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  1. Article ; Online: A Self-Assembly Method for Creating Vascularized Tumor Explants Using Biomaterials for 3D Culture.

    Munn, Lance L / Bazou, Despina

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2645, Page(s) 211–220

    Abstract: Validation of potential therapeutic targets in cancer requires functional live assays that recapitulate the biology, anatomy, and physiology of human tumors. We present a methodology for maintaining mouse and patient tumor samples ex vivo for in vitro ... ...

    Abstract Validation of potential therapeutic targets in cancer requires functional live assays that recapitulate the biology, anatomy, and physiology of human tumors. We present a methodology for maintaining mouse and patient tumor samples ex vivo for in vitro drug-screening as well as for the guidance of patient-specific chemotherapies. The harvested tumor biopsy, excised from mice or patients, is integrated into a support tissue that includes extended stroma and vasculature. The methodology is more representative than tissue culture assays, faster than patient-derived xenograft models, easy to implement, amenable to high-throughput assays and does not carry the ethical issues or expense associated with animal studies. Our physiologically relevant model can be successfully used for high-throughput drug screening.
    MeSH term(s) Humans ; Mice ; Animals ; Biocompatible Materials ; Neoplasms ; Drug Evaluation, Preclinical ; Disease Models, Animal ; High-Throughput Screening Assays
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2023-05-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3056-3_12
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  2. Article ; Online: Computational simulations of tumor growth and treatment response: Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization.

    Nikmaneshi, Mohammad R / Jain, Rakesh K / Munn, Lance L

    PLoS computational biology

    2023  Volume 19, Issue 6, Page(s) e1011131

    Abstract: Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three- ... ...

    Abstract Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three-dimensional mathematical model of the TME to simulate tumor growth and angiogenesis and then employed the model to evaluate an array of single and combination therapy approaches. Treatments included maximum tolerated dose or metronomic (i.e., frequent low doses) scheduling of anti-cancer drugs combined with anti-angiogenic therapy. The results show that metronomic therapy normalizes the tumor vasculature to improve drug delivery, modulates cancer metabolism, decreases interstitial fluid pressure and decreases cancer cell invasion. Further, we find that combining an anti-cancer drug with anti-angiogenic treatment enhances tumor killing and reduces drug accumulation in normal tissues. We also show that combined anti-angiogenic and anti-cancer drugs can decrease cancer invasiveness and normalize the cancer metabolic microenvironment leading to reduced hypoxia and hypoglycemia. Our model simulations suggest that vessel normalization combined with metronomic cytotoxic therapy has beneficial effects by enhancing tumor killing and limiting normal tissue toxicity.
    MeSH term(s) Humans ; Pharmaceutical Preparations ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Neoplasms/pathology ; Antineoplastic Agents/pharmacology ; Immunotherapy ; Neovascularization, Pathologic/metabolism ; Tumor Microenvironment
    Chemical Substances Pharmaceutical Preparations ; Angiogenesis Inhibitors ; Antineoplastic Agents
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1011131
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  3. Article ; Online: Vascular regulation of antitumor immunity.

    Munn, Lance L / Jain, Rakesh K

    Science (New York, N.Y.)

    2020  Volume 365, Issue 6453, Page(s) 544–545

    MeSH term(s) Cancer-Associated Fibroblasts/immunology ; Humans ; Immune Tolerance ; Immunotherapy, Adoptive/methods ; Neoplasms/blood supply ; Neoplasms/therapy ; Neovascularization, Pathologic/immunology ; Neovascularization, Pathologic/therapy ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes, Regulatory/immunology ; Tumor Hypoxia/immunology ; Tumor Microenvironment
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2020-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aaw7875
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  4. Article ; Online: Cancer and inflammation.

    Munn, Lance L

    Wiley interdisciplinary reviews. Systems biology and medicine

    2017  Volume 9, Issue 2

    Abstract: The relationship between inflammation and cancer has been recognized since the ... ...

    Abstract The relationship between inflammation and cancer has been recognized since the 17
    MeSH term(s) Adaptive Immunity ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/metabolism ; Cell Adhesion Molecules/metabolism ; Cytokines/metabolism ; Humans ; Immune System/metabolism ; Inflammation ; MicroRNAs/metabolism ; NF-kappa B/metabolism ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy
    Chemical Substances B7-H1 Antigen ; Cell Adhesion Molecules ; Cytokines ; MicroRNAs ; NF-kappa B
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2503323-2
    ISSN 1939-005X ; 1939-5094
    ISSN (online) 1939-005X
    ISSN 1939-5094
    DOI 10.1002/wsbm.1370
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    Zs.A 6790: Show issues Location:
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  5. Article ; Online: The effects of gravity and compression on interstitial fluid transport in the lower limb.

    Baish, James W / Padera, Timothy P / Munn, Lance L

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 4890

    Abstract: Edema in the limbs can arise from pathologies such as elevated capillary pressures due to failure of venous valves, elevated capillary permeability from local inflammation, and insufficient fluid clearance by the lymphatic system. The most common ... ...

    Abstract Edema in the limbs can arise from pathologies such as elevated capillary pressures due to failure of venous valves, elevated capillary permeability from local inflammation, and insufficient fluid clearance by the lymphatic system. The most common treatments include elevation of the limb, compression wraps and manual lymphatic drainage therapy. To better understand these clinical situations, we have developed a comprehensive model of the solid and fluid mechanics of a lower limb that includes the effects of gravity. The local fluid balance in the interstitial space includes a source from the capillaries, a sink due to lymphatic clearance, and movement through the interstitial space due to both gravity and gradients in interstitial fluid pressure (IFP). From dimensional analysis and numerical solutions of the governing equations we have identified several parameter groups that determine the essential length and time scales involved. We find that gravity can have dramatic effects on the fluid balance in the limb with the possibility that a positive feedback loop can develop that facilitates chronic edema. This process involves localized tissue swelling which increases the hydraulic conductivity, thus allowing the movement of interstitial fluid vertically throughout the limb due to gravity and causing further swelling. The presence of a compression wrap can interrupt this feedback loop. We find that only by modeling the complex interplay between the solid and fluid mechanics can we adequately investigate edema development and treatment in a gravity dependent limb.
    MeSH term(s) Edema ; Extracellular Fluid ; Humans ; Lower Extremity ; Models, Biological ; Pressure
    Language English
    Publishing date 2022-03-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-09028-9
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  6. Article ; Online: Mechanosensing tensile solid stresses.

    Munn, Lance L / Nia, Hadi T

    Proceedings of the National Academy of Sciences of the United States of America

    2019  Volume 116, Issue 44, Page(s) 21960–21962

    MeSH term(s) Mechanotransduction, Cellular/physiology ; Stress, Mechanical ; Tensile Strength
    Language English
    Publishing date 2019-10-16
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1916115116
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
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  7. Article ; Online: Computational simulations of tumor growth and treatment response

    Mohammad R. Nikmaneshi / Rakesh K. Jain / Lance L. Munn

    PLoS Computational Biology, Vol 19, Iss

    Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization

    2023  Volume 6

    Abstract: Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three- ... ...

    Abstract Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three-dimensional mathematical model of the TME to simulate tumor growth and angiogenesis and then employed the model to evaluate an array of single and combination therapy approaches. Treatments included maximum tolerated dose or metronomic (i.e., frequent low doses) scheduling of anti-cancer drugs combined with anti-angiogenic therapy. The results show that metronomic therapy normalizes the tumor vasculature to improve drug delivery, modulates cancer metabolism, decreases interstitial fluid pressure and decreases cancer cell invasion. Further, we find that combining an anti-cancer drug with anti-angiogenic treatment enhances tumor killing and reduces drug accumulation in normal tissues. We also show that combined anti-angiogenic and anti-cancer drugs can decrease cancer invasiveness and normalize the cancer metabolic microenvironment leading to reduced hypoxia and hypoglycemia. Our model simulations suggest that vessel normalization combined with metronomic cytotoxic therapy has beneficial effects by enhancing tumor killing and limiting normal tissue toxicity. Author summary Effective treatment of solid tumors with injected drugs requires that sufficient exposure of cancer cells to the cytotoxic drugs. However, non-uniform and poorly functioning blood vessels make this difficult. The amount of drug that reaches a given cancer cells depends on many factors, including the drug chemistry, its lifetime in the blood circulation, its ability to cross the blood vessel wall and enter the tissue, and the schedule of the injections. We present a mathematical model of tumor growth, angiogenesis, metabolism and drug transport that examines how these processes affect the response to treatment. We find that low dose, high frequency (metronomic) therapy normalizes the tumor ...
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Transport Barriers Influence the Activation of Anti-Tumor Immunity: A Systems Biology Analysis.

    Nikmaneshi, Mohammad R / Baish, James W / Zhou, Hengbo / Padera, Timothy P / Munn, Lance L

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2023  Volume 10, Issue 36, Page(s) e2304076

    Abstract: Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical ... ...

    Abstract Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and trafficking of naïve T cells into the lymph nodes are key parameters and that treatments designed to enhance tumor antigen production can improve immune checkpoint therapies. The model underscores the potential of radiation therapy in augmenting tumor immunogenicity and neoantigen production for improved ICB therapy, while emphasizing the need for careful consideration in cases where antigen levels are already sufficient to avoid compromising the immune response.
    MeSH term(s) Humans ; Neoplasms/pathology ; T-Lymphocytes ; Antigens, Neoplasm ; Immunotherapy/methods
    Chemical Substances Antigens, Neoplasm
    Language English
    Publishing date 2023-11-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202304076
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  9. Article ; Online: Endothelial mechanobiology in atherosclerosis.

    Wang, Xiaoli / Shen, Yang / Shang, Min / Liu, Xiaoheng / Munn, Lance L

    Cardiovascular research

    2023  Volume 119, Issue 8, Page(s) 1656–1675

    Abstract: Cardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays a central role in maintaining vascular integrity and homeostasis and is ... ...

    Abstract Cardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays a central role in maintaining vascular integrity and homeostasis and is in direct contact with the blood flow. Research over the past century has shown that mechanical perturbations of the vascular wall contribute to the formation and progression of atherosclerosis. While the straight part of the artery is exposed to sustained laminar flow and physiological high shear stress, flow near branch points or in curved vessels can exhibit 'disturbed' flow. Clinical studies as well as carefully controlled in vitro analyses have confirmed that these regions of disturbed flow, which can include low shear stress, recirculation, oscillation, or lateral flow, are preferential sites of atherosclerotic lesion formation. Because of their critical role in blood flow homeostasis, vascular endothelial cells (ECs) have mechanosensory mechanisms that allow them to react rapidly to changes in mechanical forces, and to execute context-specific adaptive responses to modulate EC functions. This review summarizes the current understanding of endothelial mechanobiology, which can guide the identification of new therapeutic targets to slow or reverse the progression of atherosclerosis.
    MeSH term(s) Humans ; Endothelial Cells/pathology ; Atherosclerosis/pathology ; Endothelium, Vascular ; Hemodynamics ; Cardiovascular Diseases ; Stress, Mechanical ; Mechanotransduction, Cellular
    Language English
    Publishing date 2023-05-12
    Publishing country England
    Document type Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvad076
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    Zs.A 565: Show issues Location:
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  10. Article ; Online: In silico clinical studies for optimal COVID-19 vaccination schedules in patients with cancer.

    Voutouri, Chrysovalantis / Hardin, C Corey / Naranbhai, Vivek / Nikmaneshi, Mohammad R / Khandekar, Melin J / Gainor, Justin F / Stylianopoulos, Triantafyllos / Munn, Lance L / Jain, Rakesh K

    Cell reports. Medicine

    2024  Volume 5, Issue 3, Page(s) 101436

    Abstract: This study introduces a tailored COVID-19 model for patients with cancer, incorporating viral variants and immune-response dynamics. The model aims to optimize vaccination strategies, contributing to personalized healthcare for vulnerable groups. ...

    Abstract This study introduces a tailored COVID-19 model for patients with cancer, incorporating viral variants and immune-response dynamics. The model aims to optimize vaccination strategies, contributing to personalized healthcare for vulnerable groups.
    MeSH term(s) Humans ; COVID-19 Vaccines/therapeutic use ; COVID-19/prevention & control ; Neoplasms ; Vaccination
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2024-03-20
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2024.101436
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