PubMed Health⌕ Search

Biomedical subjects

G Dardanoni

Publications and source records attributed to G Dardanoni.

At least 19 recordsLinked to original sources
PubMed2006

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.

Adenocarcinoma↗
PubMed2006

Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques.

Aged↗
PubMed2005

Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study.

BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13. CONCLUSION: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.

Adenocarcinoma↗
PubMed2004

Clinical relevance of thymidylate synthase expression in the signet ring cell histotype component of colorectal carcinoma.

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas.

Adult↗
PubMed2003

Analogous IgG subclass response to pertussis toxin in vaccinated children, healthy or affected by whooping cough.

The study of antigen specific IgG subclass distribution during disease, or during any other natural or artificial immunisation, can provide useful information on the kind of the immune response and the expected levels of protection. This is particularly true for diseases, such as pertussis in which the mechanisms underlying specific defence are still not completely understood. An investigation was therefore performed to evaluate the IgG subclass response to pertussis toxin (PT) in sera from 89 healthy vaccinated children and 131 vaccinated or unvaccinated children convalescent after a confirmed B. pertussis symptomatic infection. Antibody titres were expressed in arbitrary ELISA units/ml, and statistical analyses were performed. In unvaccinated convalescent children IgG1 and IgG3 were prevalent whereas in children immunised with two different acellular pertussis (aP) vaccines, both healthy and convalescent, IgG1, IgG2 and IgG4 antibodies were mainly produced. Maintenance of the same anti-PT antibody response pattern in healthy acellular pertussis vaccine recipients and in vaccinated children who later acquire the disease is an interesting result indicative of the priming effect induced by these vaccines in the direction of a relatively higher Th2 cell-polarisation of the immune response.

Antibodies, Bacterial↗
PubMed2002

DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.

PURPOSE: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis. METHODS: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. RESULTS: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P<0.05) and DNA aneuploid tumors (P<0.05) tumors. DNA-aneuploidy was associated with distal tumors (P<0.01), histological grade (G3) (P<0.05), advanced Dukes' stage (C and D) (P<0.01), lymph node metastases (P<0.01) and high SPF (>18.3%) (P<0.01). The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA-aneuploidy, and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death. CONCLUSIONS: Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.

Adenocarcinoma↗
PubMed2002

Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype.

BACKGROUND: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. PATIENTS AND METHODS: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for primary colorectal carcinoma, were prospectively studied for K-ras mutations by PCR/single strand conformation polymorphism sequencing. RESULTS: Seventy-four of the 160 (46%) primary colorectal carcinomas presented mutations in K-ras: 54% in codon 12, 42% in codon 13 (particularly G-->A transition) and 4% in both. Codon 12 K-ras mutations were associated with mucinous histotype (P <0.01), while codon 13 K-ras mutations were associated with advanced Dukes' stage (P <0.05), lymph-node metastasis (P <0.05) and high S-phase fraction (P <0.05). Multivariate analysis showed that codon 13 K-ras mutations, but not any mutation, were independently related to risk of relapse or death. CONCLUSIONS: Our results suggest that codon 12 K-ras mutations may have a role in the mucinous differentiation pathway, while codon 13 mutations have biological relevance in terms of colorectal cancer clinical outcome.

Adenocarcinoma↗
PubMed2001

DNA aneuploidy and high proliferative activity but not K-ras-2 mutations as independent predictors of clinical outcome in operable gastric carcinoma: results of a 5-year Gruppo Oncologico dell'Italia Meridonale (GDIM) prospective study.

BACKGROUND: The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras-2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim of this study was to clarify the association between biomolecular variables, tumor characteristics, and clinical outcome in GC patients. METHODS: Resected specimens from a consecutive series of 69 patients with GC who underwent potentially curative surgery were studied prospectively. DNA ploidy and SPF were assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2 mutations were detected by polymerase chain reaction followed by single-strand conformation polymorphism. All the patients involved in this study were followed up for a mean of 95 months. RESULTS: DNA aneuploidy was present in 72% of the cases (50 of 69), whereas 10% of these (5 out of 50) showed multiclonality. Mutations of K-ras-2 were detected in 8% of the tumors (5 of 63). Both DNA ploidy and SPF were associated with TNM stage (American Joint Committee on Cancer [AJCC] staging system) and node status. Moreover, DNA aneuploidy was significantly related to high SPF. K-ras-2 mutations were not associated with clinicopathologic variables or flow cytometric indicators. At univariate analysis, advanced TNM stage, node involvement, diffuse histotype, depth of invasion, DNA aneuploidy, and high SPF proved to be significantly related to quicker tumor relapse and to shorter overall patient survival. With multivariate analysis, DNA aneuploidy, high SPF, and depth of invasion were related to risk of tumor relapse and patient death, whereas diffuse histotype was independently related to patient risk of tumor relapse. CONCLUSIONS: DNA ploidy and SPF, when associated with clinicopathologic staging, might be useful for the identification of GC patients who have different risks for death or relapse of disease.

Adult↗
PubMed2000

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma.

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC.

Adenocarcinoma↗
PubMed1999

Pseudocysts in acute nonalcoholic pancreatitis: incidence and natural history.

Epidemiological studies on pancreatic pseudocysts are retrospective analyses on alcoholic patients. The aims of this study were to investigate the incidence, natural history, and predictors of the appearance and disappearance of pancreatic fluid collections and pseudocysts after nonalcoholic acute pancreatitis. We carried out a prospective cohort study in a series of 926 patients with acute pancreatitis. Pancreatic fluid collections or pseudocysts were treated only after complications. We studied pancreatic fluid collections from 83 patients (8.9%): 48 of whom developed pseudocysts (5.1%). Both were less frequent after biliary pancreatitis (P < 0.0001). In the first 60 days of follow-up, patients with fluid collections or pseudocysts showed more complications than spontaneous disappearance; two of them died. After the 60th day, spontaneous disappearance was more frequent, and at one year the cumulative incidence of complications and spontaneous disappearance was 36% and 56%, respectively. A total of 33 patients with fluid collection needed interventional treatment (surgery or percutaneous or endoscopic drainage). Pseudocysts that were small (<5 cm) or developed in the tail had a higher incidence of spontaneous disappearance: 22/24 (91.7%) and 11/12 (91.7%), respectively. In conclusion, fluid collections and pseudocysts after non-alcoholic pancreatitis have a low incidence of complications and mortality with a high rate of spontaneous disappearance. We suggest treating them only after complications.

Adult↗
PubMed1998

Dextropropoxyphene versus morphine in opioid-naive cancer patients with pain.

The role of opioids for moderate pain (so-called "weak" opioids) in the second step of the World Health Organization's analgesic ladder has been investigated in a prospective randomized study. Sixteen patients were administered dextropropoxyphene (DPP) in a dosage ranging from 120 mg to 240 mg daily (group 1), and 16 patients were administered the lowest doses (20 mg daily) of commercially available controlled-release morphine (group 2). Equianalgesic doses of oral morphine, pain relief, and symptoms during the first 10 days of therapy and during the last 4 weeks before death were assessed. Three of 16 patients maintained DPP until death, whereas three patients in group 2 were switched to DPP due to the occurrence of intolerable side effects. Intensity and frequency of nausea and vomiting, drowsiness, and dry mouth were higher in group 2 than in group 1 during the initial treatment. These results stress the role of "weak" opioids during the induction of opioid therapy in opioid-naive cancer patients.

Aged↗
PubMed1997

Monitoring of opioid therapy in advanced cancer pain patients.

Until now, there have not been any parameters to monitor opioid therapy in cancer patients with pain. In this study, 325 consecutive advanced cancer patients were scheduled for a prospective longitudinal survey. After exclusions, 67 patients were surveyed. All included patients were advanced cancer patients with pain that required opioid therapy for more than 6 weeks before death. Opioid escalation, symptoms associated with opioid therapy, pain mechanism, and pain intensity were recorded. Indices were calculated to categorize the response to opioids. The opioid escalation index (OEI) was used to index the mean increase of the starting opioid dosage, expressed as a percentage or in mg. The length of the period of stable dose (MLD) and the effective analgesic score (EAS), that is, the analgesic consumption/pain relief ratio calculated at fixed intervals, were also used. Patients with a mean visual analogue scale score (VAS) of less than 4 and regular OEI and EAS were considered responsive; patients with a mean VAS less than 4 but with an OEI more than 5 or increases of more than 100% of EAS when compared to that calculated the week before were considered mildly responsive; and patients with a mean VAS more than 4 were considered unresponsive. Advanced age, female gender, and previous chemotherapy were all factors reducing OEI. Head and neck cancer was associated with a higher OEI. Regarding the influence of the opioid-related symptoms, an increased OEI was associated with the presence of confusion. Moreover the presence of confusion was associated with neuropathic pain. Neuropathic pain taken alone, however, did not influence this score. Gender-specific cancer, such as breast cancer, influenced the gender differences reported for MLD (significantly longer than that reported for males and other primary tumor). Good responsiveness was observed in 28 patients, partial responsiveness in 33 patients, unresponsiveness in six patients. Psychological factors were associated with poor pain relief, probably reducing the patient's compliance. The tools used in this study may be useful in monitoring the effects of opioid therapy in cancer pain patients. Simple numbers are easy to compare and make it possible to profile opioid responsiveness and differences among patients.

Aged↗
PubMed1997

Opioid-sparing effect of diclofenac in cancer pain.

This study investigated the opioid-sparing effect of diclofenac using patient-controlled analgesia with oral methadone. Fifteen patients with advanced cancer participated. After achieving adequate analgesia with regular dosing of oral methadone (T1), patient-controlled analgesia with methadone was administered for 3 days (T2). Intramuscular diclofenac 75 mg twice daily was then added to this regimen for 3 days (T3). Compared to T2 values, methadone dose was significantly reduced at T2 and T2, and pain report (recorded on a visual analogue scale) was significantly reduced at T3. A reduction in methadone plasma concentration was also observed at T2 and T3, although it did not attain statistical significance. Significant decreases in the intensity of several symptoms other than pain were also found at T2 and T3. Diclofenac appears to have a relevant opioid-sparing effect when using patient-controlled analgesia with oral methadone.

Aged↗
PubMed1996

Ascites, pleural, and pericardial effusions in acute pancreatitis. A prospective study of incidence, natural history, and prognostic role.

Ascites and pleural and pericardial effusions can be observed during acute pancreatitis. The aims of this study were to evaluate their incidence, natural history, and prognostic role in patients with acute pancreatitis. One hundred patients consecutively admitted with a diagnosis of acute pancreatitis were prospectively submitted to abdominal, pleural, and cardiac ultrasonography at admission and during follow-up. Ascites was found in 18 patients, pleural effusion in 20, and pericardial effusion in 17. Twenty-four patients of this series had severe pancreatitis; three of them died. All effusions disappeared spontaneously in patients who survived pancreatitis up to two months after dismissal. At multivariate analysis ascites and pleural effusion were demonstrated to be accurate independent predictors of severity. The respective odds ratios were 5.9 [95% confidence interval (CI), 1.5-23.0%) and 8.6 (95% CI, 2.3-32.5%). Furthermore the presence of pleural effusion, ascites, and pericardial effusion were associated with an increased incidence of pseudocyst during follow-up. Ascites and pleural and pericardial effusions are frequent during acute pancreatitis. Pleural effusion and ascites are accurate predictors of severity in these patients.

Acute Disease↗
PubMed1996

Pleomorphic adenoma and adenoid-cystic carcinoma of salivary glands: immunohistochemical assessment of proliferative activity in comparison with flow-cytometric study.

In this study, 32 pleomorphic adenomas (PAs) and seven adenoid cystic carcinomas (ACCs) were analysed for the evaluation of proliferating cell nuclear antigen (PCNA) indices and flow cytometric variables. Our aim was to assess any possible relationship between these parameters and the clinico-pathological variables and to clarify their histogenesis and reasons for their biological differences. The tumours were divided into three groups, mainly epithelial (E), myxoid (M) and chondroid (C); PCNA labelling index (LI) and weighted mean index (WI) and the WI/LI ratio were analysed in the predominant components; a single PCNA index, weighted by the percentage of each component, was also calculated. Only WI/LI was found to be significantly different in the three components, while PCNA single index did not show either significant differences by sex, age, site and size, or any correlation with the S phase fraction. A significant difference was found between PAs and ACCs by site (P < 0.01) and DNA ploidy (P < 0.05); furthermore, all PCNA indices (single index) were significantly lower in PAs than in ACCs.

Adenoma, Pleomorphic↗
PubMed1995

Flow cytometric DNA analysis and lysosomal cathepsins B and L in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters and prognostic significance.

BACKGROUND: The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment. METHODS: Flow cytometric DNA ploidy and S-phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC: Lysosomal cathepsin B and L activity levels were determined biochemically in matched paired sets of tumor tissue and normal mucosa samples. RESULTS: By univariate analysis, lymph node positivity, poor histologic differentiation, DNA aneuploidy, high SPF, and high tumor/mucosa ratio of cathepsin B activity were significantly related to risk of relapse, whereas only DNA aneuploidy and high SPF proved to be significantly related to risk of death. Multivariate analysis showed that high histologic grade and high SPF values (> 15.1%) were independent prognostic factors related to risk of relapse (relative risk [RR] = 3.54; 95% confidence limits [CL] = 1.05-12.0; and RR = 4.22; CL = 1.54-11.6, respectively), whereas only high SPF was related to risk of death (RR = 3.63; CL = 1.17-11.3). CONCLUSIONS: S-phase fraction is an independent predictor of relapse free and overall survival in patients with locally advanced LSCC. On the basis of these findings, SPF should be used in addition to other established prognostic factors to refine the prognostic assessment of these patients further. More studies are needed for a better evaluation of the prognostic significance of DNA ploidy and that of lysosomal cysteine proteinases in these tumors.

Adult↗
PubMed1995

Cancers of the female genital tract in Ragusa, Sicily.

A descriptive study of cancers of the female genital tract (cervix, endometrium, ovary, labia, vulva and vagina) in the province of Ragusa (Sicily) was carried out using incidence and mortality data of the Ragusa Cancer Registry, covering the years 1981-1987. Corpus uteri was the most frequent site of cancer, followed by cervix utery and ovary; the highest mortality rates were exhibited by ovary cancer, whose survival at five years was 18.1 percent. A comparison of incidence and mortality rates with those observed by Italian and European registries shows that while in Ragusa rates for cancers of all sites were lower, female genital tract cancers, particularly of the uterus, were more frequent in Ragusa than in other Italian and European areas. In contrast with what has been reported by cancer registries of most developed countries, incidence of cervix cancer in Ragusa has apparently not decreased between 1981 and 1987, while mortality has increased.

Age Distribution↗