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Article ; Online: The Impact of the First 11 Months of the COVID-19 Pandemic on Vascular Patients' Care and Hospitalisation Rate in the Vascular Surgery Divisions of Southern Italy.

Martelli, Eugenio / Sotgiu, Giovanni / Saderi, Laura / Martelli, Allegra R / Settembrini, Alberto M

European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery

2022 Volume 64, Issue 2-3, Page(s) 274–275

MeSH term(s)	Humans ; COVID-19 ; Pandemics/prevention & control ; Vascular Surgical Procedures ; Aortic Aneurysm, Abdominal/surgery ; Hospitalization ; Italy/epidemiology ; Ischemia/surgery ; Amputation ; Retrospective Studies ; Limb Salvage ; Risk Factors ; Treatment Outcome
Language	English
Publishing date	2022-04-26
Publishing country	England
Document type	Letter
ZDB-ID	1225869-6
ISSN	1532-2165 ; 1078-5884
ISSN (online)	1532-2165
ISSN	1078-5884
DOI	10.1016/j.ejvs.2022.04.021
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Article: Focus on the Most Common Paucisymptomatic Vasculopathic Population, from Diagnosis to Secondary Prevention of Complications.

Martelli, Eugenio / Enea, Iolanda / Zamboni, Matilde / Federici, Massimo / Bracale, Umberto M / Sangiorgi, Giuseppe / Martelli, Allegra R / Messina, Teresa / Settembrini, Alberto M

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 14

Abstract: Middle-aged adults can start to be affected by some arterial diseases (ADs), such as abdominal aortic or popliteal artery aneurysms, lower extremity arterial disease, internal carotid, or renal artery or subclavian artery stenosis. These vasculopathies ... ...

Abstract	Middle-aged adults can start to be affected by some arterial diseases (ADs), such as abdominal aortic or popliteal artery aneurysms, lower extremity arterial disease, internal carotid, or renal artery or subclavian artery stenosis. These vasculopathies are often asymptomatic or paucisymptomatic before manifesting themselves with dramatic complications. Therefore, early detection of ADs is fundamental to reduce the risk of major adverse cardiovascular and limb events. Furthermore, ADs carry a high correlation with silent coronary artery disease (CAD). This study focuses on the most common ADs, in the attempt to summarize some key points which should selectively drive screening. Since the human and economic possibilities to instrumentally screen wide populations is not evident, deep knowledge of semeiotics and careful anamnesis must play a central role in our daily activity as physicians. The presence of some risk factors for atherosclerosis, or an already known history of CAD, can raise the clinical suspicion of ADs after a careful clinical history and a deep physical examination. The clinical suspicion must then be confirmed by a first-level ultrasound investigation and, if so, adequate treatments can be adopted to prevent dreadful complications.
Language	English
Publishing date	2023-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13142356
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Article ; Online: Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).

Martelli, Alberto M / Paganelli, Francesca / Truocchio, Serena / Palumbo, Carla / Chiarini, Francesca / McCubrey, James A

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as ... ...

Abstract	The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL.
MeSH term(s)	Humans ; Hedgehog Proteins/metabolism ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Lymphopoiesis ; T-Lymphocytes/metabolism ; Signal Transduction/physiology
Chemical Substances	Hedgehog Proteins
Language	English
Publishing date	2023-02-03
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/ijms24032962
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Article ; Online: The potential of the nutraceutical berberine in the treatment of hepatocellular carcinoma and other liver diseases such as NAFLD and NASH.

Cervello, Melchiorre / Augello, Giuseppa / Cocco, Lucio / Ratti, Stefano / Follo, Matilde Y / Martelli, Alberto M / Cusimano, Antonella / Montalto, Giuseppe / McCubrey, James A

Advances in biological regulation

2024 , Page(s) 101032

Abstract: Hepatocellular carcinoma (HCC) is a common cancer which unfortunately has poor outcomes. Common anti-cancer treatments such as chemotherapy and targeted therapy have not increased patient survival significantly. A common treatment for HCC patients is ... ...

Abstract	Hepatocellular carcinoma (HCC) is a common cancer which unfortunately has poor outcomes. Common anti-cancer treatments such as chemotherapy and targeted therapy have not increased patient survival significantly. A common treatment for HCC patients is transplantation, however, it has limitations and complications. Novel approaches are necessary to more effectively treat HCC patients. Berberine (BBR) is a nutraceutical derived from various fruits and trees, which has been used for centuries in traditional medicine to treat various diseases such as diabetes and inflammation. More recently, the anti-proliferation effects of BBR have been investigated in the treatment of patients with various cancers, especially colorectal cancer, and in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we will focus on studies with BBR in liver diseases.
Language	English
Publishing date	2024-04-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2667413-0
ISSN	2212-4934 ; 2212-4926
ISSN (online)	2212-4934
ISSN	2212-4926
DOI	10.1016/j.jbior.2024.101032
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Article ; Online: Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies.

Martelli, Alberto M / Paganelli, Francesca / Evangelisti, Camilla / Chiarini, Francesca / McCubrey, James A

Cells

2022 Volume 11, Issue 11

Abstract: Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which ... ...

Abstract	Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. In the early 1990s, GSK-3 isoforms were implicated as key players in cancer cell pathobiology. Active GSK-3 facilitates the destruction of multiple oncogenic proteins which include β-catenin and Master regulator of cell cycle entry and proliferative metabolism (c-Myc). Therefore, GSK-3 was initially considered to be a tumor suppressor. Consistently, GSK-3 is often inactivated in cancer cells through dysregulated upstream signaling pathways. However, over the past 10-15 years, a growing number of studies highlighted that in some cancer settings GSK-3 isoforms inhibit tumor suppressing pathways and therefore act as tumor promoters. In this article, we will discuss the multiple and often enigmatic roles played by GSK-3 isoforms in some chronic hematological malignancies (chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B-cell non-Hodgkin's lymphomas) which are among the most common blood cancer cell types. We will also summarize possible novel strategies targeting GSK-3 for innovative therapies of these disorders.
MeSH term(s)	Glycogen Synthase Kinase 3 ; Hematologic Neoplasms ; Humans ; Multiple Myeloma/drug therapy ; Protein Isoforms/metabolism ; Protein Serine-Threonine Kinases
Chemical Substances	Protein Isoforms ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
Language	English
Publishing date	2022-05-31
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11111812
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Article ; Online: Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Alberto M. Martelli / Francesca Paganelli / Camilla Evangelisti / Francesca Chiarini / James A. McCubrey

Cells, Vol 11, Iss 1812, p

2022 Volume 1812

Abstract	Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. In the early 1990s, GSK-3 isoforms were implicated as key players in cancer cell pathobiology. Active GSK-3 facilitates the destruction of multiple oncogenic proteins which include β-catenin and Master regulator of cell cycle entry and proliferative metabolism (c-Myc). Therefore, GSK-3 was initially considered to be a tumor suppressor. Consistently, GSK-3 is often inactivated in cancer cells through dysregulated upstream signaling pathways. However, over the past 10–15 years, a growing number of studies highlighted that in some cancer settings GSK-3 isoforms inhibit tumor suppressing pathways and therefore act as tumor promoters. In this article, we will discuss the multiple and often enigmatic roles played by GSK-3 isoforms in some chronic hematological malignancies (chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B-cell non-Hodgkin’s lymphomas) which are among the most common blood cancer cell types. We will also summarize possible novel strategies targeting GSK-3 for innovative therapies of these disorders.
Keywords	GSK-3 ; paralogs ; chronic hematological malignancies ; targeted therapy ; chronic myelogenous leukemia ; chronic lymphocytic leukemia ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

Alberto M. Martelli / Francesca Paganelli / Serena Truocchio / Carla Palumbo / Francesca Chiarini / James A. McCubrey

International Journal of Molecular Sciences, Vol 24, Iss 2962, p

2023 Volume 2962

Abstract	The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL.
Keywords	Hedgehog signaling ; thymocyte differentiation ; T-ALL ; targeted therapy ; crosstalk ; signaling pathways ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Role Played by Wnt/β-Catenin Signaling Pathway in Acute Lymphoblastic Leukemia.

Chiarini, Francesca / Paganelli, Francesca / Martelli, Alberto M / Evangelisti, Camilla

International journal of molecular sciences

2020 Volume 21, Issue 3

Abstract: Acute lymphoblastic leukemia (ALL) is an aggressive hematologic neoplastic disorder that arises from the clonal expansion of transformed T-cell or B-cell precursors. Thanks to progress in chemotherapy protocols, ALL outcome has significantly improved. ... ...

Abstract	Acute lymphoblastic leukemia (ALL) is an aggressive hematologic neoplastic disorder that arises from the clonal expansion of transformed T-cell or B-cell precursors. Thanks to progress in chemotherapy protocols, ALL outcome has significantly improved. However, drug-resistance remains an unresolved issue in the treatment of ALL and toxic effects limit dose escalation of current chemotherapeutics. Therefore, the identification of novel targeted therapies to support conventional chemotherapy is required. The Wnt/β-catenin pathway is a conserved signaling axis involved in several physiological processes such as development, differentiation, and adult tissue homeostasis. As a result, deregulation of this cascade is closely related to initiation and progression of various types of cancers, including hematological malignancies. In particular, deregulation of this signaling network is involved in the transformation of healthy HSCs in leukemic stem cells (LSCs), as well as cancer cell multi-drug-resistance. This review highlights the recent findings on the role of Wnt/β-catenin in hematopoietic malignancies and provides information on the current status of Wnt/β-catenin inhibitors with respect to their therapeutic potential in the treatment of ALL.
MeSH term(s)	Animals ; Hematopoiesis ; Humans ; Molecular Targeted Therapy/methods ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Wnt Signaling Pathway
Language	English
Publishing date	2020-02-07
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/ijms21031098
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Article ; Online: Regulation of p53 and NF-κB transactivation activities by DGKζ in catalytic activity-dependent and -independent manners.

Tanaka, Toshiaki / Nakano, Tomoyuki / Hozumi, Yasukazu / Martelli, Alberto M / Goto, Kaoru

Biochimica et biophysica acta. Molecular cell research

2021 Volume 1868, Issue 4, Page(s) 118953

Abstract: Diacylglycerol kinase (DGK) constitutes a family of enzymes that phosphorylate diacylglycerol to phosphatidic acid (PA). These lipids serve as second messengers, thereby activating distinct downstream cascades and different cellular responses. Therefore, ...

Abstract	Diacylglycerol kinase (DGK) constitutes a family of enzymes that phosphorylate diacylglycerol to phosphatidic acid (PA). These lipids serve as second messengers, thereby activating distinct downstream cascades and different cellular responses. Therefore, DG-to-PA conversion activity induces a phase transition of signaling pathways. One member of the family, DGKζ, is involved closely with stress responses. Morphological data showing that DGKζ localizes predominantly to the nucleus and that it shuttles between the nucleus and the cytoplasm implicate DGKζ in the regulation of transcription factors during stress responses. Tumor suppressor p53 and NF-κB are major stress-responsive transcription factors. They exert opposing effects on cellular pathophysiology. Herein, we summarize DGKζ catalytic activity-dependent and -independent regulatory mechanisms of p53 and NF-κB transactivation activities, including p53 degradation and NF-κB nuclear translocation. We also discuss how each component of DGKζ-interacting protein complex modulates the specificity and selectivity of target gene expression.
MeSH term(s)	Animals ; Cell Nucleus/metabolism ; Diacylglycerol Kinase/metabolism ; Diglycerides/metabolism ; Humans ; NF-kappa B/metabolism ; Phosphatidic Acids/metabolism ; Protein Transport ; Proteolysis ; Second Messenger Systems ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Diglycerides ; NF-kappa B ; Phosphatidic Acids ; TP53 protein, human ; Tumor Suppressor Protein p53 ; DGKZ protein, human (EC 2.7.1.107) ; Diacylglycerol Kinase (EC 2.7.1.107)
Language	English
Publishing date	2021-01-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamcr.2021.118953
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Article ; Online: GSK-3: a multifaceted player in acute leukemias.

Martelli, Alberto M / Evangelisti, Camilla / Paganelli, Francesca / Chiarini, Francesca / McCubrey, James A

Leukemia

2021 Volume 35, Issue 7, Page(s) 1829–1842

Abstract: Glycogen synthase kinase 3 (GSK-3) consists of two isoforms (α and β) that were originally linked to glucose metabolism regulation. However, GSK-3 is also involved in several signaling pathways controlling many different key functions in healthy cells. ... ...

Abstract	Glycogen synthase kinase 3 (GSK-3) consists of two isoforms (α and β) that were originally linked to glucose metabolism regulation. However, GSK-3 is also involved in several signaling pathways controlling many different key functions in healthy cells. GSK-3 is a unique kinase in that its isoforms are constitutively active, while they are inactivated mainly through phosphorylation at Ser residues by a variety of upstream kinases. In the early 1990s, GSK-3 emerged as a key player in cancer cell pathophysiology. Since active GSK-3 promotes destruction of multiple oncogenic proteins (e.g., β-catenin, c-Myc, Mcl-1) it was considered to be a tumor suppressor. Accordingly, GSK-3 is frequently inactivated in human cancer via aberrant regulation of upstream signaling pathways. More recently, however, it has emerged that GSK-3 isoforms display also oncogenic properties, as they up-regulate pathways critical for neoplastic cell proliferation, survival, and drug-resistance. The regulatory roles of GSK-3 isoforms in cell cycle, apoptosis, DNA repair, tumor metabolism, invasion, and metastasis reflect the therapeutic relevance of these kinases and provide the rationale for combining GSK-3 inhibitors with other targeted drugs. Here, we discuss the multiple and often conflicting roles of GSK-3 isoforms in acute leukemias. We also review the current status of GSK-3 inhibitor development for innovative leukemia therapy.
MeSH term(s)	Animals ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Leukemia/metabolism ; Protein Isoforms/metabolism ; Signal Transduction/physiology
Chemical Substances	Protein Isoforms ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
Language	English
Publishing date	2021-04-02
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/s41375-021-01243-z
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