Gaetana A Tonti's research while affiliated with Università degli Studi di Urbino "Carlo Bo" and other places

Publications (36)

Article
Metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs), produced in the brain by cells of non-neural and neural origin, including neural progenitors (NPs), are emerging as regulators of nervous system development and adult brain functions. In the present study we explored whether MMP-2, MMP-9 and TIMP-2, abundantly produced in the brain,...
Article
Aluminium is not a physiological component of the breast but has been measured recently in human breast tissues and breast cyst fluids at levels above those found in blood serum or milk. Since the presence of aluminium can lead to iron dyshomeostasis, levels of aluminium and iron-binding proteins (ferritin, transferrin) were measured in nipple aspi...
Article
Oxygen is a fundamental element for all living organisms, and modifications in its concentration influence several physiological and pathological events such as embryogenesis, development and also aging. Regulation of oxygen levels is an important factor in neural stem cell biology (e.g. differentiation, growth and the capacity to generate more dif...
Article
Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess metabolic activity in breast microenvironment. Premalignant and malignant cell alterations may produce biochemical signals that deliver inflammatory...
Article
To investigate the effects of sulfur-based spa therapies on oxidation, inflammation and cartilage degradation biomarkers in osteoarthritis (OA) patients. Analyses were performed before therapy (T0), after therapy (T1) and 1 month after its suspension (T2), in OA subjects undergoing mud bath treatments in combination (group A) or not (group B) with...
Article
Analysis of nipple aspirate fluid (NAF) allows the noninvasive identification of both cellular and biomolecular markers of human breast cancer, the most common female malignancy in developed countries. Cytosolic superoxide dismutase (SOD-1) represents a detoxifying enzyme able to regulate the balance between oncogenic and oncosuppressor reactive ox...
Article
Breast cancer, a complex and multifactorial disease, is the most commonly diagnosed malignancy affecting women. Methods currently available for breast cancer detection have well-described limitations; in this respect, the intraductal approaches directly assess the microenvironment of the breast. Nipple aspirate fluid (NAF) can be noninvasively obta...
Article
Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors), cholesterol-lowering agents widely prescribed for cardiovascular health, have been shown to exert several pleiotropic effects. Although some studies reported that statins have no effects on malignancies of any kind, results of several epidemiologic and in vitro studies highlighte...
Article
Protein and proteomic high-throughput technologies provide the polypeptide signatures of nipple aspirate fluid (NAF), a breast secretion collected noninvasively from healthy individuals and cancer patients. As breast cancer develops from ductal-lobular epithelium, the analysis of NAF (mirroring the ductal-lobular microenvironment) is a useful tool...
Article
Full-text available
Matrix metalloproteinases (MMP) constitute a family of more than 25 enzymes which process a large number of pericellular substrates. Even though initially reported to have an ability to degrade almost all of the extracellular components, MMP are now known to play roles which are not limited to the breakdown of extracellular barriers. In fact, MMPs...
Article
Full-text available
Protein carbonyl levels are the most frequently used biomarker of protein oxidation in several human diseases, including cancer. Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium from which nipple aspirate fluid can be collected and analysed to assess tissue metabolic activity. Our aims were to pe...
Article
Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts is involved in the etiology of gross breast cyst formation, it might be expected that aluminium would be at elevated levels in human breast cyst fluid (B...
Article
Protein and proteomic high-throughput technologies provide the polypeptide signatures of nipple aspirate fluid (NAF), a breast secretion collected noninvasively from healthy individuals and cancer patients. As breast cancer develops from ductal-lobular epithelium, the analysis of NAF (mirroring the ductal-lobular microenvironment) is a useful tool...
Article
Full-text available
Background : Protein carbonyl levels are the most frequently used biomarker of protein oxidation in several human diseases, including cancer. Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium from which nipple aspirate fluid can be collected and analysed to assess tissue metabolic activity. Our ai...
Article
Blood sampling/handling alters matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) expression. The aim of this study is to evaluate the effects of high molecular weight heparin on MMP and TIMP expression in blood. We analyzed by gelatin zymography and ELISA assays the effects of different heparin salts, dose- and time...
Article
Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess breast metabolic activity. P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer...
Article
The expression of erythropoietin (Epo) and the Epo receptor (EpoR) has been detected in healthy tissue as well as in a variety of human cancers, including breast. Functional Epo/EpoR signaling in cancer cells, which contributes to disease initiation/progression, is not completely straightforward and is difficult to reconcile with the clinical pract...
Article
The aetiology of breast cancer is complex and multifactorial, and may include diet and xenobiotic compounds. A change in diet affects nutrient levels in blood, but to what extent diet can affect micronutrient concentrations in the breast is not yet well established. Breast nipple aspirate fluids (NAF) can be non-invasively obtained from the breast...
Article
Matrix metalloproteinases (MMPs) are promising diagnostic tools, and blood sampling/handling alters MMP concentrations between plasma and serum and between serum with and without clot activators. To explain the higher MMP-9 expression in serum collected with clot accelerators relative to serum with no additives and to plasma, we analyzed the effect...
Article
Bone marrow-derived mesenchymal stem cells are a multipotent adult cellular population endowed with broad differentiation potential. Their regeneration capability, ease to undergo gene modifications, and immuno-suppressive capacity makes them optimal tools for tissue engineering, gene- and immuno-therapy. Due to the ever-increasing number of studie...
Article
Full-text available
Erythropoietin (Epo) is an important regulator of erythropoiesis, and controls proliferation and differentiation of both erythroid and non-erythroid tissues. Epo is actively synthesized by breast cells during lactation, and also plays a role in breast tissues promoting hypoxia-induced cancer initiation. Our aims are to perform an exploratory invest...
Article
Whether serum or plasma is the best specimen for determination of matrix metalloproteinases (MMPs) is a matter of debate, as are the influences of sample collection and processing on MMP concentrations (1)(2)(3). MMP-2 concentrations do not differ significantly in plasma and serum, whereas MMP-9 concentrations are significantly higher in serum than...
Article
The matrix metalloproteinases (MMPs), responsible for the degradation of extracellular matrix (ECM) proteins, may regulate brain cellular functions. Choline acetyltransferase (ChAT) transfected murine neuroblastoma cell line N18TG2, that synthesize acetylcholine and show enhancement of several neurospecific markers (i.e., sinapsin I, voltage gated...
Article
Arachidonic acid, a bioactive molecule metabolized into prostaglandins and leukotrienes, contributes to cellular proliferation and tumor progression. Group IIa secretory phospholipase A2 (sPLA2-IIa) can facilitate arachidonate release from cellular phospholipids, suggesting its involvement in tumor evolution. Analysis of breast nipple aspirate flui...
Article
The choice of an optimal strategy of stem cell culture is at the moment an impossible task, and the elaboration of a culture medium adapted to the production of embryonic and adult mesenchymal stem cells for the clinical application of cell therapy remains a crucial matter. To make an informed choice, it is crucial to not underestimate the theoreti...
Article
The role and function of dentin matrix metalloproteinases (MMPs) are not well-understood, but they may play a key role in dentinal caries and the degradation of resin-bonded dentin matrices. To test the null hypothesis that MMP-9 is not found in dentin matrix, we used gelatin zymography to extract and isolate all molecular forms of gelatinolytic MM...
Article
Breast cancer (BC), a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess breast metabolic activity. Whether lipid peroxidation in the mammary gland promotes or prevents tumorigenesis is unclear. Malondialdehyde (MDA)...
Article
For more than one and a half century the cystic disease of the breast has been recognized as the most frequent female benign breast lesion. Although some conundrums and controversies exist about the relation between gross cysts and breast cancer, recent evidence suggests that the multidisciplinary study of gross cystic breast disease (GCBD) may be...
Article
Matrix metalloproteinases (MMPs), known as matrixins, are Ca- and Zn-dependent endoproteinases involved in a wide variety of developmental and disease-associated processes, proving to be crucial protagonists in many physiological and pathological mechanisms. The ability of MMPs to alter, by limited proteolysis and through the fine control of tissue...
Article
Matrix metalloproteinases (MMPs), also designated as matrixins, play a central role in many biological processes and are involved both in physiologic cellular processes and in pathologic situations such as tumor growth, invasion and metastasis. For more than 30 years MMPs have been considered as promising targets for cancer therapy and a number of...
Article
It is more and more evident that the matrix metalloproteinase (MMP) system is not a characteristicfeature of vertebrate animals only, as it can also be found in many invertebrate organisms. Thisendopeptidase family has been widely studied since its first member was described 40 years agoduring metamorphosis in tadpole tails. Many researches have be...

Citations

... The work of Mannello et al. (Figure S2) started with publications in the beginning of the 21st century and mostly focused on the biochemical constituents of nipple aspirate such as P-cadherin [93], proteins involved in the of lipid peroxidation and oxidative stress [94][95][96], C-reactive protein [97], and aluminum [98][99][100]. Methodologically, for these investigations, Mannello et al. usually compared NAF from cohorts of healthy women with cohorts of women with breast cancer; comparing biomarker concentrations between NAF, plasma, and serum. ...
... Most of his studies were observational, but he also performed an interventional study by investigating the levels of urokinase-type plasminogen activator (uPa) in NAF after oral administration of colecoxib, a non-steroidal anti-inflammatory drug [101]. He also wrote four reviews summarizing current knowledge about proteins, hormones and aluminum detected in NAF of breast cancer patients compared to healthy controls [47,[102][103][104]. His latest publication was a comment reflecting on the potential of investigating biomarkers in NAF [105]. ...
... It has been shown that the physiological expression of FUS seems to be reduced during differentiation of cortical neural progenitor cells by miR-141 [41]. Upon growth factor depletion and in the presence of DAPT (see Material and Methods), a gamma secretase inhibitor affecting Notch signaling activation, NSPCs undergo differentiation into a cell population enriched in neurons [20,42,43]. ...
... To reach a confluence of 50% up to 80% in 24 h up to 72 h, cells were seeded in an appropriate concentration. To reduce analytical interference and avoid an artificial increase of possible effects of our treatment through stimulation of cell proliferation (19)(20)(21), medium was exchanged for the experiments by serum-reduced cell culture medium (2% FBS) including 10 µl of various palbociclib concentrations. Previously, we checked if serum starvation influences our cell death analysis (data shown in Supplementary Figure S1). ...
... Indeed, in a composite study of published data on NAF cell content, cellularity or proliferative epithelial disease was observed to be an independent risk determinant for breast cancer development [84]. This reflects the increased exfoliation of epithelial cells lining the ducts and lobules as they proliferate through hyperplasia, in situ carcinoma and invasive carcinoma with disease progression [85]. The released cells not only increase in number but also change in appearance, exhibiting morphological differences (irregularly shaped nuclei, rough endoplasmic cisternae and well-developed Golgi complexes associated with nucleic acid and protein synthesis) [86]. ...
... It is well known that microenvironment is essential for cancer progression. At last decades, there were many successful attempts to create the molecular profile of tumor microenvironment [1][2][3][4][5][6][7]. ...
... However, the optimal concentration and duration of low O 2 tension to induce or maintain pluripotency have not yet been defined. Low O 2 tension has been used in in vitro microenvironments to support several stem cell types: 0-5% O 2 for hematopoietic stem cells [5]; 2% for adipose stem cells [9], 1-5% for neural stem cells (NSCs) [10], 3% during 7 days for human cord blood cells [11], and 2% for MSCs [12]. Recent studies have focused on searching for the in vitro factor combination necessary to control the proliferation of stem cells that would enable them to remain viable and undifferentiated [13] and to prevent apoptosis, senescence, or gene mutations. ...
... The work of Mannello et al. (Figure S2) started with publications in the beginning of the 21st century and mostly focused on the biochemical constituents of nipple aspirate such as P-cadherin [93], proteins involved in the of lipid peroxidation and oxidative stress [94][95][96], C-reactive protein [97], and aluminum [98][99][100]. Methodologically, for these investigations, Mannello et al. usually compared NAF from cohorts of healthy women with cohorts of women with breast cancer; comparing biomarker concentrations between NAF, plasma, and serum. ...
... Breast cancer usually occurs due to cell multiplication under the influence of estrogen and infringing on other tissue which spreads to other regions of the body [11,12]. C-reactive protein (CRP), which are acutephase proteins, are considered a extrapolative marker of inflammation and their serum levels are elevated in patients with breast carcinomas [13]. Clear evidence has been found regarding the involvement of soluble and cell-bound iron-binding protein Ferritin (FTN) and Transferrin (TRF) in breast inflammation and cancer [14]. ...
... NAF is in theory present in every breast. The success percentages of obtaining NAF are very high (77-95%) [17][18][19][20]. Unsuccessful aspiration can be explained by factors like the collection procedure, the number and duration of attempts, use of oxytocin to release NAF and whether the existing NAF is able to reach the nipple. ...