Molecular Oncology最新文献_第3页

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IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-08-01 DOI: 10.1002/1878-0261.13002

引用次数: 0

Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II-IIIA NSCLC patients. 变体检测和片段长度分析相结合提高了对II-IIIA期NSCLC患者术后循环肿瘤DNA中最小残留疾病的检测

IF 5 2区医学

Molecular Oncology Pub Date : 2022-07-01 Epub Date: 2022-06-27 DOI: 10.1002/1878-0261.13267

Daan C L Vessies, Milou M F Schuurbiers, Vincent van der Noort, Irene Schouten, Theodora C Linders, Mirthe Lanfermeijer, Kalpana L Ramkisoensing, Koen J Hartemink, Kim Monkhorst, Michel M van den Heuvel, Daan van den Broek

{"title":"Combining variant detection and fragment length analysis improves detection of minimal residual disease in postsurgery circulating tumour DNA of stage II-IIIA NSCLC patients.","authors":"Daan C L Vessies, Milou M F Schuurbiers, Vincent van der Noort, Irene Schouten, Theodora C Linders, Mirthe Lanfermeijer, Kalpana L Ramkisoensing, Koen J Hartemink, Kim Monkhorst, Michel M van den Heuvel, Daan van den Broek","doi":"10.1002/1878-0261.13267","DOIUrl":"10.1002/1878-0261.13267","url":null,"abstract":"<p><p>Stage II-IIIA nonsmall cell lung cancer (NSCLC) patients receive adjuvant chemotherapy after surgery as standard-of-care treatment, even though only approximately 5.8% of patients will benefit. Identifying patients with minimal residual disease (MRD) after surgery using tissue-informed testing of postoperative plasma circulating cell-free tumour DNA (ctDNA) may allow adjuvant therapy to be withheld from patients without MRD. However, the detection of MRD in the postoperative setting is challenging, and more sensitive methods are urgently needed. We developed a method that combines variant calling and a novel ctDNA fragment length analysis using hybrid capture sequencing data. Among 36 stage II-IIIA NSCLC patients, this method distinguished patients with and without recurrence of disease in a 20 times repeated 10-fold cross validation with 75% accuracy (P = 0.0029). In contrast, using only variant calling or only fragment length analysis, no signification distinction between patients was shown (P = 0.24 and P = 0.074 respectively). In addition, a variant-level fragmentation score was developed that was able to classify variants detected in plasma cfDNA into tumour-derived or white-blood-cell-derived variants with 84% accuracy. The findings in this study may help drive the integration of various types of information from the same data, eventually leading to cheaper and more sensitive techniques to be used in this challenging clinical setting.</p>","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2719-2732"},"PeriodicalIF":5.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49047359","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

Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity 根治性前列腺切除术后前列腺癌复发与HLA类型和局部巨细胞病毒免疫有关

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-16 DOI: 10.1002/1878-0261.13273

J. Classon, Margherita Zamboni, Camilla Engblom, K. Alkass, G. Mantovani, Christian Pou, Dieudonné Nkulikiyimfura, P. Brodin, H. Druid, Jeff E. Mold, J. Frisén

{"title":"Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity","authors":"J. Classon, Margherita Zamboni, Camilla Engblom, K. Alkass, G. Mantovani, Christian Pou, Dieudonné Nkulikiyimfura, P. Brodin, H. Druid, Jeff E. Mold, J. Frisén","doi":"10.1002/1878-0261.13273","DOIUrl":"https://doi.org/10.1002/1878-0261.13273","url":null,"abstract":"Prostate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T‐cells. Two alleles, HLA‐A*02:01 and HLA‐A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer. We leveraged the next‐generation sequenced cohorts CPC‐GENE and TCGA‐PRAD to examine HLA alleles, antiviral T‐cell receptors and prostate cancer disease recurrence after prostatectomy. Carrying HLA‐A*02:01 (111/229; 48% of patients) was independently associated with disease recurrence in patients with low‐intermediate risk prostate cancer. HLA‐A*11 (carried by 42/441; 10% of patients) was independently associated with rapid disease recurrence in patients with high‐risk prostate cancer. Moreover, HLA‐A*02:01 carriers in which anti‐cytomegalovirus T‐cell receptors (CMV‐TCR) were identified in tumors (13/144; 10% of all patients in the cohort) had a higher risk of disease recurrence than CMV‐TCR‐negative patients. These findings suggest that HLA‐type and CMV immunity may be valuable biomarkers for prostate cancer progression.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"3452 - 3464"},"PeriodicalIF":6.6,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48045198","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: 6

Vandetanib drives growth arrest and promotes sensitivity to imatinib in chronic myeloid leukemia by targeting ephrin type‐B receptor 4 范德塔尼通过靶向肾上腺素B型受体4，在慢性粒细胞白血病中驱动生长停滞并提高对伊马替尼的敏感性

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-10 DOI: 10.1002/1878-0261.13270

Weina Ma, Man Zhu, Bo Wang, Zhengyan Gong, Xia Du, Tianfeng Yang, Xianpeng Shi, B. Dai, Y. Zhan, Dongdong Zhang, Yanhong Ji, Yang Wang, Song Li, Yanmin Zhang

{"title":"Vandetanib drives growth arrest and promotes sensitivity to imatinib in chronic myeloid leukemia by targeting ephrin type‐B receptor 4","authors":"Weina Ma, Man Zhu, Bo Wang, Zhengyan Gong, Xia Du, Tianfeng Yang, Xianpeng Shi, B. Dai, Y. Zhan, Dongdong Zhang, Yanhong Ji, Yang Wang, Song Li, Yanmin Zhang","doi":"10.1002/1878-0261.13270","DOIUrl":"https://doi.org/10.1002/1878-0261.13270","url":null,"abstract":"The oncogenic role of ephrin type‐B receptor 4 (EPHB4) has been reported in many types of tumors, including chronic myeloid leukemia (CML). Here, we found that CML patients have a higher EPHB4 expression level than healthy subjects. EPHB4 knockdown inhibited growth of K562 cells (a human immortalized myelogenous leukemia cell line). In addition, transient transfection of EPHB4 siRNA led to sensitization to imatinib. These growth defects could be fully rescued by EPHB4 transfection. To identify an EPHB4‐specific inhibitor with the potential of rapid translation into the clinic, a pool of clinical compounds was screened and vandetanib was found to be most sensitive to K562 cells, which express a high level of EPHB4. Vandetanib mainly acts on the intracellular tyrosine kinase domain and interacts stably with a hydrophobic pocket. Furthermore, vandetanib downregulated EPHB4 protein via the ubiquitin‐proteasome pathway and inhibited PI3K/AKT and MAPK/ERK signaling pathways in K562 cells. Vandetanib alone significantly inhibited tumor growth in a K562 xenograft model. Furthermore, the combination of vandetanib and imatinib exhibited enhanced and synergistic growth inhibition against imatinib‐resistant K562 cells in vitro and in vivo. These findings suggest that vandetanib drives growth arrest and overcomes the resistance to imatinib in CML via targeting EPHB4.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2747 - 2765"},"PeriodicalIF":6.6,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44369767","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: 4

Corrigendum to: iRGD‐modified exosomes effectively deliver CPT1A siRNA to colon cancer cells, reversing oxaliplatin resistance by regulating fatty acid oxidation iRGD修饰的外泌体有效地将CPT1A siRNA传递到结肠癌细胞，通过调节脂肪酸氧化逆转奥沙利铂耐药性

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-08 DOI: 10.1002/1878-0261.13258

引用次数: 0

PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway PGAM1通过cAMP/AMPK/CEBPB途径调控ASS1参与乳腺癌的进展

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-08 DOI: 10.1002/1878-0261.13259

Min Liu, Runmei Li, Min Wang, Ting Liu, Qiuru Zhou, D. Zhang, Jian Wang, Meng Shen, X. Ren, Qian Sun

{"title":"PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway","authors":"Min Liu, Runmei Li, Min Wang, Ting Liu, Qiuru Zhou, D. Zhang, Jian Wang, Meng Shen, X. Ren, Qian Sun","doi":"10.1002/1878-0261.13259","DOIUrl":"https://doi.org/10.1002/1878-0261.13259","url":null,"abstract":"Phosphoglycerate mutase 1 (PGAM1) is a crucial glycolytic enzyme, and its expression status has been confirmed to be associated with tumor progression and metastasis. However, the precise role and other biological functions of PGAM1 remain unclear. Here, we report that PGAM1 expression is upregulated and related to poor prognosis in patients with breast cancer (BC). Functional experiments showed that knockdown of PGAM1 could suppress the proliferation, invasion, migration, and epithelial–mesenchymal transition of BC cells. Through RNA sequencing, we found that argininosuccinate synthase 1 (ASS1) expression was markedly upregulated in BC cells following PGAM1 knockdown, and it is required to suppress the malignant biological behavior of BC cells. Importantly, we demonstrated that PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB axis. In vivo experiments further validated that PGAM1 promoted tumor growth in BC by altering ASS1 expression. Finally, immunohistochemical analysis showed that downregulated ASS1 levels were associated with PGAM1 expression and poor prognosis in patients with BC. Our study provides new insight into the regulatory mechanism of PGAM1‐mediated BC progression that might shed new light on potential targets and combination therapeutic strategies for BC treatment.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2843 - 2860"},"PeriodicalIF":6.6,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43392142","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: 2

RNA polymerase I inhibition induces terminal differentiation, growth arrest, and vulnerability to senolytics in colorectal cancer cells RNA聚合酶I抑制诱导结直肠癌癌症细胞的末端分化、生长停滞和对解毒剂的易感性

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-08 DOI: 10.1002/1878-0261.13265

C. Otto, C. Kastner, S. Schmidt, Konstantin L. Uttinger, Apoorva Baluapuri, S. Denk, M. Rosenfeldt, A. Rosenwald, F. Roehrig, C. Ade, Christina Schuelein-Voelk, M. Diefenbacher, Christoph‐Thomas Germer, E. Wolf, M. Eilers, A. Wiegering

{"title":"RNA polymerase I inhibition induces terminal differentiation, growth arrest, and vulnerability to senolytics in colorectal cancer cells","authors":"C. Otto, C. Kastner, S. Schmidt, Konstantin L. Uttinger, Apoorva Baluapuri, S. Denk, M. Rosenfeldt, A. Rosenwald, F. Roehrig, C. Ade, Christina Schuelein-Voelk, M. Diefenbacher, Christoph‐Thomas Germer, E. Wolf, M. Eilers, A. Wiegering","doi":"10.1002/1878-0261.13265","DOIUrl":"https://doi.org/10.1002/1878-0261.13265","url":null,"abstract":"Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461‐induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC‐interacting zinc‐finger protein 1 (MIZ1)‐ and retinoblastoma protein (Rb)‐dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine‐ and patient‐derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"2788 - 2809"},"PeriodicalIF":6.6,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45440442","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

Targeting cellular senescence to combat cancer and ageing 靶向细胞衰老对抗癌症和衰老

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-08 DOI: 10.1002/1878-0261.13266

Chen Wang, Xue Hao, Rugang Zhang

引用次数: 4

The sex‐dependent role of the androgen receptor in glioblastoma: results of molecular analyses 雄激素受体在胶质母细胞瘤中的性别依赖性作用：分子分析结果

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-05 DOI: 10.1002/1878-0261.13262

M. Łysiak, Małgorzata Trybuła, M. Mudaisi, C. Bratthäll, M. Strandeus, P. Milos, M. Hallbeck, A. Malmström

{"title":"The sex‐dependent role of the androgen receptor in glioblastoma: results of molecular analyses","authors":"M. Łysiak, Małgorzata Trybuła, M. Mudaisi, C. Bratthäll, M. Strandeus, P. Milos, M. Hallbeck, A. Malmström","doi":"10.1002/1878-0261.13262","DOIUrl":"https://doi.org/10.1002/1878-0261.13262","url":null,"abstract":"We sought to analyse the androgen receptor (AR) in glioblastoma (GBM) due to the location of the AR gene on chromosome X, often reported with shorter survival and higher prevalence of GBM among males. Copy number (CN) and mRNA expression of AR were tested with droplet digital PCR in 91 fresh‐frozen GBM samples and 170 formalin‐fixed, paraffin‐embedded samples collected at Linköping University Hospital. The fresh‐frozen cohort was also subjected to pyrosequencing methylation analysis of 17 CpG sites in the AR promoter. Additionally, the gene expression of AR was analysed in the fresh‐frozen cohort and The Cancer Genome Atlas (TCGA) cohort of isocitrate dehydrogenase wild‐type primary GBM (135 females and 219 males). The association of AR expression and overall survival (OS) was tested with Kaplan–Meier log rank analysis after dichotomisation by maximally selected rank statistics. We found that AR CN alterations were more common in female GBM. AR gene expression correlated with methylation levels of different CpG sites in males and females but there was no difference in expression between sexes. Survival analysis of TCGA cohort revealed the opposite effect of AR overexpression on OS of males and females, with high AR expression correlating with shorter OS in females and longer OS in males. Additional gene set enrichment analysis showed that AR expression correlated with DNA repair response, especially in the male group. In summary, we found that high AR gene expression in GBM exhibits sex‐dependent effects on patient survival, which, for males, is linked to DNA repair response.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"3436 - 3451"},"PeriodicalIF":6.6,"publicationDate":"2022-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46398931","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: 2

Metabolic reprogramming: a bridge between aging and tumorigenesis 代谢重编程:衰老和肿瘤发生之间的桥梁

IF 6.6 2区医学

Molecular Oncology Pub Date : 2022-06-05 DOI: 10.1002/1878-0261.13261

S. Drápela, Didem Ilter, Ana P. Gomes

{"title":"Metabolic reprogramming: a bridge between aging and tumorigenesis","authors":"S. Drápela, Didem Ilter, Ana P. Gomes","doi":"10.1002/1878-0261.13261","DOIUrl":"https://doi.org/10.1002/1878-0261.13261","url":null,"abstract":"Aging is the most robust risk factor for cancer development, with more than 60% of cancers occurring in those aged 60 and above. However, how aging and tumorigenesis are intertwined is poorly understood and a matter of significant debate. Metabolic changes are hallmarks of both aging and tumorigenesis. The deleterious consequences of aging include dysfunctional cellular processes, the build‐up of metabolic byproducts and waste molecules in circulation and within tissues, and stiffer connective tissues that impede blood flow and oxygenation. Collectively, these age‐driven changes lead to metabolic reprogramming in different cell types of a given tissue that significantly affects their cellular functions. Here, we put forward the idea that metabolic changes that happen during aging help create a favorable environment for tumorigenesis. We review parallels in metabolic changes that happen during aging and how these changes function both as adaptive mechanisms that enable the development of malignant phenotypes in a cell‐autonomous manner and as mechanisms that suppress immune surveillance, collectively creating the perfect environment for cancers to thrive. Hence, antiaging therapeutic strategies that target the metabolic reprogramming that occurs as we age might provide new opportunities to prevent cancer initiation and/or improve responses to standard‐of‐care anticancer therapies.","PeriodicalId":51134,"journal":{"name":"Molecular Oncology","volume":"16 1","pages":"3295 - 3318"},"PeriodicalIF":6.6,"publicationDate":"2022-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42508530","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: 7