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Biomedical subjects

L Castagnetta

Publications and source records attributed to L Castagnetta.

48 records · Page 3Linked to original sources
PubMed1989

Morphometry of in vitro systems. An image analysis of two human prostate cancer cell lines (PC3 and DU-145).

Morphometric analysis on two human prostate cancer cell lines (PC3 and DU-145) was carried out to better characterize these cells and to approach some problems concerning their polymorphism. In our hands, these cells appear to differ either in their ability to oxidize testosterone or in their androgen receptor content. Morphometric evaluation was performed by means of an Interactive Image Analysis System (IBAS 1), which computes several parameters related to the whole cell and to the nucleus. Our results clearly indicate that nuclear parameters alone may discriminate PC3 from DU-145 cells. Particularly, the Nuclear Roundness Factor appeared important, since it quantifies changes in nuclear shape. Nevertheless, the value of this parameter for "in vitro" morphometry may be overshadowed by the polymorphism common to the cultured cells. However, morphometric evaluation of PC3 and DU-145 cells is relevant to a better understanding and definition of the biologic nature of these cells, even if polymorphism, heterogeneity and genetic instability, specially of PC3, require further investigations.

Cell Nucleus↗
PubMed1989

Do multiple oestrogen receptor assays give significant additional information for the management of breast cancer?

In 101 breast cancer patients, measurement of oestrogen receptor status in multiple biopsies across a tumour reveals a highly significant difference in the proportion of patients remaining either disease-free (P less than 0.04) or alive (P less than 0.005), when those with uniformly receptor positive (++) primary tumours are matched with clinically comparable patients whose tumours were homogeneously receptor negative (--). Mean follow-up time was 85 months. The prognostic value of this discriminant is particularly striking in the 53 patients with involved nodes at presentation. Of these, 13 were (++) and seven remain alive of whom six are disease-free, whereas 24 of the 29 (--) patients are dead. These results further suggest that receptor assay on a single homogenate gives less clinical information than do assays on multiple biopsies across the tumour. For patients with involved nodes, clinical management may best be decided after determination of 'macroheterogeneity'.

Breast Neoplasms↗
PubMed1987

Heterogeneity of soluble and nuclear oestrogen receptor status of involved nodes in relation to primary breast cancer.

Both soluble and nuclear oestrogen receptors were measured in at least two different portions of primary breast cancer and in concurrent metastatic tissue from axillary nodes. Oestrogen receptor (ER) status of involved nodes was found highly consistent with that of primary tumours. Of the 67 patients studied, 30 had metastatic nodes which contained both soluble and nuclear ER. Of these, 27 were associated with a primary cancer which also had both soluble and nuclear ER, determined in at least two separate parts of the primary cancer. Conversely, none of the completely negative primaries gave rise to fully receptor positive metastatic tissue. Surprisingly, 17 out of 20 heterogeneous primary tumours, i.e. those containing both receptor positive and negative components, generated receptor negative metastatic nodes. Moreover, in 7 of the 8 patients with N-2 stage nodal involvement, the metastatic disease had arisen from primaries which were either completely receptor negative or with a heterogeneous ER status. It is suggested that macroscopic heterogeneity of ER status in primary breast cancer is associated with poor prognosis.

Adult↗
PubMed1987

Soluble and nuclear oestrogen receptor status of advanced endometrial cancer in relation to subsequent clinical prognosis.

Both soluble and nuclear oestrogen receptors have been measured in at least two separate sections from 72 endometrial cancers and 12 normal endometria. Concentration of oestrogen receptor is shown to be, in our hands, more meaningful when expressed per unit DNA than per unit protein, whether for soluble or nuclear receptor. Endometrial cancer cells from the central part of the tumour are shown to be receptor negative more frequently than those from peripheral tumour. Thus, in large cancers, biopsies from different areas are required before a tumour can be correctly designated as receptor positive, heterogeneous or receptor negative. The intratumoral variation of receptor status may relate to poor prognosis, since patients with homogeneous receptor-positive disease survive significantly longer than those with tumours showing either heterogeneous distribution of receptor or homogeneous absence of receptor. Intratumoral variation in receptor status is found to be more common in the group of patients who are within 7 years of their menopause, than in older patients.

Adult↗
PubMed1986

Estrone conversion rates by human endometrial cancer cell lines.

Studies on estrone metabolism by long term human endometrial cancer HEC-1A and Ishikawa cell lines are reported. These cell lines grow well in epithelial mono or plurilayer form, as previously reported. Ishikawa cells appear to be estrogen responsive whereas HEC-1A appear non responsive. In our experience Ishikawa cells show high affinity--low capacity estrogen binding sites in both soluble and nuclear fractions of the same range of ZR 75-1 and of MCF7, but HEC-1A cytosols gave Kd values in the order of 10(-8)-10(-9). These values are probably more representative of estrogen receptors of low affinity-high capacity (site II) and this is in agreement with previous results regarding their poor response to estrogens. These two different endometrial cancer cell lines exhibit at the same time, common and quite dissimilar metabolic patterns of estrogens. In fact, metabolic conversion studies carried out after 24th incubation at not far from physiological concentrations by using high pressure liquid chromatography in reverse phase mode plus "on line" radioactive detection showed: Both these well established cell lines are fast growing in culture with sufficient morphological or biochemical stability, at least during a limited number of passages and appear a useful material for studies on steroid metabolism. In both, estradiol (E2) and estrone (E1) were most part of converted products (more than 95%); negligible amounts of other radio-metabolites were observed. Quite different conversion rates of E1 to E2 have been shown by HEC-1A cells (6 times or more), with respect to Ishikawa.

Cell Line↗
PubMed1986

Steroid profiles and optimization of high-performance liquid chromatographic analytic procedure.

This paper presents a short review of the results obtained to date in our laboratory, with respect to the studies of steroid excretion profiles in both breast and endometrial cancer patients, by using gas-liquid chromatographic analysis. These data demonstrate the importance of minor estrogens, including catechol estrogens, and of their ratios with the classical ones, in studies of steroid metabolism in both breast and endometrial cancer. New data concerning postmenopausal endometrial cancer are consistent with our previous observations and demonstrate the necessity of measuring these steroids directly in tumors and examining patterns of metabolism in vitro. In order to analyze steroid metabolic patterns in vitro, however, high-performance liquid chromatography rather than gas-liquid chromatography methods are preferable on account of their selectivity, specificity, sensitivity and capacity to handle labile materials. With the aim of providing methods suitable for the complete resolution and analysis of these complex natural mixtures a method of computer-aided optimization of HPLC has been developed and its practical utility has been tested.

Adrenal Cortex Hormones↗
PubMed1985

Modulation of oestrogen excretion profiles by adjuvant chemotherapy in pre- and postmenopausal breast cancer.

Modulation of steroid status by conventional chemotherapy was studied in 31 breast cancer patients receiving CMF and in 31 age-matched breast cancer patients without any therapy, taken as controls. This was achieved through the study of oestrogen excretion profiles using previously identified parameters and referring not only to classical but also to the "other", namely catechol and unusual, oestrogen metabolites. After CMF treatment the premenopausal patients exhibit a modified excretion pattern, mainly concerning a marked and significant reduction of classical oestrogens, as shown by pattern indices. Because there is evidence that oestriol metabolism is not markedly affected by CMF treatment, such a significant decrease in classical oestrogens must be attributed to the secretory function, presumably ovarian ab origine. To the contrary, after treatment, pattern indices show significantly higher median values in postmenopausal patients. Mean oestriol ratio values also display a significant increase, thus supporting the hypothesis that conventional cytotoxic drugs may act by enhancing oestrogen metabolic rates. In fact, the postmenopausal treated subgroup proved to have significantly higher excretion levels of most of the oestrogens considered to date. Surprisingly, E1 + E1-S fractions were strongly reduced in this subgroup and this leads to the suggestion of an increased steroid metabolic rate by CMF treatment. However, comparing 9 breast cancer patients, when having had both short-term and non-short-term CMF treatment, the effects on steroid excretion patterns appear to arise at an early stage.

Adrenal Cortex↗
PubMed1984

Solvent optimization of reversed-phase high-performance liquid chromatography for polar adrenal steroids using computer-predicted retentions.

Computer-aided optimization of a mobile phase has been applied to the isocratic reversed-phase separation of ten polar adrenocortical steroids, including aldosterone and reduced metabolites of cortisol and cortisone. A method based on a seven-step procedure for calculation of the Chromatographic Optimization Function (COF) has been used. Logarithmically transformed retention indices were used for computing multiple polynomial regressions for the retention times of compounds as a function of solvent composition, with the resultant COF as a dependent parameter used for selection of the better mobile phase. Peak crossovers and overlaps are accommodated in this method and the maximum acceptable analysis time factor is incorporated as well as weighting factors for priority separations. The utility of this procedure for complex mixtures of closely eluting compounds is discussed with respect to the Overlapping Resolution Map method and with the COF method of Glajch and Kirkland as used for automated optimization. Its application to aldosterone-containing samples from human adrenocortical tumours is illustrated.

Adrenal Cortex Hormones↗
PubMed1983

Intra-tumoural variation of oestrogen receptor status in endometrial cancer.

Soluble and nuclear oestrogen receptor status was determined in both the central and peripheral portions of tumour for 37 cases of adenocarcinoma of the endometrium. Of these, 29 had functional receptor in the peripheral biopsy, but only 19 retained functional receptor in the centre. Six of the 10 patients whose tumours showed this difference came from the group of 12 patients who were immediately post-menopausal (4.50 +/- 1.45 y post-menopausal age). Receptor status was not related to tumour classification into histological grades I and II. However, receptor-negative central biopsies were significantly more likely (P less than 0.05) to be Grade III. Early relapse was also related to a receptor-negative central biopsy.

Adenocarcinoma↗
PubMed1981

Breast cancer: a comparison of response to endocrine therapy and oestrogen excretion patterns including unusual metabolites.

The urinary excretion patterns of oestrogen metabolites, including unusual metabolites, were determined by gas chromatography and mass spectrometry for 63 women with advanced breast cancer and 39 normal postmenopausal women. The concentration of total unusual metabolites excreted was found to be an excellent discriminant between breast-cancer patients and controls (P less than 0.0001). Discrimination between responders and non-responders to endocrine therapy was attempted, using several different indices. Of these, the ratio of Classical Oestrogens to Unusual Metabolites (CE/UM) proved a fair discriminant, but the product of this ratio and the oestriol ratio (CE/UM x E3R) was much the best discriminant. This product, termed a Pattern Index, has considerable potential, not only as a discriminant for selecting therapy, but also as a rapid index of patient response to that therapy.

Aged↗