Biomedical subjects

Isabella Tognarini

Publications and source records attributed to Isabella Tognarini.

3 recordsLinked to original sources

PubMed2006

Multiple endocrine neoplasia type 2.

Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare hereditary complex disorder characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma (PHEO) and other hyperplasia and/or neoplasia of different endocrine tissues within a single patient. MEN2 has been reported in approximately 500 to 1000 families worldwide and the prevalence has been estimated at approximately 1:30,000. Two different forms, sporadic and familial, have been described for MEN2. Sporadic form is represented by a case with two of the principal MEN2-related endocrine tumors. The familial form, which is more frequent and with an autosomal pattern of inheritance, consists of a MEN2 case with at least one first degree relative showing one of the characteristic endocrine tumors. Familial medullary thyroid carcinoma (FMTC) is a subtype of MEN2 in which the affected individuals develop only medullary thyroid carcinoma, without other clinical manifestations of MEN2. Predisposition to MEN2 is caused by germline activating mutations of the c-RET proto-oncogene on chromosome 10q11.2. The RET gene encodes a single-pass transmembrane tyrosine kinase that is the receptor for glial-derived neurotrophic growth factors. The combination of clinical and genetic investigations, together with the improved understanding of the molecular and clinical genetics of the syndrome, helps the diagnosis and treatment of patients. Currently, DNA testing makes possible the early detection of asymptomatic gene carriers, allowing to identify and treat the neoplastic lesions at an earlier stage. In particular, the identification of a strong genotype-phenotype correlation in MEN2 syndrome may enable a more individualized treatment for the patients, improving their quality of life. At present, surgical treatment offers the only chance of cure and therefore, early clinical and genetic detection and prophylactic surgery in subjects at risk are the main therapeutic goal.

Carcinoma, Medullary↗

PubMed2005

ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components.

Several strands of evidence indicate that oestrogens exert a protective role against the development of colon cancer through indirect and direct effects on colonic epithelium. Oestrogen receptor beta (ERbeta), the predominant ER subtype in human colon, is significantly decreased in colonic tumours compared with normal mucosa suggesting a potential role in the regulation of colon tumour growth. To investigate this hypothesis we engineered human colon cancer ERalpha-negative HCT8 cells in order to obtain ERbeta protein over-expression. Stably transfected cells were cloned and ERbeta expression and functionality were monitored by RT-PCR, Western blotting and transactivation in an assay using oestrogen-responsive reporter constructs. Over-expression of ERbeta inhibited cell proliferation and increased cell adhesion in a ligand-independent manner. Its constitutive activation is possibly due to cross-talk with intracellular signalling pathways, as epidermal growth factor and IGF-I were able to induce ERbeta transactivation. A possible mechanism by which ERbeta over-expression inhibits proliferation in HCT8 cells is by modulation of some key regulators of the cell cycle; there is a decrease in cyclin E and an increase in the cdk inhibitor p21CIP1. In fact, flow cytometry analysis provided evidence for blocking of the G1-S phase progression induced by ERbeta over-expression. The magnitude of this effect was affected by the level of ERbeta expression. These results provide the first direct evidence that ERbeta plays an important role in colon cancer as a regulator of cell proliferation through the control of key cell cycle modulators and arrest in G1-S phase transition. These findings are compatible with the hypothesis that the loss of ERbeta expression could be one of the events involved in the development or progression of colon cancer.

Apoptosis↗

PubMedDate not supplied

Growth response of colon cancer cell lines to selective estrogen receptor modulators.

BACKGROUND: The purpose of this study was to compare the "in vitro" effects of the selective estrogen receptor modulators, tamoxifen and raloxifene, on two human colon cancer cell lines. MATERIALS AND METHODS: Serial concentrations (0.1, 1, 5 and 10 microM) of tamoxifen and raloxifene were used and evaluated for cell proliferation, viability and apoptosis in HCT8 and HCT116 cells. RESULTS: Micromolar doses of raloxifene significantly reduced HCT116 and HCT8 cell proliferation. Tamoxifen (5 microM) strongly reduced HCT8 cell growth with minor effects on HCT116 cells. Raloxifene (10 microM) was lethal on both cell lines, while 10 microM tamoxifen caused lethality only in HCT8 cells. Five microM raloxifene reduced cell viability in HCT8 and HCT116 cells, while 5 microM tamoxifen halved only HCT8 cell viability. Raloxifene and tamoxifen did not induce apoptosis in the two cell lines. CONCLUSION: Tamoxifen, and even more raloxifene, were effective in reducing HCT8 and HCT116 cell proliferation and viability, suggesting their potential application in the prevention and therapy of colorectal cancer.

Apoptosis↗