Search PubMed⌕ Search

Biomedical subjects

E Seregni

Publications and source records attributed to E Seregni.

90 records · Page 5Linked to original sources
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

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

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Evaluation on serum 2'-5'oligoadenylate synthetase (2'-5'oligoAS) and beta 2 microglobulin (B2M) in patients with nodal metastases from cutaneous malignant melanoma treated with rIFN-alpha 2A.

UNLABELLED: IFN-alpha is a promising adjuvant agent in patients with regional melanomatous metastases (stage IIIB). The aim of this study was to verify whether serum evaluation of the interferon induced proteins 2'-5'oligoAS and B2M can predict the clinical response to rIFN-alpha 2A therapy. PATIENTS AND METHODS: Forty-two patients who had undergone radical dissection of nodal metastases were evaluated. All patients received adjuvant rIFN-alpha 2A (3 million units s.c. three times weekly) for 3 years or until progression. The patients were followed for a medium period of 43 months (range 19-46). During follow-up 22 of the 42 patients had disease progression. In all patients blood samples were obtained before starting adjuvant therapy and after 1 and 6 months of therapy with rIFN-alpha 2A. 2'-5' oligoAS and B2M were measured by radioimmunoassay. RESULT: During the first month of adjuvant therapy with rIFN-alpha 2A the serum levels of 2'- 5' oligoAS increased 10-fold, and this trend was maintained in the following 6 months. Similar results were obtained for B2M serum levels. However, we did not find any significant difference in AS and B2M serum levels between responders and non-responders. CONCLUSION: Our results, therefore, indicate that AS and B2M are markers of the biological activity of administered IFN but that they have little efficacy in predicting the clinical outcome of the treated patients.

2',5'-Oligoadenylate Synthetase↗