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  1. Article: Editorial: Risk factors in multiple myeloma identified before and during treatment: are we ready to personalize treatment?

    D'Agostino, Mattia / Terragna, Carolina / van Duin, Mark

    Frontiers in oncology

    2023  Volume 13, Page(s) 1247808

    Language English
    Publishing date 2023-07-31
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1247808
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  2. Article: Risk Stratification Before and During Treatment in Newly Diagnosed Multiple Myeloma: From Clinical Trials to the Real-World Setting.

    Bonello, Francesca / Cani, Lorenzo / D'Agostino, Mattia

    Frontiers in oncology

    2022  Volume 12, Page(s) 830922

    Abstract: Multiple Myeloma (MM) is a hematologic malignancy characterized by a wide clinical and biological heterogeneity leading to different patient outcomes. Various prognostic tools to stratify newly diagnosed (ND)MM patients into different risk groups have ... ...

    Abstract Multiple Myeloma (MM) is a hematologic malignancy characterized by a wide clinical and biological heterogeneity leading to different patient outcomes. Various prognostic tools to stratify newly diagnosed (ND)MM patients into different risk groups have been proposed. At baseline, the standard-of-care prognostic score is the Revised International Staging System (R-ISS), which stratifies patients according to widely available serum markers (i.e., albumin, β 2-microglobulin, lactate dehydrogenase) and high-risk cytogenetic abnormalities detected by fluorescence
    Language English
    Publishing date 2022-03-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.830922
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  3. Article ; Online: Anti-BCMA CAR T-cell therapy in multiple myeloma: can we do better?

    D'Agostino, Mattia / Raje, Noopur

    Leukemia

    2019  Volume 34, Issue 1, Page(s) 21–34

    Abstract: Despite a substantial survival improvement and the availability of many new drugs in the last 2 decades, multiple myeloma (MM) remains largely incurable. Immunotherapeutic approaches are changing the current landscape in MM with B-cell maturation antigen ...

    Abstract Despite a substantial survival improvement and the availability of many new drugs in the last 2 decades, multiple myeloma (MM) remains largely incurable. Immunotherapeutic approaches are changing the current landscape in MM with B-cell maturation antigen (BCMA) as one of the most promising target antigens. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA produced unprecedented results in heavily pretreated relapsed and/or refractory MM. Data on more than 300 MM patients treated with anti-BCMA directed CAR T cells are available and these numbers are rapidly increasing. The response rate and the depth of responses induced by anti-BCMA CAR T cells are impressive; however, the majority of patients eventually relapse. Understanding the underlying mechanisms of response and resistance in treated MM patients will be critical to the rational development of this therapy. Moreover, the ideal place of this therapy in the treatment paradigm for MM is an important question that needs biological and clinical correlative data to help elucidate. T-cell-related, tumor-related and microenvironmental factors may play a role in the efficacy of anti-BCMA CAR T-cell therapy. In this review we summarize key clinical and correlative data on anti-BCMA CAR T-cell therapy. Based on available data we will try to highlight opportunities to further optimize this potential game-changing therapy for MM.
    MeSH term(s) B-Cell Maturation Antigen/antagonists & inhibitors ; B-Cell Maturation Antigen/immunology ; Humans ; Immunotherapy, Adoptive/methods ; Multiple Myeloma/therapy ; Receptors, Chimeric Antigen
    Chemical Substances B-Cell Maturation Antigen ; Receptors, Chimeric Antigen ; TNFRSF17 protein, human
    Language English
    Publishing date 2019-11-28
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-019-0669-4
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2295: Show issues Location:
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  4. Article ; Online: MRD Assessment in Multiple Myeloma: Progress and Challenges.

    Bertamini, Luca / D'Agostino, Mattia / Gay, Francesca

    Current hematologic malignancy reports

    2021  Volume 16, Issue 2, Page(s) 162–171

    Abstract: Purpose of review: Over the last decade, the development of effective treatment approaches for multiple myeloma (MM) has been associated with higher response rates and longer survival. In patients who achieve complete response, several high sensitivity ... ...

    Abstract Purpose of review: Over the last decade, the development of effective treatment approaches for multiple myeloma (MM) has been associated with higher response rates and longer survival. In patients who achieve complete response, several high sensitivity techniques have been studied to assess minimal residual disease (MRD) and detect residual neoplastic cells within the bone marrow (by flow cytometry or molecular biology techniques) or outside the bone marrow (by imaging or circulating disease markers in the peripheral blood). This is of utmost importance, since residual disease can drive clinical relapse. This review focuses on the progress made in the assessment of MRD in MM.
    Recent findings: The achievement of MRD negativity after therapy is considered prognostically important for MM patients, and data from clinical trials and meta-analyses have confirmed that it is strongly associated with better survival. Along with well-known techniques, such as next-generation sequencing (NGS), next-generation flow (NGF), and positron emission tomography/computed tomography (PET/CT), other methods such as mass spectrometry (MS) and circulating tumor cells are under study. Intensive treatment regimens at diagnosis can lead up to 70% of MRD negativity in MM patients, although the current proportion of curable patients is still unknown. Today, clinicians who treat MM deal with MRD assessment in routine clinical practice. Its appropriate use in therapeutic decision making may be the most fascinating and challenging issue to be addressed over the next few years.
    MeSH term(s) Biomarkers, Tumor ; Bone Marrow/pathology ; Combined Modality Therapy/methods ; Disease Management ; Disease Susceptibility ; Flow Cytometry/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Magnetic Resonance Imaging ; Multiple Myeloma/diagnosis ; Multiple Myeloma/etiology ; Multiple Myeloma/metabolism ; Multiple Myeloma/therapy ; Neoplasm, Residual/diagnosis ; Positron Emission Tomography Computed Tomography ; Prognosis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Treatment Outcome
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2021-05-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2229765-0
    ISSN 1558-822X ; 1558-8211
    ISSN (online) 1558-822X
    ISSN 1558-8211
    DOI 10.1007/s11899-021-00633-5
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6332: Show issues Location:
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  5. Article ; Online: Anti-CD38 monoclonal antibodies in multiple myeloma: another cook in the kitchen?

    D'Agostino, Mattia / Mina, Roberto / Gay, Francesca

    The Lancet. Haematology

    2020  Volume 7, Issue 5, Page(s) e355–e357

    MeSH term(s) Antibodies, Monoclonal ; Humans ; Multiple Myeloma
    Chemical Substances Antibodies, Monoclonal
    Language English
    Publishing date 2020-03-11
    Publishing country England
    Document type Journal Article
    ISSN 2352-3026
    ISSN (online) 2352-3026
    DOI 10.1016/S2352-3026(19)30254-6
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  6. Article ; Online: Normalization of the Immunological Microenvironment and Sustained Minimal Residual Disease Negativity: Do We Need Both for Long-Term Control of Multiple Myeloma?

    Bertuglia, Giuseppe / Cani, Lorenzo / Larocca, Alessandra / Gay, Francesca / D'Agostino, Mattia

    International journal of molecular sciences

    2022  Volume 23, Issue 24

    Abstract: Over the past two decades, the treatment landscape for multiple myeloma (MM) has progressed significantly, with the introduction of several new drug classes that have greatly improved patient outcomes. At present, it is well known how the bone marrow (BM) ...

    Abstract Over the past two decades, the treatment landscape for multiple myeloma (MM) has progressed significantly, with the introduction of several new drug classes that have greatly improved patient outcomes. At present, it is well known how the bone marrow (BM) microenvironment (ME) exerts an immunosuppressive action leading to an exhaustion of the immune system cells and promoting the proliferation and sustenance of tumor plasma cells. Therefore, having drugs that can reconstitute a healthy BM ME can improve results in MM patients. Recent findings clearly demonstrated that achieving minimal residual disease (MRD) negativity and sustaining MRD negativity over time play a pivotal prognostic role. However, despite the achievement of MRD negativity, patients may still relapse. The understanding of immunologic changes in the BM ME during treatment, complemented by a deeper knowledge of plasma cell genomics and biology, will be critical to develop future therapies to sustain MRD negativity over time and possibly achieve an operational cure. In this review, we focus on the components of the BM ME and their role in MM, on the prognostic significance of MRD negativity and, finally, on the relative contribution of tumor plasma cell biology and BM ME to long-term disease control.
    MeSH term(s) Humans ; Multiple Myeloma/pathology ; Neoplasm, Residual/pathology ; Neoplasm Recurrence, Local/pathology ; Plasma Cells/pathology ; Bone Marrow/pathology ; Tumor Microenvironment
    Language English
    Publishing date 2022-12-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms232415879
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  7. Article ; Online: Crystal structure of archaeal IF5A-DHS complex reveals insights into the hypusination mechanism.

    D'Agostino, Mattia / Simonetti, Angelita / Motta, Stefano / Wolff, Philippe / Romagnoli, Alice / Piccinini, Astra / Spinozzi, Francesco / Di Marino, Daniele / La Teana, Anna / Ennifar, Eric

    Structure (London, England : 1993)

    2024  

    Abstract: The translation factor IF5A is highly conserved in Eukarya and Archaea and undergoes a unique post-translational hypusine modification by the deoxyhypusine synthase (DHS) enzyme. DHS transfers the butylamine moiety from spermidine to IF5A using NAD as a ... ...

    Abstract The translation factor IF5A is highly conserved in Eukarya and Archaea and undergoes a unique post-translational hypusine modification by the deoxyhypusine synthase (DHS) enzyme. DHS transfers the butylamine moiety from spermidine to IF5A using NAD as a cofactor, forming a deoxyhypusine intermediate. IF5A is a key player in protein synthesis, preventing ribosome stalling in proline-rich sequences during translation elongation and facilitating translation elongation and termination. Additionally, human eIF5A participates in various essential cellular processes and contributes to cancer metastasis, with inhibiting hypusination showing anti-proliferative effects. The hypusination pathway of IF5A is therefore an attractive new therapeutic target. We elucidated the 2.0 Å X-ray crystal structure of the archaeal DHS-IF5A complex, revealing hetero-octameric architecture and providing a detailed view of the complex active site including the hypusination loop. This structure, along with biophysical data and molecular dynamics simulations, provides new insights into the catalytic mechanism of the hypusination reaction.
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1213087-4
    ISSN 1878-4186 ; 0969-2126
    ISSN (online) 1878-4186
    ISSN 0969-2126
    DOI 10.1016/j.str.2024.03.008
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4141: Show issues Location:
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  8. Article: Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma.

    Oliva, Stefania / D'Agostino, Mattia / Boccadoro, Mario / Larocca, Alessandra

    Frontiers in oncology

    2020  Volume 10, Page(s) 1

    Abstract: In the last years, the life expectancy of multiple myeloma (MM) patients has substantially improved thanks to the availability of many new drugs. Our ability to induce deep responses has improved as well, and the treatment goal in patients tolerating ... ...

    Abstract In the last years, the life expectancy of multiple myeloma (MM) patients has substantially improved thanks to the availability of many new drugs. Our ability to induce deep responses has improved as well, and the treatment goal in patients tolerating treatment moved from the delay of progression to the induction of the deepest possible response. As a result of these advances, a great scientific effort has been made to redefine response monitoring, resulting in the development and validation of high-sensitivity techniques to detect minimal residual disease (MRD). In 2016, the International Myeloma Working Group (IMWG) updated MM response categories defining MRD-negative responses both in the bone marrow (assessed by next-generation flow cytometry or next-generation sequencing) and outside the bone marrow. MRD is an important factor independently predicting prognosis during MM treatment. Moreover, using novel combination therapies, MRD-negative status can be achieved in a fairly high percentage of patients. However, many questions regarding the clinical use of MRD status remain unanswered. MRD monitoring can guide treatment intensity, although well-designed clinical trials are needed to demonstrate this potential. This mini-review will focus on currently available techniques and data on MRD testing and their potential future applications.
    Language English
    Publishing date 2020-01-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2020.00001
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  9. Article ; Online: Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True.

    D'Agostino, Mattia / Innorcia, Salvatore / Boccadoro, Mario / Bringhen, Sara

    International journal of molecular sciences

    2020  Volume 21, Issue 21

    Abstract: Immunotherapy is increasingly used in the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) are safe and effective ways to elicit immunotherapeutic responses. In 2015, daratumumab has become the first mAb approved by the Food and Drug ... ...

    Abstract Immunotherapy is increasingly used in the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) are safe and effective ways to elicit immunotherapeutic responses. In 2015, daratumumab has become the first mAb approved by the Food and Drug Administration for clinical use in MM and, in the last 5 years, a lot of clinical and preclinical research has been done to optimize the use of this drug class. Currently, mAbs have already become part of standard-of-care combinations for the treatment of relapsed/refractory MM and very soon they will also be used in the frontline setting. The success of simple mAbs ('naked mAbs') prompted the development of new types of molecules. Antibody-drug conjugates (ADCs) are tumor-targeting mAbs that release a cytotoxic payload into the tumor cells upon antigen binding in order to destroy them. Bispecific antibodies (BiAbs) are mAbs simultaneously targeting a tumor-associated antigen and an immune cell-associated antigen in order to redirect the immune cell cytotoxicity against the tumor cell. These different constructs produced solid preclinical data and promising clinical data in phase I/II trials. The aim of this review article is to summarize all the recent developments in the field, including data on naked mAbs, ADCs and BiAbs.
    MeSH term(s) Animals ; Antibodies, Bispecific/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Humans ; Immunoconjugates/therapeutic use ; Immunologic Factors/therapeutic use ; Immunotherapy/methods ; Multiple Myeloma/immunology ; Multiple Myeloma/pathology ; Multiple Myeloma/therapy
    Chemical Substances Antibodies, Bispecific ; Antibodies, Monoclonal ; Antineoplastic Agents ; Immunoconjugates ; Immunologic Factors ; daratumumab (4Z63YK6E0E)
    Language English
    Publishing date 2020-11-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21218192
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  10. Article ; Online: Moving Toward a Tailored Therapy in Multiple Myeloma.

    D'Agostino, Mattia / Palumbo, Antonio

    Journal of oncology practice

    2016  Volume 12, Issue 4, Page(s) 293–294

    MeSH term(s) Humans ; Multiple Myeloma
    Language English
    Publishing date 2016-04
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2236338-5
    ISSN 1935-469X ; 1554-7477
    ISSN (online) 1935-469X
    ISSN 1554-7477
    DOI 10.1200/JOP.2016.011627
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