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Relationship between basic fibroblast growth factor and transforming growth factor-beta 2 in breast cyst fluid.

Women with "apocrine" breast cysts (usually having intracystic Na/K < 3) may have a higher risk of developing breast cancer than women with breast cysts lined by flattened epithelium (usually having intracystic Na/K > 3). In this study the concentrations of basic fibroblast growth factor (bFGF), a potent mitogen, and transforming growth factor-beta 2 (TGF-beta 2), which exerts a growth inhibitory effect on epithelial cell types, were measured in breast cyst fluid and their relationship studied. Both growth factors were measured by "sandwich" enzyme immunometric assays. The concentrations of both bFGF and TGF-beta 2 were significantly higher (P < 0.001) in the Na/K > 3 group (median 444 fmol/L, range: < 56 fmol/L-7,890 fmol/L, n = 23 and median 1,776 pmol/L, range: 20.4 pmol/L-5,000 pmol/L, n = 19 respectively) than in the Na/K < 3 group (median < 56 fmol/L, range: < 56 fmol/L-2,722 fmol/L, n = 21 and median 176 pmol/L, range: 12 pmol/L-1,940 pmol/L, n = 23 respectively). Significantly positive correlations were found between bFGF and TGF-beta 2 (rS = 0.496, n = 37, P = 0.002), bFGF and Na/K (rS = 0.599, n = 44, P < 0.001) and TGF-beta 2 and Na/K (rS = 0.521, n = 42, P < 0.001). The significantly higher concentrations of the growth inhibitory TGF-beta 2 in the Na/K > 3 cyst group may provide an explanation for the lower risk of breast cancer which has been observed in this group of women. The role of bFGF in mammary carcinogenesis is unclear as lower levels of this growth factor are present in breast cancer tissue and breast cancer cell lines than in normal breast tissue and cell lines. The positive correlation between bFGF and TGF-beta 2 may indicate regulation by a common factor or that one of these growth factors may regulate the production of the other. This is the subject of further study.

Electrolytes↗

Serological diagnosis of hydatid disease by enzyme linked immunosorbent assay (ELISA) using partially purified hydatid cyst fluid antigens.

Experimentally, two hydatid cyst fluid (HCF) antigens (antigens 4 and 5) were found to be the most immunogenic antigens in HCF. The two antigens were precipitated together from HCF. This was done by adding 2M phosphotungstic acid and 2M magnesium chloride solutions to clarified HCF while continuously stirring the mixture. The precipitate formed was suspended in physiological saline (P.S.). This antigens' solution was used to coat microtitre plates for indirect ELISA. Indirect ELISA was performed on 180 randomly selected bovine sera. The sensitivity of the test was found to be 98% while the specificity was 70%. The predictive value was 89%. Although the specificity of the test was relatively low, the test using these partially purified antigens was found to be useful because of its high sensitivity.

Animals↗

Growth inhibitory substances in human breast cyst fluid.

Women who have breast cysts with intracystic Na/K < 3 may have a higher risk of breast cancer than those with intracystic Na/K > 3. Low/undetectable concentrations of TNF alpha and IL-4, both of which have been shown to inhibit growth of human breast cancer cell lines, were found in the majority of breast cyst fluid samples. Intracystic oestradiol concentrations were significantly higher in the low electrolyte ratio group than in the high electrolyte ratio group. Imbalance between growth stimulatory and growth inhibitory substances in cystic breast disease may be an explanation for the higher risk of breast cancer particularly in the low electrolyte ratio group.

Estradiol↗

Immunoblot evaluation of the 100 and 130 kDa antigens in camel hydatid cyst fluid for the serodiagnosis of human cystic echinococcosis in Libya.

Two high molecular weight antigens with molecular masses approximately 100 kDa and 130 kDa were identified by immunoblotting camel hydatid cyst fluid, with 94% sensitivity in sera from surgically confirmed Libyan cystic echinococcosis cases. 40% of sera from surgically confirmed alveolar echinococcosis cases cross-reacted with the 100 and 130 kDa antigens, as did 5.3% of sera from human Taenia solium cysticercosis patients. No cross-reaction occurred with sera from human schistosomiasis mansoni or onchocerciasis patients. In addition, all sera from patients with non-hydatid space-occupying lesions (i.e. simple liver cysts, kidney cysts, lung tuberculosis, pulmonary carcinoma, pulmonary empyema, and lung abscess) were seronegative against the same antigens, as were control serum samples from healthy individuals. The 100 and 130 kDa antigens were strongly recognized by sera from cystic echinococcosis patients when camel or horse hydatid cyst fluid was used in immunoblotting but were only weakly recognized if sheep or human hydatid cyst fluid was used. Camel hydatid cyst fluid could be an important source of diagnostic antigens for human cystic echinococcosis in the Middle East endemic region.

Animals↗

Simple bone cyst. Treatment by trepanation and studies on bone resorptive factors in cyst fluid with a theory of its pathogenesis.

Simple bone cysts were treated by trepanation. The technique consists of drainage of cyst fluid, lavage of the cystic cavity with saline, and the making of multiple drilling holes through the cortical and the medullary bone of the cyst wall. Injection of corticosteroid was omitted. In 11 cases treated by this method, the clinical outcome was good. Biochemical analyses of the cyst fluid showed bone-resorptive factors, i.e., prostaglandins, interleukin 1, proteolytic enzymes. Electrophoretic analysis of proteolytic enzymes in polyacrylamide gel containing sodium dodecyl sulfate and polymerized gelatin showed proteins with molecular weights of about 130,000, 92,000, 72,000, and lower than 50,000. Increase in such bone-resorbing activities seems to be one of the causative factors in simple bone cysts. The technique was effective in decompressing the internal pressure of the cysts, improving the blood flow through the medullary bone of the cyst wall, stimulating the periosteum to induce bone formation, and eliminating bone destruction.

Adolescent↗

Preoperative cyst fluid analysis is useful for the differential diagnosis of cystic lesions of the pancreas.

BACKGROUND/AIMS: It has been suggested that activity of pancreatic enzymes and concentrations of tumoral markers in cyst fluid may help to distinguish pseudocyst, serous, and mucinous cystadenomas. The aim of this study was to prospectively assess the reliability of preoperative biochemical and tumor marker analysis in cyst fluids obtained by fine-needle aspiration for pathological diagnosis. METHODS: Cyst fluid was obtained preoperatively by fine-needle aspiration, and biochemical and tumoral marker values were measured. The diagnosis of cystic tumors (7 serous cystadenomas and 12 mucinous tumors) was established by surgical specimen analysis. Thirty-one pancreatic pseudocysts complicating well-documented chronic pancreatitis were also studied. RESULTS: Carbohydrate antigen 19.9 levels of > 50,000 U/mL had a 75% sensitivity and a 90% specificity for distinguishing mucinous tumors from other cystic lesions. Carcinoembryonic antigen levels of < 5 ng/mL had a 100% sensitivity and an 86% specificity for distinguishing serous cystadenomas from other cystic lesions. Amylase levels of > 5000 U/mL had a 94% sensitivity and a 74% specificity for distinguishing pseudocysts from other cystic lesions. CONCLUSIONS: High carbohydrate antigen 19.9, low carcinoembryonic antigen, and high amylase levels in cyst fluid are very indicative of mucinous tumors, serous cystadenomas, and pseudocysts, respectively.

Amylases↗

Cyst fluid NB/70K concentration and leukocyte esterase: two new markers for differentiating pancreatic serous tumors from pseudocysts.

Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors, some of which are malignant. Preoperative clinical and radiological parameters are unreliable and may result in incorrect diagnosis and inappropriate treatment. Cyst fluid analysis for cytology, viscosity, carcino-embryonic antigen, CA 72-4, and CA 15-3 will distinguish mucinous from nonmucinous lesions and usually help in determining malignancy. Currently, there is no reliable method to differentiate inflammatory pseudocysts from serous cystadenomas. This distinction is important because the treatment of these two lesions is different; pseudocysts are either observed or drained, whereas serous tumors are usually resected. The tumor marker NB/70K was measured in aspirated cyst fluid from 13 inflammatory pseudocysts and 11 serous cystadenomas by a commercial immunoassay. Leukocyte esterase was measured using Chemstrip SG urine test strips and amylase and lipase on a routine chemistry analyzer. The cyst fluid NB/70K concentration was significantly higher in pseudocysts (mean, 555 U/ml; range, 42-1,926 U/ml) than in serous cystadenomas (mean, 12 U/ml; range 0-130 U/ml) and this difference was significant (p < 0.0002). Leukocyte esterase was detected in 7 of 11 pseudocysts but was absent in 10 of 10 serous tumors (p = 0.002). Amylase and lipase values were generally higher in pseudocysts but these markers were unreliable due to marked outliers. Cyst fluid NB/70K and leukocyte esterase are promising markers to help differentiate pseudocysts from serous tumors on percutaneous aspirates. When combined with previously reported cyst fluid parameters (amylase, lipase, cytology, and amylase isoenzymes), these two cystic lesions can be reliably distinguished.

Antigens, Neoplasm↗

Cytologic examination of ovarian cyst fluid for the distinction between benign and malignant tumors.

OBJECTIVE: To assess the feasibility of using cytologic examination of ovarian cyst fluid for distinguishing between benign and malignant tumors. METHODS: Cyst fluid was aspirated at surgery in 83 women with benign and 35 women with malignant (25 invasive and ten borderline) ovarian tumors and submitted for routine cytologic examination. RESULTS: The specificity of the cytologic examination was 100%, but the sensitivity and negative predictive value were only 26 and 76%, respectively. CONCLUSION: The low sensitivity and negative predictive value of cytologic cyst fluid examination preclude its use for the distinction between benign and malignant ovarian tumors.

Adolescent↗

Relationship between p53 and c-erbB-2 overexpression in tissue sections and cyst fluid cells of patients with ovarian cancer.

The expression of p53 protein and overexpression of c-erbB-2 oncoprotein was examined immunohistochemically and compared on frozen tissue sections and cyst fluid cells in patients with epithelial malignant and benign ovarian neoplasms. p53 was detected in 52.6% of carcinomas and c-erbB-2 expression was identified in 47.3% of cases. The relationship between p53 and c-erbB-2 overexpression in tissue sections and detached cyst fluid cells was evident. Moreover, a significant association between the presence of p53 and overexpression of c-erbB-2 proteins in tumor tissue sections and loose cyst fluid cells in individual patients was demonstrated. In tissue sections and loose cyst fluid cells of benign ovarian tumors no overexpression of p53 and c-erbB-2 proteins was found.

Animals↗

A specific test for the identification of cyst fluid samples from suspected human hydatid infections.

A simple and sensitive two-step enzyme immunoassay for Echinococcus antigen was developed, using peroxidase conjugated IgG fractions of rabbit anti-Echinococcus granulosus cyst fluid serum or of pooled sera from human hydatid patients, to assay samples of cystic fluid taken from patients with suspected hydatid cyst infections. The assay was 100% positive with nine proven human hydatid cyst fluids; in six patients with cysts where serology was negative, there was no evidence of Echinococcus antigen in the cyst fluid. This simple procedure is therefore of value in confirming or excluding the diagnosis of hydatid in cystic fluid obtained by biopsy or after surgery.

Antigens, Helminth↗

Plasma and cyst fluid levels of delta 5 and delta 4 steroid hormones in women with gross cystic breast disease.

delta 5 and delta 4 steroid levels were studied in the plasma and cyst fluid of women with gross cystic breast disease (GCBD). In luteal phase a significant increase in plasma levels (mean +/- SEM) of DHA (11.2 +/- 2.4 ng/ml), DHAS (1.45 +/- 0.6 micrograms/ml) and cortisol 277 +/- 15.7 ng/ml) was found; in follicular phase the mean levels were 4.09 +/- 0.47 ng/ml for DHA, 0.65 +/- 0.08 microgram/ml for DHAS and 190 +/- 46.3 micrograms/ml for cortisol. The DHA/DHAS and cortisol/androstenedione ratios were significantly higher in the plasma and lower in the cyst fluid of GCBD patients, than in the plasma of controls; the androstenedione/DHA ratio was higher in the cyst fluid than in the plasma of controls. The hormonal situation of the GCBD patients thus differed from that of the controls both in the plasma and cyst fluid, particularly as regards the delta 5 steroids.

Adult↗

Biochemical profiles of hydatid cyst fluids of Echinococcus granulosus of human and animal origin in Libya.

A comparative study on the biochemical parameters in hydatid cyst fluids of sheep, goats, camels, cattle and human cystic forms of Echinococcus granulosus has been made in Libya. Quantitative variations in the levels of sodium, potassium, calcium, cholesterol, glucose, urea, creatinine and gamma glutamyl transpeptidase (gamma GT) were found in the cystic fluids of different host origins although these differences were statistically insignificant compared with the hydatid fluids of sheep. However, the concentration of triglycerides and proteins were significantly elevated in the cyst fluids of sheep compared with the other fluids studied. Similarities in the biochemical composition of different hydatid cyst fluids suggest the existence of sheep strains of E. granulosus in human and other domestic animal intermediate hosts in Libya.

Animals↗

Fas and Fas ligand in cyst fluids, serum and tumors of patients with benign and (borderline) malignant ovarian tumors.

Drug resistance in ovarian cancer treatment urges the exploration of new targets for drugs against this malignancy. Fas is a cell membrane receptor which, after engagement with Fas ligand (FasL), triggers apoptotic death. In this study Fas and FasL levels in cyst fluids and sera of patients with benign, borderline and malignant ovarian tumors and in corresponding tumors are determined. Fas and FasL were determinded by ELISA and immunohistochemistry in 30 patients with benign, 5 patients with borderline and 24 patients with malignant epithelial ovarian tumors. In serum there were no differences in median Fas levels, while median FasL levels were higher in healthy women (p=0.02). In malignant cyst fluids, median Fas levels where higher compared to benign cyst fluids (p<0.01). FasL immunostaining was more frequent in malignant ovarian tumors (p=0.002). In conclusion, serum Fas or FasL levels do not seem useful markers. Elevated Fas and equal FasL levels in malignant cyst fluids, suggest an increased production of Fas, and not of FasL by malignant cells. High expression of both Fas and FasL, in malignant ovarian tumors present Fas/FasL as an interesting route to explore for innovative cancer therapy.

Blotting, Western↗

Digoxinlike materials in human breast cyst fluids.

Digoxinlike materials (DLMs) are compounds found in animals that (1) cross-react with digoxin antibodies in specific radioimmunoassay procedures and (2) bind to Na+, K(+)-ATPase and inhibit its activity. DLMs may play a part in the regulation of electrolyte composition. We have determined DLM concentrations in breast cyst fluids and found that these fluids were a rich source of DLMs. Total DLMs were elevated in fluids with type 1 electrolyte composition (high K+ and low Na+ content) when compared to fluids with type 2 composition (low K+ and high Na+ content). Chromatographic studies showed that the basis for the increase was the presence of an additional DLM in the type 1 cyst fluids rather than an increased concentration of the same DLM present in both types of fluids. We propose that this additional DLM may have a role in the accumulation of K+ ions in type 1 fluids. In addition, 7 of 80 cyst fluid samples subjected to high-performance liquid chromatography had a large UV-absorbing peak at 6.4 minutes. Four of these samples were taken from women who later developed breast cancer; information on the subsequent medical history of the other 3 women was unavailable. We suggest that the presence of this material in cyst fluid may be a marker of risk for development of breast cancer.

Biomarkers, Tumor↗

Biliary cyst fluid from common bile duct-ligated rats stimulates endothelial nitric oxide synthase in pulmonary artery endothelial cells: a potential role in hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) results from pulmonary microvascular dilatation in cirrhosis and is associated with increased pulmonary endothelial nitric oxide synthase (eNOS) levels. In the common bile duct ligation (CBDL) model, endothelin-1 (ET-1) released from the liver contributes to the rise in pulmonary eNOS and intrapulmonary vasodilatation. Whether substances, including ET-1, are found in the biliary tree and selectively enter the circulation after CBDL to influence the pulmonary vasculature is unknown. We assessed if control bile and fluid obtained from the obstructed biliary tree in CBDL animals contains ET-1 and alters eNOS expression and activity in bovine pulmonary artery endothelial cells (BPAECs). Control bile and biliary cyst fluid contained concentrations of ET-1 25- to 42-fold normal plasma levels, and hepatic venous concentrations of ET-1 were selectively increased after CBDL. Biliary cyst fluid caused a dose-dependent induction of eNOS messenger RNA (mRNA) (1.9-fold control), protein (2.5-fold control), and enzyme activity (2.2-fold control) maximal at a 1:10 dilution. The increases were associated with enhanced nitric oxide (NO) production (3.1-fold control) and were inhibitable with an ET(B) receptor antagonist. Bile from sham and portal vein-ligated animals did not increase eNOS expression and at dilutions of 1:100 and 1:10 caused cell toxicity. These results show that bile and biliary cyst fluid contain high concentrations of ET-1 that are specifically increased in hepatic venous blood after CBDL. Biliary cyst fluid increases eNOS expression and activity in an ET(B) receptor-dependent manner in BPAECs. The findings suggest a novel mechanism for the susceptibility of CBDL animals to the HPS.

Animals↗

Circulating levels and breast cyst fluid concentrations of human chorionic gonadotropin, progesterone and testosterone in women with gross cystic breast disease.

Circulating levels and cyst fluid concentrations of human chorionic gonadotropin, progesterone and testosterone were measured in 30 premenopausal women with gross cystic breast disease. Specific radioimmunoassay procedures were used. Amounts of human chorionic gonadotropin exceeding 5.0 mIU/ml were found in cyst fluid of many patients, but not in serum. Progesterone and testosterone concentrations in breast cyst fluid were significantly higher than in serum (p less than 0.01 and p less than 0.001, respectively).

Adult↗

Placental protein 10: levels in benign and malignant ovarian cyst fluids and pleural exudates.

Placental protein 10 (PP10) was measured in benign (n = 47) and malignant (n = 10) ovarian cyst fluids and in pleural fluid specimens from 19 patients with pleural metastases of various carcinomas (n = 15) or infectious pleurisy (n = 4). PP10 was found in 9 out of 18 follicular or luteal cyst fluids (range 2.0-42.0 micrograms/l) and in 24 out of 29 benign ovarian tumours (range 2.6-38.0 micrograms/l). Nine out of ten malignant ovarian cyst fluids contained detectable PP10 (range 4.0-55.2 micrograms/l). PP10 was found in all the pleural fluids from 15 patients with metastatic bronchial, pulmonary, breast or pancreatic carcinomas (range 5.1-100.2 micrograms/l), as well as from four patients with pleurisy (range 5.0-28.6 micrograms/l). Our results indicate that PP10 is tumour-associated, but not tumour-specific.

Female↗

Studies on cholesterol accumulation in radicular cyst fluid--origin of heat-stable cholesterol-binding protein.

1. The amount of apolipoprotein B (apo B) was measured using slit-immunoblotting in 20 specimens of radicular cyst fluids. Apo B was detected in all the cyst fluids with varying amounts. 2. Relationship between the amounts of apo B and free cholesterol or activity of heat-stable cholesterol-binding protein (HCBP) were examined. The amount of apo B was correlated well with the activity of HCBP (n = 20, r = 0.72, P less than 0.01) and with the amount of free cholesterol (n = 20, r = 0.45, P less than 0.05). 3. Anti-human apo B antibody inhibited cholesterol-binding activity in radicular cyst fluid. 4. When human-serum was chromatographed on a HPLC ion-exchange column, both cholesterol-binding activity and apo B had exactly the same retention time. 5. These results suggest that HCBP originates from beta-lipoprotein, and beta-lipoprotein may have an important role in cholesterol accumulation on radicular cysts.

Apolipoproteins B↗