PubMed Health⌕ Search

Biomedical subjects

A Ercoli

Publications and source records attributed to A Ercoli.

At least 19 recordsLinked to original sources

Postoperative ileus after para-aortic lymphadenectomy: a prospective study.

OBJECTIVE: To evaluate GI symptoms in patients submitted to systematic para-aortic lymphadenectomy (PALN) and to compare them in a contemporary series of patients only submitted to systematic pelvic lymphadenectomy (PLN). METHODS: A prospective study of 51 consecutive patients submitted to systematic (minimum number of aortic nodes removed > or =10) laparotomic para-aortic lymphadenectomy for any gynecological cancer. The following parameters have been monitored prospectively: nausea and vomiting, bowel movements, nasogastric tube insertion or reinsertion, the time of removal of the nasogastric tube, duration of ileus, time to first passage of stool, regular diet consumption and postoperative stay and complications. RESULTS: Twenty-three of 46 valuable patients (50%) submitted to systematic para-aortic lymphadenectomy complain of GI symptoms during recovery and 2 more cases have been readmitted for the appearance of nausea and vomiting with respect to 3 cases (5%) in the group of only pelvic lymphadenectomies (p=0.00001). According to multivariate analysis, the main determinant of post/operative GI dysfunction is the systematic aortic lymphadenectomy. Twenty-two out of a total of 28 symptomatic patients (78.6%) have accused mild symptoms and have been therefore treated by fasting, by intravenous fluid administration and by anti-emetic drugs. Out of the six remaining patients, three patients (10.7%) have been classified as moderate cases because they have required the insertion of a nasogastric tube for gastric decompression, whereas in the remaining refractory patients (10.7%, severe cases) prokinetics drugs have been used. An exploratory laparotomy has never been performed. CONCLUSIONS: GI dysfunction symptoms are very common in patients submitted to systematic para-aortic lymphadenectomy. However, only 20% of the patients complain about moderate/severe symptoms. In these cases, we strongly recommend a conservative management.

Aorta, Abdominal↗

Classical and nerve-sparing radical hysterectomy: an evaluation of the risk of injury to the autonomous pelvic nerves.

Radical hysterectomy represents the treatment of choice for FIGO stage IA2-IIA cervical cancer. It is associated with several serious complications such as urinary and anorectal dysfunction due to surgical trauma to the autonomous nervous system. In order to determine those surgical steps involving the risk of nerve injury during both classical and nerve-sparing radical hysterectomy, we investigated the relationships between pelvic fascial, vascular and nervous structures in a large series of embalmed and fresh female cadavers. We showed that the extent of potential denervation after classical radical hysterectomy is directly correlated with the radicality of the operation. The surgical steps that carry a high risk of nerve injury are the resection of the uterosacral and vesicouterine ligaments and of the paracervix. A nerve-sparing approach to radical hysterectomy for cervical cancer is feasible if specific resection limits, such as the deep uterine vein, are carefully identified and respected. However, a nerve-sparing surgical effort should be balanced with the oncological priorities of removal of disease and all its potential routes of local spread.

Aged↗

Microsatellite instability is an independent indicator of recurrence in sporadic stage I-II endometrial adenocarcinoma.

PURPOSE: The aim of this study was to define the prognostic role of microsatellite status in 65 stage I-II primary sporadic endometrioid endometrial adenocarcinoma (EEA) patients. PATIENTS AND METHODS: Familiarity for neoplasia was ascertained in all patients on the basis of a questionnaire. Microsatellite status was assessed by matching normal and tumoral DNA probed for five dinucleotide repeats and one mononucleotide repeat marker. Microsatellite status was analyzed in relation to clinicopathologic characteristics of the patients and length of disease-free survival (DFS). RESULTS: Eleven tumors (17%) of 65 had instability at two or more loci and were considered as unstable or microsatellite instability (MI). Tumors with no instability or instability at one locus were classified as microsatellite stable (MS). The percentage of MI was significantly higher in poorly than in well to moderately differentiated tumors (50% v 9%; P =.003). The 5-year DFS rate of MI patients was 63% (95% confidence interval [CI], 35% to 91%) versus 96% (95% CI, 91% to 101%) of MS patients (P =.0004). In multivariate analysis, only the presence of MI, stage II of disease, and depth of myometrial invasion greater than 50% retained independent prognostic roles. CONCLUSION: The assessment of microsatellite status may provide useful information for preoperative prognostic characterization of stage I-II primary sporadic EEA patients in which more individualized treatment options can be attempted.

Adaptor Proteins, Signal Transducing↗

Activity of cisplatin and ICI 182,780 on estrogen receptor negative ovarian cancer cells: cell cycle and cell replication rate perturbation, chromatin texture alteration and apoptosis induction.

The activity of cisplatin (CP, range of concentrations 0.25-1 microg/ml), the pure steroidal antiestrogen compound ICI 182,780 (range of concentrations, 0.01-10 microM) and various combinations of, was investigated on an estrogen receptor negative ovarian cancer cell line (A2780 WT) and its CP-resistant derivative subline (A2780 CP3). CP markedly reduced A2780 WT cell growth but marginally affected A2780 CP3, whereas ICI 182,780 was effective on both cell lines. CP but not ICI 182,780 provoked a significant blockade in late S/G(2) phase in both cell lines, particularly in the parental line. Measuring the number of rounds of cell replications showed that CP diminished the cell replication rate of both cell lines, particularly in A2780 WT. Conversely, ICI 182,780 reduced the cell replication rate of A2780 CP3 but not A2780 WT cells. Both drugs provoked apoptosis in A2780 WT cells, as assessed by the appearance of large (50-300 kbp) DNA fragmentation. However, laser scanning cytometry showed that only CP induced a measurable alteration of chromatin texture in A2780 WT but not in A2780 CP3 cells. The combination CP and ICI 182,780 resulted in a synergistic inhibitory activity of cell growth with a CP potentiation up to 4 and 11-fold in A2780 WT and A2780 CP3 cells, respectively. This reflected an enhanced reduction of the cell replication rate and did not involve perturbations of the cell cycle other than those provoked by CP alone. Apoptosis induction and the level of CP-DNA adducts were not influenced by adding ICI 182,780 to CP in both cell lines.

Antineoplastic Combined Chemotherapy Protocols↗

hMSH2 and GTBP expression in advanced stage epithelial ovarian cancer.

Defects in DNA mismatch repair have been associated with both hereditary and sporadic forms of human cancer. Most of the attention has been focused on the incidence and genetics of mismatch repair defects, while little is known about the expression levels of the mismatch repair proteins and their significance in cancer cell biology. In this study, both the expression levels of hMSH2 and GTBP proteins were investigated by Western blotting in 20 untreated epithelial ovarian cancers. For these analyses, a commercial anti-hMSH2 monoclonal antibody and a newly generated mouse monoclonal anti-GTBP antibody were used. hMSH2 and GTBP proteins were detected by Western blotting in 19 out of 20 (95%) samples analysed and were found to be directly correlated (r= +0.51, P = 0.025). hMSH2 expression was significantly higher in ovarian cancer cells originating from solid tumours than from ascites (H = 4.5, P = 0.033), whereas GTBP content did not significantly differ according to the origin of cancer cells. No statistically significant differences were found in the distribution of hMSH2 and GTBP levels according to the age of the patients, grade of differentiation, histotype and extent of surgical debulking. The amount of hMSH2 protein was demonstrated to be significantly lower in stage IV than in stage III patients (H = 7.35, P = 0.007). Moreover, significantly lower hMSH2 levels were observed in non-responding patients compared to patients who achieved complete or partial response to cisplatin-based chemotherapy (H = 4.88, P = 0.027). Conversely, GTBP levels were not distributed differently according to stage of disease and chemotherapy response. Our study suggests a possible involvement of hMSH2 in ovarian cancer cell biology and susceptibility to chemotherapy. The possible biological and/or clinical role of GTBP expression in ovarian cancer patients remains to be elucidated.

Adult↗

Comparative study on the induction of cytostasis and apoptosis by ICI 182,780 and tamoxifen in an estrogen receptor-negative ovarian cancer cell line.

We have compared the effects of a broad range of clinically relevant concentrations (0.1 to 10 microM) of the steroidal pure anti-estrogen ICI 182,780 and the non-steroidal partial anti-estrogen tamoxifen (TAM) on cell proliferation and induction of apoptosis in the estrogen receptor (ER)-negative ovarian carcinoma cell line A2780. Cell proliferation was assessed by evaluating the number of viable cells, changes in cell-cycle distribution and cell replication rate; while apoptosis induction was assessed by examining nuclear morphological changes associated with apoptotic death and DNA cleavage into 300 and 50 kbp units (large DNA fragmentation) and into 180 bp units (internucleosomal DNA fragmentation). We provide evidence that 0.1 to 10 microM ICI 182,780 and TAM significantly inhibit the growth of A2780 cells in a dose-dependent fashion. Cytokinetic analysis revealed that only 10 microM TAM caused a significant blockade in G1 and a diminished replication rate. Conversely, we show that 0.1 to 10 microM ICI 182,780 and TAM induce apoptosis in a dose-dependent fashion. The earliest recognizable apoptotic change induced by treating the cells with these 2 drugs was DNA cleavage into 300 and 50 kbp units. This started to be visible in adherent cells, implying that apoptosis induction by ICI 182,780 and TAM was not determined by the loss of cell-substrate interaction. A further degradation of 300 and 50 kbp DNA fragments occurred in cells that had lost their adhesion to the culture plate. We observed the ladder pattern typical of internucleosomal DNA cleavage by treating A2780 cells with the highest dose (10 microM) of ICI 182,780 and TAM. Lower concentrations of these 2 drugs (0.1 to 1 microM) did not produce such a pattern of DNA fragmentation. Typical features of apoptotic nuclei were detectable after both drug treatments. However, cells undergoing apoptosis induced by ICI 182,780 showed hyper-aggregation of chromatin, whereas TAM-treated cells preferentially exhibited chromatin clumping.

Antineoplastic Agents↗

Tamoxifen synergizes the antiproliferative effect of cisplatin in human ovarian cancer cells: enhancement of DNA platination as a possible mechanism.

We investigated the chemosensitizing activity of tamoxifen (TAM) on estrogen receptor negative ovarian cancer cell lines sensitive (A2780 WT) and resistant to cisplatin (CP) (A2780 CP3). Our results showed that the treatment of both cell lines with the association TAM + CP (concentration range 0.01-1 microN and 0.1-1 microgram/ml, respectively) results in a synergistic antiproliferative activity and a complete reversal of the acquired CP-resistant phenotype. We demonstrated that in A2780 cells the addition of TAM to CP treatment is able to significantly enhance at every tested CP dose (P < 0.001) the amount of platinum (Pt) bound to the DNA. Since Pt-DNA levels in the genome are clearly related to the growth inhibitory effect of CP (correlation value = 0.97, P < 0.001) in our experimental model, we hypothesized that TAM could act synergistically with CP and overcome the acquired CP-resistance by enhancing Pt binding to the DNA. We suggest that, from a clinical point of view, TAM may be usefully included in CP-based chemotherapy regimens for ovarian cancer patients since plasma concentrations of the drug capable of in vitro CP resistance modulation are achievable in vivo. A prospective clinical trial to verify the clinical usefulness of combined TAM + CP treatment in ovarian cancer patients refractory to prior Pt-based chemotherapy is now underway in our department.

Antineoplastic Agents↗

Bisdioxopiperazine, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187), enhances the antiproliferative effect of cisplatin on human ovarian cancer cells.

The bisdioxopiperazine ICRF 187 is a potent intracellular chelating agent which effectively diminishes Adriamycin cardiotoxicity without compromising its antitumor activity. Our study aimed at verifying whether ICRF 187 can modulate the cytotoxic action of cisplatin (CDDP) on ovarian cancer cells. We used the A2780 ovarian cancer cell line and a subline resistant to CDDP (A2780-CDDP) obtained in our laboratory by continuous exposure of the parenatal cells to progressively increasing CDDP doses. In both cell lines ICRF 187 (0.1-0.5 microgram/ml) used in combination with CDDP (0.01-1 microgram/ml) produced a dose-dependent reduction of CDDP IC50 (the concentration inhibiting 50% of cell growth). Moreover, when ICRF 187 was used in combination with CDDP, analysis of the data by the isobole method showed that the combination of the two drugs produced a synergistic antiproliferative activity in both cell lines, with a CDDP potentiation up to fivefold. Our in vitro data show that ICRF 187 can synergize with CDDP. Prospective clinical trials are now needed to verify whether the addition of ICRF 187 to CDDP-containing regimens will result in an improved clinical response in ovarian cancer.

Antineoplastic Agents↗

Effect of synthetic and naturally occurring chalcones on ovarian cancer cell growth: structure-activity relationships.

This study was carried out to determine the effect of 15 different natural and synthetic chalcones on the proliferation of both established and primary ovarian cancer cells expressing type II oestrogen binding sites (type II EBS). The binding affinity of chalcones for type II EBS was also tested. At concentrations from 0.1 to 10 microM, chalcones inhibited ovarian cancer cell proliferation and [3H]oestradiol ([3H]E2) binding to type II EBS. Considering the structure-related variation in IC50 (concentration resulting in a 50% inhibition of cell growth) and Di50 (concentration resulting in a 50% displacement of [3H]E2 bound to type II EBS), it appeared that the presence of an alpha-beta double bond, the hydroxylation in 3 or 2 of ring B and the absence of a prenyl group were important to both the antiproliferative and binding activity. Structure-related variations in IC50 and Di50 were significantly concordant (Fisher's exact test: P = 0.0291), suggesting that there may be a type II EBS-mediated mechanism for chalcone antiproliferative activity. Our data indicate that chalcones could be considered as potential new anticancer drugs.

Binding Sites↗

Clinical significance of cathepsin D in primary ovarian cancer.

Cathepsin D (Cath D) levels were assayed in a prospective series of 72 patients with primary ovarian carcinoma, by using an immunoradiometric assay. Cath D levels ranged from 2.00 to 45.60 pmol/mg protein with a median value of 15.80 pmol/mg protein. Cath D levels were higher in metastatic deposits than in primary tumors (median 24.12, range 9.33-98.33 pmol/mg protein versus median 12.76, range 2.00-45.20 pmol/mg protein; P = 0.04). The cut-off levels of the lower, median and upper quartiles of the distribution of Cath D were identified to distinguish patients with low, intermediate, and high Cath D content. Cases with low Cath D content showed a lower percentage of complete response to chemotherapy than cases with intermediate and high Cath D content (22% versus 65% and 47%, respectively) (P = 0.003). Moreover cases with high Cath D content showed a worse prognosis with respect to patients with intermediate Cath D levels (P = 0.09). Interestingly, cases with low Cath D content had a shorter progression-free survival with respect to cases with intermediate Cath D content (P = 0.04). Cath D status retained an independent prognostic value when assessed in the multivariate analysis.

Adult↗

Cytogenetic findings in echographically defined blighted ovum abortions.

A sample of 52 spontaneous blighted ovum abortions (BO) was examined cytogenetically and compared with a sample of abortions with echographic evidence of the embryo (AE). Abnormal karyotypes were 67% in the BO sample and 53% in the AE sample, a non significant difference. In the BO abortions trisomies were 74% of the abnormal karyotypes but 35% in the AE abortion, and the 45,X karyotype was absent among the BO but was found in 10 cases of AE. The prevalence of trisomies 16 and 22 in the BO abortions indicates that genes on these chromosome may be responsible for the early arrest of embryonic development.

Abortion, Spontaneous↗

One case of "prune belly" syndrome: prenatal and prognostic valuation.

A case of "Prune Belly" syndrome, its sonographic diagnosis, from the 15th week and its monitoring by sonography and biochemical exams of fetal urine for study of renal function is described. The good relation between prenatal prognosis and neonatal renal function is verified after birth.

Female↗