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A Amorosi

Publications and source records attributed to A Amorosi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Estimation of prostate cancer volume by endorectal coil magnetic resonance imaging vs. pathologic volume.

OBJECTIVE: Since tumor volume is recognized as an important predictor of clinical stage and disease outcome of prostate cancer, accurate preoperative estimation of tumor volume can play an important role in planning the appropriate treatment and establishing a patient's prognosis. We performed this study to evaluate the accuracy of the endorectal coil magnetic resonance (MR) technique for reliable prediction of tumor volume in patients with prostatic cancer. MATERIAL AND METHODS: Endorectal coil MR imaging was performed in 57 consecutive men who were suspected to have prostate cancer. Subsequent ultrasound-guided transrectal biopsy revealed prostate cancer in 44 cases. The pathological volume of the surgical specimens of 25 selected patients who underwent radical prostatectomy was retrospectively compared to the volume estimated by endorectal coil MR studies, and the Pearson correlation coefficient was calculated. RESULTS: In 15 patients the estimated size of the tumor was within 15% of the true tumor volume; in the remaining 10 cases MR imaging tended to underestimate large tumors and overestimate small ones. A significant correlation between the volumes as determined with MR imaging and measurements of surgical specimens was observed (r 0.94; slope 0.82). To our knowledge, this is the best correlation found between pathological volume and tumor volume as evaluated by any other imaging modality. CONCLUSIONS: Endorectal coil MR imaging is a powerful means of evaluating the prostate gland; however, further improvements in imaging and/or volume calculation are required to provide a more accurate preoperative assessment of prostate cancer volume.

Aged↗
PubMed1998

Mutations at coding mononucleotide repeats in gastric cancer with the microsatellite mutator phenotype.

We analysed 50 gastric carcinomas (GCs) to verify whether mutations at coding repeats were associated with microsatellite instability (MSI). The tumors included: ten cases with no MSI, 14 cases with MSI = 1 locus, 13 cases with MSI = two loci and 13 cases with MSI > or = 3 loci. We investigated coding repeats within the TGF-beta RII, IGFIIR, BAX, hMSH6, hMSH3 and BRCA2 genes. The TGF-beta RII, IGFIIR, BAX, hMSH6 and hMSH3 repeats were altered in 11 (22%), five (10%), four (8%), 16 (32%) and five (10%) cases respectively. Mutations occurred only in MSI-positive (MSI+) tumors and correlated with increasing MSI levels. No alterations of the BRCA2 repeat were found. Mutations in genes other than hMSH6 were strongly associated to hMSH6 mutations, suggesting a key role of this gene. The non-coding BAT-26 and E-Cadherin 3' UTR poly(A)8/(T)15 repeats were analysed in 44 of the 50 cases. Novel tumor-associated alleles were observed only in MSI-positive GCs and were in most cases associated with mutations at coding repeats. Further investigations with BAT-40 confirmed that four cases manifested mononucleotide repeat alterations restricted to hMSH6 and one case to TGF-beta RII. A subset of tumors with MSI at two or more dinucleotide loci resulted negative for mutations at coding and non-coding mononucleotide repeats.

Aged↗
PubMed1998

Implications of p53 mutation spectrum for cancer etiology in gastric cancers of various histologic types from a high-risk area of central Italy.

Examination of p53 mutation spectra may provide clues to molecular mechanisms involved in different histologic types of gastric cancer. A total of 105 gastric cancer cases classified according to the Laurén's system were selected from a high-risk area around Florence, Italy. Exons 5-8 of the p53 gene were examined for mutations by the polymerase chain reaction-single strand conformation polymorphism technique and DNA sequencing, using DNA from formalin-fixed paraffin-embedded tissues. Mutation frequency was similar in intestinal-type (12/28) and unclassified tumors (9/18), but was significantly lower in diffuse cancers (12/57, P < 0.05). A similar frequency of p53 mutations was observed among tumor stages in both intestinal-type and unclassified cancers, but in diffuse tumors mutations tended to be associated with invasion beyond the muscularis propria. When base changes were considered, G:C-->A:T transitions at CpG sites were the most common mutations for all the three tumor types with 6 of 11 (55%) in intestinal type, 8 of 12 (67%) in diffuse type, and 5 of 8 (63 %) in unclassified tumors. Frequent p53 mutations in both intestinal-type and unclassified tumors support the hypothesis that unclassified tumors represent variants of the intestinal type and suggest that unclassified tumors, like the intestinal type, may also associate with environmental exposures. The predominance of G:C-->A:T transitions at CpG sites, which are associated with methyltransferase-induced DNA methylation at carbon 5 of cytosine, in all three tumor types suggests that the status of DNA methylation may be the major determinant for p53 mutations and may be also equally important in gastric carcinogenesis regardless of histology.

Adult↗
PubMed1998

Substance P and vasoactive intestinal polypeptide but not calcitonin gene-related peptide concentrations are reduced in patients with moderate and severe ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation. METHODS: A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.

Adult↗
PubMed1997

Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany.

We studied the presence of microsatellite instability (MSI) in a series of 108 gastric cancers (GCs) previously identified in an epidemiological study carried out in a high-risk area around Florence. To investigate associations between MSI and GC family history, 34 cases (31.5%) who had a GC-affected first-degree relative were included in the series. A family history positive for colorectal cancer was reported quite rarely (5.6%). The analysis of 6 microsatellite loci in DNA from paired normal tissue and tumor samples microdissected from paraffin-embedded specimens revealed varying degrees of instability: 56 cases (51.8%) did not show instability at any of the 6 loci; 19 (17.6%) showed instability at 1 locus; 16 (14.8%) showed instability at 2 loci; 11 (10.2%) showed instability at 3 loci; 4 (3.7%) showed instability at 4 loci; and 2 (1.9%) showed instability at 5 loci. The replication error-positive (RER+) phenotype, defined as the presence of MSI at 2 or more loci, had a frequency of 30.6% (33 of 108) and tended to be positively associated with female sex, intestinal histological type, advanced tumor stage, vascular invasion, positive GC family history, and blood group of A type. No correlation emerged between age at diagnosis and RER+ phenotype, whereas a significant association with the RER+ phenotype was shown by the antral location. A multivariate analysis adjusting for a selected group of potential confounding factors confirmed the strong association of the RER+ phenotype with the antral location (P = 0.001) and with a positive GC family history (P < 0.05). Survival analyses at 5 and 8 years showed no difference between RER+ and RER- patients, even when corrected for stage distribution. By the microdissection technique, we also used microsatellite allele patterns to investigate intratumoral heterogeneity and genetic relationships between tumors and adjacent dysplasia and/or intestinal metaplasia. Areas of metaplasia and dysplasia demonstrated MSI only in cases with MSI-positive tumors. In MSI-positive tumors, there was consistent evidence of intratumoral microsatellite allele heterogeneity, indicating the presence of genetically divergent tumor cell clones within the same neoplasm.

Age Factors↗
PubMed1997

Prediction of pathological tumor volume in clinically localized prostate cancer: value of endorectal coil magnetic resonance imaging.

The purpose of this study was to determine whether endorectal coil magnetic resonance imaging (MRI) enables accurate assessment of pathologic tumor volume in patients with clinically localized prostate carcinoma. Twenty-four patients with biopsy-proved prostate carcinoma underwent MRI at 0.5 T before radical prostatectomy. Tumor volumes were determined independently on axial fast-spin-echo (SE) T2-weighted MR images and whole-mount pathology slides of the surgical specimens. At pathology, tumor volumes ranged from 0.17 to 9.42 cm3 (mean +/- SD, 3.11 +/- 2.99 cm3). A strong correlation (r = .944) was found between measurements of tumor volume based on MR images and pathological specimens. The error was less than 0.5 cm3 in 14 cases, in the range of 0.5-1 cm3 in 7 cases, and more than 1 cm3 in 3 cases. By using an MR tumor volume of 2 cm3 as cutoff value, extracapsular tumor spread could be predicted with a sensitivity of 81.2%, a specificity of 100%, and an accuracy of 87.5%. Tumor volume determinations based on MR images seem to be accurate enough to be helpful in clinical decision-making.

Humans↗
PubMed1997

Epidemiology of carcinoid tumours in central Italy.

Between 1985 and 1991, 83 carcinoid tumours were diagnosed in the province of Florence where the Tuscany Tumour Registry is active. There were 44 males and 39 females. The age-adjusted incidence was 0.65 cases/100,000 population/year. The most common location was the lung (30.1%), followed by colorectum (25.2%) and small intestine (22.8%). The 5-year observed and relative survival rates were 70.8% and 78.9% respectively. The relative risk of developing multiple primary cancers was 0.79 (CI 95% 0.28-8.33).

Carcinoid Tumor↗
PubMed1997

Expression of epidermal growth factor, transforming growth factor-alpha and their receptor in the human oesophagus.

Increasing evidence indicates that epidermal growth factor and transforming growth factor-alpha are involved in the maintenance of oesophageal mucosal integrity. However, their cellular origin and the exact localization of their receptor in the oesophagus are still unclear. Therefore, we examined the expression of the two growth factors and their shared receptor in the normal human oesophagus at both mRNA and protein level, by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction. In addition to being expressed in the proliferative compartment of the oesophageal epithelium, the receptor was found in a variety of cells, including smooth muscle cells, submucosal gland cells and the epithelium lining their ducts. Immunohistochemically, the pattern of distribution of epidermal growth factor paralleled that of its receptor. In situ hybridization demonstrated epidermal growth factor mRNA expression in the oesophageal epithelium and submucosal glands. Additionally, amplified transcripts of predicted size were detected by reverse transcription-polymerase chain reaction, thus confirming that authentic transcripts of the growth factor exist in the normal human oesophagus. Transforming growth factor-alpha mRNA and protein expression, while similar to that of epidermal growth factor, predominated in the more differentiated cell layers of the stratified squamous epithelium. These results demonstrate that the normal oesophagus can synthesize both growth factors. Moreover, the peculiar distribution of these peptides and the concomitant expression of their receptor in multiple cell types suggest that the two growth factors may exert diverse physiological functions in the oesophagus and participate in defence and reparative events following mucosal injury.

Adult↗
PubMed1997

Retrospective evaluation of c-erbB-2 oncogene amplification using competitive PCR in collecting duct carcinoma of the kidney.

PURPOSE: To evaluate retrospectively c-erbB-2 oncogene amplification in paraffin embedded specimens of collecting duct carcinoma of the kidney (CDC) with competitive polymerase chain reaction (PCR). MATERIALS AND METHODS: Eleven CDC specimens were evaluated with a novel PCR procedure for oncogene amplification measurement, which provides sensitive and accurate results even in presence of low-quality DNA, unsuitable for Southern blot techniques. RESULTS: c-erbB-2 oncogene amplification was present in 5 out of 11 cases (45%) with a number of copies ranging from 4 to 12. All patients presenting oncogene amplification decreased within one year, while 50% (3/6) of those without amplification are alive with a mean follow-up of 42 months. CONCLUSIONS: The high incidence of c-erbB-2 oncogene amplification in CDC further characterizes this tumor as a separate entity from renal cell carcinoma, and shows some genetic characteristics in common with transitional cell carcinoma.

Adult↗
PubMed1997

Cytofluorometric and cytogenetic evaluation of renal cell carcinoma: correlations with the clinical course.

The tumor specimens of 20 patients who underwent radical nephrectomy for nonfamiliar unifocal renal cell carcinoma were evaluated with conventional histopathology, cytogenetic analysis and evaluation of nuclear ploidy with cytofluorometry. The pathological stages were 1 T1N0M0, 10 T2N0M0, 1 T2N + M0, 6 T3N0M0 and 2 T3N + M0. Eleven tumors presented clonal chromosomal abnormalities, 2 had chromosomal instability and 7 normal karyotype. Rearrangement of chromosome 3 was documented in 2 cases only, in contrast with previous observations in the literature. Ten patients had a diploid or peridiploid DNA tumor content, 1 tetraploid, 4 triploid and 5 multiclonal. No correlation was found between nuclear ploidy and karyotype. Chromosomal abnormalities did not impact on survival, while a statistically significant correlation was found with diploid nuclear DNA content, since with a mean follow-up of 45.7 months, 9 out of 10 patients with diploid and peridiploid tumors are alive (p < 0.02), while 8 out of 10 nondiploid died of disease progression.

Adult↗
PubMed1997

Allelic loss in parathyroid tumors from individuals homozygous for multiple endocrine neoplasia type 1.

Homozygosity for the multiple endocrine neoplasia type 1 (MEN1) gene mutation was described in two of three affected siblings of a kindred in which both parents and the third daughter were heterozygotes. Surprisingly, in the two homozygotes, the disease history did not differ from the one of the heterozygotes. In the attempt to unravel genetic differences in parathyroid tumorigenesis between homozygotes and heterozygotes, restriction fragment length polymorphism analysis and microsatellite PCR analysis for loss of heterozygosity (LOH) at the MEN1 gene region on chromosome 11q13 was performed in parathyroid tissues removed at surgery from the mother, her heterozygous sister, and the three siblings. Allelic losses were evidenced in the larger glands of each patient, with a similar pattern of chromosome 11q12-13 losses. The somatic mutation consisted of a large lose of genetic material from chromosome 11. No gross differences exist in the 11q12-13 LOH observed between homozygous and heterozygous carriers. Interestingly, one of the parathyroid tumors from one heterozygote exhibited region of skipped LOH at the 11q12-13 region. The region in the depth of the critical interval retained heterozygosity, whereas those flanking it shared LOH. These findings indicate that inactivation of both copies of the MEN1 gene are not sufficient for parathyroid tumor development in MEN 1 patients and that tumor suppressor genes, other than the MEN1 gene on chromosome 11 or on other chromosomes, can be involved in the pathogenesis of parathyroid tumorigenesis in MEN 1 syndrome.

Chromosome Deletion↗
PubMed1997

HPE cells: a clonal endothelial cell line established from human parathyroid tissue (human parathyroid cell line).

We report the culture and cloning of human endothelial cells derived from parathyroid tissue surgically removed from a patient affected by Multiple Endocrine Neoplasia Type 1 syndrome. These cells, known as HPE, have been isolated and maintained in culture by serial passages for more than 15 months. The clonal cell line grows in a medium containing serum substitutes which favour endothelial cell growth. HPE cells replicate with a mean doubling time of 120 h, showing typical functional and morphological features of endothelial cells, such as uptake of acetylated low density lipoprotein and positive reaction for Factor VIII-Related Antigen. Basic fibroblast growth factor, vascular endothelial growth factor, insulin-like growth factor type I and ascorbic acid stimulate cell proliferation, whereas transforming growth factor beta and heparin act as inhibitory factors. Prostaglandin E2, secretin and epinephrine increased cAMP production, while human parathyroid hormone, histamine and glucagon were inert. Cells were found to express pro-collagen alpha 1 (type I) mRNA. In HPE cells Restriction Fragments Length Polymorphism and PCR analysis did not show allelic loss at chromosome 11q12-13, known to be a typical feature of MEN 1 parathyroid tumors. These cells are the first example of an established normal human clonal cell line with an endothelial phenotype.

Cell Division↗
PubMed1997

[Comparison of flow-cytometry and immunohistochemistry with proliferating monoclonal antibody. Cell nuclear antigen (PCNA) in the study of proliferative kinetics of renal carcinoma].

Tumor Proliferative Fraction (TPF) has been shown to correlate with prognosis in some malignancies. A reliable, accurate method for application in a clinical practice is still being sought. The aim of this study is to compare TPF as determined by Proliferating Cell Nuclear Antigen (PCNA) and Flow Cytometry (FC) in 36 consecutive patients affected by Renal Cell Carcinoma (RCC). Proliferating cells were identified in paraffined sections using a anti-PCNA monoclonal antibody (PC 10 Dako). Cell suspension for FC were prepared from fresh/frozen samples DNA index and S phase were evaluated using a computerized program (Multicycle, Phoenix). 16 samples (47.1%) were found to be aneuploid by FC (DI range 0.72-2.40). Aneuploid vs diploid tumors had significantly higher mean FC-S phase (p = 0.049) and PCNA LI (p = 0.034). Weak correlation (r-Spearman 0.416 p = 0.01) was found between PCNA LI and grading and near to significativity between PCNA LI and tumor size (r = 0.335 p = 0.0061). When patients are classified according to nuclear grading, is evident that all PCNA G4 are aneuploid and that 62.5% of PCNA G1 are diploid. A week correlation near to significativity is found between PCNA LI and S phase only in the aneuploid tumors. A more reliable measurement of TPF in RCC could be provided by combining the two methods. Further research on larger series is needed.

Adult↗
PubMed1997

Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study.

OBJECTIVES: To assess the efficacy of a combination of oral and topical 5-aminosalicylic acid (5-ASA) for the maintenance treatment of ulcerative colitis, we undertook a double-blind randomized clinical trial. METHODS: Patients aged 18 to 65 yr (with disease extent greater than proctitis only) were eligible for inclusion in the study if they met the following criteria: (a) history of two or more relapses in the last year; (b) achievement of remission in the last 3 months (with maintenance of remission for at least 1 month). Patients enrolled in the study were randomly assigned to one of the two following 1-yr treatments: (1) combined therapy with 5-ASA tablets 1.6 g/day and 5-ASA enemas 4 g/100 ml twice weekly; (2) oral therapy with 5-ASA tablets 1.6 g/day and placebo enemas/twice weekly. The main end point of the study was the maintenance of remission at 12 months. RESULTS: Upon completion of the study, relapse occurred in 13 of 33 patients in the combined treatment group versus 23 of 36 patients in the oral treatment group (39 vs 69%; p = 0.036). No significant side effects related to treatment were observed in either group. A simplified pharmacoeconomic analysis shows that this form of combined treatment can have a favorable cost-effectiveness ratio. CONCLUSIONS: Our results indicate that 5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. This form of combination treatment can be appropriate for patients at high risk of relapse.

Administration, Oral↗
PubMed1997

Diet, Helicobacter pylori, and p53 mutations in gastric cancer: a molecular epidemiology study in Italy.

A series of 105 gastric cancer (GC) cases with paraffin-embedded specimens interviewed in a previous population-based case-control study conducted in a high-risk area around Florence, Italy, was examined for the presence of p53 mutations. Overall, 33 of 105 cases had a mutation (p53+) identified by single-strand conformational polymorphism and confirmed by sequencing (Y-H. Shiao et al., submitted for publication). p53+ cases had a more traditional dietary pattern (i.e., corn meal mush, meat soup, and other homemade dishes) and reported less frequent consumption of raw vegetables (particularly lettuce and raw carrots). A positive association with a high nitrite intake and a negative association with raw vegetables and diffuse type histology persisted in a multivariate analysis. In addition, p53+ cases tended to be located in the upper portion of the stomach and to be associated with advanced age and blood group A. No relation was found between the presence of p53 mutations and histologically defined Helicobacter pylori infection, smoking history, family history of gastric cancer, education, and social class. Of the 33 p53+ cases, 19 had G:C-->A:T transitions at CpG sites. These tumors tended to occur in females and in association with H. pylori infection but not other risk factors. The remaining 14 cases with a p53 mutation had mainly transversions but also two deletions and two transitions at non-CpG sites. These tumors showed a strong positive association with a traditional dietary pattern and with the estimated intake of selected nutrients (nitrite, protein, and fat, particularly from animal sources). The findings of this case-case analysis suggest that p53 mutations at non-CpG sites are related to exposure to alkylating compounds from diet, whereas p53 mutations at CpG sites might be related to H. pylori infection.

Aged↗
PubMed1997

[Magnetic resonance with an endorectal coil and a fast spin echo sequence in the staging of prostatic carcinoma. The correlation with histopathological data].

INTRODUCTION: We investigated the accuracy of endorectal coil Magnetic Resonance Imaging (MRI) and Fast Spin Echo (FSE) technique in staging prostate cancer. MATERIAL AND METHODS: MRI was performed in 70 patients with biopsy proved prostatic cancer. A total of 33 patients subsequently underwent radical prostatectomy. T2-weighted FSE sequences (TR 3400-4100, TE 120, Echo train length 13) were acquired in all patients. Axial, sagittal and coronal 4-5 mm images were obtained with 13-14 cm field of view and 256 x 256 matrix. Additional T1-weighted spin echo images were acquired in 9 patients. Lesion staging on MR images was performed according to the American Urological System. MR data were compared with the pathologic findings of whole-mount sections of the surgical specimens. RESULTS: Overall accuracy for endorectal coil MR imaging was 60%; ten cases were underestimated and 3 cases were overestimated. The sensitivity and the specificity of endorectal coil MRI in diagnosing capsular penetration were 77% and 81%, respectively. Seminal vesicle invasion was detected with 87% sensitivity and 96% specificity. CONCLUSIONS: Endorectal coil MRI provides a more accurate preoperative local staging.

Aged↗
PubMed1996

Clonal analysis by chromosome 11 microsatellite-PCR of microdissected parathyroid tumors from MEN 1 patients.

Loss of heterozygosity (LOH) at chromosome 11q13 loci has been described in the majority of larger parathyroid tumors from patients affected by Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome. Since classical histology of the whole parathyroid gland does not permit a clear morpho-genetic correlation, the clonal composition of abnormal parathyroid tissue was analyzed in DNA obtained from single nodules and non-nodular areas within MEN 1 parathyroid lesions. Microdissected sections were analyzed by chromosome 11q13 microsatellite-PCR for LOH and by patterns of X-inactivation. We detected LOH for chromosome 11q13 loci in at least one microdissected area for each familial MEN 1 patient, but not in the single sporadic case. X-inactivation pattern of two "clonal" tumors exhibited a polyclonal cell composition of these microdissected samples, indicating the existence of a genetic heterogeneity in MEN 1 parathyroid microareas exhibiting a "clonal" pattern for allelic losses.

Adolescent↗