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L Padovan

Publications and source records attributed to L Padovan.

8 recordsLinked to original sources
PubMed1999

Apoptosis-prone phenotype of human colon carcinoma cells with a high level amplification of the c-myc gene.

Although apoptosis can be induced by the enforced expression of exogenously introduced c-myc genes, it is not clear whether overexpression resulting from the amplification of the resident c-myc gene in tumor cells is sufficient to induce apoptosis. We have investigated the relationship between c-myc gene amplification and the propensity of tumor cells to undergo apoptosis, using the SW613-12A1 and SW613-B3 cell lines, which are representatives, respectively, of tumorigenic and non-tumorigenic clones isolated from the SW613-S human colon carcinoma cell line. Tumorigenic clones are characterized by a high level of amplification and expression of the c-myc gene, whereas cells of non-tumorigenic clones have a small number of copies and a lower level of expression of this gene. Analysis of c-myc mRNA level in cells cultured under low serum conditions indicated that the expression of the gene is tightly regulated by serum growth factors in non-tumorigenic B3 cells, whereas it is poorly regulated in tumorigenic 12A1 cells, the level of mRNAs remaining relatively high in serum-starved 12A1 cells. Under these conditions, 12A1 cells showed clear evidence of apoptosis, whereas B3 cells were completely refractory to the induction of apoptosis. Moreover, the study of cell lines derived from non-tumorigenic apoptosis-resistant clones following the introduction by transfection of exogenous c-myc gene copies showed that they have acquired an apoptosisprone phenotype. Altogether, our results strongly suggest that deregulated c-myc expression due to high-level amplification confers an apoptosis-prone phenotype to tumor cells. The possible consequences of these observations for cancer therapy are discussed.

Clone Cells↗
PubMed1998

Analysis and clinical implications of p53 gene mutations and human papillomavirus type 16 and 18 infection in primary adenocarcinoma of the uterine cervix.

Mutant p53 is frequently detected in endometrial and ovarian carcinoma, but it is rare in cervical cancers. Previous reports focused on cervical squamous cell carcinoma, whereas cervical adenocarcinoma was given little attention. We searched for p53 gene mutations in 74 primary cervical adenocarcinomas with known human papillomavirus (HPV) status. Our aim was to evaluate the prevalence of p53 mutations and to investigate their possible role as an independent prognostic factor. We found mutations in 13.5% with a high rate of G:C --> A:T transitions as observed in endometrial adenocarcinoma. As p53 mutations are more frequently detected in malignancies of high grade, high stage, and large size, this molecular event seems to play a role in the progression rather than in the induction of cervical adenocarcinoma. In our series, patients with HPV-negative tumors and patients with mutated neoplasms, irrespective of HPV infection, had a shorter survival. Yet the absence of HPV infection and presence of p53 mutations are not independent risk factors for tumor-related death after adjustment for clinicopathological confounders. The only significant and independent predictors of survival are age of patient, stage of disease, tumor grade, and presence of lymph node metastases.

Adenocarcinoma↗
PubMed1997

Microsatellite instability in intestinal- and diffuse-type gastric carcinoma.

To investigate the role of genetic instability in the development of intestinal- and diffuse-type gastric cancers, six microsatellite loci were analysed in 98 carcinomas of the two main histotypes, at both early and advanced stages of progression, and in five preneoplastic lesions. RER+ phenotype frequency proved to be significantly higher (P = 0.013) in intestinal (23 per cent) than in diffuse cancers (5 per cent) and slightly higher in advanced (19 per cent) than in early (12 per cent) tumours. When comparing early and advanced tumours of the same histotype, a similar frequency was found for diffuse tumours (4 per cent vs. 6 per cent), and an increase from 19 to 30 per cent for intestinal cancers. Instability at more than one locus was limited to intestinal tumours and replication errors were also detected in an intestinal dysplasia. On the whole, these data suggest that genetic instability has an important and early role in gastric carcinogenesis of the intestinal type and a less important role in gastric carcinogenesis of the diffuse type. Most tumours of this panel had previously been characterized for p53 gene mutations. p53 screening was extended to all samples, to investigate the possible association between gene mutations and microsatellite instability. Analysis showed a trend (P = 0.07, Fisher's exact test) towards a negative association between these two genetic lesions in tumours of the intestinal type.

Adenocarcinoma↗
PubMed1996

Intestinal and diffuse gastric cancers arise in a different background of Helicobacter pylori gastritis through different gene involvement.

Investigation of extensively sampled nontumor gastric mucosa from 205 early gastric cancers showed Helicobacter pylori colonization in 85% of cases, including 100% of diffuse and 78% (83% in 97 cases with Swiss rolls) of glandular or mixed cancers. Intestinal metaplasia, including its type III variant, was prominent in the mucosa associated with glandular and mixed (but not diffuse) early cancers. Both glandular (usually called "intestinal") and diffuse-type cancers showed admixtures of intestinal and gastric tumor cell phenotypes. Both p53 gene mutations and p53 protein immunostaining were essentially restricted to glandular or mixed cancers and associated dysplastic lesions. Their appearance in the advanced stage of diffuse cancer was partly due to a change of the histologic pattern from glandular to diffuse during progression of some tumors. Loss of laminin, beta I integrin, or zonula adherens junctions was a common finding in both early and advanced diffuse cancer. It is concluded that two main pathways operate in gastric carcinogenesis, both starting from H. pylori gastritis and both leading to phenotypically variable, often mixed gastric/intestinal tumor growth. However, only one of the two pathways involves intestinal metaplasia, its type III variant, p53 gene alteration, and dysplasia to end in glandular cancer. In the other pathway, diffuse cancer apparently arises directly from hyperplastic, sometimes atypical necks of mostly nonmetaplastic gastric glands, through primary involvement of genes affecting cell-cell and cell-matrix junctional proteins.

Age Factors↗
PubMed1985

[Blood coagulation in 222 cases of solid malignant neoplasms].

We have examined 222 patients with nonterminal solid malignant tumors in order to study the possible variations on the hemocoagulation system due to neoplasia. Only patients whose hemocoagulation system could be proven normal by test made before the malignant neoplasia appeared were taken into consideration. Our study was based on the following tests: platelet count, platelet adhesiveness and aggregation, prothrombin time, thrombin time, thrombotest, antithrombin 3, thrombin-coagulase, activity partial thromboplastin time, fibrinogen, reptilase time. Our study showed there was no relevant difference between the results tests of healthy people taken as points or reference and those of our patients. We did find however a slight but diffuse alteration of all, or almost all, the components of the hemostatic and coagulation system. These variations however were not significant enough to enable us to prove any connection between the neoplasia and the whole hemocoagulation system.

Adult↗
PubMed1985

[Quantitative and functional assay of AT III in neoplastic pathology].

Our study compares the results obtained through the assay of AT III following two methods, the functional and the immunological one, carried out on plasma of 222 patients affected with solid malignant neoplasia. The purpose of our research was to examine the behaviour of AT III, a protein having a peculiar function in the complex coagulation mechanism. At least among healthy people, this function was and is correlated to its blood concentration. All examined subjects suffered from solid malignant neoplasia either of the respiratory tract or gastro-intestinal tract or sexual organs or urinary tract. From our research patients with liver neoplasia diagnosis have been excluded since the cancer seat might have significant implications on the genesis of coagulation factors and therefore on AT III itself. The age of patients as well as controls - formed by 100 clinically healthy donors-ranged between 30 and 70. At the very beginning patients were divided into groups according to the basic pathology (cancer seat) but then, since no great differences were noted between the groups, all patients were examined irrespective of the type and seat of neoplasia. The followed methods are: a functional method which tends to measure the total AT III capacity assay acting in enzyme excess. S 2238 (Kabi) being the chromogene substratum used; an immunological method which tends to measure the molecule blood concentration taking advantage of its antigenic properties. While on one hand the obtained results have shown a good correlation between the two methods in controls i.c. healthy subjects, on the other hand a significant difference has been noted between the AT III activity and its blood concentration in non healthy subjects as if to prove the interference of neoplasia in the blood coagulation process. In the patients affected with neoplasia the functional as well as the quantitative aspect - which can be considered synonyms in healthy subjects being the one indicative of the other - show that the delicate balance on which the coagulation mechanism is based has been upset.

Adult↗