PubMed Health⌕ Search

Biomedical subjects

R Ponzone

Publications and source records attributed to R Ponzone.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prostate specific antigen molecular forms in breast cyst fluid and serum of women with fibrocystic breast disease.

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 alpha1-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).

Adult↗
PubMed1999

Immunoenzymatically determined pepsinogen C concentration in breast tumor cytosols: an independent favorable prognostic factor in node-positive patients.

The aim of this study was to determine the concentration and to evaluate the prognostic value of pepsinogen C (PepC) in breast cancer patients. PepC is an aspartic proteinase that is involved in the digestion of proteins in the stomach and is also synthesized by a subset of human breast tumors. PepC concentrations were measured with a highly sensitive immunofluorometric assay, which uses two monoclonal antibodies that are specific for PepC and has a detection limit of 0.1 ng/ml. Breast tumor cytosols from 151 patients (median follow-up, 67 months), stratified according to nodal status, were evaluated. An optimal cutoff value, equal to 1.75 ng/mg of extracted protein, was first defined by statistical analysis. PepC status was then compared with other established prognostic factors, in terms of disease-free survival (DFS) and overall survival (OS). High PepC concentrations were found in small (P = 0.003) and well-differentiated tumors (P = 0.042) as well as in stage I (P = 0.003) and node-negative patients (P = 0.040). Statistically significant associations of PepC concentration with patient age and estrogen receptor and progesterone receptor status were not observed. In univariate Cox regression analysis of the entire cohort of patients, negative PepC proved to be a significant predictor of reduced DFS (P = 0.0086) and OS (P = 0.025). Multivariate analysis in subgroups of patients defined by nodal status indicated that PepC status was a strong predictor of DFS (P = 0.0039) and the strongest factor for predicting OS (P = 0.0046) in node-positive but not in node-negative patients. Our results suggest that PepC may be used as an independent favorable prognostic factor in node-positive breast cancer patients because there were no significant associations between PepC and the other prognostic factors evaluated in this group of patients.

Adult↗
PubMed1998

Immunofluorometrically determined p53 accumulation as a prognostic indicator in Italian breast cancer patients.

The prognostic value of p53 protein accumulation in breast cancer, especially as detected by methods other than immunohistochemistry, has not been established unequivocally. A sensitive immunofluorometric assay of p53 protein employing DO-1 and CM-1 antibodies was used in this study to assay extracts of 171 breast carcinomas from northern Italy. p53 over-expression, demonstrated in 36 (21%) tumours, was associated with lack of oestrogen receptor (ER) expression but was not related to patient age, stage, lymph node status, tumour size, histologic type, grade or progesterone receptor (PR) expression status in contingency tables. An increased risk for cancer relapse of p53-positive patients compared to p53-negative patients was determined using multivariate Cox regression analysis, which also showed that p53 protein over-expression was an independent predictor of reduced disease-free survival in node-positive and ER+ patients but not in node-negative or ER- individuals. The equivalent analysis for assessing the impact of p53 status on overall survival was not statistically significant, possibly reflecting the short patient follow-up. Our results suggest that an immunoassay of p53 protein, applicable to cytosolic extracts prepared for steroid hormone receptor analyses, may provide information for breast cancer prognosis.

Adult↗
PubMed1997

Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases.

Using a highly sensitive immunofluorometric procedure, we measured the total prostate-specific antigen (PSA) concentration in 632 sera obtained from female blood donors and women with idiopathic hirsutism, breast cancer or benign breast diseases. A total of 50 sera with total PSA > 15 ng l(-1) were fractionated by high-performance liquid chromatography (HPLC) in order to resolve the two immunoreactive molecular forms, i.e. free PSA (approximately 30 kDa) and PSA bound to alpha1-antichymotrypsin (PSA-ACT, 100 kDa). We found that breast cancer patients have presurgical serum total PSA levels similar to those of blood donors. Total serum PSA concentration decreases with age in women with idiopathic hirsutism, in cancer patients and in patients with benign breast diseases. The major molecular form of PSA in the serum of all normal and hirsute women (n = 15) is PSA bound to the proteinase inhibitor alpha1-antichymotrypsin. The major molecular form in 44% of presurgical cancer patient sera is free PSA. A total of 58% of benign breast disease patients also have in their serum mainly free PSA. We conclude that about half the patients with breast cancer or benign breast diseases have free PSA as the major molecular form in their serum, whereas patients without breast pathologies (normal blood donors, idiopathic hirsutism) have PSA bound to alpha1-antichymotrypsin as the major molecular form. The ratio of PSA/PSA-ACT may have value as a simple biochemical test for diagnosis of breast pathologies including breast cancer.

Adolescent↗
PubMed1996

Prostate specific antigen in breast cancer, benign breast disease and normal breast tissue.

Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that PSA may also be produced by breast tumors. In this report we examined quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant amounts of PSA (> or = 0.030 ng of PSA per mg of total protein) were found in 28% of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA positivity in breast tumors was highest in stage I disease (34%) and decreased with disease stage (24% in stage II and 18% in stage III-IV). Using polymerase chain reaction amplification we have shown PSA mRNA presence in patients with PSA protein-positive tissues (benign and malignant) but not in patients with PSA protein-negative tissues. Our data suggest that PSA is expressed frequently by normal breast tissue, by tissue of benign breast diseases, and by breast cancer tissue. Highest expression is seen in benign breast disease and lowest expression in advanced stage cancerous tissue. As PSA production is mediated by steroid hormones and their receptors, we propose that PSA may be a new marker of steroid hormone action in the normal or diseased female breast. The role of this enzyme in the development of breast diseases including breast cancer is currently unknown.

Adolescent↗
PubMed1996

Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients.

Creatinine kinase BB (CK-BB) is elevated in many tumours including those of the breast. We have recently described a new, highly sensitive and specific method for measuring CK-BB, based on monoclonal antibodies and time-resolved fluorometry. Using this method, we quantitated CK-BB in 172 breast tumour cytosols and examined the associations between CK-BB and other clinicopathological variables and patient survival. High CK-BB levels were seen more frequently in tumours from patients who were younger (age < 50 years), patients who qualified for chemotherapy and patients with oestrogen receptor-positive tumours. No association was seen between CK-BB and tumour stage, grade, size, histological type or the progesterone receptor. In univariate analysis, the risk of relapse or death was higher in the group with tumours containing high CK-BB levels but the difference did not reach statistical significance. In multivariate analysis, the risk of death was statistically significantly higher in the high-CK-BB group. Analysis of subsets of patients revealed that patients with oestrogen receptor-negative cancer have higher risk of death if their tumours contain high levels of CK-BB. Our data suggest that, in general, CK-BB is associated with more aggressive tumours but its value as a prognostic indicator is limited. CK-BB content of breast tumours may be more useful as an aid in selecting therapy directed at inhibiting this enzyme activity and thus depriving tumour cells of their energy source.

Adult↗
PubMed1995

Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer.

Prostate-specific antigen (PSA) is thought to be produced exclusively by prostatic epithelial cells and is currently used as a tumor marker of prostatic adenocarcinoma. We recently found that 30% of breast cancers contain PSA immunoreactivity (IR-PSA). To examine the prognostic value of PSA in female breast cancer, we measured IR-PSA in tumor cytosols of 174 breast cancer patients and classified the breast cancers as either PSA positive or PSA negative based on an IR-PSA cutoff level of 0.03 ng/mg. IR-PSA was present in 27% of the patients. IR-PSA presence was associated with early disease stage, small tumors, and estrogen receptor-positive tumors. We used the Cox proportional hazards regression model to analyze survival of patients in association with PSA status and found that patients with IR-PSA-positive tumors had a reduced risk for relapse and death in univariate analysis (P = 0.02 and 0.06, respectively) and a reduced risk for relapse in multivariate analysis (P = 0.03). Further analysis indicated that the effect of IR-PSA on relapse-free survival was evident in node-positive or estrogen receptor-negative patients. Our study suggests that IR-PSA is an independent favorable prognostic marker for breast cancer and may be used to identify a subgroup of estrogen receptor-negative and/or node-positive patients who have good prognoses.

Adult↗
PubMed1995

Prostate-specific antigen in serum of women with breast cancer.

Prostate-specific antigen (PSA) was recently found in 30% of female breast tumours. In this study we have examined if PSA circulates in the blood of breast cancer patients and if serum PSA has any clinical application. We have compared serum PSA levels between women with and without breast cancer, between women with PSA-positive and PSA-negative breast cancer and between women with breast cancer before and after surgical removal of the tumour. We found that for women > or = 50 years, there is no difference in serum PSA between normal or breast cancer patients. We also could not find any difference in presurgical or post-surgical serum PSA between women who have PSA-positive or PSA-negative breast cancer. We found no correlation between PSA concentrations in matched presurgical and post-surgical sera, between presurgical sera and tumour cytosols and between post-surgical sera and tumour cytosols. High-performance liquid chromatography has shown that PSA in normal male serum consists mostly of PSA bound to alpha 1-antichymotrypsin (molecular weight approximately 100,000), and PSA in breast tumours and presurgical and post-surgical serum consists mostly of free PSA (molecular weight approximately 33,000). These data suggest that female serum PSA is not associated with tumour PSA levels. We speculate that most of the circulating PSA in women originates from the normal breast. It appears that serum PSA in women does not have potential for breast cancer diagnosis or monitoring, but our previous data are consistent with the view that tumour PSA concentration is a favourable prognostic indicator in women with breast cancer.

Adult↗
PubMed1993

Hyperphenylalaninemia and pterin metabolism in serum and erythrocytes.

The relationship between blood phenylalanine concentrations and serum and erythrocyte biopterin and neopterin concentrations was investigated in 20 phenylketonuric patients with different dietary compliance. At serum phenylalanine concentrations ranging from 43 to 1004 mumol/l, a good correlation was found with serum biopterin (r = 0.76, P < 0.001) and with red blood cell biopterin (r = 0.62, P < 0.001). A similar correlation was found between serum neopterin and phenylalanine (r = 0.60, P < 0.001). The correlation between red blood cell neopterin and serum phenylalanine was less evident, however (r = 0.47, P < 0.005). After oral loading with phenylalanine (100 mg/kg body weight), serum and red blood cell biopterin concentrations increased in patients with classical phenylketonuria as well as in one patient with dihydropteridine reductase deficiency in response to the induced acute hyperphenylalaninemia. One patient suffering from 6-pyruvoyl tetrahydropterin synthase deficiency was loaded orally with tetrahydrobiopterin (20 mg/kg body weight). The kinetics of administered cofactor confirmed its rapid absorption, with early increase of serum concentrations followed by its transport into the red blood cells. The half-life of biopterin was approximately 7 h in serum and 15 h in red blood cells. Because both values are less than the half-life of phenylalanine (20-30 h) in serum, biopterin measurement offers no advantage in monitoring dietary control in hyperphenylalaninemic patients.

Alcohol Oxidoreductases↗
PubMed1993

Differential diagnosis of hyperphenylalaninaemia by a combined phenylalanine-tetrahydrobiopterin loading test.

We describe a new fully reliable method for the differential diagnosis of tetrahydrobiopterin-dependent hyperphenylalaninaemia (HPA). The method comprises the combined phenylalanine (Phe) plus tetrahydrobiopterin (BH4) oral loading test and enables the selective screening of BH4 deficiency when pterin analysis is not available or when a clear diagnosis has not been previously made. It should be performed together with the measurement of dihydropteridine reductase (DHPR) activity in blood. The new combined loading test was performed in nine patients with primary HPA, three with classical phenylketonuria (PKU), three with DHPR deficiency, and three with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency. Three hours after oral Phe loading (100 mg/kg body weight), synthetic BH4 was administered orally at doses of either 7.5 or 20 mg/kg body weight. Amino acid (Phe and tyrosine) and pterin (neopterin and biopterin) metabolism and kinetics were analysed. By exploiting the decrease in serum Phe 4 and 8 h after administration, a clear response was obtained with the higher BH4 dose (20 mg/kg body weight), allowing detection of all cases of BH4 deficiency, as well as differentiation of BH4 synthesis from regeneration defects. Since DHPR deficient patients who were previously shown to be non-responsive to the simple BH4 loading test gave a positive response, the combined Phe plus BH4 loading test can be used as a more reliable tool for the differential diagnosis of HPA in these patients. Moreover, it takes advantage of being performed while patients are on a Phe-restricted diet.

Alcohol Oxidoreductases↗
PubMed1993

Catalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment.

It is now widely accepted that tetrahydrobiopterin (BH4), the natural cofactor of aromatic amino acid hydroxylases, in the absence of its regenerating enzyme dihydropteridine reductase (DHPR), will function only stoichiometrically in the phenylalanine (Phe) hydroxylating system. This has limited the use of pterin cofactor in diagnosis and treatment of patients suffering from inherited DHPR deficiency, one of the most common forms of hyperphenylalaninemia caused by BH4 deficiency. This is despite the observation of a dramatic fall in serum Phe concentration after BH4 loading in such patients. In this study, quantitation of this phenomenon was obtained by comparing the kinetics of serum Phe after either a simple Phe or a combined Phe plus BH4 oral loading in patients with Phe hydroxylase or with DHPR deficiency. Only in the latter was the total body clearance of Phe enhanced up to 5 times by the cofactor administration, resulting in the molar equivalent of Phe hydroxylated/mol of BH4 ranging from at least 6 to 10, against the postulated 1. As a consequence, BH4 administration should be attempted therapeutically in DHPR-deficient patients, thus avoiding a lifelong Phe-restricted diet. Preliminary experience with such treatment is given with two cases.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

RFLPs of the phenylalanine hydroxylase gene in the Italian population.

Different mutations of the phenylalanine hydroxylase (PAH) gene leading to phenylketonuria (PKU) have been described associated with specific haplotypes in several European countries. In order to investigate the distribution of DNA haplotypes in Italy, restriction fragment length polymorphism (RFLP) analysis of the PAH gene was performed in nine Italian PKU patients from eight unrelated families, and in the available relatives. The analysis of eight polymorphic sites revealed haplotypes 1 and 6 in association with PKU. This pattern appears to differ from those reported for other European populations. The majority of the 14 PKU subjects studied showed compound heterozygosity for different haplotypes, as observed for other European series. RFLP analysis at the PAH locus allowed us to offer the possibility of prenatal diagnosis to six of the studied families. One prenatal diagnosis was performed and a normal fetus was diagnosed.

Alleles↗
PubMedDate not supplied

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: the prevalent mutation G985 (K304E) is subject to a strong founder effect from northwestern Europe.

Medium-chain acyl CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited defect of fatty acid beta-oxidation. Approximately 90% of the disease-causing alleles in diagnosed patients are due to a single base mutation, an A (adenine) to G (guanine) transition at position 985 of MCAD cDNA (G985). In a limited number of cases it was found that this mutation was always associated with a particular haplotype, defined by three intragenic restriction fragment length polymorphisms, indicating a founder effect [Kølvraa et al.; Hum Genet 1991; 87: 425-429]. In addition, recent studies of American patients and their ancestors suggested the existence of a founder from northern Europe [Yokota et al.; Am J Hum Genet 1991; 49: 1280-1291]. In the present study we document (1) that the G985 heterozygous frequency in the Caucasian population of North Carolina in the USA is 1/84, which is 5- to 10-fold higher than in non-Caucasian Americans; (2) that there exists a 100% association of the G985 mutation in 17 families with MCAD-deficient patients to a certain haplotype, defined by the restriction endonucleases BanII, PstI and TaqI; (3) that MCAD deficiency due to the G985 mutation is more frequent in the Netherlands, Ireland, England, Belgium and Denmark than in other western European countries, and (4) that the frequency distribution of G985 mutation carriers is 1/68-1/101 in newborns in the United Kingdom and Denmark, and 1/333 in Italy. These results support the notion of a founder effect in northwestern Europe.

Acyl-CoA Dehydrogenase↗
PubMedDate not supplied

Quantitative real-time RT-PCR analysis of eight novel estrogen-regulated genes in breast cancer.

BACKGROUND: Biological markers capable of predicting the risk of recurrence and the response to treatment in breast cancer are eagerly awaited. Estrogen and progesterone receptors (ER, PgR) in tumor cells mark cancers that are more likely to respond to endocrine treatment, but up to 40% of such patients do not respond. Here, the expression of a group of estrogen-regulated genes, previously identified by microarray analysis of in vitro models, was measured in breast tumors and possible associations with other clinicopathological variables were investigated. METHODS: The expression of CD24, CD44, HAT-1, BAK-1, G1P3, TIEG, NRP-1 and RXRalpha was measured by quantitative real-time RT-PCR on RNA from eighteen primary breast tumors. Statistical analyses were used to identify correlations among the eight genes and the available clinicopathological data. RESULTS: Variable expression levels of all the genes were observed in all the samples examined. Significant associations of CD24 with tumor size, CD44 with lymph node invasion, and HAT-1 and BAK-1 with ER positivity were found. The possible combinatorial value of these genes was assessed. Unsupervised hierarchical clustering analysis demonstrated that the expression profile of these genes was able to predict ER status with an acceptable approximation. CONCLUSIONS: Eight novel potential markers for breast cancer have been preliminarily characterized. As expected from in vitro data, their expression is able to discriminate ER- versus ER+ tumors.

Acetyltransferases↗
PubMedDate not supplied

Prognostic and predictive relevance of c-erbB-2 and ras expression in node positive and negative breast cancer.

The protein product of c-erbB-2 and ras oncogene has been examined for its prognostic potential in both node positive and node negative breast cancer. Using a western blot analysis, levels of these proteins were determined in 159 primary human breast tumor specimens. We examined relationships between gene expression and coexpression with other established markers of prognosis, as well as clinical outcome. Multivariate analysis showed that nodal involvement was the most powerful prognostic factor for predicting overall survival (< 0.000) and disease-free survival (p = 0.001), whereas c-erbB-2 expression was second only to nodal status for predicting overall survival in the whole series (p = 0.05). A separated stepwise analysis was conducted for node negative patients who did not receive any kind of adjuvant treatment and for node positive ones who underwent adjuvant chemo or hormonotherapy. c-erbB-2 expression independently predicted poor survival among node negative tumors (p = 0.001) and was associated with ras expression among node positive cases (p = 0.04). If adjuvant treatment is included in the model, coexpressing tumors are less responsive to Tamoxifen and CMF regimens than those with low levels of protein expression (p = 0.04). These results are potentially of clinical value in separating a subset of node positive breast cancer patients for more intense postsurgical treatment. Among node negative patients, the sole expression of c-erbB-2 enhanced levels, is more likely to retain a predictive value in relation to the response after conventional adjuvant treatment.

Breast Neoplasms↗