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Biomedical subjects

M G Daidone

Publications and source records attributed to M G Daidone.

105 records · Page 6Linked to original sources
PubMed1981

Relationship among estrogen receptors, proliferative activity and menopausal status in breast cancer.

Kinetic and estrogen receptor (ER) determinations were performed on 357 primary breast cancers. The proliferative activity of the cell population was determined by the autoradiographic technique and expressed as [3H]thymidine labeling index (LI): the ER status was assessed by the absorption charcoal technique. From the overall analysis of the relationship between proliferative activity and ER status, by using the median LI value as cutoff of low and high proliferating tumors, a correlation between ER + status and low proliferative activity and between ER- status and high proliferative activity was observed in 64% of the cases. Menopausal status proved to be an important determinant of kinetic and ER features. In fact, the proliferative activity was always higher in ER--tumors than in ER + tumors within the same menopausal group, and a decrease in proliferative activity was observed from premenopause to postmenopause within ER + and ER--tumors. The analysis of the relation between ER levels and proliferative activity in ER + tumors also evidenced three main ER/LI clusters significantly related to premenopause, paramenopause and postmenopause. A particular indication of nodal involvement was evidenced for a cluster of tumors with low ER levels and high LI from postmenopausal patients. The three different, previously proposed kinetic groups of potential relevance for prognostic and therapeutic purposes were confirmed and more precisely defined by considering not only premenopause and postmenopause but also paramenopause.

Adult↗
PubMed1979

Short-term tissue culture of human breast cancer: presence of estrogen receptors and 17 beta-estradiol stimulation of RNA synthesis.

The stimulation of RNA synthesis induced by estradiol has been studied on 60 breast cancers in short-term cultures. In the same tumors the estrogen receptor (ER) assay was carried out. In 35% of the cases studied the stimulating effect by estradiol in vitro was observed. The frequency of response to in vitro hormone treatment was higher (42%) in ER+ cancers and lower (25%) in ER- cancers. The specificity of the in vitro test was assessed by the use of tamoxifen.

Breast Neoplasms↗
PubMed1979

Relationship between proliferative activity and estrogen receptors in breast cancer.

The proliferative activity of breast cancer has been analyzed in relation to the hormonal characteristics of the host and of the tumor for 199 patients. The analyses of labeling index frequency distributions of estrogen receptor positive (ER+) and negative (ER-) cancers from premenopausal and postmenopausal patients have allowed us to identify three different kinetic groups. A first group, with a very low proliferative activity, includes ER+ cancers from postmenopausal patients; a second group, with an intermediate proliferative activity, includes ER+ cancers from premenopausal and ER- cancers from postmenopausal patients; and a third group, with a very high proliferative activity, includes ER- cancers from premenopausal patients. Generally, the amount of estrogen receptors in ER+ cancers is inversely correlated with the proliferative activity. Lower levels of ER in premenopausal in comparison to postmenopausal patients were found in low proliferative activity tumors.

Adult↗
PubMed1978

Prognostic significance of the labeling index in non-Hodgkin human malignant lymphomas.

The labeling index has been determined in 34 non-Hodgkin malignant lymphomas. The kinetic parameter has been analyzed in relation to the different histologic types, according to the Kiel calssification, and a kinetic classification with three main groups at low, intermediate, and high proliferative activity has been proposed. The analysis of the survival of the patients in relation to the labeling index of the malignant lymphoma cell population has shown that the potential proliferative activity has an important prognostic significance.

Humans↗
PubMedDate not supplied

Quality control for biomarker determination in oncology: the experience of the Italian Network for Quality Assessment of Tumor Biomarkers (INQAT).

Biomarker analysis and evaluation in oncology is the product of a number of processes (including managerial, technical and interpretation steps) which need to be monitored and controlled to prevent and correct errors and guarantee a satisfactory level of quality. Several biomarkers have recently moved to clinical validation studies and successively to clinical practice without any definition of standard procedures and/or quality control (QC) schemes necessary to guarantee the reproducibility of the laboratory information. In Italy several national scientific societies and single researchers have activated -- often on a pilot level -- specific external quality assessment protocols, thereby potentially jeopardizing the clinical reality even further. In view of the seriousness of the problem, in 1998 the Italian Ministry of Health sponsored a National Survey Project to coordinate and standardize the procedures and to develop QC programs for the analysis of cancer biomarkers of potential clinical relevance. Twelve QC programs focused on biomarkers and concerning morphological, immunohistochemical, biochemical, molecular, and immunoenzymatic assays were coordinated and implemented. Specifically, external QC programs for the analytical phase of immunohistochemical p53, Bcl-2, c-erb-2/neu/HER2, and microvessel density determination, of morphological evaluation of tumor differentiation grade, and of molecular p53 analysis were activated for the first time within the project. Several hundreds of Italian laboratories took part in these QC programs, the results of which are available on the web site of the Network (www.cqlaboncologico.it). Financial support from the Italian Government and the National Research Council (CNR) will guarantee the pursuit of activities that will be extended to new biomarkers, to preanalytical phases of the assays, and to revision of the criteria of clinical usefulness for evaluating the cost/benefit ratio.

Autoradiography↗
PubMedDate not supplied

Questioning the utility of pooling samples in microarray experiments with cell lines.

We describe a microarray experiment using the MCF-7 breast cancer cell line in two different experimental conditions for which the same number of independent pools as the number of individual samples was hybridized on Affymetrix GeneChips. Unexpectedly, when using individual samples, the number of probe sets found to be differentially expressed between treated and untreated cells was about three times greater than that found using pools. These findings indicate that pooling samples in microarray experiments where the biological variability is expected to be small might not be helpful and could even decrease one's ability to identify differentially expressed genes.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Relationship between steroid receptors (as continuous variables) and response to adjuvant treatments in postmenopausal women with node-positive breast cancer.

In current clinical practice for breast cancer patients, estrogen (ER) and progesterone receptor (PgR) concentrations, quantified by the dextran-coated charcoal assay, are categorized by an arbitrary cutoff into a negative or positive status. However, although the results obtained with this approach are easy to interpret, such a representation could oversimplify the relationship between ER and PgR content and patient outcome and imply an assumption of monotonicity, which is generally expected but rarely proven. We evaluated the relationship between ER and PgR content (considered on a continuous scale) and clinical outcome, using a flexible statistical model, in a group of postmenopausal patients with N-positive operable tumors who were submitted to surgery and different adjuvant treatments (tamoxifen or CMF). Univariate analysis indicated that in the tamoxifen-treated group, ER level, number of metastatic nodes (pN) and age, but not PgR, were significant indicators of clinical outcome (p = 0.032, p = 0.021 and p = 0.029, respectively). Multivariate analysis indicated that in this group of patients there was no interaction between variables, and in the final model for disease-free survival (DFS) only ER and pN were retained with an overall predictive ability of the regression model of 0.723, as evaluated by Harrell's c. However, pN markedly contributed to the predictive ability of the model with respect to ER, since a marked decrease in Harrell's c statistic (c = 0.582) was observed when pN was removed from the model. In the CMF-treated group, only pN affected clinical outcome. When the estimated DFS curves obtained from the final Cox regression models were plotted according to four values of ER (in the tamoxifen-treated group) or three values of pN (in the CMF-treated group) we observed that in the tamoxifen-treated group patients with an ER concentration equal to 0 fmol/mg cytosol protein had the worst prognosis, whereas a marked improvement of the expected DFS was observed for patients with a low but detectable ER level (generally classified as ER-negative because falling below the conventional cutoff value of 10 fmol/mg cytosol protein). Our results seem to suggest that the use of steroid receptor concentrations on a continuous scale, instead of dichotomous "status", is to be preferred in the choice of adequate therapeutic strategies.

Aged↗
PubMedDate not supplied

Flexible modelling in survival analysis. Structuring biological complexity from the information provided by tumor markers.

The aim of the present article is to introduce and discuss the problem of optimal modelling of the prognostic information provided by putative prognostic variables, possibly measured on a quantitative scale. A number of methodological aspects will be treated, with particular reference to the role of spline functions and artificial neural networks, which will be discussed in the context of the analysis of survival data. The problem of the evaluation and the choice of the optimal statistical models will be examined, with particular attention to the critical aspects related to the definition of prognostic indexes on the basis of the results of the selected models. Clinical examples in breast cancer on the evaluation of the prognostic impact of several tumor markers are provided. This paper is addressed to all researchers who are interested in the evaluation of the prognostic role of tumor markers, therefore we will stress the necessity of integrating the methodologies of biological, clinical and statistical research in the assessment of prognosis.

Biomarkers, Tumor↗
PubMedDate not supplied

Cholesteryl butyrate in solid lipid nanospheres as an alternative approach for butyric acid delivery.

BACKGROUND: Cholesteryl-butyrate chosen as lipid matrix of solid lipid nanospheres (SLNs) could be a suitable pro-drug to deliver butyric acid and overcome one of the most limiting disadvantages of the compound: the short half-life due to a rapid metabolism. METHODS: We evaluated the antiproliferative effect, with respect to that of sodium butyrate, of four SLNs (SLN1, SLN2, SLN3 and SLN4) characterized by a different concentration of cholesteryl-butyrate (range, 1.7-30 mM) on NIH-H460, a non-small cell lung carcinoma cell line. RESULTS: After 6 days of treatment, all SLN preparations induced a dose-dependent inhibition of NHI-H460 cell growth: the most effective SLN preparation (SLN1) was able to induce a complete growth inhibition already at 0.25 mM, a concentration at which sodium butyrate induced only a 55% inhibition. Fluorescence microscopy showed that 6-coumarin-tagged SLNs were almost completely internalized by cells after 5 min of treatment. CONCLUSIONS: The present results indicate that owing to their peculiar characteristics, SLNs could be an interesting alternative approach for butyric acid delivery into tumor cells.

Butyrates↗
PubMedDate not supplied

Immunoreactivity to MIB-1 in breast cancer: methodological assessment and comparison with other proliferation indices.

The recent availability of the monoclonal antibody MIB-1 (which is able to detect the human nuclear cell proliferation-associated antigen Ki-67 even on formalin-fixed, paraffin-embedded sections, microwave-treated and routinely processed for immunohistochemistry) could open new avenues for validation of the clinical role of tumour cell proliferation on large, consecutive and unselected series of human tumours. However, the routine use of such a marker requires a methodological standardization as well as the comparative assessment of some technical and biological aspects. The MIB-1 index was determined in parallel samples from 50 consecutive invasive breast carcinomas processed with different fixatives for different times. The median values of MIB-1 indices following 2, 6 and 24 h of formalin fixation were similar (29.4%, 30.6% and 29.7%, respectively) and consistent with those reported in the literature; squared linear regression coefficients were 0.99. The median values of MIB-1 indices were markedly lower in Bouin-fixed, paraffin embedded, and in frozen samples (20.0% and 19.8%, respectively), with a poor correlation coefficient with the values detected following formalin fixation (R2 = 0.456). Moderate and poor correlations were observed between Ki-67 index and MIB-1 detected on frozen (rs, 0.78) or formalin-fixed, paraffin-embedded samples (rs, 0.47) and a minimal concordance was observed between TLI and MIB-1 or Ki-67 (rs, 0.25 and 0.22, respectively). Our results indicate interference of the fixative type on immunoreactivity to MIB-1 and also suggest that Ki-67 and MIB-1 reacted with different epitopes of the same antigen.

Antibodies, Monoclonal↗