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  1. Article: The current role of secondary cytoreductive surgery for recurrent ovarian cancer.

    de Bree, Eelco / Michelakis, Dimosthenis / Anagnostopoulou, Elisavet

    Frontiers in oncology

    2022  Volume 12, Page(s) 1029976

    Abstract: ... impairment of quality of life and costs. In platinum-resistant recurrent disease, i.e., relapse after less ...

    Abstract Ovarian cancer represents worldwide the second most frequent and the most fatal gynecological malignancy, with approximately two thirds of the patients presenting with advanced disease. Cytoreductive surgery, primary or after neoadjuvant chemotherapy, in combination with platinum-based chemotherapy is the standard of care for these patients. Despite the improvement in quality of cytoreductive surgery as well as development of novel drugs and chemotherapy regimens, still most women with ovarian cancer will ultimately develop recurrent disease and die of their disease. In contrast to the management of primary disease, the standard treatment of patients with recurrent ovarian cancer remains a topic of debate. While platinum-based or second line systemic chemotherapy, depending on the time after last platinum treatment, is standard of care, the role of secondary cytoreductive surgery has been a controversial issue for the last decades. Potential outcome benefit must be also weighed against the risk of severe surgical morbidity, impairment of quality of life and costs. In platinum-resistant recurrent disease, i.e., relapse after less than 6 months from the last platinum-based chemotherapy for primary disease, secondary cytoreduction seems generally not to be indicated due to its aggressive biological behavior and the absence of effective systemic treatment. In this comprehensive review, the current role of cytoreductive surgery in platinum-sensitive recurrent ovarian cancer is discussed thoroughly in view of the results of most recent randomized trials and a meta-analysis. There seems to be definitely a role for secondary cytoreductive surgery in selected patients with ovarian cancer recurrence in whom complete resection of macroscopic disease is feasible. However, its role should be continuously reviewed due to the changing systemic treatment of patients with ovarian cancer recurrence over time.
    Language English
    Publishing date 2022-10-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1029976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: An overview and update of hyperthermic intraperitoneal chemotherapy in ovarian cancer.

    de Bree, Eelco / Michelakis, Dimosthenis

    Expert opinion on pharmacotherapy

    2020  Volume 21, Issue 12, Page(s) 1479–1492

    Abstract: Introduction: Despite, the strong rationale and evidence of the benefit of postoperative intraperitoneal chemotherapy in advanced ovarian cancer, it has not been widely adopted, mainly due to its high morbidity and logistical difficulties. ... ...

    Abstract Introduction: Despite, the strong rationale and evidence of the benefit of postoperative intraperitoneal chemotherapy in advanced ovarian cancer, it has not been widely adopted, mainly due to its high morbidity and logistical difficulties. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a more tolerable and technically feasible method of intraperitoneal chemotherapy, whereas other potential advantages include homogenous drug distribution, application before tumor regrowth and combination with hyperthermia, which is directly cytotoxic and enhances the efficacy of many drugs.
    Areas covered: In this review, the authors explain the rationale and indications for cytoreductive surgery (CRS) and HIPEC in advanced ovarian cancer. Data of major clinical studies, meta-analyses, and recent randomized trials are discussed.
    Expert opinion: After many encouraging clinical studies and meta-analyses, a recent randomized study demonstrated survival benefit for HIPEC during interval CRS in primary ovarian cancer, without increased morbidity, whereas another implied its benefit in recurrent ovarian cancer. Results of recently completed and numerous ongoing randomized studies will further determine the benefit of HIPEC in ovarian cancer at different time points. Patient selection and appraisal of the best protocols are crucial. The field of gynecological oncology will most likely evolve to include HIPEC eventually as a routine treatment for ovarian cancer.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Carcinoma, Ovarian Epithelial/drug therapy ; Carcinoma, Ovarian Epithelial/surgery ; Carcinoma, Ovarian Epithelial/therapy ; Combined Modality Therapy ; Cytoreduction Surgical Procedures/methods ; Female ; Humans ; Hyperthermia, Induced/methods ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/surgery ; Neoplasm Recurrence, Local/therapy ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/surgery ; Ovarian Neoplasms/therapy ; Randomized Controlled Trials as Topic
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2020-06-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2001535-5
    ISSN 1744-7666 ; 1465-6566
    ISSN (online) 1744-7666
    ISSN 1465-6566
    DOI 10.1080/14656566.2020.1766024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Oncovascular Resection and Reconstruction of Recurrent Retroperitoneal Liposarcoma Adherent to the Iliac Veins and Vena Cava.

    Kontopodis, Nikolaos / Bree, Eelco de / Michelakis, Demosthenis / Ioannou, Christos V

    Vascular specialist international

    2021  Volume 37, Issue 1, Page(s) 58–59

    Language English
    Publishing date 2021-03-22
    Publishing country Korea (South)
    Document type Journal Article
    ISSN 2288-7970
    ISSN 2288-7970
    DOI 10.5758/vsi.210017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The impact of sentinel lymph node mapping with hybrid single photon emission computed tomography/computed tomography in patients with melanoma. Comparison to planar radioisotopic lymphoscintigraphy.

    Stathaki, Maria I / Kapsoritakis, Nikolaos / Michelakis, Dimosthenis / Anagnostopoulou, Elisavet / Bourogianni, Olga / Tsaroucha, Angeliki / Papadaki, Emmanouela / de Bree, Eelco / Koukouraki, Sophia

    Melanoma research

    2023  Volume 33, Issue 3, Page(s) 239–246

    Abstract: We studied the diagnostic value of 16 slices of single photon emission computed tomography (SPECT)/computed tomography (CT) in the anatomical localization, image interpretation and extra-sentinel lymph nodes (SLNs) detection compared to dynamic and ... ...

    Abstract We studied the diagnostic value of 16 slices of single photon emission computed tomography (SPECT)/computed tomography (CT) in the anatomical localization, image interpretation and extra-sentinel lymph nodes (SLNs) detection compared to dynamic and static planar radioisotopic lymphoscintigraphy (PLS) in patients with melanoma. Eighty-two patients with melanoma underwent dynamic PLS, static PLS and SPECT/CT. Data were obtained using a dual head SPECT/CT 16 slices γ-camera. We evaluated the number and localization of SLNs detected with each imaging method. SPECT/CT demonstrated 48 additional SLNs in comparison with PLS in 29 patients. In five truncal and seven head-neck lesions, dynamic and static PLS failed to detect the SLNs found on SPECT/CT (false negative). In one case of truncal and one case of lower limb melanoma, the foci of increased activity interpreted on PLS as possible SLNs were confirmed to be non-nodal sites of uptake on SPECT/CT (false positive). PLS underestimated the number of SLNs detected, whereas SPECT/CT revealed higher agreement compared to the respective number from histological reports. SPECT/CT showed a better prediction of the number of SLNs and higher diagnostic parameters in comparison to planar imaging. SPECT/CT is an important complementary diagnostic modality to PLS, that improves detection, preoperative evaluation, anatomical landmarks of SLNs and surgical management of patients with melanoma.
    MeSH term(s) Humans ; Melanoma/pathology ; Sentinel Lymph Node/diagnostic imaging ; Sentinel Lymph Node/pathology ; Lymphoscintigraphy/methods ; Skin Neoplasms/pathology ; Sentinel Lymph Node Biopsy/methods ; Single Photon Emission Computed Tomography Computed Tomography/methods ; Tomography, Emission-Computed, Single-Photon/methods ; Lymph Nodes/diagnostic imaging ; Lymph Nodes/pathology
    Language English
    Publishing date 2023-04-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 1095779-0
    ISSN 1473-5636 ; 0960-8931
    ISSN (online) 1473-5636
    ISSN 0960-8931
    DOI 10.1097/CMR.0000000000000893
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Case report: The devil was hidden in the mastocytes - an unusually fulminant case of indolent systemic mastocytosis in a 45-year-old patient, missed for almost 20 years.

    Boukouris, Aristeidis E / Michelakis, Ioannis / Metaxas, Dionysios / Karapati, Gianna / Kanellis, George / Lioni, Athina / Tzavara, Vasiliki

    Frontiers in immunology

    2023  Volume 14, Page(s) 1134587

    Abstract: Indolent systemic mastocytosis (ISM) represents the most common form of SM, typically following a slow clinical course. While anaphylactic reactions may come up in the life course of an ISM patient, these are often moderate and do not pose a threat to ... ...

    Abstract Indolent systemic mastocytosis (ISM) represents the most common form of SM, typically following a slow clinical course. While anaphylactic reactions may come up in the life course of an ISM patient, these are often moderate and do not pose a threat to patient's health. Here, we present an undiagnosed case of ISM with recurrent severe anaphylactic episodes following consumption of food and emotional stress. One of these episodes led to anaphylactic shock, necessitating temporary mechanical ventilation and intensive care unit (ICU) support. Besides hypotension, a diffuse, itchy, red rash was the only notable clinical finding. Upon recovery, we found abnormally high baseline serum tryptase level as well as 10% bone marrow (BM) infiltration by multifocal, dense clusters of CD117
    MeSH term(s) Humans ; Middle Aged ; Mastocytosis, Systemic/diagnosis ; Mastocytosis, Systemic/drug therapy ; Mast Cells ; Bone Marrow ; Tryptases ; Anaphylaxis/etiology
    Chemical Substances Tryptases (EC 3.4.21.59)
    Language English
    Publishing date 2023-02-10
    Publishing country Switzerland
    Document type Case Reports ; Research Support, Non-U.S. Gov't ; Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1134587
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: MFN2-driven mitochondria-to-nucleus tethering allows a non-canonical nuclear entry pathway of the mitochondrial pyruvate dehydrogenase complex.

    Zervopoulos, Sotirios D / Boukouris, Aristeidis E / Saleme, Bruno / Haromy, Alois / Tejay, Saymon / Sutendra, Gopinath / Michelakis, Evangelos D

    Molecular cell

    2022  Volume 82, Issue 5, Page(s) 1066–1077.e7

    Abstract: The mitochondrial pyruvate dehydrogenase complex (PDC) translocates into the nucleus, facilitating histone acetylation by producing acetyl-CoA. We describe a noncanonical pathway for nuclear PDC (nPDC) import that does not involve nuclear pore complexes ( ...

    Abstract The mitochondrial pyruvate dehydrogenase complex (PDC) translocates into the nucleus, facilitating histone acetylation by producing acetyl-CoA. We describe a noncanonical pathway for nuclear PDC (nPDC) import that does not involve nuclear pore complexes (NPCs). Mitochondria cluster around the nucleus in response to proliferative stimuli and tether onto the nuclear envelope (NE) via mitofusin-2 (MFN2)-enriched contact points. A decrease in nuclear MFN2 levels decreases mitochondria tethering and nPDC levels. Mitochondrial PDC crosses the NE and interacts with lamin A, forming a ring below the NE before crossing through the lamin layer into the nucleoplasm, in areas away from NPCs. Effective blockage of NPC trafficking does not decrease nPDC levels. The PDC-lamin interaction is maintained during cell division, when lamin depolymerizes and disassembles before reforming daughter nuclear envelopes, providing another pathway for nPDC entry during mitosis. Our work provides a different angle to understanding mitochondria-to-nucleus communication and nuclear metabolism.
    MeSH term(s) Acetyl Coenzyme A/metabolism ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Lamins/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Nuclear Envelope/metabolism ; Pyruvate Dehydrogenase Complex/genetics ; Pyruvate Dehydrogenase Complex/metabolism
    Chemical Substances Lamins ; Pyruvate Dehydrogenase Complex ; Acetyl Coenzyme A (72-89-9)
    Language English
    Publishing date 2022-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2022.02.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Soluble guanylate cyclase stimulators as a potential therapy for PAH: enthusiasm, pragmatism and concern.

    Michelakis, E D

    The European respiratory journal

    2009  Volume 33, Issue 4, Page(s) 717–721

    MeSH term(s) Animals ; Guanylate Cyclase/biosynthesis ; Guanylate Cyclase/physiology ; Humans ; Hypertension, Pulmonary/drug therapy ; Hypertension, Pulmonary/enzymology ; Hypertension, Pulmonary/physiopathology ; Nitric Oxide Synthase Type II/pharmacology ; Oxidation-Reduction ; Pulmonary Circulation/physiology ; Pyrimidines/pharmacology ; Rats ; Receptors, Cytoplasmic and Nuclear/biosynthesis ; Receptors, Cytoplasmic and Nuclear/physiology ; Signal Transduction ; Soluble Guanylyl Cyclase
    Chemical Substances Pyrimidines ; Receptors, Cytoplasmic and Nuclear ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Guanylate Cyclase (EC 4.6.1.2) ; Soluble Guanylyl Cyclase (EC 4.6.1.2)
    Language English
    Publishing date 2009-04
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/09031936.00010609
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Metabolic Enzymes Moonlighting in the Nucleus: Metabolic Regulation of Gene Transcription.

    Boukouris, Aristeidis E / Zervopoulos, Sotirios D / Michelakis, Evangelos D

    Trends in biochemical sciences

    2016  Volume 41, Issue 8, Page(s) 712–730

    Abstract: ... This metabolism-epigenetics axis facilitates adaptation to a changing environment in normal (e.g., development ... stem cell differentiation) and disease states (e.g., cancer), providing a potential novel therapeutic target. ...

    Abstract During evolution, cells acquired the ability to sense and adapt to varying environmental conditions, particularly in terms of fuel supply. Adaptation to fuel availability is crucial for major cell decisions and requires metabolic alterations and differential gene expression that are often epigenetically driven. A new mechanistic link between metabolic flux and regulation of gene expression is through moonlighting of metabolic enzymes in the nucleus. This facilitates delivery of membrane-impermeable or unstable metabolites to the nucleus, including key substrates for epigenetic mechanisms such as acetyl-CoA which is used in histone acetylation. This metabolism-epigenetics axis facilitates adaptation to a changing environment in normal (e.g., development, stem cell differentiation) and disease states (e.g., cancer), providing a potential novel therapeutic target.
    MeSH term(s) Cell Nucleus/enzymology ; Cell Nucleus/genetics ; Gene Expression Regulation ; Humans ; L-Lactate Dehydrogenase/metabolism ; Transcription, Genetic
    Chemical Substances L-Lactate Dehydrogenase (EC 1.1.1.27)
    Language English
    Publishing date 2016-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2016.05.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Retroperitoneal Soft Tissue Sarcoma: Emerging Therapeutic Strategies.

    de Bree, Eelco / Michelakis, Dimosthenis / Heretis, Ioannis / Kontopodis, Nikolaos / Spanakis, Konstantinos / Lagoudaki, Eleni / Tolia, Maria / Zografakis-Sfakianakis, Michail / Ioannou, Christos / Mavroudis, Dimitrios

    Cancers

    2023  Volume 15, Issue 22

    Abstract: Retroperitoneal soft tissue sarcoma (RPS) is a rare and heterogenous disease for which surgery is the cornerstone of treatment. However, the local recurrence rate is much higher than in soft tissue sarcoma of the extremities since wide resection is ... ...

    Abstract Retroperitoneal soft tissue sarcoma (RPS) is a rare and heterogenous disease for which surgery is the cornerstone of treatment. However, the local recurrence rate is much higher than in soft tissue sarcoma of the extremities since wide resection is usually unfeasible in RPS due to its large size, indistinct tumour borders, anatomical constraints and the thinness of the overlying peritoneum. Local recurrence is the leading cause of death for low-grade RPS, whereas high-grade tumours are prone to distant metastases. In recent decades, the role of emerging therapeutic strategies, such as more extended surgery and (neo)adjuvant treatments to improve oncological outcome in primary localised RPS, has been extensively investigated. In this review, the recent data on the evolving multidisciplinary management of primary localised RPS are comprehensively discussed. The heterogeneity of RPS, with their different histological subtypes and biological behaviour, renders a standard therapeutic 'one-size-fits-all' approach inappropriate, and treatment should be modified according to histological type and malignancy grade. There is sufficient evidence that frontline extended surgery with compartmental resection including all ipsilateral retroperitoneal fat and liberal en bloc resection of adjacent organs and structures, even if they are not macroscopically involved, increases local tumour control in low-grade sarcoma and liposarcoma, but not in leiomyosarcoma for which complete macroscopic resection seems sufficient. Additionally, preoperative radiotherapy is not indicated for all RPSs, but seems to be beneficial in well-differentiated liposarcoma and grade I/II dedifferentiated liposarcoma, and probably in solitary fibrous tumour. Whether neoadjuvant chemotherapy is of benefit in high-grade RPS remains unclear from retrospective data and is subject of the ongoing randomised STRASS 2 trial, from which the results are eagerly awaited. Personalised, histology-tailored multimodality treatment is promising and will likely further evolve as our understanding of the molecular and genetic characteristics within RPS improves.
    Language English
    Publishing date 2023-11-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15225469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: MFN2-driven mitochondria-to-nucleus tethering allows a non-canonical nuclear entry pathway of the mitochondrial pyruvate dehydrogenase complex

    Zervopoulos, Sotirios D. / Boukouris, Aristeidis E. / Saleme, Bruno / Haromy, Alois / Tejay, Saymon / Sutendra, Gopinath / Michelakis, Evangelos D.

    Molecular cell. 2022 Mar. 03, v. 82, no. 5

    2022  

    Abstract: The mitochondrial pyruvate dehydrogenase complex (PDC) translocates into the nucleus, facilitating histone acetylation by producing acetyl-CoA. We describe a noncanonical pathway for nuclear PDC (nPDC) import that does not involve nuclear pore complexes ( ...

    Abstract The mitochondrial pyruvate dehydrogenase complex (PDC) translocates into the nucleus, facilitating histone acetylation by producing acetyl-CoA. We describe a noncanonical pathway for nuclear PDC (nPDC) import that does not involve nuclear pore complexes (NPCs). Mitochondria cluster around the nucleus in response to proliferative stimuli and tether onto the nuclear envelope (NE) via mitofusin-2 (MFN2)-enriched contact points. A decrease in nuclear MFN2 levels decreases mitochondria tethering and nPDC levels. Mitochondrial PDC crosses the NE and interacts with lamin A, forming a ring below the NE before crossing through the lamin layer into the nucleoplasm, in areas away from NPCs. Effective blockage of NPC trafficking does not decrease nPDC levels. The PDC-lamin interaction is maintained during cell division, when lamin depolymerizes and disassembles before reforming daughter nuclear envelopes, providing another pathway for nPDC entry during mitosis. Our work provides a different angle to understanding mitochondria-to-nucleus communication and nuclear metabolism.
    Keywords acetyl coenzyme A ; acetylation ; histones ; imports ; metabolism ; mitochondria ; mitosis ; nuclear pore ; pyruvate dehydrogenase (lipoamide)
    Language English
    Dates of publication 2022-0303
    Size p. 1066-1077.e7.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2022.02.003
    Database NAL-Catalogue (AGRICOLA)

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