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Breast cancer immunotherapy: Realities and advances 乳腺癌免疫疗法:现实与进步
Pub Date : 2024-09-22 DOI: 10.1002/cai2.140
Aixa Medina, Jeismar Carballo, Eglys González-Marcano, Isaac Blanca, Ana F. Convit

Breast cancer (BC) is the most common malignant tumor and the main cause of death in women worldwide. With increased knowledge regarding tumor escape mechanisms and advances in immunology, many new antitumor strategies such as nonspecific immunotherapies, monoclonal antibodies, anticancer vaccines, and oncolytic viruses, among others, make immunotherapy a promising approach for the treatment of BC. However, these approaches still require meticulous assessment and readjustment as resistance and modest response rates remain important barriers. In this article, we aim to summarize the most recent data available in BC immunotherapy to include the results of ongoing clinical trials and approved therapies used as monotherapies or in combination with conventional treatments.

乳腺癌(BC)是最常见的恶性肿瘤,也是全球女性的主要死因。随着对肿瘤逃逸机制认识的加深和免疫学的进步,许多新的抗肿瘤策略,如非特异性免疫疗法、单克隆抗体、抗癌疫苗和溶瘤病毒等,使免疫疗法成为治疗乳腺癌的一种前景广阔的方法。然而,这些方法仍然需要细致的评估和重新调整,因为耐药性和反应率不高仍然是重要的障碍。在本文中,我们将总结BC免疫疗法的最新数据,包括正在进行的临床试验结果和已获批准的作为单一疗法或与传统疗法联合使用的疗法。
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引用次数: 0
Inetetamab combined with sirolimus and chemotherapy for the treatment of HER2-positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR pathway after trastuzumab treatment 伊奈他单抗联合西罗莫司和化疗治疗曲妥珠单抗治疗后PI3K/Akt/mTOR通路异常激活的HER2阳性转移性乳腺癌患者
Pub Date : 2024-09-19 DOI: 10.1002/cai2.145
Qiao Li, Dan Lv, Xiaoying Sun, Mengyuan Wang, Li Cai, Feng Liu, Chenghui Li, Jiuda Zhao, Jing Sun, Yehui Shi, Fei Ma

Background

We explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2 (HER2)-positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR (PAM) pathway after trastuzumab treatment.

Methods

For this prospective multicenter clinical study, HER2-positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022. Patients were randomly assigned to a trial or control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, while the control group patients received pyrotinib and chemotherapy. The RECIST v1.1 standard was used to evaluate efficacy. Descriptive statistics were used to summarize the clinicopathological features, and the Kaplan–Meier method was used to generate survival curves. The log-rank test was used to compare progression-free survival (PFS) between the two groups.

Results

A total of 59 HER2-positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included, of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment. The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group, with no statistically significant difference (p = 0.507). The objective response rates were 27.3% for the inetetamab group and 29.4% for the pyrotinib group. The safety assessment indicated that the adverse event (AE) incidences were 86.1% (31/36) in the inetetamab group and 78.9 (15/19) in the pyrotinib group, with 9 (25%) and four (21.1%) Grade 3/4 AEs in the inetetamab and pyrotinib groups, respectively.

Conclusions

For metastatic HER2-positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway-activated metastatic HER2-positive breast cancer patients.

背景 我们探讨了伊奈他单抗联合西罗莫司和化疗治疗曲妥珠单抗治疗后PI3K/Akt/mTOR(PAM)通路异常激活的人表皮因子受体2(HER2)阳性转移性乳腺癌患者的有效性和安全性。 方法 在这项前瞻性多中心临床研究中,2021 年 7 月至 2022 年 9 月期间,招募了经组织学或外周血基因检测证实存在 PAM 通路突变的 HER2 阳性转移性乳腺癌患者。患者被随机分配到试验组和对照组。试验组患者接受伊奈他单抗联合西罗莫司和化疗,对照组患者接受吡罗替尼和化疗。疗效评估采用 RECIST v1.1 标准。描述性统计用于总结临床病理特征,Kaplan-Meier法用于生成生存曲线。采用对数秩检验比较两组患者的无进展生存期(PFS)。 结果 共纳入59例PAM通路异常激活的HER2阳性转移性乳腺癌患者,其中37例接受依替他单抗联合西罗莫司和化疗治疗,22例接受吡罗替尼和化疗治疗。依奈他单抗组的中位生存期为4.64个月,派罗替尼组的中位生存期为5.69个月,差异无统计学意义(P = 0.507)。依奈他单抗组和派罗替尼组的客观反应率分别为27.3%和29.4%。安全性评估显示,依奈他单抗组的不良事件(AE)发生率为86.1%(31/36),派罗替尼组的不良事件发生率为78.9%(15/19),其中依奈他单抗组和派罗替尼组分别发生了9起(25%)和4起(21.1%)3/4级不良事件。 结论 对于PAM通路激活异常且既往接受过曲妥珠单抗治疗的转移性HER2阳性乳腺癌患者,依奈他单抗联合西罗莫司与化疗的疗效等同于吡罗替尼与化疗的疗效。因此,该方案可作为PAM通路激活的转移性HER2阳性乳腺癌患者的治疗选择。
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引用次数: 0
Multiomics and single-cell sequencings reveal the specific biological characteristics of low Ki-67 triple-negative breast cancer 多组学和单细胞测序揭示低 Ki-67 三阴性乳腺癌的特殊生物学特征
Pub Date : 2024-09-19 DOI: 10.1002/cai2.146
Boyue Han, Xiangchen Han, Hong Luo, Javaria Nasir, Chao Chen, Zhiming Shao, Hong Ling, Xin Hu

Background

Triple-negative breast cancer (TNBC) displays high heterogeneity. The majority of TNBC cases are characterized by high Ki-67 expression. TNBC with low Ki-67 expression accounts for only a small fraction of cases and has been relatively less studied.

Methods

This study analyzed a large single-center multiomics TNBC data set, combined with a single-cell data set. The clinical, genomic, and metabolic characteristics of patients with low Ki-67 TNBC were analyzed.

Results

The clinical and pathological characteristics were analyzed in 2217 TNBC patients. Low Ki-67 TNBC was associated with a higher patient age at diagnosis, a lower proportion of invasive ductal carcinoma, increased alterations in the PI3K-AKT-mTOR pathway, upregulated lipid metabolism pathways, and enhanced infiltration of M2 macrophages. High Ki-67 TNBC exhibited a higher prevalence of TP53 gene mutations, elevated nucleotide metabolism, and increased infiltration of M1 macrophages.

Conclusions

We identified specific genomic and metabolic characteristics unique to low Ki-67 TNBC, which have implications for the development of precision therapies and patient stratification strategies.

背景 三阴性乳腺癌(TNBC)具有高度异质性。大多数 TNBC 病例以高 Ki-67 表达为特征。低 Ki-67 表达的 TNBC 仅占病例的一小部分,研究相对较少。 方法 本研究分析了一个大型单中心多组学 TNBC 数据集和一个单细胞数据集。分析了低 Ki-67 TNBC 患者的临床、基因组和代谢特征。 结果 分析了 2217 例 TNBC 患者的临床和病理特征。低 Ki-67 TNBC 与患者确诊年龄较高、浸润性导管癌比例较低、PI3K-AKT-mTOR 通路改变增加、脂质代谢通路上调以及 M2 巨噬细胞浸润增强有关。高 Ki-67 TNBC 表现出更高的 TP53 基因突变发生率、核苷酸代谢升高以及 M1 巨噬细胞浸润增加。 结论 我们发现了低Ki-67 TNBC特有的基因组和代谢特征,这对开发精准疗法和患者分层策略具有重要意义。
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引用次数: 0
Role of liquid–liquid phase separation in cancer: Mechanisms and therapeutic implications 液-液相分离在癌症中的作用:机制和治疗意义
Pub Date : 2024-09-17 DOI: 10.1002/cai2.144
Xuesong Li, Zhuo Yu

Liquid–liquid phase separation (LLPS) has emerged as a pivotal biological phenomenon involved in various cellular processes, including the formation of membrane-less organelles and the regulation of biomolecular condensates through precise spatiotemporal coordination of signaling pathways in cells. Dysregulation of LLPSs results in aberrant biomolecular condensates, which are widely implicated in tumorigenesis and cancer progression. Here, we comprehensively summarize the multifaceted roles of LLPS in tumor biology from the perspective of cancer hallmarks, including genomic stability, metabolic reprogramming progression, ferroptosis, and metastasis, to unveil the intricate mechanisms by which LLPS occurs in tumorigenesis. We discuss current discoveries related to therapeutic involvement and potential clinical applications of LLPS in cancer treatment, highlighting the potential of targeting LLPS-driven processes as novel therapeutic strategies. Additionally, we discuss the challenges associated with new approaches for cancer treatment based on LLPS. This in-depth discussion of the impact of LLPS on fundamental aspects of tumor biology provides new insights into overcoming cancer.

液-液相分离(LLPS)已成为一种关键的生物现象,它涉及多种细胞过程,包括无膜细胞器的形成以及通过精确时空协调细胞内信号通路对生物分子凝聚体的调控。LLPSs 失调会导致生物分子凝聚物异常,而生物分子凝聚物异常与肿瘤发生和癌症进展有着广泛的联系。在此,我们从基因组稳定性、代谢重编程进展、铁变态和转移等癌症标志的角度,全面总结了 LLPS 在肿瘤生物学中的多方面作用,揭示了 LLPS 在肿瘤发生中的复杂机制。我们讨论了当前与 LLPS 在癌症治疗中的治疗参与和潜在临床应用相关的发现,强调了以 LLPS 驱动的过程为靶点作为新型治疗策略的潜力。此外,我们还讨论了基于 LLPS 的癌症治疗新方法所面临的挑战。深入探讨 LLPS 对肿瘤生物学基本方面的影响,为战胜癌症提供了新的见解。
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引用次数: 0
A pan-cancer analysis of Wnt family member 7B in human cancers 对人类癌症中 Wnt 家族成员 7B 的泛癌症分析
Pub Date : 2024-09-09 DOI: 10.1002/cai2.139
Rui Wang, Ni-sha Wu, Li Wang, Zhi-zhao Zhang, Cheng-fang Wang, Yan Wang, Yan Liang, Yi Zhang, Xiao-wei Qi

Background

Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored.

Methods

In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors.

Results

Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers.

Conclusion

We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

背景 以前的研究强调了 Wnt7B 在乳腺癌、胰腺癌和胃癌等各种癌症的发展过程中的关键作用。然而,有关 Wnt7B 参与作用的研究往往局限于特定的肿瘤类型,明显缺乏横跨多种癌症类型的综合性研究。Wnt7B作为癌症诊断或预后生物标志物的潜力尚未得到充分挖掘。 方法 在本研究中,我们结合生物信息学和免疫组化分析,研究了 Wnt7B 在多种肿瘤的癌组织和邻近非癌组织中的表达模式和功能。 结果 我们的数据表明,Wnt7B 可作为某些癌症的新型预后生物标志物和治疗靶点。 结论 我们发现在大多数癌症病例中,Wnt7B 的表达水平明显上调。此外,Wnt7B 可通过调节肿瘤微环境、免疫细胞浸润和肿瘤干性等因素影响癌症预后。此外,我们还研究了抗癌药物敏感性与 Wnt7B 表达之间的关联,这有助于开发更精确的临床疗法。
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引用次数: 0
Chinese expert consensus on an innovative patient-centered approach to diagnosis and treatment of cancer 中国专家就以患者为中心的癌症诊断和治疗创新方法达成共识。
Pub Date : 2024-07-30 DOI: 10.1002/cai2.137
Hongnan Mo, Ruiqi Zhong, Fei Ma

Patient-centered care (PCC) is an innovative approach to the diagnosis and treatment of malignancy that aims to improve patients' experience during the management of their disease. However, despite growing interest, the concept and specifics of PCC remain unclear. This consensus document addresses this gap by providing a literature review and a clear definition of PCC and outlines its main components as observed in real-world practice. These components include daytime diagnostic and treatment procedures, in-hospital and community-based infusion centers, home-based diagnostic and treatment services, smart healthcare solutions, and integration of traditional Chinese medicine. This document delves into the implementation of PCC and explores its potential benefits.

以患者为中心的护理(PCC)是诊断和治疗恶性肿瘤的一种创新方法,旨在改善患者在疾病治疗过程中的体验。然而,尽管人们对 PCC 的兴趣与日俱增,但其概念和具体内容仍不明确。本共识文件通过提供文献综述和明确的 PCC 定义来弥补这一不足,并概述了在实际实践中观察到的 PCC 的主要组成部分。这些组成部分包括日间诊断和治疗程序、院内和社区输液中心、家庭诊断和治疗服务、智能医疗解决方案以及传统中医药的整合。本文件深入探讨了 PCC 的实施情况,并探讨了其潜在的益处。
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引用次数: 0
Explainable artificial intelligence in breast cancer detection and risk prediction: A systematic scoping review 可解释人工智能在乳腺癌检测和风险预测中的应用:系统性范围审查
Pub Date : 2024-07-03 DOI: 10.1002/cai2.136
Amirehsan Ghasemi, Soheil Hashtarkhani, David L. Schwartz, Arash Shaban-Nejad

With the advances in artificial intelligence (AI), data-driven algorithms are becoming increasingly popular in the medical domain. However, due to the nonlinear and complex behavior of many of these algorithms, decision-making by such algorithms is not trustworthy for clinicians and is considered a black-box process. Hence, the scientific community has introduced explainable artificial intelligence (XAI) to remedy the problem. This systematic scoping review investigates the application of XAI in breast cancer detection and risk prediction. We conducted a comprehensive search on Scopus, IEEE Explore, PubMed, and Google Scholar (first 50 citations) using a systematic search strategy. The search spanned from January 2017 to July 2023, focusing on peer-reviewed studies implementing XAI methods in breast cancer datasets. Thirty studies met our inclusion criteria and were included in the analysis. The results revealed that SHapley Additive exPlanations (SHAP) is the top model-agnostic XAI technique in breast cancer research in terms of usage, explaining the model prediction results, diagnosis and classification of biomarkers, and prognosis and survival analysis. Additionally, the SHAP model primarily explained tree-based ensemble machine learning models. The most common reason is that SHAP is model agnostic, which makes it both popular and useful for explaining any model prediction. Additionally, it is relatively easy to implement effectively and completely suits performant models, such as tree-based models. Explainable AI improves the transparency, interpretability, fairness, and trustworthiness of AI-enabled health systems and medical devices and, ultimately, the quality of care and outcomes.

随着人工智能(AI)的发展,数据驱动算法在医疗领域越来越受欢迎。然而,由于许多此类算法的非线性和复杂行为,临床医生对此类算法的决策并不信任,认为这是一个黑箱过程。因此,科学界引入了可解释人工智能(XAI)来解决这一问题。本系统性范围综述调查了 XAI 在乳腺癌检测和风险预测中的应用。我们采用系统性检索策略,在 Scopus、IEEE Explore、PubMed 和 Google Scholar(前 50 篇引文)上进行了全面检索。搜索时间跨度为 2017 年 1 月至 2023 年 7 月,重点关注在乳腺癌数据集中采用 XAI 方法的同行评审研究。有 30 项研究符合我们的纳入标准并被纳入分析。结果显示,在乳腺癌研究中,SHapley Additive exPlanations(SHAP)在使用、解释模型预测结果、生物标记物的诊断和分类以及预后和生存分析方面是最重要的模型诊断 XAI 技术。此外,SHAP 模型主要解释了基于树的集合机器学习模型。最常见的原因是,SHAP 与模型无关,这使得它在解释任何模型预测结果时既受欢迎又有用。此外,它相对容易有效实现,完全适合性能良好的模型,如基于树的模型。可解释的人工智能提高了人工智能医疗系统和医疗设备的透明度、可解释性、公平性和可信度,并最终提高了医疗质量和结果。
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引用次数: 0
Radiomics models to predict bone marrow metastasis of neuroblastoma using CT 利用CT预测神经母细胞瘤骨髓转移的放射组学模型
Pub Date : 2024-06-28 DOI: 10.1002/cai2.135
Xiong Chen, Qinchang Chen, Yuanfang Liu, Ya Qiu, Lin Lv, Zhengtao Zhang, Xuntao Yin, Fangpeng Shu

Background

Bone marrow is the leading site for metastasis from neuroblastoma and affects the prognosis of patients with neuroblastoma. However, the accurate diagnosis of bone marrow metastasis is limited by the high spatial and temporal heterogeneity of neuroblastoma. Radiomics analysis has been applied in various cancers to build accurate diagnostic models but has not yet been applied to bone marrow metastasis of neuroblastoma.

Methods

We retrospectively collected information from 187 patients pathologically diagnosed with neuroblastoma and divided them into training and validation sets in a ratio of 7:3. A total of 2632 radiomics features were retrieved from venous and arterial phases of contrast-enhanced computed tomography (CT), and nine machine learning approaches were used to build radiomics models, including multilayer perceptron (MLP), extreme gradient boosting, and random forest. We also constructed radiomics-clinical models that combined radiomics features with clinical predictors such as age, gender, ascites, and lymph gland metastasis. The performance of the models was evaluated with receiver operating characteristics (ROC) curves, calibration curves, and risk decile plots.

Results

The MLP radiomics model yielded an area under the ROC curve (AUC) of 0.97 (95% confidence interval [CI]: 0.95–0.99) on the training set and 0.90 (95% CI: 0.82–0.95) on the validation set. The radiomics-clinical model using an MLP yielded an AUC of 0.93 (95% CI: 0.89–0.96) on the training set and 0.91 (95% CI: 0.85–0.97) on the validation set.

Conclusions

MLP-based radiomics and radiomics-clinical models can precisely predict bone marrow metastasis in patients with neuroblastoma.

背景:骨髓是神经母细胞瘤转移的主要部位,影响神经母细胞瘤患者的预后。然而,由于神经母细胞瘤在空间和时间上的高度异质性,骨髓转移的准确诊断受到了限制。放射组学分析已应用于多种癌症,以建立准确的诊断模型,但尚未应用于神经母细胞瘤的骨髓转移:我们回顾性地收集了 187 例经病理诊断为神经母细胞瘤患者的信息,并按 7:3 的比例将其分为训练集和验证集。我们从造影剂增强计算机断层扫描(CT)的静脉期和动脉期提取了共 2632 个放射组学特征,并使用九种机器学习方法建立放射组学模型,包括多层感知器(MLP)、极梯度提升和随机森林。我们还构建了放射组学-临床模型,将放射组学特征与年龄、性别、腹水和淋巴腺转移等临床预测因素相结合。我们用接收者操作特征曲线(ROC)、校准曲线和风险十等分图来评估模型的性能:MLP 放射组学模型在训练集上的 ROC 曲线下面积(AUC)为 0.97(95% 置信区间 [CI]:0.95-0.99),在验证集上的 ROC 曲线下面积(AUC)为 0.90(95% 置信区间 [CI]:0.82-0.95)。使用 MLP 的放射组学-临床模型在训练集上的 AUC 为 0.93(95% CI:0.89-0.96),在验证集上的 AUC 为 0.91(95% CI:0.85-0.97):基于MLP的放射组学和放射组学-临床模型可以准确预测神经母细胞瘤患者的骨髓转移。
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引用次数: 0
High-fat-diet-induced obesity promotes simultaneous progression of lung cancer and atherosclerosis in apolipoprotein E-knockout mice 高脂饮食诱发的肥胖会同时促进载脂蛋白 E 基因敲除小鼠肺癌和动脉粥样硬化的发展
Pub Date : 2024-06-05 DOI: 10.1002/cai2.127
Yihao Wang, Kaixin Yan, Han Duan, Ning Tao, Shaoning Zhu, Yuning Zhang, Yonggang You, Zhen Zhang, Hua Wang, Shunying Hu

Background

Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co-exist in the same individual. The present study aimed to investigate the role of high-fat-diet (HFD)-induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E-knockout (ApoE−/−) mice.

Methods

Male ApoE−/− mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence-activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured.

Results

At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer (p = 0.0004), heavier tumors (p = 0.0235), more metastatic cancer in the lungs (p < 0.0001), a larger area of lung involved in metastatic cancer (p = 0.0031), and larger areas of atherosclerosis in the aorta (p < 0.0001). At Week 12, serum LOX-1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group (p = 0.0002, p = 0.0029, p = 0.0480, and p = 0.0106, respectively); this trend persisted until Week 15 (p = 0.0014, p = 0.0012, p = 0.0001, and p = 0.0204).

Conclusions

In this study, HFD-induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD-induced upregulation of LOX-1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.

背景 临床研究表明,动脉粥样硬化性心血管疾病和癌症往往在同一个人身上同时存在。本研究旨在通过载脂蛋白 E 基因敲除(ApoE-/-)小鼠,探讨高脂饮食(HFD)诱导肥胖在两种疾病并存中的作用及其内在机制。 方法 雄性载脂蛋白E-/-小鼠以高密度脂蛋白饮食(HFD)或正常饮食(ND)喂养15周。第 13 周的第一天,在小鼠右腋窝皮下接种 Lewis 肺癌细胞。第12周和第15周,用酶联免疫吸附试验测定血清凝集素样氧化低密度脂蛋白受体-1(LOX-1)和血管内皮生长因子水平,用荧光激活细胞分选法测定血液中的单核细胞和巨噬细胞。第 15 周时,测量局部皮下肺癌和转移性肺癌的体积和重量以及主动脉粥样硬化的程度。 结果 第15周时,与ND组小鼠相比,HFD组小鼠的局部皮下癌体积更大(p = 0.0004)、肿瘤更重(p = 0.0235)、肺部转移癌更多(p < 0.0001)、转移癌涉及的肺部面积更大(p = 0.0031)、主动脉粥样硬化面积更大(p < 0.0001)。第 12 周时,HFD 组的血清 LOX-1、血清血管内皮生长因子以及血液中单核细胞和巨噬细胞的比例显著高于 ND 组(分别为 p = 0.0002、p = 0.0029、p = 0.0480 和 p = 0.0106);这一趋势一直持续到第 15 周(p = 0.0014、p = 0.0012、p = 0.0001 和 p = 0.0204)。 结论 在本研究中,HFD 诱导的肥胖可同时促进肺癌和动脉粥样硬化在同一只小鼠中的发展。高频分解膳食诱导的 LOX-1 上调可能通过炎症反应和血管内皮生长因子在这两种疾病的同时进展中发挥了重要作用。
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引用次数: 0
Efficacy and safety of first-line regimens for advanced HER2-positive breast cancer: A Bayesian network meta-analysis 晚期 HER2 阳性乳腺癌一线治疗方案的疗效和安全性:贝叶斯网络荟萃分析
Pub Date : 2024-05-22 DOI: 10.1002/cai2.126
Lixi Li, Yun Wu, Bo Lan, Fei Ma

Background

The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first-line therapy. However, with the development of newer treatment regimens, there is a lack of evidence regarding which is the optimal treatment strategy. The aim of this network meta-analysis was to evaluate the efficacy and safety of first-line regimens for advanced HER2-positive breast cancer by indirect comparisons.

Methods

A systematic review and Bayesian network meta-analysis were conducted. The PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published through to December 2023. The hazard ratio (HR) and 95% credible interval (CrI) were used to compare progression-free survival (PFS) between treatments, and the odds ratio and 95% CrI were used to compare the objective response rate (ORR) and safety.

Results

Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed. Compared with the traditional trastuzumab and docetaxel regimen, PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen (HR: 0.41, 95% CrI: 0.22–0.75) and the pertuzumab and trastuzumab plus docetaxel regimen (HR: 0.65, 95% CrI: 0.43–0.98). Consistent with the results for PFS, the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen. The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR. Comparable results were found for grade ≥3 AE rates of ≥10%.

Conclusions

Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first-line therapy for patients with HER2-positive breast cancer.

背景晚期人表皮生长因子受体 2 (HER2) 阳性乳腺癌目前的一线治疗标准是百妥珠单抗加曲妥珠单抗和多西他赛。然而,随着新治疗方案的不断开发,关于哪种治疗方法是最佳治疗策略的证据仍然缺乏。本网络荟萃分析旨在通过间接比较评估晚期HER2阳性乳腺癌一线治疗方案的有效性和安全性。 方法 进行了系统综述和贝叶斯网络荟萃分析。在 PubMed、EMBASE 和 Cochrane Library 数据库中检索了截至 2023 年 12 月发表的相关文章。采用危险比(HR)和 95% 可信区间(CrI)来比较不同疗法的无进展生存期(PFS),采用几率比和 95% 可信区间(CrI)来比较客观反应率(ORR)和安全性。 结果 分析了20项随机临床试验,包括15种方案和7094名患者。与传统的曲妥珠单抗和多西他赛方案相比,吡罗替尼和曲妥珠单抗加多西他赛方案(HR:0.41,95% CrI:0.22-0.75)以及百妥珠单抗和曲妥珠单抗加多西他赛方案(HR:0.65,95% CrI:0.43-0.98)的PFS更长。与PFS结果一致,吡罗替尼和曲妥珠单抗加多西他赛方案以及pertuzumab和曲妥珠单抗加多西他赛方案的ORR优于传统的曲妥珠单抗和多西他赛方案。累积排名曲线下表面显示,在获得最佳PFS和ORR方面,吡罗替尼和曲妥珠单抗加多西他赛方案最有可能排名第一。≥10%的≥3级AE发生率也有类似结果。 结论 我们的研究结果表明,对于HER2阳性乳腺癌患者,吡罗替尼和曲妥珠单抗加多西他赛方案最有可能成为最佳一线疗法。
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Cancer Innovation
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