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Ferdinando Mannello – 1st expert on this subject based on the ideXlab platform
Breast Cyst fluid heparan sulphate is distinctively n sulphated depending on apocrine or flattened typeCell Biochemistry and Function, 2015Co-Authors: Ferdinando Mannello, Francesca Maccari, Daniela Ligi, Fabio Galeotti, Martina Santi, Francesco Gatto, Robert J Linhardt, Nicola VolpiAbstract:
Breast Cyst fluid (BCF) contained in gross cists is involved with its many biomolecules in different stages of Breast Cystic development. Type I apocrine and type II flattened Cysts are classified based on biochemical, morphological and hormonal differences, and their different patterns of growth factors and active biocompounds may require different regulation. In a previous paper, hyaluronic acid in a very low content and chondroitin sulphate/dermatan sulphate were identified and characterized in BCF. In this new study, various apocrine and flattened BCFs were analyzed for HS concentration and disaccharide pattern. Apocrine HS was found specifically constituted of N-acetyl groups contrary to flattened HS richer in N-sulphate disaccharides with an overall N-acetylated/N-sulphated ratio significantly increased in apocrine compared with flattened (13.5 vs 3.7). Related to this different structural features, the charge density significantly decreased (-30%) in apocrine versus flattened BCFs. Finally, no significant differences were observed for HS amount (0.9-1.3 mu gml(-1)) between the two BCF types even if a greater content was determined for flattened samples. The specifically N-sulphated sequences in flattened BCF HS can exert biologic capacity by regulating growth factors activity. On the other hand, we cannot exclude a peculiar regulation of the activity of biomolecules in apocrine BCF by HS richer in N-acetylated disaccharides. In fact, the different patterns of growth factors and active biocompounds in the two types of Cysts may require different regulation by specific sequences in the HS backbone possessing specific structural characteristics and distinctive chemical groups.
characterization of oversulfated chondroitin sulfate rich in 4 6 o disulfated disaccharides in Breast Cyst fluids collected from human Breast gross CystsCell Biochemistry and Function, 2014Co-Authors: Ferdinando Mannello, Francesca Maccari, Daniela Ligi, Matteo Canale, Fabio Galeotti, Nicola VolpiAbstract:
Glycosaminoglycans (GAGs) from Breast Cyst fluid (BCF) of gross Cysts, subdivided into apocrine and flattened, directly collected from 27 gross-Cystic-Breast-disease (GCBD)-affected women were analysed. Heparan sulfate, not further investigated, and chondroitin sulfate were identified. This last polysaccharide, in a content of 25–27 μgml 1 BCF and having a high molecular mass (~20000–22000), was found rich in glucuronic acid (~96%–98%) and mainly sulfated in position 4 of the N-acetyl-galactosamine (~60%–64%). Moreover, the presence of ~19%–24% of uncommon 4,6-O-disulfated disaccharides CS-E inside the polysaccharide chains with a high charge density of ~1.15–1.20 was determined. No substantial differences between apocrine and flattened Cysts were observed. The current study describes the first effort to examine the yield and distribution of complex macromolecules like GAGs in BCF, and the understanding of their structure may help explain some functions associated with physiological and pathological conditions. Copyright © 2013 John Wiley & Sons, Ltd. key words—Breast Cyst fluids; glycosaminoglycan; human gross Breast Cyst disease; chondroitin sulfate; Breast cancer; dermatan sulfate list of abbreviations—BCF, Breast Cyst fluid; CS, chondroitin sulfate; DS, dermatan sulfate; GAG, glycosaminoglycan; GalNAc, Nacetyl-galactosamine; GCBD, gross Cystic Breast disease; GlcNAc, N-acetyl-glucosamine; GlcUA, glucuronic acid; IdoUA, iduronic acid; PG proteoglycan
concentration of aluminium in Breast Cyst fluids collected from women affected by gross Cystic Breast diseaseJournal of Applied Toxicology, 2009Co-Authors: Ferdinando Mannello, Gaetana A Tonti, Philippa D DarbreAbstract:
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 (BCF). Aluminium was measured by ICP-MS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human Breast milk at different stages of lactation (colostrum, intermediate, mature). The median level of aluminium in apocrine type I BCF (n:= 27, 150 mu g I-1) was significantly higher than in transuclative type II BCF (n = 21, 32 mu g I-1; P < 0.0001). By comparison, aluminium measurements gave a median concentration of 6 mu g I-1 in human serum and 25 mu g I-1 in human Breast milk, with no difference between colostrum, intermediate and mature milk. Levels of aluminium were significantly higher in both types of BCF than in human serum (P < 0.0001). However when compared with human Breast milk, aluminium levels were only significantly higher in apocrine type I BCF (P < 0.0001) and not in transudative type II BCF (P = 0.152). It remains to be identified why such high levels of aluminium were found in the apocrine type I BCF and from where the aluminium originated. However, if aluminium-based antiperspirants are found to be the source and to play any causal role in development of Breast Cysts, then it might become possible to prevent this common Breast disorder. Copyright (C) 2008 John Wiley & Sons, Ltd.
Eleftherios P Diamandis – 2nd expert on this subject based on the ideXlab platform
human glandular kallikrein in Breast milk amniotic fluid and Breast Cyst fluidClinical Chemistry, 1999Co-Authors: Angeliki Magklara, Carlos Lopezotin, Andreas Scorilas, F Vizoso, A Ruibal, Eleftherios P DiamandisAbstract:
Background: Human glandular kallikrein (hK2) belongs to the serine protease family of enzymes and has high sequence homology with prostate-specific antigen (PSA). The physiological role of hK2 has not as yet been determined, but there is evidence that it can regulate the proteolytic activity of PSA through processing and activating pro-PSA, an inactive precursor. Thus, it is conceivable that these two secreted proteins may coexist in biological fluids. Currently, hK2 is considered an androgen-regulated and prostate-specific protein. Recently, it has been demonstrated that hK2 is expressed in the Breast cancer cell line T-47D after stimulation by steroid hormones, and we reported that hK2 can be detected in a subset of Breast tumor extracts. These data suggest that hK2 may be expressed in tissues other than the prostate, such as those in which PSA has already been detected. Because hK2 is a secreted protein, it may be present in various biological fluids. Methods: We analyzed milk samples from lactating women, amniotic fluid from pregnant women, and Breast Cyst fluid from patients with gross Breast Cystic disease, using a highly sensitive and specific immunoassay for hK2. Results: hK2 was present in all three biological fluids. We suggest that the female Breast may produce hK2 and provide evidence that hK2 may have value as an additional marker for the discrimination between type I and type II Breast Cysts. Conclusions: The female Breast produces hK2 in addition to PSA. More studies are necessary to establish the role of this kallikrein in nondiseased Breast, gross Breast Cystic disease, and Breast cancer. © 1999 American Association for Clinical Chemistry
quantification of pepsinogen c and prostaglandin d synthase in Breast Cyst fluid and their potential utility for Cyst type classificationClinical Biochemistry, 1999Co-Authors: Gudrun H Borchert, Eleftherios P Diamandis, Dimitrios N Melegos, He Yu, M Giai, R Roagna, R Ponzone, L SgroAbstract:
Abstract Objective: To quantify pepsinogen C (PEPC) and prostaglandin D synthase (PGDS) in Breast Cyst fluid and examine if these two parameters can be used for Breast Cyst type classification. Design and Methods: We quantified PEPC and PGDS in 92 and 50 Breast Cyst fluids, respectively, using previously established immunofluorometric procedures. We then examined if the levels of PEPC or PGDS correlate with the type of Cyst or with other clinicopathological variables. Results: Quantitative analysis of the Breast Cyst fluids indicated that PEPC is present in all Cyst fluids at various concentrations ranging from 3 to 31,000 ng/mL. PGDS positivity was confined to 30% of the Cyst fluids. PEPC and PGDS levels were correlated with the Breast Cyst fluid cation ratio and were associated with the type of the Cyst. Increased PEPC levels in Breast Cyst fluids were significantly correlated with a ≥ 1.5 K + /Na + ratio and were associated with the secretory/apocrine type of Cyst (Type I) ( p = 0.011). Immunoreactive PGDS levels were highly correlated with a low cation ratio and were associated with the transudative/flattened type of Breast Cyst (Type II) ( p = 0.0003). A weak association was observed between PEPC levels in Breast Cyst fluid and menopausal status ( p = 0.093). No significant associations were observed for either PEPC or PGDS concentration in Breast Cyst fluid and number of Cysts, recurrence of the disease, family history of Breast cancer, number of children, abortion, and Breast feeding. Conclusions: Quantification of PEPC and PGDS in Breast Cyst fluid may be useful in the subclassification of Cyst type in patients with gross Cystic disease.
prostate specific antigen molecular forms in Breast Cyst fluid and serum of women with fibroCystic Breast diseaseJournal of Clinical Laboratory Analysis, 1999Co-Authors: Gudrun H Borchert, Eleftherios P Diamandis, He Yu, M Giai, R Roagna, R Ponzone, L Sgro, George TomlinsonAbstract:
We have analyzed matched serum and Breast Cyst fluid samples for total PSA from 148 patients with fibroCystic Breast disease. We have also determined the molecular forms of PSA (free PSA and PSA bound to α1-antichymotrypsin) in 78 Breast Cyst fluid samples. We found that total PSA can be detected in all Cyst fluids and in about 75% of female sera. The median total PSA concentration in Breast Cyst fluid (bcf) is about 30 times higher than the median in the corresponding sera. Breast Cyst fluid and serum PSA are not correlated with each other. Total serum PSA is inversely associated with patient age but the inverse association between bcf PSA and age is weak. Lower total PSA in bcf was seen in women who Breast feed, and higher bcf PSA is associated with multiple Cysts. Type I Cysts (with a high K+/Na+ ratio) tend to have higher total PSA than Type II Cysts. All but three of the fractionated Cyst fluids (75/78; 96%) had free PSA as the predominant molecular form. The most consistent finding of our study was the positive association between the Cyst fluid K+/Na+ ratio and the free to bound PSA ratio. This association was confirmed by Spearman correlation as well as by Wilcoxon and chi-square analysis. Secretory/apocrine Cysts (Type I) tend to have more total PSA and proportionally more free PSA than transudative/flattened Cysts (Type II). J. Clin. Lab. Anal. 13:75–81, 1999. © 1999 Wiley-Liss, Inc.
Giancarlo Gazzanelli – 3rd expert on this subject based on the ideXlab platform
Prostate‐specific antigen found in Type I Breast Cyst fluids is a secretory product of the apocrine cells lining Breast gross CystsBreast Cancer Research and Treatment, 1999Co-Authors: Manuela Malatesta, Ferdinando Mannello, Giuseppe Bianchi, Maurizio Sebastiani, Giancarlo GazzanelliAbstract:
Prostate‐specific antigen (PSA), a serine protease thought to be exclusively produced by the prostate epithelial cells, has been recently found in human Breast tissues and fluids. PSA in Breast cancer is associated with the presence of steroid‐hormones and receptors, and its presence seems to be a favourable prognostic indicator. In order to clarify whether the cells lining Breast Cysts may represent the source of PSA found in human Breast Cyst fluid, we performed an ultrastructural immunolocalization of PSA in the cells surrounding Type I Breast Cysts, obtained from Breast Cyst fluids of women affected by Breast gross Cystic disease, the most commonly occurring benign Breast lesions associated with increased cancer risk. These apocrine cells show morphological features typical of actively synthesizing and secreting cells, and a PSA labelling distributed on free ribosomes, RER cisternae, and secretory granules, indicating that the metabolically active apocrine cells lining the Type I Cysts are responsible for the production and secretion of PSA in Type I Breast Cyst fluids. The synthesis and intraCystic accumulation of this serine protease in biosynthetically active apocrine Type I Cysts can play an important role in the natural history of Breast gross Cystic disease as well as in the mechanism of Cyst evolution.
Conjugated bile acids in Breast Cyst fluids: relationship to cation-related Cyst subpopulations.Cancer Letters, 1997Co-Authors: Ferdinando Mannello, Maurizio Sebastiani, Silvana Amati, Giancarlo GazzanelliAbstract:
Abstract Gross Cystic Breast disease is a benign lesion occurring in 7% of adult women. Apocrine changes of epithelium lining the Breast Cysts cause a higher risk of developing Breast cancer. According to the possible role of bile acids in the pathogenesis of cancer, we analysed Breast Cyst fluids aspirated from 96 women for distribution of conjugated bile acid concentrations in the two subsets of Breast Cysts. Bile acid levels were correlated to K+ concentrations (P Na K metabolically active apocrine Cyst as compared with Na K > 3 flattened Cyst (P
Quantification of prostate-specific antigen immunoreactivity in human Breast Cyst fluidsBreast Cancer Research and Treatment, 1996Co-Authors: Ferdinando Mannello, G.d. Bocchiotti, Giuseppe Bianchi, Francesco Marcheggiani, Giancarlo GazzanelliAbstract:
The frequency of gross Cystic Breast disease in premenopausal women and its possible association with in-creased Breast cancer risk emphasises the importance of investigations relating to Breast Cyst fluid composition. In order to contribute to a better analysis of this medium, we have measured the presence of prostate-specific antigen immuno-reactivity in sixty-four human Breast Cyst fluids. Data analyses show that 35% of samples presented a level of this antigen < 0.05 µg/L, whereas 42 out of 64 Cysts show a significant increase in the mean value of metabolically active apocrine Cysts when compared to flattened Cysts (p < 0.01). We report the first evidence that Breast epithelium of gross Cysts produces, secretes, and accumulates large amounts of prostate-specific antigen, a glycoprotein produced by prostatic tissue but recently detected in Breast tumours, normal tissues, and during pregnancy. The production and intraCystic accumulation of this serine protease in biosynthetically active apocrine type Cyst can play a feasible role in the natural history of gross Cystic Breast disease as well as in the mechanism of Cyst formation, enlargement, and transformation.