Search PubMed⌕ Search

Biomedical subjects

G Bevilacqua

Publications and source records attributed to G Bevilacqua.

At least 19 recordsLinked to original sources
PubMed2003

Can breast-feeding protect against schizophrenia? Case-control Study.

BACKGROUND: Human milk, unlike formula feeds, contains long-chain polyunsatured fatty acids, such as docosahexaenoic acid and arachidonic acid which are essential in the development of the central nervous system. If human milk is the optimal food for brain development, and if schizophrenia is a neurodevelopment disorder, might people who become schizophrenic in adult life be less likely to have been breast-fed? AIMS: To compare the incidence and length of breast-feeding in patients, siblings and normal controls and to examine the relationship between the duration of breast-feeding and age at onset of schizophrenia. METHOD: 113 schizophrenic patients were recruited, as were 140 siblings of the patients and 113 nonschizophrenic controls. The breast-feeding history of the patients, their siblings and controls was obtained through interviews with the mothers of the patients and controls. RESULTS: There were no significant differences between groups in the incidence of breast- feeding. The duration of breast-feeding was positively correlated with the age at onset of illness (r = +0.25, p < 0.02). CONCLUSION: Breast-feeding is no less common in those who develop schizophrenia in later life. However, breast milk might postpone the onset of the illness in schizophrenic patients.

Adult↗
PubMed2003

Dentin matrix protein 1 is expressed in human lung cancer.

UNLABELLED: We have previously shown that breast and prostate cancers express bone matrix proteins. DMP1 expression was evaluated in 59 human lung cancer samples at the protein and mRNA levels. It was detectable in 80% of the cases, suggesting a potential role for DMP1 in tumor progression and bone metastasis. INTRODUCTION: Previously, we and others have shown that bone extracellular matrix proteins such as bone sialoprotein (BSP) and osteopontin (OPN) are expressed in various types of cancer that are characterized by a high affinity for bone including breast, prostate, and lung adenocarcinoma. Based on biochemical and genetic features, BSP, OPN, dentin matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP) have been recently classified in a unique family named SIBLING (small integrin-binding ligand, N-linked glycoprotein). Therefore, we investigated whether DMP1 could also be detected in osteotropic cancers. MATERIALS AND METHODS: We first used a cancer array for evaluating the relative abundance of DMP1 transcript in a broad spectrum of human cancer tissues. This screening showed that DMP1 was strongly detectable in lung tumors compared with normal corresponding tissue. In a second step, we used an immunophosphatase technique and a specific polyclonal antibody directed against DMP1 to examine the expression of DMP1 in 59 human non-small cell lung cancer samples, including 29 squamous carcinoma, 20 adenocarcinoma, and 10 bronchioloalveolar carcinoma. Student's t-test was used to determine the statistical significance of immunostaining scores between the lung cancer histological groups studied and between cancer and normal lung tissues. RESULTS: Our results show that DMP1 is detectable in 90% of the adenocarcinoma and squamous carcinoma analyzed while 8 of 10 bronchioloalveolar specimens were negative. DMP1 immunostaining intensity and extent scores were significantly higher in adenocarcinoma (p = 0.0004) and squamous carcinoma (p < 0.0001) samples compared with adjacent normal lung tissue. In situ hybridization experiments confirmed that DMP1 mRNA is localized in lung cancer cells. CONCLUSION: In this study, we show that a third SIBLING protein is ectopically expressed in lung cancer. The role of DMP1 in lung cancer is largely unknown. Further studies are required to determine the implication of this protein, next to its sisters SIBLING proteins, in tumor progression and bone metastasis development.

Adenocarcinoma↗
PubMed2002

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Adult↗
PubMed2002

Breast MR imaging screening in eight women proved or suspected to be carriers of BRCA1&2 gene mutations.

The aim of this study was to evaluate the efficacy of MR imaging for the early detection of breast tumor in women at high genetic risk compared to conventional strategies such as ultrasonography and mammography. This study included 8 women, 5 of which had undergone surgery for breast cancer. BRCA germ line mutations were detected in 7 women, one patient was enrolled for more than 50% probability to be carrier of BRCA mutation. RM imaging screening was negative in 7 patients and strongly indicative of a malignant lesion in one. The gold standard was surgery for the suspicious cases and follow-up with clinical examination and conventional imaging every six months for the others. MR imaging proved itself to be a reliable technique in familial breast cancer high risk women.

Adult↗
PubMed2001

Bcl-2 expression in pancreas development and pancreatic cancer progression.

Apoptosis is important for both tissue development and differentiation; its deregulation may contribute to tumourigenesis. In order to clarify the role of Bcl-2, an apoptosis-inhibiting protein, in pancreatic morphogenesis and tumour progression, its immunohistochemical expression was evaluated in 12 samples of fetal pancreas, in 10 samples of adult pancreas with ductal hyperplastic lesions, in 120 cases of primary pancreatic ductal adenocarcinoma, and in 43 synchronous metastatic lymph nodes. To evaluate the role of apoptosis in pancreatic cancer, p53 expression was also studied in tumour samples. Bcl-2 cytoplasmic acinar and ductal immunostaining was found in all fetal and adult tissue samples; ductal hyperplastic lesions were constantly negative. Thirty out of 120 (25%) tumours and 3 out of 43 (7%) lymph nodes expressed Bcl-2, whereas 67 out of 120 (56%) expressed nuclear p53. Well-differentiated tumours (G1) were more frequently Bcl-2-positive (p=0.002); furthermore, there was an inverse correlation between Bcl-2 and p53 expression in primary tumours (p=0.02). Neither Bcl-2 nor p53 influenced patients' prognosis, which was instead affected by N (p=0.02) and M (p<0.0001) status and stage of the disease (p=0.002). It is concluded that Bcl-2 regulates pancreatic morphogenesis and tissue homeostasis from early fetal to adult life and can be considered a phenotypic marker of normal exocrine pancreas. On the other hand, the lack of expression in preneoplastic lesions and the low positivity found in primary tumours and lymph node metastases suggest that Bcl-2 does not play a centralrole in pancreatic tumourigenesis and cancer progression.

Adenocarcinoma↗
PubMed2001

mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients.

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-->GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17%-55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histological evidence of metastatic disease. Ninety-seven per cent of the patients with histologically involved nodes showed expression of mammaglobin mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicating the presence of metastases not detected by routine histological examination of one lymph node section. These results show that both mammaglobin RT-PCR and CEA RT-PCR are useful tools for the detection of breast cancer metastases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly one-third of cases.

Axilla↗
PubMed2001

Failure of primary breast cancer neoangiogenesis to predict pattern of distant metastasis.

In the present study, the primary tumor neoangiogenesis characteristics of 81 stage IV previously untreated breast cancers with synchronous metastasis to different distant sites (10 patients with soft tissue metastases, 31 with bone metastases, and 40 with visceral metastases) were analyzed. The primary intratumor microvessel density was assessed by immunohistochemical assay on paraffin-embedded primary tumor samples, using a monoclonal anti-CD34 antibody. The mean primary intratumor microvessel density (at 400x fields) was 78 +/- 39 (SD) microvessels per field. The microvessel density was not significantly related to the main clinical/pathological features of the tumor (age, cytohistological grade, DNA ploidy, diameter, and receptor status). The percentage of tumor cases with high primary intratumor microvessel density (cut-off median value of the series 73 +/- 39 microvessels/field) did not significantly differ in patients with bone, soft tissue, or visceral metastatic disease. Analysis of clinical outcome showed a significantly shorter time to progression and overall survival for patients with visceral metastases (P<0.001 and P<0.0002 by log-rank, respectively). Presence of visceral metastases was confirmed to be the only independent prognostic factor related to a worse TTP (hazard risk 2.15, 95% confidence interval 1.14-4.03, P<0.02) and overall survival (hazard risk 1.81, 95% confidence interval 0.98-3.35, P<0.06) by multivariate analysis. In conclusion, the assessment of neoangiogenesis of primary breast cancer by CD34 expression does not provide information predictive of different distant sites of metastasis.

Adult↗
PubMed2000

Cyclins of phases G1, S and G2/M are overexpressed in aneuploid mammary carcinomas.

Expression of cyclins A, B1 and D1 in human breast cancer was analyzed using dual-parameter flow cytometry with simultaneous evaluation of the DNA content. The asynchronous MCF-7 breast adenocarcinoma cells were used to implement flow cytometry analysis and to analyze the cell cycle distribution of cyclins. The patterns of the cyclin expression were also analyzed in vivo in fresh tissue specimens of human breast carcinomas. The combined measurement of DNA and cyclins showed a higher cyclin expression in aneuploid (11.5 +/- 2.0%, 4.3 +/- 1.1%, and 19.5 +/- 3.4% positive cells for cyclins A, B, and D1, respectively) than in diploid carcinomas (3.9 +/- 1.2%, 1.1 +/- 0.4%, and 5.0 +/- 1.2% positive cells for cyclins A, B, and D1, respectively). A positive relationship was also found between cyclin A and D1 expression and H(3)-thymidine labeling index. In the in vitro model, the asynchronous growing MCF-7 cells showed a variable number of cells expressing cyclins in an unscheduled way, unrelated to the phase at which these cyclins are expressed in normal cells. A similar condition was also observed in tumors. In conclusion, the data showed a deregulated expression of cyclins in a transformed adenocarcinoma cell line and in breast tumors. Furthermore, overexpression of these proteins is related to the aneuploid and high proliferative activity of human mammary carcinomas.

Aneuploidy↗
PubMed2000

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty.

Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intrauterine hormonal status, especially a change in estrogen status, could predispose to carcinogenesis. In an attempt to achieve new information on early breast growth, a series of developing human breasts have been analyzed, namely: 4 fetal breasts (28-32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphological features, we studied the immunohistochemical expression of some markers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal profile, and smooth-muscle actin for myoepithelial differentiation. The results were as follows: (a) lobules, absent between 28 weeks and 2 days, were well evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from 28 weeks onward and persisted later with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two different patterns: periductal vascularization (PDV) and interductal vascularization (IDV), IDV being always present, whereas PDV was found only in infant breasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; (g) stromal cells had no hormonal receptors and were heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial compartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation.

Antigens, CD34↗
PubMed2000

Mutational analysis of the NM23.H1 gene in human breast cancer.

NM23.H1 is a protein connected with tumor progression. Loss of heterozygosity and reduced expression of the gene have been associated with poor prognosis and increased incidence of metastases in many epithelial tumors. The aim of this study was to detect the presence of NM23.H1 point mutations or small deletions in human breast carcinomas by using the single-strand-conformation polymorphism (SSCP) technique. Mutational analysis was performed on 76 breast tumors, 10 of which had allelic deletion of the gene. The NM23.H1 mRNA content also was evaluated in each sample. Only a C-to-A transversion leading to a stop codon was found in the 5' untranslated region of exon 1. A polymorphic SSCP pattern was identified in exon 1; direct sequencing showed a C-to-T transition 30 nucleotides upstream from the 5' splice site flanking exon 1. None of the tumors analyzed presented both alleles inactivated. Our results suggest that NM23.H1 is rarely inactivated by point mutations.

Breast Neoplasms↗
PubMed2000

Manumycin inhibits ras signal transduction pathway and induces apoptosis in COLO320-DM human colon tumour cells.

The aim of the present study was to assess the cytotoxicity of manumycin, a specific inhibitor of farnesyl:protein transferase, as well as its effects on protein isoprenylation and kinase-dependent signal transduction in COLO320-DM human colon adenocarcinoma which harbours a wild-type K-ras gene. Immunoblot analysis of isolated cell membranes and total cellular lysates of COLO320-DM cells demonstrated that manumycin dose-dependently reduced p21 ras farnesylation with a 50% inhibitory concentration (IC50) of 2.51 +/- 0.11 microM and 2.68 +/- 0.20 microM, respectively, while the geranylgeranylation of p21 rhoA and p21rap1 was not affected. Manumycin dose-dependently inhibited (IC50 = 2.40 +/- 0.67 microM) the phosphorylation of the mitogen-activated protein kinase/extracellular-regulated kinase 2 (p42MAPK/ERK2), the main cytoplasmic effector of p21ras, as well as COLO320-DM cell growth (IC50 = 3.58 +/- 0.27 microM) without affecting the biosynthesis of cholesterol. Mevalonic acid (MVA, 100 microM), a substrate of the isoprenoid synthesis, was unable to protect COLO320-DM cells from manumycin cytotoxicity. Finally, manumycin 1-25 microM for 24-72 h induced oligonucleosomal fragmentation in a dose- and time-dependent manner and MVA did not protect COLO320-DM cells from undergoing DNA cleavage. The present findings indicate that the inhibition of p21ras processing and signal transduction by manumycin is associated with marked inhibition of cell proliferation and apoptosis in colon cancer cells and the effect on cell growth does not require the presence of a mutated ras gene for maximal expression of chemotherapeutic activity.

Alkyl and Aryl Transferases↗
PubMed2000

Normal values of reactive oxygen metabolites on the cord-blood of full-term infants with a colorimetric method.

The main end-point of the study was to evaluate the normal values of reactive oxygen metabolites (ROMs) in healthy full-term babies. Secondary end-points were differences between groups related to modality of delivery, Apgar score, birth weight, gestational age and sex. All apparently healthy babies born at our institution between 8 a.m. and 8 p.m. Monday to Friday with gestational age 37-42 weeks, delivered both vaginally or by caesarean section and without foetal distress and perinatal asphyxia. ROMs were evaluated by a colorimetric method (d-ROM test) on cord-blood immediately after birth. The values are reported as arbitrary unit U. Carr. Statistical analysis was performed by t-test and by multiple and stepwise regression analysis. We have analyzed 80 babies with mean birth weight 3301 +/- 446 g. and mean gestational age 39.5 +/- 1.0 weeks. The male:female ratio was 1.56 and the median (range) Apgar score was 9 (7-10) at 1' and 10 (9-10) at 5'. The babies born by vaginal delivery were 37 out of 80 while the remaining 43 were delivered by cesarean section. Because the two groups did not differ for the clinical characteristics they were considered together for the determination of the mean value of ROMs and indicated as "total". The mean value +/- SD of ROMs of the "total" was 115.5 +/- 32.6 U. Carr. Significant differences in the mean value of ROMs were not found related to type of delivery, birth weight, gestational age, and Apgar score at 1' and 5'. Instead the female infants had a significantly lower mean value of ROMs than the male babies (respectively 104.4 +/- 32.2 vs 120.2 +/- 30.6 U. Carr.; p = 0.031). Multiple and stepwise regression analyses both demonstrated that the sex of the neonate is able to independently influence the value of ROMs (respectively p = 0.025 and p = 0.035). The main end-point of the study was to determine the standard reference values for this method in the healthy full-term infant at birth: the values of ROMs we found in the "total" population are lower than those of healthy adults (between 250-300 U. Carr.) and similar to those of adults treated with steroids or antioxidant drugs. The finding that the female sex is able to independently determine lower values of ROMs at birth compared to the male sex, lets speculate that the female infants are less prone to oxidative stress in the first moments of life.

Colorimetry↗
PubMed2000

[Neonatal emergency in the delivery room].

Perinatal asphyxia is the main cause of morbidity and mortality in the new-borns and in the infants. During delivery the risk of severe asphyxia is high not only in pre-term infants but also in those at term. A correct assistance during the first minutes of life is crucial for the outcome of the asphyxiated babies. The interventions to perform are few and quite simple but they must be performed carefully. There are some standardised steps in the correct assistance of the new-borns in the delivery room: A)--airways gentle cleaning. B)--breathing, maintain a good ventilation with manual assistance avoiding the use of oxygen. Oxygen is toxic not only for preterm infants but also for babies at term. C)--cardiac activity, check in order to maintain a good blood pressure. Permanent brain damages are related not only to the length and the severity of asphyxia but mainly to the cardiac activity and to the circulation., D)--drugs: only few drugs are seldom necessary for rescutation of the new-borns in the delivery room--beta-mimetics, Na-bicarbonate, surfactant--and they must be used carefully. The time is another critical point to prevent permanent damages, in the severe asphyxia only few minutes and for this reason it is mandatory the presence in delivery room of a person with very good experience in the newborn resuscitation.

Asphyxia Neonatorum↗
PubMed2000

Timing of exogenous surfactant administration in clinical practice. Report of a multi-center Italian Observational Study.

UNLABELLED: We now have convincing data that surfactant administration in newborns with the respiratory distress syndrome (RDS) is effective in reducing the need for respiratory supports and improves the clinical outcomes. To evaluate the different strategies adopted in clinical practice for the surfactant use we performed an observational multicenter study. All newborns with gestational age (g.a.) between 24-32 wk. with RDS and that were in need of mechanical ventilation and treated with exogenous surfactant from 1994 to 1996 in twelve Neonatal Intensive Care Units have been evaluated. The patients have been divided into two groups: one includes babies that were given surfactant within the first 15 minutes of life (very early -VE- treated) and the other includes those that received the treatment at age 16- 180 minutes (early -E- treated). The analysis concerned 246 cases, 54 VE treated and 192 E treated. The two groups were comparable with regards to sex, Apgar score at one and five minutes, maternal treatment with steroids and multiple pregnancy. Mean birth weight and g.a. were significantly lower and the rate of caesarean sections was higher in the VE than in the E. Almost 80% of the VE newborns had a g.a. equal or less than 28 wks. One single dose of surfactant was administered in 77.8% of VE babies and 45.3% in the E group, while 18.5% VE and 36.8% E received two doses, 3.7% VE and 16.3% E were given three doses. The mean number of doses used per patient was 1.3 in VE and 1.7 in E. 62.5% of cases with g.a. equal to or less than 26 wks and 80.8% of those with g.a. 27-28 wk. received a single dose if VE, compared to 31.9% and 49.1% respectively if E treated. Prenatal prophylaxis of RDS with steroids, considering only the mothers that received a complete course between 48 hrs and 7 days before the delivery, did not modify the number of doses of surfactant required in both groups. The main outcomes did not differ in the two groups: mortality at 28 days of life, age at death, pneumothorax, intraventricular haemorrhage grade 3-4, retinopathy of prematurity grade 3-4, patent ductus arteriosus and oxygen dependency at 36 wks post-conceptional age. CONCLUSIONS: Very early surfactant administration in clinical practice reserved for newborns with the lowest g.a., improves the outcome and does not increase surfactant consumption.

Female↗
PubMed1999

Cyclin-D1 expression in node-positive (N+) and node-negative (N-) infiltrating human mammary carcinomas.

Cyclin-D1 (CD1) expression was analyzed in human mammary carcinomas by immunohistochemical (IHC) and flow-cytometry (FCM) methods: 52.5% and 50% of cases were strong expressors of CD1 by IHC and FCM analysis respectively. The percentage of CD1-positive cells was especially high in node-negative (N-) estrogen-receptor-positive (ER+) tumors, probably as a consequence of CD1 induction by estrogens in steroid-responsive tissues. However, CD1 expression was not related to ER positivity in node-positive tumors (N+). An interesting relationship between CD1 expression and H3-thymidine labelling index (H3Td-LI) was also found: CD1 and H3Td-LI were unrelated in N- tumors, while high CD1 expression was observed in N+ tumors with high DNA synthesis, as assessed by H3Td-LI. The combined measurement of DNA and CD1 showed that 27 specimens were aneuploid, 19 of them (19/27; 70%) strongly expressing CD1. Further studies are needed to clarify the role of CD1 in DNA abnormality of breast tumors. However, we cannot exclude that the CD1 may be differently de-regulated in the last phase of tumor progression, and that CD1 over-expression may contribute to the aneuploidy of mammary carcinomas.

Breast Neoplasms↗