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Article ; Online: Canine mortality in Umbria Region (Central Italy): a population-based analysis.

Dettori, Annalisa / Ferroni, Laura / Felici, Andrea / Scoccia, Eleonora / Maresca, Carmen

2023 Volume 47, Issue 4, Page(s) 2301–2306

Abstract: Companion dogs may be valuable sentinels to better understand the environmental determinants of morbidity and mortality in humans. This study aimed to assess the dog population and mortality in Umbria Region. The source of data was the local Canine ... ...

Abstract	Companion dogs may be valuable sentinels to better understand the environmental determinants of morbidity and mortality in humans. This study aimed to assess the dog population and mortality in Umbria Region. The source of data was the local Canine Registry. Attribute-specific crude mortality rates by sex, age, and breed were produced on a five-year basis (2014-2018). The human ICD-10 was employed to code the causes of deaths. Over 2014-2018, an annual average population of 226,875 specimens and a total of 46,743 deaths were estimated. Mortality rate was higher in young males than in young females. A specific cause of death was reported for 5,209 dogs; the 62.8 per cent (95%CI = 61.4-64.1) was due to external causes. Neoplasms were the fourth cause of death. Differences in mortality between sexes were consistent with human ones. The death registration procedure needs improvement by a systematic coding of the causes. An adjustment of the human ICD could address the lack of a coding system until the introduction of international standards for animals.
MeSH term(s)	Male ; Female ; Humans ; Dogs ; Animals ; Neoplasms/veterinary ; Neoplasms/epidemiology ; Italy/epidemiology ; Dog Diseases
Language	English
Publishing date	2023-06-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	406735-6
ISSN	1573-7446 ; 0165-7380
ISSN (online)	1573-7446
ISSN	0165-7380
DOI	10.1007/s11259-023-10146-6
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Article ; Online: Canine prostatic serum esterase and strain and 2D‐shear wave sonoelastography for evaluation of normal prostate in dogs: Preliminary results

Bucci, Roberta / Del Signore, Francesca / Vignoli, Massimo / Felici, Andrea / Russo, Marco / Maresca, Carmen / Carluccio, Augusto

Reproduction in Domestic Animals. 2023 Sept., v. 58, no. 9 p.1311-1319

2023

Abstract: Canine prostatic serum esterase (CPSE) is considered a useful tool to identify prostate disorders in dogs, with increasing interest in ultrasound (US)‐based sonoelastography to non‐invasively detect prostate disorders. Since no report is available about ... ...

Abstract	Canine prostatic serum esterase (CPSE) is considered a useful tool to identify prostate disorders in dogs, with increasing interest in ultrasound (US)‐based sonoelastography to non‐invasively detect prostate disorders. Since no report is available about a possible correlation between these diagnostic tools, we aimed to investigate a possible correlation between strain elastography (SE) and 2D‐shear wave elastography (SWE) and CPSE. Twenty‐one dogs were included and, on each animal, CPSE was evaluated followed by a complete US examination and SE and 2D‐SWE application. Healthy dogs were identified based on the CPSE results. All the dogs included were characterized by normal CPSE values (<52.3 ng/mL) and normal US prostate appearance. The prostate was characterized by intermediate stiffness with SE (pattern III – 84.7% for the left lobe and 79.27% for the right lobe) and softer than the abdominal wall (SR 0.6 for the left lobe and 0.56 for the right lobe), with low values for both m/s and kilopascals (kPa) for 2D‐SWE, pointing that the healthy tissue is not hard. 2D‐SWE results were, respectively, 13.51 ± 5.55 kPa and 2.31 ± 0.42 m/s for the left lobe and 18.05 ± 6.47 kPa and 2.39 ± 0.43 m/s for the right lobe. The significant difference between the right and left measurements expressed with kPa, not evidenced with m/s, can be considered indicative of m/s as the most reliable measurement to be considered regarding the prostate parenchyma. Even though no linear correlation was detected between CPSE and elastography values, these preliminary results evidence that the healthy prostates were characterized by a similar elastographic pattern, thus pointing that these techniques can be potentially useful to be applied in case of prostatic disorders to improve the accuracy of the final diagnosis in a non‐invasive way.
Keywords	blood serum ; dogs ; elasticity imaging techniques ; esterases ; reproduction ; ultrasonics
Language	English
Dates of publication	2023-09
Size	p. 1311-1319.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	1015187-4
ISSN	1439-0531 ; 0936-6768
ISSN (online)	1439-0531
ISSN	0936-6768
DOI	10.1111/rda.14435
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Article ; Online: Canine prostatic serum esterase and strain and 2D-shear wave sonoelastography for evaluation of normal prostate in dogs: Preliminary results.

Bucci, Roberta / Del Signore, Francesca / Vignoli, Massimo / Felici, Andrea / Russo, Marco / Maresca, Carmen / Carluccio, Augusto

Reproduction in domestic animals = Zuchthygiene

2023 Volume 58, Issue 9, Page(s) 1311–1319

Abstract: Canine prostatic serum esterase (CPSE) is considered a useful tool to identify prostate disorders in dogs, with increasing interest in ultrasound (US)-based sonoelastography to non-invasively detect prostate disorders. Since no report is available about ... ...

Abstract	Canine prostatic serum esterase (CPSE) is considered a useful tool to identify prostate disorders in dogs, with increasing interest in ultrasound (US)-based sonoelastography to non-invasively detect prostate disorders. Since no report is available about a possible correlation between these diagnostic tools, we aimed to investigate a possible correlation between strain elastography (SE) and 2D-shear wave elastography (SWE) and CPSE. Twenty-one dogs were included and, on each animal, CPSE was evaluated followed by a complete US examination and SE and 2D-SWE application. Healthy dogs were identified based on the CPSE results. All the dogs included were characterized by normal CPSE values (<52.3 ng/mL) and normal US prostate appearance. The prostate was characterized by intermediate stiffness with SE (pattern III - 84.7% for the left lobe and 79.27% for the right lobe) and softer than the abdominal wall (SR 0.6 for the left lobe and 0.56 for the right lobe), with low values for both m/s and kilopascals (kPa) for 2D-SWE, pointing that the healthy tissue is not hard. 2D-SWE results were, respectively, 13.51 ± 5.55 kPa and 2.31 ± 0.42 m/s for the left lobe and 18.05 ± 6.47 kPa and 2.39 ± 0.43 m/s for the right lobe. The significant difference between the right and left measurements expressed with kPa, not evidenced with m/s, can be considered indicative of m/s as the most reliable measurement to be considered regarding the prostate parenchyma. Even though no linear correlation was detected between CPSE and elastography values, these preliminary results evidence that the healthy prostates were characterized by a similar elastographic pattern, thus pointing that these techniques can be potentially useful to be applied in case of prostatic disorders to improve the accuracy of the final diagnosis in a non-invasive way.
MeSH term(s)	Male ; Dogs ; Animals ; Prostate/diagnostic imaging ; Elasticity Imaging Techniques/veterinary ; Elasticity Imaging Techniques/methods ; Esterases ; Ultrasonography/veterinary ; Prostatic Diseases/veterinary ; Dog Diseases/diagnosis
Chemical Substances	Esterases (EC 3.1.-)
Language	English
Publishing date	2023-07-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1015187-4
ISSN	1439-0531 ; 0936-6768
ISSN (online)	1439-0531
ISSN	0936-6768
DOI	10.1111/rda.14435
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Article ; Online: Preliminary Investigation about

Cruciani, Deborah / Crotti, Silvia / Maresca, Carmen / Pecorelli, Ivan / Verdini, Emanuela / Rodolfi, Marinella / Scoccia, Eleonora / Spina, Sara / Valentini, Andrea / Agnetti, Francesco

Journal of fungi (Basel, Switzerland)

2022 Volume 8, Issue 11

Abstract: Among the fungi responsible for deep mycosis, the ... ...

Abstract	Among the fungi responsible for deep mycosis, the genus
Language	English
Publishing date	2022-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof8111213
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Article ; Online: Drug repositioning strategy for the identification of novel telomere-damaging agents: A role for NAMPT inhibitors.

Rizzo, Angela / Maresca, Carmen / D'Angelo, Carmen / Porru, Manuela / Di Vito, Serena / Salvati, Erica / Sacconi, Andrea / Berardinelli, Francesco / Sgura, Antonella / Kuznetsov, Sergey / Potdar, Swapnil / Hassinen, Antti / Stoppacciaro, Antonella / Zizza, Pasquale / Biroccio, Annamaria

Aging cell

2023 Volume 22, Issue 11, Page(s) e13944

Abstract: Drug repositioning strategy represents a valid tool to accelerate the pharmacological development through the identification of new applications for already existing compounds. In this view, we aimed at discovering molecules able to trigger telomere- ... ...

Abstract	Drug repositioning strategy represents a valid tool to accelerate the pharmacological development through the identification of new applications for already existing compounds. In this view, we aimed at discovering molecules able to trigger telomere-localized DNA damage and tumor cell death. By applying an automated high-content spinning-disk microscopy, we performed a screening aimed at identifying, on a library of 527 drugs, molecules able to negatively affect the expression of TRF2, a key protein in telomere maintenance. FK866, resulting from the screening as the best candidate hit, was then validated at biochemical and molecular levels and the mechanism underlying its activity in telomere deprotection was elucidated both in vitro and in vivo. The results of this study allow us to discover a novel role of FK866 in promoting, through the production of reactive oxygen species, telomere loss and deprotection, two events leading to an accumulation of DNA damage and tumor cell death. The ability of FK866 to induce telomere damage and apoptosis was also demonstrated in advanced preclinical models evidencing the antitumoral activity of FK866 in triple-negative breast cancer-a particularly aggressive breast cancer subtype still orphan of targeted therapies and characterized by high expression levels of both NAMPT and TRF2. Overall, our findings pave the way to the development of novel anticancer strategies to counteract triple-negative breast cancer, based on the use of telomere deprotecting agents, including NAMPT inhibitors, that would rapidly progress from bench to bedside.
MeSH term(s)	Humans ; Triple Negative Breast Neoplasms ; Drug Repositioning ; Cell Death ; Apoptosis ; Telomere ; Telomeric Repeat Binding Protein 2/genetics ; Cell Line, Tumor
Chemical Substances	Telomeric Repeat Binding Protein 2
Language	English
Publishing date	2023-10-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13944
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Article: G-quadruplex Stabilization Fuels the ALT Pathway in ALT-positive Osteosarcoma Cells

Amato, Roberta / Valenzuela, Martina / Berardinelli, Francesco / Salvati, Erica / Maresca, Carmen / Leone, Stefano / Antoccia, Antonio / Sgura, Antonella

Genes. 2020 Mar. 13, v. 11, no. 3

2020

Abstract: Most human tumors maintain telomere lengths by telomerase, whereas a portion of them (10–15%) uses a mechanism named alternative lengthening of telomeres (ALT). The telomeric G-quadruplex (G4) ligand RHPS4 is known for its potent antiproliferative effect, ...

Abstract	Most human tumors maintain telomere lengths by telomerase, whereas a portion of them (10–15%) uses a mechanism named alternative lengthening of telomeres (ALT). The telomeric G-quadruplex (G4) ligand RHPS4 is known for its potent antiproliferative effect, as shown in telomerase-positive cancer models. Moreover, RHPS4 is also able to reduce cell proliferation in ALT cells, although the influence of G4 stabilization on the ALT mechanism has so far been poorly investigated. Here we show that sensitivity to RHPS4 is comparable in ALT-positive (U2OS; SAOS-2) and telomerase-positive (HOS) osteosarcoma cell lines, unlinking the telomere maintenance mechanism and RHPS4 responsiveness. To investigate the impact of G4 stabilization on ALT, the cardinal ALT hallmarks were analyzed. A significant induction of telomeric doublets, telomeric clusterized DNA damage, ALT-associated Promyelocytic Leukaemia-bodies (APBs), telomere sister chromatid exchanges (T-SCE) and c-circles was found exclusively in RHPS4-treated ALT cells. We surmise that RHPS4 affects ALT mechanisms through the induction of replicative stress that in turn is converted in DNA damage at telomeres, fueling recombination. In conclusion, our work indicates that RHPS4-induced telomeric DNA damage promotes overactivation of telomeric recombination in ALT cells, opening new questions on the therapeutic employment of G4 ligands in the treatment of ALT positive tumors.
Keywords	DNA damage ; cell lines ; cell proliferation ; chromatids ; human diseases ; ligands ; models ; neoplasm cells ; osteosarcoma ; telomerase ; telomeres ; therapeutics
Language	English
Dates of publication	2020-0313
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes11030304
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Article: Modifications of H3K4 methylation levels are associated with DNA hypermethylation in acute myeloid leukemia

Scalea, Stefania / Maresca, Carmen / Catalanotto, Caterina / Marino, Rachele / Cogoni, Carlo / Reale, Anna / Zampieri, Michele / Zardo, Giuseppe

FEBS journal. 2020 Mar., v. 287, no. 6

2020

Abstract: The ‘instructive model’ of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also ...

Abstract	The ‘instructive model’ of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also link methylation of CpG islands to the methylation status of H3K4, where H3K4me3 is inversely correlated with DNA methylation. To provide insight into these conflicting findings, we generated DNA methylation profiles for acute myeloid leukemia samples from patients and leukemic cell lines and integrated them with publicly available ChIp‐seq data, containing H3K4me3 and H3K27me3 CpG island occupation in hESC, or hematopoietic stem or progenitor cells (hHSC/MPP). Hypermethylated CpG islands in AML samples displayed H3K27me3 enrichments in hESC and hHSC/MPP; however, ChIp analysis of specific hypermethylated CpG islands revealed a significant reduction in H3K4me3 signal with a concomitant increase in H3K4me0 levels as opposed to a nonsignificant increase in H3K27me3 marks. The integration of AML DNA methylation profiles with the ChIp‐seq data in hESC and hHSC/MPP also led to the identification of Iroquois homeobox 2 (IRX2) as a previously unknown factor promoting differentiation of leukemic cells. Our results indicate that in contrast to the ‘instructive model’, H3K4me3 levels are strongly associated with DNA methylation patterns in AML and have a role in the regulation of critical genes, such as the putative tumor suppressor IRX2.
Keywords	DNA hypermethylation ; chromatin ; chromatin immunoprecipitation ; genomic islands ; humans ; myeloid leukemia ; occupations
Language	English
Dates of publication	2020-03
Size	p. 1155-1175.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	NAL-AP-2-clean ; JOURNAL ARTICLE
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15086
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Article ; Online: BRCA2 Deletion Induces Alternative Lengthening of Telomeres in Telomerase Positive Colon Cancer Cells.

Pompili, Luca / Maresca, Carmen / Dello Stritto, Angela / Biroccio, Annamaria / Salvati, Erica

Genes

2019 Volume 10, Issue 9

Abstract: BRCA1/2 are tumor suppressor genes controlling genomic stability also at telomeric and subtelomeric loci. Their mutation confers a predisposition to different human cancers but also sensitivity to antitumor drugs including poly(ADP-ribose) polymerase ( ... ...

Abstract	BRCA1/2 are tumor suppressor genes controlling genomic stability also at telomeric and subtelomeric loci. Their mutation confers a predisposition to different human cancers but also sensitivity to antitumor drugs including poly(ADP-ribose) polymerase (PARP) inhibitors and G-quadruplex stabilizers. Here we demonstrate that BRCA2 deletion triggers TERRA hyperexpression and alternative lengthening mechanisms (ALT) in colon cancer cells in presence of telomerase activity. This finding opens the question if cancer patients bearing BRCA2 germline or sporadic mutation are suitable for anti-telomerase therapies, or how ALT activation could influence the short or long-term response to anti-PARP inhibitors or anti-G-quadruplex therapies.
MeSH term(s)	BRCA1 Protein/genetics ; Colonic Neoplasms/genetics ; Gene Deletion ; HCT116 Cells ; Humans ; Telomere Homeostasis
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human
Language	English
Publishing date	2019-09-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes10090697
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Article ; Online: Serum protein concentrations and protein fractions in clinically healthy Italian Heavy Draft Horses using agarose gel electrophoresis.

Miglio, Arianna / Morelli, Chiara / Maresca, Carmen / Felici, Andrea / Di Gianbattista, Andrea / Antognoni, Maria Teresa

Veterinary clinical pathology

2019 Volume 48, Issue 4, Page(s) 677–682

Abstract: Background: Serum protein electrophoresis (SPE) reference intervals (RIs) have been evaluated in different horses, but no specific values are shown for equine breeds as previously described in other species (dogs, cats), and no studies have been ... ...

Abstract	Background: Serum protein electrophoresis (SPE) reference intervals (RIs) have been evaluated in different horses, but no specific values are shown for equine breeds as previously described in other species (dogs, cats), and no studies have been performed on SPE in draft horses. Objectives: This study aimed to determine RIs for SPE in heavy draft horses (Italian Heavy Draft Horse-IHDH) living in central Italy. A comparison between different physiologic states (pregnancy and no pregnancy) and ages (foals and adults) was executed. Materials and methods: Blood samples were collected from 215 apparently healthy horses (mares, stallions, and foals). SPE (total proteins, albumin, α1-, α2-, β1-, β2-, and γ-fractions, A/G) was evaluated in the Veterinary Teaching Hospital of the University of Perugia. RIs were determined using well-described, modern analytical and statistical methods. The normality of distributions was assessed using the Anderson-Darling test. Differences between subgroups were evaluated using the Mann-Whitney U test. A P < .05 was considered statistically significant for all analyses. Results: Our results showed that IHDHs had increases in TPs and the α2-, β1-, β2-, and γ-fractions, and decreases in albumin, α1-globulins, and A/G ratios compared with the data reported in other horses. We also found that foals had significantly higher α1-globulins and significantly lower albumin concentrations, and A/G ratios compared with those of the adult horses. Conclusions: In the present study, SPE RIs using agarose gels have been determined for the first time in a large number of draft horses (represented by IHDH). The obtained results provide a basis for the further investigation of equine breeds with natural breeding, and the impact of age and physiologic states on SPE.
MeSH term(s)	Animals ; Blood Proteins/analysis ; Electrophoresis, Agar Gel/veterinary ; Female ; Horses/blood ; Male ; Pregnancy ; Reference Values
Chemical Substances	Blood Proteins
Language	English
Publishing date	2019-11-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2114702-4
ISSN	1939-165X ; 0275-6382
ISSN (online)	1939-165X
ISSN	0275-6382
DOI	10.1111/vcp.12793
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Article ; Online: TRF2 as novel marker of tumor response to taxane-based therapy: from mechanistic insight to clinical implication.

Iachettini, Sara / Terrenato, Irene / Porru, Manuela / Di Vito, Serena / Rizzo, Angela / D'Angelo, Carmen / Petti, Eleonora / Dinami, Roberto / Maresca, Carmen / Di Benedetto, Anna / Palange, Aldo / Mulè, Antonino / Santoro, Angela / Palazzo, Antonella / Fuso, Paola / Stoppacciaro, Antonella / Vici, Patrizia / Filomeno, Lorena / Di Lisa, Francesca Sofia /

Arcuri, Teresa / Krasniqi, Eriseld / Fabi, Alessandra / Biroccio, Annamaria / Zizza, Pasquale

Journal of experimental & clinical cancer research : CR

2024 Volume 43, Issue 1, Page(s) 75

Abstract: Background: Breast Cancer (BC) can be classified, due to its heterogeneity, into multiple subtypes that differ for prognosis and clinical management. Notably, triple negative breast cancer (TNBC) - the most aggressive BC form - is refractory to ... ...

Abstract	Background: Breast Cancer (BC) can be classified, due to its heterogeneity, into multiple subtypes that differ for prognosis and clinical management. Notably, triple negative breast cancer (TNBC) - the most aggressive BC form - is refractory to endocrine and most of the target therapies. In this view, taxane-based therapy still represents the elective strategy for the treatment of this tumor. However, due variability in patients' response, management of TNBC still represents an unmet medical need. Telomeric Binding Factor 2 (TRF2), a key regulator of telomere integrity that is over-expressed in several tumors, including TNBC, has been recently found to plays a role in regulating autophagy, a degradative process that is involved in drug detoxification. Based on these considerations, we pointed, here, at investigating if TRF2, regulating autophagy, can affect tumor sensitivity to therapy. Methods: Human TNBC cell lines, over-expressing or not TRF2, were subjected to treatment with different taxanes and drug efficacy was tested in terms of autophagic response and cell proliferation. Autophagy was evaluated first biochemically, by measuring the levels of LC3, and then by immunofluorescence analysis of LC3-puncta positive cells. Concerning the proliferation, cells were subjected to colony formation assays associated with western blot and FACS analyses. The obtained results were then confirmed also in mouse models. Finally, the clinical relevance of our findings was established by retrospective analysis on a cohort of TNBC patients subjected to taxane-based neoadjuvant chemotherapy. Results: This study demonstrated that TRF2, inhibiting autophagy, is able to increase the sensitivity of TNBC cells to taxanes. The data, first obtained in in vitro models, were then recapitulated in preclinical mouse models and in a cohort of TNBC patients, definitively demonstrating that TRF2 over-expression enhances the efficacy of taxane-based neoadjuvant therapy in reducing tumor growth and its recurrence upon surgical intervention. Conclusions: Based on our finding it is possible to conclude that TRF2, already known for its role in promoting tumor formation and progression, might represents an Achilles' heel for cancer. In this view, TRF2 might be exploited as a putative biomarker to predict the response of TNBC patients to taxane-based neoadjuvant chemotherapy.
MeSH term(s)	Humans ; Animals ; Mice ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/pathology ; Retrospective Studies ; Taxoids/pharmacology ; Taxoids/therapeutic use ; Bridged-Ring Compounds/pharmacology ; Bridged-Ring Compounds/therapeutic use ; Cell Line, Tumor
Chemical Substances	taxane (1605-68-1) ; Taxoids ; Bridged-Ring Compounds
Language	English
Publishing date	2024-03-09
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-024-02998-w
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