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Yawen Chen - One of the best experts on this subject based on the ideXlab platform.

  • endothelial cell Colony Forming Units derived from malignant breast diseases are resistant to tumor necrosis factor α induced apoptosis
    Scientific Reports, 2016
    Co-Authors: Chenpin Chou, Shih Sheng Jiang, Huayben Pan, Yichen Yen, Huihwa Tseng, Yuting Hung, Ssuhan Wang, Yu Lin Chen, Yawen Chen
    Abstract:

    Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based Colony Forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell Colony-Forming Units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection. Gene expression profiles revealed a genetic difference between CD34+ VEGFR2+ EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor 2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)-induced signalling were demonstrated in EC-CFUs derived from patients with malignant breast disease in comparison with those from healthy controls. Interestingly, our data provided the first evidence that EC-CFUs derived from patients with malignant breast disease were resistant to TNF-α-induced apoptosis, indicating a plausible target for future therapeutic interventions.

Vibha N Lama - One of the best experts on this subject based on the ideXlab platform.

  • prognostic significance of mesenchymal cell Colony Forming Units in bronchoalveolar lavage fluid for restrictive chronic lung allograft dysfunction
    Journal of Heart and Lung Transplantation, 2019
    Co-Authors: M P Combs, Meng Xia, David Wheeler, Elizabeth A Belloli, D M Lyu, N M Walker, Susan Murray, Vibha N Lama
    Abstract:

    Purpose Restrictive chronic lung allograft dysfunction (rCLAD) is associated with decreased survival but individual prognosis remains variable. Increased numbers of Colony-Forming Units (CFU) of mesenchymal stromal cells (MSC)—the effector cells in fibroproliferation—derived from bronchoalveolar lavage (BAL) fluid have been associated with developing bronchiolitis obliterans syndrome (BOS). However, the prognostic significance of MSC in rCLAD is unknown. Methods We analyzed 82 BAL samples collected at CLAD onset and 82 paired CLAD free samples, matched on the basis of time-post transplant. MSC were quantified as CFU count per 2 × 106 cells in BAL and analyzed as Results Average mesenchymal CFU counts were higher in samples from CLAD onset vs. CLAD free controls (10.99 vs. 4.37, p Conclusion rCLAD is associated with increased BAL MSC numbers, and higher mesenchymal CFU counts at time of CLAD onset are associated with progressive lung function decline and mortality. Mesenchymal CFU represent a biomarker for active fibroproliferation, which has implications for RAS pathogenesis and progression.

  • prognostic significance of mesenchymal cell Colony Forming Units in bronchoalveolar lavage fluid for restrictive chronic lung allograft dysfunction
    Journal of Heart and Lung Transplantation, 2019
    Co-Authors: M P Combs, Meng Xia, Elizabeth A Belloli, D M Lyu, N M Walker, Susan Murray, David S Wheeler, Vibha N Lama
    Abstract:

    Purpose Restrictive chronic lung allograft dysfunction (rCLAD) is associated with decreased survival but individual prognosis remains variable. Increased numbers of Colony-Forming Units (CFU) of mesenchymal stromal cells (MSC)—the effector cells in fibroproliferation—derived from bronchoalveolar lavage (BAL) fluid have been associated with developing bronchiolitis obliterans syndrome (BOS). However, the prognostic significance of MSC in rCLAD is unknown. Methods We analyzed 82 BAL samples collected at CLAD onset and 82 paired CLAD free samples, matched on the basis of time-post transplant. MSC were quantified as CFU count per 2 × 106 cells in BAL and analyzed as were classified as BOS. CFU counts were compared using pair-wise Wicoxon rank-sum tests . Survival analyses were performed using a restricted means model and presented as Kaplan Meier curves . Results Average mesenchymal CFU counts were higher in samples from CLAD onset vs. CLAD free controls (10.99 vs. 4.37, p Conclusion rCLAD is associated with increased BAL MSC numbers, and higher mesenchymal CFU counts at time of CLAD onset are associated with progressive lung function decline and mortality. Mesenchymal CFU represent a biomarker for active fibroproliferation, which has implications for RAS pathogenesis and progression.

Malcolm A S Moore - One of the best experts on this subject based on the ideXlab platform.

  • identification of dendritic cell Colony Forming Units among normal human cd34 bone marrow progenitors that are expanded by c kit ligand and yield pure dendritic cell colonies in the presence of granulocyte macrophage Colony stimulating factor and tumor necrosis factor alpha
    Journal of Experimental Medicine, 1995
    Co-Authors: James W Young, Paul Szabolcs, Malcolm A S Moore
    Abstract:

    Several cytokines, especially granulocyte/macrophage Colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha), have been identified that foster the development of dendritic cells from blood and bone marrow precursors in suspension cultures. These precursors are reported to be infrequent or to yield small numbers of dendritic cells in Colony-Forming assays. Here we readily identify dendritic cell Colony-Forming Units (CFU-DC) that give rise to pure dendritic cell colonies. Human CD34+ bone marrow progenitors were expanded in semi-solid cultures with serum-replete medium containing c-kit-ligand, GM-CSF, and TNF-alpha. The addition of TNF-alpha to GM-CSF did not alter the number of typical GM colonies but did generate pure dendritic cell colonies that accounted for approximately 40% of the total Colony growth. When the two distinct types of colonies were plucked from methylcellulose and tested for T cell-stimulatory activity in the mixed leukocyte reaction, the potency of Colony-derived dendritic cells exceeded that of CFU-GM progeny from the same cultures by at least 1.5-2 logs. Immunophenotyping and cytochemical staining of the CFU-DC-derived progeny was also characteristic of dendritic cells. Other myeloid cells were not identified in these colonies. The addition of c-kit-ligand to GM-CSF- and TNF-alpha-supplemented suspensions of CD34+ bone marrow cells expanded CFU-DCs almost 100-fold by 14 d. We conclude that normal human CD34+ bone marrow cells include substantial numbers of clonogenic progenitors, distinct from CFU-GMs, that can give rise to pure dendritic cell colonies. These CFU-DCs can be expanded for several weeks by in vitro culture with c-kit-ligand, and their differentiation requires exogenous TNF-alpha in addition to GM-CSF. We speculate that this dendritic cell-committed pathway may in the steady state contribute cells to the epidermis and afferent lymph, where dendritic cells are the principal myeloid cell type, and may increase the numbers of these specialized antigen-presenting cells during T cell-mediated immune responses.

Roy Krumbholz - One of the best experts on this subject based on the ideXlab platform.

  • bone marrow and tumor cell Colony Forming Units and human tumor xenograft efficacy of noncamptothecin and camptothecin topoisomerase i inhibitors
    Molecular Cancer Therapeutics, 2008
    Co-Authors: Leslie Kurtzberg, Traci Battle, Cecile Rouleau, Rebecca G Bagley, Naoki Agata, Min Yao, Steven Schmid, Stephanie Roth, Jennifer Crawford, Roy Krumbholz
    Abstract:

    Topoisomerase I (TopoI), an established anticancer target, is an enzyme producing a single-strand DNA break during transcription. Several noncamptothecin TopoI inhibitors have been identified. One of these, ARC-111, was compared with two clinically used camptothecins, topotecan and irinotecan/SN-38. In mouse and human bone marrow Colony formation [Colony-Forming Units granulocyte-macrophage (CFU-GM)] assays, the IC90 values were 519 and 331 nmol/L for topotecan and SN-38 mouse CFU-GM and were 19 and 26 nmol/L for human CFU-GM, giving mouse to human differentials of 28- and 13-fold. ARC-111 produced IC90 values of 28 nmol/L in mouse and 6.2 nmol/L in human CFU-GM, thus only a 4.5-fold differential between species. Human bone marrow CFU-GM was more sensitive to topotecan than were several human cancer cell lines, but ARC-111 cytotoxicity was similar for human bone marrow CFU-GM and the seven human tumor cell lines tested. In HCT-116 xenografts, tumor growth delays (TGD) were 17 days for irinotecan and 20 days for ARC-111. In HT-29 xenografts, the TGD was 9 days for both irinotecan and ARC-111. Both ARC-111 and docetaxel had a TGD of 21 days in NCI-H460 xenografts, and both ARC-111 and gemcitabine had a TGD of 7 days in MiaPaCa2 xenograft. Current TopoI inhibitors have broad antitumor activity in human tumor xenografts that is not achieved in the clinic. This may be due to greater sensitivity of human bone marrow than mouse to the cytotoxicity of these agents. It may be possible to achieve similar levels of ARC-111 in patients as in mice allowing improved antitumor activity. [Mol Cancer Ther 2008;7(10):3212–22]

M P Combs - One of the best experts on this subject based on the ideXlab platform.

  • prognostic significance of mesenchymal cell Colony Forming Units in bronchoalveolar lavage fluid for restrictive chronic lung allograft dysfunction
    Journal of Heart and Lung Transplantation, 2019
    Co-Authors: M P Combs, Meng Xia, David Wheeler, Elizabeth A Belloli, D M Lyu, N M Walker, Susan Murray, Vibha N Lama
    Abstract:

    Purpose Restrictive chronic lung allograft dysfunction (rCLAD) is associated with decreased survival but individual prognosis remains variable. Increased numbers of Colony-Forming Units (CFU) of mesenchymal stromal cells (MSC)—the effector cells in fibroproliferation—derived from bronchoalveolar lavage (BAL) fluid have been associated with developing bronchiolitis obliterans syndrome (BOS). However, the prognostic significance of MSC in rCLAD is unknown. Methods We analyzed 82 BAL samples collected at CLAD onset and 82 paired CLAD free samples, matched on the basis of time-post transplant. MSC were quantified as CFU count per 2 × 106 cells in BAL and analyzed as Results Average mesenchymal CFU counts were higher in samples from CLAD onset vs. CLAD free controls (10.99 vs. 4.37, p Conclusion rCLAD is associated with increased BAL MSC numbers, and higher mesenchymal CFU counts at time of CLAD onset are associated with progressive lung function decline and mortality. Mesenchymal CFU represent a biomarker for active fibroproliferation, which has implications for RAS pathogenesis and progression.

  • prognostic significance of mesenchymal cell Colony Forming Units in bronchoalveolar lavage fluid for restrictive chronic lung allograft dysfunction
    Journal of Heart and Lung Transplantation, 2019
    Co-Authors: M P Combs, Meng Xia, Elizabeth A Belloli, D M Lyu, N M Walker, Susan Murray, David S Wheeler, Vibha N Lama
    Abstract:

    Purpose Restrictive chronic lung allograft dysfunction (rCLAD) is associated with decreased survival but individual prognosis remains variable. Increased numbers of Colony-Forming Units (CFU) of mesenchymal stromal cells (MSC)—the effector cells in fibroproliferation—derived from bronchoalveolar lavage (BAL) fluid have been associated with developing bronchiolitis obliterans syndrome (BOS). However, the prognostic significance of MSC in rCLAD is unknown. Methods We analyzed 82 BAL samples collected at CLAD onset and 82 paired CLAD free samples, matched on the basis of time-post transplant. MSC were quantified as CFU count per 2 × 106 cells in BAL and analyzed as were classified as BOS. CFU counts were compared using pair-wise Wicoxon rank-sum tests . Survival analyses were performed using a restricted means model and presented as Kaplan Meier curves . Results Average mesenchymal CFU counts were higher in samples from CLAD onset vs. CLAD free controls (10.99 vs. 4.37, p Conclusion rCLAD is associated with increased BAL MSC numbers, and higher mesenchymal CFU counts at time of CLAD onset are associated with progressive lung function decline and mortality. Mesenchymal CFU represent a biomarker for active fibroproliferation, which has implications for RAS pathogenesis and progression.