Showing papers by "Matilde Todaro published in 2007"

Identification and expansion of human colon-cancer-initiating cells

Abstract: Colon carcinoma is the second most common cause of death from cancer. The isolation and characterization of tumorigenic colon cancer cells may help to devise novel diagnostic and therapeutic procedures. Although there is increasing evidence that a rare population of undifferentiated cells is responsible for tumour formation and maintenance, this has not been explored for colorectal cancer. Here, we show that tumorigenic cells in colon cancer are included in the high-density CD133+ population, which accounts for about 2.5% of the tumour cells. Subcutaneous injection of colon cancer CD133+ cells readily reproduced the original tumour in immunodeficient mice, whereas CD133- cells did not form tumours. Such tumours were serially transplanted for several generations, in each of which we observed progressively faster tumour growth without significant phenotypic alterations. Unlike CD133- cells, CD133+ colon cancer cells grew exponentially for more than one year in vitro as undifferentiated tumour spheres in serum-free medium, maintaining the ability to engraft and reproduce the same morphological and antigenic pattern of the original tumour. We conclude that colorectal cancer is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells, which should therefore be the target of future therapies.

The Antiapoptotic Protein BAG3 Is Expressed in Thyroid Carcinomas and Modulates Apoptosis Mediated by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

Abstract: Context: We previously showed that BAG3 protein, a member of the BAG (Bcl-2-associated athanogene) co-chaperone family, modulates apoptosis in human leukemias. The expression of BAG3 in other tumor types has not been extensively investigated so far. Objective: The objective of this study was to analyze BAG3 expression in thyroid neoplastic cells and investigate its influence in cell apoptotic response to TNF-related apoptosis-inducing ligand (TRAIL). Design, Setting, and Patients: We investigated BAG3 expression in human thyroid carcinoma cell lines, including NPA, and the effect of BAG3-specific small interfering RNA on TRAIL-induced apoptosis in NPA cells. Subsequently, we analyzed BAG3 expression in 30 benign lesions and 56 carcinomas from patients of the Naples Tumor Institute Fondazione Senatore Pascale. Main Outcome Measures: The main outcome measures were: analysis of BAG3 protein in NPA cells by Western blot and immunocytochemistry; analysis of apoptosis in TRAIL-stimulated NPA cells by flow cytom...

MUC1 oncoprotein promotes refractoriness to chemotherapy in thyroid cancer cells.

Abstract: Overexpression of MUC1 oncoprotein is frequently observed in cancer and contributes to confer resistance to genotoxic agents Papillary, follicular, and anaplastic thyroid carcinomas are the three forms of thyroid epithelial cancer Anaplastic tumors are less differentiated and extremely aggressive, characterized by a poor prognosis Little is known about the role of MUC1 in thyroid cancer We recently showed that autocrine production of interleukin (IL)-4 and IL-10 controls thyroid cancer cell survival, growth, and resistance to chemotherapy through activation of Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositide 3'-OH kinase (PI3K)/Akt pathways In the present study, we showed that MUC1 COOH-terminal subunit (MUC1-C) is overexpressed in all the histologic variants of thyroid cancer cells and localizes to mitochondria where it interferes with the release of mitochondrial proapoptotic proteins Moreover, IL-4 and IL-10 promote the increase of MUC1-C expression levels in normal thyroid cells, whereas blockage of both cytokines or neutralization of JAK/STAT and PI3K/Akt pathways through the exogenous expression of SOCS-1 and Akt(K179M) leads to a significant decrease of MUC1-C in primary thyroid cancer cells Interestingly, down-regulation of MUC1 expression by direct targeting with RNA interference sensitizes anaplastic thyroid cancer cells to chemotherapy-induced apoptosis in vitro Thus, MUC1 is a main component of the survival network acting in thyroid cancer and could be considered a key molecular target for sensitizing cancer cells to conventional or novel treatments

Antibody specific for human il-4 for the treatment of cancer

Abstract: The present invention relates to the use of an antibody or an antigen-binding fragment thereof with specific binding activity for human interleukin-4 for the prevention and/or treatment of cancer.

Differential cytokine expression in human cancer

Abstract: The invention concerns a method for diagnosing a cancer type, whereby the expression of anti-apoptotic cytokines is determined in the tumour cells. The differential diagnosis of the present invention is used to classify tumour disorders and to recommend the required treatment and to monitor the progress and response to the treatment.

Differential il-4 and/or il-10 cytokine expression in human cancer

Abstract: The invention concerns a method for diagnosing a cancer type, whereby the expression of anti-apoptotic cytokines is determined in the tumour cells. The differential diagnosis of the present invention is used to classify tumour disorders and to recommend the required treatment and to monitor the progress and response to the treatment.

Expression différentielle de la cytokine dans les cancers chez l'homme

Abstract: L'invention concerne un procede de diagnostic du type de cancer consistant a determiner l'expression de cytokines anti-apoptotiques dans les cellules cancereuses. Le diagnostic differentiel de la presente invention permet de classifier les troubles tumoraux, de recommander le traitement adequat et de suivre le progres dudit traitement et la reponse au traitement.