Molecular Oncology最新文献_第7页

The accumulation of myeloid-derived suppressor cells participates in abdominal infection-induced tumor progression through the PD-L1/PD-1 axis. 髓源性抑制细胞的积累通过PD-L1/PD-1轴参与腹腔感染诱导的肿瘤进展。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-05-01 Epub Date: 2025-01-21 DOI: 10.1002/1878-0261.13767

Yiding Wang, Ting Guo, Xiaofang Xing, Xijuan Liu, Xuejun Gan, Yingai Li, Yan Liu, Fei Shan, Zhouqiao Wu, Jiafu Ji, Ziyu Li

{"title":"The accumulation of myeloid-derived suppressor cells participates in abdominal infection-induced tumor progression through the PD-L1/PD-1 axis.","authors":"Yiding Wang, Ting Guo, Xiaofang Xing, Xijuan Liu, Xuejun Gan, Yingai Li, Yan Liu, Fei Shan, Zhouqiao Wu, Jiafu Ji, Ziyu Li","doi":"10.1002/1878-0261.13767","DOIUrl":"10.1002/1878-0261.13767","url":null,"abstract":"Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide, with gastrectomy being the primary treatment option. Sepsis, a systemic inflammatory response to infection, may influence tumor growth by creating an immunosuppressive environment conducive to cancer cell proliferation and metastasis. Here, the effect of abdominal infection on tumor growth and metastasis was investigated through the implementation of a peritoneal metastasis model and a subcutaneous tumor model. In a murine model induced by cecal ligation and puncture (CLP) to simulate the effects of sepsis, we observed significant immune dysregulation, including T-cell exhaustion and the release of myeloid-derived suppressor cells (MDSCs). This immune alteration was associated with increased programmed cell death protein 1 (PD-1) expression on T cells and programmed cell death 1 ligand 1 (PD-L1) expression on MDSCs within the tumor microenvironment, fostering an immune-suppressive environment. Polymorphonuclear MDSCs (PMN-MDSCs) expressing elevated PD-L1 after sepsis demonstrated more substantial suppressive effects on T-cell proliferation than controls. Treatment with anti-PD-1 monoclonal antibodies successfully restored T-cell function, reduced mortality, and decreased metastasis in CLP mice. These findings emphasize the impact of sepsis on tumor progression and suggest targeting the PD-1/PD-L1 axis as a potential therapeutic strategy for managing immune dysfunction in patients with cancer.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1532-1545"},"PeriodicalIF":6.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007823","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

KMT2A degradation is observed in decitabine-responsive acute lymphoblastic leukemia cells. 在地西他滨反应性急性淋巴细胞白血病细胞中观察到KMT2A降解。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-05-01 Epub Date: 2025-01-04 DOI: 10.1002/1878-0261.13792

Luisa Brock, Lina Benzien, Sandra Lange, Maja Huehns, Alexandra Runge, Catrin Roolf, Anett Sekora, Gudrun Knuebel, Hugo Murua Escobar, Christian Junghanss, Anna Richter

{"title":"KMT2A degradation is observed in decitabine-responsive acute lymphoblastic leukemia cells.","authors":"Luisa Brock, Lina Benzien, Sandra Lange, Maja Huehns, Alexandra Runge, Catrin Roolf, Anett Sekora, Gudrun Knuebel, Hugo Murua Escobar, Christian Junghanss, Anna Richter","doi":"10.1002/1878-0261.13792","DOIUrl":"10.1002/1878-0261.13792","url":null,"abstract":"Hypermethylation of tumor suppressor genes is a hallmark of leukemia. The hypomethylating agent decitabine covalently binds, and degrades DNA (cytosine-5)-methyltransferase 1 (DNMT1). Structural similarities within DNA-binding domains of DNMT1, and the leukemic driver histone-lysine N-methyltransferase 2A (KMT2A) suggest that decitabine might also affect the latter. In acute lymphoblastic leukemia (ALL) cell lines, and xenograft models, we observed increased DNMT1, and KMT2A expression in response to decitabine-induced demethylation. Strikingly, KMT2A protein expression was diminished in all cell lines that experienced DNMT1 degradation. Moreover, only cells with reduced KMT2A protein levels showed biological effects following decitabine treatment. KMT2A wild-type, and rearranged cells were locked in G2 and G1 cell cycle phases, respectively, likely due to p27/p16 activation. Primary sample gene expression profiling confirmed different patterns between KMT2A wild-type, and translocated cells. This newly discovered decitabine mode of action via KMT2A degradation evokes anti-leukemic activity in adult ALL cells, and can act synergistically with menin inhibition. Following the successful clinical implementation of decitabine for acute myeloid leukemia, the drug should be considered a potential promising addition to the therapeutic portfolio for ALL as well.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1404-1421"},"PeriodicalIF":6.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927634","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

MIF as an oncogenic driver of low-heterogeneity melanomas. MIF 是低异质性黑色素瘤的致癌驱动因素。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-05-01 Epub Date: 2025-03-25 DOI: 10.1002/1878-0261.70031

Thuy T Tran, Gabriela Athziri Sánchez-Zuno, Rajan P Kulkarni, Harriet M Kluger, Richard Bucala

引用次数: 0

TRPM4 contributes to cell death in prostate cancer tumor spheroids, and to extravasation and metastasis in a zebrafish xenograft model system. 在斑马鱼异种移植模型系统中，TRPM4参与前列腺癌肿瘤球体的细胞死亡以及外渗和转移。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-05-01 Epub Date: 2025-01-16 DOI: 10.1002/1878-0261.13795

Florian Bochen, Saurav Subedi, Federico La Manna, Sofia Jarrin, Irida Papapostolou, Marianna Kruithof-de Julio, Christine Peinelt

{"title":"TRPM4 contributes to cell death in prostate cancer tumor spheroids, and to extravasation and metastasis in a zebrafish xenograft model system.","authors":"Florian Bochen, Saurav Subedi, Federico La Manna, Sofia Jarrin, Irida Papapostolou, Marianna Kruithof-de Julio, Christine Peinelt","doi":"10.1002/1878-0261.13795","DOIUrl":"10.1002/1878-0261.13795","url":null,"abstract":"Transient receptor potential melastatin-4 (TRPM4) ion channel expression is upregulated in prostate cancer (PCa), contributing to increased cell proliferation, migration, adhesion, epithelial-to-mesenchymal transition, cell cycle shift, and alterations of intracellular Ca2+ signaling. GEO2R platform analysis of messenger RNA (mRNA) expression of ~ 6350 genes in normal and malignant prostate tissue samples from 15 PCa patients demonstrates that TRPM4 expression is upregulated sixfold and is among the most significantly upregulated genes in PCa. We find that absence of TRPM4 reduced PCa tumor spheroid size and decreased PCa tumor spheroid outgrowth. In addition, lack of TRPM4 increased cell death in PCa tumor spheroids, a phenotype that is absent in two-dimensional (2D) cancer cell systems. Lastly, absence of TRPM4 in PCa cells reduced extravasation and metastatic burden in a preclinical zebrafish cancer model. Taken together, our findings show that TRPM4 is an attractive therapeutic target in PCa and highlights the need for future development of pharmacological tools.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1299-1309"},"PeriodicalIF":6.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007939","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

Chemoresistome mapping in individual breast cancer patients unravels diversity in dynamic transcriptional adaptation. 个体乳腺癌患者的化疗抵抗体定位揭示了动态转录适应的多样性。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-04-28 DOI: 10.1002/1878-0261.70030

Maya Dadiani, Gilgi Friedlander, Gili Perry, Nora Balint-Lahat, Shlomit Gilad, Dana Morzaev-Sulzbach, Anjana Shenoy, Noa Bossel Ben-Moshe, Anya Pavlovsky, Rinat Bernstein-Molho, Eytan Domany, Iris Barshack, Tamar Geiger, Bella Kaufman, Einav Nili Gal-Yam

{"title":"Chemoresistome mapping in individual breast cancer patients unravels diversity in dynamic transcriptional adaptation.","authors":"Maya Dadiani, Gilgi Friedlander, Gili Perry, Nora Balint-Lahat, Shlomit Gilad, Dana Morzaev-Sulzbach, Anjana Shenoy, Noa Bossel Ben-Moshe, Anya Pavlovsky, Rinat Bernstein-Molho, Eytan Domany, Iris Barshack, Tamar Geiger, Bella Kaufman, Einav Nili Gal-Yam","doi":"10.1002/1878-0261.70030","DOIUrl":"https://doi.org/10.1002/1878-0261.70030","url":null,"abstract":"Nongenetic adaptive resistance to chemotherapy, driven by transcriptional rewiring, is emerging as a significant mechanism in tumor survival. In this study we combined longitudinal transcriptomics with temporal pattern analysis to investigate patient-specific mechanisms underlying acquired resistance in breast cancer. Matched tumor biopsies (pretreatment, posttreatment, and adjacent normal) were collected from breast cancer patients who received neoadjuvant chemotherapy. Transcriptomes were analyzed by longitudinal gene-pattern classification to track patient-specific gene expression alterations that occur during treatment. Our findings reveal that resistance-associated genes were already dysregulated in primary tumors, suggesting the presence of a preexisting drug-tolerant state. While each patient displayed unique resistance-associated gene rewiring, these alterations converged into a limited number of dysregulated functional modules. Notably, patients receiving the same treatment exhibited distinct rewiring of genes and pathways, revealing parallel, individualized routes to resistance. In conclusion, we propose that tumor cells survive chemotherapy by sustaining or amplifying a preexisting drug-tolerant state that circumvents drug action. We suggest that individualized \"chemoresistome maps\" could identify cancer vulnerabilities and inform personalized therapeutic strategies to overcome or prevent resistance.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030030","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

Determination of ADP/ATP translocase isoform ratios in malignancy and cellular senescence. 恶性肿瘤和细胞衰老中ADP/ATP转位酶异构体比值的测定。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-04-27 DOI: 10.1002/1878-0261.70039

Zuzana Liblova, Dominika Maurencova, Barbora Salovska, Marek Kratky, Tomas Mracek, Zuzana Korandova, Alena Pecinova, Pavla Vasicova, David Rysanek, Ladislav Andera, Ivo Fabrik, Rudolf Kupcik, Pavel Kashmel, Pinky Sultana, Vojtech Tambor, Jiri Bartek, Josef Novak, Marie Vajrychova, Zdenek Hodny

{"title":"Determination of ADP/ATP translocase isoform ratios in malignancy and cellular senescence.","authors":"Zuzana Liblova, Dominika Maurencova, Barbora Salovska, Marek Kratky, Tomas Mracek, Zuzana Korandova, Alena Pecinova, Pavla Vasicova, David Rysanek, Ladislav Andera, Ivo Fabrik, Rudolf Kupcik, Pavel Kashmel, Pinky Sultana, Vojtech Tambor, Jiri Bartek, Josef Novak, Marie Vajrychova, Zdenek Hodny","doi":"10.1002/1878-0261.70039","DOIUrl":"https://doi.org/10.1002/1878-0261.70039","url":null,"abstract":"Cellular senescence has recently been recognized as a significant contributor to the poor prognosis of glioblastoma, one of the most aggressive brain tumors. Consequently, effectively eliminating senescent glioblastoma cells could benefit patients. Human ADP/ATP translocases (ANTs) play a role in oxidative phosphorylation in both normal and tumor cells. Previous research has shown that the sensitivity of senescent cells to mitochondria-targeted senolytics depends on the level of ANT2. Here, we systematically mapped the transcript and protein levels of ANT isoforms in various types of senescence and glioblastoma tumorigenesis. We employed bioinformatics analysis, targeted mass spectrometry, RT-PCR, immunoblotting, and assessment of cellular energy state to elucidate how individual ANT isoforms are expressed during the development of senescence in noncancerous and glioblastoma cells. We observed a consistent elevation of ANT1 protein levels across all tested senescence types, while ANT2 and ANT3 exhibited variable changes. Alterations in ANT protein isoform levels correlated with shifts in the cellular oxygen consumption rate. Our findings suggest that ANT isoforms are mutually interchangeable for oxidative phosphorylation and manipulating individual ANT isoforms could have potential for senolytic therapy.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033525","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

Does Porphyromonas gingivalis truly inhibit the oral carcinogenesis? 牙龈卟啉单胞菌真的能抑制口腔癌变吗？

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-04-25 DOI: 10.1002/1878-0261.70037

Chen-Xi Li, Zhong-Cheng Gong

引用次数: 0

Targeted protein degradation in oncology: novel therapeutic opportunity for solid tumours? 肿瘤靶向蛋白降解：实体瘤的新治疗机会？

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-04-23 DOI: 10.1002/1878-0261.70034

Noé Herbel, Sophie Postel-Vinay

引用次数: 0

Early metastasis is characterized by Gr1+ cell dysregulation and is inhibited by immunomodulatory nanoparticles. 早期转移的特点是Gr1+细胞失调，并被免疫调节纳米颗粒抑制。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-04-23 DOI: 10.1002/1878-0261.70040

Jeffrey A Ma, Sophia M Orbach, Kate V Griffin, Kathryn Kang, Yining Zhang, Rebecca S Pereles, Ian A Schrack, Guillermo Escalona, Jacqueline S Jeruss, Lonnie D Shea

{"title":"Early metastasis is characterized by Gr1+ cell dysregulation and is inhibited by immunomodulatory nanoparticles.","authors":"Jeffrey A Ma, Sophia M Orbach, Kate V Griffin, Kathryn Kang, Yining Zhang, Rebecca S Pereles, Ian A Schrack, Guillermo Escalona, Jacqueline S Jeruss, Lonnie D Shea","doi":"10.1002/1878-0261.70040","DOIUrl":"https://doi.org/10.1002/1878-0261.70040","url":null,"abstract":"Cancer metastasis is supported by dysregulated myeloid-derived suppressor cells, but myeloid cells are highly heterogeneous populations with distinct subsets that may support or inhibit tumor cell colonization. We hypothesize that Gr1+ myeloid cells transform in phenotype to support tumor cell colonization at the metastatic niche. In the 4T1 model of metastatic breast cancer, we investigate changes in the composition and phenotype of Gr1+ cells between premetastatic disease and early metastasis. Gr1+ cells in the lung were found to transition towards immunosuppressive and tumor-supportive phenotypes with disease progression. While the composition of myeloid cells becomes dysregulated systemically, cells in the blood do not develop tumor-supportive phenotypes, indicating that protumor functions are specific to the lung. In vitro assays demonstrate that Gr1+ cells from early metastatic lungs support tumor cell survival, migration, and proliferation, which is linked to chitinase-3-like protein 1 (CHI3L1) signaling. The intravenous injection of polymeric nanoparticles reprograms Gr1+ cell phenotypes, reduces the secretion of CHI3L1, and inhibits metastasis. These findings indicate that dysregulated Gr1+ cells are a therapeutic target for early metastasis and can be targeted with polymeric nanoparticles.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030031","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

Detecting homologous recombination deficiency for breast cancer through integrative analysis of genomic data. 通过基因组数据的综合分析检测乳腺癌同源重组缺陷。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-04-22 DOI: 10.1002/1878-0261.70041

Rong Zhu, Katherine Eason, Suet-Feung Chin, Paul A W Edwards, Raquel Manzano Garcia, Richard Moulange, Jia Wern Pan, Soo Hwang Teo, Sach Mukherjee, Maurizio Callari, Carlos Caldas, Stephen-John Sammut, Oscar M Rueda

{"title":"Detecting homologous recombination deficiency for breast cancer through integrative analysis of genomic data.","authors":"Rong Zhu, Katherine Eason, Suet-Feung Chin, Paul A W Edwards, Raquel Manzano Garcia, Richard Moulange, Jia Wern Pan, Soo Hwang Teo, Sach Mukherjee, Maurizio Callari, Carlos Caldas, Stephen-John Sammut, Oscar M Rueda","doi":"10.1002/1878-0261.70041","DOIUrl":"https://doi.org/10.1002/1878-0261.70041","url":null,"abstract":"Homologous recombination deficiency (HRD) leads to genomic instability, and patients with HRD can benefit from HRD-targeting therapies. Previous studies have primarily focused on identifying HRD biomarkers using data from a single technology. Here we integrated features from different genomic data types, including total copy number (CN), allele-specific copy number (ASCN) and single nucleotide variants (SNV). Using a semi-supervised method, we developed HRD classifiers from 1404 breast tumours across two datasets based on their BRCA1/2 status, demonstrating improved HRD identification when aggregating different data types. Notably, HRD-positive tumours in ER-negative disease showed improved survival post-adjuvant chemotherapy, while HRD status strongly correlated with neoadjuvant treatment response. Furthermore, our analysis of cell lines highlighted a sensitivity to PARP inhibitors, particularly rucaparib, among predicted HRD-positive lines. Exploring somatic mutations outside BRCA1/2, we confirmed variants in several genes associated with HRD. Our method for HRD classification can adapt to different data types or resolutions and can be used in various scenarios to help refine patient selection for HRD-targeting therapies that might lead to better clinical outcomes.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034235","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