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Biomedical subjects

E Bombardieri

Publications and source records attributed to E Bombardieri.

At least 199 records · Page 11Linked to original sources

Single determination of CA 15.3 and bone scintigraphy in the diagnosis of skeletal metastases of breast cancer.

Single determination of CA 15.3 and bone scintigraphy were performed on the same day as follow-up procedures in 864 patients with breast cancer. The sensitivity and specificity of bone scintigraphy for skeletal metastases were 99% and 88.8%, respectively. The overall sensitivity and specificity of CA 15.3 (cut-off for pathological values greater than 30 U/mL) for cancer recurrence or distant metastases were 69.2% and 92.1%, respectively. The sensitivity of CA 15.3 for bone metastases was lower (69.4%) than that of bone scintigraphy. This was mainly due to the relatively high proportion of false-negative CA 15.3 levels in patients with 1-2 bone metastases (sensitivity = 33.3%). According to this result, the circulating levels of CA 15.3 showed a good correlation with tumor extension and, in patients with bone metastases, with the number of skeletal lesions. As regards the contribution of CA 15.3 to the diagnosis of bone metastases, the demonstration of elevated CA 15.3 values in patients with positive bone scintigraphy could support the diagnosis of skeletal metastases. In fact, the positive predictive value of CA 15.3 in patients with positive bone scintigraphy was significantly higher than with only bone scintigraphy (53.8%) or CA 15.3 (50.4%). Finally, very high values of CA 15.3 in patients with known bone metastases could indicate the presence of visceral metastases (mean CA 15.3 in patients with bone metastases = 125.8 U/mL; mean CA 15.3 in patients with bone and visceral metastases = 420.5 U/mL).

Adult↗

Circulating tumor markers in breast cancer (review).

The clinical application of circulating tumor markers remains a controversial subject in terms of useful methods and correct interpretation of findings. In particular and despite numerous investigations in the field, we do not have as yet specific or highly sensitive biological markers in breast cancer. Nevertheless, many oncologists often utilize circulating tumor markers in various phases of this malignancy to obtain additional information about disease extent and clinical course. For this reason, we have reviewed the present status of the most widely used serum tumor markers in this neoplasm. Both CEA and TPA are well known, but their organ specificity is not related to breast. Among novel biological markers identified by monoclonal antibodies, special attention has been devoted to circulating agents that are recognized by immunoreagents and that were obtained by immunization with breast-derived products. Both CA 15.3 and MCA are now being validated at the clinical level. From the present review it is clear that today we are still far from being able to make the diagnosis of breast cancer on the sole basis of laboratory findings. On the contrary, some of the available markers can be utilized as prognostic indicators of disease extent and treatment response. Their value greatly increases when combined with conventional diagnostic methods that can be prescribed on the basis of abnormal laboratory findings to confirm or rule out disease recurrence.

Antigens, Neoplasm↗

Effects of alpha, beta and gamma recombinant interferons on CEA production from HT-29 human colon adenocarcinoma cell line.

The human colon adenocarcinoma derived cell line HT-29 is a good in vitro model for the study of CEA production and release under various experimental conditions. Many studies indicate that CEA secretion is correlated with cell proliferation and seems to depend on the growth conditions and differentiation characteristics induced by the culture medium. The present study demonstrates that recombinant interferons alpha, beta and gamma (rIFN alpha, rIFN beta, rIFN gamma) can modify CEA production and release by HT-29 cell-line. rIFN gamma in particular causes an enhancement of CEA production and release in the culture medium. This dose-depending effect is in some way correlated to cell growth inhibition since the enhancement of CEA expression in the interferon treated cells is evident in the presence of a reduction in cell proliferation. The activity of rIFN alpha and rIFN beta on CEA release is much less remarkable than that demonstrated by rIFN gamma, and is probably only due to the fact that HT-29 colon adenocarcinoma cells respond poorly to the effects of rIFN alpha and rIFN beta at the doses we used. These findings suggest that CEA production, expression and release can be modulated in a variety of ways under the influence of different rIFN treatment and this situation must be taken into account in immunodiagnostic and immunotherapeutic applications of anti-CEA monoclonal antibodies in the cancer patient.

Adenocarcinoma↗

Effects of cholesterol and alfa-2-recombinant interferon on cell growth and cell antigen production in the HT 29 cells, an established cell line of human colon adenocarcinoma.

HT 29 cells, an established cell line of human colon adenocarcinoma, were grown in RPMI 1640 medium without or with cholesterol at 25, 50, 100 micrograms/ml concentrations. In some experiments 100 or 200 U/ml alfa-2-A recombinant Interferon were added to the medium. Only in the case of the highest cholesterol concentration there was a reduced number of cells at confluence. Moreover, only the production of CEA increased in the presence of cholesterol. Interferon did not affect cell growth appreciably but stimulated CEA release into the medium during the first three days of culture. Morphological analysis of cells in the presence of cholesterol seems to indicate an attempt of the cells to differentiate.

Adenocarcinoma↗

Biochemical characteristics and clinical applications of alpha-fetoprotein isoforms.

Alphafetoprotein (AFP) is an oncofetal glycoprotein that frequently reappears in sera of patients affected by hepatocellular carcinoma (HCC) and yolk-sac tumours (YST). In these cases AFP determination represents a useful marker for monitoring the therapeutic response and the clinical evolution of the neoplastic disease. AFP is a heterogeneous molecule with respect to the carbohydrate moiety and the different AFP glycoforms can be separated and characterized by their affinity for lectins, such as Concanavalin A (con A), and Lens culinaris agglutinin (LCA). Increased production of LCA-reactive AFP has been proposed as a specific and early marker for HCC, while Con A non-reactive AFP could be a marker for YST and gastrointestinal malignancies. In this review the molecular basis of AFP microheterogeneity and the clinical application of AFP isoforms will be discussed.

Carbohydrate Sequence↗

Thymidine kinase (TK) activity as a prognostic parameter of survival in lymphoma patients.

ATP-thymidine 5'-phosphotransferase (TK) is a cellular enzyme involved in DNA synthesis, activated during the G1/S phase of the cell cycle. Elevated TK serum levels can be found in cancer patients due to the active proliferation of tumor cells. TK serum activity was tested by a radioenzymatic technique (Prolifigen TK REA, Sangtec Medical, Sweden) based on the conversion of 125 I deoxyuridine to 125 I deoxyuridine monophosphate. A total of 181 patients were enrolled in this study: 133 lymphomas (Hodgkin, HL and Non-Hodgkin, NHL) 48 benign diseases including acute (n = 17) and chronic inflammatory diseases (n = 13), myocardial infarction (n = 11), liver cirrhosis (n = 2), renal failures (n = 2), and diabetes (n = 3). Lymphoma patients were classified according to the Ann Arbor staging system, and 103 NHL patients were classified according to the Working Formulation histologic grade (21 low, 72 intermediate, and 10 high grade lymphomas). The patients were treated with standard chemo-radiotherapeutic protocols according to the stage and the histologic grade; the evaluation of the response to the treatments and the follow-up were performed according to the serial examinations currently used in our Institute. Given a TK cut-off of 5 U/L, the diagnostic sensitivity of TK test at lymphoma presentation was 81.8% and 75.7% in HL and NHL patients, respectively. Values exceeding 50 U/L were found only in NHL patients. The overall sensitivity of TK resulted higher than that of LDH (16.7%), copper (42.6%), IgG (23.5%), IgM (26.8%) and IgA (9.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Pattern of mucin gene expression in normal and neoplastic lung tissues.

This work evaluates the expression in lung cancer of the most well characterized mucin genes (MUC1, MUC2, MUC3) and of the recently described MUC4 in lung tissues, to check a correlation between the expression of any particular gene and this tumor. Hybridization with synthetic oligonucleotides obtained from a part of the sequences of MUC1, MUC2, MUC3 and MUC4, was performed on blotted RNA from 18 lung cancer tissue specimens and from 10 normal tissues samples taken, when possible, from the normal lung counterpart. By means of Northern blot analysis MUC1 revealed to be the most expressed mucin gene in lung cancer, followed by MUC4; by contrast, the expression of MUC2 and MUC3 was almost undetectable in all cancer specimens. The intensity of expression of MUC1 and MUC4 was always superior in cancer tissue than in the normal counterpart. As expected, the highest reactivity for MUC1 and MUC4 expression was observed mainly in the adenocarcinoma histotype which is mucin secreting. These findings represent a contribution to the study of mucin gene pattern in lung cancer, and, in particular, indicate that MUC4, in association with the MUC1 gene, seems to be strongly expressed in this neoplastic disease.

Base Sequence↗

Prone scintimammography in patients with non-palpable breast lesions.

Non-palpable breast lesions are a clinical problem due to the low specificity of mammography and the resulting difficulty in choosing the type and extent of surgery. Twenty-four patients with non-palpable mammographic lesions underwent prone scintimammography after the i.v. injection of 740 MBq of 99m Tc-SestaMIBI (MIBI). For this purpose, we designed a special bed which allows the widest exposure of the breast to the detector and better visualisation of deep mammary tissue without interference from intra-thoracic activity. The day after the scintigraphy, all patients underwent quadrantectomy or a more limited excision. The specimens were X-rayed to check the presence of mammographic microcalcifications or opacities. All surgical specimens were histologically evaluated. The mammographic and scintigraphic findings were compared with the histological ones. Under these conditions, we observed that the MIBI scan has a good specificity (90%) but low sensitivity (50%) for this selected population. When the MIBI scan was positive, the probability of breast cancer was very high (positive predictive value of the test = 88%) as a consequence, a wider excision would be the most accurate surgical choice. On the other hand, if the MIBI scan is normal, the high number of false negative results does not allow any final diagnosis (negative predictive value of the test = 56%). The preliminary results of this work suggest that radionuclide imaging can help the surgeon in surgical planning.

Adult↗

Cancer of the uterine cervix: clinical value of squamous cell carcinoma antigen (SCC) measurements.

The clinical value of SCC levels has been evaluated in four groups of women affected by cervical carcinoma. Among the 116 newly diagnosed patients, the SCC pretreatment level was elevated in 57% of cases and was strictly correlated with clinical stage (Ib to IV: p = < 0.01) and histotype (squamous cell carcinoma versus others: p = 0.0005). No significant difference was found in relation to nodal status. For the 28 patients submitted to neoadjuvant chemotherapy clinical response was correlated with the change in serum SCC level: stable or rising serum level indicated that the disease was unchanged or progressive, respectively. In the group of 48 patients affected by recurrent carcinoma, a raised SCC level was found in 71% of cases, with a lead time ranging from 0 to 12 months. No identification of the site of recurrence could be extrapolated from the value of SCC. As to the 108 regularly monitored patients, no significant difference in the risk to develop recurrence was shown for patients with a raised SCC level at the time of primary diagnosis (NED) versus relapsed: p = > 0.05).

Adult↗

Effects of steroid-free fetal serum and steroid supplementation on MUC1 gene expression in human breast cancer cell line MCF7.

MUC1 is a gene expressed by many normal epithelial tissues and aberrantly expressed by carcinomas. Studies regarding the expression of MUC1 in endometrial tissues and the constitution of its promoter region suggest a possible role for hormonal regulation of this gene. The aim of the present work was to evaluate the regulation of MUC 1 expression by 17 beta-estradiol (E2), progesterone (Pg) and by steroid-free fetal calf serum (FCS) in the hormone-sensitive cell line MCF7. MUC1 mRNA proved to be detectable by means of Northern-blot analysis in MCF7 cells, and its levels were strongly increased in cells grown with 10% steroid-free FCS. By contrast, the steady-state MUC1 mRNA levels of steroid-supplemented cells did not change compared to those of unsupplemented cells (controls). In conclusion, MUC1 expression is regulated by substances present in the steroid-stripped FCS (growth factors, e.g. Insulin-like Growth Factor). The lack of any observed MUC1 modulation by steroids could be due to: a) a low FCS concentration preventing the manifestation (permissive action) of possible gene regulation; b) an immediate stimulatory effect occuring in the first phases of the treatment, which could subsequently be lost.

Breast Neoplasms↗

[Nuclear medicine approach for the detection and characterization of liver metastasis].

Nuclear Medicine procedures include in vitro techniques able to detect and characterize liver metastases. Among the in vitro applications, circulating tumour markers level determination provides information about the response to therapy and the presence of active disease. While after a successful antineoplastic treatment the serum biological marker level usually falls, a progressive increase represents an alarm signal of occult/residual tumour or metastatic dissemination. However, this method is not able to identify the site of the lesion, therefore complementary imaging techniques are needed to confirm or exclude the diagnostic suspicion. The main advantages of the in vitro methods are the low cost and, consequently, the possibility of periodically checking of tumour activity. The in vivo nuclear medicine techniques are usually performed as second level test. In fact, they can play a role in detecting and characterizing hepatic metastases when radiological methods are inconclusive or when selected tumour seeking agents (i.e. radiolabelled antibodies, radioiodinated mIBG, Octreotide, etc.) can be used. Moreover, the introduction of PET procedures has provided physicians with a useful tool for the evaluation of tumour behaviour (glucose consumption, proteic, synthesis, receptor expression). A further significant diagnostic improvement is represented by the recent introduction of the multimodality co-registration of images (including CT scan, MRI, SPET, PET). The fusion imaging allows a superimposition of the functional and metabolic information to the morphological one.

Biomarkers, Tumor↗

Development of a rapid and ultrasensitive RIA method for estrogen (E2, E1, E1-S) determination with selective solid phase extraction.

The inhibition of the proliferative stimulation exercised by estrogens on neoplastic cells is the goal of all endocrine therapies in breast cancer. Under various circumstances, e.g. with the use of aromatase inhibitors, this result can be obtained by blocking the synthetic pathway and, consequently, by lowering the circulating levels of estradiol (E2), estrone (E1), and estrone sulfate (E1-S). The evaluation of these hormones in plasma could therefore represent a useful indicator of the biological efficacy of the therapy. However, the measurement of circulating steroids in a large series of patients is often a complicated procedure. Indirect methods of extraction are time consuming and expensive while the analytical sensitivity of direct methods is not sufficient to measure the residual levels of E2, E1, and E1-S. In this paper we describe a novel extraction method for the evaluation of plasma levels of E2, E1, and E1-S. This new method consists of solid phase extraction followed by a highly specific radioimmunoassay. The sensitivity of the assay is 0.6 pg/ml, 2.0 pg/ml and 7.0 pg/ml for E2, E1, and E1-S, respectively.

Estradiol↗

A simple and semi-automated system for increasing the recovery of aqueous [18F] fluoride from target.

A simple semi-automated apparatus is described for rinsing the transport line from the [18F] fluoride. target to the hot-cell after recovery of aqueous [18F] fluoride. The additional activity thus recovered can then be added to that previously trapped on Dowex 1X8 (CO3=) or, alternatively, diverted to a second vial for other uses such as research, PET-camera calibration or bone investigations by PET. Inclusion of the target chamber in the rinsing procedure increased the additional recovery of activity up to ca. 15%, without a noticeable effect on the isotopic integrity of the recovered [18O]H2O.

Anion Exchange Resins↗