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Coexistent Pulmonary Tuberculosis and Lung Cancer: An Analysis of Incidence Trends, Financial Burdens and Influencing Factors 肺结核与肺癌共存:发病率趋势、经济负担及影响因素分析
Pub Date : 2025-04-07 DOI: 10.1002/cai2.70009
Fei Qi, Hongjie Yang, Yi Han, Yujie Dong, Fan Zhang, Yishuo Wang, Juan Du, Yuan Gao, Xueguang Hu, Liqun Zhang, Tongmei Zhang

Background

Tuberculosis (TB) and lung cancer (LC) are both major global health threats. However, coexistent pulmonary TB and LC (TBLC) is a unique condition for which incidence trends and risk factors have not been fully defined.

Methods

We retrospectively reviewed the medical records of patients with TBLC and LC alone between 2010 and 2022 at Beijing Chest Hospital, the standard authority for the diagnosis and treatment of TB and LC in China. The cumulative incidence rate (CIR) of TBLC was calculated as the number of new TBLC cases/number of LC cases at risk per 100,000 annually. The comparative incidence rate ratio (IRR) was estimated to be the TB incidence in LC patients/TB incidence in the general population. Logistic regression was used to explore risk factors for TBLC.

Results

The CIR of TBLC has rapidly increased each year since 2014 and reached 7027 per 100,000 LC patients in 2022. Patients with LC had a higher risk of developing active TB than the general population (IRR = 25.21, 95% confidence interval [CI]: 21.54–29.89). Medical expenditure per patient was 100.60 thousand yuan for those with TBLC and 105.60 thousand yuan for patients with LC (p = 0.687). Patients with TBLC were older (63.61 ± 10.46 vs. 61.08 ± 10.77, p < 0.001) and had a higher male-to-female ratio (2.82 vs. 1.59, p = 0.044) than those with LC alone. A tendency of earlier disease onset was observed in patients with LC rather than TBLC. A majority (44.92%) of TBLC lesions were located in the upper lobes of the lung and had a higher proportion of squamous cell carcinomas than LC alone (32.24% vs. 27.49%, p = 0.002). TBLC also presented more aggressively, with more lymph node involvement and distant metastases. Multivariate analysis revealed that older age, the male sex, mediastinal lymph node invasion, lung/bone metastases, anemia, hypoalbuminemia, malnutrition, pulmonary fibrosis, and chronic obstructive pulmonary disease were risk factors for active TBLC.

Conclusions

There has been a rise in the incidence of coexistent TBLC and a concomitant increase in its financial burden in China that deserves more awareness and attention.

背景 结核病(TB)和肺癌(LC)都是威胁全球健康的主要疾病。然而,肺结核和肺癌并存(TBLC)是一种独特的疾病,其发病趋势和风险因素尚未完全明确。 方法 我们回顾性分析了 2010 年至 2022 年期间北京胸科医院(中国肺结核和肺癌诊断和治疗的标准权威机构)收治的肺结核合并肺癌患者的病历。肺结核累积发病率(CIR)的计算方法是每年每 10 万人中肺结核新发病例数/肺结核高危病例数。比较发病率比(IRR)估计为 LC 患者的肺结核发病率/普通人群的肺结核发病率。采用逻辑回归法探讨肺结核LC 的风险因素。 结果 自 2014 年以来,肺结核发病率比值逐年快速上升,到 2022 年,每 10 万名肺结核患者中,肺结核发病率比值达到 7027。肺结核患者罹患活动性肺结核的风险高于普通人群(IRR = 25.21,95% 置信区间 [CI]:21.54-29.89)。肺结核LC 患者的人均医疗支出为 10.06 万元,肺结核 LC 患者的人均医疗支出为 10.56 万元(P = 0.687)。与单纯 LC 患者相比,TBLC 患者年龄更大(63.61 ± 10.46 vs. 61.08 ± 10.77,p < 0.001),男女比例更高(2.82 vs. 1.59,p = 0.044)。在 LC 而非 TBLC 患者中观察到发病较早的趋势。大多数(44.92%)TBLC 病灶位于肺上叶,与单纯 LC 相比,鳞状细胞癌的比例更高(32.24% 对 27.49%,p = 0.002)。TBLC的表现也更具侵袭性,有更多淋巴结受累和远处转移。多变量分析显示,年龄较大、男性、纵隔淋巴结受侵、肺/骨转移、贫血、低白蛋白血症、营养不良、肺纤维化和慢性阻塞性肺病是活动性 TBLC 的危险因素。 结论 在中国,并存肺结核的发病率有所上升,其经济负担也随之增加,这值得引起更多的关注和重视。
{"title":"Coexistent Pulmonary Tuberculosis and Lung Cancer: An Analysis of Incidence Trends, Financial Burdens and Influencing Factors","authors":"Fei Qi,&nbsp;Hongjie Yang,&nbsp;Yi Han,&nbsp;Yujie Dong,&nbsp;Fan Zhang,&nbsp;Yishuo Wang,&nbsp;Juan Du,&nbsp;Yuan Gao,&nbsp;Xueguang Hu,&nbsp;Liqun Zhang,&nbsp;Tongmei Zhang","doi":"10.1002/cai2.70009","DOIUrl":"https://doi.org/10.1002/cai2.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tuberculosis (TB) and lung cancer (LC) are both major global health threats. However, coexistent pulmonary TB and LC (TBLC) is a unique condition for which incidence trends and risk factors have not been fully defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively reviewed the medical records of patients with TBLC and LC alone between 2010 and 2022 at Beijing Chest Hospital, the standard authority for the diagnosis and treatment of TB and LC in China. The cumulative incidence rate (CIR) of TBLC was calculated as the number of new TBLC cases/number of LC cases at risk per 100,000 annually. The comparative incidence rate ratio (IRR) was estimated to be the TB incidence in LC patients/TB incidence in the general population. Logistic regression was used to explore risk factors for TBLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CIR of TBLC has rapidly increased each year since 2014 and reached 7027 per 100,000 LC patients in 2022. Patients with LC had a higher risk of developing active TB than the general population (IRR = 25.21, 95% confidence interval [CI]: 21.54–29.89). Medical expenditure per patient was 100.60 thousand yuan for those with TBLC and 105.60 thousand yuan for patients with LC (<i>p</i> = 0.687). Patients with TBLC were older (63.61 ± 10.46 vs. 61.08 ± 10.77, <i>p</i> &lt; 0.001) and had a higher male-to-female ratio (2.82 vs. 1.59, <i>p</i> = 0.044) than those with LC alone. A tendency of earlier disease onset was observed in patients with LC rather than TBLC. A majority (44.92%) of TBLC lesions were located in the upper lobes of the lung and had a higher proportion of squamous cell carcinomas than LC alone (32.24% vs. 27.49%, <i>p</i> = 0.002). TBLC also presented more aggressively, with more lymph node involvement and distant metastases. Multivariate analysis revealed that older age, the male sex, mediastinal lymph node invasion, lung/bone metastases, anemia, hypoalbuminemia, malnutrition, pulmonary fibrosis, and chronic obstructive pulmonary disease were risk factors for active TBLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There has been a rise in the incidence of coexistent TBLC and a concomitant increase in its financial burden in China that deserves more awareness and attention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic Effect of Neck Dissection and Risk Factors for Occult Lymph Node Metastasis in cN0 Parotid Carcinoma 颈部清扫对cN0腮腺癌隐匿淋巴结转移的预后影响及危险因素分析
Pub Date : 2025-04-07 DOI: 10.1002/cai2.70007
Yudong Ning, Yixuan Song, Yuqin He, Han Li, Shaoyan Liu

Objective

This study aimed to explore the prognostic effect of neck dissection and to identify risk factors associated with occult lymph node metastasis (OLNM) in clinically node-negative (cN0) parotid carcinoma (PC).

Methods

A retrospective analysis was conducted on cN0 PC patients who underwent primary surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, between 2012 and 2022. Kaplan–Meier (KM) survival analyses were carried out to evaluate differences in progression-free survival (PFS) and overall survival (OS) between patients undergoing neck dissection and those who did not. Clinical variables associated with OLNM in the neck dissection group were assessed using univariate and multivariate logistic regression analyses.

Results

Among 472 PC patients, 133 were classified as cN0 following initial surgery, of whom 75 (56.4%) underwent neck dissection. Pathological lymph node metastases were confirmed in 20 (26.7%) patients in the neck dissection cohort. Poor tumor differentiation was identified as an independent risk factor for OLNM (p = 0.017). No significant differences in PFS or OS were observed between the no-neck dissection and neck dissection groups for patients with low-grade or well-differentiated tumors (p > 0.05). However, neck dissection was associated with significantly prolonged PFS in patients with tumors of higher grade or low to moderate differentiation (p < 0.05). Notably, OS did not improve with neck dissection across all subgroups (p > 0.05).

Conclusion

Poorly differentiated tumors in cN0 PC are independently associated with a higher risk of OLNM. While prophylactic neck dissection may enhance PFS in patients with higher grade or poorly differentiated tumors, it does not confer a survival benefit in terms of OS. These findings support the selective use of neck dissection in patients with higher risk tumor profiles.

目的探讨颈部清扫对临床淋巴结阴性(cN0)腮腺癌(PC)预后的影响,并探讨与隐匿淋巴结转移(OLNM)相关的危险因素。方法回顾性分析2012年至2022年在中国医学科学院国家肿瘤中心/肿瘤医院接受原发性手术的cN0例PC患者。Kaplan-Meier (KM)生存分析用于评估接受和未接受颈部剥离的患者的无进展生存期(PFS)和总生存期(OS)的差异。采用单因素和多因素logistic回归分析评估与颈部清扫组OLNM相关的临床变量。结果472例PC患者中,133例术后为cN0,其中75例(56.4%)行颈部清扫术。20例(26.7%)颈部夹层患者确诊有病理性淋巴结转移。肿瘤分化差被认为是OLNM的独立危险因素(p = 0.017)。低分级、高分化肿瘤患者无颈清扫组与无颈清扫组PFS、OS差异无统计学意义(p > 0.05)。然而,在肿瘤级别较高或中低分化的患者中,颈部清扫与PFS显著延长相关(p < 0.05)。值得注意的是,在所有亚组中,颈部清扫并没有改善OS (p > 0.05)。结论cN0型PC中低分化肿瘤与OLNM的高危险性独立相关。虽然预防性颈部清扫可能会提高高级别或低分化肿瘤患者的PFS,但就OS而言,它并没有带来生存益处。这些发现支持在高风险肿瘤患者中选择性使用颈部清扫术。
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引用次数: 0
A Survey of Clinical Practices for Hepatocellular Carcinoma Among Experts at Tertiary Hospitals in China From 2020 to 2021 2020 - 2021年中国三级医院肝癌专家临床实践调查
Pub Date : 2025-04-07 DOI: 10.1002/cai2.70006
Hong Zhao, Yilei Mao, Hongguang Wang, Aiping Zhou, Zhengqiang Yang, Yue Han, Gong Li, Xinyu Bi, Chunyi Hao, Xiaodong Wang, Jun Zhou, Chaoliu Dai, Feng Wen, Jingdong Zhang, Ruibao Liu, Tao Li, Lei Zhao, Zuoxing Niu, Tianfu Wen, Qiu Li, Hongmei Zhang, Xiaoming Chen, Minshan Chen, Ming Zhao, Yajin Chen, Jun Yu, Jie Shen, Xiangchen Li, Lianxin Liu, Zhiyong Huang, Wei Zhang, Feng Shen, Weiping Zhou, Zhengang Yuan, Jian Zhai, Ningling Ge, Yongjun Chen, Huichuan Sun, Jianqiang Cai

Background

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death in China. The rapid progress in systemic therapies has led to the approval of many therapeutic methods that have quickly changed clinical guidelines and practices. Because of the high heterogeneity of HCC, there are still some gaps between the guidelines and real-world clinical practice. The present study surveyed experts in China to investigate the current treatment concepts and clinical practice regarding HCC.

Methods

A questionnaire survey on the treatment concepts and clinical practice of HCC was administered to 310 experts with senior professional titles in 2020 and 312 experts in 2021. The results were analyzed and compared.

Results

For treating patients with resectable HCC, 28% of hepatobiliary surgeons indicated neoadjuvant therapy, and 7% chose systemic therapy ± locoregional therapy as 1 L therapy in 2021 compared with 20% and 1% in 2020. More experts chose adjuvant treatment within 1 month in 2021 compared with 2020, and 6 months and 12 months were the leading choices for the duration of adjuvant treatment. In 2021, 79% of surgeons and 19% of interventionalists were willing to conduct downstaging/conversion therapy for patients with potentially resectable HCC, and 78% chose tyrosine kinase inhibitors (TKI) + immunotherapy (IO) + locoregional therapy for cases in which R0 resection could not be achieved. For completely unresectable HCC, more experts preferred TKI + IO-based therapy as 1 L therapy in 2021 compared with 2020 (78% vs. 55%). The proportion of experts who indicated TKI + IO-based therapy as 2 L therapy increased from 32% in 2020 to 40% in 2021.

Conclusion

The survey results indicated that in 2021, compared with 2020, more experts opted to administer IO + TKI for the treatment of liver cancer, and more experts and patients were willing to participate in clinical research.

背景:肝细胞癌(HCC)是中国癌症相关死亡的第二大原因。全身治疗的快速进展导致许多治疗方法的批准,这些方法迅速改变了临床指南和实践。由于HCC的高度异质性,指南与实际临床实践之间仍存在一些差距。本研究调查了中国的专家,以调查目前HCC的治疗理念和临床实践。方法对2020年310名高级职称专家和2021年312名专家进行HCC治疗理念和临床实践问卷调查。对结果进行了分析比较。结果对于可切除的HCC患者,2021年28%的肝胆外科医生选择新辅助治疗,7%选择全身治疗±局部治疗作为1l治疗,而2020年这一比例分别为20%和1%。与2020年相比,2021年选择1个月内辅助治疗的专家更多,6个月和12个月是辅助治疗时间的主要选择。2021年,79%的外科医生和19%的介入医师愿意对可能可切除的HCC患者进行降期/转化治疗,78%的患者选择酪氨酸激酶抑制剂(TKI) +免疫治疗(IO) +局部治疗,无法实现R0切除。对于完全不可切除的HCC,与2020年相比,2021年更多的专家选择TKI + io治疗作为1 L治疗(78%对55%)。认为TKI + io为2 L治疗的专家比例从2020年的32%上升到2021年的40%。调查结果显示,与2020年相比,2021年更多的专家选择使用IO + TKI治疗肝癌,更多的专家和患者愿意参与临床研究。
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引用次数: 0
Guideline for the Management Pathway and Quality Control of Breast Cancer Prevention and Treatment in China's Counties 中国县域乳腺癌防治管理途径与质量控制指南
Pub Date : 2025-03-26 DOI: 10.1002/cai2.70005
Breast Cancer Expert Committee of National Cancer Quality Control Center, Cancer Prevention and Treatment Committee of Healthy China Research Center

Breast cancer is one of the most common malignant tumors among women in China, with approximately 306,000 new cases reported in 2016. Notably, around 33% (100,400) of these cases occurred in rural areas. County-level hospitals, encompassing counties and county-level cities, serve as the primary diagnostic units for the majority of rural breast cancer patients. These hospitals are integral to cancer prevention, screening, maintenance treatment, rehabilitation, follow-up, and referral processes. However, economic and geographical constraints result in county-level hospitals being relatively deficient in medical equipment, health human resources, and drug accessibility. Consequently, there is a critical need for breast cancer prevention and management guidelines that are tailored to the specific conditions of China's counties. In response to this need, and within the policy framework of hierarchical diagnosis and treatment, a Chinese expert group has developed the Guideline for the Management Pathway and Quality Control of Breast Cancer Prevention and Treatment in China's Counties (2023 Edition). This guideline aims to expand the availability of quality medical resources, ensure better distribution of these resources across regions, and enhance the capacity for breast cancer prevention and treatment. Ultimately, the goal is to improve the prognosis and quality of life for breast cancer patients in China's counties. This guideline includes clear and concise path diagrams that are easy to implement in clinical practice, serving as a valuable reference for clinicians in county-level hospitals.

乳腺癌是中国女性最常见的恶性肿瘤之一,2016年报告的新病例约为30.6万例。值得注意的是,这些病例中约33%(100400例)发生在农村地区。包括县和县级市在内的县级医院是大多数农村乳腺癌患者的初级诊断单位。这些医院是癌症预防、筛查、维持治疗、康复、随访和转诊过程中不可或缺的一部分。然而,由于经济和地理条件的限制,县级医院在医疗设备、卫生人力资源和药品可及性方面相对不足。因此,迫切需要制定适合中国各县具体情况的乳腺癌预防和管理指南。针对这一需求,在分级诊疗的政策框架下,中国专家组制定了《中国县级乳腺癌防治管理路径与质量控制指南(2023年版)》。该指南旨在扩大优质医疗资源的可用性,确保这些资源在各区域之间更好地分配,并提高乳腺癌预防和治疗的能力。最终目标是改善中国各县乳腺癌患者的预后和生活质量。该指南包括清晰简明的路径图,易于在临床实践中实施,对县级医院临床医生有参考价值。
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引用次数: 0
Individualized Analysis of Nipple-Sparing Mastectomy Versus Modified Radical Mastectomy Using Deep Learning 利用深度学习对保留乳头乳房切除术与改良根治术的个体化分析
Pub Date : 2025-03-26 DOI: 10.1002/cai2.70002
Enzhao Zhu, Linmei Zhang, Pu Ai, Jiayi Wang, Chunyu Hu, Huiqing Pan, Weizhong Shi, Ziqin Xu, Yidan Fang, Zisheng Ai

Background

This study aimed to evaluate the impact of nipple-sparing mastectomy (NSM) and modified radical mastectomy (MRM) on individual survival outcomes and to assess the potential of neoadjuvant systemic therapy (NST) in reducing surgical intervention requirements.

Methods

To develop treatment recommendations for breast cancer patients, five machine learning models were trained. To mitigate bias in treatment allocation, advanced statistical methods, including propensity score matching (PSM) and inverse probability treatment weighting (IPTW), were applied.

Results

NSM demonstrated either superior or noninferior survival outcomes compared with MRM across all breast cancer stages, irrespective of adjustments for IPTW and PSM. Among all models and National Comprehensive Cancer Network guidelines, the Balanced Individual and Mixture Effect (BIME) for survival regression model proposed in this study showed the strongest protective effects in treatment recommendations, as evidenced by an IPTW hazard ratio of 0.39 (95% CI: 0.26–0.59), an IPTW risk difference of 19.66% (95% CI: 18.20–21.13), and an IPTW difference in restricted mean survival time of 17.77 months (95% CI: 16.37–19.21). NST independently reduced the probability of surgical intervention by 1.4% (95% CI: 0.9%–2.0%), with the greatest impact observed in patients with locally advanced breast cancer, in whom a 4.5% reduction (95% CI: 3.8%–5.2%) in surgical selection was noted.

Conclusions

The BIME model provides superior accuracy in recommending surgical approaches for breast cancer patients, leading to improved survival outcomes. These findings underscore the potential of BIME to enhance clinical decision-making. However, further investigation incorporating comprehensive prognostic evaluation is needed to optimize the surgical selection process and refine its clinical utility.

本研究旨在评估保留乳头乳房切除术(NSM)和改良根治性乳房切除术(MRM)对个体生存结果的影响,并评估新辅助全身治疗(NST)在减少手术干预需求方面的潜力。方法通过训练5个机器学习模型,为乳腺癌患者制定治疗建议。为了减轻治疗分配中的偏倚,采用了倾向得分匹配(PSM)和逆概率治疗加权(IPTW)等先进的统计方法。结果:与MRM相比,NSM在所有乳腺癌分期中表现出优越或非低劣的生存结果,与IPTW和PSM的调整无关。在所有模型和国家综合癌症网络指南中,本研究提出的平衡个体和混合效应(BIME)生存回归模型在治疗建议中显示出最强的保护作用,IPTW风险比为0.39 (95% CI: 0.26-0.59), IPTW风险差为19.66% (95% CI: 18.20-21.13), IPTW限制平均生存时间差为17.77个月(95% CI: 16.37-19.21)。NST独立降低手术干预的概率1.4% (95% CI: 0.9%-2.0%),对局部晚期乳腺癌患者影响最大,手术选择减少4.5% (95% CI: 3.8%-5.2%)。结论BIME模型为乳腺癌患者推荐手术入路提供了更高的准确性,从而改善了生存结果。这些发现强调了BIME在提高临床决策方面的潜力。然而,需要进一步的研究,包括全面的预后评估,以优化手术选择过程和完善其临床应用。
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引用次数: 0
Investigating the Mechanism of IFN-γ-Inducible Lysosomal Thiol Reductase-Mediated Inhibition of Breast Cancer Cell Proliferation IFN-γ诱导的溶酶体硫醇还原酶介导的乳腺癌细胞增殖抑制机制的研究
Pub Date : 2025-03-15 DOI: 10.1002/cai2.161
Qin Liu, Xiaoning Yuan, Youcheng Shao, Xiaoqing Guan, Kaixiang Feng, Mengfei Chu, Le Chen, Hui Li, Hanhui Liu, Jingwei Zhang, Yihao Tian, Lei Wei

Background

Breast cancer has become a severe threat to human health, making it imperative to identify effective drugs and therapeutic targets.

Methods

Various molecular biology experiments, such as western blot analysis, cytologic effect, co-immunoprecipitation, and immunofluorescence assays, as well as a nude mouse xenograft tumor model, were used to comprehensively analyze the impact of gamma-interferon-inducible lysosomal thiol reductase (GILT) on the malignant phenotype of breast cancer cells. This work was performed to examine GILT expression levels and explore the potential mechanism in breast cancer.

Results

GILT protein expression levels were significantly lower in breast cancer cells than in normal breast epithelial cells. Overexpressing GILT inhibited breast cancer cell proliferation and migration and slowed tumor growth. GILT inhibited the interaction between the MYC and WDR5 transcription complex and played a tumor-suppressive role. The MYC/WDR5 transcription complex inhibitor OICR-9429 could synergize with GILT to inhibit breast cancer cell proliferation.

Conclusion

This study reveals a potential mechanism by which GILT can slow breast cancer growth, as well as identifying the possible clinical application value of small molecule inhibitor OICR-9429. These data collectively provide novel treatment strategies for breast cancer therapy.

乳腺癌已成为人类健康的严重威胁,寻找有效的药物和治疗靶点势在必行。方法采用western blot分析、细胞学效应、共免疫沉淀、免疫荧光等多种分子生物学实验,结合裸鼠异种移植肿瘤模型,综合分析γ -干扰素诱导溶酶体硫醇还原酶(GILT)对乳腺癌细胞恶性表型的影响。这项工作是为了检测GILT的表达水平,并探讨其在乳腺癌中的潜在机制。结果GILT蛋白在乳腺癌细胞中的表达水平明显低于正常乳腺上皮细胞。过表达GILT抑制乳腺癌细胞增殖和迁移,减缓肿瘤生长。GILT抑制MYC和WDR5转录复合物之间的相互作用,发挥肿瘤抑制作用。MYC/WDR5转录复合物抑制剂OICR-9429可与GILT协同抑制乳腺癌细胞增殖。结论本研究揭示了GILT减缓乳腺癌生长的潜在机制,并确定了小分子抑制剂OICR-9429可能的临床应用价值。这些数据共同为乳腺癌治疗提供了新的治疗策略。
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引用次数: 0
Inhibition of Putative Ibrutinib Targets Promotes Atrial Fibrillation, Conduction Blocks, and Proarrhythmic Electrocardiogram Indices: A Mendelian Randomization Analysis 依鲁替尼的抑制作用可促进心房颤动、传导阻滞和促心律失常心电图指标:孟德尔随机分析
Pub Date : 2025-03-12 DOI: 10.1002/cai2.70004
Hongxuan Xu, Bingxun Li, Pinchao Lv, Ying Chen, Yanyun Lin, An Zhang, Jing Zhao, Guoxiong Zhou, Lin Wu

Background

The mechanism by which ibrutinib, a Bruton's tyrosine kinase inhibitor, can elevate the risk of arrhythmias is not fully elucidated. In this study, we explored how inhibition of off-target kinases can contribute to this phenomenon.

Methods

We performed a Mendelian randomization analysis to examine the causal associations between genetically proxied inhibition of six putative ibrutinib drug targets (ErbB2/HER2, CSK, JAK3, TEC, BLK, and PLCG2) and the atrial fibrillation (AF) risk, proarrhythmic ECG indices, and cardiometabolic traits and diseases. Inverse-variance weighted random-effects models and Wald ratio were used to examine the associations between genetically proxied inhibition of these drug targets and the risk of outcomes. Colocalization analyses were employed to examine the robustness of the causally significant findings. ELISAs were used to measure ErbB2 levels in intracardiac plasma samples.

Results

Genetically proxied ErbB2 inhibition was associated with an increased AF risk, higher P wave terminal force, and prolonged QTc interval. Patients with AF had significantly higher intracardiac ErbB2 levels compared with patients with paroxysmal supraventricular tachycardia. CSK inhibition prolonged the QRS duration, decreased the QTc interval, and was potentially linked to conduction blocks. PLCG2 inhibition led to decreased P wave terminal force, shorter QTc interval, and increased risk of left bundle branch block. BLK inhibition shortened the QTc interval and was also associated with atrioventricular block.

Conclusion

The off-target effects and downstream targets of ibrutinib, including CSK, PLCG2, ERBB2, TEC, and BLK, may lead to cardiac electrical homeostasis imbalances and lethal cardiovascular diseases. Using drugs that inhibit these targets should be given extra caution.

伊鲁替尼是一种布鲁顿酪氨酸激酶抑制剂,其提高心律失常风险的机制尚不完全清楚。在这项研究中,我们探讨了如何抑制脱靶激酶可以促进这种现象。方法采用孟德尔随机化分析,研究6种依鲁替尼药物靶点(ErbB2/HER2、CSK、JAK3、TEC、BLK和PLCG2)的遗传抑制与房颤(AF)风险、心电促心律失常指标、心脏代谢特征和疾病之间的因果关系。使用反方差加权随机效应模型和沃尔德比来检查这些药物靶点的遗传代理抑制与结局风险之间的关系。采用共定位分析来检验因果显著性发现的稳健性。elisa法检测心内血浆样品中ErbB2水平。结果基因介导的ErbB2抑制与房颤风险增加、P波终末力升高和QTc间期延长有关。与阵发性室上性心动过速患者相比,房颤患者心内ErbB2水平明显升高。CSK抑制延长QRS持续时间,缩短QTc间隔,并可能与传导阻滞有关。PLCG2抑制导致P波终末力降低,QTc间隔缩短,左束支阻滞风险增加。BLK抑制可缩短QTc间期,并与房室传导阻滞相关。结论依鲁替尼的脱靶效应和下游靶点CSK、PLCG2、ERBB2、TEC和BLK可能导致心电稳态失衡和致死性心血管疾病。使用抑制这些靶标的药物应该格外小心。
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引用次数: 0
Computed Tomography-Based Habitat Analysis for Prognostic Stratification in Colorectal Liver Metastases 基于计算机断层扫描的结直肠肝转移预后分层分析
Pub Date : 2025-03-12 DOI: 10.1002/cai2.70000
Chaoqun Zhou, Hao Xin, Lihua Qian, Yong Zhang, Jing Wang, Junpeng Luo

Background

Colorectal liver metastasis (CRLM) has a poor prognosis, and traditional prognostic models have certain limitations in clinical application. This study aims to evaluate the prognostic value of CT-based habitat analysis in CRLM patients and compare it with existing traditional prognostic models to provide more evidence for individualized treatment of CRLM patients.

Methods

This retrospective study included 197 patients with CRLM whose preoperative contrast-enhanced CT images and corresponding DICOM Segmentation Objects (DSOs) were obtained from The Cancer Imaging Archive (TCIA). Tumor regions were segmented, and habitat features representing distinct subregions were extracted. An unsupervised K-means clustering algorithm classified the tumors into two clusters based on their habitat characteristics. Kaplan–Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), and liver-specific DFS. The habitat model's predictive performance was compared with the Clinical Risk Score (CRS) and Tumor Burden Score (TBS) using the concordance index (C-index), Integrated Brier Score (IBS), and time-dependent area under the curve (AUC).

Results

The habitat model identified two distinct patient clusters with significant differences in OS, DFS, and liver-specific DFS (p < 0.01). Compared with CRS and TBS, the habitat model demonstrated superior predictive accuracy, particularly for DFS and liver-specific DFS, with higher time-dependent AUC values and improved model calibration (lower IBS).

Conclusions

CT-based habitat analysis captures spatial tumor heterogeneity and provides enhanced prognostic stratification in CRLM. The method outperforms conventional models and offers potential for more personalized treatment planning.

结直肠癌肝转移(Colorectal liver metastasis, CRLM)预后较差,传统预后模型在临床应用中存在一定局限性。本研究旨在评价基于ct的栖息地分析在CRLM患者中的预后价值,并将其与现有传统预后模型进行比较,为CRLM患者的个体化治疗提供更多依据。方法回顾性研究197例CRLM患者,术前CT增强图像及相应的DICOM分割目标(dso)均来自The Cancer Imaging Archive (TCIA)。对肿瘤区域进行分割,提取代表不同亚区域的栖息地特征。一种无监督k均值聚类算法根据肿瘤的栖息地特征将肿瘤分为两类。Kaplan-Meier分析用于评估总生存期(OS)、无病生存期(DFS)和肝脏特异性生存期(DFS)。采用一致性指数(C-index)、综合Brier评分(IBS)和随时间变化的曲线下面积(AUC),将栖息地模型的预测性能与临床风险评分(CRS)和肿瘤负担评分(TBS)进行比较。结果habitat模型确定了两个不同的患者群,在OS、DFS和肝脏特异性DFS方面存在显著差异(p < 0.01)。与CRS和TBS相比,栖息地模型具有更高的预测精度,特别是对DFS和肝脏特异性DFS,具有更高的时间依赖性AUC值和改进的模型校准(更低的IBS)。结论基于ct的栖息地分析捕获了肿瘤的空间异质性,并为CRLM的预后分层提供了增强的依据。该方法优于传统模型,并为更个性化的治疗计划提供了潜力。
{"title":"Computed Tomography-Based Habitat Analysis for Prognostic Stratification in Colorectal Liver Metastases","authors":"Chaoqun Zhou,&nbsp;Hao Xin,&nbsp;Lihua Qian,&nbsp;Yong Zhang,&nbsp;Jing Wang,&nbsp;Junpeng Luo","doi":"10.1002/cai2.70000","DOIUrl":"https://doi.org/10.1002/cai2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal liver metastasis (CRLM) has a poor prognosis, and traditional prognostic models have certain limitations in clinical application. This study aims to evaluate the prognostic value of CT-based habitat analysis in CRLM patients and compare it with existing traditional prognostic models to provide more evidence for individualized treatment of CRLM patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included 197 patients with CRLM whose preoperative contrast-enhanced CT images and corresponding DICOM Segmentation Objects (DSOs) were obtained from The Cancer Imaging Archive (TCIA). Tumor regions were segmented, and habitat features representing distinct subregions were extracted. An unsupervised K-means clustering algorithm classified the tumors into two clusters based on their habitat characteristics. Kaplan–Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), and liver-specific DFS. The habitat model's predictive performance was compared with the Clinical Risk Score (CRS) and Tumor Burden Score (TBS) using the concordance index (C-index), Integrated Brier Score (IBS), and time-dependent area under the curve (AUC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The habitat model identified two distinct patient clusters with significant differences in OS, DFS, and liver-specific DFS (<i>p</i> &lt; 0.01). Compared with CRS and TBS, the habitat model demonstrated superior predictive accuracy, particularly for DFS and liver-specific DFS, with higher time-dependent AUC values and improved model calibration (lower IBS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CT-based habitat analysis captures spatial tumor heterogeneity and provides enhanced prognostic stratification in CRLM. The method outperforms conventional models and offers potential for more personalized treatment planning.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100212,"journal":{"name":"Cancer Innovation","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cai2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunological Effects of Proton Radiotherapy: New Opportunities and Challenges in Cancer Therapy 质子放疗的免疫效应:癌症治疗的新机遇与挑战
Pub Date : 2025-03-07 DOI: 10.1002/cai2.70003
Anhang Zhang, Liyuan Fan, Qi Liu, Xiaoxin Zuo, Jian Zhu

Radiation therapy can be categorised by particle type into photon, proton and heavy ion therapies. Proton radiotherapy is highlighted due to its unique physical properties, such as the Bragg peak and minimal exit dose, which offer superior dose distribution. This makes proton radiotherapy especially advantageous for treating tumours near vital organs with complex structures, such as gliomas near the brain, nasopharyngeal carcinoma near the brainstem and mediastinal tumours near the heart. Proton irradiation can induce distant effects through immunogenicity within the target area. The reduced low-dose zone outside the target provides better lymphatic system protection and immune benefits. Additionally, combining proton radiotherapy with immunotherapy may offer further biological advantages. These features make proton radiotherapy a promising option in cancer treatment. This article may aid in the understanding of proton radiotherapy and its immune effects and lead to new effective options for tumour treatment.

放射治疗可按粒子类型分为光子、质子和重离子治疗。质子放射治疗因其独特的物理特性而备受关注,如布拉格峰和最小的出口剂量,提供了优越的剂量分布。这使得质子放射治疗在治疗结构复杂的重要器官附近的肿瘤时特别有利,例如脑附近的胶质瘤、脑干附近的鼻咽癌和心脏附近的纵隔肿瘤。质子照射可通过靶区的免疫原性诱导远处效应。目标外减少的低剂量区提供更好的淋巴系统保护和免疫益处。此外,质子放射治疗与免疫治疗相结合可能提供进一步的生物学优势。这些特点使质子放疗成为癌症治疗中一个很有前途的选择。本文可能有助于理解质子放疗及其免疫效应,并为肿瘤治疗提供新的有效选择。
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引用次数: 0
T-Cadherin in Biliary Tract Cancer Stroma, a Potent Pharmacological Target for Biliary Tract Carcinogenesis 胆道癌基质中的t -钙粘蛋白是胆道癌变的有效药理靶点
Pub Date : 2025-02-28 DOI: 10.1002/cai2.70001
Yuki Hanamatsu, Chiemi Saigo, Tamotsu Takeuchi
<p>Based on the empirical data, we propose that T-cadherin could be a molecular target for disrupting the stroma of patients with biliary tract cancer (BTC).</p><p>BTC comprises carcinomas originating in the bile ducts, including cholangiocarcinomas (cancers arising in the intrahepatic or extrahepatic bile ducts) and gallbladder carcinomas [<span>1</span>]. BTC often exhibits an aggressive clinicopathological course [<span>1</span>]. Surgical resection remains the most curative treatment option for patients with BTC; however, it may be limited to the early stages of cancer [<span>1</span>]. Owing to their poor sensitivity to chemotherapeutic agents, new therapeutic approaches are required for patients with advanced BTC.</p><p>One of the remarkable pathological features of BTC is the dense fibrous stroma harboring cancer cell nests. It is well established that stromal cells play a crucial role in the tumor microenvironment. Therefore, several targeting therapies are attempted against cancer stroma. For example, lysyl oxidases (LOXs) are a family of five secreted copper-dependent amine oxidases (LOX and LOXL1–4) that promote carcinogenesis by generating cancer stroma. Very recently, Burchard et al. [<span>2</span>] demonstrated that PXS-5505, which is a small molecule inhibitor of all LOX isoforms, improved chemotherapeutic penetration and reduced the inflammatory reaction of intrahepatic cholangiocarcinoma, thereby enhancing antitumor immunity in autochthonous and orthotopic murine models. Unfortunately, efforts to target individual LOX isoforms have failed to achieve clinical impact, likely due to the compensatory action of other LOX family members. Combination therapies targeting multiple stromal components are warranted.</p><p>T-cadherin is an atypical cadherin attached to the plasma membrane by a glycosylphosphatidylinositol anchor without a cytosolic domain [<span>2</span>]. Notably, it is overexpressed in endothelial cells of tumor-penetrating vessels in several malignant tumors [<span>3, 4</span>].</p><p>In this study, we investigated whether T-cadherin was also expressed in the tumor endothelial cells of BTC. Immunohistochemical staining using a tissue microarray, with a core diameter of 1.5 mm, demonstrated T-cadherin immunoreactivity in cancer stromal niches in BTC, especially in the cancer invasion microenvironment with a desmoplastic reaction (Figure 1a–d). Furthermore, T-cadherin expression was detected in the endothelial cells of tumor vessels and stromal mesenchymal cells of all 27 intrahepatic cholangiocarcinomas and 32 of 43 extrahepatic biliary duct adenocarcinomas. Consistent with previous research [<span>3</span>], T-cadherin immunoreactivity was also observed in the endothelial cells of tumor-penetrating vessels in breast and colorectal cancers. However, little T-cadherin immunoreactivity was observed in the stromal mesenchymal cells of these cancers (Figure 1e,f).</p><p>Here, we could not unravel whether stromal T-cadherin ex
基于实验数据,我们提出t -钙粘蛋白可能是破坏胆道癌(BTC)患者间质的分子靶点。BTC包括起源于胆管的癌,包括胆管癌(发生在肝内或肝外胆管的癌症)和胆囊癌[1]。BTC常表现为侵袭性的临床病理过程。手术切除仍然是BTC患者最有效的治疗选择;然而,它可能仅限于癌症的早期阶段。由于对化疗药物的敏感性较差,晚期BTC患者需要新的治疗方法。BTC的一个显著病理特征是致密的纤维间质窝藏癌细胞巢。基质细胞在肿瘤微环境中起着至关重要的作用。因此,一些针对癌症基质的靶向治疗被尝试。例如,赖氨酸氧化酶(LOXs)是一个由五种分泌的铜依赖胺氧化酶(LOX和LOXL1-4)组成的家族,它们通过产生癌症基质来促进致癌。最近,Burchard等人证实PXS-5505是所有LOX亚型的小分子抑制剂,可以改善化疗渗透,减少肝内胆管癌的炎症反应,从而增强原位和原位小鼠模型的抗肿瘤免疫。不幸的是,针对单个LOX异构体的努力未能取得临床效果,可能是由于其他LOX家族成员的代偿作用。针对多种基质成分的联合治疗是必要的。t -钙粘蛋白是一种非典型的钙粘蛋白,通过糖基磷脂酰肌醇锚点附着在质膜上,没有胞质结构域[2]。值得注意的是,它在几种恶性肿瘤的穿瘤血管内皮细胞中过表达[3,4]。在本研究中,我们研究了T-cadherin是否也在BTC的肿瘤内皮细胞中表达。使用组织微阵列(核心直径为1.5 mm)进行免疫组化染色,显示T-cadherin在BTC的癌间质壁龛中具有免疫反应性,特别是在伴有结缔组织增生反应的癌症侵袭微环境中(图1a-d)。此外,27例肝内胆管癌和43例肝外胆管腺癌中32例肿瘤血管内皮细胞和间质细胞中均检测到T-cadherin的表达。与先前的研究一致[3],在乳腺癌和结直肠癌的穿瘤血管内皮细胞中也观察到T-cadherin的免疫反应性。然而,在这些癌症的间质细胞中观察到很少的t -钙粘蛋白免疫反应性(图1e,f)。在这里,我们无法揭示基质t -钙粘蛋白表达是否与临床病理特征有关,包括预后、治疗耐药性或转移。此外,由于肿瘤内的异质性,后续的研究探索t -钙粘蛋白间质表达的病理生物学特性使用整个组织标本执行各种临床病理参数是必要的。坚固的纤维间质是BTC的一个特征,它阻碍了免疫细胞的渗透。引人注目的是,最近的研究表明,外泌体PD-L1赋予癌细胞免疫逃避能力。因此,免疫检查点抑制剂治疗面临着诸如BTC[7]应答率低的挑战。几种临床前方法使用外泌体抑制剂GW4869来抑制癌症进展[8]。值得注意的是,脂联素- t -钙粘蛋白途径也介导外泌体的生物发生[9]。我们假设靶向T-cadherin可能是一种新的治疗策略,可能会降低外泌体PD-L1并增加免疫检查点抑制剂在BTC中的作用。T-cadherin缺失小鼠存活且可生育,这表明其他分子可以补充T-cadherin的生理特性。我们认为靶向T-cadherin可以提高BTC患者的免疫治疗效果。此外,PXS-5505、GW4869或更多靶向多种基质成分的联合治疗可能更有效。花松幸:资金获取(相等),调查(相等),撰写-原创草案(相等)。Chiemi Saigo:数据整理(平等),调查(支持),撰写-原创草案(领导)。Tamotsu Takeuchi:概念化(平等),数据管理(平等),资金获取(平等),写作-审查和编辑(领先)。作者没有什么可报告的。作者没有什么可报告的。作者声明无利益冲突。
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引用次数: 0
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Cancer Innovation
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