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New roles of tumor-derived exosomes in tumor microenvironment. 肿瘤外泌体在肿瘤微环境中的新作用
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.05
Shiqian Chen, Jinzhe Sun, Huan Zhou, Hongbin Lei, Dan Zang, Jun Chen

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment (TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes (TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

在整个肿瘤发生过程中,肿瘤细胞及其周围微环境的共同演变导致了恶性表型的形成。肿瘤微环境(TME)中的细胞交流在影响肿瘤进展的各个方面(包括侵袭和转移)中发挥着至关重要的作用。体内大多数细胞类型释放的外泌体(一种细胞外囊泡)是细胞间交流的重要媒介。越来越多的研究表明,肿瘤源性外泌体(TDEs)通过多种机制显著加速肿瘤进展,诱导上皮-间质转化和巨噬细胞极化,增强血管生成,并帮助肿瘤细胞逃避免疫。在此,我们描述了肿瘤组织生长因子的形成和特点,总结了肿瘤组织生长因子的内容及其在调节肿瘤发生发展中的多种功能。此外,我们还探讨了 TDEs 在肿瘤诊断和治疗中的潜在应用。
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引用次数: 0
Advances in regional nodal management of early-stage breast cancer. 早期乳腺癌区域结节管理的进展。
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.08
Zhao Bi, Yongsheng Wang

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node (SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment (systemic/radiotherapy) that may result from de-escalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging node-positive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy (SLNB), the regional nodal management of breast cancer should adhere to the concept of "updating ideas, making bold assumptions, and carefully seeking proof", make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the "net benefit" of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

随着全身治疗的不断改进,早期乳腺癌合理的局部区域控制可转化为生存获益。对于局限性前哨淋巴结(SLN)转移的患者,如何优化区域结节管理需要权衡手术并发症、区域复发风险和淋巴结状态,以及去势手术可能导致的其他升级治疗(全身治疗/放疗)。在全身治疗和放疗的有效支持和补充下,腋窝手术的管理正呈降级趋势发展。新辅助治疗的广泛应用有助于优化临床结节阴性/影像学结节阳性患者的治疗。在临床实践中,对于SLN局限性阳性而未进行腋窝淋巴结清扫的患者,在制定最佳照射野时有必要考虑区域淋巴结的残余肿瘤负荷。基因组检测和美国外科医生学会肿瘤学组 Z0011/AMAROS 标准的联合应用可为患者提供更好的双重降级治疗策略,包括腋窝手术和全身治疗的降级。在前哨淋巴结活检(SLNB)时代,乳腺癌区域结节治疗应坚持 "更新观念、大胆假设、小心求证 "的理念,充分利用全身治疗和放射治疗的优势,减少手术范围和并发症,扩大疗效和生活质量的 "净获益"。本综述探讨了 SLNB 时代区域结节管理的优化,以期为临床医生提供参考信息。
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引用次数: 0
Hypoxic tumor microenvironment: Destroyer of natural killer cell function. 缺氧的肿瘤微环境:自然杀伤细胞功能的破坏者
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.04
Yongfei Zhang, Feifei Guo, Yufeng Wang

In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer (NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment (TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.

近年来,免疫疗法在治疗某些肿瘤和血液恶性肿瘤方面取得了显著进展。然而,自然杀伤(NK)细胞作为用于抗癌免疫疗法的先天性淋巴细胞的一个重要亚群,其疗效仍然有限。缺氧是肿瘤微环境(TME)的一个重要特征,它参与了肿瘤的发展以及对放疗、化疗和免疫疗法的抵抗。此外,缺氧会导致 NK 细胞功能受损,可能是限制其治疗效果的一个重要因素。有针对性的缺氧疗法已成为提高 NK 细胞疗效的一个前景广阔的研究领域。因此,了解缺氧TME如何影响NK细胞功能对于改善抗肿瘤治疗效果至关重要。
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引用次数: 0
Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors. 派罗替尼对曲妥珠单抗敏感和原发耐药的 HER2 阳性乳腺肿瘤均有效。
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-04-30 DOI: 10.21147/j.issn.1000-9604.2024.02.03
Jialin Zhang, Gengshen Yin, Chunmiao Ye, Man Feng, Changhua Ji, Wenzhong Zhou, Fei Wang, Lixiang Yu, Shuya Huang, Zhigang Yu

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.

Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.

Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.

Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

目的:人表皮生长因子受体 2 (HER2) 阳性 (+) 乳腺癌患者经常对曲妥珠单抗产生原发性耐药性,这仍然是一项临床挑战。派罗替尼是一种新型酪氨酸激酶抑制剂,已显示出治疗HER2+乳腺癌的疗效。方法:用曲妥珠单抗、派罗替尼或其组合治疗对曲妥珠单抗敏感或主要耐药的 HER2+ 乳腺癌细胞。分析了细胞增殖、迁移、侵袭和 HER2 下游信号通路。在体外乳腺癌细胞和曲妥珠单抗原发耐药的异种移植小鼠模型中,比较了派罗替尼加曲妥珠单抗和pertuzumab加曲妥珠单抗的效果:结果:派罗替尼通过抑制磷酸肌酸3-激酶(PI3K)/蛋白激酶B(AKT)和大鼠肉瘤病毒(RAS)/快速加速纤维肉瘤(RAF)/介导激活蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)通路,对曲妥珠单抗敏感的HER2+乳腺癌细胞具有治疗作用。在曲妥珠单抗耐药的原代细胞中,派罗替尼抑制细胞生长、迁移、侵袭和HER2下游通路,而曲妥珠单抗则没有影响。与单独使用派罗替尼相比,与曲妥珠单抗联合使用派罗替尼的效果并没有增加。与pertuzumab联合曲妥珠单抗相比,派罗替尼联合曲妥珠单抗在抑制乳腺癌细胞增殖和HER2下游通路以及曲妥珠单抗耐药的HER2+乳腺癌异种移植模型中的肿瘤生长方面更为有效:结论:含派罗替尼的疗法对曲妥珠单抗敏感和原发耐药的HER2+乳腺癌细胞具有抗癌作用。值得注意的是,在对曲妥珠单抗原发耐药的HER2+乳腺癌中,派罗替尼加曲妥珠单抗比曲妥珠单抗加百妥珠单抗更有效地抑制肿瘤生长和HER2下游通路。这些研究结果支持对细胞内小分子与细胞外抗体相结合的双重抗 HER2 治疗的疗效进行临床测试。
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引用次数: 0
Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years. 植物性饮食模式与食道癌风险:一项长达 17 年的前瞻性队列研究。
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-02-29 DOI: 10.21147/j.issn.1000-9604.2024.01.04
Xiaorui Zhang, Feifan He, Jiayue Li, Ru Chen, Xinqing Li, Li Li, Fen Liu, Shaoming Wang, Wenqiang Wei

Objective: Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.

Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups.

Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.

Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

目的:植物性膳食对癌症有多种健康益处;然而,人们对植物性膳食模式与食管癌(EC)之间的关系知之甚少。本研究对植物性膳食模式的三个预定指标与食管癌风险之间的前瞻性关系进行了调查:方法:2005年1月至2009年12月,我们对来自中国两个高风险地区的15709名40-69岁的参与者进行了内镜筛查,并随访至2022年12月31日。通过调查问卷评估膳食模式,计算出总体植物性膳食指数(PDI)、健康植物性膳食指数(hPDI)和不健康植物性膳食指数(uPDI)。我们采用考克斯比例危险回归法估算了三种植物性膳食指数中EC的多变量危险比(HRs)和95%置信区间(95% CIs),并进一步按亚组进行了分层分析:最终研究样本包括 15 184 名队列参与者。在 219,365 人年的随访期间,共发现了 176 名心肌梗死患者。如果将最高四分位数与最低四分位数进行比较,那么经多变量调整后,hPDI的EC合并HR为0.50(95% CI,0.32-0.77)。此外,hPDI 评分每增加 10 分,EC 的 HR 为 0.42(95% CI,0.27-0.66)。相反,uPDI 与心肌梗死风险呈正相关,HR 为 1.80(95% CI,1.16-2.82)。uPDI得分每增加10分,EC的HR为1.90(95% CI,1.26-2.88)。在大多数亚组中,这些评分与EC风险之间的关系是一致的。这些结果在敏感性分析中仍保持稳定:结论:健康的植物性膳食模式与降低EC风险有关。强调植物性膳食的健康和质量可能对预防心肌梗死的发生非常重要。
{"title":"Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years.","authors":"Xiaorui Zhang, Feifan He, Jiayue Li, Ru Chen, Xinqing Li, Li Li, Fen Liu, Shaoming Wang, Wenqiang Wei","doi":"10.21147/j.issn.1000-9604.2024.01.04","DOIUrl":"10.21147/j.issn.1000-9604.2024.01.04","url":null,"abstract":"<p><strong>Objective: </strong>Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.</p><p><strong>Methods: </strong>We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups.</p><p><strong>Results: </strong>The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32-0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27-0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16-2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.</p><p><strong>Conclusions: </strong>A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 1","pages":"36-45"},"PeriodicalIF":5.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058809","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
Manufacturing CAR-NK against tumors: Who is the ideal supplier? 生产抗肿瘤的 CAR-NK:谁是理想的供应商?
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-02-29 DOI: 10.21147/j.issn.1000-9604.2024.01.01
Feifei Guo, Yi Zhang, Jiuwei Cui

Chimeric antigen receptor-natural killer (CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice. However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.

嵌合抗原受体-自然杀伤(CAR-NK)细胞已成为继 CAR-T 细胞之后肿瘤免疫疗法领域的又一佼佼者。CAR-NK 细胞的独特性使其有可能弥补 CAR-T 疗法的不足,如生产过程的复杂性、临床不良事件和实体瘤的挑战。迄今为止,不同异体来源的 CAR-NK 产品已在临床前研究中表现出显著的抗肿瘤效果,并逐渐应用于临床实践。然而,每种来源各有利弊。选择合适的来源有助于最大限度地提高 CAR-NK 细胞的疗效,增加临床转化的可行性。因此,本综述探讨了不同来源的CAR-NK细胞的发展与挑战,为今后的探索提供参考。
{"title":"Manufacturing CAR-NK against tumors: Who is the ideal supplier?","authors":"Feifei Guo, Yi Zhang, Jiuwei Cui","doi":"10.21147/j.issn.1000-9604.2024.01.01","DOIUrl":"10.21147/j.issn.1000-9604.2024.01.01","url":null,"abstract":"<p><p>Chimeric antigen receptor-natural killer (CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice. However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 1","pages":"1-16"},"PeriodicalIF":5.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058776","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
Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer. 利用远处转移性分化型甲状腺癌的分子改变对放射性碘难治性进行风险分层。
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-02-29 DOI: 10.21147/j.issn.1000-9604.2024.01.03
Zhuanzhuan Mu, Xin Zhang, Dongquan Liang, Jugao Fang, Ge Chen, Wenting Guo, Di Sun, Yuqing Sun, Zhentian Kai, Lisha Huang, Jun Liang, Yansong Lin

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.

Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.

Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041).

Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

目的:放射性碘难治性分化型甲状腺癌(RAIR-DTC)患者往往被延误诊断,治疗方案有限。RAI 难治性与潜在遗传特征之间的相关性尚未得到广泛研究:方法:招募远处转移性 DTC 的成年患者,并分配他们接受定制的 26 个基因面板(ThyroLead)的新一代测序。患者被分为RAIR-DTC组和非RAIR组,以确定临床病理和分子特征的差异。根据发现的分子改变与 RAI 难治性之间的关联构建分子风险分层(MRS),并将结果分为高、中、低 MRS:结果:共纳入了 220 例远处转移患者,其中 63.2% 被确定为 RAIR-DTC。90%的患者都发现了基因改变,RAIR-DTC组的BRAF(59.7%对17.3%)、TERT启动子(43.9%对7.4%)和TP53突变(11.5%对3.7%)发生率高于非RAIR组,但RET融合(15.8%对39.5%)的发生率与非RAIR组相反。BRAF和TERT启动子是RAIR-DTC的独立预测因子,占RAIR-DTC患者的67.6%。MRS 与 RAI 难治性密切相关(PConclusions:分子改变与 RAI 难治性相关,BRAF 和 TERT 启动子突变是主要因素,其次是 TP53 和 DICER1 突变。MRS可作为一种有价值的工具,用于预测临床结果和指导精准治疗干预。
{"title":"Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer.","authors":"Zhuanzhuan Mu, Xin Zhang, Dongquan Liang, Jugao Fang, Ge Chen, Wenting Guo, Di Sun, Yuqing Sun, Zhentian Kai, Lisha Huang, Jun Liang, Yansong Lin","doi":"10.21147/j.issn.1000-9604.2024.01.03","DOIUrl":"10.21147/j.issn.1000-9604.2024.01.03","url":null,"abstract":"<p><strong>Objective: </strong>Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.</p><p><strong>Methods: </strong>Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.</p><p><strong>Results: </strong>A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with <i>BRAF</i> (59.7% <i>vs</i>. 17.3%), <i>TERT</i> promoter (43.9% <i>vs.</i> 7.4%), and <i>TP53</i> mutations (11.5% <i>vs.</i> 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for <i>RET</i> fusions (15.8% <i>vs.</i> 39.5%), which had the opposite pattern. <i>BRAF</i> and <i>TERT</i> promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041).</p><p><strong>Conclusions: </strong>Molecular alterations were associated with RAI refractoriness, with <i>BRAF</i> and <i>TERT</i> promoter mutations being the predominant contributors, followed by <i>TP53</i> and <i>DICER1</i> mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 1","pages":"25-35"},"PeriodicalIF":5.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058810","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
A phase I study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer. Hemay022是一种不可逆的表皮生长因子受体/HER2酪氨酸激酶双重抑制剂,在中国HER2阳性晚期乳腺癌患者中的I期研究。
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-02-29 DOI: 10.21147/j.issn.1000-9604.2024.01.05
Pin Zhang, Lin Wang, Yueying Zhen, Zhihong Wang, Hesheng Zhang, Richard Jones, Binghe Xu

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics, tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.

Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles. Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.

Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea (85.7%), vomiting (28.6%), nausea (25.0%) and decreased appetite (17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response (CR), and three achieved partial response (PR). The objective response rate (ORR) and disease control rate (DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival (PFS) was 3.98 months.

Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase III trial (No. NCT05122494).

目的:Hemay022是一种新型小分子、不可逆的酪氨酸激酶抑制剂,以表皮生长因子受体(EGFR)/人表皮生长因子受体2(HER2)为靶点,在临床前研究中显示出抗肿瘤活性。这项首次人体研究评估了Hemay022在HER2阳性晚期乳腺癌患者中的安全性、药代动力学、耐受性和初步抗肿瘤活性。方法:HER2阳性晚期乳腺癌重度预处理患者以3+3剂量递增模式被分配到8个剂量组群,剂量为50-600毫克QD和300毫克BID。符合条件的患者在第0周的第1天服用单剂量的Hemay022,然后以28天为一个周期,连续服用4周,每天1次。在第 1 天和第 28 天采集药代动力学样本。临床反应每八周评估一次:28名晚期乳腺癌患者接受了Hemay022治疗。最常报告的药物相关不良事件是腹泻(85.7%)、呕吐(28.6%)、恶心(25.0%)和食欲下降(17.9%)。没有四级药物相关不良事件的报告。在 50-600 毫克剂量下,稳态浓度-时间曲线下面积和峰值浓度随剂量增加而增加。一名患者获得了完全应答(CR),三名患者获得了部分应答(PR)。28名患者的客观反应率(ORR)和疾病控制率(DCR)分别为14.3%和46.4%。中位无进展生存期(PFS)为3.98个月:结论:Hemay022的耐受性良好,剂量为500毫克,每天一次。Hemay022在晚期乳腺癌患者中的药代动力学特性和令人鼓舞的抗肿瘤活性证明,在目前的III期试验(NCT05122494号)中,有必要进一步评估Hemay022治疗乳腺癌患者的效果。
{"title":"A phase I study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer.","authors":"Pin Zhang, Lin Wang, Yueying Zhen, Zhihong Wang, Hesheng Zhang, Richard Jones, Binghe Xu","doi":"10.21147/j.issn.1000-9604.2024.01.05","DOIUrl":"10.21147/j.issn.1000-9604.2024.01.05","url":null,"abstract":"<p><strong>Objective: </strong>Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics, tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.</p><p><strong>Methods: </strong>Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles. Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.</p><p><strong>Results: </strong>Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea (85.7%), vomiting (28.6%), nausea (25.0%) and decreased appetite (17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response (CR), and three achieved partial response (PR). The objective response rate (ORR) and disease control rate (DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival (PFS) was 3.98 months.</p><p><strong>Conclusions: </strong>Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase III trial (No. NCT05122494).</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 1","pages":"46-54"},"PeriodicalIF":5.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058773","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
Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study. 针对 HER2 阳性乳腺癌,使用聚乙二醇多柔比星和环磷酰胺进行序贯新辅助化疗,然后使用紫杉类药物和曲妥珠单抗及百妥珠单抗进行完全治疗:II期单臂研究。
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-02-29 DOI: 10.21147/j.issn.1000-9604.2024.01.06
Yaping Yang, Liang Jin, Yudong Li, Nanyan Rao, Chang Gong, Shunrong Li, Jiannan Wu, Jinghua Zhao, Linxiaoxiao Ding, Fengxia Gan, Jun Zhang, Ruifa Feng, Zhenzhen Liu, Qiang Liu

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC).

Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 90-100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity).

Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin.

Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

目的:尽管存在心脏毒性重叠,但曲妥珠单抗/培珠单抗和蒽环类药物的联合用药因其显著疗效而仍然至关重要。聚乙二醇脂质体多柔比星(PLD)是一种心脏毒性较低的蒽环类药物,在与环磷酰胺联合使用后,再用紫杉类药物与曲妥珠单抗/pertuzumab联合治疗人表皮生长因子受体-2(HER2)阳性早期乳腺癌(BC)时,对其疗效和心脏安全性进行了评估:在这项多中心II期研究中,确诊为HER2阳性的早期乳腺癌患者先接受4个周期的PLD(30-35毫克/平方米)和环磷酰胺(600毫克/平方米)治疗,然后接受4个周期的紫杉类药物治疗(多西他赛,90-100毫克/平方米或纳布紫杉醇,260毫克/平方米),同时每3周接受8个周期的曲妥珠单抗治疗(8毫克/公斤负荷剂量,然后6毫克/公斤)和百妥珠单抗治疗(840毫克负荷剂量,然后420毫克)。主要终点是总病理完全应答(tpCR,ypT0/is ypN0)。次要终点包括乳腺病理完全反应(bpCR)、客观反应率(ORR)、疾病控制率、保乳手术率(BCS)和安全性(重点关注心脏毒性):2020年5月27日至2022年5月11日期间,78名患者接受了手术治疗,其中42人(53.8%)接受了保乳手术。新辅助治疗后,47 名患者[60.3%,95% 置信区间(95% CI),48.5%-71.2%]获得了 tpCR,49 名患者(62.8%)获得了 bpCR。经过4个周期和8个周期的新辅助治疗后,ORR分别为76.9%(95% CI,66.0%-85.7%)和93.6%(95% CI,85.7%-97.9%)。9例(11.5%)患者的无症状左心室射血分数(LVEF)较基线下降≥10%,最低值均>55%。平均N-末端前BNP(NT-proBNP)、肌钙蛋白I或高敏肌钙蛋白均未观察到与治疗相关的心功能异常变化:这种HER2双阻断联合序贯多化疗方案在HER2阳性的BC中显示出良好的活性,肿瘤可迅速消退。重要的是,该方案具有可接受的安全性,尤其是发生心脏事件的风险较低,这表明它是一种具有吸引力的治疗方法,具有良好的风险-效益平衡。
{"title":"Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study.","authors":"Yaping Yang, Liang Jin, Yudong Li, Nanyan Rao, Chang Gong, Shunrong Li, Jiannan Wu, Jinghua Zhao, Linxiaoxiao Ding, Fengxia Gan, Jun Zhang, Ruifa Feng, Zhenzhen Liu, Qiang Liu","doi":"10.21147/j.issn.1000-9604.2024.01.06","DOIUrl":"10.21147/j.issn.1000-9604.2024.01.06","url":null,"abstract":"<p><strong>Objective: </strong>Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC).</p><p><strong>Methods: </strong>In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m<sup>2</sup>) and cyclophosphamide (600 mg/m<sup>2</sup>), followed by four cycles of taxanes (docetaxel, 90-100 mg/m<sup>2</sup> or nab-paclitaxel, 260 mg/m<sup>2</sup>), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity).</p><p><strong>Results: </strong>Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin.</p><p><strong>Conclusions: </strong>This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 1","pages":"55-65"},"PeriodicalIF":5.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058811","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
Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer: A retrospective study. 晚期胃癌中Claudin 18.2表达的临床病理意义和免疫治疗结果:一项回顾性研究。
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2024-02-29 DOI: 10.21147/j.issn.1000-9604.2024.01.08
Changsong Qi, Xiaoyi Chong, Ting Zhou, Mingyang Ma, Jifang Gong, Miao Zhang, Jian Li, Jun Xiao, Xiaohui Peng, Zhen Liu, Zonghai Li, Lin Shen, Xiaotian Zhang

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive (CLDN18.2-positive) gastric cancer (GC) vary in different clinical studies, making it difficult to optimize anti-CLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.

Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01 clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells (2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells (2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.

Results: CLDN18.2 was expressed in 57.6% (cut-off: 2+, 40%) and 48.9% (cut-off: 2+, 70%) of patients. Programmed death-ligand 1 (PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score (CPS)≥1, CLDN18.2 (cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2 (cut-off: 2+, 70%)] of patients. CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction (non-GEJ), and diffuse phenotype (P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC (both P<0.05). Uterine adnexa metastasis (P<0.001) was more frequent and liver metastasis (P<0.001) was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival (irPFS) were inferior in the CLDN18.2-positive group.

Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

目的在不同的临床研究中,克劳丁18同工酶2阳性(CLDN18.2阳性)胃癌(GC)的免疫治疗结果和临床特征各不相同,因此很难优化抗CLDN18.2治疗。我们进行了一项回顾性分析,探讨CLDN18.2表达与GC临床病理特征和免疫治疗结果的关系:分析纳入了2019年至2021年参加CT041-CG4006和CT041-ST-01临床试验的536例晚期GC患者。CLDN18.2表达≥40%的肿瘤细胞(2+,40%)和CLDN18.2表达≥70%的肿瘤细胞(2+,70%)被认为是GC阳性表达的两个水平。根据CLDN18.2的表达情况分析了GC患者的临床病理特征和免疫治疗结果:57.6%(临界值:2+,40%)和48.9%(临界值:2+,70%)的患者表达CLDN18.2。19.8%的患者[合并阳性评分(CPS)≥1,CLDN18.2(截止值:2+,40%)]和17.2%的患者[CPS≥5,CLDN18.2(截止值:2+,70%)]中程序性死亡配体1(PD-L1)和CLDN18.2共同表达。CLDN18.2的表达与年轻、女性、非胃食管交界处(non-GEJ)和弥漫表型呈正相关(P0.05)。子宫附件转移(PConclusions:CLDN18.2阳性GC与预后不良和免疫治疗效果较差有关。抗CLDN18.2疗法、抗PD-L1/PD-1疗法和化疗联合治疗GC需要进一步研究。
{"title":"Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer: A retrospective study.","authors":"Changsong Qi, Xiaoyi Chong, Ting Zhou, Mingyang Ma, Jifang Gong, Miao Zhang, Jian Li, Jun Xiao, Xiaohui Peng, Zhen Liu, Zonghai Li, Lin Shen, Xiaotian Zhang","doi":"10.21147/j.issn.1000-9604.2024.01.08","DOIUrl":"10.21147/j.issn.1000-9604.2024.01.08","url":null,"abstract":"<p><strong>Objective: </strong>Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive (CLDN18.2-positive) gastric cancer (GC) vary in different clinical studies, making it difficult to optimize anti-CLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.</p><p><strong>Methods: </strong>A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01 clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells (2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells (2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.</p><p><strong>Results: </strong>CLDN18.2 was expressed in 57.6% (cut-off: 2+, 40%) and 48.9% (cut-off: 2+, 70%) of patients. Programmed death-ligand 1 (PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score (CPS)≥1, CLDN18.2 (cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2 (cut-off: 2+, 70%)] of patients. CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction (non-GEJ), and diffuse phenotype (P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC (both P<i><</i>0.05). Uterine adnexa metastasis (P<0.001) was more frequent and liver metastasis (P<0.001) was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival (irPFS) were inferior in the CLDN18.2-positive group.</p><p><strong>Conclusions: </strong>CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 1","pages":"78-89"},"PeriodicalIF":5.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058774","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
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Chinese Journal of Cancer Research
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