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Biomedical subjects

G Biagini

Publications and source records attributed to G Biagini.

207 records · Page 12Linked to original sources
PubMedDate not supplied

Bone mineral density across the normal rat femour.

The post-ovariectomy osteoporotic rat model is widely used to mimic post menopausal human osteoporosis and to test the efficacy of the therapies used in its treatment An experimental study was performed in order to improve the reliability of bone mineral density (BMD) measurements by correcting also the relocation error. In addition, a BMD map of the whole femur was carried out to detect the areas of uniform density, where the reliability of measuring was improved. Right femurs were taken from 5 Sprague Dawley female rats, 10 months old, and tested every 2 mm from the supracondylar line to the peritrochanteric line (6 scans for each site). Repositioning error was tested for each site of measurement, and measurements done by 3 different operators in a double blind test were compared. At site 4 and 24 (where the differences are high) and site 10 (where the differences of BMD are low) the coefficient of variability (CV) was calculated repositioning the bone after each measurement scan for a total of 6 scans. The CV at sites 4 and 24 were significantly higher than at site 10 (p < 0.05). In our opinion, the bone segment between 8 and 14 mm from the supracondylar line is that which presents the highest homogeneity and where it is preferable to perform the measurements in order to obtain the maximum effect of the method (improvement of precision of about 30%) in comparison with the other femur sites tested.

Absorptiometry, Photon↗
PubMedDate not supplied

Immunohistochemical evaluation of type IV collagenase (72-kd metalloproteinase) in prostatic intraepithelial neoplasia.

The aim of this study was to investigate the expression of type IV collagenase (72-kd metalloproteinase, MMP-2) in prostatic intraepithelial neoplasia (PIN) in relation to normal prostate (NP) and prostatic adenocarcinoma (PAc). Twenty formalin-fixed, paraffin-embedded prostatectomy specimens, in which NP, PIN and PAc were present, were immunohistochemically examined. The NP ducts and acini not contiguous with PIN and PAc showed slight MMP-2 immunostaining in the secretory cells, with some increase in intensity at the apical border, and moderate to strong immunoreactivity of some basal cells. In NP adjacent to PIN and PAc, rare ducts and acini showed strongly stained cells either isolated or in small groups of two, located within the thickness of the epithelium, close to the basement membrane. In the majority of PIN ducts and acini, the stratified secretory cells showed moderate staining. Most of these ducts and acini also showed strongly stained cells, which were mostly isolated, and either in contact with the basement membrane or scattered among the secretory cells. Low and high grade PIN showed some difference in the frequency of dark cells, which were more numerous in the latter. A small group of neoplastic acini adjacent to high grade PIN (early invasive adenocarcinoma) was observed in one of the 20 cases. Intense immunostaining was present in the acini originating from the PIN lesion. MMP-2 immunostaining of PAc was heterogeneous in intensity and location. Cribriform and solid/trabecular PAc showed weak cytoplasmic immunostaining; both moderately and intensely stained cells were seen in the cell layer adjacent to the stroma, intense immunostaining was shown by small clusters of neoplastic cells or single neoplastic cells located in the stroma. In acinar PAc, weak cytoplasmic immunostaining for MMP-2 was seen throughout most areas of the tumours, whereas moderately and intensely stained cells were observed less frequently than in cribriform and solid/trabecular adenocarcinoma. Intense immunostaining of single or small clusters of neoplastic cells located in the stroma was occasionally observed and, as with cribriform and solid/trabecular PAc, mainly located towards the periphery of the tumour nodules. Occasional ducts and acini with PIN and foci of PAc were either completely negative or very weakly stained. In conclusion, MMP-2 immunostaining increases progressively from NP, through PIN, up to invasive PAc. These results directly support the hypothesis that increased expression of metalloproteinases is a marker of malignant conversion.

Adenocarcinoma↗
PubMedDate not supplied

Increased serum 72 KDa metalloproteinase in serous ovarian tumors: comparison with CA 125.

72 KDa metalloproteinase (MMP-2) is an enzyme present in neoplastic cells and also in normal fibroblasts. It specifically cleaves type IV collagen, and therefore may play a critical role in tumor invasion and metastasis mechanisms. The aim of the present study was to determine serum levels of MMP-2 in serous ovarian tumors, and compare these with serum levels of CA 125. Ten primary ovarian serous cystadenocarcinomas, 5 borderline tumors, and 10 serous cystadenomas, all treated with primary surgery, were recruited from our series of serous ovarian tumors, and studied. Patients' serum samples were obtained before surgery, and the MMP-2 levels were measured by the substrate capture enzyme-linked immunosorbet assay. The analysis of serum MMP-2, gave values significantly higher in cystadenocarcinomas than in borderline tumors and cystadenomas (one way analysis of variance, P < 0.001); in particular, serum MMP-2 was significantly correlated to the MMP-2 immunostaining of the tumor (Spearman correlation, r = 0.82, and P < 0.001). An arbitrary cutoff of the median value of normal adult female samples (0.22 units) was chosen, and all except for one patient with cystadenocarcinoma was shown to have serum MMP-2 levels above the cutoff value, with 90% sensitivity, 70% specificity, and a 75% positive predictive value (50% of Cohen's Kappa); on the other hand, CA 125 showed 80% sensitivity, and a 73% positive predictive value. The association of serum MMP-2 with CA 125 increased sensitivity to 100% in patients with cystadenocarcinoma, with 70% persisting specificity and a 77% positive predictive value (54% of Cohen's Kappa). Serum MMP-2 levels were found to be significantly increased in patients with cystadenocarcinoma in comparison with borderline tumors and cystadenomas, showing a direct relationship with tissutal MMP-2 expression in serous ovarian tumors. Although our results were preliminary, they clearly suggested that serum MMP-2 may be an interesting diagnostic marker for cystadenocarcinomas.

Adult↗
PubMedDate not supplied

Expression of p53 and apoptosis of tumor cells in locally advanced cervical carcinoma after cisplatin based neoadjuvant chemotherapy.

Various chemoantiblastic agents cause DNA damage followed by apoptotic cell death through the activation of the p53 suppressor gene. The aim of our study was to evaluate the relationship between p53 protein expression, apoptosis of autologous tumor cells, and clinical response to neoadjuvant chemotherapy in patients with cervical carcinoma. Our study included 14 women with stage II squamous cervical carcinoma who had been admitted to the Institute of Gynecology and Obstetrics, Ancona University, between January 1990 and December 1995. The patients received neoadjuvant combination chemotherapy, consisting of three cycles of cisplatin (80 mg/m2) and bleomycin (30 mg/m2). After chemotherapy, radical surgery was performed. Bioptic specimens were obtained from cervical tumors before and after chemotherapy, and processed for DNA staining and apoptosis, and immunohistochemical staining with a monoclonal antibody against p53. Ten patients (71.4%) showed a clinical response (2 complete, and 8 partial), while of the remaining 4 cases (28.6%) 3 had no change and 1 showed progression after neoadjuvant combination chemotherapy. A significant relationship was observed between the overexpression of p53 and sensitivity to chemotherapy; responder patients showed a higher frequency of p53 positive cells than non-responders (p = .05). A significant direct relationship was observed between p53 protein immunostaining and apoptosis of tumor cells both before (p = .02) and after (p = .01) chemotherapy. Our study seems to define the relationship between p53 expression and sensitivity to cisplatin based chemotherapy in locally advanced cervical carcinoma, supporting the notion that the cytotoxic action of cisplatin can activate p53 mediated apoptosis. However, the limited number of patients in our series does not permit judgement on the clinical implications of the expression of p53 in patients undergoing neoadjuvant combination chemotherapy for locally advanced cervical carcinoma.

Adult↗
PubMedDate not supplied

p53 immunostaining and HPV DNA detection by PCR in cervical intraepithelial neoplasia: clinical implications of a combinated evaluation.

We analyzed p53 immunoreactivity and clinical outcome in a series of cervical intraepithelial neoplasias (CIN), with respect to HPV DNA positivity. Cervical biopsy samples were obtained from 86 women who attended our Colposcopic Service from January 1993 to June 1994 due to abnormal pap-smear suspicious for CIN and/or human papillomavirus infection. Forty-one women with histologically confirmed CIN were included in the study. p53 positivity was immunohistochemically detected by monoclonal antibody anti-human p53 (pAb D0-7, Dako Denmark; dilution 1:50), and expressed as the percentage of positive cells. p53 positivity was observed in 78% of CIN lesions. In particular, all the HPV DNA-negative dysplasias expressed p53 protein while only 12 out of 21 (57%) HPV DNA-positive were p53 immunoreactive; (P = .003) the p53 immunostaining was also significantly higher in HPV DNA-negative than in positive CIN (P = .049). By analyzing p53 positivity with respect to clinical-pathologic evolution of the disease, among HPV DNA-negative cases, progressive dysplasia had significantly higher values of p53 immunostaining when compared to persistent and/or regressive lesions (P = .002). These findings imply that p53 immunostaining, when analyzed with respect to HPV DNA status, may help to understand the behavior of dysplastic lesions and define their therapeutic approach. Extensive p53 staining in HPV DNA-negative CIN is probably correlated with a high risk of progression.

Adult↗
PubMedDate not supplied

Ras p21 immunostaining in early stage squamous cervical carcinoma: relationship with lymph nodal involvement and 72 kDa-metalloproteinase index.

BACKGROUND: Ras p21 expression seems to be associated with aggressiveness of neoplastic growth and metastatic potentially in human solid tumors. In our series of early-stage squamous cervical carcinoma, we evaluated ras p21 expression with respect to lymph nodal involvement; the aim was to analyse the ras p21 immunostaining as potential marker of lymphatic spread, and investigate the relationship between ras p21 expression and 72 kDa-metalloproteinase immunostaining. PATIENTS AND METHODS: 46 patients with FIGO stage I squamous cell cervical carcinoma, who had undergone primary radical surgery with systematic pelvic and paraaortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, were recruited from our series of 59 consecutive cases, and included the study. Any characteristic that could be relevant for prognosis was recorded such as: histologic grade of differentiation, tumor size, lymphatic spread, or adjuvant radiotherapy. Immunohistochemical staining was performed using the avidin-biotin peroxidase complex method (LSAB, Dako, Copenhagen, Denmark). Monoclonal antibody anti-pan ras (Ab-1) (Oncogene Science) and affinity purified rabbit anti-72 kDa-metalloproteinase antibody were used. Positivity for ras p21 was evaluated by semiquantitative analysis, while 72 kDa-metalloproteinase staining was expressed as the percentage of positive cells per 10(3) counted neoplastic cells (index). RESULTS: The expression of ras p21 was observed in 31 patients (67%) with FIGO stage I squamous cervical carcinoma. No connection was found between ras p21 expression and tumor size (P = 0.2), or histologic grade (P = 0.9), while a significant relationship was observed with respect to lymph nodal status (p = 0.048). By analysing 72 kDa-metalloproteinase immunostaining, ras p21 positive carcinomas showed significantly higher 72 kDa-metalloproteinase index than the negative ones (mean + standard deviation, 23.3% + 7.7% and 13.8% + 5.1% respectively, and P < 0.001). CONCLUSIONS: Though the relatively small size of our series does not allow any definitive conclusion, a significant relationship between ras p21 expression and risk of lymphatic spread was detected in early-stage cervical carcinoma. ras p21 positivity seems to be an indicator of neoplastic aggressiveness and lymphatic spread, and is associated with significantly higher expression of 72 kDa-metalloproteinase.

Adult↗