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Biomedical subjects

E Bombardieri

Publications and source records attributed to E Bombardieri.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Bladder cancer monitoring using two novel urinary markers.

Bladder cancer shows extreme variability in its behavior. Even the superficial forms, when surgically treated, are characterized by a high recurrence rate and therefore regular and intensive post-treatment monitoring is an important aspect of the management of this tumor. The standard follow-up of patients with a bladder cancer history is based on cystoscopic examination of the internal bladder, which is an invasive procedure causing discomfort to the patient. In this context, the availability of a non-invasive laboratory test which measures circulating markers associated with bladder cancer could facilitate with monitoring of patients and could be of help in understanding the metastatic potential of bladder tumors, especially the superficial forms.

Antigens, Neoplasm↗
PubMedDate not supplied

Chromogranin A measurement in neuroendocrine tumors.

Neuroendocrine tumors (NETs) are rare neoplasms characterized by a low proliferative index and, in some cases, a favorable prognosis. These tumors often overproduce and release biologically active substances that are responsible for severe syndromes. Tumor marker measurement provides the clinician with useful information for the management of NET patients. The substances released by overproducing tumors are currently used as biomarkers, but there is a need for sensitive markers also for the "biochemically silent" NETs. The most effective and reliable blood marker available today is chromogranin A (CgA). Because of its high sensitivity and specificity, this glycoprotein can be used for the diagnosis, prognosis and followup of NETs. Furthermore, CgA measurement can be used for monitoring those tumors not over-producing or releasing any hormones or biological amines. This paper is a synthetic review on the value of CgA in NET management and reports our experiences with CgA measurement in NET patients.

Adenoma, Islet Cell↗
PubMedDate not supplied

Immunosuppressive factors: role in cancer development and progression.

The concept of the immunological surveillance against neoplastic cells was initially proposed by Erlich in 1909 and later elaborated by Burnet. This hypothesis states that the normal function of the immune system, in particular the cell-mediated immunity, is to recognize and destroy the transformed and proliferating tumor cells. The role of cell-mediated immunity during the first steps of tumorigenesis remains controversial. However, there is certain evidence about its importance in the progression and dissemination of cancer. The frequent immunosuppressed condition of cancer patients at tumor relapse or recurrence of secondary tumors is a clinical sign supporting this hypothesis, and many studies have demonstrated a defective immune response in patients diagnosed with advanced cancer. Several mechanisms of escape from the immune surveillance have been described, including the immunoselection of tumor antigen-negative variants, the downregulation of MHC class I expression, suppressive T cells, and the elaboration of immunosuppressive cytokines and other factors. Because of the technical difficulty of isolating the very small amounts from culture supernatants or body fluids, only a few of these substances have been characterized and studied with respect to their biological activity: transforming growth factor-beta (TGF-beta), the protein p15E, interleukin 10 (IL-10), prostaglandin E2 (PGE2), mucins, suppressive E-receptor (SER), immunosuppressive acidic protein (IAP), and adhesion molecules. The possibility of monitoring cancer patients by testing biochemical factors related to cancer growth led to a proposal to measure a number of these factors as tumor markers. Some of them, e.g. mucins, enjoy the consensus of the oncologic community, as for some indications they can help the clinician in the management of cancer patients. Except for the class of mucins, the other above-mentioned immunosuppressive factors have not found any clinical application in the laboratory routine because the information deriving from their measurement, although of speculative and scientific interest, has limited clinical value at present. Nevertheless, even if they have no impact on patient management, these substances do have a potential role to play in the study of cancer patients, and should be taken into account when developing new therapeutic strategies.

Animals↗
PubMedDate not supplied

Hormonal regulation of MUC1 expression.

Several circulating mucinous markers, including CA 15.3, MCA, CA 459, CASA, and Truquant BR, are secreted products of the polymorphic MUC1 gene, and are used as diagnostic tools in patients with breast cancer. In clinical practice the measurement of the levels of these markers in the blood can give important information on the tumor's response to treatment and its biological behavior during disease monitoring. Since the marker levels reflect the activity of the tumor, it is important to know all factors influencing the production/secretion and the blood concentrations of MUC1 mucin. Recent findings suggest that MUC1 gene expression is regulated by steroid hormones and other substances present in the serum. Such observations are very important not only because of their biological significance but also for their clinical implications, as one approach to breast cancer therapy is based on chemical hormone manipulation. Nevertheless, we have preliminarily demonstrated that endocrine treatment in breast cancer patients does not influence the circulating CA 15.3 serum levels, so changes in marker levels are related only to the clinical evolution of the tumor.

Biomarkers, Tumor↗
PubMedDate not supplied

Preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels as prognostic indicators in resected non-small cell lung cancer.

In 62 patients affected by resectable non-small cell lung cancer (NSCLC) submitted to radical surgery we evaluated the prognostic significance of CEA, NSE, SCC, TPA, and CYFRA 21.1 serum levels at diagnosis, as well as the predictive ability of these tumor markers with respect to histological type and pathological stage. The group was composed of 56 male and 6 female patients; the median age was 62 years (range 29-73 years). Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinoma; with regard to pathological stage, 32 patients had stage 1, 4 patients stage II and 23 patients stage IIIA disease. A good predictive ability with respect to histological type was obtained with SCC serum levels; as for pathological stage, TPA and CYFRA 21.1 were found to have moderate predictive ability. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at diagnosis were reliable predictors of overall survival, high values of these markers being associated with a worse prognosis.

Adult↗
PubMedDate not supplied

S100 protein serum levels in cutaneous malignant melanoma.

We investigated the utility of serum S100 determined by means of immunoradiometric assay in a cohort of 438 patients affected by cutaneous melanoma (126 untreated and 312 previously treated). Using 0.2 microg/l cut-off value, determined in 134 healthy blood donors, the sensitivity was 4.2% in stage I patients (4/94), 5.3% in stage II patients (1/19), and 38.5% in stage III patients (5/13). Even though the sensitivity increased progressively from stage I to stage II and III, these differences were not statistically significant. The prognostic significance of S100 evaluation at diagnosis was investigated in terms of survival but no statistical correlation between S100 basal levels and survival was found. In the 312 previously treated patients serum S100 levels were correlated to disease extent, high levels of the marker were observed in 42.8% (9/21) of patients with local recurrence, in 32% (16/50) of patients with lymph node and/or in-transit metastases, in 77.3% (17/22) of patients with distant metastases, and in patients with NED, the specificity of the marker was 96.8% (212/219). The difference between these groups were statistically significant. In conclusion, S100 protein was abnormally high in patients with metastatic malignant melanoma. Serial S100 measurements in a follow-up study are necessary to test the importance of the protein in the management of patients with metastatic malignant melanoma.

Adolescent↗
PubMedDate not supplied

Accuracy and clinical correlates of two different methods for chromogranin A assay in neuroendocrine tumors.

Measurement of chromogranin A (CgA) plays a major role in the management of neuroendocrine tumors (NET); however, reliable assaying of CgA is made difficult by the rapid hydrolysis following its release into the bloodstream. This study was aimed at the assessment of two assays for CgA in NET patients. CgA was measured in 93 patients by means of an enzyme-linked immunosorbent assay (ELISA) and an immunoradiometric assay (IRMA). The specificity and sensitivity of CgA were evaluated in relation to tumor histology. The clinical accuracy of the two assays was evaluated by receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated different immunoreactivity for CgA of the antibodies used in the two kits (r = 0.61). The two assays had different accuracy also in classifying patients according to their clinical condition (91% vs 64% specificity and 79% vs 79% sensitivity for the ELISA and IRMA assay, respectively) and tumor histology (81% vs 85% sensitivity for the ELISA and IRMA assays, respectively, in carcinoids; 92% vs 67% sensitivity for the ELISA and IRMA assays, respectively, in pancreatic islet cell tumors). The different clinical accuracy of the two assays was confirmed by the ROC analysis (AUC = 0.90 vs AUC = 0.87 for the ELISA and IRMA assays, respectively). In conclusion, because of the poor standardization of the commercially available measurement tools the clinical accuracy of CgA measurement depends on the assay used. This makes it difficult to compare CgA values measured with different kits and affects the clinical accuracy of the different assays for CgA.

Adolescent↗
PubMedDate not supplied

The breast cancer cell line MCF7 as a model of 99mTc-SestaMIBI, 99mTc-tetrofosmin and 99mTc-Medronate incorporation.

Hexakis-2-methoxyisobutylisonitrile (SestaMIBI) and 1,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) are 99mtechnetium compounds widely used in oncologic imaging. We investigated the uptake and release of SestaMIBI and tetrofosmin together with 99mTc-medronate in the MCF7 breast carcinoma cell line. All the tracers showed similar uptake kinetics, with a rapid increase in the first 30 minutes and a slower trend up to 120 minutes. Cell-associated activity was the same for SestaMIBI and tetrofosmin (4% of administered activity) and considerably lower for medronate (0.8%). For all tracers, almost all the accumulated activity was released within 1 hour. Furthermore, to verify an association between cell proliferation and tracer uptake, we performed growth-curve uptake experiments. Tetrofosmin uptake was lower in the logarithmic phase and higher in the plateau phase, whilst SestaMIBI showed the opposite trend. The differences between the tracers could be due to a relationship between proliferation and SestaMIBI uptake, or even to the influence of medium pH on membrane potential.

Breast Neoplasms↗
PubMedDate not supplied

Premenopausal breast cancer patients treated with a gonadotropin-releasing hormone analog alone or in combination with an aromatase inhibitor: a comparative endocrine study.

BACKGROUND: The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients. MATERIAL AND METHODS: Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg i.m. monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg i.m. fortnightly; n = 11) to compare the effect of both treatments on the patients' estrogenic milieu. Therefore, serum estrogen, gonadotropin and sex hormone-binding globulin (SHBG) levels were investigated before the start of treatment and subsequently over a three-month period. RESULTS: There was a significant between-group difference in estrogen suppression during therapy. In comparison with baseline values, after four weeks of treatment the estradiol levels decreased by an average of 86.9% (95% CI, 70.5-94.2%) in the group treated with triptorelin alone and by 97.3% (95% CI, 94.1-98.8%; P = 0.0422) in the combination group; the respective figures for estrone were 48.5% (95% CI, 27.5-63.5%) and 70.4% (95% CI, 52.3-81.6%; P = 0.0007) and for estrone sulfate 56.7% (95% CI, 40-68.8%) and 80.5% (95% CI, 69.4-87.6%; P = 0.0055). No difference was observed between the groups in terms of gonadotropin suppression; both treatment modalities led to a slight but delayed decrease in SHBG levels. Three of the patients treated with triptorelin alone experienced tumor regression compared with four patients in the combination group. No appreciable side effects of the combination therapy were observed. CONCLUSION: The treatment of premenopausal patients with triptorelin plus 4-OHA is feasible and leads to a much greater inhibition of main circulating estrogens than treatment with the analog alone. Since the combination of a GnRH analog and an aromatase inhibitor might potentially enhance the anti-tumor efficacy of the analog alone owing to more favorable endocrine effects, such a therapeutic approach deserves more extensive evaluation in the clinical setting.

Adult↗
PubMedDate not supplied

The biological characteristics of chromogranin A and its role as a circulating marker in neuroendocrine tumours.

This paper reviews the biology of chromogranin A (CgA) and CgA-derived peptides and their possible role as markers for neuroendocrine tumours (NETs). NETs are neoplasms characterized by a low proliferation rate and, in some cases, a favourable prognosis. NETs often overproduce and release biologically active substances that are responsible for severe syndromes. The hormones and the biogenic amines released by biologically active NETs are currently used as biomarkers, but there is a need for sensitive markers for those NETs that are "biochemically silent". Circulating CgA levels have been demonstrated to be augmented in NET patients irrespective of the presence of syndromes related to hormone overproduction. Because of the high sensitivity and specificity of CgA, this glycoprotein can be successfully used in diagnosis, prognosis and follow-up of NETs. CgA blood evaluation seems of particular interest in the management of the gastroenteropancreatic tract NETs and in carcinoids.

Biomarkers, Tumor↗
PubMedDate not supplied

Tumour markers CEA, NSE, SCC, TPA and CYFRA 21.1 in resectable non-small cell lung cancer.

BACKGROUND: In the last few years, several prognostic factors have been investigated in order to identify among patients with completely resected non-small cell lung cancer (NSCLC) subsets at high risk of recurrence. In this context, the actual role of serum tumour markers is still unclear. The aim of this study was to evaluate the prognostic significance of preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels in 62 patients submitted to radical surgery for non-small cell lung cancer (NSCLC). The predicting ability of these tumour markers with respect to histological type and pathological stage was also assessed. PATIENTS AND METHODS: After informed consent was obtained, the preoperative serum concentrations of the tumour markers CEA, NSE, SCC, TPA and CYFRA 21.1 were measured by means of immunometric assays in 62 patients referred to our Institutions from January to December 1992. All patients had resectable, histologically proven NSCLC and were submitted to radical surgery. Overall survival (OS) was calculated as the time elapsed from surgery to the date of death or last clinical evaluation; the prognostic effect of the tumour markers was investigated by Cox multiple regression models. RESULTS: Fifty-six patients were male and 6 female; median age was 62 years. Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinomas. With regard to pathological stage, 32 patients had stage I, 4 patients had stage II and 23 patients had stage IIIA disease. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at the time of diagnosis were reliable predictors of overall survival high values of these markers being associated with worse prognosis. CONCLUSIONS: Our findings suggest that in completely resected NSCLC, TPA and CYFRA 21.1 preoperative serum levels might provide a useful tool for stratifying subgroups of patients with different chances of disease recurrence after surgery.

Adenocarcinoma↗
PubMedDate not supplied

The role of bone SPET study in diagnosis of single vertebral metastases.

The spine is the preferential site of metastases from several neoplasms. In the past years whole body bone scan (BS) with 99mTc-diphosphonates has been considered the first choice in detecting the skeletal involvement. However the presence of vertebral non-neoplastic pathology in oncologic patients can cause several false positive results and this increases the difficulty in defining the etiology of a focal uptake. Nowadays, technological development has provided new gamma cameras, which are able to perform tomographic acquisition (single photon emission tomography, SPET). This technique allows one to better define the anatomical location of the areas of increased uptake. In our study, 81 cancer patients, with suspected single skeletal metastases not defined by BS, were studied by SPET. The skeletal involvement was confirmed during at least 12 months follow up by means of clinical, radiological and nuclear medicine examinations. The overall malignant bone alterations were 14 while the benign ones were 67. The performances of SPET were: diagnostic sensitivity 92.8% (13/14), specificity 92.5% (62/67) positive predictive value 72.2% (13/18), negative predictive value 98.4% (62/63), accuracy 92.6% (75/81). Our conclusion is that bone SPET proved to be a very reliable tool in differentiating benign disease from metastatic involvement.

Breast Neoplasms↗
PubMedDate not supplied

BTA-TRAK combined with urinary cytology is a reliable urinary indicator of recurrent transitional cell carcinoma (TCC) of the bladder.

This study evaluated the diagnostic accuracy of BTA-TRAK in combination with urinary cytology (UC) in the follow-up of patients with a history of transitional cell carcinoma (TCC) of the bladder. The overall sensitivity of BTA-TRAK, UC and the two tests combined for the detection of recurrences was 82.7% (48/58), 84.2% (48/57) and 91.2% (52/57), respectively. BTA and UC showed comparable sensitivity for superficial recurrences (76.7% (33/43) and 78.5% (33/42), respectively) and for invasive recurrences (100% (15/15)); when the two tests were used in combination, the sensitivity for superficial lesions increased to 88% (37/42). BTA-TRAK was more sensitive than UC for G1 recurrences (81.2% (13/16) vs. 68.7% (11/16)), and when the two tests were combined the sensitivity increased to 87.5% (14/16). The sensitivity of the combination was 100% (15/15) for G3 lesions. The differences in urinary BTA-TRAK levels between patients with recurrences and those without evidence of disease were statistically significant (Wilcoxon's test, p<0.05); among patients with recurrences BTA levels were significantly higher in the invasive and poorly differentiated subtypes. In the series of patients studied by us, BTA-TRAK combined with UC was shown to be a non-invasive, accurate test to predict TCC recurrences. Periodic measurement of BTA-TRAK combined with urinary cytology seems to provide additional information for the monitoring of patients treated for TCC; however, due to the presence of false positive and false negative results, this test cannot replace cystoscopy. In a selected group of patients it could, if combined with cytology and ultrasonography and if correctly used and interpreted, orient the timing and indication for cystoscopy.

Adult↗
PubMedDate not supplied

p53 evaluation in gastric mucosa of patients with chronic Helicobacter pylori infection.

Gastric cancer is often associated with p53 over-expression and Helicobacter pylori (HP) infection. In this study we have investigated the production of the p53 protein and mutation of its gene in precancerous gastric lesions with HP infection. For this purpose 130 patients who underwent endoscopy for dyspepsia were enrolled in the study. To assess p53 production and mutation of the p53 gene we employed an immunoluminometric assay and polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) analysis, respectively. Histologically, 52 of the 130 enrolled patients showed intestinal metaplasia type I (IM) (90.4% of these were also HP positive), 47 had HP-related gastritis and 31 were normal. p53 cytosol levels were significantly higher in patients with IM or HP-related gastritis than in normal patients (p = 0.0137 and p = 0.0411, respectively). All DNAs extracted from gastric mucosa samples with higher p53 values and examined for p53 mutations by PCR-SSCP analysis were characterized by a normal run. Our data indicate, that irreversible genetic changes in the p53 protein has not yet occurred in morphologically non-neoplastic gastric mucosa with IM and HP-related chronic gastritis. In conclusion, the increase in p53 cytosolic levels found in our study is due to an increased production of the wild-type protein probably related to an inflammatory response induced by HP infection.

Adult↗
PubMedDate not supplied

Preliminary study on oncogene product immunohistochemistry (c-erbB-2, c-myc, ras p21, EGFR) in breast pathology.

The expression of oncogene products related to cell growth (c-erbB-2, c-myc, ras p21, EGFR) was investigated in benign (15 cases) and malignant breast lesions (20 cases) by means of immunohistochemistry using the avidin-biotin-peroxidase technique with polyclonal and monoclonal antibodies. The aim of this study was to evaluate the relationship between the staining positivity and various morphological and biological features, such as tumour type, grading, hormone receptor status and cell kinetic parameters. In benign breast lesions, as expected, the kinetic parameters were low, both for Ki-67 and LI. All the specimens showed a diploid condition (the DI being equal to 1) and we found a limited degree of immunoreactivity for all the growth factors and oncogene products. In breast cancer we studied the distribution of immunohistochemical positivity for EGFR, c-erbB-2, c-myc, ras p21 and Ki-67, which was related to age, nodal status, ER and PgR receptor status, LI, DI and histopathological grading. A significant positive correlation was found both between ras p21 expression and nodal status and ER-ICA positivity. We observed a strong correlation between LI and Ki-67 and an inverse relation between Ki-67 and ER expression. These findings suggest the importance of studying the relationship between prognostic factors which may provide preoperative prediction in the biological behaviour of breast cancer, not only on biopsy specimens, but also on fine needle aspirates.

Adult↗