖性肿瘤中的免疫失调和 JAK2V617F+ 克隆的选择性增殖。此外，炎性体激活和无菌性炎症会导致炎性微环境和骨髓增生异常综合征的发生。其他免疫失调，如 T 细胞和 NK 细胞衰竭、调节性 T 细胞增加和抗原递呈障碍，也是髓系恶性肿瘤的常见症状。在这篇综述中，我们将讨论骨髓微环境的改变在诱发伴随髓系恶性肿瘤的免疫失调中的作用。我们还考虑了在髓系恶性肿瘤中恢复正常免疫系统功能的现有和新型治疗策略。

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引用次数: 0

Potential therapeutic effects of apigenin for colorectal adenocarcinoma: A systematic review and meta-analysis 芹菜素对结直肠腺癌的潜在治疗作用：系统综述和荟萃分析

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-10 DOI: 10.1002/cam4.70171

Koohyar Ahmadzadeh, Shayan Roshdi Dizaji, Fatemeh Ramezani, Farnad Imani, Jebreil Shamseddin, Arash Sarveazad, Mahmoud Yousefifard

Purpose

Therapeutic management of colorectal cancer (CRC) does not yet yield promising long-term results. Therefore, there is a need for further investigation of possible therapeutic options. Various experiments have studied the effects of apigenin on CRC and have shown conflicting results. This systematic review and meta-analysis investigates the currently existing evidence on the effect of apigenin on CRC.

Methods

Medline, Embase, Scopus, and Web of Science databases were searched for articles related to apigenin and its effect on CRC in the preclinical setting. Cell viability, growth inhibition, apoptosis, and cell cycle arrest for in-vitro, and body weight, tumor size, and mortality in in-vivo studies were extracted as outcomes.

Results

Thirty-nine articles investigating colorectal adenocarcinoma were included in this meta-analysis. Thirty-seven of these studies had data for in vitro experiments, with eight studies having data for in vivo experiments. Six articles had both in vitro and in vivo assessments. Our analysis showed apigenin reduces cell viability and induces growth inhibition, apoptosis, and cell cycle arrest in in vitro studies. The few in vivo studies indicate that apigenin decreases tumor size while showing no effects on the body weight of animal colorectal adenocarcinoma models.

Conclusion

Our results demonstrated that apigenin, through reducing cell viability, inducing growth inhibition, apoptosis, and cell cycle arrest, and also by decreasing the tumor size, can be considered as a possible adjuvant agent in the management of colorectal adenocarcinoma. However, further in vivo studies are needed before any efforts to translate the current evidence into clinical studies.

目的结直肠癌（CRC）的长期治疗效果尚不乐观。因此，有必要进一步研究可能的治疗方案。各种实验研究了芹菜素对 CRC 的影响，但结果相互矛盾。本系统综述和荟萃分析调查了芹菜素对 CRC 影响的现有证据。方法在 Medline、Embase、Scopus 和 Web of Science 数据库中搜索与芹菜素及其在临床前环境中对 CRC 的影响有关的文章。提取体外研究中的细胞活力、生长抑制、细胞凋亡和细胞周期停滞，以及体内研究中的体重、肿瘤大小和死亡率作为研究结果。结果本次荟萃分析共纳入 39 篇研究结直肠腺癌的文章。其中 37 项研究有体外实验数据，8 项研究有体内实验数据。六篇文章同时进行了体外和体内评估。我们的分析表明，在体外研究中，芹菜素能降低细胞活力，诱导生长抑制、细胞凋亡和细胞周期停滞。为数不多的体内研究表明，芹菜素能缩小肿瘤大小，但对动物结直肠腺癌模型的体重没有影响。结论我们的研究结果表明，芹菜素通过降低细胞活力、诱导生长抑制、细胞凋亡和细胞周期停滞，以及通过缩小肿瘤体积，可被视为治疗结直肠腺癌的一种可能的辅助药物。不过，在将现有证据转化为临床研究之前，还需要进一步的体内研究。

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引用次数: 0

Clinical relevance and druggability of sole reciprocal kinase fusions: A large-scale study 唯一互作激酶融合的临床相关性和可药性：大规模研究

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-10 DOI: 10.1002/cam4.70191

Jiao Feng, Tonghui Ma, Chunyang Wang, Baoming Wang, Qian Liu, Zhengchuang Liu, Houquan Tao, Zaiyuan Ye

Background

Building on our prior work that RNA alternative splicing modulates the druggability of kinase fusions, this study probes the clinical significance of sole reciprocal fusions. These rare genomic arrangements, despite lacking kinase domains at the DNA level, demonstrated potential RNA-level druggability in sporadic cases from our prior research.

Methods

Utilizing the large-scale multicenter approach, we performed RNA sequencing and clinical follow-up to evaluate a broad spectrum of kinase fusions, including ALK, ROS1, RET, BRAF, NTRK, MET, NRG1, and EGFR, in 1943 patients.

Results

Our findings revealed 51 instances (2.57%) of sole reciprocal fusions, predominantly in lung (57%), colorectal (14%), and glioma (10%) cancers. Comparative analysis with an MSKCC cohort confirmed the prevalence in diverse cancer types and identified unique fusion partners and chromosomal locales. Cross-validation through RNA-NGS and FISH authenticated the existence of functional kinase domains in subsets including ALK, ROS1, RET, and BRAF, which correlated with positive clinical responses to targeted kinase inhibitors (KIs). Conversely, fusions involving EGFR, NRG1, and NTRK1/2/3 generated nonfunctional transcripts, suggesting the need for alternative therapeutic interventions.

Conclusion

This inaugural multicenter study introduces a novel algorithm for detecting and treating sole reciprocal fusions in advanced cancers, expanding the patient population potentially amenable to KIs.

研究背景基于我们之前的研究，即 RNA 替代剪接可调节激酶融合的可药性，本研究探究了唯一互变融合的临床意义。这些罕见的基因组排列尽管在 DNA 水平上缺乏激酶结构域，但在我们之前的研究中，这些罕见的基因组排列在散发性病例中显示出了潜在的 RNA 水平上的可药性。方法利用大规模多中心方法，我们对 1943 例患者进行了 RNA 测序和临床随访，以评估包括 ALK、ROS1、RET、BRAF、NTRK、MET、NRG1 和 EGFR 在内的多种激酶融合。结果我们的发现揭示了51例（2.57%）唯一的相互融合，主要发生在肺癌（57%）、结直肠癌（14%）和胶质瘤（10%）。与MSKCC队列的比较分析证实了不同癌症类型中的流行率，并确定了独特的融合伙伴和染色体位置。通过RNA-NGS和FISH交叉验证，证实了包括ALK、ROS1、RET和BRAF在内的亚群中存在功能性激酶域，这与靶向激酶抑制剂（KIs）的阳性临床反应相关。相反，涉及表皮生长因子受体（EGFR）、NRG1和NTRK1/2/3的融合则会产生无功能转录本，这表明需要采取其他治疗干预措施。结论这项首创的多中心研究引入了一种新型算法，用于检测和治疗晚期癌症中的唯一互变，从而扩大了KIs的潜在适用患者人群。

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引用次数: 0

Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study 甲氨蝶呤的早期治疗药物监测及其与急性肾损伤的关系：回顾性队列研究

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-10 DOI: 10.1002/cam4.70176

Nicolás Tentoni, Miriam Hwang, Gabriela Villanueva, Ryan Combs, Jennifer Lowe, Laura B. Ramsey, Zachary L. Taylor, Thais Murciano Carrillo, María Dolores Aumente, Teresa López-Viñau López, Carmelo Rizzari, Scott C. Howard

Introduction

High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment.

Methods

This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t_½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves were synthesized for each elimination t_½ (biomarker) with respect to AKI and delayed methotrexate elimination (DME); the biomarker with the highest area under the ROC curve (AUC) was tested in a multiple variable logistic regression model.

Results

Data from 169 patients who received a total of 556 courses of HDMTX were analyzed. ROC analysis revealed MTX elimination t_½ calculated from the second and third time periods had the highest AUC for AKI at 0.62 (interquartile range [IQR] 0.56–0.69) and DME at 0.86 (IQR 0.73–1.00). After adjusting for age, sex, dose (mg/m²), infusion duration, HDMTX course, and baseline estimated glomerular filtration rate, it remained significant for AKI with an OR of 1.29 and 95% confidence interval of 1.03–1.65.

Conclusion

Early MTX elimination t_½ measured within 16 h of infusion completion was significantly associated with the development of AKI and serves as an early clearance biomarker that may identify patients who benefit from increased hydration, augmented leucovorin rescue, and glucarpidase administration.

导言大剂量甲氨蝶呤（HDMTX）的使用可能会因急性肾损伤（AKI）的发生而受到限制。要防止进一步的肾损伤和不可逆的毒性，早期发现 AKI 至关重要。本研究旨在确定 MTX 的早期消除模式是否可作为 HDMTX 治疗中 AKI 的生物标记物。方法这项回顾性队列研究包括两个在 MTX 输注结束后 16 小时内采集 MTX 水平≥2 的研究机构。对早期水平进行标记，并根据三个不同早期时间段中两个时间段的组合计算 MTX 消除半衰期 (t½)。为每种消除半衰期（t½）（生物标记物）合成与 AKI 和甲氨蝶呤延迟消除（DME）相关的接收者操作特征（ROC）曲线；在多变量逻辑回归模型中测试 ROC 曲线下面积（AUC）最大的生物标记物。结果分析了169名患者的数据，这些患者共接受了556个疗程的HDMTX治疗。ROC分析显示，从第二和第三个时间段计算的MTX消除t/½对AKI的AUC最高，为0.62（四分位距[IQR] 0.56-0.69），对DME的AUC最高，为0.86（IQR 0.73-1.00）。在对年龄、性别、剂量（毫克/平方米）、输注时间、HDMTX疗程和基线肾小球滤过率进行调整后，其对AKI的影响仍然显著，OR值为1.29，95%置信区间为1.03-1.65。结论输注结束后 16 小时内测量的早期 MTX 清除率 t½ 与 AKI 的发生显著相关，它是一种早期清除生物标志物，可识别出哪些患者可从增加水合、加强白消安抢救和服用葡萄糖苷酶中获益。

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引用次数: 0

Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer 激活素水平与上皮性卵巢癌的淋巴细胞浸润有关。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-09 DOI: 10.1002/cam4.7368

Elizabeth T. Evans, Emily F. Page, Alex Seok Choi, Zainab Shonibare, Andrea G. Kahn, Rebecca C. Arend, Karthikeyan Mythreye

Objective

The TGF-β superfamily member activin, a dimer of the gene products of INHBA and/or INHBB, has been implicated in immune cell maturation and recruitment, but its immune impact within epithelial ovarian cancer (EOC) is not well characterized. We sought to explore differences in activin (INHBA/ Inhibin-βA and INHBB/ Inhibin-βB) between malignant and ovarian tissues at the RNA and protein level and assess the relationship between activin and immune cells in EOC.

Methods

Publicly available RNA sequencing data were accessed from GEO (#GSE143897) with normalization and quantification performed via DESeq2. Immune gene expression profile was further explored within the TCGA-OV cohort derived from The Cancer Genome Atlas (TCGA). Immunohistochemical analysis was performed to evaluate activin A and T-cell markers CD8 and FoxP3 at the protein level. ELISA to activin-A was used to assess levels in the ascites of advanced EOC patients. Kaplan–Meier curves were generated to visualize survival outcomes.

Results

Gene expression levels of components of the activin signaling pathway were elevated within EOC when compared to a benign cohort, with differences in activin type I/II receptor gene profiles identified. Additionally, INHBA gene expression was linked to lymphocytic immune markers in EOC samples. Immunohistochemistry analysis revealed a positive correlation of CD8 and FOXP3 staining with activin A at the protein level in both primary and metastatic epithelial ovarian cancer samples. Furthermore, Activin-A (inhibin-βA) is significantly elevated in EOC patient ascites.

Conclusion

INHBA expression is elevated within EOC, correlating with worse survival, with activin protein levels correlating with specific immune infiltration. Our findings suggest that activin-A may play a role in suppressing anti-tumor immunity in EOC, highlighting its potential as a therapeutic target.

目的：TGF-β超家族成员活化素是INHBA和/或INHBB基因产物的二聚体，被认为与免疫细胞的成熟和招募有关，但其在上皮性卵巢癌（EOC）中的免疫影响尚未得到很好的描述。我们试图从RNA和蛋白质水平探讨恶性肿瘤组织和卵巢组织中活化素（INHBA/抑制素-βA和INHBB/抑制素-βB）的差异，并评估活化素与EOC中免疫细胞之间的关系：方法：从GEO（#GSE143897）获取公开的RNA测序数据，并通过DESeq2进行归一化和量化。在癌症基因组图谱（The Cancer Genome Atlas，TCGA）的TCGA-OV队列中进一步探讨了免疫基因表达谱。免疫组化分析在蛋白质水平上评估了活化素A和T细胞标记物CD8及FoxP3。用酶联免疫吸附法评估晚期EOC患者腹水中的活化素A水平。生成的 Kaplan-Meier 曲线显示了生存结果：结果：与良性病例相比，EOC中活化素信号通路成分的基因表达水平升高，活化素I型/II型受体基因谱存在差异。此外，INHBA基因表达与EOC样本中的淋巴细胞免疫标记物有关。免疫组化分析表明，在原发性和转移性上皮性卵巢癌样本中，CD8和FOXP3染色与蛋白水平的激活素A呈正相关。此外，EOC患者腹水中的活化素A（抑制素-βA）明显升高：结论：INHBA 在 EOC 中的表达升高，与生存恶化相关，而激活素蛋白水平与特异性免疫浸润相关。我们的研究结果表明，活化素-A可能在EOC中起到抑制抗肿瘤免疫的作用，这凸显了其作为治疗靶点的潜力。

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引用次数: 0

Effectiveness of mobile health for exercise promotion on cardiorespiratory fitness after a cancer diagnosis: A systematic review and meta-analysis 移动医疗对癌症确诊后心肺功能的锻炼促进效果：系统回顾与荟萃分析。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-09 DOI: 10.1002/cam4.7079

Megan E. Gregory, Weidan Cao, Saurabh Rahurkar, Fadi Haroun, James C. Stock, Sanam M. Ghazi, Daniel Addison

Background

Cancer survivors are at greater risk for cardiovascular-related mortality. Mobile health (mHealth) is an increasingly prevalent strategy for health promotion, but whether it consistently improves cardiorespiratory outcomes after a cancer diagnosis is unknown. We sought to determine the effectiveness of mHealth fitness/physical activity interventions on cardiorespiratory fitness outcomes among cancer patients and survivors.

Methods

Leveraging MEDLINE/PubMed, Scopus, and ClinicalTrials.gov, we identified studies through May 2023. Included studies provided a quantitative evaluation of an mHealth intervention in a primary or secondary capacity on cardiorespiratory fitness (6-minute walk test, VO₂max, 3-minute step test, or systolic blood pressure; or any mention of cardiac measure) and were meta-analyzed (using a random effects model) if they were a randomized controlled trial with sufficient quantitative information. Four coders were involved in applying inclusion/exclusion criteria, coding using a standardized data extraction sheet, and assessing study quality, with each study coded by at least two.

Results

Of 656 articles, nine (n = 392) met systematic review inclusion criteria (mean age range 19–62 years, 71.9% female, 60.9% breast cancer). Interventions included mobile apps (k = 6), smartwatches (k = 2), or a smartwatch plus a supplemental web/mobile/tablet app (k = 1); median duration of mHealth-use was 12 weeks. Seven (n = 341) fit criteria for meta-analysis. mHealth was associated with improved cardiorespiratory fitness (d = 0.33; 95% CI = 0.07–0.60) compared to a control group. Relationships remained after accounting for lipid-based outcomes (d = 0.30; 95% CI = 0.03–0.56). There was no evidence for heterogeneity or publication-bias.

Conclusions

mHealth exercise interventions appear to be a viable strategy for improving cardiorespiratory fitness after a cancer diagnosis.

背景：癌症幸存者的心血管相关死亡率风险更高。移动医疗（mHealth）是一种日益普遍的健康促进策略，但它是否能持续改善癌症确诊后的心肺功能结果还不得而知。我们试图确定移动医疗健身/体育活动干预对癌症患者和幸存者心肺功能结果的影响：利用 MEDLINE/PubMed、Scopus 和 ClinicalTrials.gov，我们确定了截至 2023 年 5 月的研究。纳入的研究提供了移动医疗干预措施对心肺功能（6 分钟步行测试、VO2max、3 分钟台阶测试或收缩压；或任何提及的心脏指标）的主要或次要能力的定量评估，如果这些研究是随机对照试验，且具有足够的定量信息，则对其进行荟萃分析（使用随机效应模型）。四名编码员参与了纳入/排除标准的应用、标准化数据提取表的编码以及研究质量的评估，每项研究至少由两名编码员进行编码：在 656 篇文章中，有 9 篇（n = 392）符合系统综述纳入标准（平均年龄范围为 19-62 岁，71.9% 为女性，60.9% 为乳腺癌）。干预措施包括移动应用程序（k = 6）、智能手表（k = 2）或智能手表加辅助网络/移动/平板应用程序（k = 1）；移动医疗使用的中位持续时间为 12 周。与对照组相比，移动健康与心肺功能改善相关（d = 0.33；95% CI = 0.07-0.60）。在考虑血脂结果（d = 0.30; 95% CI = 0.03-0.56）后，相关性依然存在。结论：移动医疗运动干预似乎是癌症确诊后改善心肺功能的可行策略。

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引用次数: 0

Impact of positive CD4 cells on event-free survival in follicular lymphoma patients CD4 细胞阳性对滤泡淋巴瘤患者无事件生存期的影响。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-09 DOI: 10.1002/cam4.70117

Cong Li, Na Guo, Shuiyun Han, Haifeng Yu, Tao Lei, Xi Chen, Shuailing Peng, Haiyan Yang, Meijuan Wu

Objective

Previous results about prognostic value of CD4+ T cells in follicular lymphoma (FL) remain controversial.

Methods

Immunohistochemistry was used to examine expression of positive CD4 cells in 103 patients with FL 1-3A. Early failure was described as failing to achieve event-free survival (EFS) at 12 or 24 months.

Results

There were 49 (47.6%) male and 54 (52.4%) females, with a median age of 54 years. Compared to patients with <20% of positive CD4 cells, patients with ≥20% of positive CD4 cells exhibited a significant lower risk of early failure (2-year EFS rate: 56.7% vs 73.5%, p = 0.047). When patients were stratified based on positive CD4 cell combined with FLIPI, the median EFS (p = 0.002) and median OS (p = 0.007) were significantly different.

Conclusions

This study demonstrated that higher expression of positive CD4 cells predicts lower risk of early failure in follicular lymphoma, and combination analysis of CD4 and FLIPI could better predict disease relapse and survival outcome.

目的以往关于滤泡性淋巴瘤（FL）中 CD4+ T 细胞预后价值的研究结果仍存在争议：方法：采用免疫组化方法检测103例FL 1-3A患者CD4阳性细胞的表达。结果：103例FL 1-3A患者中，有49例（47.6%）CD4细胞表达阳性：结果：103 名 FL 1-3A 患者中有 49 名男性（47.6%）和 54 名女性（52.4%），中位年龄为 54 岁。结果：男性 49 人（47.6%），女性 54 人（52.4%），中位年龄 54 岁：这项研究表明，CD4细胞阳性表达越高，预测滤泡性淋巴瘤早期失败的风险越低，CD4和FLIPI的联合分析能更好地预测疾病复发和生存结果。

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引用次数: 0

Evaluating implementation of a hospital-based cancer registry to improve childhood cancer care in low- and middle-income countries 评估以医院为基础的癌症登记处的实施情况，以改善中低收入国家的儿童癌症护理。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-09 DOI: 10.1002/cam4.70125

Melissa R. Maas, Allison Yang, Michele A. Muir, James B. Collins IV, Courtney Canter, Gevorg Tamamyan, Inam Chitsike, Francine Kouya, Kim Hoa Nguyen, Alia Ahmad, Ana Patricia Alcasabas, Yi-Jin Gao, Kimberly J. Johnson, Gia Ferrara, Nickhill Bhakta, Benyam Muluneh

Purpose

Cancer is a leading cause of global childhood mortality, affecting 400,000 children annually. While treatable with modern therapies, children living in low- and middle-income countries (LMICs) have limited access to care and lower survival rates. Hospital-based cancer registries (HBCRs) collect detailed patient information to critically evaluate and evolve care. The St. Jude Global Childhood Cancer Analytics Resource and Epidemiological Surveillance System (SJCARES) is a cloud-based HBCR network facilitating quality data collection of pediatric cancer. Wide variation in the success of implementation has warranted further research into the implementation approach, to create a sustainable and adaptable HBCR in LMICs.

Methods

Seven of 89 sites using the SJCARES registry were selected, stratified by global region and stage of implementation. Semi-structured interviews were conducted with key groups (clinicians, administrators, data clerks) using an interview guide developed from the Consolidation Framework for Implementation Research (CFIR). Interviews were conducted via a video-telephone software program and transcribed by a transcription service. Transcripts were thematically coded using rapid qualitative analysis.

Results

A total of 18 participants (11 clinicians, 4 administrators, 3 data clerks) were interviewed. Several barrier themes were identified, including: difficulty integrating the registry into existing workflow; lack of resources; lack of government or administrative support; and damaged, misplaced, or illegible medical records. Facilitator themes were identified, including: internal support for the registry; clear and extensive training; and dedicated support staff.

Conclusion

Interviewed participants identified key barriers and facilitators to the implementation of the SJCARES registry across multiple phases. We plan to use these results to develop targeted implementation strategies including a readiness assessment tool to help guide more successful implementation of the SJCARES registry and other HBCRs in LMICs.

目的：癌症是全球儿童死亡的主要原因，每年影响 40 万儿童。虽然现代疗法可以治疗癌症，但生活在中低收入国家（LMICs）的儿童获得治疗的机会有限，存活率较低。医院癌症登记处（HBCR）收集了详细的患者信息，用于严格评估和发展医疗服务。圣裘德全球儿童癌症分析资源和流行病学监测系统（SJCARES）是一个基于云的 HBCR 网络，有助于收集高质量的儿童癌症数据。由于实施成功与否存在很大差异，因此有必要对实施方法进行进一步研究，以便在低收入国家和地区建立一个可持续和适应性强的 HBCR：方法：按照全球地区和实施阶段，从 89 个使用 SJCARES 登记册的地点中选择了 7 个。采用根据实施研究整合框架 (CFIR) 制定的访谈指南，对关键群体（临床医生、管理人员、数据员）进行了半结构化访谈。访谈通过视频电话软件程序进行，并由转录服务公司进行转录。采用快速定性分析法对记录誊本进行主题编码：共有 18 名参与者（11 名临床医生、4 名管理人员、3 名数据员）接受了访谈。确定了几个障碍主题，包括：难以将登记册整合到现有工作流程中；缺乏资源；缺乏政府或行政支持；医疗记录损坏、错位或难以辨认。确定的促进因素主题包括：对登记处的内部支持；明确而广泛的培训；专职支持人员：受访者指出了在多个阶段实施 SJCARES 登记的主要障碍和促进因素。我们计划利用这些结果制定有针对性的实施策略，包括准备就绪评估工具，以帮助指导 SJCARES 登记册和其他 HBCR 在低收入国家/地区更成功地实施。

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引用次数: 0

Heat shock transcription factor 1 facilitates liver cancer progression by driving super-enhancer-mediated transcription of MYCN 热休克转录因子 1 通过驱动超级增强子介导的 MYCN 转录促进肝癌进展。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-09-09 DOI: 10.1002/cam4.70157

Yizhe Liu, Qili Shi, Yue Su, Zhiao Chen, Xianghuo He

Background

Heat shock transcription factors (HSFs) play crucial roles in the development of malignancies. However, the specific roles of HSFs in hepatocellular carcinoma (HCC) have yet to be fully elucidated.Aims:To explore the involvement of the HSF family, particularly HSF1, in the progression and prognosis of HCC.

Materials & Methods

We conducted a thorough analysis of HSF expression and copy number variations across various cancer datasets. Specifically focusing on HSF1, we examined its expression levels and prognostic implications in HCC. In vitro and in vivo experiments were carried out to evaluate the impact of HSF1 on liver cancer cell proliferation. Additionally, we utilized CUT&Tag, H3K27 acetylation enrichment, and RNA sequencing (RNA-seq) to investigate the super-enhancer (SE) regulatory landscapes of HSF1 in liver cancer cell lines.

Results

HSF1 expression is elevated in HCC and is linked to poor prognosis in several datasets. HSF1 stimulates liver cancer cell proliferation both in vitro and in vivo, partly through modulation of H3K27ac levels, influencing enhancer distribution. Mechanistically, our findings demonstrate that HSF1 transcriptionally activates MYCN expression by binding to its promoter and SE elements, thereby promoting liver cancer cell proliferation. Moreover, increased MYCN expression was detected in HCC tumors and correlated with unfavorable patient outcomes.

Discussion

Our study sheds light on previously unexplored aspects of HSF1 biology, identifying it as a transcription factor capable of shaping the epigenetic landscape in the context of HCC. Given HSF1's potential as an epigenetic regulator, targeting the HSF1-MYCN axis could open up new therapeutic possibilities for HCC treatment.

Conclusion

The HSF1-MYCN axis constitutes a transcription-dependent regulatory mechanism that may function as both a prognostic indicator and a promising therapeutic target in liver cancer. Further exploration of this axis could yield valuable insights into novel treatment strategies for HCC.

背景：热休克转录因子（HSFs）在恶性肿瘤的发展过程中起着至关重要的作用。然而，HSFs在肝细胞癌（HCC）中的具体作用尚未完全阐明。目的：探讨HSF家族（尤其是HSF1）参与HCC进展和预后的情况：我们对各种癌症数据集中的 HSF 表达和拷贝数变异进行了全面分析。我们特别关注了 HSF1，研究了其在 HCC 中的表达水平和预后影响。我们进行了体外和体内实验，以评估 HSF1 对肝癌细胞增殖的影响。此外，我们还利用CUT&Tag、H3K27乙酰化富集和RNA测序（RNA-seq）研究了肝癌细胞系中HSF1的超级增强子（SE）调控图谱：结果：在多个数据集中，HSF1在HCC中表达升高，并与预后不良有关。HSF1在体外和体内都能刺激肝癌细胞增殖，部分原因是通过调节H3K27ac水平影响了增强子的分布。从机理上讲，我们的研究结果表明，HSF1通过与其启动子和SE元件结合，转录激活MYCN的表达，从而促进肝癌细胞增殖。此外，HCC肿瘤中检测到MYCN表达增加，并与患者的不良预后相关：讨论：我们的研究揭示了 HSF1 生物学中以前未探索的方面，确定它是一种转录因子，能够在 HCC 中塑造表观遗传景观。鉴于HSF1作为表观遗传调控因子的潜力，以HSF1-MYCN轴为靶点可为HCC的治疗提供新的可能性：HSF1-MYCN轴是一种转录依赖性调控机制，可作为肝癌的预后指标和有希望的治疗靶点。对这一轴心的进一步探索可为HCC的新型治疗策略提供有价值的见解。

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引用次数: 0