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  1. Article ; Online: Engineering tumor constructs to study matrix-dependent angiogenic signaling of breast cancer cells.

    Nasser, Malak / Ghosh, Gargi

    Biotechnology progress

    2022  Volume 38, Issue 3, Page(s) e3250

    Abstract: Breast cancer is the leading cause of cancer deaths among females globally. The crosstalk between tumor microenvironment and neoplastic cells is the key for promoting tumor growth, stimulating tumor angiogenesis, and metastasis to distant organs. Thus, ... ...

    Abstract Breast cancer is the leading cause of cancer deaths among females globally. The crosstalk between tumor microenvironment and neoplastic cells is the key for promoting tumor growth, stimulating tumor angiogenesis, and metastasis to distant organs. Thus, it is highly important to investigate tumor cell-matrix interactions to facilitate screening of different anti-cancer agents, individually or in combination. We, herein report, the development of an in vitro three-dimensional (3D) breast cancer model to investigate the effect of stromal crosslinking and consequent, stiffening on the angiogenic activity of cancer cells. Crosslinking of collagen gels was altered via non-enzymatic glycation and highly aggressive breast cancer cells, MDA-MB-231, were encapsulated in these gels. Cells encapsulated in glycated/stiffer matrices displayed an increased expression of pro-angiogenesis-related signals. Inhibition of mechanotransduction pathways on the angiogenic activity of aggressive tumor cells in stiff matrices was investigated using Y-27632, blebbistatin, and cytochalasin D. Rho-associated kinase (ROCK) inhibitor, Y-27632, diminished the pro-angiogenic signaling, thereby suggesting the potential dependence of breast cancer cells on the Rho/ROCK pathway in regulating tumor angiogenesis. Our findings highlight the potential of the developed model to be used as a tool to investigate matrix-associated tumor angiogenesis and screen different therapeutic agents towards inhibiting it.
    MeSH term(s) Breast Neoplasms/pathology ; Cell Line, Tumor ; Female ; Gels ; Humans ; Mechanotransduction, Cellular ; Neovascularization, Pathologic ; Signal Transduction ; Tumor Microenvironment
    Chemical Substances Gels
    Language English
    Publishing date 2022-03-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 165657-0
    ISSN 1520-6033 ; 8756-7938
    ISSN (online) 1520-6033
    ISSN 8756-7938
    DOI 10.1002/btpr.3250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Engineering microenvironments towards harnessing pro-angiogenic potential of mesenchymal stem cells.

    Nasser, Malak / Wu, Yang / Danaoui, Youssef / Ghosh, Gargi

    Materials science & engineering. C, Materials for biological applications

    2019  Volume 102, Page(s) 75–84

    Abstract: Mesenchymal stem cell (MSC)-based therapy for promoting vascular regeneration is a promising strategy for treating ischemic diseases. However, low engraftment and retention rate of MSCs at the target site highlights the importance of paracrine signaling ... ...

    Abstract Mesenchymal stem cell (MSC)-based therapy for promoting vascular regeneration is a promising strategy for treating ischemic diseases. However, low engraftment and retention rate of MSCs at the target site highlights the importance of paracrine signaling of MSCs in the reparative process. Thus, harnessing MSC-secretome is essential for rational design of MSC-based therapies. The role of microenvironment in regulating the paracrine signaling of MSCs is not well known. In this study, human bone marrow-derived MSCs were seeded on matrices with varying stiffness or cell adhesive sites, and conditioned media was collected. The concentrations of angiogenic molecules in the media was measured via ELISA. In addition, the bioactivity of the released molecules was investigated via assessing the proliferation and capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) incubated with conditioned media. Our study revealed that secretion of vascular endothelial growth factor (VEGF) is dependent on substrate stiffness. Maximal secretion was observed when MSCs were seeded on hydrogel matrices of 5.0 kPa stiffness. Proliferation and tubulogenesis of HUVECs supported ELISA data. On the other hand, variation of cell adhesive sites while maintaining a uniform optimal stiffness, did not influence the pro-angiogenic activity of MSCs.
    MeSH term(s) Animals ; Biocompatible Materials/pharmacology ; Cell Adhesion/drug effects ; Compressive Strength ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Hydrogels/pharmacology ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/drug effects ; Neovascularization, Physiologic/drug effects ; Signal Transduction/drug effects ; Swine ; Tissue Engineering/methods
    Chemical Substances Biocompatible Materials ; Hydrogels
    Language English
    Publishing date 2019-04-12
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2012160-X
    ISSN 1873-0191 ; 0928-4931
    ISSN (online) 1873-0191
    ISSN 0928-4931
    DOI 10.1016/j.msec.2019.04.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Investigation of Integrated Effects of Hydroxyapatite and VEGF on Capillary Morphogenesis of Endothelial Cells.

    Wu, Yang / Fu, Rong / Mohanty, Swetaparna / Nasser, Malak / Guo, Bingxin / Ghosh, Gargi

    ACS applied bio materials

    2019  Volume 2, Issue 6, Page(s) 2339–2346

    Abstract: Major drawbacks of using autografts and allografts for repairing large bone defects/injuries are the shortage of available tissues and potential disease transmission. Bone tissue engineering is believed to be a promising alternative to bone grafts. The ... ...

    Abstract Major drawbacks of using autografts and allografts for repairing large bone defects/injuries are the shortage of available tissues and potential disease transmission. Bone tissue engineering is believed to be a promising alternative to bone grafts. The concomitant formation of vascular networks within the tissue engineered constructs for successful bone regeneration still remains a challenge. The physicochemical properties of a tissue microenvironment are known to regulate vascular network formation. However, our understanding of the mechanism, by which endothelial cells integrate these physicochemical signals emanating from the microenvironment to undergo capillary morphogenesis, is limited. In this study, the integrated effects of the vascular endothelial growth factor (VEGF), pro-angiogenic molecule, and hydroxyapatite (HA), widely used as an additive and a scaffold in bone reconstructive surgery, on capillary formation of human umbilical vein endothelial cells (HUVECs) were investigated. Toward this, HUVECs were seeded on scaffolds composed of 15% (w/v) poly(ethylene glycol) diacrylate, 5% (w/v) gelatin methacrylate (GelMA), and 1% (w/v) photoinitiator. The concentration of HA was varied from 0% to 0.2% (w/v). The study demonstrated that HA elicited an inhibitory response. The presence of VEGF promoted a sprouting response with a significant enhancement in the number of sprouts observed in the case of gels with higher concentrations of HA.
    Language English
    Publishing date 2019-06-04
    Publishing country United States
    Document type Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.8b00780
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: ROR2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma.

    Benitz, Simone / Steep, Alec / Nasser, Malak / Preall, Jonathan / Mahajan, Ujjwal M / McQuithey, Holly / Loveless, Ian / Davis, Erick T / Wen, Hui-Ju / Long, Daniel W / Metzler, Thomas / Zwernik, Samuel / Louw, Michaela / Rempinski, Donald / Salas-Escabillas, Daniel / Brender, Sydney / Song, Linghao / Huang, Ling / Zhang, Zhenyu /
    Steele, Nina G / Regel, Ivonne / Bednar, Filip / Crawford, Howard C

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We ... ...

    Abstract Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia (SPEM)-like identity in the pancreas. Ablation of
    Language English
    Publishing date 2024-01-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.13.571566
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Potency of Combining

    Nasser, Mohamad / Damaj, Raghida / Merah, Othmane / Hijazi, Akram / Trabolsi, Christine / Wehbe, Nour / Nasser, Malak / Al-Khatib, Batoul / Damaj, Ziad

    Medicines (Basel, Switzerland)

    2020  Volume 7, Issue 8

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2020-07-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2777965-8
    ISSN 2305-6320
    ISSN 2305-6320
    DOI 10.3390/medicines7080040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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