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  1. Article ; Online: Preparing for a “Haplo” Tsunami in India

    Ravi Vij

    MAMC Journal of Medical Sciences, Vol 1, Iss 3, Pp 115-

    2015  Volume 117

    Keywords Medicine ; R
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Wolters Kluwer Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Ablation of VLA4 in multiple myeloma cells redirects tumor spread and prolongs survival

    Deep Hathi / Chantiya Chanswangphuwana / Nicholas Cho / Francesca Fontana / Dolonchampa Maji / Julie Ritchey / Julie O’Neal / Anchal Ghai / Kathleen Duncan / Walter J. Akers / Mark Fiala / Ravi Vij / John F. DiPersio / Michael Rettig / Monica Shokeen

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: Abstract Multiple myeloma (MM) is a cancer of bone marrow (BM) plasma cells, which is increasingly treatable but still incurable. In 90% of MM patients, severe osteolysis results from pathological interactions between MM cells and the bone ... ...

    Abstract Abstract Multiple myeloma (MM) is a cancer of bone marrow (BM) plasma cells, which is increasingly treatable but still incurable. In 90% of MM patients, severe osteolysis results from pathological interactions between MM cells and the bone microenvironment. Delineating specific molecules and pathways for their role in cancer supportive interactions in the BM is vital for developing new therapies. Very Late Antigen 4 (VLA4, integrin α 4 β 1) is a key player in cell–cell adhesion and signaling between MM and BM cells. We evaluated a VLA4 selective near infrared fluorescent probe, LLP2A-Cy5, for in vitro and in vivo optical imaging of VLA4. Furthermore, two VLA4-null murine 5TGM1 MM cell (KO) clones were generated by CRISPR/Cas9 knockout of the Itga4 (α 4) subunit, which induced significant alterations in the transcriptome. In contrast to the VLA4+ 5TGM1 parental cells, C57Bl/KaLwRij immunocompetent syngeneic mice inoculated with the VLA4-null clones showed prolonged survival, reduced medullary disease, and increased extramedullary disease burden. The KO tumor foci showed significantly reduced uptake of LLP2A-Cy5, confirming in vivo specificity of this imaging agent. This work provides new insights into the pathogenic role of VLA4 in MM, and evaluates an optical tool to measure its expression in preclinical models.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma

    Kinan Alhallak / Amanda Jeske / Pilar de la Puente / Jennifer Sun / Mark Fiala / Feda Azab / Barbara Muz / Ilyas Sahin / Ravi Vij / John F. DiPersio / Abdel Kareem Azab

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Abstract Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is ... ...

    Abstract Abstract Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) technology that closely recapitulate the pathophysiological conditions in the bone marrow and allows ex vivo proliferation of tumor cells of hematologic malignancies. In this study, we used the 3DTEBM to predict the clinical response of individual multiple myeloma (MM) patients to different therapeutic regimens. We found that while no correlation was observed between in vitro efficacy in classic 2D culture systems of drugs used for MM with their clinical efficacious concentration, the efficacious concentration in the 3DTEBM were directly correlated. Furthermore, the 3DTEBM model retrospectively predicted the clinical response to different treatment regimens in 89% of the MM patient cohort. These results demonstrated that the 3DTEBM is a feasible platform which can predict MM clinical responses with high accuracy and within a clinically actionable time frame. Utilization of this technology to predict drug efficacy and the likelihood of treatment failure could significantly improve patient care and treatment in many ways, particularly in the relapsed and refractory setting. Future studies are needed to validate the 3DTEBM model as a tool for predicting clinical efficacy.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Evolution and structure of clinically relevant gene fusions in multiple myeloma

    Steven M. Foltz / Qingsong Gao / Christopher J. Yoon / Hua Sun / Lijun Yao / Yize Li / Reyka G. Jayasinghe / Song Cao / Justin King / Daniel R. Kohnen / Mark A. Fiala / Li Ding / Ravi Vij

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Multiple myeloma is characterised by frequent gene fusions. Here, the authors use data from the Multiple Myeloma Research Foundation CoMMpass Study to further investigate fusion genes in this disease and their clinical relevance. ...

    Abstract Multiple myeloma is characterised by frequent gene fusions. Here, the authors use data from the Multiple Myeloma Research Foundation CoMMpass Study to further investigate fusion genes in this disease and their clinical relevance.
    Keywords Science ; Q
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Evolution and structure of clinically relevant gene fusions in multiple myeloma

    Steven M. Foltz / Qingsong Gao / Christopher J. Yoon / Hua Sun / Lijun Yao / Yize Li / Reyka G. Jayasinghe / Song Cao / Justin King / Daniel R. Kohnen / Mark A. Fiala / Li Ding / Ravi Vij

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Multiple myeloma is characterised by frequent gene fusions. Here, the authors use data from the Multiple Myeloma Research Foundation CoMMpass Study to further investigate fusion genes in this disease and their clinical relevance. ...

    Abstract Multiple myeloma is characterised by frequent gene fusions. Here, the authors use data from the Multiple Myeloma Research Foundation CoMMpass Study to further investigate fusion genes in this disease and their clinical relevance.
    Keywords Science ; Q
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Cross center single-cell RNA sequencing study of the immune microenvironment in rapid progressing multiple myeloma

    William Pilcher / Beena E. Thomas / Swati S. Bhasin / Reyka G. Jayasinghe / Lijun Yao / Edgar Gonzalez-Kozlova / Surendra Dasari / Seunghee Kim-Schulze / Adeeb Rahman / Jonathan Patton / Mark Fiala / Giulia Cheloni / Taxiarchis Kourelis / Madhav V. Dhodapkar / Ravi Vij / Shaadi Mehr / Mark Hamilton / Hearn Jay Cho / Daniel Auclair /
    David E. Avigan / Shaji K. Kumar / Sacha Gnjatic / Li Ding / Manoj Bhasin

    npj Genomic Medicine, Vol 8, Iss 1, Pp 1-

    2023  Volume 18

    Abstract: Abstract Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM’s progression is facilitated by complex interactions with the surrounding ... ...

    Abstract Abstract Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM’s progression is facilitated by complex interactions with the surrounding bone marrow (BM) cells, forming a microenvironment that supports tumor growth and drug resistance. Understanding the immune microenvironment is key to identifying factors that promote rapid progression of MM. To accomplish this, we performed a multi-center single-cell RNA sequencing (scRNA-seq) study on 102,207 cells from 48 CD138- BM samples collected at the time of disease diagnosis from 18 patients with either rapid progressing (progression-free survival (PFS) < 18 months) or non-progressing (PFS > 4 years) disease. Comparative analysis of data from three centers demonstrated similar transcriptome profiles and cell type distributions, indicating subtle technical variation in scRNA-seq, opening avenues for an expanded multicenter trial. Rapid progressors depicted significantly higher enrichment of GZMK + and TIGIT + exhausted CD8+ T-cells (P = 0.022) along with decreased expression of cytolytic markers (PRF1, GZMB, GNLY). We also observed a significantly higher enrichment of M2 tolerogenic macrophages in rapid progressors and activation of pro-proliferative signaling pathways, such as BAFF, CCL, and IL16. On the other hand, non-progressive patients depicted higher enrichment for immature B Cells (i.e., Pre/Pro B cells), with elevated expression for markers of B cell development (IGLL1, SOX4, DNTT). This multi-center study identifies the enrichment of various pro-tumorigenic cell populations and pathways in those with rapid progressing disease and further validates the robustness of scRNA-seq data generated at different study centers.
    Keywords Medicine ; R ; Genetics ; QH426-470
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Co-evolution of tumor and immune cells during progression of multiple myeloma

    Ruiyang Liu / Qingsong Gao / Steven M. Foltz / Jared S. Fowles / Lijun Yao / Julia Tianjiao Wang / Song Cao / Hua Sun / Michael C. Wendl / Sunantha Sethuraman / Amila Weerasinghe / Michael P. Rettig / Erik P. Storrs / Christopher J. Yoon / Matthew A. Wyczalkowski / Joshua F. McMichael / Daniel R. Kohnen / Justin King / Scott R. Goldsmith /
    Julie O’Neal / Robert S. Fulton / Catrina C. Fronick / Timothy J. Ley / Reyka G. Jayasinghe / Mark A. Fiala / Stephen T. Oh / John F. DiPersio / Ravi Vij / Li Ding

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 18

    Abstract: Clonal evolution in multiple myeloma (MM) needs to be understood in both the tumor and its microenvironment. Here the authors perform single-cell multi-omics profiling of samples from MM patients at different stages, finding transitions in the immune ... ...

    Abstract Clonal evolution in multiple myeloma (MM) needs to be understood in both the tumor and its microenvironment. Here the authors perform single-cell multi-omics profiling of samples from MM patients at different stages, finding transitions in the immune cell composition throughout progression.
    Keywords Science ; Q
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: 3D tissue-engineered bone marrow as a novel model to study pathophysiology and drug resistance in multiple myeloma

    de la Puente, Pilar / Abdel Kareem Azab / Barbara Muz / Feda Azab / Justin King / Micah Luderer / Ravi Vij / Rebecca C. Gilson / Samuel Achilefu

    Biomaterials. 2015 Dec., v. 73

    2015  

    Abstract: Multiple myeloma (MM) is the second most prevalent hematological malignancy and it remains incurable despite the introduction of several novel drugs. The discrepancy between preclinical and clinical outcomes can be attributed to the failure of classic ... ...

    Abstract Multiple myeloma (MM) is the second most prevalent hematological malignancy and it remains incurable despite the introduction of several novel drugs. The discrepancy between preclinical and clinical outcomes can be attributed to the failure of classic two-dimensional (2D) culture models to accurately recapitulate the complex biology of MM and drug responses observed in patients. Experimental design: We developed 3D tissue engineered bone marrow (3DTEBM) cultures derived from the BM supernatant of MM patients to incorporate different BM components including MM cells, stromal cells, and endothelial cells. Distribution and growth were analyzed by confocal imaging, and cell proliferation of cell lines and primary MM cells was tested by flow cytometry. Oxygen and drug gradients were evaluated by immunohistochemistry and flow cytometry, and drug resistance was studied by flow cytometry.3DTEBM cultures allowed proliferation of MM cells, recapitulated their interaction with the microenvironment, recreated 3D aspects observed in the bone marrow niche (such as oxygen and drug gradients), and induced drug resistance in MM cells more than 2D or commercial 3D tissue culture systems.3DTEBM cultures not only provide a better model for investigating the pathophysiology of MM, but also serve as a tool for drug development and screening in MM. In the future, we will use the 3DTEBM cultures for developing personalized therapeutic strategies for individual MM patients.
    Keywords bone marrow ; cell proliferation ; drugs ; endothelial cells ; experimental design ; flow cytometry ; image analysis ; immunohistochemistry ; models ; multiple drug resistance ; myeloma ; oxygen ; pathophysiology ; patients ; screening ; stromal cells ; tissue culture ; tissue engineering
    Language English
    Dates of publication 2015-12
    Size p. 70-84.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2015.09.017
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma

    Cinzia Federico / Kinan Alhallak / Jennifer Sun / Kathleen Duncan / Feda Azab / Gail P. Sudlow / Pilar de la Puente / Barbara Muz / Vaishali Kapoor / Luna Zhang / Fangzheng Yuan / Matea Markovic / Joseph Kotsybar / Katherine Wasden / Nicole Guenthner / Shannon Gurley / Justin King / Daniel Kohnen / Noha N. Salama /
    Dinesh Thotala / Dennis E. Hallahan / Ravi Vij / John F. DiPersio / Samuel Achilefu / Abdel Kareem Azab

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: The tumour microenvironment (TME) has a major role in chemoresistance in multiple myeloma. The authors show that a nanoparticle targeted to TME and loaded with bortezomib (BTZ) and Y27632 is more effective than free drugs, non-targeted and single-agent ... ...

    Abstract The tumour microenvironment (TME) has a major role in chemoresistance in multiple myeloma. The authors show that a nanoparticle targeted to TME and loaded with bortezomib (BTZ) and Y27632 is more effective than free drugs, non-targeted and single-agent controls and reduces BTZ-related side effects.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Germinal center B-cells resist transformation by Kras independently of tumor suppressor Arf.

    Chelsea D Mullins / Mack Y Su / Vishwanathan Hucthagowder / Liang Chu / Lan Lu / Shashikant Kulkarni / Deborah Novack / Ravi Vij / Michael H Tomasson

    PLoS ONE, Vol 8, Iss 6, p e

    2013  Volume 67941

    Abstract: Activating mutations in Ras (N- and K-) are the most common point mutations found in patients with multiple myeloma (MM) and are associated with poor clinical outcome. We sought to directly examine the role of Ras activation in MM pathogenesis and used ... ...

    Abstract Activating mutations in Ras (N- and K-) are the most common point mutations found in patients with multiple myeloma (MM) and are associated with poor clinical outcome. We sought to directly examine the role of Ras activation in MM pathogenesis and used two different tissue-specific Cre recombinase mouse lines (Cγ1-Cre and AID-Cre), to generate mice with mutant Kras (Kras(G12D) ) activated specifically in germinal center B-cells. We also generated mice with activation of the Kras(G12D) allele in a tumor-prone Arf-null genetic background. Surprisingly, we observed no significant disruption in B-cell homeostasis in any of these models by serum immunoglobulin ELISA, SPEP, flow cytometry and histological examination. We observed development of non-overlapping tumor types due to off-target Cre expression, but despite successful recombination in germinal center and later B-cell populations, we observed no B-cell phenotype. Together, these data demonstrate that Ras activation is not sufficient to transform primary germinal center B-cells, even in an Arf-null context, and that the temporal order of mutation acquisition may be critical for myeloma development. Specific pathways, yet to be identified, are required before Kras can contribute to the development of MM.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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