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Biomedical subjects

G Milano

Publications and source records attributed to G Milano.

At least 217 records · Page 12Linked to original sources

Intrahepatic polyamine levels during rat liver carcinogenesis induced by N-2-fluorenylacetamide.

During a period of 200 days, the chronological changes of polyamine levels (putrescine, spermidine and spermine) were observed in the liver of adult female Sprague Dawley rats submitted to hepatocarcinogenesis by N-2-fluorenylacetamide (FAA). Three groups of 70 rats each were used: (1) Control 1: normal diet; (2) Control 2: low protein and low riboflavin diet; and (3) EXPERIMENTAL: 0.06% FAA added to the diet. No significant differences were noted for tissue levels of the three polyamines when the two control groups were compared. In contrast, considerable variations of these molecules were observed as a function of time in the FAA treated group: (a) an early and constant rise was seen in putrescine, with 3 maxima at days 10, 60 and 150. This last peak was the highest: 25 +/- 6 nmol/g (8 times the value for the controls at this time), and coincided with the appearance of cancerous lesions. (b) While spermidine levels varied during the experiment, no significant differences were noted in comparison with the control groups. Mean levels (nmol/g) were: 535 +/- 108 Control 1; 552 +/- 95 Control 2; 633 +/- 160 FAA-treated group. (c) Spermine levels were significantly lowered, with 3 minima corresponding to the putrescine maxima. The lowest minima was observed on day 60: 114 +/- 67 nmol/g, i.e., 4 times lower than the controls. This work shows that polyamine metabolism is profoundly modified during chemical carcinogenesis, but the possible effect of polyamines on tumorigenesis itself cannot be assessed at this point since modifications of polyamine levels are probably also associated with phenomena of liver necrosis and compensatory tissue proliferation observed during the experiment.

2-Acetylaminofluorene↗

An improved method for routine analysis of polyamines in biological fluids with a conventional amino acid analyzer.

An accurate and precise mechanized ion-exchange chromatographic method for the estimation of polyamines in biological fluids is described. The method includes the recent improvements developed for ion-exchange analysis of polyamines: the use of sulfonated polystyrene cation-exchange resin with a bead diameter of less than 10 micrometers and a continuous fluorescent detection with o-phthalaldehyde. Four different procedures for the removal of protein before analysis of polyamines in plasma have been compared. Linearity of the fluorescence detection, reproducibility (intra, inter assay) and precision of the retention times are reported. Furthermore, the method is characterised by the simplicity of the sample preparation, a clear and rapid elution programme and especially by its routine applicability, as shown during the last six months in the Centre Antoine-Lacassagne.

Amino Acids↗

[Polyamines and malignant diseases (author's transl)].

The aliphatic polyamines (putrescine, spermidine, spermine) are associated with the phenomena of normal and neoplastic cellular growth. Two third of cancers generally show elevated urinary excretion of polyamines. The urinary levels of polyamines are significantly higher in cancer in evolution than in cancer in remission. The variable association of polyamines with different localisations is reviewed. The potential interest of polyamines analysis in the diagnosis and prognosis of cancer is discussed. The more exciting application of this test remains in the possibility of a short term appreciation of the oncostatic treatment efficiency.

Cell Division↗

Polyamines in lymphomas: their value in disease staging and monitoring of therapy efficiency.

The urinary polyamines putrescine and spermindine were evaluated in a population of 49 patients with malignant lymphomas (40 with non-Hodgkin's lymphoma and 9 with Hodgkin's disease). Analyses were performed on a regular basis during the course of treatment. Polyamine levels were found to increase significantly with the disease stage. Results show that: (a) polyamines closely reflect disease evolution (clinical deterioration/clinical improvement); (b) comparison of polyamine measurements effected 24 h prior to and 48 h after initiation of a chemotherapy course allows evaluation of the response to treatment.

Cell Transformation, Neoplastic↗

The clinical value of urinary polyamine analyses in cancer patients.

The polyamines, putrescine (P) and spermidine (S), have been measured in 185 cancer patients. Patients in remission exhibited significantly different levels from those with active disease. In a dynamic patient study, followed over a period of 5-6 months, the urinary polyamine levels correlated closely with the clinical status. Furthermore, polyamines have been measured 24 h before beginning chemotherapy (P1, S1) and 48 h after its onset (P2, S2). The value of the ratio, (S2/P2)/(S1/P1), was found to correlate with the type of response to chemotherapy.

Adolescent↗

Serum prealbumin, retinol-binding protein, transferrin, and albumin levels in patients with large bowel cancer.

In a study of the levels of serum prealbumin (PALB), retinol-binding protein (RBP), transferrin (TF), and albumin (ALB) in patients with large bowel cancer, critical values were established as (g/liter): PALB, 0.15; RBP, 40 X 10(-3); TF, 2.0; and ALB, 30. Values consistently below these were taken as a sign of malnutrition. The proteins in this system were interrelated and tended to show a similar pattern of change. Metastatic colon cancer caused a relatively small decline of ALB compared to the mean in tumor-free patients. PALB was the most sensitive indicator of nutrition, and its levels and rates of change had a prognostic significance. A rapid fall of PALB often occurred 2--3 months prior to the patients's death; this preterminal phase in ambulant patients was frequently heralded by a progressive rise in the level of C-reactive protein in the absence of any obvious infection.

Carcinoembryonic Antigen↗

Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas.

Epidermal growth factor (EGF) stimulates the growth of several types of epithelial tissues and possesses a strong mitogenic activity that is mediated through its cell surface receptor (EGFR). The aim of this study was to characterize EGFR and measure its levels in head and neck tumors biopsies (70 patients); use of a simplified competition technique with a radiolabeled ligand allowed evaluation of functional EGFR. Five samples (4 tumors and 1 control) were used to characterize EGF binding. Graphic representation identified a single family of binding sites. Kd values revealed high affinity for EGF binding: mean Kd, 0.156 +/- 0.108 nM (0.095-0.347 nM). EGF-binding characteristics (Kd) were similar in nontumoral tissue samples (controls) and in tumor material. In 59 of 60 cases, EGFR levels were higher in the tumor than in the corresponding controls. A significant correlation was found between EGFR levels and tumor size and stage. Controls exhibited a trend toward higher EGFR levels in elevated sizes and stages. According to a cutoff EGFR value of 100 fmol/mg protein, which separated all controls from tumors, EGFR-positive tumors (greater than 100 fmol/mg protein) had a greater probability of complete response to chemotherapy than EGFR-negative tumors; other tumor characteristics, such as the degree of tumoral differentiation, tumor size, or stage, were unable to operate such a discrimination in the response to chemotherapy. EGFR may thus be an interesting biological marker for head and neck cancer.

Adult↗

Sedimentation rate and serum thymidine kinase activity: prognostic factors in squamous cell head and neck cancer.

Identification of prognostic factors in squamous cell head and neck cancers involves analysis of highly diverse clinical and biological parameters. This study analyzed the prognostic value of clinical variables (age, sex, tumor site, stage) and biologic parameters (squamous cell carcinoma antigen [SCC], serum thymidine kinase activity [TK], fibrin, sedimentation rate [SR]) at the time of diagnosis of squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx) in 189 patients. Among the clinical variables investigated, UICC stage III-IV disease (p < .0002), a hypopharyngeal site (p < .02), and age over 60 years (p < .01) were all associated with a poor prognosis. Similarly, analysis of biological blood variables allowed definition of cut-off values above which the prognosis was poor: SCC 2.5 ng/mL (p < .01), fibrin 3.5 g/L (p < .01), TK 7 IU/L (p < .0005), and SR 15 mm per first hour (p < .0000). Cox regression analysis of overall survival identified the UICC stage (p < .000), the SR (p < .001), and serum TK (p < .02) as the main independent prognostic factors. A separate study on a small number of head and neck cancer patients revealed higher TK levels in malignant squamous cell carcinoma tissue than in adjacent healthy tissue.

Adult↗

Epidermal growth factor receptor assay: validation of a single point method and application to breast cancer.

Epidermal growth factor (EGF) is a 6000 kDa peptide which exerts its biological effects by binding to a specific cell membrane receptor (EGF-R). Extensive studies on EGF-R in breast tumors have demonstrated the prognostic value of such assays. EGF-R measurement is also reportedly potentially useful in other tumors. Classically, the EGF-R content of tumor cell membrane preparations is evaluated by competition between a given concentration of labeled ligand and various concentrations of unlabeled ligand. The large quantity of tumor tissue required (approx. 0.5 g) is a serious limitation for wide-spread use of EGF-R assays. In order to validate a miniaturized EGF-R assay method, the principle of a single-dose technique (SD) using a single concentration of labeled ligand (1 nM) was investigated in the present work. Only 100-150 mg wet tissue were required for routine analysis by the SD method. The correlation between the SD method and Scatchard analysis calculated from 41 different breast carcinoma samples was very satisfactory (r = 0.973, p less than 0.001). Analysis of intra-assay and inter-assay reproducibility revealed a comparable EGF-R status in given samples. The correlation between EGF-R levels and steroid receptors was investigated in 105 individual breast tumors. EGF-R levels were inversely correlated with the estradiol receptor values. No correlation was found with progesterone receptors. The simplified SD method for EGF-R measurement appears suitable for large scale clinical studies aimed at investigating the potential utility of this biological tumor marker.

Biomarkers, Tumor↗