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  1. Article ; Online: The Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs.

    Hendrix, Amanda Y / Kheradmand, Farrah

    Progress in molecular biology and translational science

    2017  Volume 148, Page(s) 1–29

    Abstract: Normal gas exchange after birth requires functional lung alveolar units that are lined with epithelial cells, parts of which are intricately fused with microvascular capillaries. A significant phase of alveolar lung development occurs in the perinatal ... ...

    Abstract Normal gas exchange after birth requires functional lung alveolar units that are lined with epithelial cells, parts of which are intricately fused with microvascular capillaries. A significant phase of alveolar lung development occurs in the perinatal period, continues throughout early stages in life, and requires activation of matrix-remodeling enzymes. Failure to achieve an optimum number of alveoli during lung maturation can cause several untoward medical consequences including disabling obstructive and/or restrictive lung diseases that limit physiological endurance and increase mortality. Several members of the matrix metalloproteinase (MMP) family are critical in lung remodeling before and after birth; however, their resurgence in response to environmental factors, infection, and injury can also compromise lung function. Therefore, temporal expression, regulation, and function of MMPs play key roles in developing and maintaining adequate oxygenation under steady state, as well as in diseased conditions. Broadly, with the exception of MMP2 and MMP14, most deletional mutations of MMPs fail to perturb lung development; however, their individual absence can alter the pathophysiology of respiratory diseases. Specifically, under stressed conditions such as acute respiratory infection and allergic inflammation, MMP2 and MMP9 can play a protective role through bacterial clearance and production of chemotactic gradient, while loss of MMP12 can protect mice from smoke-induced lung disease. Therefore, better understanding of the expression and function of MMPs under normal lung development and their resurgence in response respiratory diseases could provide new therapeutic options in the future.
    MeSH term(s) Animals ; Humans ; Lung/embryology ; Lung/enzymology ; Lung/pathology ; Lung Injury/enzymology ; Lung Injury/pathology ; Matrix Metalloproteinases/metabolism ; Pulmonary Alveoli/enzymology ; Pulmonary Alveoli/pathology ; Wound Healing
    Chemical Substances Matrix Metalloproteinases (EC 3.4.24.-)
    Language English
    Publishing date 2017
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2471995-X
    ISSN 1878-0814 ; 0079-6603 ; 1877-1173
    ISSN (online) 1878-0814
    ISSN 0079-6603 ; 1877-1173
    DOI 10.1016/bs.pmbts.2017.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells.

    Botta, Gregory P / Chao, Joseph / Ma, Hong / Hahn, Michael / Sierra, Gloria / Jia, Jie / Hendrix, Amanda Y / Nolte Fong, Joy V / Ween, Audrey / Vu, Peter / Miller, Aaron / Choi, Michael / Heyman, Benjamin / Daniels, Gregory A / Kaufman, Dan / Jamieson, Catriona / Li, Zonghai / Cohen, Ezra

    Journal for immunotherapy of cancer

    2024  Volume 12, Issue 2

    Abstract: Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell ... ...

    Abstract Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy.
    MeSH term(s) Humans ; Receptors, Antigen, T-Cell ; Stomach Neoplasms/therapy ; Quality of Life ; T-Lymphocytes ; Receptors, Chimeric Antigen ; Pathologic Complete Response ; Antigens, CD19 ; Leukemia ; Tumor Microenvironment
    Chemical Substances Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; Antigens, CD19
    Language English
    Publishing date 2024-02-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-007927
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A novel BCMA CAR-T-cell therapy with optimized human scFv for treatment of relapsed/refractory multiple myeloma: results from phase I clinical trials.

    Yang, Min / Zhang, Wenhao / Yu, Kang / Wang, Peng / Jiang, Hua / Chen, Linjun / Meng, Haitao / Weng, Yiqin / Tao, Rong / Huang, Xin / Xing, Chongyun / Wang, Huamao / Wan, Jiangbo / Wang, Shasha / Dai, Lihui / Hendrix, Amanda Y / Xiao, Jun / Wang, Wei / Ma, Hong /
    Hao, Siguo / Jin, Jie / Li, Zonghai / Jiang, Songfu

    Haematologica

    2022  Volume 107, Issue 8, Page(s) 1960–1965

    MeSH term(s) B-Cell Maturation Antigen ; Cell- and Tissue-Based Therapy ; Clinical Trials, Phase I as Topic ; Humans ; Immunotherapy, Adoptive/methods ; Multiple Myeloma/therapy ; Neoplasms, Plasma Cell ; Receptors, Chimeric Antigen/genetics
    Chemical Substances B-Cell Maturation Antigen ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2022-08-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2022.280629
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema.

    You, Ran / Lu, Wen / Shan, Ming / Berlin, Jacob M / Samuel, Errol Lg / Marcano, Daniela C / Sun, Zhengzong / Sikkema, William Ka / Yuan, Xiaoyi / Song, Lizhen / Hendrix, Amanda Y / Tour, James M / Corry, David B / Kheradmand, Farrah

    eLife

    2015  Volume 4, Page(s) e09623

    Abstract: Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non- ... ...

    Abstract Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.
    MeSH term(s) Animals ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/physiology ; DNA Cleavage/drug effects ; Dendritic Cells/drug effects ; Dendritic Cells/physiology ; Inflammasomes/metabolism ; Inflammation/chemically induced ; Mice ; Nanoparticles/toxicity ; Phagocytes/metabolism ; Pulmonary Emphysema/pathology ; Smoke ; Smoking ; Soot/toxicity ; Th17 Cells/drug effects ; Th17 Cells/physiology
    Chemical Substances Inflammasomes ; Smoke ; Soot
    Language English
    Publishing date 2015-10-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.09623
    Database MEDical Literature Analysis and Retrieval System OnLINE

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