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Biomedical subjects

C D'Angelo

Publications and source records attributed to C D'Angelo.

At least 19 recordsLinked to original sources
PubMed2003

Bio-pathological factors of prognostic value in colorectal adenocarcinomas.

About 40% of patients bearing a colorectal carcinoma will develop local or distant tumor recurrences. Integrated analyses of biopathological markers, predictive of tumor aggressiveness, may offer a more rational approach to adjuvant therapy planning. To this end we analyzed the correlation between p53 accumulation, bcl-2 expression with cell proliferation, DNA ploidy, and conventional histological parameters, by testing the prognostic significance of these variables in a series of 214 patients bearing a colorectal carcinoma. When these parameters were examined in the univariate analysis, significantly shorter disease free and overall survival were observed in patients bearing p53+ and bcl-2- tumors. In the multivariate analysis p53 accumulation and bcl-2 expression emerged as independent predictors respectively of worse and better clinical outcome also in Dukes' B stage identifying patients at higher risk to develop liver metastases.. These results indicate that in colorectal adenocarcinomas a biological profile, based on the combined evaluation of p53 and bcl-2, can be useful in identifying high risk patients to be enrolled in an adjuvant setting mainly in early stage of the disease.

Adenocarcinoma↗
PubMed2001

c-Myb and Bcl-x overexpression predicts poor prognosis in colorectal cancer: clinical and experimental findings.

The aim of this study was twofold: to assess the relationship between c-Myb and Bcl-x expression and to evaluate the prognostic significance of their expression in colorectal carcinoma (CRC) patients. Analysis of tumors from 91 CRC patients for expression of c-Myb and Bcl-x revealed a significant relationship between these two proteins. Kaplan-Meier's analysis showed an increased risk of relapse and death in patients whose tumor specimens displayed high c-Myb levels and Bcl-x positivity. Similar results were also observed excluding Dukes' D patients. Molecular analysis using three c-Myb-overexpressing LoVo clones indicated that c-Myb overexpression was accompanied by up-regulation of Bcl-x(L) protein and mRNA. Tumors originating from these clones injected in nude mice were significantly larger than those formed in mice injected with parental or vector-transfected LoVo cells. Moreover, tumors derived from parental and control vector-transfected but not from c-Myb-overexpressing LoVo cells showed high frequency of apoptotic cells. These results provide direct evidence of an association between c-Myb and Bcl-x expression and suggest that expression of both molecules might be a useful prognostic marker in CRC.

Carcinoma↗
PubMed2001

p53 nuclear accumulation and multiploidy are adverse prognostic factors in surgically resected stage II colorectal cancers independent of fluorouracil-based adjuvant therapy.

To identify the prognostically highest risk patients, DNA content and p53 nuclear or cytoplasmic accumulation, evaluated by monoclonal antibody DO7 and polyclonal antibody CM1, were determined in 94 surgically resected stage II (Dukes B2) colorectal cancers, treated or not with adjuvant 5-fluorouracil-based chemotherapy. Sixty-one (65%) of the tumors were aneuploid, 16 (17%) of which had a multiploid DNA content; 50 (53%) displayed DO7 nuclear p53 accumulation, and 44 (47%) showed cytoplasmic CM1 positivity. In multivariate analysis, only multiploidy and p53 nuclear positivity emerged as independent prognostic indicators of a poorer outcome. Positivity for p53 was associated with shorter survival in 5-fluorouracil-treated and untreated patients. Therefore, in patients with Dukes B2 colorectal cancer, a biologic profile based on the combined evaluation of DNA multiploidy and p53 status can provide valuable prognostic information, identifying patients to be enrolled in alternative, more aggressive therapeutic trials.

Adenocarcinoma↗
PubMed1999

Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2.

About 40% of patients with colorectal carcinoma will develop local or distant tumour recurrences. Integrated analyses of bio-pathological markers, predictive of tumour aggressiveness, may offer a more rational approach to planning adjuvant therapy. To this end, we analysed the correlation between p53 accumulation, Bcl-2 expression, DNA ploidy, cell proliferation and conventional clinico-pathological parameters by testing the prognostic significance of these variables in a series of 171 colorectal carcinoma patients with long-term follow-up. The relationships among the various bio-pathological parameters, analysed by multiple correspondence analysis, showed 2 different clinico-biological profiles. The first, characterised by p53 negativity, Bcl-2 positivity, diploidy, low percentage of cells in S-phase (%S-phase), a low Ki-67 score, is associated with Dukes' A-B stage, well differentiated tumours and lack of relapse. The second, defined by p53 positivity, Bcl-2 negativity, aneuploidy, high %S-phase and elevated Ki-67 score, correlates with Dukes' C-D stage, poorly differentiated tumours and presence of relapse. When these parameters were examined according to Kaplan-Meier's method, significantly shorter disease-free (DFS) and overall survival (OS) were also observed in patients bearing p53 positive and Bcl-2 negative tumours, in Dukes' B stage. In multivariate analysis, p53 accumulation and Bcl-2 expression emerged as independent predictors of a worse and better clinical outcome, respectively. Our results indicate that, in colorectal adenocarcinomas, a biological profile, based on the combined evaluation of p53 and Bcl-2, may be useful for identifying high risk patients to be enrolled in an adjuvant setting, mainly in an early stage of the disease. Int. J. Cancer (Pred. Oncol.) 84:545-552, 1999.

Adenocarcinoma↗
PubMed1999

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule.

In this article, we investigated the effect induced by the reintroduction of wild-type p53 (wt-p53) protein on BCNU sensitivity in the ADF glioblastoma line. Using a wt-p53 recombinant adenovirus (Ad-p53), we demonstrated that exogenous wt-p53 expression was able to increase the sensitivity to BCNU in ADF cells. Interestingly, this effect was more evident when Ad-p53 infection was performed after BCNU treatment compared with the opposite sequence. To understand the biological basis of these different behaviors, we analyzed the cell cycle of the differently treated cells. We found that Ad-p53 infection induced a persistent accumulation of cells in the G0/G1 phase while, as expected, BCNU induced a block in the G2-M phase. Ad-p53-->BCNU sequence did not significantly modify the cell cycle profile in respect of Ad-p53 infected cells. In contrast, BCNU-->Ad-p53 sequence provoked G2-M arrest similar to that observed after treatment with BCNU alone, but prevented the later recovery of the cells through the cell cycle, by driving the cells to apoptotic death. These results demonstrate that the administration sequence is important to increase drug sensitivity. To generalize the phenomenon observed on ADF line, the antiproliferative effect of the two different schedules was analyzed on other glioblastoma lines (A172, CRS-A2, U373MG) with different BCNU sensitivity and p53 status. The data obtained confirm that the wt-p53 gene transfer enhances BCNU sensitivity in glioblastoma cells depending on the administration sequence.

Adenoviridae↗
PubMed1997

Destabilization of human serum albumin by polyethylene glycols studied by thermodynamical equilibrium and kinetic approaches.

Both polyethylene glycols (PEG) of MW 8,000 and that of 10000 stabilize the native compact state of human albumin showing negative preferential interaction with the protein. Interaction between these polymers and the protein is thermodynamically unfavorable, and becomes even more unfavorable for denatured protein whose surface areas are larger than those of native ones. PEG of low MW 1000 and 4000 did not show steric exclusion, interacting favorably with hydrophobic side chains made available when the protein was unfolded and leading to a stabilization of the unfolded state, which is manifested as a lowering of the thermal transition temperature. Perturbation of the absorption spectrum of albumin by PEGs confirms that at high temperature the polymers preferentially interact with the denatured state of albumin, but is excluded from the native state at low temperature. This observation is consistent with the fact that PEG is hydrophobic in nature and may interact favorably with the hydrophobic side chain exposed upon unfolding. The lower activation energy for thermal unfolding in the presence of PEG 1000 is in favour of preferential interaction of this polymer with human albumin. PEG of low MW favours the ionization of the tyrosine residues of albumin. It is apparent that pKa decreased with the increase in MW of synthetic polymer. Such variation might be a consequence of the change in dielectric constant at the domain of the protein by PEG binding.

Guanidine↗
PubMed1996

Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene.

Lonidamine, a dichlorinated derivative of indazole-3-carboxylic acid, was shown to play a significant role in reversing or overcoming multidrug resistance. Here, we show that exposure to 50 microg/ml of lonidamine induces apoptosis in adriamycin and nitrosourea-resistant cells (MCF-7 ADR(r) human breast cancer cell line, and LB9 glioblastoma multiform cell line), as demonstrated by sub-G1 peaks in DNA content histograms, condensation of nuclear chromatin, and internucleosomal DNA fragmentation. Moreover, we find that apoptosis is preceded by accumulation of the cells in the G0/G1 phase of the cell cycle. Interestingly, lonidamine fails to activate the apoptotic program in the corresponding sensitive parental cell lines (ADR-sensitive MCF-7 WT, and nitrosourea-sensitive LI cells) even after long exposure times. The evaluation of bcl-2 protein expression suggests that this different effect of lonidamine treatment in drug-resistant and -sensitive cell lines might not simply be due to dissimilar expression levels of bcl-2 protein. To determine whether the lonidamine-induced apoptosis is mediated by p53 protein, we used cells lacking endogenous p53 and overexpressing either wild-type p53 or dominant-negative p53 mutant. We find that apoptosis by lonidamine is independent of the p53 gene.

Antineoplastic Agents↗
PubMed1996

[Induratio penis plastica: the diagnostic possibilities of gradient-echo sequences (magnetic resonance angiography)].

The authors investigated the diagnostic capabilities of gradient echo sequences (magnetic resonance angiography) in the study of induratio penis plastica. Twenty patients (mean age: 39 years) were examined. MRA was performed with a superconductive magnet (1.5 T) and a Helmoutz coil; the dynamic test with PGE (20-40 mg) was also carried out. The images acquired on the axial and sagittal planes were processed according to the MIP. The FLASH 2D sequence was used with the following parameters: FA 18 degrees, TR 40 ms, TE ms, MA 256 x 256, slice thickness 5 mm. A multiple choice card was filled in by a reader with the following diagnostic information: identification and localization of the plaques and involvement by the plaques of the albuginea, corpora cavernosa, septum and dorsal vein; surgery was the gold standard. MRA showed 10/11 plaques ranging 8-30 mm in diameter and missed a 5-mm plaque. Moreover, MRA depicted the infiltration of the albuginea in 10/10 cases, of the septum in 3/3 cases, of the dorsal vein in 4/4 cases and of the corpora cavernosa in 9/9 cases. Our preliminary experience shows that in the study of induratio penis plastica, the gradient echo sequence (MRA) permits better depiction of the plaques and of the infiltration of the corpora cavernosa, septum and albuginea.

Adult↗
PubMed1995

DNA ploidy, proliferative index, and epidermal growth factor receptor: expression and prognosis in patients with gastric cancers.

BACKGROUND: The 5-year survival rate of patients with stomach cancer is usually around 20%. The clinico-pathological features that are presently used to assess patient prognosis are not sufficient to define gastric tumor behavior. Therefore, an accurate analysis of different biological characteristics of gastric cancer cells could allow the course of disease to be predicted and may help to improve treatment strategies. EXPERIMENTAL DESIGN: The prognostic values of DNA ploidy, proliferative activity and epidermal growth factor receptor (EGF-R) expression were studied in gastric tumors from a series of 63 patients. DNA ploidy and proliferative activity, evaluated in terms of DNA index (DI) and proliferative index (PI), respectively, were determined by flow cytometry on paraffin-embedded tumor tissues. EGF-R expression was detected by immunohistochemistry on paraffin-embedded tumor sections of the same specimens. The clinico-pathological and the biological parameters were then correlated, and the patients overall survival was calculated using a chi-square test and the Kaplan-Meier method. RESULTS: DNA ploidy abnormal cell clones were found in 44% of cases (median DI = 1.4, range 1.04-2.5). Aneuploid tumors showed high PI more frequently than diploids (71% versus 36%, p = 0.01). The analysis of the expression of EGF-R revealed that 88% of aneuploid tumors were positive for receptor expression. On the contrary, diploid tumors showed the presence of EGF-R only in 56% of cases (p = 0.01). DI, PI, and EGF-R expression were not related to histological grade. Conversely, the three biological parameters were significantly correlated to clinical stage and tumor invasion. The Kaplan-Meier survival curves showed a 73% 5-year survival rate in patients with diploid tumors whereas only 33% of patients with aneuploid lesions had a good prognosis (p = 0.001). CONCLUSIONS: We demonstrate that DNA ploidy, PI, and EGF-R expression are closely related to some pathological and clinical characteristics in gastric cancer. The close relationship between aneuploidy, EGF-R positive expression, node involvement, and tumor invasion suggests that these parameters may be indicators of high malignancy. Finally, the results also show that aneuploidy and EGF-R-positive expression are indicative of a worse prognosis in gastric cancer patients. The study of these parameters might allow a more accurate stratification of patients, so that a targeted therapeutic protocol may be defined.

Aged↗
PubMed1995

[Diagnostic pitfalls in magnetic resonance angiography].

The authors report on their clinical experience with Magnetic Resonance angiography (MRA) pitfalls. January, 1989, to February, 1995, six hundred MRA examinations were performed in different vascular districts, with a 1.5-T superconductive magnet, the time-of-flight (TOF) technique and 2D and 3D acquisitions. Intracranial arteries, epiaortic vessels and renal arteries were studied with FISP 3D sequences; intracranial veins, thoracic vessels, vena cava and pelvic vessels were studied with FISP 2D sequences. Pitfalls were observed in 56 of 600 MRA exams (9.3%). Of 56 pitfalls, 26 (46.4%) were in epiaortic vessels, 15 (26.7%) in intracranial vessels, 6 (10.7%) in renal arteries, 6 (10.7%) in thoracic vessels, 1 (1.7%) in the inferior vena cava and 2 (3.5%) in iliac vessels. Stenoses were overestimated in 21 patients and underestimated in three; 16 patients were misdiagnosed and 16 were false positives. As for cerebral vascular lesions, 5 aneurysms and 7 transverse sinus thromboses were false positives, while 3 lesions were misdiagnosed as venous angiomas. As for 26 MRA exams of thoracic vessels, stenoses were overestimated in 16 patients and underestimated in 10 patients with subclavian steal syndrome, where the left vertebral artery was misinterpreted as occluded. In 6 MRA exams of thoracic vessels, 1 patient was misdiagnosed as having an aneurysm and 5 patients were misdiagnosed as having lung cancer infiltrating aorta and superior vena cava. As for renal vessels, 2 normal renal arteries were misdiagnosed as false positives and 4 stenoses were overestimated. In the inferior vena cava, a partial agenesis was misinterpreted as thrombosis. In 2 MRA exams of iliac vessels, a stenosis and a thrombosis were misinterpreted as false positives. Our experience suggests that MRA pitfalls are caused by the incorrect use of the various techniques. The pitfalls we observed can be classified as caused by three types of artifacts: saturation, turbulence and paramagnetic substance artifacts.

Diagnostic Errors↗
PubMed1991

Circulating diphtheria antitoxin levels in children aged 11-14 years in relation to the vaccinal history.

Diphtheria antitoxin level in serum samples obtained from 204 healthy children aged 11-14 years was determined by means of an indirect haemagglutination technique and related to the vaccinal history of the subjects. Irrespective of the time since the last toxoid inoculation, the mean antitoxin titre per ml of serum in the individuals who had received incomplete/irregular anti-diphtheria vaccination in childhood was significantly higher when the number of toxoid doses was higher (from two to more than four doses); the same was not observed for individuals given primary vaccination (three toxoid doses) according to the schedule for childhood vaccination in Italy (regular vaccinees) and one or more booster doses. Between 8 and 13 years after the last of three toxoid doses, a significantly negative association between mean antitoxin titre and time was observed only in irregularly vaccinated children (r = -0.82; p less than 0.05); nevertheless, up to thirteen years after the last vaccine dose, more than 95% of the children exhibited protective levels of antitoxin (greater than 0.125 turkey red blood cells passive haemagglutination units per ml). No significant decrease in mean antitoxin titre was observed between 4 and 10 years after the last of four either regularly or irregularly administered toxoid doses.

Adolescent↗
PubMed1990

[Total intravenous anesthesia with propofol vs. propofol/N2O anesthesia].

The authors have compared two groups of 31 patients each, undergone an anaesthesia with propofol-O2/N2O (group I) and propofol-O2/air (group II). The average anaesthetic dosage and the neuromuscular recovery time have been valued, keeping constant the dose of analgesic. The average consumption of propofol (except the inductive dose of 2 mg/kg) was 7.41 +/- 1.71 mg/kg/h in group I, and 7.47 +/- 1.76 in group II (p = 0.88; not significant) and the neuromuscular recovery time 56.12 +/- 34.55 m' and 49.48 +/- 40.50 m' respectively (p = 0.53; not significant). The cardiocirculatory parameters have been compared at the time of induction, surgical incision and for all the operation time, reporting every undesired effect. The awakening has been monitored until 15 m' from the interruption of propofol infusion. The data obtained don't permit to observe significant differences with regard to analgesia, neuromuscular block and awakening time. Therefore the authors put the question of the real necessity to use nitrous oxide, when it has utilized an efficient intravenous anaesthetic as the propofol has proved to be.

Adult↗