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PubMed1997

Evidence for inflammatory and secretagogue lipids in cyst fluids from patients with autosomal dominant polycystic kidney disease.

Advanced autosomal dominant polycystic kidney disease (ADPKD) is characterized morphologically by massive cyst enlargement, moderate interstitial infiltration with mononuclear cells, and extensive fibrosis. In patients affected by a common genotype (PKD1), it has been suggested that the progressive decline in renal function that transpires over a highly variable time course may be due to endogenous or exogenous epigenetic factors. We have postulated that a neutral lipid, discovered in human cyst fluid and stimulating the rates of transepithelial fluid secretion and cellular proliferation of renal epithelial cells in vitro may have a potential role in cyst growth and the progressive decline of kidney function. In this study, we used thin-layer chromatography (TLC) and high-performance TLC (HPTLC) to determine whether lipid extracts of human cyst fluid stimulated monocyte chemotaxis in vitro. Monocyte chemotactic activity, determined by the transmembrane migration of murine RAW 264.7 cells, was stimulated (delta 26.0 +/- 1.5 optical density units) by a lipid fraction less polar than sphingosine but more polar by TLC and HPTLC than 1-monooleoylglycerol. A high level of secretagogue activity was detected in this fraction (delta 0.336 +/- 0.022 microliter/cm2 1 hr) and to a lesser extent (delta 0.253 +/- 0.022 microliter/cm2/hr) in a neighboring fraction that encompassed the 1-monooleoylglycerol standard. Cyst fluid with undetectable secretagogue activity had a monocyte chemotactic-activity level only 18% as great as fluids with high levels of secretagogue activity. The secretagogue and chemotactic activities in TLC-HPTLC fractions were resistant to treatment with KOH, but both were diminished by HCl, borohydride, or periodate. Rat proximal tubule cultures incubated with oleate complexed with albumin elaborated secretagogue and chemotactic activities in the conditioned medium, with TLC-HPTLC mobility characteristics similar to the biologically active cyst fluid lipids. On the basis of these studies, we conclude that human cyst fluids harbor potent secretagogue and chemotactic lipids that may have a role in determining the functional course of ADPKD. On the basis of preliminary chemical characterizations, we suggest that the secretatogue and monocyte chemotactic activities of cyst fluid may reflect the action of lipid molecules of similar structure, the source of which may be renal epithelial cells.

Animals↗

PubMedDate not supplied

Similarities of human hydatid cyst fluid components and the host serum.

Nine lung hydatid cyst fluid of Echinococcus granulosus species from man were analysed by electrophoresis, immunoelectrophoresis and by biochemical tests. In addition respective sera of the host were analysed for comparison. Analysis revealed striking similarities in cellulose acetate and agarose gel electro- and immunoelectrophoretic patterns of proteins from hydatid cyst fluid and the serum of the respective hosts. It is presumed that serum proteins (albumin and globulins) occur in hydatid cyst fluid, but in smaller amount than in serum, an we believe that the host proteins can penetrate the membranes of the hydatid cyst.

Adolescent↗

PubMed1978

Similarities of human hydatid cyst fluid components and the host serum.

Nine lung hydatid cyst fluid of Echinococcus granulosus species from man were analysed by electrophoresis, immunoelectrophoresis and biochemical tests. In addition respective sera of the host were analysed for comparison. Analysis revealed striking similarities in cellulose acetate and agarose gel electrophoretic and immunoelectrophoretic Patterns of proteins from hydatid cyst fluid and the serum of the respective hosts. It is presumed that serum proteins (albumins and globulins) occur in hydatid cyst fluid, but in small amount than in the host serum, and we believe that the host proteins can penetrate the membranes of the hydatid cyst.

Adolescent↗

PubMed1994

Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk.

Patients bearing macrocysts of the breast are at higher risk of later developing cancer. The fluid filling the cysts (breast cysts fluid, BCF) contains unusual amounts of steroid conjugates, first androgen and estrogen sulfates. Measuring BCF cations (K+,Na+) allows categorization of cysts into two major subsets (type I and type II) that are associated with a different degree and/or turnover of apocrine metaplastic cells in the lining epithelium. Type I cysts (high K+/Na+ ratio) accumulate hugh amounts of dehydroepiandrosterone sulfate, estrone sulfate, androstane-3 alpha,17 beta-diol glucuronide, androsterone glucuronide and contain more testosterone and dihydrotestosterone than type II. Conversely, type II cysts (low K+/Na+ ratio) contain more progesterone and pregnenolone. A cohort study was started in 1983 at the Cancer Prevention Center, Ravenna, Italy, with the aim of evaluating the relationships between the biochemistry of BCF and the incidence of breast cancer in women with gross cystic disease (GCD) of the breast. The bimodal distribution of the cationic pattern has been confirmed from data obtained in 798 patients aspirated. The risk of cyst relapse was significantly higher among women with type I cysts or with multiple cysts at presentation. Twelve incident cases of breast cancer have been diagnosed among women whose BCF was categorized. Eleven out of 12 cases had type I or multiple cysts. The cumulative incidence of breast cancer among patients bearing type I cysts was 2.5%. We conclude that women with GCD bearing type I cysts have an increased breast cancer risk when compared with the counterpart bearing type II cysts or the general population.

Adult↗

PubMedDate not supplied

Effect of breast cyst fluid on oestrone sulphatase activity in MCF-7 breast cancer cells.

Breast cyst fluid is a rich source of growth factors and sex hormones but the pathophysiology of cystic breast disease is largely unknown. In this study the net effects of breast cyst fluid on growth of, and oestrone sulphatase activity (oestrone sulphate --> oestrone) in the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines were assessed. Using a final breast cyst fluid dilution of 16.7% (v/v) MCF-7 cell growth was significantly inhibited by 7 of 21 samples (16% - 54%) while MDA-MB-231 cell growth was significantly inhibited by 17 of 20 samples (15% - 45%). Oestrone sulphatase activity was significantly inhibited in the MCF-7 cell line by 19 of 21 samples (22% - 81%) while significant stimulation of oestrone sulphatase activity was observed in MDA-MB-231 cells in 11 of 20 samples (17% - 149%). The presence of endogenous substances in breast cyst fluid which inhibit oestrone sulphatase activity in the MCF-7 cell line is exciting because of the therapeutic potential of oestrone sulphatase inhibition in hormone-dependent breast cancers.

Arylsulfatases↗

PubMed1993

Human brain tumor cyst fluid is mitogenic for primary astrocytes in culture.

Tumor cyst fluid from five patients with malignant glial neoplasms was assayed for mitogenic activity by measuring [3H]thymidine uptake by rat astrocyte cultures in serum-free defined media. Cyst fluid from all patients stimulated [3H]thymidine uptake three- to fourfold in astrocyte cultures in comparison with untreated controls. Mitogenic activity was found to be soluble and resistant to freezing, but inactivated by heat and trypsin. The activity was retained by ultrafiltration through a 100-kd molecular weight filter. It appears from these results that mitogenic factor(s) for nonneoplastic astrocytes are present in human brain tumor cyst fluid and that such factors appear to be protein in nature and associated with a complex of molecular weight greater than 100,000.

Animals↗

PubMed1994

Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer.

Expression of insulin-like growth factor-I (IGF-I), its receptor, and IGF-binding proteins (IGFBPs) by epithelial ovarian cancer cells and its mitogenic effect on these cells in vitro suggest that IGF-I may have a role in the regulation of human ovarian cancer. To examine this role in vivo, we explored the IGF-I/IGFBP system in sera and cyst fluids of women undergoing surgery for simple and other benign cysts (n = 20) and borderline (n = 5) and invasive malignant epithelial neoplasms (n = 11). The IGF-I level was significantly higher in cyst fluid from invasive malignant compared to cyst fluid in benign neoplasms (16.1 +/- 2.2 vs. 7.3 +/- 1.2 nmol/L; P = 0.002). Although benign cysts contained almost no IGFBP, high IGFBP-2 levels were detected in malignant cysts regardless of histological type. Serum IGFBP-2 levels were also higher in women with invasive malignancy than in benign controls (1.32 +/- 0.32 vs. 0.53 +/- 0.07 relative units; P = 0.004). IGFBP-2 was higher in cyst fluids than in the corresponding sera, implying local production of this protein. Estradiol was high in fluid from invasive malignant cysts of postmenopausal women and correlated with IGF-I in the cyst fluid. Levels of IGF-I, IGFBP-2, and estradiol in cyst fluid could discriminate between benign and malignant neoplasms, except for the endometrioid-type tumors (n = 2). Our data support a role for IGF-I in the proliferation of ovarian cancer and suggest that IGF-I and estradiol interact in regulating this malignancy.

Adult↗

PubMed2003

Demonstration of species-specific and cross-reactive components of hydatid cyst fluid antigens.

ELISA-hydatid cyst fluid antigen (HCF-Ag-ELISA) and conventional echinococcosis IHAT were assessed for cystic hydatid disease (CHD), confirmed by HCF-Ag immunoblotting assay. The sensitivity of the tests was 94.4% and 83.3% for HCF-Ag-ELISA and IHA respectively. HCF-Ag-ELISA showed some cross-reaction in tumor cases (5.5%), but no cross-reaction was observed in Rheumatoid arthritis patients. IHA showed 100% specificity. To confirm this data SDS-PAGE immunoblotting using HCF-Ag was applied. Echinococcus specific reactions were reported with 44Kda, 34Kda, 29Kda and 8Kda HCF-Ag resolved bands. Cross-reaction was found with 27Kda, 21Kda, 16Kda and 13Kda bands in tumor patients. Moreover, cross-reaction was found with 200Kda, 175Kda, 62Kda, 52Kda and 40Kda in serological anti-Schistosoma antibodies positive cases. So, using specific HCF-Ag components, immunoblotting provided 100% sensitivity and specificity in CHD.

Animals↗

PubMed1994

Breast-gut connection: origin of chenodeoxycholic acid in breast cyst fluid.

The notion that a breast-gut connection might modulate the microenvironment of breast tissue was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines. To establish that the gut, rather than circulating steroid precursors, is the source of bile acids in breast cyst fluid, we gave two patients deuterium-labelled chenodeoxycholic acid (three 200 mg doses by mouth), starting 9 days before aspiration of breast cysts. The chenodeoxycholic acid concentration of seven samples of aspirated cyst fluid ranged from 42 to 94 mumol/L. The corresponding serum concentrations of chenodeoxycholic acid on the same day were 0.8 and 2.9 mumol/L, of which the labelled compound comprised 13.0% (0.38 mumol/L) and 28.2% (0.23 mumol/L). The deuterated chenodeoxycholic acid concentrations in cyst fluid were 0.79 and 1.26 mumol/L in two samples from patient 1 and 3.22 mumol/L in patient 2; these values are equivalent to 11-17% of the serum concentrations [corrected]. This study shows that intestinal bile acids rapidly gain access to cyst fluid. Further studies should investigate the mechanisms that govern the exchange processes and the maintenance of the high cyst fluid to plasma concentration gradients, and the biological half-lives of individual constituents.

Adult↗

PubMed1996

Migration of human glioma cells in response to tumour cyst fluids.

Glial tumours often show high degrees of local invasion that lead to local recurrence of the disease. Extracellular matrix components as well as soluble factors may play a critical role in this poorly understood process. Cyst fluid from human brain tumours may accumulate such autocrine produced factors and may represent a source were those factors may be easily obtained and studied. We have studied the effect of cyst fluids harvested from 17 glial tumours, 3 meningiomas, and three metastases on the motility of established human glioma cell lines. Both cyst fluids of high grade and low grade gliomas contained varying degrees of motility enhancing activity. No such activity was identified in cyst fluids obtained from meningiomas. The relation of mitogenic and motogenic activity in three selected cyst fluids was analysed using a quantitative monolayer migration assay. Quantitative analysis of cyst fluid effects on both proliferation and migration indicate that tumour cyst fluids contain factors that strongly stimulate cell migration and that maximum stimulation of migration did not occur at concentrations optimal for cell proliferation. Our findings indicate that glial tumours in fact produce and secrete soluble factors that may contribute to their dissemination in brain tissue.

Adult↗

PubMed1993

Identification of multiple proliferative growth factors in breast cyst fluid.

Gross cystic disease is a common benign breast disease that is associated with a twofold to fourfold increase in breast cancer risk. Both diseases are hormonally induced and may share a common biochemical environment conducive to abnormal proliferative responses. A large collection of breast cyst fluid samples was analyzed for growth factors associated with cell proliferation: epidermal growth factor (EGF), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), platelet-derived growth factor (PDGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta (TGF-beta). The data demonstrate that significant amounts of proliferative growth factors are present in breast cyst fluid of all cyst subtypes. The presence of IGF-II, PDGF, and TGF-beta in breast cyst fluid was confirmed for the first time. EGF, PDGF, and TGF-beta concentrations in breast cyst fluid were several times greater than reported for serum; IGF-I and IGF-II concentrations were several times lower. In the first 100 samples tested, no TGF-alpha was detected. Only EGF and IGF-II levels demonstrated a consistent correlation with apocrine type 1 cysts. These results demonstrated that effective concentrations of proliferative growth factors are in breast cyst fluid and suggest that adjacent breast tissue may be a probable source of synthesis. Growth factor profiles of breast cyst fluid may indicate the presence in breast tissue of a hormonal and proliferative environment permissive to subsequent cancer growth.

Adult↗

PubMed1990

Evaluation of tumor and trophoblastic marker concentration in breast cyst fluid.

In our study we have examined 314 samples of cyst fluid taken from women suffering from fibrocystic breast disease (gross cystic disease). We have subdivided the cyst fluid with respect to epithelial coating and we have related trophoblastic protein content of the cyst fluid with age, seriousness of illness, and cytology of epithelial lining. We have performed RIA analysis of the trophoblastic proteins betahCG, beta1-SP-1, and alphahCG and in a smaller (n=84) group of specimens we have also tested for CEA, TPA, and ferritin. Trophoblastic proteins were positive in cystic fluids but the biological meaning of this is not known and the values are not related to clinical manifestations, except in a group of patients with apocrine metaplasia in which we tried to find a relationship between fertile age and increased betahCG. This finding presumably has a prognostic meaning that can be further understood by epidemiologic studies (of dietary intake and evaluation of lipid metabolites) and by information about inflammatory state of cystic fluid.

Adult↗

PubMed1986

Further characterization of the light breast cyst fluid protein, GCDFP-15.

A light protein of breast cyst fluid from women with gross cystic disease, termed GCDFP-15 in the literature, has been investigated. This light protein was purified by preparative electrophoresis on sodium dodecyl sulfate polyacrylamide gel. Its isoelectric point has been determined as 3.75 and its molecular weight has been estimated at 17 400. The light protein was a glycoprotein containing about 163 amino acid residues; the glucidic fraction corresponded to 11% of the molecular weight. The N-terminal amino acid was blocked and the C-terminal amino acid was determined as valine. Antisera raised against this light protein have proved to be specific. In the literature, there is evidence suggesting that apocrine secretion is of prime importance in conditioning the biochemical composition of breast cyst fluid. Further information is needed to substantiate the hypothesis that in gross cystic disease the apocrine epithelium itself or some of its functional aspects are associated with the risk of neoplasia. The physicochemical characterization of the breast cyst fluid protein can contribute to the study of its biosynthesis and provide a better understanding of the physiopathology of gross cystic disease and its relationship to breast carcinoma.

Amino Acids↗

PubMed1985

Cyst fluid antibiotic concentrations in autosomal-dominant polycystic kidney disease.

Infections involving cysts of patients with autosomal-dominant polycystic kidney disease (PCKD) are often refractory to therapy possibly because of poor penetration of antibiotics into cyst fluid. Ten patients with PCKD had blood urine and cyst fluid sampled at surgery or autopsy for antibiotic concentrations. Cysts were categorized as to their nephron site of origin by cyst fluid sodium concentrations. Drugs active against anaerobes such as metronidazole and clindamycin were present in therapeutic concentrations in both proximal and distal cysts. Ampicillin and trimethoprim-sulfamethoxazole had the best profiles considering likely infecting organisms and the antibiotic concentrations achieved in both type of cysts. It is likely that prolonged therapy with both of these drugs is necessary to insure therapeutic success. Other drugs that can be detected in cysts are lipid soluble, undergo tubular secretion, or have high pKa values. These include erythromycin, vancomycin, and cefotaxime. Aminoglycosides because of their predominant glomerular filtration and thus low filtration rate per single cystic nephron are undetectable in both proximal and distal cysts. Clinically, alternatives to aminoglycosides should be chosen for infected cysts in PCKD.

Adult↗

PubMed1987

pH as a marker of breast cyst fluid biochemical type.

A previous study reported pH levels in human breast cyst fluid ranging from 7.00 to 7.80 with the cut off between Type I (high K+, low Cl-) and Type II (high Na+, high Cl-) cysts at pH 7.40. Our data indicate a wider range of pH levels in human breast cyst fluids with Type I cysts consistently having acidic levels below pH 7.0 while Type II cysts had pH levels greater than 7.0. Type I acidic cysts characteristically also contain greater amounts of organic acids than Type II cysts. Thus, the pH of breast cyst fluid appears to be related to the electrolyte profile.

Female↗

PubMed2006

Proteomic analysis of hemangioblastoma cyst fluid.

OBJECTIVE: Hemangioblastomas are benign CNS tumors that occur sporadically or in patients with von Hippel-Lindau (VHL) disease. These tumors are characteristically associated with formation of intra- or peritumoral cysts. Hemangioblastoma cyst formation is a major cause of morbidity and mortality with these tumors. While peritumoral cysts have been suggested to result from vascular leakage, the mechanism of intratumoral cyst formation is not understood. METHODS: To elucidate the origin of intratumoral hemangioblastoma cyst fluid, we characterized its biochemical composition by two-dimensional (2D) proteomic profiling followed by sequencing of several proteins. The proteomic pattern of intratumoral cyst fluid was furthermore compared to the proteomic pattern of serum, hemangioblastoma tumor tissue, and hemangioblastoma peritumoral cyst fluid. RESULTS: We show that proteomic patterns of intra- and peritumoral cyst fluid are identical Both are highly similar to serum and not to tumor. CONCLUSIONS: Intratumoral hemangioblastoma cyst fluid originates from serum. Cyst formation associated with hemangioblastoma, whether peri- or intratumoral, is a consequence of vascular leakage. Anti-VEGF therapy may effectively control hemangioblastoma cyst formation.

Biomarkers, Tumor↗

PubMed2006

Cyst fluid analysis obtained by EUS-guided FNA in the evaluation of discrete cystic neoplasms of the pancreas: a prospective single-center experience.

BACKGROUND: Accurate assessment of pancreatic cystic neoplasms is imperative before selecting available treatment options, such as surgical resection, drainage, or conservative therapy. Available modalities, CT and magnetic resonance imaging, have been inconsistent in diagnosis. Reports involving EUS and cyst fluid analysis have been encouraging, including studies of EUS features and/or cyst fluid analysis, which may differentiate pancreatic cystic neoplasms. OBJECTIVE: To retrospectively determine cyst fluid characteristics that differentiate cystic neoplasms. DESIGN: Patient evaluation included (1) EUS features (reported elsewhere) and (2) cyst fluid analysis (carcinoembryonic antigen [CEA], carbohydrate antigen 19-9 [CA 19-9], amylase and lipase, viscosity [VIS], mucin stain, and cytology). Exclusion criteria included the following: intraductal papillary mucinous tumor lesions, bloody cyst aspirate, neuroendocrine tumors, and patients without surgical histopathology. SETTING: Pancreatic Biliary Center, St Luke's Medical Center, Milwaukee, Wisconsin. PATIENTS: A total of 102 patients (60 women, 42 men; age, 23-76 years) presented for evaluation of pancreatic cystic neoplasm; 71 underwent surgical resection. RESULTS: Seventy-one of 102 patients who underwent surgery presented the following histopathologic correlates: 23 pseudocysts (PC), 13 serous cystadenoma (SCyA), 21 mucinous cystadenoma (MCyA), and 14 mucinous cystadenocarcinoma (MCyA-CA). Cyst fluid analysis of these patients showed the following: VIS was lower in PC (mean, 1.3) and SCyA (1.27) when compared with MCyA (1.84) and MCyA-CA (1.9). All mucinous neoplasms had VIS >1.6, whereas only 2 mucinous cystic neoplasms (MCN) had VIS = 1.6 (both PC). The CEA level was significantly higher in MCyA (adenoma [878 ng/mL], carcinoma [27,581 ng/mL]) vs PC (189 ng/mL), and SCyA (121 ng/mL). Amylase levels were higher in PC (7210 U/L) compared with cystic neoplasm (SCyA, 679 U/L; MCyA, 1605 U/L; MCyA-CA, 569 U/L). CONCLUSIONS: Differential diagnosis of pancreatic cystic neoplasm is significantly enhanced by cyst fluid analysis. Elevated CEA (> or =480 ng/mL) and VIS (>1.6) accurately predict MCN from SCyA and PC. Malignant from benign MCN can be differentiated by CEA levels > or =6000 ng/mL.

Adult↗

PubMed1999

[The levels of selected hormones in serum and ovarian cyst fluid in girls and young women].

OBJECTIVES: The aim of the study was to determinate levels of the FSH, LH and E2 in serum and ovarian cyst fluid in neoplastic tumors (7 benign, 1 of low malignant potential) and functional cysts. MATERIAL AND METHODS: We measured the concentrations of the FSH, LH and E2 at 12 girls and young women hospitalized in our teaching department using immunoenzymatic method. RESULTS: We found higher levels of gonadotropins in serum and particular in ovarian cyst fluid at neoplastic tumors in comparison with functional cysts. There were also high levels of estradiol and low of gonadotropins in functional ovarian cyst fluid. CONCLUSION: The differences of FSH, LH and E2 levels in ovarian cyst fluid in neoplastic and functional cyst have cognitive character and need more investigations.

Adolescent↗