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M Fedele

Publications and source records attributed to M Fedele.

At least 37 records · Page 2Linked to original sources
PubMed1997

Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NFkappaB p65 protein expression.

We have investigated the role of the NFkappaB complex in the process of thyroid carcinogenesis by analysing thyroid carcinoma cell lines. A significant increase in p65 NFkappaB mRNA and protein expression, compared to normal thyroid cultures or tissue, was found in all of the cancer cell lines. Conversely, only a modest increase in the p50 NFkappaB mRNA and protein was found in most, but not all carcinoma cell lines. The block of p65 protein synthesis with specific antisense oligonucleotides greatly reduced the ability of two undifferentiated carcinoma cell lines to form colonies in agar and reduced their growth rate. On the other hand, no effect was observed in the same cell lines when treated with p50 specific antisense oligonucleotides. These inhibitory effects seem to be mediated by the suppression of c-myc gene expression, since treatment with antisense oligonucleotides for p65 gene interfered negatively with c-myc gene expression. Our results indicate that activation of the NFkappaB complex by overexpression of p65 plays a critical role in the process of thyroid cell transformation.

Down-Regulation↗
PubMed1997

Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product.

The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation.

Animals↗
PubMed1996

High level expression of the HMGI (Y) gene during embryonic development.

The HMGI protein family includes three proteins, named HMG-I, HMG-Y and HMGI-C. The first two proteins are coded for by the same gene, HMGI (Y), through an alternative splicing mechanism. Their expression is elevated in neoplastic tissues and cells and this overexpression has a causal role in the process of cellular neoplastic transformation. We demonstrate that the HMGI (Y) gene is expressed at very low levels in normal adult tissues, whereas in embryonic tissues it is expressed at high levels comparable to those detected in neoplastic tissues. Specifically, a very high expression of the HMGI (Y) gene was detected in all embryonic tissues at 8.5 dpc. Then in the following days, even though the gene is expressed essentially in all tissues, an abundant gene expression was restricted to some tissues. These results indicate an important role of the HMGI (Y) gene in development.

Adult↗
PubMed1996

Status and expression of the p16INK4 gene in human thyroid tumors and thyroid-tumor cell lines.

The p16INK4 tumor-suppressor gene (also known as CDKN2, CDK41 and MTS1) encodes a negative regulator of the cell cycle. This gene, located in 9p21, is mutated or homozygously deleted in a high percentage of tumor cell lines and specific types of primary tumors. We have examined the status of the p16INK4 gene in 31 thyroid tumors and 7 thyroid cell lines. No DNA abnormalities were found in primary tumors. Conversely, p16INK4 gene structural alterations, deletions and point mutations were found in 4 thyroid cell lines. The expression of the 2 different p16INK4 mRNAs, the p16alpha and p16beta transcripts, was determined by RNA-PCR experiments. All the primary thyroid tumors expressed the beta transcript, while the p16alpha was barely detectable. The thyroid cell lines always expressed the p16beta transcript, while the alpha transcript was absent or, whenever present, coded for a mutated form of the p16INK4 gene product. Taken together, our results suggest that loss of p16INK4 function is not directly involved in the process of thyroid-tumor development, but it probably gives cells in tissue culture a selective growth advantage.

Amino Acid Sequence↗
PubMed1996

Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins.

A correlation has previously been demonstrated between the presence of the three HMGI proteins (HMGI, HMGY, and HMGI-C) and the expression of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells; this being subsequently extended to experimental thyroid, lung, prostate, mammary, and skin carcinomas. Recently, we have demonstrated that expression of HMGI and HMGY proteins, coded for by the HMGI(Y) gene, is associated with the malignant phenotype of human thyroid neoplasias. Here, we show that HMGI(Y) gene expression is present both at the RNA and protein level in human colorectal carcinoma cell lines and tissues examined in this study. Conversely, no HMGI(Y) proteins were detected in normal intestinal mucosa. Therefore, these results suggest an involvement of HMGI and HMGY proteins overexpression in colorectal tumorigenesis.

Amino Acid Sequence↗
PubMed1996

Calcification of the transverse ligament of the atlas in chondrocalcinosis: computed tomography study.

OBJECTIVE: To seek an association between articular chondrocalcinosis (AC) and calcification of the transverse ligament of the atlas (TLA), and to evaluate the frequency and the main computed tomography appearances of such calcification. METHODS: Axial computed tomography slices of the cervico-occipital hinge were performed routinely in 21 patients with AC (three men, 18 women; mean age 79 years, range 67-87) and compared with those from a control group of 21 age and gender matched patients without AC. RESULTS: Calcification of the TLA was present in 14 of the 21 patients (66%) in the AC group and in none of the 21 patients (0%) in the control group (chi 2 test: p < 0.001). Calcification was localised behind the odontoid process, inserted upon the osseous tubercles of the lateral masses of C1, and had a curvilinear profile; it varied in height (1.5 to 9 mm) and appearance (thin = < 1 mm; thick = > 1 mm) and formed either a single or a double band. CONCLUSION: This study has demonstrated a relationship between AC and calcification of the TLA. Although such calcification often remains asymptomatic (nine of 14 patients in our study), it may be associated with attacks of acute neck pain with segmentary stiffness, fever, and an increased erythrocyte sedimentation rate, sometimes revealing AC.

Aged↗
PubMed1995

A mutated p53 gene alters thyroid cell differentiation.

p53 is the gene most frequently found mutated in human neoplasias. In the majority of tumors, p53 mutations contribute to the progression towards stages of increasing malignancy with the appearance of an undifferentiated phenotype. Also in thyroid cancerogenesis, p53 mutations correlate with the loss of the differentiated phenotype. The results presented here, suggest a direct involvement of p53 in the molecular mechanisms regulating cellular differentiation in thyroid since a mutated p53 gene markedly affects the growth potential and differentiated functions of the rat thyroid cell line PC Cl 3. Blockage in the expression of the PAX-8 transcription factor seems to be a key event in the loss of thyroid differentiated functions induced by the mutated p53 gene. Thyroid cells carrying a mutated p53 gene did not form colonies in soft agar or tumors in athymic mice, suggesting that a mutation of the p53 gene is not sufficient for the induction of the malignant phenotype and probably a cooperation with other oncogenes is necessary to accomplish full malignancy. No effect on either growth or differentiation of thyroid cells was exerted either by overexpression of the wild-type p53 gene, or by the vector alone.

Amino Acid Sequence↗
PubMed1995

Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines.

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies. Placenta growth factor (PlGF) is a recently identified growth factor for endothelial cells (EC); PlGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium. To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PlGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors. We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines. Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas. Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PlGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors. Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PlGF, contributes to thyroid tumor development.

Blotting, Western↗
PubMed1994

Lesch-Nyhan syndrome. A case report.

Lesch-Nyhan syndrome is a rare anomaly consisting of a deficiency in the production of hypoxanthine phosphoribosyltransferase that leads to the overproduction of purine and the accumulation of uric acid. Major manifestations include mental retardation and self-destructive behavior resulting in self-mutilation through biting and scratching. Because no medical treatment exists to alleviate the symptoms of self-mutilation, direct dental intervention is the only way these behaviors can be affected. A unique case of this type involving two male identical twins is reported.

Child↗
PubMed1991

[The Gemeprost test in the screening of endometrial pathology].

A randomized clinical trial has been performed to evaluate the efficacy of intravaginal 1 mg Gemeprost for pre-operative cervical dilatation prior to vacuum aspiration and curettage for endometrial biopsy. Eighty-nine patients were evaluated, 51 treated with Gemeprost and 38 with placebo: in the first group biopsy was possible in 94% of cases vs 86% in the second group. Pain was significantly reduced with Gemeprost improving the success rate and the patient compliance.

Alprostadil↗
PubMed1985

Primary choriocarcinoma of the fallopian tube: report of a case.

A case of the relatively rare condition of a choriocarcinoma in the fallopian tube is presented. The patient apparently recovered completely and quantitative beta hCG assay demonstrated negative results after TAHBSO and adjuvant chemotherapy. This brings the total cases reported to 77.

Adult↗