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  1. Article ; Online: Predicting cancer prognosis and drug response from the tumor microbiome.

    Hermida, Leandro C / Gertz, E Michael / Ruppin, Eytan

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2896

    Abstract: Tumor gene expression is predictive of patient prognosis in some cancers. However, RNA-seq and whole genome sequencing data contain not only reads from host tumor and normal tissue, but also reads from the tumor microbiome, which can be used to infer the ...

    Abstract Tumor gene expression is predictive of patient prognosis in some cancers. However, RNA-seq and whole genome sequencing data contain not only reads from host tumor and normal tissue, but also reads from the tumor microbiome, which can be used to infer the microbial abundances in each tumor. Here, we show that tumor microbial abundances, alone or in combination with tumor gene expression, can predict cancer prognosis and drug response to some extent-microbial abundances are significantly less predictive of prognosis than gene expression, although similarly as predictive of drug response, but in mostly different cancer-drug combinations. Thus, it appears possible to leverage existing sequencing technology, or develop new protocols, to obtain more non-redundant information about prognosis and drug response from RNA-seq and whole genome sequencing experiments than could be obtained from tumor gene expression or genomic data alone.
    MeSH term(s) Genomics ; Humans ; Microbiota/genetics ; Neoplasms/drug therapy ; Neoplasms/genetics ; RNA-Seq ; Whole Genome Sequencing
    Language English
    Publishing date 2022-05-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30512-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Race is a key determinant of the human intratumor microbiome.

    Luo, Mei / Liu, Yuan / Hermida, Leandro C / Gertz, E Michael / Zhang, Zhao / Li, Qiang / Diao, Lixia / Ruppin, Eytan / Han, Leng

    Cancer cell

    2022  Volume 40, Issue 9, Page(s) 901–902

    MeSH term(s) Ethnicity ; Humans ; Microbiota ; Neoplasms ; Racial Groups
    Language English
    Publishing date 2022-08-25
    Publishing country United States
    Document type Letter
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2022.08.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Genomic and transcriptomic analyses identify a prognostic gene signature and predict response to therapy in pleural and peritoneal mesothelioma.

    Nair, Nishanth Ulhas / Jiang, Qun / Wei, Jun Stephen / Misra, Vikram Alexander / Morrow, Betsy / Kesserwan, Chimene / Hermida, Leandro C / Lee, Joo Sang / Mian, Idrees / Zhang, Jingli / Lebensohn, Alexandra / Miettinen, Markku / Sengupta, Manjistha / Khan, Javed / Ruppin, Eytan / Hassan, Raffit

    Cell reports. Medicine

    2023  Volume 4, Issue 2, Page(s) 100938

    Abstract: Malignant mesothelioma is an aggressive cancer with limited treatment options and poor prognosis. A better understanding of mesothelioma genomics and transcriptomics could advance therapies. Here, we present a mesothelioma cohort of 122 patients along ... ...

    Abstract Malignant mesothelioma is an aggressive cancer with limited treatment options and poor prognosis. A better understanding of mesothelioma genomics and transcriptomics could advance therapies. Here, we present a mesothelioma cohort of 122 patients along with their germline and tumor whole-exome and tumor RNA sequencing data as well as phenotypic and drug response information. We identify a 48-gene prognostic signature that is highly predictive of mesothelioma patient survival, including CCNB1, the expression of which is highly predictive of patient survival on its own. In addition, we analyze the transcriptomics data to study the tumor immune microenvironment and identify synthetic-lethality-based signatures predictive of response to therapy. This germline and somatic whole-exome sequencing as well as transcriptomics data from the same patient are a valuable resource to address important biological questions, including prognostic biomarkers and determinants of treatment response in mesothelioma.
    MeSH term(s) Humans ; Mesothelioma, Malignant ; Prognosis ; Transcriptome ; Lung Neoplasms/drug therapy ; Mesothelioma/drug therapy ; Mesothelioma/metabolism ; Mesothelioma/pathology ; Genomics ; Tumor Microenvironment
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2023.100938
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Prediction of cancer treatment response from histopathology images through imputed transcriptomics.

    Hoang, Danh-Tai / Dinstag, Gal / Hermida, Leandro C / Ben-Zvi, Doreen S / Elis, Efrat / Caley, Katherine / Sammut, Stephen-John / Sinha, Sanju / Sinha, Neelam / Dampier, Christopher H / Stossel, Chani / Patil, Tejas / Rajan, Arun / Lassoued, Wiem / Strauss, Julius / Bailey, Shania / Allen, Clint / Redman, Jason / Beker, Tuvik /
    Jiang, Peng / Golan, Talia / Wilkinson, Scott / Sowalsky, Adam G / Pine, Sharon R / Caldas, Carlos / Gulley, James L / Aldape, Kenneth / Aharonov, Ranit / Stone, Eric A / Ruppin, Eytan

    Research square

    2023  

    Abstract: Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin (H&E)-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an approach for predicting response to multiple targeted and immunotherapies from H& ... ...

    Abstract Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin (H&E)-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an approach for predicting response to multiple targeted and immunotherapies from H&E-slides. In difference from existing approaches that aim to predict treatment response directly from the slides, ENLIGHT-DeepPT is an indirect two-step approach consisting of (1) DeepPT, a new deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response based on the DeepPT inferred expression values. DeepPT successfully predicts transcriptomics in all 16 TCGA cohorts tested and generalizes well to two independent datasets. Our key contribution is showing that ENLIGHT-DeepPT successfully predicts true responders in five independent patients' cohorts involving four different treatments spanning six cancer types with an overall odds ratio of 2.44, increasing the baseline response rate by 43.47% among predicted responders, without the need for any treatment data for training. Furthermore, its prediction accuracy on these datasets is comparable to a supervised approach predicting the response directly from the images, which needs to be trained and tested on the same cohort. ENLIGHT-DeepPT future application could provide clinicians with rapid treatment recommendations to an array of different therapies and importantly, may contribute to advancing precision oncology in developing countries.
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3193270/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade.

    Wang, Liangliang / Gao, Yan / Zhang, Gao / Li, Dan / Wang, Zhenda / Zhang, Jie / Hermida, Leandro C / He, Lei / Wang, Zhisong / Si, Jingwen / Geng, Shuang / Ai, Rizi / Ning, Fei / Cheng, Chaoran / Deng, Haiteng / Dimitrov, Dimiter S / Sun, Yan / Huang, Yanyi / Wang, Dong /
    Hu, Xiaoyu / Wei, Zhi / Wang, Wei / Liao, Xuebin

    Science translational medicine

    2020  Volume 12, Issue 560

    Abstract: Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in ... ...

    Abstract Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules that increased KDM5A abundance, we identified one (D18) that increased the efficacy of various ICB agents in three murine cancer models when used as a combination therapy. D18 potentiated ICB efficacy through two orthogonal mechanisms: (i) increasing KDM5A abundance, which suppressed expression of the gene
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes ; Combined Modality Therapy ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Mice ; Phosphatidylinositol 3-Kinases ; Retinoblastoma-Binding Protein 2
    Chemical Substances Immune Checkpoint Inhibitors ; KDM5A protein, human (EC 1.14.11.-) ; Retinoblastoma-Binding Protein 2 (EC 1.14.11.27)
    Language English
    Publishing date 2020-11-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.aax2282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells.

    Lichtenstein, Daniel A / Schischlik, Fiorella / Shao, Lipei / Steinberg, Seth M / Yates, Bonnie / Wang, Hao-Wei / Wang, Yanyu / Inglefield, Jon / Dulau-Florea, Alina / Ceppi, Francesco / Hermida, Leandro C / Stringaris, Kate / Dunham, Kim / Homan, Philip / Jailwala, Parthav / Mirazee, Justin / Robinson, Welles / Chisholm, Karen M / Yuan, Constance /
    Stetler-Stevenson, Maryalice / Ombrello, Amanda K / Jin, Jianjian / Fry, Terry J / Taylor, Naomi / Highfill, Steven L / Jin, Ping / Gardner, Rebecca A / Shalabi, Haneen / Ruppin, Eytan / Stroncek, David F / Shah, Nirali N

    Blood

    2021  Volume 138, Issue 24, Page(s) 2469–2484

    Abstract: Chimeric antigen receptor (CAR) T-cell toxicities resembling hemophagocytic lymphohistiocytosis (HLH) occur in a subset of patients with cytokine release syndrome (CRS). As a variant of conventional CRS, a comprehensive characterization of CAR T-cell- ... ...

    Abstract Chimeric antigen receptor (CAR) T-cell toxicities resembling hemophagocytic lymphohistiocytosis (HLH) occur in a subset of patients with cytokine release syndrome (CRS). As a variant of conventional CRS, a comprehensive characterization of CAR T-cell-associated HLH (carHLH) and investigations into associated risk factors are lacking. In the context of 59 patients infused with CD22 CAR T cells where a substantial proportion developed carHLH, we comprehensively describe the manifestations and timing of carHLH as a CRS variant and explore factors associated with this clinical profile. Among 52 subjects with CRS, 21 (40.4%) developed carHLH. Clinical features of carHLH included hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, coagulopathy, hepatic transaminitis, hyperbilirubinemia, severe neutropenia, elevated lactate dehydrogenase, and occasionally hemophagocytosis. Development of carHLH was associated with preinfusion natural killer(NK) cell lymphopenia and higher bone marrow T-cell:NK cell ratio, which was further amplified with CAR T-cell expansion. Following CRS, more robust CAR T-cell and CD8 T-cell expansion in concert with pronounced NK cell lymphopenia amplified preinfusion differences in those with carHLH without evidence for defects in NK cell mediated cytotoxicity. CarHLH was further characterized by persistent elevation of HLH-associated inflammatory cytokines, which contrasted with declining levels in those without carHLH. In the setting of CAR T-cell mediated expansion, clinical manifestations and immunophenotypic profiling in those with carHLH overlap with features of secondary HLH, prompting consideration of an alternative framework for identification and management of this toxicity profile to optimize outcomes following CAR T-cell infusion.
    MeSH term(s) Adult ; CD8-Positive T-Lymphocytes/immunology ; Cytokine Release Syndrome/diagnosis ; Cytokine Release Syndrome/etiology ; Cytokine Release Syndrome/immunology ; Female ; Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Killer Cells, Natural/immunology ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/etiology ; Lymphohistiocytosis, Hemophagocytic/immunology ; Male ; Retrospective Studies ; Sialic Acid Binding Ig-like Lectin 2/immunology
    Chemical Substances CD22 protein, human ; Sialic Acid Binding Ig-like Lectin 2
    Language English
    Publishing date 2021-09-15
    Publishing country United States
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2021011898
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: CTD2 Dashboard: a searchable web interface to connect validated results from the Cancer Target Discovery and Development Network.

    Aksoy, Bülent Arman / Dancík, Vlado / Smith, Kenneth / Mazerik, Jessica N / Ji, Zhou / Gross, Benjamin / Nikolova, Olga / Jaber, Nadia / Califano, Andrea / Schreiber, Stuart L / Gerhard, Daniela S / Hermida, Leandro C / Jagu, Subhashini / Sander, Chris / Floratos, Aris / Clemons, Paul A

    Database : the journal of biological databases and curation

    2017  Volume 2017

    Abstract: Database url: https://ctd2-dashboard.nci.nih.gov/. ...

    Abstract Database url: https://ctd2-dashboard.nci.nih.gov/.
    MeSH term(s) Computational Biology/methods ; Databases, Factual ; Humans ; Internet ; Neoplasms/genetics ; User-Computer Interface
    Language English
    Publishing date 2017-12-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2496706-3
    ISSN 1758-0463 ; 1758-0463
    ISSN (online) 1758-0463
    ISSN 1758-0463
    DOI 10.1093/database/bax054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Publisher Correction: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions.

    Bolouri, Hamid / Farrar, Jason E / Triche, Timothy / Ries, Rhonda E / Lim, Emilia L / Alonzo, Todd A / Ma, Yussanne / Moore, Richard / Mungall, Andrew J / Marra, Marco A / Zhang, Jinghui / Ma, Xiaotu / Liu, Yu / Liu, Yanling / Auvil, Jaime M Guidry / Davidsen, Tanja M / Gesuwan, Patee / Hermida, Leandro C / Salhia, Bodour /
    Capone, Stephen / Ramsingh, Giridharan / Zwaan, Christian Michel / Noort, Sanne / Piccolo, Stephen R / Kolb, E Anders / Gamis, Alan S / Smith, Malcolm A / Gerhard, Daniela S / Meshinchi, Soheil

    Nature medicine

    2019  Volume 25, Issue 3, Page(s) 530

    Abstract: In the version of this article originally published, the color key in Fig. 1a was wrong. In the Cytogenetics key, the box over t(8;21) originally was green. It should have been red, matching the color of the sections of the pie graphs below the key that ... ...

    Abstract In the version of this article originally published, the color key in Fig. 1a was wrong. In the Cytogenetics key, the box over t(8;21) originally was green. It should have been red, matching the color of the sections of the pie graphs below the key that were labeled with 15% and 19%.
    Language English
    Publishing date 2019-01-31
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-019-0369-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions.

    Bolouri, Hamid / Farrar, Jason E / Triche, Timothy / Ries, Rhonda E / Lim, Emilia L / Alonzo, Todd A / Ma, Yussanne / Moore, Richard / Mungall, Andrew J / Marra, Marco A / Zhang, Jinghui / Ma, Xiaotu / Liu, Yu / Liu, Yanling / Auvil, Jaime M Guidry / Davidsen, Tanja M / Gesuwan, Patee / Hermida, Leandro C / Salhia, Bodour /
    Capone, Stephen / Ramsingh, Giridharan / Zwaan, Christian Michel / Noort, Sanne / Piccolo, Stephen R / Kolb, E Anders / Gamis, Alan S / Smith, Malcolm A / Gerhard, Daniela S / Meshinchi, Soheil

    Nature medicine

    2018  Volume 24, Issue 4, Page(s) 526

    Abstract: This corrects the article DOI: 10.1038/nm.4439. ...

    Abstract This corrects the article DOI: 10.1038/nm.4439.
    Language English
    Publishing date 2018-04-06
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/nm0418-526b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours.

    Ma, Xiaotu / Liu, Yu / Liu, Yanling / Alexandrov, Ludmil B / Edmonson, Michael N / Gawad, Charles / Zhou, Xin / Li, Yongjin / Rusch, Michael C / Easton, John / Huether, Robert / Gonzalez-Pena, Veronica / Wilkinson, Mark R / Hermida, Leandro C / Davis, Sean / Sioson, Edgar / Pounds, Stanley / Cao, Xueyuan / Ries, Rhonda E /
    Wang, Zhaoming / Chen, Xiang / Dong, Li / Diskin, Sharon J / Smith, Malcolm A / Guidry Auvil, Jaime M / Meltzer, Paul S / Lau, Ching C / Perlman, Elizabeth J / Maris, John M / Meshinchi, Soheil / Hunger, Stephen P / Gerhard, Daniela S / Zhang, Jinghui

    Nature

    2018  Volume 555, Issue 7696, Page(s) 371–376

    Abstract: Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been ... ...

    Abstract Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.
    MeSH term(s) Alleles ; Aneuploidy ; Child ; DNA Copy Number Variations ; Exome/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome, Human/genetics ; Humans ; Leukemia/genetics ; Mutation/genetics ; Mutation/radiation effects ; Mutation Rate ; Neoplasms/genetics ; Oncogenes/genetics ; Precision Medicine/trends ; Ultraviolet Rays/adverse effects
    Language English
    Publishing date 2018-02-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature25795
    Database MEDical Literature Analysis and Retrieval System OnLINE

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