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Biomedical subjects

M Romani

Publications and source records attributed to M Romani.

At least 19 recordsLinked to original sources
PubMed2003

Biological and clinical role of p73 in neuroblastoma.

The p73 gene is a p53 homologue localized at 1p36.3, a chromosomal region frequently deleted in neuroblastoma. p73 was originally considered an oncosuppressor gene. However, it was soon realized that its mode of action did not resemble that of a classic anti-oncogene. The recent discovery of N-terminal truncated isoforms, with oncogenic properties, showed that p73 has a 'two in one' structure. Indeed, the full-length variants are strong inducers of apoptosis while the truncated isoforms inhibit the pro-apoptotic activity of p53 and of the full-length p73. This review summarizes some aspects of p73 biology with particular reference to its possible role in neuroblastoma.

Alternative Splicing↗
PubMed2002

Magnetic resonance imaging in breast cancer recurrence.

PURPOSE: To determine the sensitivity, specificity and accuracy of magnetic resonance imaging (MRI) in detecting breast cancer recurrence. MATERIALS AND METHODS: Forty women conservatively treated for breast cancer underwent MRI and confirmation on histology and cytology of suspected local recurrence. In these patients both clinical and mammographic/ultrasound features of local recurrence were nonspecific or suspicious. All patients were examined at least 1 year after completion of radiation treatment. Dynamic magnetic resonance imaging was performed with a 1.5 T unit using a dedicated bilateral breast coil. Qualitative and quantitative data were obtained. Statistical analysis was also performed with the Student T-test. RESULTS: Breast cancer recurrence was confirmed on histology in 22 patients. MRI identified all the 22 breast recurrent cancers. False-positive contrast enhancement was seen in only two patients. In four patients recurrence was classified as multifocal. In one patient the tumor was detected in the contralateral breast. MRI showed 95% accuracy, 100% sensitivity, 88.8% specificity with 5% false-positives and 100% negative predictive value. CONCLUSION: Dynamic MRI appears a valuable technique for differentiation of post-treatment changes from recurrent carcinoma and for guiding the histological confirmation. Its high negative predictive value may have an impact on follow-up of treated breast.

Adult↗
PubMed2002

Expression of DeltaNp73 is a molecular marker for adverse outcome in neuroblastoma patients.

The p73 gene is a p53 homologue which induces apoptosis and inhibits cell proliferation. Although p73 maps at 1p36.3 and is frequently deleted in neuroblastoma (NB), it does not act as a classic oncosuppressor gene. In developing sympathetic neurons of mice, p73 is predominantly expressed as a truncated anti-apoptotic isoform (DeltaNp73), which antagonizes both p53 and the full-length p73 protein (TAp73). This suggests that p73 may be part of a complex tumor-control mechanism. To determine the role of DeltaNp73 in NB we analyzed the pattern of expression of this gene in vivo and evaluated the prognostic significance of its expression. Our results indicate that DeltaNp73 expression is associated with reduced apoptosis in a NB tumor tissue. Expression of this variant in NB patients significantly correlates with age at diagnosis and VMA urinary excretion. Moreover it is strongly associated with reduced survival (HR=7.93; P<0.001) and progression-free survival (HR=5.3; P<0.001) and its role in predicting a poorer outcome is independent from age, primary tumor site, stage and MYCN amplification (OS: HR=5.24, P=0.012; PFS: HR=4.36, P=0.005). In conclusion our data seem to indicate that DeltaNp73 is a crucial gene in neuroblastoma pathogenesis.

Apoptosis↗
PubMed2001

[Esophageal cancer with esophagotracheal fistula. Treatment by esophageal prosthesis. Report of two cases].

Esophageal cancer has a bad prognosis because of late diagnosis. The rate of Survival is very low. Palliative treatment is frequently made. The aim of the treatment is to allow feeding, and treat some complications likes breathing troubles. We report two cases of esotracheal fistulae secondary to esophageal cancer. The esophageal fistula was successfully treated by esotracheal prosthesis.

Adult↗
PubMed2000

Methylation-independent silencing of the p73 gene in neuroblastoma.

p73 is a p53 homolog that, in vitro, inhibits cell growth and induce apoptosis. In some tumors p73 is monoallelically expressed and this raised the possibility that this gene is subjected to imprinting. Silencing of p73 in acute leukemia and in Burkitt's lymphoma occurs in association with the aberrant methylation of the first exon of the gene. We have analysed the methylation pattern of the p73 promoter and of upstream and downstream sequences in neuroblastoma. Our results demonstrate that p73 expression in this tumor is not regulated by methylation. We concluded that it is unlikely that p73 is imprinted in neuroblastoma and that the methylation-dependent silencing of this gene, thus far, is a characteristic of hematologic malignancies. Oncogene (2000) 19, 4553 - 4556.

Base Sequence↗
PubMed2000

Beyond prejudice as simple antipathy: hostile and benevolent sexism across cultures.

The authors argue that complementary hostile and benevolent components of sexism exist across cultures. Male dominance creates hostile sexism (HS), but men's dependence on women fosters benevolent sexism (BS)--subjectively positive attitudes that put women on a pedestal but reinforce their subordination. Research with 15,000 men and women in 19 nations showed that (a) HS and BS are coherent constructs that correlate positively across nations, but (b) HS predicts the ascription of negative and BS the ascription of positive traits to women, (c) relative to men, women are more likely to reject HS than BS, especially when overall levels of sexism in a culture are high, and (d) national averages on BS and HS predict gender inequality across nations. These results challenge prevailing notions of prejudice as an antipathy in that BS (an affectionate, patronizing ideology) reflects inequality and is a cross-culturally pervasive complement to HS.

Adult↗
PubMed1999

Stage-independent expression and genetic analysis of tp73 in neuroblastoma.

The tp73 gene, a tp53 homologue, has been sub-regionally mapped at 1p36.3, a chromosomal region frequently deleted in neuroblastoma. Due to its chromosomal localization and to the mono-allelic expression observed in some neuroblastoma cell lines, it was proposed that tp73 might be involved in the pathogenesis of neuroblastoma. Functional assays have demonstrated that tp73 can inhibit cell proliferation and induce apoptosis. The role of this gene in tumorigenesis, however, is still unclear. We analyzed tp73 expression in 95 sporadic neuroblastoma samples by RT-PCR and we detected the tp73 transcript in 46 cases (48.4%), without significant correlation with age, clinical stage or 3-year overall survival. A genetic polymorphism in the 2nd exon of tp73 was utilized to identify the transcribed allele in tumor-cell samples. Expression from only one of the tp73 alleles was found in 13 out of 16 heterozygous tumors, while in 3 samples both alleles were present. Genotype analysis of 73 patients and 150 controls showed a significant deviation (p = 0.0308) from the Hardy-Weinberg equilibrium for a tp73 allele only among neuroblastoma patients. The absence of correlation between tp73 expression and clinical stage, age and survival suggests that this gene does not play an essential function in the clinical course of the disease. However, the distribution of genomic tp73 alleles in patients indicates that a role of this gene in the development of neuroblastoma cannot be completely ruled out. Int. J. Cancer (Pred. Oncol.) 84:365-369, 1999.

Alleles↗
PubMed1999

[Critical review of 215 cases of non-palpable mammary lesions].

PURPOSE: The natural history of human breast cancer shows that lesion size correlates directly with nodal metastases and distant spread. Nodal metastases are found in only 6% of cases in the preclinical stage of the tumor and therefore imaging must detect a breast cancer before it becomes palpable. We reviewed 215 nonpalpable breast lesions studied in the last 10 years to assess observers performance and ultimately improve the interpretation of suspicious mammograms, evaluating "cost" in terms of the ratio between benign and malignant lesions (B/M). MATERIAL AND METHODS: From 1988 to October 1998, two hundred and fifteen women with nonpalpable breast lesions suspected at mammography were examined. The lesions were removed after stereotaxic or US location and a radiograph of the surgical specimen was always performed. Mammographic patterns were interpreted retrospectively by two blinded radiologist experienced in breast imaging and specialized in locating nonpalpable breast lesions. Mammographic patterns were classified as poorly/highly suspicious calcifications, regular/irregular masses, spiculated masses, masses with calcifications and parenchymal distortions. Radiographic findings were compared with surgical results and the data used to calculate the B/M, positive predictive value (PPV) for malignancy and the trend of operator's performance. RESULTS: Modern techniques permit to detect a very high number of in situ breast carcinomas. Nineteen of 22 lesions (86%) were detected by mammography as highly suspicious calcifications, 2/22 as spiculated masses and 1/22 as a mass with calcifications. No in situ carcinoma was detected as an irregular mass. All regular masses were proven to be benign at histology. B/M analysis showed a decreasing trend (from 1.94 in the first 3 years to .57 in 1994-96, to .83 in 1997-98) and an overall value of .90. The PPV for malignancy was 83.33% for spiculated masses, 65.5% for highly suspicious calcifications, 63.63% for irregular masses, 47.05% for masses with more or less dysmorphic calcifications, 32.65% for poorly suspicious calcifications, 8.33% for parenchymal distortions and 0% for regular masses. DISCUSSION AND CONCLUSIONS: All spiculated masses and highly suspicious calcifications and microcalcifications should be removed. Biopsy is recommended in parenchymal distortions, despite its low predictive value for malignancy, because these lesions are uncommon and the cost of biopsy is therefore acceptable. Needle aspiration or long-term monitoring can be reconsidered for irregular masses and poorly suspicious microcalcifications. Finally, relative to possible different interpretations of mammographic patterns by center and operator's experience, we suggest that the PPV for every single pattern be continually reassessed based on personal case records rather than on literature data. This holds true especially for microcalcifications.

Adult↗
PubMed1998

Refined chromosomal localization of the putative tumor suppressor gene TP73.

We report the refined chromosomal localization of the putative tumor suppressor gene TP73 (alias p73) within the genomic region between the anonymous loci D1Z2 and D1S47. The region measures less than 6 Mb and covers a genetic distance of 16 cM. The present mapping considerably restricts the previous cytogenetic localization of TP73.

Brain Neoplasms↗
PubMed1997

Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans.

This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours. In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated. Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater (P < .05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 micromol/micromol, respectively) compared with tauroursodeoxycholic acid (0.061 micromol/micromol for cholesterol and 0.275 micromol/micromol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 micromol/micromol) compared with taroursodeoxycholic acid (3.09 micromol/micromol) (P < .05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol. The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in non-micellar aggregates. Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.

Aged↗
PubMed1997

Search for neuroblastoma loci: characterization of tumor cell lines that could facilitate their positional cloning.

Specific chromosomal aberrations might indicate the position of genes responsible for a particular disease. Neuroblastoma is characterized by frequent deletions and/or rearrangements of the subtelomeric 1p region which, accordingly, is believed to host one or more oncosuppressor gene(s) directly or indirectly involved in the development of this and other tumors. Identification of these genes could be facilitated if cell lines with well characterized interstitial deletions or reciprocal translocations could be available for application of positional cloning strategies. In the present report we present additional and novel molecular data on three well established neuroblastoma cell lines (NLF, NMB and NGP). In one of these we have identified two sites that might be good candidates for hosting oncosuppressor genes; one of these is flanked by the D1S47 and ENO1 loci while the other is distal to the A12M2 locus.

Cloning, Molecular↗