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  1. Book: Reverse phase protein arrays

    Yamada, Tesshi / Nishizuka, Satoshi S. / Mills, Gordon B.

    from technical and analytical fundamentals to applications

    (Advances in experimental medicine and biology ; 1188)

    2019  

    Author's details Tesshi Yamada, Satoshi S. Nishizuka, Gordon B. Mills, Lance A. Liotta editors
    Series title Advances in experimental medicine and biology ; 1188
    Collection
    Language English
    Size viii, 266 Seiten, Illustrationen
    Publisher Springer
    Publishing place Singapore
    Publishing country Switzerland
    Document type Book
    HBZ-ID HT020330617
    ISBN 978-981-32-9754-8 ; 9789813297555 ; 981-32-9754-9 ; 9813297557
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    Zs A 3192 -1188- not available for loan Zeitschriften-Lesesaal

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  2. Article ; Online: Enhancing anticancer activity of macrophages through rational drug combinations.

    Mills, Gordon B / Labrie, Marilyne

    The Journal of clinical investigation

    2024  Volume 134, Issue 9

    Abstract: Targeting tumor-associated macrophages (TAMs) is an emerging approach being tested in multiple clinical trials. TAMs, depending on their differentiation state, can exhibit pro- or antitumorigenic functions. For example, the M2-like phenotype represents a ...

    Abstract Targeting tumor-associated macrophages (TAMs) is an emerging approach being tested in multiple clinical trials. TAMs, depending on their differentiation state, can exhibit pro- or antitumorigenic functions. For example, the M2-like phenotype represents a protumoral state that can stimulate tumor growth, angiogenesis, metastasis, therapy resistance, and immune evasion by expressing immune checkpoint proteins. In this issue of the JCI, Vaccaro and colleagues utilized an innovative drug screen approach to demonstrate that targeting driver oncogenic signaling pathways concurrently with anti-CD47 sensitizes tumor cells, causing them to undergo macrophage-induced phagocytosis. The combination treatment altered expression of molecules on the tumor cells that typically limit phagocytosis. It also reprogrammed macrophages to an M1-like antitumor state. Moreover, the approach was generalizable to tumor cells with different oncogenic pathways, opening the door to precision oncology-based rationale combination therapies that have the potential to improve outcomes for patients with oncogene-driven lung cancers and likely other cancer types.
    MeSH term(s) Humans ; Tumor-Associated Macrophages/metabolism ; Tumor-Associated Macrophages/drug effects ; Tumor-Associated Macrophages/immunology ; CD47 Antigen/metabolism ; CD47 Antigen/antagonists & inhibitors ; Animals ; Phagocytosis/drug effects ; Neoplasms/drug therapy ; Neoplasms/pathology ; Neoplasms/metabolism ; Macrophages/metabolism ; Macrophages/drug effects ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Lung Neoplasms/metabolism
    Chemical Substances CD47 Antigen ; CD47 protein, human
    Language English
    Publishing date 2024-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI180512
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: MIM-CyCIF: masked imaging modeling for enhancing cyclic immunofluorescence (CyCIF) with panel reduction and imputation.

    Sims, Zachary / Mills, Gordon B / Chang, Young Hwan

    Communications biology

    2024  Volume 7, Issue 1, Page(s) 409

    Abstract: Cyclic Immunofluorescence (CyCIF) can quantify multiple biomarkers, but panel capacity is limited by technical challenges. We propose a computational panel reduction approach that can impute the information content from 25 markers using only 9 markers, ... ...

    Abstract Cyclic Immunofluorescence (CyCIF) can quantify multiple biomarkers, but panel capacity is limited by technical challenges. We propose a computational panel reduction approach that can impute the information content from 25 markers using only 9 markers, learning co-expression and morphological patterns while concurrently increasing speed and panel content and decreasing cost. We demonstrate strong correlations in predictions and generalizability across breast and colorectal cancer, illustrating applicability of our approach to diverse tissue types.
    MeSH term(s) Fluorescent Antibody Technique ; Diagnostic Imaging
    Language English
    Publishing date 2024-04-03
    Publishing country England
    Document type Journal Article
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-024-06110-y
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  4. Article ; Online: Common and distinct patterns of acquired uniparental disomy and homozygous deletions between lung squamous cell carcinomas and lung adenocarcinoma.

    Tuna, Musaffe / Mills, Gordon B / Amos, Christopher I

    Neoplasia (New York, N.Y.)

    2023  Volume 45, Page(s) 100932

    Abstract: Acquired uniparental disomy (aUPD) is a chromosomal alteration that can lead to homozygosity of existing aberrations. We used data from The Cancer Genome Atlas SNP-based arrays to identify distinct and common aUPD profiles in lung adenocarcinoma (LUAD) ... ...

    Abstract Acquired uniparental disomy (aUPD) is a chromosomal alteration that can lead to homozygosity of existing aberrations. We used data from The Cancer Genome Atlas SNP-based arrays to identify distinct and common aUPD profiles in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Moreover, we tested relevance of aUPD for homozygous deletion (HMD), overall survival (OS), and recurrence-free survival (RFS). Overall, we found significantly higher aUPD (q = 5.34E-09) in LUSC than in LUAD. A significant portion of HMD was associated with aUPD in LUSC (24.9%) and LUAD (19.7%). We identified segmental, whole-chromosome arm and whole-chromosome aUPD, in which whole 7p arm aUPD was restricted to LUSC, while whole-chromosome 3 aUPD was observed only in LUAD, and whole-chromosome 21 aUPD was common to both LUSC and LUAD. The most frequent aUPD and HMD were observed at CDKN2A/B region in both LUAD and LUSC. In LUAD, aUPD and HMD at CDKN2A/B region were associated with shorter OS (q < 0.021 and q < 0.005), and RFS (q < 0.005 and q < 0.005), while heterozygous deletion was not associated with OS and RFS. In contrast, no association was found between aUPD at CDKN2A/B region and survival in LUSC. In LUAD, CTLA expression was significantly lower in samples with aUPD at CDKN2A/B regions than in samples without copy number and allele-based changes. Immune infiltration correlated with aUPD or HMD at CDKN2A/B, gain at HLA class I region, and aUPD at whole-chromosome q-arm or whole chromosome in LUAD, but not in LUSC. Both LUSC and LUAD have common and distinct patterns of aUPD regions with differing frequencies of occurrence and associations with outcome.
    MeSH term(s) Humans ; Uniparental Disomy/genetics ; Homozygote ; Sequence Deletion ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Squamous Cell/pathology ; Lung Neoplasms/pathology ; Lung/metabolism
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2023.100932
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: MIM-CyCIF: Masked Imaging Modeling for Enhancing Cyclic Immunofluorescence (CyCIF) with Panel Reduction and Imputation.

    Sims, Zachary / Mills, Gordon B / Chang, Young Hwan

    bioRxiv : the preprint server for biology

    2023  

    Abstract: CyCIF quantifies multiple biomarkers, but panel capacity is compromised by technical challenges including tissue loss. We propose a computational panel reduction, inferring surrogate CyCIF data from a subset of biomarkers. Our model reconstructs the ... ...

    Abstract CyCIF quantifies multiple biomarkers, but panel capacity is compromised by technical challenges including tissue loss. We propose a computational panel reduction, inferring surrogate CyCIF data from a subset of biomarkers. Our model reconstructs the information content from 25 markers using only 9 markers, learning co-expression and morphological patterns. We demonstrate strong correlations in predictions and generalizability across breast and colorectal cancer tissue microarrays, illustrating broader applicability to diverse tissue types.
    Language English
    Publishing date 2023-08-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.10.540265
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Graph Structured Neural Networks for Perturbation Biology.

    Evans, Nathaniel J / Mills, Gordon B / Wu, Guanming / Song, Xubo / McWeeney, Shannon

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Computational modeling of perturbation biology identifies relationships between molecular elements and cellular response, and an accurate understanding of these systems will support the full realization of precision medicine. Traditional deep learning, ... ...

    Abstract Computational modeling of perturbation biology identifies relationships between molecular elements and cellular response, and an accurate understanding of these systems will support the full realization of precision medicine. Traditional deep learning, while often accurate in predicting response, is unlikely to capture the true sequence of involved molecular interactions. Our work is motivated by two assumptions: 1) Methods that encourage mechanistic prediction logic are likely to be more trustworthy, and 2) problem-specific algorithms are likely to outperform generic algorithms. We present an alternative to Graph Neural Networks (GNNs) termed
    Availability and implementation: Our implementation of the GSNN method is available at https://github.com/nathanieljevans/GSNN. All data used in this work is publicly available.
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.28.582164
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Systematic Pan-cancer Functional Inference and Validation of Hyper, Hypo and Neomorphic Mutations.

    Tagore, Somnath / Tsang, Samuel / Mills, Gordon B / Califano, Andrea

    bioRxiv : the preprint server for biology

    2023  

    Abstract: While the functional effects of many recurrent cancer mutations have been characterized, the TCGA repository comprises more than 10M non-recurrent events, whose function is unknown. We propose that the context specific activity of transcription factor ( ... ...

    Abstract While the functional effects of many recurrent cancer mutations have been characterized, the TCGA repository comprises more than 10M non-recurrent events, whose function is unknown. We propose that the context specific activity of transcription factor (TF) proteins-as measured by expression of their transcriptional targets-provides a sensitive and accurate reporter assay to assess the functional role of oncoprotein mutations. Analysis of differentially active TFs in samples harboring mutations of unknown significance-compared to established gain (GOF/hypermorph) or loss (LOF/hypomorph) of function-helped functionally characterize 577,866 individual mutational events across TCGA cohorts, including identification of mutations that are either neomorphic (gain of novel function) or phenocopy other mutations (
    Language English
    Publishing date 2023-05-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.29.538640
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Whole-chromosome arm acquired uniparental disomy in cancer development is a consequence of isochromosome formation.

    Tuna, Musaffe / Amos, Christopher I / Mills, Gordon B

    Neoplasia (New York, N.Y.)

    2022  Volume 25, Page(s) 9–17

    Abstract: Using SNP-based microarray data from The Cancer Genome Atlas (TCGA), we investigated isochromosomes (deletion of one arm and duplication of the other arm) and related acquired uniparental disomy in 12 tumor types. We observed a high frequency of ... ...

    Abstract Using SNP-based microarray data from The Cancer Genome Atlas (TCGA), we investigated isochromosomes (deletion of one arm and duplication of the other arm) and related acquired uniparental disomy in 12 tumor types. We observed a high frequency of isochromosomes (25.98%) across all type of tumors except thyroid cancers. The highest frequency of isochromosomes was found in lung squamous cell carcinoma (54.18%). Moreover, whole-chromosome arm acquired uniparental disomy (aUPD) was common in the deleted arms of isochromosomes. These data are consistent with whole-chromosome arm aUPD likely being a consequence of isochromosomes formation. Our findings implicated aUPD as occurring through error-prone DNA repair of a deleted arm or segment of a chromosome that leads to homozygosity for existing alterations. Isochromosomes were significantly more frequent in TP53 mutated samples than wild types in 6 types of tumors with loss of TP53 function potentially contributing to development of isochromosomes. Isochromosomes are common alterations in cancer, and losing one arm of a chromosome could result in duplication of the lost arm. Duplication of the remaining arm leads promulgation of the effects on any defects in the remaining allele, due to subsequent homozygosity.
    MeSH term(s) Alleles ; Humans ; Isochromosomes/genetics ; Neoplasms/genetics ; Uniparental Disomy/genetics
    Language English
    Publishing date 2022-01-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2021.12.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The roles of

    Tsang, Yiu Huen / Mills, Gordon B

    Autophagy

    2020  Volume 16, Issue 10, Page(s) 1923–1924

    Abstract: The melanoma-associated antigen family A (MAGEA) antigens are expressed in a wide variety of malignant tumors but not in adult somatic cells, rendering them attractive targets for cancer immunotherapy. Recent studies uncovered a role ... ...

    Abstract The melanoma-associated antigen family A (MAGEA) antigens are expressed in a wide variety of malignant tumors but not in adult somatic cells, rendering them attractive targets for cancer immunotherapy. Recent studies uncovered a role for
    MeSH term(s) Adult ; Antigens, Neoplasm/genetics ; Autophagy ; Humans ; Immunotherapy ; Neoplasm Proteins/genetics ; Pancreas ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/therapy
    Chemical Substances Antigens, Neoplasm ; MAGEA6 protein, human ; Neoplasm Proteins
    Language English
    Publishing date 2020-08-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2020.1802091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Precision oncology for breast cancer through clinical trials.

    Blucher, Aurora S / Mills, Gordon B / Tsang, Yiu Huen

    Clinical & experimental metastasis

    2021  Volume 39, Issue 1, Page(s) 71–78

    Abstract: Precision treatment for breast cancers has made several notable advances in recent decades, but challenges of tumor heterogeneity, drug resistance, and aggressive recurrence and metastases remain. To meet and overcome these challenges, we must refine our ...

    Abstract Precision treatment for breast cancers has made several notable advances in recent decades, but challenges of tumor heterogeneity, drug resistance, and aggressive recurrence and metastases remain. To meet and overcome these challenges, we must refine our understanding of breast subtypes and treatment biomarkers according to the knowledge afforded across the spectrum of 'omics assays. A critical aspect of harnessing this knowledge into actionable biomarkers for treatment decision relies on our ability to integrate knowledge across data types and leverage our insight in evidence-based clinical trials. We review recent advances in cutting-edge clinical trials for precision treatment of breast cancer, including chemotherapies, targeted therapies, immunotherapies, and combination therapies. We comment on promising future areas of development for this exciting point in precision breast cancer research.
    MeSH term(s) Biomarkers ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Female ; Humans ; Immunotherapy ; Medical Oncology ; Precision Medicine/methods
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-05-05
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 604952-7
    ISSN 1573-7276 ; 0262-0898
    ISSN (online) 1573-7276
    ISSN 0262-0898
    DOI 10.1007/s10585-021-10092-0
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