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Biomedical subjects

E Seregni

Publications and source records attributed to E Seregni.

At least 55 records · Page 3Linked to original sources
PubMed1993

Bone scintigraphy in breast cancer: a ten-year follow-up study.

Two-hundred and sixty patients with T2-T3a, pN1, M0 (TNM classification) breast cancer underwent clinical and instrumental follow-up (mean 122 months) including periodic bone scintigraphy. A total of 1971 scintigraphic examinations were performed (range 3 to 15 scintigraphies/patient, mean 8). The results of scintigraphy were compared to standard radiographs and to the clinical history of the patients. Bone metastases occurred in 71% of 122 patients who suffered from tumor recurrence during the study. Bone lesions (alone or associated with other tumor lesions) represented the most common site (42%) of first tumor relapse and occurred as first site of distant metastases in 11% of 29 patients with locoregional relapse. Bone metastases were symptomatic in 41% of cases. The sensitivity and specificity of bone scintigraphy were 98% and 95%, respectively; the positive and negative predictive values were 73% and 100%; the accuracy was 96%. Scintigraphic false positive results occurred particularly in the skull and in the ribs and generally when the examination detected less than three focal abnormalities. This study demonstrates that the number of positive scintigraphies during follow-up increases over the years, reaching a plateau only at approximately 8-10 years. It is therefore not advisable to stop performing bone scintigraphies after the first years of follow-up as this may lead to the loss of important information.

Adult↗
PubMed1992

Scintigraphic documentation of an improvement in hepatobiliary excretory function after treatment with ursodeoxycholic acid in patients with cystic fibrosis and associated liver disease.

We have previously documented that ursodeoxycholic acid exerts a beneficial effect on liver function and bile acid metabolism in patients with cystic fibrosis. We hypothesized that the mechanism of action may be related in part to the choleretic properties of the administered bile acid. We therefore compared hepatobiliary scintigraphic images obtained before and 1 yr after initiation of ursodeoxycholic acid therapy to document an improvement in bile flow in 13 patients with cystic fibrosis and hepatobiliary involvement. Before therapy, hepatobiliary scintigraphy documented biliary stasis with retention of the isotope in intrahepatic and extrahepatic bile ducts in nine patients; during therapy, duct dilatation decreased substantially in eight patients, with decreased intrahepatic retention and more rapid biliary outflow of the tracer. The time of appearance of isotope in the intestine decreased (from a mean of 36.9 +/- 17.8 min to 18.8 +/- 9.0 min; p less than 0.01) in all patients in whom it had been abnormal, and the half-time of hepatic washout decreased from a mean of 35 +/- 20.7 min to 26 +/- 15.6 min (p less than 0.05). During ursodeoxycholic acid administration enrichment of bile was achieved, with the mean ursodeoxycholic acid percent composition increasing from 5.8% +/- 2.9% to 35.7% +/- 8.5%. Ursodeoxycholic acid became the predominant bile acid in serum. Liver function improved in all 10 of the patients with abnormal values at baseline. We conclude that hepatobiliary scintigraphy is of value in monitoring the therapeutic responses of cystic fibrosis patients with liver disease to ursodeoxycholic acid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

CA 15.3 determination in patients with breast cancer: clinical utility for the detection of distant metastases.

In 81 healthy women, 26 pregnant women, 25 patients with fibrocystic disease and 144 breast cancer patients, the overall diagnostic sensitivity and specificity of the CA 15.3 test was 27 and 97%, respectively. The positive and negative predictive values were 93 and 43%. In 150 node-negative patients taking part in a chemoprevention trial CA 15.3 was assayed at baseline and every 4 months for a median follow-up of 24 months (range 4-48). In these patients, 5 had local recurrences, 1 had a regional recurrence, 9 had distant metastases and 3 developed cancer in the contralateral breast. Among the patients with recurrences, those with distant metastases showed the highest ratio of CA 15.3 increase (8/9); in local and regional recurrences, this ratio was lower (2/6). The patients with contralateral breast cancer had no significant increase in CA 15.3. Patients in whom metastases were detected showed an increase in CA 15.3 4-48 months before clinical or instrumental detection of the metastases.

Adult↗
PubMed1991

Radioimmunoscintigraphy of ovarian cancer with the MOv18 monoclonal antibody.

The monoclonal antibody (Mab) 131I-MOv18 was administered to 30 patients with ovarian carcinoma intravenously (n = 20) and intraperitoneally (n = 10). After intraperitoneal administration, higher tumour uptake (mean values 1.3% vs. 0.8%) and a better tumour/background ratio (mean values 2.8 vs. 1.9) than after intravenous injection were obtained. Moreover, after intraperitoneal administration the uptake in non-affected organs, such as liver and spleen, was lower. However, occasionally the favourable results of the intraperitoneal route were cancelled by persistent pelvic non-specific accumulations of 131I-MOv18. The possibility to change the biodistribution pattern in the latter cases with peritoneal washing was evaluated. 3 patients were submitted to this procedure and an improvement in the radiotracer biodistribution was obtained in 1 case. With regard to tumour detection, the average sensitivity (73%) showed a significant difference from the sensitivities for abdominal (61%) and pelvic lesions (90%). No false positive results were noted.

Adult↗
PubMed1991

Immunoscintigraphy of colorectal carcinoma with an anti-CEA monoclonal antibody: a critical review.

An anti-CEA monoclonal antibody (FO23C5), belonging to the IgG1a class, was used to perform several preclinical and clinical studies on radioimmunoscintigraphy (RIS) in patients with colorectal carcinoma. Preliminary screening on different tissues showed high specificity of this antibody for gastric and colorectal carcinomas. A pilot study on 51 patients with 64 localizations of colorectal carcinoma was realized, followed by a multicenter validation study in which, among 509 patients bearing CEA secreting tumors, 254 patients had primary or relapsed colorectal tumors. High sensitivity and specificity values were obtained by these studies and many "unsuspected" localizations were recorded. In order to better define the clinical utility of this approach, a prospective trial was run on 59 patients previously submitted to surgery for colorectal carcinoma and with suspected local relapses. A comparative evaluation of RIS, CT scan, US and MRI was performed. RIS and MRI have the highest value of accuracy (86%) followed by CT scan (68%) and US (54%). No adverse reactions were noticed in any of the patients examined.

Antibodies, Monoclonal↗
PubMed1988

Tumor imaging of colo-rectal carcinoma with an anti-CEA monoclonal antibody.

A 131I-labelled anti-CEA monoclonal antibody (MAb) (FO23C5) was used in a preclinical in vivo study in an animal model and in a clinical study in patients with colo-rectal carcinoma. Preliminary screening on different tissue was performed with immunoperoxidase staining, which showed a good specificity of the antibody for gastric and colo-rectal carcinoma. Initially immunoscintigraphy was performed as a pilot study at the National Cancer Institute of Milan on 51 patients with 64 localizations of colo-rectal cancer. Serial scans were performed after injection of 2 radioactive reagents, namely 131I and 111In. In vivo pharmacokinetics of the compound were studied. High sensitivity (80%) and high specificity were obtained in detecting local recurrences and abdominal metastases whereas a low positivity rate was obtained in detecting liver metastases. Our data were confirmed by preliminary results of the multicentric trial organized by the Italian National Research Council on 300 patients with about 700 localizations of CEA producing tumors.

Antibodies, Monoclonal↗
PubMed1985

Tissue polypeptide antigen and carcinoembryonic antigen in colon tumors: serum levels and immunohistochemical localization.

Patients with malignant and benign colon disease (59 colon cancer and 96 polyps) were studied by means of tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) tests. The evaluation of the circulating levels of the markers showed that the overall sensitivity for the TPA test was 57.6% and for the CEA test was 55.9%. Their specificities were 89.5% and 94.7%, respectively. The analysis of results indicated no considerable difference between CEA and TPA in detecting individuals with malignant diseases. There was only a slight difference in Dukes stages: in stages A and B, TPA sensitivity was higher than CEA sensitivity. On the contrary, in the group of patients with polyps, more false-positive results were obtained with the TPA test than with the CEA test. Immunohistochemical studies on the small group of patients (12 colon cancers) allowed us to evaluate the relationship between the staining positivity for the anti-TPA and anti-CEA antibodies and the circulating levels of the markers. The staining in some cases was not correlated either with the stage of cancer or the circulating TPA or CEA levels. This fact further shows the need to investigate the mechanism that determines the blood levels of many tumor markers. All the specimens examined were positive for TPA and CEA staining, but they were composed of varying proportion of positive and negative tumor cells. The degree of positivity was frequently variable not only between the specimens but also within the same specimen.

Carcinoembryonic Antigen↗
PubMedDate not supplied

The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels.

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.

Aged↗
PubMedDate not supplied

Uptake of tritiated thymidine, deoxyglucose and methionine in three lung cancer cell lines: deoxyglucose uptake mirrors tritiated thymidine uptake.

[(18)F]-fluorodeoxyglucose and [(11)C]-methionine are tracers which are widely used in oncological positron emission tomography. This study has been designed to assess the deoxyglucose and methionine uptake behaviour in three cell lines from different lung cancer histotypes. Tracer uptake was compared with proliferative activity as determined by growth curves and tritiated thymidine uptake. Deoxyglucose paralleled thymidine in all cell lines, peaking in the lag phase, decreasing throughout the exponential phase, and reaching its minimum in the plateau phase. The correlation was statistically verified and Spearman's rho ranged from 0.79 to 0.99. The absolute methionine uptake was always highest and always peaked on day 2, followed by a quite rapid decrease. However, besides the delay in maximum uptake, methionine incorporation was also related to proliferation, although the statistical correlations were weaker. These results show for the first time a clear correlation between deoxyglucose uptake and cell proliferation in a model comparing tracer uptake in different growth phases. Although delayed, methionine uptake was also related to cell growth and its greater intensity could be of interest for clinical use.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Biochemical characteristics and recent biological knowledge on prostate-specific antigen.

Since its identification in seminal fluid in 1971, much new information has been obtained about the biology and expression of prostate-specific antigen (PSA). PSA is a glycoprotein composed of 93% amino acids and 7% carbohydrates, with a molecular weight of about 30,000 Da. Functionally and structurally PSA is a kallikrein-like serine protease, and its physiologic role is degradation of the major proteins of seminal coagulum (semenogelin I and II, fibronectin), which leads to semen liquefaction. The PSA gene is located on the 13q region of chromosome 19, and it has a high degree of homology (more than 80%) with genes of the human glandular kallikrein (hKGK1). PSA production and expression are preferentially but not exclusively associated to the normal, benign hyperplastic and cancerous tissues of the prostate. In fact, it has been demonstrated that PSA is also present in accessory male sex glands and breast cancer. It was recently reported that PSA was also present in milk of lactating women. Many factors may influence PSA synthesis and production, and among them the most important are androgen, retinoic acid and growth factor stimulation. Significant advances have been recently made as regards the molecular isoforms of PSA. In the seminal fluid PSA seems partially bound to a serpine (protein C inhibitor), whereas in serum it is predominantly associated to alpha-1-antichymotrypsin and in a small quantity to alpha-2-macroglobulin. These new findings will have implications for the clinical application of PSA as a tumor marker for prostate cancer.

Humans↗
PubMedDate not supplied

Preliminary results of clinical evaluation of the free/total prostate-specific antigen ratio in a multicentric study.

AIMS AND BACKGROUND: The free/total (F/T) prostate-specific antigen (PSA) ratio is probably the most promising tool proposed to increase the specificity of PSA in the diagnosis of prostate cancer. The aim of the present study was to evaluate the clinical value of the F/T ratio in 138 patients with benign hyperplasia, 101 with untreated prostate cancer, and 176 apparently healthy men. METHODS: We used a new immunometric assay of free PSA (FPSA-RIACT, CIS Diagnostici, Italy) which has shown good analytical performance; sample handling and storage under routine conditions did not affect the antigen stability. RESULTS: The diagnostic efficiency of the F/T ratio was significantly better than that of total PSA. In patients with total PSA ranging from 4 to 10 ng/ml, at a specificity level of 95% total PSA showed a sensitivity of 7%, whereas the sensitivity of F/T increased to 70%. Using the F/T ratio as a decision tool in association with total PSA and considering all cases candidate to biopsy (total PSA greater than 3.79 ng/ml corresponding to the 95% level), we demonstrated a 35% reduction of total biopsies that would have been required on the basis of total PSA alone. CONCLUSIONS: The determination of the percentage of F/T serum PSA significantly improves the specificity of the marker, particularly in the 4-10 ng/ml dose range where unnecessary prostate biopsies can be reduced.

Analysis of Variance↗
PubMedDate not supplied

Structure, function and gene expression of epithelial mucins.

In this review the main characteristics, i.e., structure, function and gene expression, of the different mucins are discussed. Mucin-type molecules consist of a core protein moiety (apomucin) where a number of carbohydrate chains are attached to serines and threonines by glycosidic bonds. O-linked carbohydrates form up to 80% of the molecule and the length of the glucidic side chains varies from one to more than 20 residues. At least eight mucin-like genes have been isolated so far, and the main characteristic is the presence of a central domain composed of a variable number of "tandem repeats". The sequence homology of the central domain among the different members of the mucin-type family is limited, indicating that this internal domain is unique for each mucin. Thanks to the integrated results of genetic, immunological and biochemical studies, it is now possible to identify eight apomucin genes, namely MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7. MUC1 is the best characterized mucin and it is expressed on the apical surface of most polarized epithelial cells. The MUC1 gene has been cloned and sequenced. The MUC2 gene encodes a typical secretory gel-forming mucin which represents the predominant form in human intestinal and colon tissues. Another intestinal mucin is MUC3. The MUC4, MUC5AC and MUC5B genes have been isolated from a bronchial tissue cDNA library. The MUC4 and MUC5AC genes are mainly expressed in the respiratory tract, in gastric and reproductive mucosa, while MUC5B is highly detectable only in the bronchial glands. The MUC6 gene is expressed by gastric tissue and, recently, MUC7 has been cloned and sequenced using a salivary cDNA library.

Amino Acid Sequence↗
PubMedDate not supplied

Two novel monoclonal antibodies against the MUC4 tandem repeat reacting with an antigen overexpressed by lung cancer.

In this study we investigated the immunochemical and cytochemical reactivity of two monoclonal antibodies against the 16-amino acid tandem repeat of MUC4 to demonstrate a possible variation of the mucin core peptide expression related to lung cancer. The immunocytochemical anti-MUC4 reactivity was analyzed in four lung cancer cell lines (Calu-1, Calu-3, H460, SKMES) and in other tumor cell lines, as well as in frozen materials from 21 lung adenocarcinomas (ACs), including five bronchioloalveolar carcinomas (BACs), and 11 squamous cell lung carcinomas (SqCCs). A weak fluorescence anti-MUC4 positivity (range: 10.3-16.2) was observed only in acetone-fixed lung cancer cell lines Calu-1, Calu-3 and H460. These three lung cancer cell lines also showed a cytoplasmic immunoperoxidase reactivity. The immunostaining in lung cancer tissues showed a granular cytoplasmic reactivity: 15/21 (71%) and 17/21 (80%) ACs were positive with BC-LuC18.2 and BC-LuCF12, respectively. All BACs were positive. Moderate to strong reactivity was present in well-differentiated ACs. In the normal lung parenchyma counterparts weak reactivity was found only in bronchiolar cells. All SqCCs were negative. Anti-MUC4 reactivity was also observed in the alveolar mucus. In conclusion, our anti-MUC4 MAbs detect a secretion product present in mucus and this product is elaborated by lung cancer cells and overexpressed in well-differentiated lung ACs.

Adenocarcinoma↗
PubMedDate not supplied

Serum and cerebrospinal fluid human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) in intracranial germ cell tumors.

We report a retrospective study on serum and cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (betahCG) determination in a series of 30 patients bearing intracranial germ cell tumors. At diagnosis five patients had high serum and CSF AFP levels. No patient had positive serum AFP and negative CSF AFP or vice versa. Twelve of 30 patients had serum betahCG levels above 5 mlU/mL, eight had high betahCG only in CSF, and ten were completely negative. During treatment and follow-up both markers were accurate indicators of the response to therapy, decreasing rapidly and often becoming normal already after the first phase of treatment. We conclude that these two markers, and mostly betahCG, may be useful in the diagnosis and monitoring of the response to therapy of patients with intracranial germ cell tumors.

Adolescent↗
PubMedDate not supplied

Serum levels of tartrate-resistant acid phosphatase-5b in breast cancer patients treated with pamidronate.

A novel immunoassay specific for the osteoclast-produced TRAP isoform 5b has been developed recently. By means of this assay we studied the usefulness of serum TRAP-5b in monitoring the response to palliative treatment with pamidronate in breast cancer patients with bone metastases. We correlated serum TRAP-5b levels with pain intensity and intake of analgesics to assess the possible utility of the marker in identifying patients who could benefit from pamidronate treatment. Twenty-eight advanced breast cancer patients with bone metastases entered the study. Patients were treated according to the following schedule: two two-week cycles of 60 mg/week pamidronate IV, with a three-week interval in between (six infusions over seven weeks), followed by one infusion every three weeks for a total of 24 infusions over a treatment period of 61 weeks. Blood samples were taken before the start of treatment and before each infusion during two treatment cycles. To measure serum TRAP levels we employed the new immunoassay kit BoneTRAP produced by Suomen Bioanalytiikka Oy (SBA), Oulu, Finland. In order to assess the usefulness of this marker in evaluating the response to pamidronate treatment we divided patients into two groups (group A, worsened; group B, improved) with respect to pain trend and analgesic intake. Our results did not show any statistically significant difference in baseline serum TRAP levels in the two groups. However, one week after the first pamidronate infusion TRAP-5b serum levels decreased by 39% and 18% in groups A and B, respectively (p=0.01); these levels persisted throughout the treatment period. In conclusion, a decrease in TRAP-5b serum levels may reflect the pharmacological activity of pamidronate and seems to predict pain relief and a reduction in analgesic consumption.

Acid Phosphatase↗
PubMedDate not supplied

Radioimmunodetection of melanoma: preliminary results of a prospective study.

A prospective study to evaluate the clinical usefulness of radioimmunodetection of melanoma in clinical practice is ongoing at the National Cancer Institute of Milan, Italy. Technical conditions for the application of the method were previously reported. In this trial, 99mTc-labelled F(ab')2 fragments of the 225.28S monoclonal antibody were used against a high molecular weight melanoma associated antigen (HMW-MAA). Retrospective studies on radioimmunodetection of melanoma have already been made by our group and by other Centers in about 300 patients. This study concerns the evaluation of the regional extension of primary melanoma. 23 patients with 32 suspected lymphatic involvements of melanoma on the trunk and arms underwent immunoscintigraphy. No false positive results were observed; 3 false negatives, one corresponding to a micrometastasis, were noticed. Specificity corresponds to 100% and sensitivity to 78.6%.

Adolescent↗