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Dynamics of epithelial–mesenchymal plasticity driving cancer drug resistance 驱动癌症耐药性的上皮-间充质可塑性动态变化
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.07.002
Rashmi Bangarh , Reena V. Saini , Adesh K. Saini , Tejveer Singh , Hemant Joshi , Seema Ramniwas , Moyad Shahwan , Hardeep Singh Tuli
Epithelial–mesenchymal transition (EMT) promotes several cancers by increasing tumor cell motility, disrupting epithelial cell phenotypes, apical–basal polarity, and intracellular connections, and enhancing tumor resistance to immunotherapy and chemotherapy. Mesenchymal–epithelial transition (MET), the opposite of EMT, causes tumor metastasis. EMT drives primary tumor cells, whereas MET inhibits them. Importantly, the complex network of EMT includes cell–cell interactions in the tumor microenvironment. Transcription factors, post-translational regulation, cytokine-mediated signaling, and microRNAs control EMT. In this review, we discussed how molecular mechanisms, signaling networks, and epithelial/mesenchymal states affect cancer treatment resistance and the tumor microenvironment. Research on immunotherapy and chemotherapy problems associated with EMT suggests that targeting EMT might be a potential cancer treatment resistance strategy.
上皮-间质转化(epithelial - mesenchymal transition, EMT)通过增加肿瘤细胞运动、破坏上皮细胞表型、顶基极性和细胞内连接,以及增强肿瘤对免疫治疗和化疗的抗性,促进多种癌症的发生。与EMT相反的间充质-上皮转化(Mesenchymal-epithelial transition, MET)导致肿瘤转移。EMT驱动原发肿瘤细胞,而MET抑制它们。重要的是,EMT的复杂网络包括肿瘤微环境中的细胞-细胞相互作用。转录因子、翻译后调控、细胞因子介导的信号传导和microrna控制EMT。在这篇综述中,我们讨论了分子机制、信号网络和上皮/间充质状态如何影响癌症治疗耐药性和肿瘤微环境。对与EMT相关的免疫治疗和化疗问题的研究表明,靶向EMT可能是一种潜在的癌症耐药治疗策略。
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引用次数: 0
Predictive models and therapeutic strategies for breast cancer 乳腺癌的预测模型和治疗策略
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.06.008
Lei Liu, Peng Yuan, Xue Wang
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引用次数: 0
Factors affecting the place of death in patients with liver cancer in China, 2013–2020: A population-based study 2013-2020年影响中国肝癌患者死亡地点的因素:基于人口的研究
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.04.001
Xiaosheng Ding , Weiwei Shi , Jinlei Qi , Juan An , Weiran Xu , Hui Shi , Xixi Zheng , Xiaoyan Li

Background

Despite the country's substantial liver cancer burden, there is limited research on the factors influencing the place of death (POD) of patients with liver cancer in China. This study aimed to delineate POD distribution among patients with liver cancer, identify the factors associated with hospital deaths, and offer valuable insights for the government to develop healthcare policies.

Methods

Data from 2013 to 2020 were obtained from the National Mortality Surveillance System (NMSS) of China. This analysis focused on the distribution of POD among individuals who succumbed to liver cancer. Variations in characteristic distributions across different categories were evaluated using a chi-squared test. We also applied a multilevel logistic regression analysis to identify the factors associated with hospital liver cancer deaths. The proportional change in variance was computed to evaluate the contributions of different factors in the model.

Results

From 2013 to 2020, the NMSS reported a total of 608,789 liver cancer-related deaths, of which 440,079 (72.29%) died at home, and 158,291 (26.00%) died in the hospital. Home remained the preferred POD among patients with liver cancer. The results demonstrated that female patients, aged between 0 and 14 years, of Han ethnicity, living in urban areas, unmarried, highly educated, and either employed in a professional, staff, or civil servant capacity, or retired patients tended to end their lives in the hospital.

Conclusions

In China, home continues to be the predominant POD for patients with liver cancer, with demographic and socioeconomic factors significantly influencing whether a hospital is their POD. Enhancing healthcare policymakers' understanding of the factors influencing the place of death for patients with liver cancer may assist in creating a more equitable distribution of healthcare resources and providing a variety of choices for minorities with distinct preferences for end-of-life care.
尽管中国的肝癌负担很大,但对中国肝癌患者死亡地点(POD)的影响因素的研究有限。本研究旨在描述肝癌患者POD分布,确定与医院死亡相关的因素,并为政府制定医疗保健政策提供有价值的见解。方法2013 - 2020年数据来自中国国家死亡率监测系统(NMSS)。这一分析集中在死于肝癌的个体中POD的分布。使用卡方检验评估不同类别间特征分布的变化。我们还应用了多水平logistic回归分析来确定与医院肝癌死亡相关的因素。计算方差的比例变化来评估模型中不同因素的贡献。结果2013 - 2020年,NMSS共报告肝癌相关死亡608,789例,其中家中死亡440,079例(72.29%),医院死亡158,291例(26.00%)。Home仍然是肝癌患者首选的POD。结果表明,年龄在0 - 14岁之间、居住在城市地区、未婚、受过高等教育、从事专业、工作人员或公务员工作的女性患者或退休患者倾向于在医院结束生命。结论在中国,家庭仍然是肝癌患者最主要的就诊地点,人口统计学和社会经济因素显著影响着医院是否是肝癌患者的就诊地点。加强医疗政策制定者对影响肝癌患者死亡地点的因素的理解,可能有助于创造更公平的医疗资源分配,并为具有不同临终关怀偏好的少数群体提供多种选择。
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引用次数: 0
Cardiotoxicity in platinum-based chemotherapy: Mechanisms, manifestations, and management 铂类化疗的心脏毒性:机制、表现和处理
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.04.004
Betty Rachma , Merlyna Savitri , Henry Sutanto
Platinum-based chemotherapy, a cornerstone in the treatment of various malignancies, is often limited by its potential cardiotoxic effects. Understanding these effects is crucial for optimizing patient outcomes and guiding treatment decisions. This review explores the mechanisms, clinical manifestations, detection, management, and future directions in the research of cardiotoxicity associated with platinum-based chemotherapy. The mechanisms discussed here include oxidative stress, reactive oxygen species production, DNA damage, and alterations in signaling pathways. Clinical manifestations range from mild symptoms to severe complications, including Takotsubo cardiomyopathy, as highlighted by recent case studies. The role of diagnostic tools such as echocardiography, cardiac magnetic resonance imaging, and cardiac biomarkers in early detection is emphasized, underscoring the importance of regular cardiac monitoring. Management strategies focus on cardioprotective agents, alternative chemotherapy regimens, and emerging therapeutic approaches, including the potential of nano liposomal and cubosomal formulations. The review also delves into the future of personalized medicine in predicting and managing cardiotoxicity, advocating for ongoing research to mitigate these adverse effects. This comprehensive overview aims to enhance the understanding of cardiotoxicity in platinum-based chemotherapy, informing clinical practices and promoting patient-centric care.
以铂为基础的化疗是治疗各种恶性肿瘤的基石,但由于其潜在的心脏毒性作用而受到限制。了解这些影响对于优化患者预后和指导治疗决策至关重要。本文就铂类化疗引起心脏毒性的机制、临床表现、检测、处理及未来研究方向进行综述。这里讨论的机制包括氧化应激、活性氧产生、DNA损伤和信号通路的改变。最近的病例研究强调,临床表现从轻微症状到严重并发症,包括Takotsubo心肌病。强调了超声心动图、心脏磁共振成像和心脏生物标志物等诊断工具在早期检测中的作用,强调了定期心脏监测的重要性。管理策略侧重于心脏保护剂、替代化疗方案和新兴治疗方法,包括纳米脂质体和立方体制剂的潜力。这篇综述还深入探讨了个性化医疗在预测和管理心脏毒性方面的未来,并倡导正在进行的研究以减轻这些不良反应。本综述旨在提高对铂基化疗中心脏毒性的认识,为临床实践提供信息,促进以患者为中心的护理。
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引用次数: 0
Risk of autoimmunity, cancer seeding, and adverse events in human trials of whole-tissue autologous therapeutic vaccines 全组织自体治疗疫苗人体试验中的自身免疫风险、癌症播种和不良事件
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.05.003
Garrett Gianneschi , Anthony Scolpino , James Oleske

Background

Whole-tissue autologous therapeutic vaccines (WATVs) are a form of cancer immunotherapy that use a patient's own pathological tissue. Concerns exist regarding the potential of WATVs to induce autoimmunity or the spread of cancer; however, their adverse events (AEs) have not been adequately studied. This literature review primarily aimed to evaluate the risks of autoimmunity and cancer seeding associated with using WATVs in human clinical trials. Its secondary objectives included assessing the incidence of AEs graded 1–5 using the Common Terminology Criteria for Adverse Events v5.0.

Methods

The inclusion criteria were any clinical trial using human subjects in which at least part of the cancer vaccine was derived from the patient's own tumor tissue, which likely preserved the unique tumor-associated antigens (TAAs) present in the patient's tumor (i.e., whole-tissue). Tumor vaccine trials that used limited TAAs or highly processed tumor antigens were excluded. Published clinical trials were searched using Google Scholar until March 2024. The authors elaborated on the risk of bias in such cases, as indicated. All reviewed publications were searched for evidence of autoimmunity, cancer seeding, and other AEs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement guided the review.

Results

Data from 55 human clinical trials, abstracts, case reports, and unpublished data were analyzed, including 3323 patients treated with WATVs for various cancers. The primary outcomes were: (1) no documented cases of WATV-induced autoimmunity, (2) no documented cases of WATV-induced spreading or seeding of noninfectious cancers, and (3) the observed 0.24% (2/838) risk of spreading or seeding infectious cancers was attributed to inadequate sterilization. The secondary outcomes were: (1) no deaths were attributed to WATV therapy, (2) 0.18% (6/3323) incidence of grade 4 AEs, (3) 0.42% (14/3323) incidence of grade 3 AEs, (4) the incidence of grades 1–2 AEs was 52.21% (478/916).

Conclusions

WATVs carry no risk of inducing autoimmunity and essentially no risk of cancer seeding if properly sterilized. WATVs also exhibit a side effect profile comparable to that of routine vaccinations, with common, mild, and transient adverse effects. The combined risk of grade 3 and 4 AEs was 0.60% (20/3323). No deaths were causally associated with WATV treatment.
背景:全组织自体治疗性疫苗(WATVs)是一种利用患者自身病理组织的癌症免疫疗法。对WATVs诱导自身免疫或癌症扩散的可能性存在担忧;然而,它们的不良事件(ae)尚未得到充分的研究。本文献综述的主要目的是评估在人体临床试验中使用WATVs相关的自身免疫和癌症播种的风险。次要目标包括使用不良事件通用术语标准v5.0评估1-5级ae的发生率。方法纳入标准是任何使用人类受试者的临床试验,其中至少部分癌症疫苗来自患者自身的肿瘤组织,可能保留了患者肿瘤(即整个组织)中存在的独特肿瘤相关抗原(TAAs)。排除了使用有限TAAs或高度加工肿瘤抗原的肿瘤疫苗试验。使用b谷歌Scholar检索已发表的临床试验,直至2024年3月。如所示,作者详细阐述了这种情况下的偏见风险。对所有被审查的出版物进行检索,以寻找自身免疫、癌症播种和其他不良事件的证据。《2020年系统评价和荟萃分析首选报告项目》声明指导了本次评价。研究人员分析了55项人类临床试验、摘要、病例报告和未发表的数据,包括3323例接受WATVs治疗的各种癌症患者。主要结局是:(1)没有记录的watv诱导的自身免疫病例,(2)没有记录的watv诱导的非传染性癌症扩散或播种的病例,(3)观察到的0.24%(2/838)的传染性癌症扩散或播种的风险归因于消毒不充分。次要结局为:(1)无死亡归因于WATV治疗,(2)4级ae发生率0.18%(6/3323),(3)3级ae发生率0.42%(14/3323),(4)1 - 2级ae发生率52.21%(478/916)。结论经适当灭菌处理的watv无自身免疫诱导风险,基本无癌苗风险。WATVs也表现出与常规疫苗相当的副作用,具有常见,轻微和短暂的不良反应。3级和4级ae的合并风险为0.60%(20/3323)。没有死亡与WATV治疗有因果关系。
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引用次数: 0
Handy “tools” for studying brain tumors 研究脑肿瘤的便捷 "工具
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.06.009
Gangfeng Yu, Fanghui Lu, Liangxue Zhou
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引用次数: 0
A Bayesian network meta-analysis of EGFR-tyrosine kinase inhibitor treatments in patients with EGFR mutation-positive non-small cell lung cancer EGFR突变阳性非小细胞肺癌患者EGFR-酪氨酸激酶抑制剂治疗的贝叶斯网络meta分析
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.06.004
Jianqiong Yin , Jing Huang , Min Ren , Rui Tang , Linshen Xie , Jianxin Xue

Background

To date, no direct comparisons have been performed to compare the effectiveness of all epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) against EGFR mutation-positive non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of EGFR-TKIs in patients with EGFR mutation-positive NSCLC.

Methods

We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Pooled estimations of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity (grade ≥ 3 adverse events) were performed within the Bayesian framework.

Results

Twenty-three trials involving 11 treatments were included. All EGFR-TKIs improved PFS relative to chemotherapy, except for icotinib (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.26–1.44). All EGFR-TKIs demonstrated significant ORR benefits over chemotherapy. Osimertinib seemed to prolong PFS compared with icotinib (HR = 0.29, 95% CI: 0.1–0.86), gefitinib (HR = 0.39, 95% CI: 0.21–0.74), and erlotinib (HR = 0.53, 95% CI: 0.29–1.0). In addition, osimertinib showed favorable superiority in improving OS compared with chemotherapy (HR = 0.6, 95% CI: 0.43–0.82), gefitinib (HR = 0.61, 95% CI: 0.45–0.83), erlotinib (HR = 0.65, 95% CI: 0.48–0.89), and afatinib (HR = 0.65, 95% CI: 0.44–0.94). Among these regimens, afatinib showed the highest ORR (cumulative probability: 96.96%). Icotinib was associated with minimal toxicity among the EGFR-TKIs, followed by furmonertinib and osimertinib. Moreover, the toxicity spectra differed among the EGFR-TKIs. Subgroup analyses of patients with two common types of EGFR mutations indicated that furmonertinib possessed the greatest PFS benefit in patients with exon 19 deletion, and lazertinib showed the greatest PFS benefit in patients with Leu858Arg mutation. We also identified differences between EGFR-TKIs in prolonging PFS in patients with brain metastasis.

Conclusions

Osimertinib is the first choice of treatment with considerable efficacy and safety for EGFR mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively.
迄今为止,还没有直接比较所有表皮生长因子受体酪氨酸激酶抑制剂(EGFR- tkis)对EGFR突变阳性的非小细胞肺癌(NSCLC)的有效性。本研究旨在探讨EGFR- tkis在EGFR突变阳性NSCLC患者中的疗效和安全性。方法对随机对照试验进行网络荟萃分析,比较奥希替尼、拉泽替尼、奥莫替尼、比福替尼、福莫替尼、达科替尼、阿法替尼、厄洛替尼、吉非替尼、伊可替尼和化疗。在贝叶斯框架内对无进展生存期(PFS)、总生存期(OS)、客观缓解率(ORR)和毒性(≥3级不良事件)进行汇总估计。结果共纳入23项试验,涉及11种治疗方法。除伊可替尼外,所有EGFR-TKIs均改善了化疗后的PFS(风险比[HR] = 0.61, 95%可信区间[CI]: 0.26-1.44)。与化疗相比,所有EGFR-TKIs均表现出显著的ORR益处。与伊科替尼(HR = 0.29, 95% CI: 0.1-0.86)、吉非替尼(HR = 0.39, 95% CI: 0.21-0.74)和厄洛替尼(HR = 0.53, 95% CI: 0.29 - 1.0)相比,奥西替尼似乎延长了PFS。此外,与化疗相比,奥西替尼在改善OS方面表现出良好的优势(HR = 0.6, 95% CI: 0.43-0.82),吉非替尼(HR = 0.61, 95% CI: 0.45-0.83),厄洛替尼(HR = 0.65, 95% CI: 0.48-0.89),阿法替尼(HR = 0.65, 95% CI: 0.44-0.94)。在这些方案中,阿法替尼显示最高的ORR(累积概率:96.96%)。伊科替尼对egfr - tki的毒性最小,其次是福莫尼替尼和奥西替尼。此外,EGFR-TKIs的毒性谱存在差异。对两种常见类型EGFR突变患者的亚组分析表明,福莫那替尼对外显子19缺失患者的PFS益处最大,而拉泽替尼对Leu858Arg突变患者的PFS益处最大。我们还发现了EGFR-TKIs在延长脑转移患者PFS方面的差异。结论索西替尼是EGFR突变阳性NSCLC的首选治疗方案,具有相当的疗效和安全性。在外显子19缺失和Leu858Arg突变患者中,与最佳PFS相关的治疗分别是福莫那替尼和拉泽替尼。
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引用次数: 0
Overview of skin cancer types and prevalence rates across continents 各大洲皮肤癌类型和发病率概览
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.08.002
Amdad Hossain Roky , Mohammed Murshedul Islam , Abu Mohammed Fuad Ahasan , Md Saqline Mostaq , Md Zihad Mahmud , Mohammad Nurul Amin , Md Ashiq Mahmud
Skin cancer is one of the most prevalent cancers in the world, and its incidence and mortality rates are increasing continuously, mostly in regions with white-skinned inhabitants. The types of skin cancer vary in their origin and clinical appearances and also differ in their extensiveness. The continents of the world have different scenarios of skin cancer prevalence. This review aims to explore the different types of skin cancer, their clinical features, and their worldwide prevalence based on the literature. Literature from different electronic databases, including Google Scholar, ResearchGate, PubMed, Scopus, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Elsevier, and Springer, were collected through a literature search using specific keywords such as “skin cancer”, “skin cancer types”, “melanoma”, “non-melanoma”, “skin cancer continental prevalence” or similar keywords. The search included English publications from 2000 to 2024. Melanoma skin cancer (MSC) ranks 17th in global prevalence, with the highest incidence and deaths occurring in Europe, However, Australia and New Zealand record the highest incidence and mortality rates. Asia has a lower incidence rate of melanoma, but a higher mortality rate. Superficial spreading melanoma (SSM) is the most common type of MSC. Non-melanoma skin cancers (NMSCs) have the highest incidence in North America, with the highest number of deaths occurring in Asia, Australia and New Zealand have the highest incidence rates for basal cell carcinoma (BCC). BCC is the most commonly diagnosed skin cancer worldwide and the most prevalent form of NMSCs; however, squamous cell carcinoma is the most aggressive form of NMSCs, causing more deaths. NMSCs are the most prevalent cancers worldwide, causing most skin cancer-related deaths. The prevalence of skin cancer rising globally, with several continents experiencing higher incidence and mortality rates. The types and subtypes of skin cancer are becoming more common among clinically diagnosed cancers. This review comprehensively describes skin cancer types and their prevalence worldwide. However, the actual prevalence of skin cancer in these countries should be investigated. Further research on the prevalence of skin cancer across different continents is required to develop more effective cancer management strategies and control the spread of the disease.
皮肤癌是世界上最常见的癌症之一,其发病率和死亡率不断上升,主要发生在白皮肤居民的地区。皮肤癌的类型在其起源和临床表现上各不相同,在其广泛性上也各不相同。世界各大洲有不同的皮肤癌流行情况。本文旨在探讨不同类型的皮肤癌,他们的临床特点,并在文献的基础上,他们在世界范围内的患病率。通过使用“皮肤癌”、“皮肤癌类型”、“黑色素瘤”、“非黑色素瘤”、“皮肤癌大陆患病率”或类似关键词进行文献检索,收集来自谷歌Scholar、ResearchGate、PubMed、Scopus、Web of Science、Embase、care and Allied Health Literature Cumulative Index to Nursing (CINAHL)、Elsevier和施普林格等不同电子数据库的文献。搜索包括2000年至2024年的英文出版物。黑色素瘤皮肤癌(MSC)在全球患病率中排名第17位,欧洲的发病率和死亡率最高,然而,澳大利亚和新西兰的发病率和死亡率最高。亚洲的黑色素瘤发病率较低,但死亡率较高。浅表性扩散黑色素瘤(SSM)是最常见的MSC类型。非黑色素瘤皮肤癌(NMSCs)在北美的发病率最高,亚洲的死亡人数最多,澳大利亚和新西兰的基底细胞癌(BCC)发病率最高。BCC是世界上最常见的皮肤癌,也是NMSCs最普遍的形式;然而,鳞状细胞癌是NMSCs最具侵袭性的形式,导致更多的死亡。NMSCs是世界上最常见的癌症,导致大多数皮肤癌相关死亡。皮肤癌的流行在全球范围内不断上升,有几个大陆的发病率和死亡率更高。皮肤癌的类型和亚型在临床诊断的癌症中越来越常见。本文综述了皮肤癌的类型及其在世界范围内的流行情况。然而,应该调查这些国家皮肤癌的实际流行情况。需要进一步研究皮肤癌在不同大陆的流行情况,以制定更有效的癌症管理战略并控制该疾病的传播。
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引用次数: 0
Integrating multi-omics methods for personalized treatment of refractory chronic myelomonocytic leukemia with NRAS and TET2 mutations 整合多组学方法个体化治疗NRAS和TET2突变难治性慢性髓细胞白血病
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.12.001
Chuandong Hou , Bo Yang , Yue Wang , Lili Cai , Ran Qin , Bo Guo , Jie Geng , XueChun Lu
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引用次数: 0
Gastrointestinal stromal tumors with an uncommon primary mutation responded well to imatinib 具有罕见原发性突变的胃肠道间质瘤对伊马替尼反应良好
Pub Date : 2025-03-01 DOI: 10.1016/j.cpt.2024.08.005
Gilani Shahid, Mujeeb Qudsia, Ikram Naima, Khir Ibrahim
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引用次数: 0
期刊
Cancer pathogenesis and therapy
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