Cancer Science最新文献_第5页

PHAX enhanced LIN28B-mediated PBX3 mRNA stability to promote esophageal cancer development. PHAX 可增强 LIN28B 介导的 PBX3 mRNA 的稳定性，从而促进食管癌的发展。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-12 DOI: 10.1111/cas.16420

Jie Peng, Liang Lv, Yuqian Zhou, Xuehong Wang, Changmei Hu

引用次数: 0

Tumor exosomal RNPEP promotes lung metastasis of liver cancer via inducing cancer-associated fibroblast activation. 肿瘤外泌体RNPEP通过诱导癌症相关成纤维细胞活化促进肝癌肺转移。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-10 DOI: 10.1111/cas.16417

Yuankun Chen, Gaofeng Pan, Yijun Yang, Haifeng Wu, Minhua Weng, Qiuping Wu, Yufeng Gao, Wenting Li

{"title":"Tumor exosomal RNPEP promotes lung metastasis of liver cancer via inducing cancer-associated fibroblast activation.","authors":"Yuankun Chen, Gaofeng Pan, Yijun Yang, Haifeng Wu, Minhua Weng, Qiuping Wu, Yufeng Gao, Wenting Li","doi":"10.1111/cas.16417","DOIUrl":"https://doi.org/10.1111/cas.16417","url":null,"abstract":"Cancer-associated fibroblasts (CAFs) are essential players in the tumor microenvironment (TME) due to their roles in facilitating tumor progression and metastasis. It is worth noting that the high-metastatic hepatocellular carcinoma (HCC) cell-derived exosomes have exhibited the ability to transform normal fibroblasts into CAFs, which further fosters the lung metastasis of low-metastatic HCC cells. Yet, the mechanisms underlying this tumor exosome-induced metastatic niche formation are poorly explored. In this study, the secreted protein arginyl aminopeptidase (RNPEP) was highly expressed in the plasma of patients with HCC. In addition, high-metastatic HCC cells showed augmented RNPEP expression levels in their exosomes. These exosomes induced obvious CAF-like properties in the human fibroblast cell line MRC-5, as evidenced by the increased CAF marker expression, and enhanced migratory ability. More strikingly, the secretions from high-metastatic tumor exosome-educated MRC-5 cells increased tumor stemness and promoted epithelial-mesenchymal transition (EMT) in MHCC-97L cells, a low-metastatic HCC cell line. However, the knockdown of RNPEP in exosomes from high-metastatic HCC cells abated the changes described above. Animal studies in vivo highlighted the pro-tumor and pro-metastatic effects of exosomal RNPEP on MHCC-97L cells by inducing CAF activation. Furthermore, tumor-derived exosomal RNPEP induced the activation of NF-κB signaling in MRC-5 cells, a critical pathway associated with CAF activation. Collectively, these results provide novel insight into tumor-derived exosomal RNPEP for its crosstalk with CAFs during HCC lung metastasis.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase II study of perioperative camrelizumab and XELOX for locally advanced gastric or gastroesophageal junction adenocarcinoma. 局部晚期胃癌或胃食管交界腺癌围手术期康瑞珠单抗和XELOX的II期研究。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-10 DOI: 10.1111/cas.16425

Jiaxing He, Bo Zhang, Shuai Zhou, Ying Yang, Zhuo Han, Tao Wu, Qing Qiao, Haicheng Yang, Xianli He, Nan Wang

{"title":"Phase II study of perioperative camrelizumab and XELOX for locally advanced gastric or gastroesophageal junction adenocarcinoma.","authors":"Jiaxing He, Bo Zhang, Shuai Zhou, Ying Yang, Zhuo Han, Tao Wu, Qing Qiao, Haicheng Yang, Xianli He, Nan Wang","doi":"10.1111/cas.16425","DOIUrl":"https://doi.org/10.1111/cas.16425","url":null,"abstract":"Immune checkpoint inhibitors combined with chemotherapy have shown promising efficacy in treating gastric or gastroesophageal junction (G/GEJ) adenocarcinoma in the neoadjuvant setting. This phase II trial (NCT05715632) aimed to investigate the efficacy and safety of perioperative camrelizumab plus XELOX in patients with locally advanced G/GEJ adenocarcinoma. Treatment-naive patients with cT3-4aN1-3 M0 resectable locally advanced G/GEJ adenocarcinoma were recruited to receive camrelizumab (200 mg, intravenously) on Day 1 combined with XELOX (oxaliplatin at 130 mg/m2 on Day 1 and capecitabine at 1000 mg/m2 on Days 1-14) every 3 weeks for four cycles, followed by surgery and adjuvant camrelizumab combined with XELOX every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR; ypT0N0) rate. From September 2020 to January 2023, 46 patients were enrolled, and all patients completed neoadjuvant therapy. Among them, 43 underwent D2 resection. In the intention-to-treat population, pCR was achieved in nine patients (19.6%, 95% confidence interval [CI]: 9.9%-34.4%), and the major pathological response was achieved in 25 patients (54.3%, 95% CI: 39.2%-68.8%). The objective response rate was 69.6%, of which 12 patients achieved a complete response and 20 patients achieved a partial response. The 1-year event-free survival and disease-free survival rates were both 93.1%. Treatment-related adverse events (TRAEs) occurred in 42 (91.3%) patients, and grade 3 TRAEs occurred in nine (19.6%) patients. No grades 4-5 TRAEs were observed. Perioperative camrelizumab combined with XELOX showed promising pathological response with an acceptable safety profile in patients with resectable locally advanced G/GEJ adenocarcinoma.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BCR::ABL1-induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia. BCR: abl1诱导的线粒体形态改变作为慢性髓性白血病潜在的临床生物标志物。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-09 DOI: 10.1111/cas.16424

Kohjin Suzuki, Naoki Watanabe, Satoru Torii, Satoko Arakawa, Kiyosumi Ochi, Shun Tsuchiya, Kazuhiro Yamada, Yoko Kawamura, Sadao Ota, Norio Komatsu, Shigeomi Shimizu, Miki Ando, Tomoiku Takaku

{"title":"BCR::ABL1-induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia.","authors":"Kohjin Suzuki, Naoki Watanabe, Satoru Torii, Satoko Arakawa, Kiyosumi Ochi, Shun Tsuchiya, Kazuhiro Yamada, Yoko Kawamura, Sadao Ota, Norio Komatsu, Shigeomi Shimizu, Miki Ando, Tomoiku Takaku","doi":"10.1111/cas.16424","DOIUrl":"https://doi.org/10.1111/cas.16424","url":null,"abstract":"The BCR::ABL1 oncogene plays a crucial role in the development of chronic myeloid leukemia (CML). Previous studies have investigated the involvement of mitochondrial dynamics in various cancers, revealing potential therapeutic strategies. However, the impact of BCR::ABL1 on mitochondrial dynamics remains unclear. In this study, we demonstrated that BCR::ABL1 is sufficient to induce excessive mitochondrial fragmentation by activating dynamin-related protein (DRP)1 through the mitogen-activated protein kinase (MAPK) pathway. Leukocytes obtained from patients with CML and the BCR::ABL1-positive cell lines exhibited increased mitochondrial fragmentation compared to leukocytes obtained from healthy donors and BCR::ABL1-negative cells. Furthermore, the analysis of BCR::ABL1-transduced cells showed increased phosphorylation of DRP1 at serine 616 and extracellular signal-regulated kinase (ERK) 1/2. Moreover, the inhibition of DRP1 and upstream mitogen-activated extracellular signal-regulated kinase (MEK) 1/2 suppressed mitochondrial fragmentation. Strikingly, DRP1 inhibition effectively reduced the viability of BCR::ABL1-positive cells and induced necrotic cell death. Additionally, a label-free artificial intelligence-driven flow cytometry successfully identified not only the BCR::ABL1-transduced cells but also peripheral leukocytes from CML patients by assessing mitochondrial morphological alterations. These findings suggested the crucial role of BCR::ABL1-induced mitochondrial fragmentation in driving BCR::ABL1-positive cell proliferation, and the potential use of mitochondrial morphological alterations as a clinical biomarker for the label-free detection of CML cells.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer-associated fibroblast-derived MMP11 promotes tumor progression in pancreatic cancer. 癌症相关成纤维细胞衍生的MMP11促进胰腺癌的肿瘤进展。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-05 DOI: 10.1111/cas.16418

Zhuoyin Wang, Xu Guo, Xinming Li, Jing Wang, Nengwei Zhang, Buhe Amin, Guangzhong Xu, Bin Zhu

{"title":"Cancer-associated fibroblast-derived MMP11 promotes tumor progression in pancreatic cancer.","authors":"Zhuoyin Wang, Xu Guo, Xinming Li, Jing Wang, Nengwei Zhang, Buhe Amin, Guangzhong Xu, Bin Zhu","doi":"10.1111/cas.16418","DOIUrl":"https://doi.org/10.1111/cas.16418","url":null,"abstract":"Matrix metalloproteinase 11 (MMP11), a zinc-dependent endopeptidase involved in extracellular matrix degradation and remodeling, has been identified as a tumor promoter in multiple cancer types. However, its expression pattern and role in pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, elevated MMP11 expression was identified in PDAC tissues and was associated with diminished survival. Integrated single-cell RNA sequencing and co-immunofluorescence staining revealed that MMP11 was predominantly expressed in cancer-associated fibroblasts (CAFs). Mechanistically, cancer cell-derived TGF-β1 mediated CAF activation via the pSmad2/3 pathway and accompanied by MMP11 production. Additionally, MMP11 knockdown in CAFs impaired the proliferative and invasive abilities of AsPC-1 and BxPC-3 cells in vitro; which could be rescued by adding recombinant MMP11. Similarly, co-injection of AsPC-1 cells with MMP11-knockdown CAFs into nude mice significantly suppressed tumor growth and liver metastasis compared with tumors bearing unmodified CAFs. Furthermore, we confirmed that CAF-derived MMP11 may drive the epithelial-mesenchymal transition process of PDAC cells to promote tumor invasion via the PI3K/AKT pathway rather than extracellular matrix remodeling. Collectively, we uncovered a crosstalk between cancer cells and CAFs mediated by TGF-β1 and MMP11 that drives the progression of PDAC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of BTK knockdown on lung adenocarcinoma growth and immune response. BTK基因敲低对肺腺癌生长和免疫应答的影响。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-04 DOI: 10.1111/cas.16394

Jilan Huang, Yufan Yuan, Linghong Guo, Guojin Xia, Yan Chen, Qi Chen, Min Wang

引用次数: 0

The protective role of anti-parkinsonian drugs in pancreatic cancer risk: A comprehensive case-control study in Taiwan. 抗帕金森药物对胰腺癌风险的保护作用：台湾地区一项全面的病例对照研究。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-04 DOI: 10.1111/cas.16422

Hsuan-Chia Yang, Wen-Chi Chou, Phung-Anh Nguyen, Nhi Thi Hong Nguyen, Nguyen Thi Phuong, Ching-Huan Wang, Jason C Hsu, Ming-Chin Lin, Chih-Wei Huang

{"title":"The protective role of anti-parkinsonian drugs in pancreatic cancer risk: A comprehensive case-control study in Taiwan.","authors":"Hsuan-Chia Yang, Wen-Chi Chou, Phung-Anh Nguyen, Nhi Thi Hong Nguyen, Nguyen Thi Phuong, Ching-Huan Wang, Jason C Hsu, Ming-Chin Lin, Chih-Wei Huang","doi":"10.1111/cas.16422","DOIUrl":"https://doi.org/10.1111/cas.16422","url":null,"abstract":"Pancreatic cancer is among the deadliest cancers, with a grim prognosis despite advances in treatment. We conducted a population-based case-control study from Taiwan, linking Health and Welfare Data Science Center data to the Taiwan Cancer Registry, which offers a promising strategy for its treatment through drug repurposing. The study aims to identify the association of anti-parkinsonian drugs with pancreatic cancer risk across different age groups. The analysis encompassed 18,921 pancreatic cancer cases and 75,684 matched controls, employing conditional logistic regression to assess the impact of anti-parkinsonian drugs on the risk of pancreatic cancer. Key findings revealed a statistically significant association of the administration with specific anti-parkinsonian medications, including anticholinergic agents, tertiary amines, dopa derivatives, and dopamine receptor agonists, with a reduction in pancreatic cancer risk. These associations were represented as adjusted odds ratios (aORs), ranging from 0.620 (95% CI 0.470-0.810) to 0.764 (95% CI 0.655-0.891). Further, age-stratified analysis revealed variations in efficacy across different age groups. Anticholinergic agents and tertiary amines exhibited greater effectiveness in the 40-64-year age group (aOR, 0.653; 95% CI, 0.489-0.872), whereas dopa derivatives and dopamine receptor agonists were particularly efficacious in the cohort aged ≥65 years (aOR, 0.728; 95% CI, 0.624-0.850 and aOR, 0.665; 95% CI, 0.494-0.894, respectively). Notably, specific drugs such as trihexyphenidyl, levodopa/dopa decarboxylase inhibitor (DDCI), and pramipexole demonstrated a significant decrease in cancer risk, especially in the elderly population. These preliminary findings can contribute to the possible therapeutic role of anti-parkinsonian drugs in the treatment of pancreatic cancer.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study. 肺癌风险与吸烟无关的DNA甲基化标记物：一项大型人群队列研究的外部验证。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-03 DOI: 10.1111/cas.16414

Zitong Zhao, Megha Bhardwaj, Ziwen Fan, Xianzhe Li, Petra Schrotz-King, Hermann Brenner

{"title":"Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study.","authors":"Zitong Zhao, Megha Bhardwaj, Ziwen Fan, Xianzhe Li, Petra Schrotz-King, Hermann Brenner","doi":"10.1111/cas.16414","DOIUrl":"https://doi.org/10.1111/cas.16414","url":null,"abstract":"Smoking-associated epigenetic changes have been linked to lung cancer (LC) risk; however, the role of epigenetic alterations independent of smoking is yet to be fully understood. This study aimed to validate 16 previously reported CpG sites that are independent of smoking yet associated with LC risk within a population-based prospective cohort. Using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay, DNA methylation (DNAm) in whole blood was assessed in four subsets (n = 736, 1027, 997, and 312) of a population-based cohort from Germany. The DNAm levels of the 16 smoking-independent CpG sites were analyzed. Hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to assess associations of DNAm at the 16 CpG sites with LC risk, adjusting for multiple covariates, including smoking habits and a smoking-associated DNAm score. Over 17 years of follow-up, a total of 199 LCs were observed. Among the 16 CpGs, cg02211449 showed a negative association with LC risk (HR [95% CI] per SD increase, = 0.70 [0.63-0.78]), while cg11385536 (1.04 [1.01-1.07]), cg09736286 (1.64 [1.10-2.44]), cg19907023 (1.64 [1.01-2.66]), and cg22032485 (1.52 [1.04-2.21]) displayed positive associations with LC risk. Five of the 16 suggested smoking-independent CpGs could be externally validated as predictors of LC risk. Further research should address their potential contribution to enhanced LC risk stratification.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatial immune heterogeneity in a mouse tumor model after immunotherapy. 免疫治疗后小鼠肿瘤模型的空间免疫异质性。

IF 5.7 2区医学

Cancer Science Pub Date : 2024-12-03 DOI: 10.1111/cas.16421

Michal Smahel, Shweta Dilip Johari, Jana Smahelova, Lucie Pfeiferova, Jaroslav Nunvar

{"title":"Spatial immune heterogeneity in a mouse tumor model after immunotherapy.","authors":"Michal Smahel, Shweta Dilip Johari, Jana Smahelova, Lucie Pfeiferova, Jaroslav Nunvar","doi":"10.1111/cas.16421","DOIUrl":"https://doi.org/10.1111/cas.16421","url":null,"abstract":"Cancer immunotherapy is increasingly used in clinical practice, but its success rate is reduced by tumor escape from the immune system. This may be due to the genetic instability of tumor cells, which allows them to adapt to the immune response and leads to intratumoral immune heterogeneity. The study investigated spatial immune heterogeneity in the tumor microenvironment and its possible drivers in a mouse model of tumors induced by human papillomaviruses (HPV) following immunotherapy. Gene expression was determined by RNA sequencing and mutations by whole exome sequencing. A comparison of different tumor areas revealed heterogeneity in immune cell infiltration, gene expression, and mutation composition. While the mean numbers of mutations with every impact on gene expression or protein function were comparable in treated and control tumors, mutations with high or moderate impact were increased after immunotherapy. The genes mutated in treated tumors were significantly enriched in genes associated with ECM metabolism, degradation, and interactions, HPV infection and carcinogenesis, and immune processes such as antigen processing and presentation, Toll-like receptor signaling, and cytokine production. Gene expression analysis of DNA damage and repair factors revealed that immunotherapy upregulated Apobec1 and Apobec3 genes and downregulated genes related to homologous recombination and translesion synthesis. In conclusion, this study describes the intratumoral immune heterogeneity, that could lead to tumor immune escape, and suggests the potential mechanisms involved.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0