Enhancement of splenic-macrophage Fcgamma receptor expression by treatment with estrogens.

Splenic-macrophage Fcgamma receptors (FcgammaRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of macrophage FcgammaR expression is an immuno-therapeutic target. Glucocorticoids, sex steroids, and dopaminergic drugs modulate macrophage FcgammaR expression. Previous data indicate that estradiol increases macrophage FcgammaR expression. Nevertheless, the effects of clinically used estrogens upon macrophage FcgammaR expression are unknown. We assessed the effects of treatment with commonly used estrogens on the expression of macrophage FcgammaRs using a guinea pig experimental model. Six estrogens have been studied: ethynylestradiol (Et), mestranol (M), chlortianisene (Ct), promestriene, 17-epiestriol, and 17beta-estradiol. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic-macrophage FcgammaR cell surface expression. Estrogens enhance the clearance of IgG-sensitized erythrocytes by increasing splenic-macrophage FcgammaR expression. Et, M, and Ct were more effective than the other estrogens. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that estrogens increase the cell surface expression of FcgammaR1 and -2 more than that of FcgammaR2. These data indicate that treatment with commonly used estrogens enhances the clearance of IgG-sensitized cells by improving splenic-macrophage FcgammaR expression.

La proteína p53 y el cáncer de mama. Revisión crítica / The p53 protein and breast cancer

Es una revisión crítica de las bases biológicas de la proteína p53 en la apoptosis, su importancia en la carcinogénesis experimental y humana y los procedimientos técnicos de laboratorio que pueden emplearse para su determinación en los enfermos de cáncer. La hiperexpresión de p53 por la presencia de una mutación origina una acumulación excesiva en los tejidos, relacionada con la vida media de la proteína mutada que es aproximadamente unas 60 veces más larga que la proteína natural. Los clínicos hablan de positividad de la p53 como la presencia de p53 mutada. Quizás, uno de los aspectos mejor estudiados de esta proteína es su comportamiento en el cáncer de mama. Actualmente puede ser considerada un factor pronóstico del cáncer de mama y es recomendable incluirla entre las determinaciones inmunohistoquímicas a realizar en la pieza por el anatomopatólogo clínico. Los procedimientos empleados para investigar la p53 son:a) análisis molecular; b) análisis inmunohistoquímico, y c) análisis serológico. El último es un nuevo y prometedor procedimiento serológico para detectar la p53 mutada en sangre periférica que abre importantes expectativas. Es útil para identificar los casos de mal pronóstico entre el grupo favorable con N0 (ganglios axilares negativos) (AU)

Serum ceruloplasmin as a diagnostic marker of cancer.

The pursuit of the ideal tumor marker has generated many tests for use in the diagnosis and management of cancer, several of which are now widely available. The objective of this study was to evaluate the diagnostic utility as a cancer marker of plasmatic levels of ceruloplasmin. Ceruloplasmin is a glucoprotein that transports serum copper. A case-control design was used. Serum values were evaluated in 144 patients and 103 normal controls by receiver operating characteristic (ROC) curve analysis to define the optimal cut-off levels for the serum values of ceruloplasmin in the diagnosis of cancer. The ROC analysis showed that ceruloplasmin is considerably sensitive in men (80%) at the specificity level of 80.3% and in women the sensitivity (Se) was (63.2%) and the specificity (Sp) was (63.3%). According to this study, it would seem optimal to use the cut-off level of 358 mg/l in men and 383 mg/l in women. In conclusion, serum ceruloplasmin was significantly elevated in advanced stages of solid malignant tumors, however, locally advanced or locoregionally spreading tumors did lead to significant increases (P < 0.01). Finally, the results of ROC curve analysis suggest that the ceruloplasmin is characteristic of good diagnostic markers.

Evaluation of lipid-bound sialic acid (LSA) as a tumor marker.

The objective of this study is the evaluation of serum levels of lipid-bound sialic acid (LSA) as a of marker cancer. This is a case-control study, and the levels of LSA were determined with blinded duplicates of cases and controls. Histologic verification of all cancer cases was used to confirm the diagnosis. The study included 135 patients with cancer (breast carcinoma, head and neck squamous cell carcinoma, lung cancer and gastrointestinal cancer) and 95 controls (57 normal subjects and 38 with chronic non-malignant diseases). Marker determination was done by the spectrophotometric procedure of Katopodis with resorcinol. The mean LSA level in the 57 healthy individuals was 15.09 mg/dl(95% C.I., 13.51-16.67), in the entire control group of 95 non-tumoral individuals it was 19.21 mg/dl (17.18-21.24), and in the 135 cancer patients it was 26.64 mg/dl (24.42-28.87). There was a statistically significant difference between patients with chronic non-tumoral diseases and healthy individuals (p < 0.001) and also between cancer patients and healthy individuals (p > 0.001), but not between cancer patients and patients with chronic non-tumoral diseases (p> 0.05). The mean LSA serum values related to tumor site were (mg/dl): breast cancer, 21.49; gastrointestinal tumors, 28.45; head and neck cancer, 28.61 and lung cancer, 32.54. The means according to clinical stage were: complete remission, 18.50 significantly higher than the healthy controls (p< 0.05); local disease, 23.50 (p < 0.01); locoregional disease, (p < 0.05); local disease, 23.50 (p < 0.01); locoregional disease, 27.21 (p < 0.001); metastatic disease, 34.49 (p < 0.001), and relapses, 20.87 (p< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Utility of plasmatic levels of alpha-1-antiprotease (A1AP) as a cancer marker.

The objective of this study was to evaluate the diagnostic utility as a cancer marker of plasmatic levels of A1AP. This case-control study included 135 cancer patients from different sites, confirmed histologically, and 95 controls (57 normal individuals plus 38 chronically ill patients with non-tumoral diseases). Determination of A1AP was done by a nephelometric procedure using a laser nephelometer as the measuring instrument. There were no sex or age related variations in plasmatic A1AP. Mean values of A1AP in 57 normal controls was 2.87 milligrams (95% C.I., 2.58-3.15); in 95 non-tumoral individuals, including 38 chronic non-malignant diseases plus 57 normal controls, 3.09 milligrams (2.46-3.72) and in malignant tumors, 4.12 milligrams (3.80-4.45). There was a statistically significant difference between chronic diseases and normal controls (P < 0.05) and also between cancer patients and non-tumoral individuals, normal control and chronic non-tumoral diseases (P < 0.001). The means of plasmatic A1AP by tumoral site are increasing in this order: breast, gastrointestinal, head and neck, and lung. The means by clinical stage are increasing in this order: complete remission, local disease, local-regional disease and metastatic disease. The calculated cutoff value, excluding complete remission cases, is 3.37 milligrams, with sensitivity 67.7% and specificity 67.7%. We conclude that there is an increase of plasmatic A1AP in cases of clinically active cancer compared with normal controls and normal range values in clinical complete remission. It can be an acceptable cancer marker that discriminates cancer from chronic non-tumoral diseases and complete clinical remission from relapses.

Utility of serum activity of angiotensin-converting enzyme as a tumor marker.

The objective of this study was to evaluate the diagnostic utility of the measurement of the serum activity of angiotensin-converting enzyme (SACE) as a cancer marker. This case-control study included 135 patients with cancer of different sites, confirmed histologically, and 145 controls (107 normal individuals plus 38 chronically ill patients with nontumoral diseases). Determination of SACE activity was done by a spectrophotometric method using as substrate the synthetic tripeptide N-(3-[2-furyl]acryloyl)-L-phenylalanylglycine. There were no sex- or age-related variations in SACE activity. Mean SACE activity in 107 normal controls was 51.6 U/l (95% C.I., 50.1-53.1); in 145 nontumoral individuals, including 38 chronic nonmalignant diseases plus 107 normal controls, 51.5 (50.1-53.1) and in malignant tumors 35.7 (32.8-38.5). There was no statistically significant difference between chronic diseases and normal controls (p > 0.05); but there was one between cancer patients and nontumoral individuals, normals and chronic nontumoral diseases. The mean of SACE activity values by tumoral site are (U/l; 95% C.I.): breast, 41.3 (36.2-46.5); gastrointestinal 31.5 (24.3-38.8); head and neck, 32.3 (26.7-37.8), and lung 27.6 (21.6-33.6) (p < 0.001). The means by clinical stage are: complete remission, 58.0 (53.7-62.3), significantly higher than in normal controls (p < 0.001); local disease, 40.56 (34.5-46.5); locoregional disease, 35.09 (30.7-39.4); metastatic disease, 23.04 (19.5-26.5), and in relapse at diverse stages, 30.86 (25.1-36.5). In clinical active cases, there is a statistically significant decrease of SACE activity, especially in metastatic disease (p < 0.001). The calculated cutoff value, excluding complete remission cases, is 40.7 U/l, with sensitivity of 69.5% and specificity of 91.6%. We conclude that there is a decrease of SACE activity in cases of clinically active cancer and an increase in clinical complete remission.

Plasmatic fibronectin in malignancies.

Plasmatic fibronectin has been studied in tumor patients on the basis of the role that unspecific opsonin may play in tumor growth and spreading. Alterations in fibronectin levels might be used as a biological marker and our purpose has been to evaluate the significance of this test in the biological diagnosis of cancer. When comparing the levels found in the control group (22.86 +/- 1.40 mg/dl) and in tumor patients (23.80 +/- 1.90 mg/dl), we observed no difference in the overall group. However, in relation to the localization of tumors, a significant increase was found in breast cancer (31.83 +/- 3.83 mg/dl) and a significant decrease in squamous cell carcinoma of the head and neck (9.56 +/- 1.68 mg/dl). These results suggest that plasmatic fibronectin could be useful as a biomarker in some types of tumors. Our conclusion was confirmed by analysis of ROC curves related to every one of the studied tumors.

[Ceruloplasmin levels in patients with chronic obstructive bronchopneumopathy]. / Niveles de ceruloplasmina en enfermos con bronconeumopatía crónica obstructiva.

The seric levels of ceruloplasmin in a group of 20 patients suffering of chronic obstructive lung disease were studied. Levels in this group of patients (51.42 +/- 11.15 mg/dl) (p less than 0.005) were significantly higher than those of the control group (36.59 +/- 13.37 mg/dl). There was no correlation between ceruloplasmin levels and PaO2, PaCO2, SaO2, HCO3- measurements. Results show a possible oxidation reaction; owing to the fact that ceruloplasmin is a general oxidase which, combined with an antioxidant stimulus of patients with chronic respiratory insufficiency, can produce this reaction.

[Results of the functional tests using calcitonin in patients with chronic diffuse hepatopathy]. / Resultados de la prueba funcional con calcitonina en pacientes con hepatopatía crónica difusa.

A group of ten patients suffering cirrhosis who were treated with 100 U/l of calcitonin was studied with the aim of knowing whether in patients with cirrhosis the calcitonin is able to provoke the usual characteristic biologic modifications on the basis of the knowledge of their hormonal high levels accompanied of oesteopenia. Regarding their baseline determinations, no statistically significant modifications have been observed in calcium, phosphorous, alkaline phosphatase or its thermostable and thermolabile fractions, magnesium, uric acid and creatinine plasma concentrations respectively. This absence of a biological response to calcitonin could be due either to a numeric or functional damage of the hormone receptors or a diminished biodisponibility, although there are facts suggesting a lesser hormone biopotenciality in these patients.