Cancer Medicine最新文献_第5页

Pan-Cancer Survival Impact of Immune Checkpoint Inhibitors in a National Healthcare System 免疫检查点抑制剂对全国医疗保健系统中泛癌症生存率的影响。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-07 DOI: 10.1002/cam4.70379

Sean R. Miller, Matthew Schipper, Lars G. Fritsche, Ralph Jiang, Garth Strohbehn, Erkin Ötleş, Benjamin H. McMahon, Silvia Crivelli, Rafael Zamora-Resendiz, Nithya Ramnath, Shinjae Yoo, Xin Dai, Kamya Sankar, Donna M. Edwards, Steven G. Allen, Michael D. Green, Alex K. Bryant

Background

The cumulative, health system-wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real-world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system-wide survival impact of ICIs.

Methods

We identified all patients receiving PD-1/PD-L1 or CTLA-4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non-ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer-related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life-years gained system-wide were calculated from the difference in adjusted 5-year restricted mean survival times.

Results

There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, p < 0.001; urothelial: aHR 0.91, 95% CI 0.83–1.01, p = 0.066). The relative benefit of ICI was stable across patient age, comorbidity, and self-reported race subgroups. Across VHA, 15,859 life-years gained were attributable to ICI within 5-years of treatment, with NSCLC contributing the most life-years gained.

Conclusion

We demonstrated substantial increase in survival due to ICIs across a national health system, including in patient subgroups poorly represented on clinical trials.

背景：免疫检查点抑制剂（ICIs）对整个卫生系统的累积生存益处尚不明确，尤其是在预期寿命有限的现实世界患者中，以及在临床试验中代表性较差的亚群体中。我们试图确定 ICIs 对整个医疗系统的生存影响：我们确定了全国退伍军人健康管理局（VHA）系统中 2010 年至 2023 年接受 PD-1/PD-L1 或 CTLA-4 抑制剂治疗的所有患者（ICI 队列），以及 ICI 批准前几年接受非 ICI 系统治疗的所有患者（历史对照）。ICI队列和历史对照队列在多个癌症相关预后因素、合并症和人口统计学方面进行了匹配。ICI 对总生存期的影响通过包含匹配权重的 Cox 回归进行量化。根据调整后的 5 年限制性平均生存时间的差异计算出全系统获得的累积寿命年数：ICI队列中有27322名患者，历史对照队列中有69801名患者。在 ICI 患者中，最常见的癌症类型是 NSCLC（46%）和黑色素瘤（10%）。ICI 在大多数癌症类型中都显示出巨大的生存期获益，但不同癌症类型之间存在异质性（NSCLC：调整 HR [aHR] 0.56，95% 置信区间 [CI] 0.54-0.58，P 结论：ICI 患者的生存期获益显著：我们证明，在一个国家的医疗系统中，包括在临床试验中表现不佳的患者亚群中，使用 ICIs 可显著提高生存率。

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引用次数: 0

Isobutyric Acid Promotes Immune Evasion in Colorectal Cancer via Increased PD-L1 Expression 异丁酸通过增加 PD-L1 表达促进结直肠癌的免疫逃避

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-06 DOI: 10.1002/cam4.70397

Qiuhua Lin, Han Wang, Wenbo Chen, Xinjie Wei, Jinglian Chen, Ying Deng, Chunyin Wei, Hao Lai, Xianwei Mo, Weizhong Tang, Tao Luo

Introduction

Isobutyric acid (IBA), a short-chain fatty acid, has been unequivocally demonstrated to exert significant influence on the progression of colorectal cancer (CRC). Nevertheless, a comprehensive understanding of its intricate regulatory mechanisms remains elusive.

Methods

Employing advanced techniques such as western blot, RT-qPCR, and flow cytometry, we systematically investigated the impact of IBA on the expression of PD-L1 in CRC cells. Concurrently, employing RNA silencing technology and small-molecule inhibitors, we delved into the molecular intricacies underlying the regulatory axis of IBA involving ROCK1/c-Myc/PD-L1. Furthermore, through flow cytometry analysis, we examined the alterations in the tumor immune microenvironment following anti-PD-L1 antibody therapy in a murine tumor model treated with IBA.

Results

Elevated levels of IBA were found to robustly activate PD-L1 expression in CRC cells both in vitro and in vivo, concomitantly reshaping the tumor immune microenvironment. Subsequent mechanistic investigations unveiled that IBA, through its interaction and activation of ROCK1, promotes the activation of c-Myc, thereby enhancing the transcription of PD-L1. Silencing of ROCK1 and application of ROCK1 inhibitors effectively reversed the regulatory effects of IBA on PD-L1. Additionally, IBA inhibited the activity of infiltrating CD8⁺ T cells, resulting in diminished antitumor immunity and attenuating the sensitivity to anti-PD-L1 therapy.

Conclusion

Our study elucidates a novel mechanism by which IBA inhibits the sensitivity of CRC to anti-PD-L1 antibody therapy. Emphasizing IBA and its downstream pathways as potential therapeutic targets for immune therapy resistance mechanisms, our findings provide a novel theoretical foundation for overcoming immune therapy resistance.

导言：异丁酸（IBA）是一种短链脂肪酸，已被明确证实对结直肠癌（CRC）的进展有显著影响。然而，对其错综复杂的调控机制的全面了解仍然遥遥无期：方法：我们采用 Western 印迹、RT-qPCR 和流式细胞术等先进技术，系统研究了 IBA 对 CRC 细胞中 PD-L1 表达的影响。同时，我们采用 RNA 沉默技术和小分子抑制剂，深入研究了 IBA 的调控轴涉及 ROCK1/c-Myc/PD-L1 的复杂分子机制。此外，我们还通过流式细胞术分析，研究了使用 IBA 治疗的小鼠肿瘤模型在接受抗 PD-L1 抗体治疗后肿瘤免疫微环境的变化：结果：研究发现，IBA 水平的升高可在体外和体内强力激活 CRC 细胞中 PD-L1 的表达，同时重塑肿瘤免疫微环境。随后的机理研究发现，IBA 通过与 ROCK1 的相互作用和激活，促进了 c-Myc 的活化，从而增强了 PD-L1 的转录。抑制 ROCK1 和使用 ROCK1 抑制剂可有效逆转 IBA 对 PD-L1 的调控作用。此外，IBA还抑制了浸润CD8+ T细胞的活性，导致抗肿瘤免疫力下降，并降低了抗PD-L1疗法的敏感性：我们的研究阐明了IBA抑制CRC对抗PD-L1抗体治疗敏感性的新机制。我们的研究结果强调了IBA及其下游通路是免疫治疗耐药机制的潜在治疗靶点，为克服免疫治疗耐药提供了新的理论基础。

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引用次数: 0

Improved Therapeutic Efficacy of Doxorubicin Chemotherapy With Cannabidiol in 4T1 Mice Breast Cancer Model 用大麻二酚改善 4T1 小鼠乳腺癌模型中多柔比星化疗的疗效

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-06 DOI: 10.1002/cam4.70395

Koorosh Tabatabaei, Sara Moazzezi, Mohammadreza Emamgholizadeh, Haleh Vaez, Behzad Baradaran, Behrooz Shokouhi

Background

High dose chemotherapy is one of the therapeutic strategies for breast cancer and doxorubicin (DOX) as a chemotherapy agent is widely used. DOX indication is limited due to its dose-depended cardiotoxicity. Recently, cannabidiol (CBD) shows antitumoral and cardioprotective effects, so we hypothesized that CBD administration with high-dose DOX chemotherapy can improve anticancer activity and reduce cardiotoxic side effects.

Method

Mice breast cancer model established by injecting 4T1 cell lines. One group was not injected by 4T1 cells as a not cancerous group and received normal saline (NS, 0.1 mL). In cancerous groups, first group was considered as cancerous control and received NS (0.1 mL); the second group received CBD (5 mg/kg, IP) on Days 1,7, and 14; in the third group DOX (5 mg/kg, IV) as CBD schedule was administrated; the fourth group treated with CBD 1 day before DOX injection as pretreatment, and the last group was treated with CBD and DOX at same time with previous doses and schedules. On Day 21, all mice were sacrificed, heart and lungs tissues were obtained and histological sections were isolated. SOD2, iNOS, MMP2, MMP9 were evaluated through western blot and TUNEL test preformed for breast tumor.

Results

Tumor size and weight significantly decreased in DOX, pretreatment CBD + DOX and CBD + DOX groups. Administration of CBD with DOX could not prevent weight loss. TUNEL test demonstrated the highest tumor cell apoptosis in pretreatment CBD + DOX and CBD + DOX. In lungs belonged to CBD + DOX, there was not any sign of metastasis. Cardiac histopathological examination of pretreatment CBD + DOX and CBD + DOX did not show any sign of congestion or inflammation. In CBD + DOX SOD2 increased, also iNOS, MMP2, and MMP9 decreased compared to DOX.

Conclusions

This study demonstrated that simultaneous administration of CBD and DOX can increase antitumoral effect and reduce DOX cardiotoxicity. Nevertheless, CBD can induce cardiotoxicity as administrated alone.

背景：大剂量化疗是乳腺癌的治疗策略之一，多柔比星（DOX）作为一种化疗药物被广泛使用。由于多柔比星（DOX）具有剂量依赖性心脏毒性，其适应症受到限制。最近，大麻二酚（CBD）显示出抗肿瘤和保护心脏的作用，因此我们假设在大剂量 DOX 化疗的同时服用 CBD 可以提高抗癌活性并减少心脏毒性副作用：方法：通过注射 4T1 细胞株建立小鼠乳腺癌模型。方法：通过注射 4T1 细胞株建立小鼠乳腺癌模型。癌变组中，第一组为癌变对照组，接受 NS（0.1 mL）治疗；第二组在第 1、7 和 14 天接受 CBD（5 mg/kg，IP）治疗；第三组按 CBD 治疗方案注射 DOX（5 mg/kg，IV）；第四组在注射 DOX 前 1 天接受 CBD 治疗作为预处理，最后一组按之前的剂量和方案同时接受 CBD 和 DOX 治疗。第 21 天，所有小鼠处死，取心肺组织并进行组织学切片。对乳腺肿瘤的 SOD2、iNOS、MMP2、MMP9 进行 Western 印迹检测，并进行 TUNEL 检测：结果：DOX组、预处理CBD + DOX组和CBD + DOX组的肿瘤大小和重量均明显减少。在服用 DOX 的同时服用 CBD 不能阻止体重减轻。TUNEL检测显示，CBD + DOX和CBD + DOX组的肿瘤细胞凋亡率最高。在CBD + DOX组的肺部，没有任何转移迹象。CBD + DOX和CBD + DOX治疗前的心脏组织病理学检查未显示任何充血或炎症迹象。与 DOX 相比，CBD + DOX 的 SOD2 增加，iNOS、MMP2 和 MMP9 减少：这项研究表明，同时服用 CBD 和 DOX 可以提高抗肿瘤效果，降低 DOX 的心脏毒性。尽管如此，单独使用 CBD 仍会诱发心脏毒性。

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引用次数: 0

Autoimmune Diseases and Risk of Non-Hodgkin Lymphoma: A Mendelian Randomisation Study 自身免疫性疾病与非霍奇金淋巴瘤风险：孟德尔随机研究

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-06 DOI: 10.1002/cam4.70327

Xiaoting Shi, Joshua D. Wallach, Xiaomei Ma, Tormod Rogne

Background

Non-Hodgkin lymphoma (NHL) is one of the most common haematologic malignancies in the world. Despite substantial efforts to identify causes and risk factors for NHL, its aetiology is largely unclear. Autoimmune diseases have long been considered potential risk factors for NHL. We carried out Mendelian randomisation (MR) analyses to examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of NHL.

Methods

Two-sample MR was performed using publicly available summary statistics from cohorts of European ancestry. For NHL and four NHL subtypes, we used data from UK Biobank, Kaiser Permanente cohorts, and FinnGen studies.

Results

Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92–0.98, p = 5 × 10⁻³, and OR 0.92, 95% CI: 0.85–0.99, p = 2.8 × 10⁻², respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk.

Conclusion

These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL.

背景：非霍奇金淋巴瘤（NHL）是世界上最常见的血液恶性肿瘤之一。尽管为确定NHL的病因和风险因素做出了大量努力，但其病因在很大程度上仍不清楚。长期以来，自身免疫性疾病一直被认为是 NHL 的潜在风险因素。我们进行了孟德尔随机化（MR）分析，以研究基因预测的十种自身免疫性疾病（白塞氏病、乳糜泻、疱疹性皮炎、狼疮、银屑病、类风湿性关节炎、肉样瘤病、斯约格伦综合征、系统性硬化症和 1 型糖尿病）的易感性是否与 NHL 的风险有关：使用欧洲血统队列中可公开获得的汇总统计数据进行了双样本 MR 分析。对于 NHL 和四种 NHL 亚型，我们使用了来自英国生物库、Kaiser Permanente 队列和 FinnGen 研究的数据：结果：1 型糖尿病和肉样瘤病与 NHL 风险呈负相关（几率比 [OR] 0.95，95% 置信区间 [CI]：0.92-0.98，P＜0.05）：0.95，95%置信区间[CI]：0.92-0.98，p = 5 × 10-3；OR 0.92，95%置信区间：0.85-0.99，p = 2.8 × 10-2）。考虑到潜在的多效性和微弱的工具偏差进行的敏感性分析也支持这些结果。其他八种自身免疫性疾病与 NHL 风险之间没有发现明显的关联：这些研究结果表明，从基因上预测的1型糖尿病易感性，以及在一定程度上预测的肉样瘤病，可能会降低NHL风险。然而，未来的研究需要采用不同的数据集、方法和人群，以进一步研究这些自身免疫性疾病与 NHL 风险之间的潜在关联。

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引用次数: 0

Correction to “Exploring the Anticancer Mechanism of Cardiac Glycosides Using Proteome Integral Solubility Alteration Approach” 利用蛋白质组整体溶解度改变方法探索强心苷的抗癌机制 "的更正。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-06 DOI: 10.1002/cam4.70381

Qin, W, Deng, Y, Ren, H, Liu, Y, Liu, L, Liu, W, Zhao, Y, Li, C, Yang, Z. Exploring the Anticancer Mechanism of Cardiac Glycosides Using Proteome Integral Solubility Alteration Approach. Cancer Medicine 2024; 13(18):e70252. https://doi.org/10.1002/cam4.70252.

In the first of the affiliations, the text “The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital)” was incorrect. This should have read: “Hunan Provincial People's Hospital, (The First Affiliated Hospital of Hunan Normal University)”.

We apologize for this error.

Qin, W, Deng, Y, Ren, H, Liu, Y, Liu, L, Liu, W, Zhao, Y, Li, C, Yang, Z. 利用蛋白质组整体溶解度改变方法探索强心苷的抗癌机制。Cancer Medicine 2024; 13(18):e70252. https://doi.org/10.1002/cam4.70252. 第一处隶属关系中的 "湖南师范大学第一附属医院（湖南省人民医院）"有误。应为"湖南省人民医院（湖南师范大学第一附属医院）"。我们对此错误深表歉意。

引用次数: 0

The Use of CellCollector Assay to Detect Free Cancer Cells in the Peritoneal Cavity of Colorectal Cancer Patients: An Experimental Study 使用细胞收集器检测结直肠癌患者腹腔中的游离癌细胞：一项实验研究。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-06 DOI: 10.1002/cam4.70378

Yudi Wu, Fangxun He, Liang Liu, Wei Jiang, Jiao Deng, Yujie Zhang, Zhixin Cao, Xiangshang Xu, Jianping Gong

Background

Colorectal cancer (CRC) is associated with high incidence and mortality rates globally. The presence of intraperitoneal free cancer cells (IFCCs) is recognized as an independent prognostic factor for CRC patients. However, a clinical gold standard for IFCCs detection is lacking. The GILUPI CellCollector has demonstrated high sensitivity and specificity in detecting free cancer cells, yet its application for CRC IFCCs detection remains unreported.

Methods

We selected CRC and normal cell lines to evaluate the CellCollector's ability to detect tumor cells. A total of 70 CRC patients and 17 patients with benign disease undergoing laparoscopic procedures were investigated. Peritoneal lavage fluid was collected pre- and post-operation, and both real-time PCR (CEA mRNA) and CellCollector detection were performed. We compared the sensitivity and specificity of these two methods.

Results

CellCollector can distinguish well between CRC and normal cells in cell line experiments. CellCollector detects IFCCs better than real-time PCR (CEA) in CRC patients in different TNM Stages. The sensitivity of CellCollector was higher than that of real-time PCR (84.6% vs. 48.4%), and the specificity of CellCollector was also higher than real-time PCR (79.1% vs. 60.4%). There was no significant difference in the results of IFCCs detected by CellCollector before and after total mesorectal excision (TME) or complete mesocolic excision (CME) radical colorectomy (p > 0.05), but there was a significant difference in real-time PCR detection (p < 0.05).

Conclusions

The CellCollector demonstrates superior sensitivity and specificity compared to real-time PCR for detecting IFCCs in CRC patients, suggesting its potential as a clinical tool for IFCCs detection.

Trial Registration

ClinicalTrials.gov identifier: NCT01978444

背景：结直肠癌（CRC）在全球的发病率和死亡率都很高。腹腔内游离癌细胞（IFCCs）的存在被认为是 CRC 患者的一个独立预后因素。然而，目前还缺乏检测游离癌细胞的临床金标准。GILUPI CellCollector 在检测游离癌细胞方面具有很高的灵敏度和特异性，但其在 CRC IFCCs 检测中的应用仍未见报道：我们选择了 CRC 和正常细胞系来评估 CellCollector 检测肿瘤细胞的能力。我们共调查了 70 名接受腹腔镜手术的 CRC 患者和 17 名良性疾病患者。我们收集了手术前后的腹腔灌洗液，并进行了实时 PCR（CEA mRNA）和 CellCollector 检测。我们比较了这两种方法的灵敏度和特异性：结果：在细胞系实验中，CellCollector 能很好地区分 CRC 和正常细胞。在不同 TNM 分期的 CRC 患者中，CellCollector 检测 IFCC 的效果优于实时 PCR（CEA）。CellCollector 的灵敏度比实时 PCR 高（84.6% 对 48.4%），特异性也比实时 PCR 高（79.1% 对 60.4%）。在全直肠系膜切除术（TME）或完全结肠系膜切除术（CME）根治性结肠切除术前后，CellCollector 检测到的 IFCC 结果无明显差异（P > 0.05），但实时 PCR 检测到的 IFCC 结果有明显差异（P 结论：CellCollector 的灵敏度和特异性均高于实时 PCR：与实时 PCR 相比，CellCollector 检测 CRC 患者 IFCCs 的灵敏度和特异性均优于实时 PCR，这表明它有潜力成为检测 IFCCs 的临床工具：试验注册：ClinicalTrials.gov identifier：NCT01978444。

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引用次数: 0

Multidimensional Healthcare Access Barriers to Prostate-Specific Antigen Testing: A Nation-Wide Panel Study in the United States From 2006 to 2020 前列腺特异性抗原检测的多维医疗访问障碍：2006 至 2020 年美国全国小组研究》。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-06 DOI: 10.1002/cam4.70358

Hari S. Iyer, Kevin H. Kensler, Charlotte Roscoe, Chidinma Opara, Mingchao He, Evan Kovac, Isla P. Garraway, Quoc Dien-Trinh, Timothy R. Rebbeck

Background

Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors.

Methods

We pooled data from male respondents to Behavior Risk Factor Surveillance Systems (BRFSS) surveys from 2006 to 2020. Questions related to affordability (insurance, cost of visits) and accommodation (regular primary care provider (PCP), physician recommending a PSA test) were considered as individual-level barriers. For availability, we linked provider density from the 2012 Area Health Resource File and estimated driving times to closest health facility within Micropolitan and Metropolitan Statistical Area (MMSA) using Google Earth Engine. These measures were used to compute a spatial accessibility index. We fit survey-weighted, covariate-adjusted logistic regression models to estimate associations of barriers with receipt of PSA within the past 2 years and examined effect modification by sociodemographic factors.

Results

There were 185,643 participants, of whom 73% were White, 11% were Black, 4% were Asian, and 11% were Hispanic. Physician recommendation was the strongest predictor of having a PSA test (aOR: 14.5, 95% CI: 13.6, 15.6). Not having a regular PCP (aOR: 0.29, 95% CI: 0.27, 0.31), insurance (aOR: 0.64, 95% CI: 0.58, 0.71), and prohibitive cost of care (aOR: 0.82, 95% CI: 0.75, 0.90) were associated with lower PSA testing. Access barriers were stronger predictors of PSA testing for Asian and White participants compared to other groups (P_het < 0.004 for insurance and regular PCP) and for those with college education compared to those without (P_het < 0.05 for insurance, perceived unaffordability).

Discussion

Physician recommendation was the strongest predictor of receipt of PSA testing, regardless of sociodemographic grouping. Future studies should consider access barriers jointly and across sociodemographic strata.

背景：转移性前列腺癌发病率的上升再次引发了有关前列腺特异性抗原（PSA）筛查益处的争论。找出致命性前列腺癌高危人群接受筛查的障碍可能会减缓发病率的上升。我们研究了接受 PSA 检测的障碍与社会人口因素的关联：我们汇总了 2006 年至 2020 年行为危险因素监测系统 (BRFSS) 调查中男性受访者的数据。与可负担性（保险、就诊费用）和便利性（固定的初级保健提供者 (PCP)、推荐进行 PSA 检测的医生）相关的问题被视为个人层面的障碍。在可获得性方面，我们将 2012 年地区卫生资源档案中的医疗服务提供者密度与谷歌地球引擎估算的到大都市和都市统计区 (MMSA) 内最近医疗机构的驾车时间联系起来。这些指标用于计算空间可及性指数。我们拟合了经过调查加权、协变量调整的逻辑回归模型，以估算障碍与过去两年内接受 PSA 的相关性，并研究了社会人口因素对影响的修正作用：共有 185,643 名参与者，其中 73% 为白人，11% 为黑人，4% 为亚裔，11% 为西班牙裔。医生建议是预测进行 PSA 检测的最有力因素（aOR：14.5，95% CI：13.6，15.6）。没有固定的初级保健医生（aOR：0.29，95% CI：0.27，0.31）、没有保险（aOR：0.64，95% CI：0.58，0.71）以及医疗费用过高（aOR：0.82，95% CI：0.75，0.90）与较少进行 PSA 检测有关。与其他群体相比，亚裔和白人参与者接受 PSA 检测的障碍更大（Phet het 讨论）：无论社会人口组别如何，医生推荐是接受 PSA 检测的最强预测因素。未来的研究应综合考虑不同社会人口阶层的获取障碍。

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引用次数: 0

Racial and Ethnic Differences in Liver Transplantation and Post–Liver Transplant Survival Among Patients With Hepatocellular Carcinoma 肝细胞癌患者肝移植和肝移植后存活率的种族和民族差异。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-06 DOI: 10.1002/cam4.70298

Udhayvir S. Grewal, Apoorva K. Chandar, Shiva J. Gaddam, Abdul Rahman Al Armashi, Akram Alkreshi, Subhash C. Garikipati

Background

Racial and ethnic disparities in diagnosis and overall outcomes for HCC are well known. We present updated real-world data on racial or ethnic differences in LT and post-LT survival among patients with HCC in a large population-based database.

Methods

We used the TriNetX database to retrospectively identify patients who had HCC (ICD-10 C22.0, C22.8) and underwent LT (CPT codes 47,135, 47,140, 47,140, 47,141, 47,142) from 2012 to 2022 and compared outcomes across racial and ethnic subgroups.

Results

Majority of the patients were Caucasians (2403/2901, 84.8%), followed by African Americans (267/2901, 9.2%) Hispanic/Asian (231/2901, 7.9%). At follow up of 5 years, we noted no significant difference in mortality between AA and Caucasian patients [HR = 1.087 (95% CI 0.76, 1.56, p = 0.59)] as well as Hispanic/Asian and Caucasian patients [HR = 1.14 (95% CI 0.73, 1.78, p = 0.10)].

Conclusions

These results indicate that stringent implementation of policies aimed at ensuring equitable access to LT may contribute to bridging disparities in overall outcomes in HCC.

背景：众所周知，HCC 的诊断和总体预后存在种族和民族差异。我们在一个基于人口的大型数据库中提供了最新的真实世界数据，说明HCC患者在LT和LT后存活率方面的种族或民族差异：我们使用 TriNetX 数据库回顾性地识别了 2012 年至 2022 年期间患有 HCC（ICD-10 C22.0、C22.8）并接受了 LT（CPT 编码 47,135、47,140、47,140、47,141、47,142）治疗的患者，并比较了不同种族和民族亚群的治疗效果：大多数患者是白种人（2403/2901，84.8%），其次是非裔美国人（267/2901，9.2%）和西班牙裔/亚洲人（231/2901，7.9%）。在 5 年的随访中，我们发现非裔美国人和高加索人患者的死亡率[HR = 1.087 (95% CI 0.76, 1.56, p = 0.59)]以及西班牙裔/亚洲人和高加索人患者的死亡率[HR = 1.14 (95% CI 0.73, 1.78, p = 0.10)]没有显著差异：这些结果表明，严格执行旨在确保公平获得 LT 的政策可能有助于缩小 HCC 总体预后的差距。

{"title":"Racial and Ethnic Differences in Liver Transplantation and Post–Liver Transplant Survival Among Patients With Hepatocellular Carcinoma","authors":"Udhayvir S. Grewal, Apoorva K. Chandar, Shiva J. Gaddam, Abdul Rahman Al Armashi, Akram Alkreshi, Subhash C. Garikipati","doi":"10.1002/cam4.70298","DOIUrl":"10.1002/cam4.70298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Racial and ethnic disparities in diagnosis and overall outcomes for HCC are well known. We present updated real-world data on racial or ethnic differences in LT and post-LT survival among patients with HCC in a large population-based database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used the TriNetX database to retrospectively identify patients who had HCC (ICD-10 C22.0, C22.8) and underwent LT (CPT codes 47,135, 47,140, 47,140, 47,141, 47,142) from 2012 to 2022 and compared outcomes across racial and ethnic subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Majority of the patients were Caucasians (2403/2901, 84.8%), followed by African Americans (267/2901, 9.2%) Hispanic/Asian (231/2901, 7.9%). At follow up of 5 years, we noted no significant difference in mortality between AA and Caucasian patients [HR = 1.087 (95% CI 0.76, 1.56, <i>p</i> = 0.59)] as well as Hispanic/Asian and Caucasian patients [HR = 1.14 (95% CI 0.73, 1.78, <i>p</i> = 0.10)].</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results indicate that stringent implementation of policies aimed at ensuring equitable access to LT may contribute to bridging disparities in overall outcomes in HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 Correlation Between the Natural Course, Pathologic Properties With Ki-67 Expression in Lung Adenocarcinoma Presenting as Ground-Glass Nodules 表现为磨玻璃结节的肺腺癌的自然病程、病理特性与 Ki-67 表达之间的相关性

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-05 DOI: 10.1002/cam4.70390

Shaohui Huang, Huanhuan Zhou, Chenchen Lin, Ziqi Wang, Lijun Shen, Ya Sun, Meihui Wei, Zhiwei Xu, Xiaoju Zhang

Background

With the increasing use of lung cancer screening, the detection of ground glass nodules (GGNs) has risen. However, the natural course of GGNs and their relationship to pathologic features remains unclear. Differentiating between invasive and pre-invasive lesions based on GGN growth may improve clinical intervention timing. Ki-67, a proliferation marker, holds value in assessing tumor malignancy. This study analyzes the association between GGN growth, pathology, and Ki-67 expression to provide new insights into early-stage lung cancer management.

Methods

We retrospectively evaluated 183 GGNs with at least two preoperative CT scans. Nodule location, type, natural course, and volume doubling time (VDT) were compared between invasive adenocarcinoma (IAC) and pre-IAC groups. We also assessed differences in Ki-67 expression and correlated VDT with Ki-67 levels.

Results

A total of 183 nodules were finally included; gender, nodule location, smoking history, and duration of follow-up did not differ between the IAC group and the pre-IAC group, whereas age was statistically different between the two groups. Of the 183 nodules, 52 showed growth and the predominant pathologic type was IAC, these IACs showed more PSN in nodule type, while the IAC group showed more significant differences in nodule type, nodules growth, and VDT than the pre-IAC group. There were also differences in pathologic type and VDT between different Ki-67 expression groups, and Ki-67 expression gradually increased as VDT decreased.

Conclusion

Lung adenocarcinoma (LUAD) presenting as GGNs exhibit distinct natural courses among pathologic subtypes. VDT effectively distinguishes these growth characteristics, with IACs showing shorter VDT. The significant correlation between VDT and Ki-67 expression suggests that combining these parameters may provide valuable insights into the biological behavior and invasiveness of LUAD.

背景：随着肺癌筛查的日益普及，磨玻璃结节（GGN）的检出率也在上升。然而，GGN 的自然病程及其与病理特征的关系仍不清楚。根据 GGN 的生长情况来区分浸润性病灶和浸润前病灶可改善临床干预时机。Ki-67是一种增殖标记物，在评估肿瘤恶性程度方面具有重要价值。本研究分析了GGN生长、病理和Ki-67表达之间的关联，以期为早期肺癌的治疗提供新的见解：我们回顾性评估了 183 个至少有两次术前 CT 扫描的 GGN。比较了浸润性腺癌（IAC）组与 IAC 前组的结节位置、类型、自然病程和体积倍增时间（VDT）。我们还评估了 Ki-67 表达的差异，并将 VDT 与 Ki-67 水平相关联：IAC组和IAC前组在性别、结节位置、吸烟史和随访时间上没有差异，而年龄在两组之间存在统计学差异。在 183 个结节中，52 个出现生长，主要病理类型为 IAC，这些 IAC 在结节类型上表现出更多的 PSN，而 IAC 组在结节类型、结节生长和 VDT 上的差异比 IAC 前组更显著。不同Ki-67表达组的病理类型和VDT也存在差异，Ki-67表达随着VDT的降低而逐渐增加：结论：以 GGNs 为表现形式的肺腺癌（LUAD）在不同病理亚型中表现出不同的自然病程。VDT可有效区分这些生长特征，其中IAC的VDT较短。VDT与Ki-67表达之间的显着相关性表明，将这些参数结合起来可为了解LUAD的生物学行为和侵袭性提供有价值的信息。

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引用次数: 0

Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma 联合抑制组蛋白甲基转移酶EZH2和DOT1L是治疗神经母细胞瘤的有效方法。

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2024-11-05 DOI: 10.1002/cam4.70082

Janith A. Seneviratne, Daenikka Ravindrarajah, Daniel R. Carter, Vicki Zhai, Amit Lalwani, Sukriti Krishan, Anushree Balachandran, Ernest Ng, Ruby Pandher, Matthew Wong, Tracy L. Nero, Shudong Wang, Murray D. Norris, Michelle Haber, Tao Liu, Michael W. Parker, Belamy B. Cheung, Glenn M. Marshall

Background

The child cancer, neuroblastoma (NB), is characterised by a low incidence of mutations and strong oncogenic embryonal driver signals. Many new targeted epigenetic modifier drugs have failed in human trials as monotherapy.

Methods

We performed a high-throughput, combination chromatin-modifier drug screen against NB cells. We screened 13 drug candidates in 78 unique combinations.

Results

We found that the combination of two histone methyltransferase (HMT) inhibitors: GSK343, targeting EZH2, and SGC0946, targeting DOT1L, demonstrated the strongest synergy across 8 NB cell lines, with low normal fibroblast toxicity. High mRNA expression of both EZH2 and DOT1L in NB tumour samples correlated with the poorest patient survival. Combination HMT inhibitor treatment caused activation of ATF4-mediated endoplasmic reticulum (ER) stress responses. In addition, glutathione and several amino acids were depleted by HMT inhibitor combination on mass spectrometry analysis. The combination of SGC0946 and GSK343 reduced tumour growth in comparison to single agents.

Conclusion

Our results support further investigation of HMT inhibitor combinations as a therapeutic approach in NB.

背景：儿童癌症--神经母细胞瘤（NB）的特点是突变发生率低，且具有较强的致癌胚胎驱动信号。许多新的靶向表观遗传修饰药物作为单一疗法在人体试验中均告失败：我们针对 NB 细胞进行了高通量、联合染色质修饰药物筛选。我们筛选了 13 种候选药物的 78 种独特组合：结果：我们发现两种组蛋白甲基转移酶（HMT）抑制剂的组合结果：我们发现两种组蛋白甲基转移酶（HMT）抑制剂的组合：靶向 EZH2 的 GSK343 和靶向 DOT1L 的 SGC0946，在 8 种 NB 细胞系中表现出最强的协同作用，而对正常成纤维细胞的毒性较低。NB 肿瘤样本中 EZH2 和 DOT1L 的高 mRNA 表达与最差的患者生存率相关。HMT抑制剂联合治疗可激活ATF4介导的内质网（ER）应激反应。此外，在质谱分析中，谷胱甘肽和几种氨基酸被HMT抑制剂联合使用所消耗。与单药相比，SGC0946和GSK343联合使用可减少肿瘤生长：我们的研究结果支持进一步研究 HMT 抑制剂组合作为 NB 的一种治疗方法。

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引用次数: 0