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  1. Book ; Online: T-Cell Leukemia

    Babusikova, Olga / Dovat, Sinisa / Payne, Kimberly J.

    2011  

    Keywords Oncology
    Size 1 electronic resource (246 pages)
    Publisher IntechOpen
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021046603
    ISBN 9789535165392 ; 9535165399
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article: Integrating Optical Genome Mapping and Whole Genome Sequencing in Somatic Structural Variant Detection.

    Budurlean, Laura / Tukaramrao, Diwakar Bastihalli / Zhang, Lijun / Dovat, Sinisa / Broach, James

    Journal of personalized medicine

    2024  Volume 14, Issue 3

    Abstract: Structural variants drive tumorigenesis by disrupting normal gene function through insertions, inversions, translocations, and copy number changes, including deletions and duplications. Detecting structural variants is crucial for revealing their roles ... ...

    Abstract Structural variants drive tumorigenesis by disrupting normal gene function through insertions, inversions, translocations, and copy number changes, including deletions and duplications. Detecting structural variants is crucial for revealing their roles in tumor development, clinical outcomes, and personalized therapy. Presently, most studies rely on short-read data from next-generation sequencing that aligns back to a reference genome to determine if and, if so, where a structural variant occurs. However, structural variant discovery by short-read sequencing is challenging, primarily because of the difficulty in mapping regions of repetitive sequences. Optical genome mapping (OGM) is a recent technology used for imaging and assembling long DNA strands to detect structural variations. To capture the structural variant landscape more thoroughly in the human genome, we developed an integrated pipeline that combines Bionano OGM and Illumina whole-genome sequencing and applied it to samples from 29 pediatric B-ALL patients. The addition of OGM allowed us to identify 511 deletions, 506 insertions, 93 duplications/gains, and 145 translocations that were otherwise missed in the short-read data. Moreover, we identified several novel gene fusions, the expression of which was confirmed by RNA sequencing. Our results highlight the benefit of integrating OGM and short-read detection methods to obtain a comprehensive analysis of genetic variation that can aid in clinical diagnosis, provide new therapeutic targets, and improve personalized medicine in cancers driven by structural variation.
    Language English
    Publishing date 2024-03-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662248-8
    ISSN 2075-4426
    ISSN 2075-4426
    DOI 10.3390/jpm14030291
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ikaros: the enhancer makes the difference.

    Dovat, Sinisa

    Blood

    2013  Volume 122, Issue 18, Page(s) 3091–3092

    MeSH term(s) Animals ; Enhancer Elements, Genetic/genetics ; Ikaros Transcription Factor/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Transcriptional Activation
    Chemical Substances IKZF1 protein, human ; Zfpn1a1 protein, mouse ; Ikaros Transcription Factor (148971-36-2)
    Language English
    Publishing date 2013-11-01
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2013-09-526343
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 364: Show issues

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  4. Article: Synergistic effect of HDAC inhibitor Chidamide with Cladribine on cell cycle arrest and apoptosis by targeting HDAC2/c-Myc/RCC1 axis in acute myeloid leukemia.

    Gu, Siyu / Hou, Yue / Dovat, Katarina / Dovat, Sinisa / Song, Chunhua / Ge, Zheng

    Experimental hematology & oncology

    2023  Volume 12, Issue 1, Page(s) 23

    Abstract: Background: More effective targeted therapy and new combination regimens are needed for Acute myeloid leukemia (AML), owing to the unsatisfactory long-term prognosis of the disease. Here, we investigated the synergistic effect and the mechanism of a ... ...

    Abstract Background: More effective targeted therapy and new combination regimens are needed for Acute myeloid leukemia (AML), owing to the unsatisfactory long-term prognosis of the disease. Here, we investigated the synergistic effect and the mechanism of a histone deacetylase inhibitor, Chidamide in combination with Cladribine, a purine nucleoside antimetabolite analog in the disease.
    Methods: Cell counting kit-8 assays and Chou-Talalay's combination index were used to examine the synergistic effect of Chidamide and Cladribine on AML cell lines (U937, THP-1, and MV4-11) and primary AML cells. PI and Annexin-V/PI assays were used to detect the cell cycle effect and apoptosis effect, respectively. Global transcriptome analysis, RT-qPCR, c-MYC Knockdown, western blotting, co-immunoprecipitation, and chromatin immunoprecipitation assays were employed to explore the molecule mechanisms.
    Results: The combination of Chidamide with Cladribine showed a significant increase in cell proliferation arrest, the G0/G1 phase arrest, and apoptosis compared to the single drug control in AML cell lines along with upregulated p21
    Conclusions: Our results demonstrated the synergistic effect of Chidamide with Cladribine on cell growth arrest, cell cycle arrest, and apoptosis in AML and primary cells with genetic defects by targeting HDAC2/c-Myc/RCC1 signaling in AML. Our data provide experimental evidence for the undergoing clinical trial (Clinical Trial ID: NCT05330364) of Chidamide plus Cladribine as a new potential regimen in AML.
    Language English
    Publishing date 2023-02-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2669066-4
    ISSN 2162-3619
    ISSN 2162-3619
    DOI 10.1186/s40164-023-00383-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Medulloblastoma: “Onset of the molecular era”

    Dhanyamraju, Pavan Kumar / Patel, Trupti N / Dovat, Sinisa

    Molecular biology reports. 2020 Dec., v. 47, no. 12

    2020  

    Abstract: Among brain tumors, Medulloblastoma (MB) is one of the most common, malignant, pediatric tumors of the cerebellum. It accounts for ~20% of all childhood central nervous system (CNS) tumors. Despite, tremendous advances in drug development processes, as ... ...

    Abstract Among brain tumors, Medulloblastoma (MB) is one of the most common, malignant, pediatric tumors of the cerebellum. It accounts for ~20% of all childhood central nervous system (CNS) tumors. Despite, tremendous advances in drug development processes, as well as novel drugs for MB the morbidity and mortality rates, remain high. Craniospinal radiation, high-dose chemotherapy, and surgical resection are the primary therapeutic strategies. Tremendous progress in the field of “genomics” with vast amounts of data has led to the identification of four distinct molecular subgroups in medulloblastoma: WNT group, SHH group, group-III, and group-IV. The identification of these subgroups has led to individualized treatment strategies for each subgroup. Here, we discuss the various molecular subgroups of medulloblastoma as well as the differences between them. We also highlight the latest treatment strategies available for medulloblastoma.
    Keywords cerebellum ; childhood ; drug development ; drug therapy ; molecular biology ; morbidity ; mortality ; resection
    Language English
    Dates of publication 2020-12
    Size p. 9931-9937.
    Publishing place Springer Netherlands
    Document type Article
    Note NAL-AP-2-clean ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-020-05971-w
    Database NAL-Catalogue (AGRICOLA)

    Full text online

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    In stock of ZB MED Bonn / Germany

    Z 78/728: Show issues

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  6. Article ; Online: Ikaros in hematopoiesis and leukemia.

    Dovat, Sinisa

    World journal of biological chemistry

    2011  Volume 2, Issue 6, Page(s) 105–107

    Abstract: Ikaros is a gene whose activity is essential for normal hematopoiesis. Ikaros acts as a master regulator of lymphoid and myeloid development as well as a tumor suppressor. In cells, Ikaros regulates gene expression via chromatin remodeling. During the ... ...

    Abstract Ikaros is a gene whose activity is essential for normal hematopoiesis. Ikaros acts as a master regulator of lymphoid and myeloid development as well as a tumor suppressor. In cells, Ikaros regulates gene expression via chromatin remodeling. During the past 15 years tremendous advances have been made in understanding the role of Ikaros in hematopoiesis and leukemogenesis. In this Topic Highlights series of reviews, several groups of international experts in this field summarize the experimental data that is shaping the emerging picture of Ikaros function at the biochemical and cellular levels. The articles provide detailed analyses of recent scientific advancements and present models that will serve as a basis for future studies aimed at developing a better understanding of normal hematopoiesis and hematological malignancies and at accelerating the application of this knowledge in clinical practice.
    Language English
    Publishing date 2011-05-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2564793-3
    ISSN 1949-8454 ; 1949-8454
    ISSN (online) 1949-8454
    ISSN 1949-8454
    DOI 10.4331/wjbc.v2.i6.105
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Medulloblastoma: "Onset of the molecular era".

    Dhanyamraju, Pavan Kumar / Patel, Trupti N / Dovat, Sinisa

    Molecular biology reports

    2020  Volume 47, Issue 12, Page(s) 9931–9937

    Abstract: Among brain tumors, Medulloblastoma (MB) is one of the most common, malignant, pediatric tumors of the cerebellum. It accounts for ~20% of all childhood central nervous system (CNS) tumors. Despite, tremendous advances in drug development processes, as ... ...

    Abstract Among brain tumors, Medulloblastoma (MB) is one of the most common, malignant, pediatric tumors of the cerebellum. It accounts for ~20% of all childhood central nervous system (CNS) tumors. Despite, tremendous advances in drug development processes, as well as novel drugs for MB the morbidity and mortality rates, remain high. Craniospinal radiation, high-dose chemotherapy, and surgical resection are the primary therapeutic strategies. Tremendous progress in the field of "genomics" with vast amounts of data has led to the identification of four distinct molecular subgroups in medulloblastoma: WNT group, SHH group, group-III, and group-IV. The identification of these subgroups has led to individualized treatment strategies for each subgroup. Here, we discuss the various molecular subgroups of medulloblastoma as well as the differences between them. We also highlight the latest treatment strategies available for medulloblastoma.
    Language English
    Publishing date 2020-11-06
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-020-05971-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1140: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article: Clinician-Scientist Faculty Mentoring Program (FAME) - A New Inclusive Training Model at Penn State Increases Scholarly Productivity and Extramural Grant Funding.

    Dovat, Sinisa / Gowda, Chandrika / Mailman, Richard B / Parent, Leslie J / Huang, Xuemei

    Advances in medical education and practice

    2022  Volume 13, Page(s) 1039–1050

    Abstract: Purpose: Clinician-scientists have a high attrition rate at the junior-faculty level, before they gain independent funding. We identified the lack of skill set, clinician-scientist community and collaboration between clinician-scientists and clinicians ... ...

    Abstract Purpose: Clinician-scientists have a high attrition rate at the junior-faculty level, before they gain independent funding. We identified the lack of skill set, clinician-scientist community and collaboration between clinician-scientists and clinicians with predominantly clinical duties, as key problems in our medium-size college of medicine.
    Methods: We designed a novel two-year educational program, the Clinician-scientist Faculty Mentoring program (FAME) specifically to target junior clinician-scientists. The program enrollment included both lab-based, "traditional" and "non-traditional" clinician-scientists, with predominantly clinical duties and limited time for research. The curriculum included the novel educational tools: Emerging technology seminars and mentored work-in-progress research seminars, integrated with mock grant review.
    Results: The first class enrolled 17 clinician-scientists with diverse clinical subspecialty, previous research training, and protected research time. After two years in the program, the self-assessment of FAME scholars demonstrated strong improvement in grantsmanship skills, career development, emerging technologies, and the sense of community and collaboration. Compared to the period before initiating FAME, scholars increased annual scholarly output by 65% and new extramural funding by >20-fold ($0.189 vs $4.0 million) following completion of FAME. The "traditional" clinician-scientists, who had >50% research time, increased new extramural funding by ~25-fold ($0.134 vs $3.336 million), whereas "non-traditional" clinician-scientists who had ≤50% research time increased new extramural funding by >13-fold.
    Conclusion: Results suggest that a training program tailored specifically to clinician-scientists leads to increased scholarly productivity and grant funding regardless of research background. Implementing this type of training program nationally, with inclusion of clinician-scientists with various amounts of protected time for research, will help both "traditional" and "non-traditional" clinician-scientists to obtain a substantial independent extramural funding, fulfill their scholarly potential, and enhance their sense of community. Our model would be particularly useful for small-to-medium sized academic institutions, who have a limited clinician-scientist workforce facing competing health care system needs.
    Language English
    Publishing date 2022-09-12
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2578539-4
    ISSN 1179-7258
    ISSN 1179-7258
    DOI 10.2147/AMEP.S365953
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Characterization of Anticancer Effects of the Analogs of DJ4, a Novel Selective Inhibitor of ROCK and MRCK Kinases.

    Kale, Vijay Pralhad / Hengst, Jeremy A / Sharma, Arati K / Golla, Upendarrao / Dovat, Sinisa / Amin, Shantu G / Yun, Jong K / Desai, Dhimant H

    Pharmaceuticals (Basel, Switzerland)

    2023  Volume 16, Issue 8

    Abstract: The Rho associated coiled-coil containing protein kinase (ROCK1 and ROCK2) and myotonic dystrophy-related Cdc-42 binding kinases (MRCKα and MRCKβ) are critical regulators of cell proliferation and cell plasticity, a process intimately involved in cancer ... ...

    Abstract The Rho associated coiled-coil containing protein kinase (ROCK1 and ROCK2) and myotonic dystrophy-related Cdc-42 binding kinases (MRCKα and MRCKβ) are critical regulators of cell proliferation and cell plasticity, a process intimately involved in cancer cell migration and invasion. Previously, we reported the discovery of a novel small molecule (DJ4) selective multi-kinase inhibitor of ROCK1/2 and MRCKα/β. Herein, we further characterized the anti-proliferative and apoptotic effects of DJ4 in non-small cell lung cancer and triple-negative breast cancer cells. To further optimize the ROCK/MRCK inhibitory potency of DJ4, we generated a library of 27 analogs. Among the various structural modifications, we identified four additional active analogs with enhanced ROCK/MRCK inhibitory potency. The anti-proliferative and cell cycle inhibitory effects of the active analogs were examined in non-small cell lung cancer, breast cancer, and melanoma cell lines. The anti-proliferative effectiveness of DJ4 and the active analogs was further demonstrated against a wide array of cancer cell types using the NCI-60 human cancer cell line panel. Lastly, these new analogs were tested for anti-migratory effects in highly invasive MDA-MB-231 breast cancer cells. Together, our results demonstrate that selective inhibitors of ROCK1/2 (DJE4, DJ-Allyl) inhibited cell proliferation and induced cell cycle arrest at G2/M but were less effective in cell death induction compared with dual ROCK1/2 and MRCKα/β (DJ4 and DJ110).
    Language English
    Publishing date 2023-07-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph16081060
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: STAT5 alters the state of transcriptional networks, driving aggressive leukemia.

    Dovat, Sinisa / Payne, Kimberly J

    Nature immunology

    2017  Volume 18, Issue 6, Page(s) 597–598

    Language English
    Publishing date 2017-05-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/ni.3747
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5294: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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    Zs.MG 42: Show issues

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