EpCAM-autoantibody levels in the course of disease of ovarian cancer patients

EpCAM is a tumor-associated antigen, which is frequently expressed in ovarian cancer. Recently, autoantibodies against EpCAM have been identified in patients with ovarian cancer. It is not clear whether these autoantibodies are of prognostic importance. We evaluated whether EpCAM-autoantibodies have an impact on the clinical course of patients with ovarian cancer. EpCAM-autoantibodies were determined in sera of 28 healthy voluntary age-matched women and 84 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-protein for antibody detection by ELISA technique. The median follow-up time was 18 months. Samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. The antibody titer of healthy controls was 0.061 ± 0.015. Using a cut-off value of 0.091, we found 3/84 (4%) patients before and 12/61 (20%) patients with ovarian cancer to be positive for EpCAM-autoantibodies after first-line treatment. Using the paired T-Test, we noted a significant post-therapeutic increase of AABs (P < 0.0001). Notably, AAB-levels after first-line therapy were found to be correlated with the tumor resection status in primary surgery. Analysis of progression-free survival, FIGO stage, grading, age and sensitivity to platinum-based chemotherapy did not reveal significant associations with EpCAM-AAB titers. We observed an increase in AAB-levels during the first-line treatment of patients with ovarian cancer. EpCAM-AAB-levels after first-line treatment appear to correlate with macroscopic tumor residuals after initial surgery.     

The induction of systemic and mucosal immunity to protein vaccines delivered through skin sites exposed to UVB

It has been reported that common mucosal immunity can be efficiently induced in mice following immunization through the skin with vaccine formulations containing either the active form of vitamin D, or chemical agents capable of locally enhancing cyclic adenosine monophosphate levels. Herein, we report that exposure of skin to ultraviolet radiation B (UVB) can be employed as a means to alter systemic humoral immune responses and to promote the induction of mucosal immunity to protein antigens delivered into UVB-exposed skin sites. Our data indicates that the skin, as a vaccination site, can be manipulated to allow efficient induction of common mucosal and systemic immune responses.     

Vascular endothelial growth factor and prognosis in patients with node-negative breast cancer

Vascular endothelial growth factor (VEGF) has emerged as one of the most important angiogenic growth factors from experimental in vitro and in vivo studies. In the present study, we investigated the relationship between VEGF expression and microvessel density (MVD) and defined their prognostic relevance on a series of 242 patients with node-negative breast cancer, using immunohistochemical methods. In parallel, estrogen and progesterone receptors were quantitatively assessed using the dextran-charcoal technique and cell proliferation was evaluated as S-phase cell fraction according to (3)H-thymidine-labeling index (TLI). The percentage of VEGF-expressing cells varied from 0-95% in the different tumors and was unrelated to menopausal status, tumor size or steroid receptor status. Conversely, a significant inverse relation was observed with patient age or tumor cell proliferation, albeit with very poor correlation coefficients. A significant relation was observed between VEGF expression and MVD (r(s) = 0.55, p < 0.001). Clinical outcome analyzed as a function of high and low VEGF expression showed slight differences in terms of both disease-free survival (DFS) and overall survival (OS) that never reached statistical significance. Moreover, the trend was paradoxically in favor of patients with highly VEGF-expressing tumors. Finally, DFS and OS curves, when analyzed as a function of VEGF expression or MVD, were superimposable. In conclusion, our study did not highlight a prognostic relevance of VEGF expression in patients with node-negative breast cancer, as already observed for MVD.     

Frequency of RAS and p53 Mutations in Acute Promyelocytic Leukemias

The frequency of RAS and p53 mutations was investigated in 30 acute promyelocytic leukemias by single strand conformation polymorphism analysis and direct sequencing of ge-nomic DNA. Only two cases bore N-RAS codon 12 mutations and none had p53 mutations responsible for aminoacid substitutions. It would, therefore, seem that neither RAS nor p53 are involved in acute promyelocytic leukemogenesis.     

Direct visualization of aorto-coronary bypass grafts by two-dimensional echocardiography: A new clinical application

An attempt was made to assess noninvasively the patency of aorto-coronary bypass grafts by two-dimensional echocardiography (2-D echo) in 21 patients who underwent myocardial revascularization. Fifteen patients had one graft while the other six had two grafts. All 21 patients underwent angiography 6–18 months after operation. A day before angiography a 2-D echo was performed with the aim of visualizing the bypass grafts. In 18 patients with 23 grafts (13 with 1 graft and 5 with 2 grafts) it was possible to visualize the tract of the graft, by 2-D echo; 16 were judged patent on 2-D echo and confirmed by selective angiography, while 5 grafts were considered occluded both on 2-D echo and angiography. The other 2 grafts were considered to be occluded on 2-D echo but angiographic control displayed their patency. In 3 patients 2-D echo failed to visualize grafts that were patent angiographically. These data must be considered preliminary and need validation in a larger number of patients. However it is reasonable to conclude that 2-D echo has a reliable capacity to predict graft patency. Such an application may be of value in sequential control of patients with aorto-coronary bypass surgery, especially when combined with other clinical and/or technical data.     

Acute promyelocytic leukaemia: epidemiology and risk factors. A report of the GIMEMA Italian archive of adult acute leukaemia

Abstract: Acute promyelocytic leukaemia (APL) exhibits peculiar epidemiological, clinical, cytogenetic and molecular features, compared to the other acute myeloid leukaemias (AML). Data on epidemiology and occupational risk factors for APL desumed from the GIMEMA archive are reported and compared with those of the other AML. An exploratory case-case study was designed on AML patients from 56 haematology centres in Italy. Overall, 4296 patients older than 15 yr with a new diagnosis of acute leukaemia were recorded between July 1992 and July 1997. Of these, 335 were classified as APL, and 2894 as other AML. The median age of APL patients was 43 compared to 59 yr for the other AML (p< 0.00001). In order to identify peculiar risk factors for APL development, different parameters were compared in the 2 groups. After adjusting by age no significant differences were observed with regard to education, lifetime prevalence of cancer among siblings and previous diseases in the patient's history. Occupational exposure as a possible risk factor for APL showed no increased risk compared to other AML among farmers, builders and leather workers. A significant association was found in electricians (OR = 4.4, 95% CI = 2.0–9.7) and a weak association was found in wood workers (OR = 3.2, 95% CI = 0.8–10.8). The proportion of APL with respect to other AML was significantly higher in the north east of Italy compared to the rest of the country (OR = 1.7, 95% CI = 1.3–2.2). These data confirm the younger age of APL patients compared to the other AML. A possible role of electromagnetic fields is suggested by the higher risk of APL in electrical workers and in the more industrialized areas of the country.     

Binding of estrogenic compounds to recombinant estrogen receptor-alpha: application to environmental analysis

Estrogenic activity in environmental samples could be mediated through a wide variety of compounds and by various mechanisms. High-affinity compounds for estrogen receptors (ERs), such as natural or synthetic estrogens, as well as low-affinity compounds such as alkylphenols, phthalates, and polychlorinated biphenyls are present in water and sediment samples. Furthermore, compounds such as polycyclic aromatic hydrocarbons, which do not bind ERs, modulate estrogen activity by means of the aryl hydrocarbon receptor (AhR). In order to characterize compounds that mediate estrogenic activity in river water and sediment samples, we developed a tool based on the ER-alphaligand-binding domain, which permitted us to estimate contaminating estrogenic compound affinities. We designed a simple transactivation assay in which compounds of high affinity were captured by limited amounts of recombinant ER-alpha and whose capture led to a selective inhibition of transactivation. This approach allowed us to bring to light that water samples contain estrogenic compounds that display a high affinity for ERs but are present at low concentrations. In sediment samples, on the contrary, we showed that estrogenic compounds possess a low affinity and are present at high concentration. Finally, we used immobilized recombinant ER-alpha to separate ligands for ER and AhR that are present in river sediments. Immobilized ER-alpha, which does not retain dioxin-like compounds, enabled us to isolate and concentrate ER ligands to facilitate their further analysis.