Publications by authors named "Domenico Ribatti"

561 Publications

Epigenetics and Its Ethical Implications.

Authors:
Domenico Ribatti

Crit Rev Eukaryot Gene Expr 2021 ;31(1):23-27

Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Piazza Giulio Cesare, 11, Policlinico, 70124 Bari, Italy.

The biologist Conrad Waddington first coined the term epigenetics, defining it as "the branch of biology that studies the causal interactions between genes and their products and creates a phenotype." The molecular mechanisms underlying epigenetics are complex. Epigenetic changes are rapid, functional, nonstructural, and reversible, and these DNA changes are partly transmissible from one generation to the next. These modifications affect the activation of certain genes but not their basic structure. In this context, the epigenome of an individual allows it to better adapt to the environment in which it finds itself. Epigenetics is also involved in the pathogenesis of other diseases, such as cancer, obesity, type 2 diabetes, and neurodegenerative diseases. Epigenetic changes are potentially reversible, so new epigenetic therapies may be developed for tumors that have an epigenetic component and for other diseases. If the epigenetic markings can be passed on to future generations, the inherited advantage, more frequently the disadvantage, passes to the new generations, and in this way the injustices are perpetuated.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2020036701DOI Listing
January 2021

The role of mast cells in human skin cancers.

Clin Exp Med 2021 Feb 12. Epub 2021 Feb 12.

Department of Medicine, Section of Human Anatomy, University of Udine, Udine, Italy.

Mast cells (MCs) are immune cells derived from myeloid lineage present in all classes of vertebrates and have emerged preceding much time the development of adaptive immunity. MCs are involved in inflammatory processes, allergic reactions, and host responses to parasites and bacteria infectious diseases. MCs are located at the host-environment interface, at many sites of initial antigen entry, including skin, lung and gastrointestinal tract, and have part of a protective mechanism. Skin has an important role in protecting the host from invasion both as physical barriers and by employing an intricate network of resident immune and non-immune cells include macrophages, T and B lymphocytes, MCs, neutrophils, eosinophils, and Langerhans cells. In this review we discussed the role of MCs in human skin cancers.
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http://dx.doi.org/10.1007/s10238-021-00688-xDOI Listing
February 2021

The bursa of Hieronymus Fabricius ab Aquapendente: from original iconography to most recent research.

Rom J Morphol Embryol 2020 Apr-Jun;61(2):583-585

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy; Department of Neuroscience, Section of Anatomy, University of Padova Medical School, Padova, Italy;

Hieronymus Fabricius ab Aquapendente (1533-1619) described the homonymous bursa in the "De Formatione Ovi et Pulli", published posthumously in 1621. He also included a figure in which the bursa was depicted. We here present the figure of the bursa of Fabricius, along with corrections of some mislabeling still presents in some anastatic copies. The bursa of Fabricius is universally known as the origin of B-lymphocytes; morphogenetical and physiological issues are also considered.
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http://dx.doi.org/10.47162/RJME.61.2.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864288PMC
February 2021

The CAM assay in the study of the metastatic process.

Authors:
Domenico Ribatti

Exp Cell Res 2021 Jan 29;400(2):112510. Epub 2021 Jan 29.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy. Electronic address:

Among the in vivo experimental models, the chick embryo chorioallantoic membrane (CAM) has been routinely used to implant several malignant cell lines or tumor tissues to study their angiogenic and metastatic capability. Since the chick embryo is naturally immunodeficient, the CAM can support the engraftment of tumor cells, and their growth therein can faithfully recapitulate most of the characteristics of the carcinogenic process including: growth, invasion, angiogenesis and colonization of distant tissues. This review article is focused on the discussion of the more recent literature data concerning the use of the CAM to investigate the metastatic process.
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http://dx.doi.org/10.1016/j.yexcr.2021.112510DOI Listing
January 2021

Thrombopoietin Promotes Angiogenesis and Disease Progression in Patients with Multiple Myeloma.

Am J Pathol 2021 Jan 29. Epub 2021 Jan 29.

Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari Aldo Moro, Bari, Italy. Electronic address:

Multiple myeloma (MM) progression closely depends on bone marrow (BM) angiogenesis. Several factors sustain angiogenesis, including cytokines, growth factors, and cell-to-cell interactions. Herein, we found that BM thrombopoietin (TPO) supports angiogenesis and disease progression in MM. Patients with MM at different progression phases have higher levels of BM and circulating TPO than monoclonal gammopathy of undetermined significance/smoldering MM patients, suggesting that TPO correlates with disease progression and prognosis. Endothelial cells from monoclonal gammopathy of undetermined significance (MGECs) and endothelial cells from MM (MMECs) patients express TPO receptor, and the TPO treatment triggers their angiogenic capabilities in vitro. Indeed, TPO-treated MGECs and MMECs show enhanced angiogenesis on Matrigel and spontaneous cell migration and chemotaxis by acting as a chemotactic agent. TPO also has an angiogenic activity in vivo in the chorioallantoic membrane assay system. Finally, TPO treatment increases the release of active matrix metalloproteinase (MMP)-9 and MMP-2 in MGECs and of MMP-2 in MMECs and affects the balance between angiogenic/antiangiogenic factors in the MM BM. Our results support the angiogenic activity of TPO, and suggest that it may have a critical role in promoting the angiogenic switch during MM progression. Accordingly, TPO may be envisaged as a new angiogenic and prognostic factor in MM patients.
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http://dx.doi.org/10.1016/j.ajpath.2020.12.016DOI Listing
January 2021

The Boundary between Normal and Pathological Conditions.

Authors:
Domenico Ribatti

Crit Rev Eukaryot Gene Expr 2020 ;30(6):493-498

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Hospital Policlinico, Piazza G. Cesare, 11, 70124 Bari, Italy.

There is clinical and experimental evidence that in biomedicine, the limit between what we consider normal and what we consider pathological is not always so clear and absolute. Conditions may arise in which, apparently without any explanation, one passes from one condition to another. A key role is played by changes that occur in the microenvironment surrounding a cell population. The terms normal and pathological have no absolute meaning on their own. They have their own meaning only if they are considered in the light of the relationships between the living being and its surrounding environment. Man is able to create new environments instead of passively enduring its changes. Any individual who deviates from a statistically defined normal individual will be considered pathological.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2020036337DOI Listing
January 2020

Cerebellar ataxia and exercise intolerance in Erdheim-Chester disease.

Cerebellum Ataxias 2021 Jan 6;8(1). Epub 2021 Jan 6.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, Human Anatomy Section, University of Bari School of Medicine, Policlinico Universitario, Piazza Giulio Cesare, 11, 70124, Bari, Italy.

Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has been related to cerebellar dysfunction. To increase the awareness of this rare, protean disease, an unusual, myasthenia-like onset of ECD is reported.

Case Presentation: A 42-year-old man presented with a 6-year history of mild evening fatigability in his four limbs followed by motor and cognitive symptoms associated with cerebellar atrophy, dentate nuclei and dentato-thalamic pathway degeneration. Magnetic resonance imaging revealed hyperintense signals in T2 and fluid-attenuated inversion recovery sequences within the pons, cerebellar white matter, dentate nuclei and globi pallidi in the absence of any contrast enhancement. Whole-body bone scintigraphy with Technetium - methylene diphosphonate and fluorodeoxyglucose-positron emission tomography both revealed symmetric uptake in the lower extremities a finding suggestive of a diagnosis of ECD. Histological examination revealed diffuse infiltration of CD 68 histiocytes with foamy cytoplasms in the presence of B-type of Rapidly Accelerated Fibrosarcoma protein kinase (BRAF) activating mutation in tumor cells.

Conclusion: In patients with myasthenia-like symptoms who test negatively for myasthenia gravis, neurodegenerative diseases, and disorders of the hypothalamus, a diagnosis of ECD should be taken into consideration.
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http://dx.doi.org/10.1186/s40673-020-00125-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789415PMC
January 2021

François Jacob, Lysogeny, and the Development of the Operon Model.

Authors:
Domenico Ribatti

Crit Rev Eukaryot Gene Expr 2020 ;30(5):443-446

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Hospital Policlinico, Piazza G. Cesare, 11, 70124 Bari, Italy.

This article summarizes the fundamental contribution of Francois Jacob in the field of molecular biology. Jacob was one of the handful of scientists who initiated the revolution in biology that took place in the second half of the 20th century. In their landmark publication of 1961, entitled "Genetic Regulatory Mechanisms in the Synthesis of Proteins", François Jacob and Jacques Monod presented a model for the regulation of gene expression deduced from genetic and biochemical studies. They proposed that a new class of genes, regulatory genes, would code for repressors that bind to operator sequences upstream of operons. The impact of the operon model was great: gene expression varies constantly and is under the direct control of proteins, two ideas that were revolutionary at the time they were proposed. It was also rapidly shown that in most organisms, except bacteria, co-regulated genes are not usually grouped together on the genome.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2020035329DOI Listing
January 2020

Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin.

Proc Natl Acad Sci U S A 2021 Jan;118(2)

Department of Molecular and Translational Medicine, University of Brescia Medical School, 25123 Brescia, Italy;

The HIV-1 matrix protein p17 (p17) is a pleiotropic molecule impacting on different cell types. Its interaction with many cellular proteins underlines the importance of the viral protein as a major determinant of human specific adaptation. We previously showed the proangiogenic capability of p17. Here, by integrating functional analysis and receptor binding, we identify a functional epitope that displays molecular mimicry with human erythropoietin (EPO) and promotes angiogenesis through common beta chain receptor (βCR) activation. The functional EPO-like epitope was found to be present in the matrix protein of HIV-1 ancestors SIV originated in chimpanzees (SIVcpz) and gorillas (SIVgor) but not in that of HIV-2 and its ancestor SIVsmm from sooty mangabeys. According to biological data, evolution of the EPO-like epitope showed a clear differentiation between HIV-1/SIVcpz-gor and HIV-2/SIVsmm branches, thus highlighting this epitope on p17 as a divergent signature discriminating HIV-1 and HIV-2 ancestors. P17 is known to enhance HIV-1 replication. Similarly to other βCR ligands, p17 is capable of attracting and activating HIV-1 target cells and promoting a proinflammatory microenvironment. Thus, it is tempting to speculate that acquisition of an epitope on the matrix proteins of HIV-1 ancestors capable of triggering βCR may have represented a critical step to enhance viral aggressiveness and early human-to-human SIVcpz/gor dissemination. The hypothesis that the p17/βCR interaction and βCR abnormal stimulation may also play a role in sustaining chronic activation and inflammation, thus marking the difference between HIV-1 and HIV-2 in term of pathogenicity, needs further investigation.
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http://dx.doi.org/10.1073/pnas.2021366118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812818PMC
January 2021

microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis.

Front Oncol 2020 27;10:581007. Epub 2020 Nov 27.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy.

microRNAs (miRNAs) are small non-coding RNA molecules, evolutionary conserved. They target more than one mRNAs, thus influencing multiple molecular pathways, but also mRNAs may bind to a variety of miRNAs, either simultaneously or in a context-dependent manner. miRNAs biogenesis, including miRNA transcription, processing by Drosha and Dicer, transportation, RISC biding, and miRNA decay, are finely controlled in space and time. miRNAs are critical regulators in various biological processes, such as differentiation, proliferation, apoptosis, and development in both health and disease. Their dysregulation is involved in tumor initiation and progression. In tumors, they can act as onco-miRNAs or oncosuppressor-miRNA participating in distinct cellular pathways, and the same miRNA can perform both activities depending on the context. In tumor progression, the angiogenic switch is fundamental. miRNAs derived from tumor cells, endothelial cells, and cells of the surrounding microenvironment regulate tumor angiogenesis, acting as pro-angiomiR or anti-angiomiR. In this review, we described miRNA biogenesis and function, and we update the non-classical aspects of them. The most recent role in the nucleus, as transcriptional gene regulators and the different mechanisms by which they could be dysregulated, in tumor initiation and progression, are treated. In particular, we describe the role of miRNAs in sprouting angiogenesis, vessel co-option, and vasculogenic mimicry. The role of miRNAs in lymphoma angiogenesis is also discussed despite the scarcity of data. The information presented in this review reveals the need to do much more to discover the complete miRNA network regulating angiogenesis, not only using high-throughput computational analysis approaches but also morphological ones.
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http://dx.doi.org/10.3389/fonc.2020.581007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729128PMC
November 2020

Vascular co-option and vasculogenic mimicry mediate resistance to antiangiogenic strategies.

Cancer Rep (Hoboken) 2020 Dec 9:e1318. Epub 2020 Dec 9.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.

Background: The concept that all the tumors need the formation of new vessels to grow inspired the hypothesis that inhibition of angiogenesis would have led to "cure" cancer. The expectancy that this type of therapy would have avoided the insurgence of resistance was based on the concept that targeting normal vessels, instead of the cancer cells which easily develop new mutations, would have allowed evasion of drug caused selection is, however, more complex as it was made apparent by the discovery of nonangiogenic tumors. At the same time an increasing number of trials with antiangiogenic drugs were coming out as not as successful as expected, mostly because of the appearance of unexpected resistance.

Recent Findings: Among the several different mechanisms of resistance to antiangiogenic treatment by now described, we review the evidences that vascular co-option and vasculogenic mimicry by nonangiogenic tumors are effectively two of such mechanisms. We focused on reviewing exclusively the study, both clinical and preclinical, that offer a demonstration that vascular co-option and vasculogenic mimicry are effectively two mechanisms of both intrinsic and acquired resistance.

Conclusion: The discovery that vascular co-opting and vasculogenic mimicry are two ways of escaping antiangiogenic treatment, prompts the need for a better understanding of this phenomenon in order to improve cancer treatment.
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http://dx.doi.org/10.1002/cnr2.1318DOI Listing
December 2020

The role of vascular niche and endothelial cells in organogenesis and regeneration.

Exp Cell Res 2021 Jan 30;398(1):112398. Epub 2020 Nov 30.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.

The term vascular niche indicate the physical and biochemical microenvironment around blood vessel where endothelial cells, pericytes, and smooth muscle cells organize themselves to form blood vessels and release molecules involved in the recruitment of hematopoietic stem cells, endothelial progenitor cells and mesenchymal stem cells. The vascular niche creates a permissive environment that enables different cell types to realize their developmental or regenerative programs. In this context, the proximity between the endothelium and the new-forming cellular components of organs suggests an essential role of endothelial cells in the organs maturation. Dynamic interactions between specific organ endothelial cells and different cellular conponents are crucial for different organ morphogenesis and function. Conversely, organs provide cues shaping vascular network structure.
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http://dx.doi.org/10.1016/j.yexcr.2020.112398DOI Listing
January 2021

Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling.

Cancers (Basel) 2020 Nov 15;12(11). Epub 2020 Nov 15.

Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, 70124 Bari, Italy.

Cancer-associated neo vessels' formation acts as a gatekeeper that orchestrates the entrance and egress of patrolling immune cells within the tumor milieu. This is achieved, in part, via the directed chemokines' expression and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. The crosstalk between adaptive immune cells and the cancer endothelium is thus essential for tumor immune surveillance and the success of immune-based therapies that harness immune cells to kill tumor cells. This review will focus on the biology of the endothelium and will explore the vascular-specific molecular mediators that control the recruitment, retention, and trafficking of immune cells that are essential for effective antitumor immunity. The literature revision will also explore how abnormalities in the tumor endothelium impair crosstalk with adaptive immune cells and how targeting these abnormalities can improve the success of immune-based therapies for different malignancies, with a particular focus on the paradigmatic example represented by multiple myeloma. We also generated and provide two original bio-informatic analyses, in order to sketch the physiopathology underlying the endothelial-neoplastic interactions in an easier manner, feeding into a vicious cycle propagating disease progression and highlighting novel pathways that might be exploited therapeutically.
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http://dx.doi.org/10.3390/cancers12113380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696032PMC
November 2020

Angiogenesis-Inflammation Cross Talk in Diabetic Retinopathy: Novel Insights From the Chick Embryo Chorioallantoic Membrane/Human Vitreous Platform.

Front Immunol 2020 29;11:581288. Epub 2020 Sep 29.

Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, Bari, Italy.

Pathological angiogenesis of the retina is a key component of irreversible causes of blindness, as observed in proliferative diabetic retinopathy (PDR). The pathogenesis of PDR is complex and involves vascular, inflammatory, and neuronal mechanisms. Several structural and molecular alterations associated to PDR are related to the presence of inflammation that appears to play a non-redundant role in the neovascular response that characterizes the retina of PDR patients. Vascular endothelial growth factor (VEGF) blockers have evolved over time for the treatment of retinal neovascularization. However, several limitations to anti-VEGF interventions exist. Indeed, the production of other angiogenic factors and pro-inflammatory mediators may nullify and/or cause resistance to anti-VEGF therapies. Thus, appropriate experimental models are crucial for dissecting the mechanisms leading to retinal neovascularization and for the discovery of more efficacious anti-angiogenic/anti-inflammatory therapies for PDR patients. This review focuses on the tight cross talk between angiogenesis and inflammation during PDR and describe how the chick embryo chorioallantoic membrane (CAM) assay may represent a cost-effective and rapid tool for the study of the relationship between neovascular and inflammatory responses elicited by the vitreous humor of PDR patients and for the screening of novel therapeutic agents.
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http://dx.doi.org/10.3389/fimmu.2020.581288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552803PMC
September 2020

Branching morphogenesis - historical first evidences.

Int J Dev Biol 2020 ;64(7-8-9):397-407

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari.

Branching morphogenesis, the creation of branched structures in the body, is a key feature of animal and plant development. It requires the coordinated interplay of multiple types of epithelial cells with the surrounding extracellular matrix. Cell migration, proliferation, and extracellular matrix dynamics have different roles in driving budding in different organs. This historical review article summarizes the first founding literature data concerning branching morphogenesis occurring in kidney, lung, vascular system, mammary glands and neurons.
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http://dx.doi.org/10.1387/ijdb.200020drDOI Listing
January 2020

β-Galactosylceramidase Promotes Melanoma Growth via Modulation of Ceramide Metabolism.

Cancer Res 2020 11 30;80(22):5011-5023. Epub 2020 Sep 30.

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Disturbance of sphingolipid metabolism may represent a novel therapeutic target in metastatic melanoma, the most lethal form of skin cancer. β-Galactosylceramidase (GALC) removes β-galactose from galactosylceramide and other sphingolipids. In this study, we show that downregulation of , a zebrafish ortholog of human , affects melanoblast and melanocyte differentiation in zebrafish embryos, suggesting a possible role for GALC in melanoma. On this basis, the impact of GALC expression in murine B16-F10 and human A2058 melanoma cells was investigated following its silencing or upregulation. knockdown hampered growth, motility, and invasive capacity of B16-F10 cells and their tumorigenic and metastatic activity when grafted in syngeneic mice or zebrafish embryos. -silenced cells displayed altered sphingolipid metabolism and increased intracellular levels of ceramide, paralleled by a nonredundant upregulation of , which encodes for the ceramide-generating enzyme neutral sphingomyelinase 2. Accordingly, downregulation caused upregulation, increased ceramide levels, and inhibited the tumorigenic activity of human melanoma A2058 cells, whereas upregulation exerted opposite effects. In concordance with information from melanoma database mining, RNAscope analysis demonstrated a progressive increase of expression from common nevi to stage IV human melanoma samples that was paralleled by increases in microphthalmia transcription factor and tyrosinase immunoreactivity inversely related to SMPD3 and ceramide levels. Overall, these findings indicate that GALC may play an oncogenic role in melanoma by modulating the levels of intracellular ceramide, thus providing novel opportunities for melanoma therapy. SIGNIFICANCE: Data from zebrafish embryos, murine and human cell melanoma lines, and patient-derived tumor specimens indicate that β-galactosylceramidase plays an oncogenic role in melanoma and may serve as a therapeutic target.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-3382DOI Listing
November 2020

Carlo Flamigni, l’orgoglio di un laico.

Authors:
Domenico Ribatti

Recenti Prog Med 2020 Sep;111(9):553-554

Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università di Bari.

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http://dx.doi.org/10.1701/3421.34071DOI Listing
September 2020

IL-6 Contributes to the TGF-β1-Mediated Epithelial to Mesenchymal Transition in Human Salivary Gland Epithelial Cells.

Arch Immunol Ther Exp (Warsz) 2020 Sep 10;68(5):27. Epub 2020 Sep 10.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs (SMBNOS), Section of Human Anatomy and Histology, University of Bari "Aldo Moro", piazza Giulio Cesare 1, 70124, Bari, Italy.

To determine the role of IL-6 in bringing about the EMT, in SGEC obtained from healthy subjects. Human salivary gland (SGs) epithelial cells (SGEC) from primary Sjögren's syndrome (pSS) are able to synthesize interleukin (IL)-6, which is a critical mediator of the SGs modifications in response to chronic inflammation. Recently, a hypothetical link between epithelial-mesenchymal transition (EMT)-dependent salivary gland fibrosis and chronic inflammatory conditions has been suggested for pSS; the present study was conducted to evaluate this link. Primary cultures of human SGEC from salivary mucoceles were stimulated with increasing concentrations of IL-6 for 24-72 h. Microscopy, RT-PCR, Real-time PCR, immunoblotting and flow cytometry were used to detect morphological changes, mRNA and protein expression of the EMT markers E-Cadherin, Vimentin and Collagen type I following IL-6 stimulation. The data collected demonstrate that IL-6 can induce SGEC to undergo a morphological and phenotypical transition to a mesenchymal phenotype, in a dose-dependent manner. Decreased mRNA levels of E-Cadherin accompanied by higher mRNA levels of Vimentin and Collagen type I were observed in the IL-6-treated cells compared to control cells (all p < 0.05). This was confirmed at the protein level, demonstrating the decreased E-Cadherin expression, while Vimentin and Collagen type I expression was increased in IL-6-treated SGEC compared to controls (all p < 0.05). The results obtained corroborate the hypothesis that dysregulated cytokines IL-6 may contribute to the EMT-dependent fibrosis, offering a more complete understanding of the role of the EMT during SGs fibrosis in pSS.
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http://dx.doi.org/10.1007/s00005-020-00591-5DOI Listing
September 2020

Understanding the Complexity of Sjögren's Syndrome: Remarkable Progress in Elucidating NF-κB Mechanisms.

J Clin Med 2020 Aug 31;9(9). Epub 2020 Aug 31.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs (SMBNOS), Section of Human Anatomy and Histology, University of Bari "Aldo Moro", 70124 Bari, Italy.

Sjögren's syndrome (SS) is a systemic autoimmune inflammatory disease with a poorly defined aetiology, which targets exocrine glands (particularly salivary and lachrymal glands), affecting the secretory function. Patients suffering from SS exhibit persistent xerostomia and keratoconjunctivitis sicca. It is now widely acknowledged that a chronic grade of inflammation plays a central role in the initiation, progression, and development of SS. Consistent with its key role in organizing inflammatory responses, numerous recent studies have shown involvement of the transcription factor nuclear factor κ (kappa)-light-chain-enhancer of activated B cells (NF-κB) in the development of this disease. Therefore, chronic inflammation is considered as a critical factor in the disease aetiology, offering hope for the development of new drugs for treatment. The purpose of this review is to describe the current knowledge about the NF-κB-mediated molecular events implicated in the pathogenesis of SS.
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http://dx.doi.org/10.3390/jcm9092821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563658PMC
August 2020

Acknowledging the use of human cadaveric tissues in research papers: Recommendations from anatomical journal editors.

Clin Anat 2021 Jan 9;34(1):2-4. Epub 2020 Sep 9.

Department of Neurosurgery, Tulane Center for Clinical Neurosciences, Tulane University School of Medicine, New Orleans, Louisiana, USA.

Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors-in-chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.
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http://dx.doi.org/10.1002/ca.23671DOI Listing
January 2021

Mast cells and angiogenesis in multiple sclerosis.

Inflamm Res 2020 Nov 17;69(11):1103-1110. Epub 2020 Aug 17.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Policlinico, Piazza G. Cesare, 11, 70124, Bari, Italy.

Multiple sclerosis (MS) is an autoimmune disease, characterized by multiple demyelination of axons in both white and gray matter in the Central Nervous System (CNS). There is increasing evidence to support the notion that angiogenesis and chronic inflammation are mutually related. Different immune cells, including monocytes-macrophages, lymphocytes, neutrophils, mast cells (MCs) and dendritic cells are able to secrete an array of angiogenic cytokines, which promote growth, migration, and activation of endothelial cells. MCs play various roles in MS pathogenesis, influencing the innate immune response in peripheral tissues and in CNS. The aim of this review article is to discuss the role of MCs in MS pathogenesis with particular reference to the involvement of these inflammatory cells in the angiogenic processes occurring during MS.
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http://dx.doi.org/10.1007/s00011-020-01394-2DOI Listing
November 2020

The CAM Assay as an Alternative In Vivo Model for Drug Testing.

Handb Exp Pharmacol 2020 Aug 11. Epub 2020 Aug 11.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.

In the last decade, the chicken chorioallantoic membrane (CAM) assay has been re-discovered in cancer research to study the molecular mechanisms of anti-cancer drug effects. Literature about the CAM assay as an alternative in vivo cancer xenograft model according to the 3R principles has exploded in the last 3 years. Following a summary of the basic knowledge about the chicken embryo, we compare advantages and disadvantages with the classical mouse xenograft model, exemplify established and innovative imaging techniques that are used in the CAM model, and give examples of its successful utilization for studying major hallmarks of cancer such as angiogenesis, proliferation, invasion, and metastasis.
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http://dx.doi.org/10.1007/164_2020_375DOI Listing
August 2020

Spatial Statistics-Based Image Analysis Methods for the Study of Vascular Morphogenesis.

Methods Mol Biol 2021 ;2206:67-88

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.

Several studies are available addressing the mechanisms of vascular morphogenesis in order to unravel how cooperative cell behavior can follow from the underlying, genetically regulated behavior of endothelial cells and from cell-to-cell and cell-to-extracellular matrix interactions. From the morphological standpoint several aspects of the process are of interest. They include the way the pattern of vessels fills the available tissue space and how the network grows during the angiogenic process, namely how a main trunk divides into smaller branches, and how branching occurs at different distances from the root point of a vascular tree. A third morphological aspect of interest concerns the spatial relationship between vessels and tissue cells able to secrete factors modulating endothelial cells self-organization, thus influencing vascular rearrangement.In the present chapter image analysis methods allowing for a quantitative characterization of these morphological aspects will be detailed and discussed. They are almost based on concepts derived from the theoretical framework represented by spatial statistics.
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http://dx.doi.org/10.1007/978-1-0716-0916-3_7DOI Listing
January 2021

The Fundamental Contribution of Judah Folkman in the Setting of Angiogenesis Assays.

Authors:
Domenico Ribatti

Methods Mol Biol 2021 ;2206:15-25

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.

Judah Folkman (1933-2008) made seminal discoveries on the mechanisms of angiogenesis which have opened a field of investigation worldwide. This chapter summarizes the fundamental contribution of Folkman in the setting of angiogenesis assays in vivo and in vitro.
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http://dx.doi.org/10.1007/978-1-0716-0916-3_2DOI Listing
January 2021

Inflammatory Cells in Diffuse Large B Cell Lymphoma.

J Clin Med 2020 Jul 28;9(8). Epub 2020 Jul 28.

Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, 70124 Bari, Italy.

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells.
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http://dx.doi.org/10.3390/jcm9082418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463675PMC
July 2020

The FGF/FGFR System in the Physiopathology of the Prostate Gland.

Physiol Rev 2020 Jul 30. Epub 2020 Jul 30.

Department of Molecular and Translational Medicine, University of Brescia, Italy.

Fibroblast Growth Factors (FGFs) are a family of proteins possessing paracrine, autocrine or endocrine functions in a variety of biological processes, including embryonic development, angiogenesis, tissue homeostasis, wound repair, and cancer. Canonical FGFs bind and activate tyrosine kinase FGF receptors (FGFRs), triggering intracellular signaling cascades that mediate their biological activity. Experimental evidence indicates that FGFs play a complex role in the physiopathology of the prostate gland that ranges from essential functions during embryonic development to modulation of neoplastic transformation. The use of ligand- and receptor-deleted mouse models has highlighted the requirement for FGF signaling in the normal development of the prostate gland. In adult prostate, the maintenance of a functional FGF/FGFR signaling axis is critical for organ homeostasis and function, as its disruption leads to prostate hyperplasia and may contribute to cancer progression and metastatic dissemination. Dissection of the molecular landscape modulated by the FGF family will facilitate ongoing translational efforts directed toward prostate cancer therapy.
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http://dx.doi.org/10.1152/physrev.00005.2020DOI Listing
July 2020

New Insights into Diffuse Large B-Cell Lymphoma Pathobiology.

Cancers (Basel) 2020 Jul 11;12(7). Epub 2020 Jul 11.

Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, 70124 Bari, Italy.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL), accounting for about 40% of all cases of NHL. Analysis of the tumor microenvironment is an important aspect of the assessment of the progression of DLBCL. In this review article, we analyzed the role of different cellular components of the tumor microenvironment, including mast cells, macrophages, and lymphocytes, in the tumor progression of DLBCL. We examined several approaches to confront the available pieces of evidence, whereby three key points emerged. DLBCL is a disease of malignant B cells spreading and accumulating both at nodal and at extranodal sites. In patients with both nodal and extranodal lesions, the subsequent induction of a cancer-friendly environment appears pivotal. The DLBCL cell interaction with mature stromal cells and vessels confers tumor protection and inhibition of immune response while delivering nutrients and oxygen supply. Single cells may also reside and survive in protected niches in the nodal and extranodal sites as a source for residual disease and relapse. This review aims to molecularly and functionally recapitulate the DLBCL-milieu crosstalk, to relate niche and pathological angiogenic constitution and interaction factors to DLBCL progression.
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http://dx.doi.org/10.3390/cancers12071869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408689PMC
July 2020

Lorenzo Bonomo, un clinico che amava la ricerca e un ricercatore che amava la clinica.

Authors:
Domenico Ribatti

Recenti Prog Med 2020 Jun;111(6):379-380

Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università di Bari.

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http://dx.doi.org/10.1701/3394.33761DOI Listing
June 2020

A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche.

J Oncol 2020 18;2020:6820241. Epub 2020 May 18.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.

There is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients' chances of survival. Nevertheless, certain patients' subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological signature of aggressive disease and dismal therapeutic response can promote a dynamic, comprehensive strategic approach, better tailoring the clinical management of high-risk profiles and refractoriness to therapy and taking into account the role played by the MM milieu. By means of an extensive literature search, we have reviewed the state-of-the-art pathophysiological insights obtained from translational investigations of the MM-bone marrow microenvironment. A good knowledge of the MM niche pathophysiological dissection is crucial to tailor personalized approaches in a bench-bedside fashion. The discussion in this review pinpoints two main aspects that appear fundamental in order to gain novel and definitive results from the biology of MM. A systematic knowledge of the plasma cell disorder, along with greater efforts to face the unmet needs present in MM evolution, promises to open a new therapeutic window looking out onto the plethora of scientific evidence about the myeloma and the bystander cells.
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http://dx.doi.org/10.1155/2020/6820241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251466PMC
May 2020

The use of the chick embryo CAM assay in the study of angiogenic activiy of biomaterials.

Microvasc Res 2020 09 5;131:104026. Epub 2020 Jun 5.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.

The chick embryo chorioallantoic membrane (CAM) is a highly vascularized extraembryonic membrane, which carries out several functions during embryonic development, including exchange of respiratory gases, calcium transport from the eggshell, acid-base homeostasis in the embryo, and ion and water reabsorption from the allantoic fluid. Due to its easy accessibility, affordability and given that it constitutes an immunodeficient environment, CAM has been used as an experimental model for >50 years and in particular it has been broadly used to study angiogenesis and anti-angiogenesis. This review article describes the use of the CAM assay as a valuable assay to test angiogenic activity of biomaterials in vivo before they are further investigated in animal models. In this context, the use of CAM has become an integral part of the biocompatibility testing process for developing potential biomaterials.
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http://dx.doi.org/10.1016/j.mvr.2020.104026DOI Listing
September 2020