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  1. Article ; Online: Why do we need better omics in the breast cancer care?

    Gertych, Arkadiusz / Shiao, Stephen L

    EBioMedicine

    2021  Volume 72, Page(s) 103598

    Language English
    Publishing date 2021-09-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2021.103598
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  2. Article ; Online: Why do we need better omics in the breast cancer care?

    Arkadiusz Gertych / Stephen L. Shiao

    EBioMedicine, Vol 72, Iss , Pp 103598- (2021)

    2021  

    Keywords Medicine ; R ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Activated T cell therapy targeting glioblastoma cancer stem cells.

    Miyaguchi, Ken / Wang, Hongqiang / Black, Keith L / Shiao, Stephen L / Wang, Rongfu / Yu, John S

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 196

    Abstract: Naïve T cells become effector T cells following stimulation by antigen-loaded dendritic cells (DCs) and sequential cytokine activation. We aimed to develop procedures to efficiently activate T cells with tumor-associated antigens (TAAs) to glioblastoma ( ... ...

    Abstract Naïve T cells become effector T cells following stimulation by antigen-loaded dendritic cells (DCs) and sequential cytokine activation. We aimed to develop procedures to efficiently activate T cells with tumor-associated antigens (TAAs) to glioblastoma (GBM) stem cells. To remove antigen presentation outside of the immunosuppressive tumor milieu, three different glioma stem cell (GSC) specific antigen sources to load DCs were compared in their ability to stimulate lymphocytes. An activated T cell (ATC) protocol including cytokine activation and expansion in culture to target GSCs was generated and optimized for a planned phase I clinical trial. We compared three different antigen-loading methods on DCs to effectively activate T cells, which were GBM patient-derived GSC-lysate, acid-eluate of GSCs and synthetic peptides derived from proteins expressed in GSCs. DCs derived from HLA-A2 positive blood sample were loaded with TAAs. Autologous T cells were activated by co-culturing with loaded DCs. Efficiency and cytotoxicity of ATCs were evaluated by targeting TAA-pulsed DCs or T2 cells, GSCs, or autologous PHA-blasts. Characteristics of ATCs were evaluated by Flow Cytometry and ELISpot assay, which showed increased number of ATCs secreting IFN-γ targeting GSCs as compared with non-activated T cells and unloaded target cells. Neither GSC-lysate nor acid-eluate loading showed enhancement in response of ATCs but the synthetic peptide pool showed significantly increased IFN-γ secretion and increased cytotoxicity towards target cells. These results demonstrate that ATCs activated using a TAA synthetic peptide pool efficiently enhance cytotoxicity specifically to target cells including GSC.
    MeSH term(s) Humans ; T-Lymphocytes, Cytotoxic ; Glioblastoma/therapy ; Glioblastoma/metabolism ; Interferon-gamma/metabolism ; Antigens, Neoplasm ; Peptides/metabolism ; Neoplastic Stem Cells/metabolism ; Cell- and Tissue-Based Therapy ; Dendritic Cells
    Chemical Substances Interferon-gamma (82115-62-6) ; Antigens, Neoplasm ; Peptides
    Language English
    Publishing date 2023-01-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-27184-w
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  4. Article ; Online: Chronic antigen in solid tumors drives a distinct program of T cell residence.

    Gavil, Noah V / Scott, Milcah C / Weyu, Eyob / Smith, Olivia C / O'Flanagan, Stephen D / Wijeyesinghe, Sathi / Lotfi-Emran, Sahar / Shiao, Stephen L / Vezys, Vaiva / Masopust, David

    Science immunology

    2023  Volume 8, Issue 84, Page(s) eadd5976

    Abstract: Analyses of healthy tissue reveal signatures that identify resident memory ... ...

    Abstract Analyses of healthy tissue reveal signatures that identify resident memory CD8
    MeSH term(s) Mice ; Animals ; CD8-Positive T-Lymphocytes ; Immunologic Memory ; Neoplasms ; Antigens ; Prognosis ; Tumor Microenvironment
    Chemical Substances Antigens
    Language English
    Publishing date 2023-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.add5976
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  5. Article ; Online: Advances in Combining Radiation and Immunotherapy in Breast Cancer.

    Nguyen, Anthony T / Shiao, Stephen L / McArthur, Heather L

    Clinical breast cancer

    2021  Volume 21, Issue 2, Page(s) 143–152

    Abstract: Breast irradiation has long been utilized in the adjuvant or metastatic setting to eliminate microscopic disease or to palliate existing disease, respectively. However, preclinical data have demonstrated that radiation can also alter the tumor ... ...

    Abstract Breast irradiation has long been utilized in the adjuvant or metastatic setting to eliminate microscopic disease or to palliate existing disease, respectively. However, preclinical data have demonstrated that radiation can also alter the tumor microenvironment and induce antitumor immune responses. As a result, multiple clinical studies have been undertaken and have reported synergy between radiation and immune checkpoint blockade across various cancer types. Given recent clinical successes with immune checkpoint blockade in both early-stage and metastatic breast cancer, there has been substantial interest in combining radiation and immunotherapy to enhance local and systemic immune responses. Herein, we review the preclinical rationale for combining radiotherapy and immunotherapy, the early clinical trials that have adopted this strategy in breast cancer, and the landscape of ongoing relevant clinical trials. Finally, we propose future directions based on promising preclinical studies that integrate radiation, checkpoint blockade, and novel agents for the treatment of breast cancer.
    MeSH term(s) Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/immunology ; Breast Neoplasms/therapy ; Combined Modality Therapy ; Female ; Humans ; Immunotherapy/methods ; Lymphocyte Activation/immunology
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents
    Language English
    Publishing date 2021-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2106734-X
    ISSN 1938-0666 ; 1526-8209
    ISSN (online) 1938-0666
    ISSN 1526-8209
    DOI 10.1016/j.clbc.2021.03.007
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  6. Article ; Online: Association of x-ray velocimetry (XV) ventilation analysis compared to spirometry.

    Kirkness, Jason P / Dusting, Jonathan / Eikelis, Nina / Pirakalathanan, Piraveen / DeMarco, John / Shiao, Stephen L / Fouras, Andreas

    Frontiers in medical technology

    2023  Volume 5, Page(s) 1148310

    Abstract: Introduction: X-ray Velocimetry (XV) ventilation analysis is a 4-dimensional imaging-based method for quantifying regional ventilation, aiding in the assessment of lung function. We examined the performance characteristics of XV ventilation analysis by ... ...

    Abstract Introduction: X-ray Velocimetry (XV) ventilation analysis is a 4-dimensional imaging-based method for quantifying regional ventilation, aiding in the assessment of lung function. We examined the performance characteristics of XV ventilation analysis by examining correlation to spirometry and measurement repeatability.
    Methods: XV analysis was assessed in 27 patients receiving thoracic radiotherapy for non-lung cancer malignancies. Measurements were obtained pre-treatment and at 4 and 12-months post-treatment. XV metrics such as ventilation defect percent (VDP) and regional ventilation heterogeneity (VH) were compared to spirometry at each time point, using correlation analysis. Repeatability was assessed between multiple runs of the analysis algorithm, as well as between multiple breaths in the same patient. Change in VH and VDP in a case series over 12 months was used to determine effect size and estimate sample sizes for future studies.
    Results: VDP and VH were found to significantly correlate with FEV
    Conclusions: The performance and safety of XV analysis make it ideal for both clinical and research applications across most lung indications. Our results support continued research and provide a basis for powering future studies using XV as an endpoint to examine lung health and determine therapeutic efficacy.
    Language English
    Publishing date 2023-06-22
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2673-3129
    ISSN (online) 2673-3129
    DOI 10.3389/fmedt.2023.1148310
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  7. Article ; Online: The role of macrophage phenotype in regulating the response to radiation therapy.

    Shi, Xiaoshan / Shiao, Stephen L

    Translational research : the journal of laboratory and clinical medicine

    2017  Volume 191, Page(s) 64–80

    Abstract: Increasing experimental and clinical evidence has revealed a critical role for myeloid cells in the development and progression of cancer. The ability of monocytes and macrophages to regulate inflammation allows them to manipulate the tumor ... ...

    Abstract Increasing experimental and clinical evidence has revealed a critical role for myeloid cells in the development and progression of cancer. The ability of monocytes and macrophages to regulate inflammation allows them to manipulate the tumor microenvironment to support the growth and development of malignant cells. Recent studies have shown that macrophages can exist in several functional states depending on the microenvironment they encounter in the tissue. These functional phenotypes influence not only the genesis and propagation of tumors, but also the efficacy of cancer therapies, particularly radiation. Early classification of the macrophage phenotypes, or "polarization states," identified 2 major states, M1 and M2, that have cytotoxic and wound repair capacity, respectively. In the context of tumors, classically activated or M1 macrophages driven by interferon-gamma support antitumor immunity while alternatively activated or M2 macrophages generated in part from interleukin-4 exposure hinder antitumor immunity by suppressing cytotoxic responses against a tumor. In this review, we discuss the role that the functional phenotype of a macrophage population plays in tumor development. We will then focus specifically on how macrophages and myeloid cells regulate the tumor response to radiation therapy.
    MeSH term(s) Animals ; Cell Polarity ; Humans ; Macrophages/drug effects ; Macrophages/radiation effects ; Molecular Targeted Therapy/methods ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/radiotherapy ; Radiotherapy
    Language English
    Publishing date 2017-11-20
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2246684-8
    ISSN 1878-1810 ; 1532-6543 ; 1931-5244
    ISSN (online) 1878-1810 ; 1532-6543
    ISSN 1931-5244
    DOI 10.1016/j.trsl.2017.11.002
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  8. Article ; Online: Targeting Innate Immunity to Enhance the Efficacy of Radiation Therapy.

    Dar, Tahir B / Henson, Regina M / Shiao, Stephen L

    Frontiers in immunology

    2019  Volume 9, Page(s) 3077

    Abstract: Radiation continues to play a major role in the treatment of almost every cancer type. Traditional radiation studies focused on its ability to damage DNA, but recent evidence has demonstrated that a key mechanism driving the efficacy of ... ...

    Abstract Radiation continues to play a major role in the treatment of almost every cancer type. Traditional radiation studies focused on its ability to damage DNA, but recent evidence has demonstrated that a key mechanism driving the efficacy of radiation
    MeSH term(s) Adaptive Immunity/drug effects ; Adaptive Immunity/radiation effects ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Chemoradiotherapy/methods ; Clinical Trials as Topic ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/radiation effects ; Humans ; Immunity, Innate/drug effects ; Immunity, Innate/radiation effects ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Killer Cells, Natural/radiation effects ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/radiation effects ; Molecular Targeted Therapy/methods ; Neoplasms/immunology ; Neoplasms/therapy ; Treatment Outcome ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Tumor Microenvironment/radiation effects
    Chemical Substances Antineoplastic Agents, Immunological
    Language English
    Publishing date 2019-01-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.03077
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  9. Article: Impact of the immune system and immunotherapy in colorectal cancer.

    Markman, Janet L / Shiao, Stephen L

    Journal of gastrointestinal oncology

    2015  Volume 6, Issue 2, Page(s) 208–223

    Abstract: The development of cancer is a multi-step process involving the gradual loss of regulation over the growth and functional capabilities of normal cells. Much research has been focused on the numerous cell intrinsic factors that govern this process; ... ...

    Abstract The development of cancer is a multi-step process involving the gradual loss of regulation over the growth and functional capabilities of normal cells. Much research has been focused on the numerous cell intrinsic factors that govern this process; however, recent attention has turned to understanding the cell extrinsic factors in the tumor microenvironment that appear equally critical to the progression and treatment of cancer. One critical component of the tumor microenvironment is the immune system and it has become increasingly evident that the immune system plays an integral role in preventing and promoting the development of cancer. Understanding the immune cell types and pathways involved in this process has enabled the development of novel biomarkers for prognosis and accelerated the development of immune-based therapeutics, both of which have the potential to forever change the treatment paradigms for colorectal cancer (CRC). In this review, we discuss the impact of the immune system on the initiation, progression and treatment of cancer, specifically focusing on CRC.
    Language English
    Publishing date 2015-02-25
    Publishing country China
    Document type Journal Article ; Review
    ZDB-ID 2594644-4
    ISSN 2219-679X ; 2078-6891
    ISSN (online) 2219-679X
    ISSN 2078-6891
    DOI 10.3978/j.issn.2078-6891.2014.077
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  10. Article ; Online: A Single-Institution Retrospective Study of Three-Fraction HDR Accelerated Partial Breast Irradiation.

    Chung, Eric M / Nguyen, Anthony T / Mirhadi, Amin / Steers, Jennifer M / Phillips, Tiffany / Atkins, Katelyn M / Burnison, Michele / Shiao, Stephen L / Kamrava, Mitchell

    Brachytherapy

    2023  Volume 22, Issue 3, Page(s) 361–367

    Abstract: Purpose: Accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy is a standard of care treatment typically delivered over 10 fractions. The TRIUMPH-T multi-institutional study recently demonstrated promising results ... ...

    Abstract Purpose: Accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy is a standard of care treatment typically delivered over 10 fractions. The TRIUMPH-T multi-institutional study recently demonstrated promising results using a shorter three fraction regimen, however there are limited additional published series using this regimen. Here, we report our experience and outcomes for patients treated as per the TRIUMPH-T regimen.
    Methods and materials: This study was a retrospective single-institution analysis of patients who underwent lumpectomy followed by APBI (22.5 Gy in 3 fractions delivered over 2-3 days) using a Strut Adjusted Volume Implant (SAVI) applicator between November 2016 and January 2021. Dose-volume metrics were obtained from the clinically treated plan. Chart review was performed to determine locoregional recurrence and toxicities according to CTCAE v5.0.
    Results: Between 2016 and 2021, 31 patients were treated per the TRIUMPH-T protocol. Median followup was 31 months from completion of brachytherapy. There were no acute/late Grade 3 or higher toxicities. Cumulative late Grade 1 and 2 toxicities were seen in 58.1% and 9.7% of patients, respectively. Of note, four patients experienced locoregional recurrence: three ipsilateral breast tumor recurrences and one nodal recurrence. All three ipsilateral breast tumor recurrences occurred in patients who would be classified as "cautionary" based on ASTRO consensus guidelines due to age ≤50, lobular histology, or high grade.
    Conclusions: Three-fraction HDR brachytherapy APBI was well-tolerated with no grade 3 or higher toxicities and an acceptably small percentage of grade 2 toxicities. Given the small sample size, the number of recurrences suggests that attention to appropriate patient selection is necessary until more long-term followup data is available.
    MeSH term(s) Humans ; Female ; Brachytherapy/methods ; Retrospective Studies ; Radiotherapy Dosage ; Neoplasm Recurrence, Local/radiotherapy ; Neoplasm Recurrence, Local/etiology ; Mastectomy, Segmental ; Breast Neoplasms/radiotherapy
    Language English
    Publishing date 2023-03-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2098608-7
    ISSN 1873-1449 ; 1538-4721
    ISSN (online) 1873-1449
    ISSN 1538-4721
    DOI 10.1016/j.brachy.2023.02.006
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