Tetrastatin, the NC1 Domain of the α4(IV) Collagen Chain: A Novel Potent Anti-Tumor Matrikine

BACKGROUND: NC1 domains from α1, α2, α3 and α6(IV) collagen chains were shown to exert anti-tumor or anti-angiogenic activities, whereas the NC1 domain of the α4(IV) chain did not show such activities so far. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate in the present paper that the NC1 α4(IV) domain exerts a potent anti-tumor activity both in vitro and in an experimental human melanoma model in vivo. The overexpression of NC1 α4(IV) in human UACC-903 melanoma cells strongly inhibited their in vitro proliferative (-38%) and invasive (-52%) properties. MT1-MMP activation was largely decreased and its cellular distribution was modified, resulting in a loss of expression at the migration front associated with a loss of migratory phenotype. In an in vivo xenograft model in athymic nude mice, the subcutaneous injection of NC1 α4(IV)-overexpressing melanoma cells induced significantly smaller tumors (-80% tumor volume) than the Mock cells, due to a strong inhibition of tumor growth. Exogenously added recombinant human NC1 α4(IV) reproduced the inhibitory effects of NC1 α4(IV) overexpression in UACC-903 cells but not in dermal fibroblasts. An anti-αvβ3 integrin blocking antibody inhibited cell adhesion on recombinant human NC1 α4(IV) substratum. The involvement of αvβ3 integrin in mediating NC1 α4(IV) effect was confirmed by surface plasmon resonance (SPR) binding assays showing that recombinant human NC1 α4(IV) binds to αvβ3 integrin (K(D) = 148 ± 9.54 nM). CONCLUSION/SIGNIFICANCE: Collectively, our results demonstrate that the NC1 α4(IV) domain, named tetrastatin, is a new endogenous anti-tumor matrikine

Adénomes duodénaux. Etude rétrospective comparative d'une série d'adénomes sporadiques versus génétiques entrant dans le cadre de la polypose adénomateuse familiale

REIMS-BU Santé (514542104) / SudocSudocFranceF

L'adénocarcinome colique de type festonné : Essai de caractérisation anatomo-clinique et moléculaire à partir d'une série associant des lésions festonnées aux adénocarcinomes invasifs

REIMS-BU Santé (514542104) / SudocSudocFranceF

Etude du rôle des papillomavirus humains dans la cancérogenèse des voies aéro-digestives supérieurs

REIMS-BU Santé (514542104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

BRAFV600E Gene Mutation in Colonic Adenocarcinomas. Immunohistochemical Detection Using Tissue Microarray and Clinicopathologic Characteristics

International audienc

Design of thrombospondin-binding peptides exhibiting strong anti- angiogenesis and anti-tumor properties

International audienc

Jejunoileal Crohn's disease: a case-control study.

AIMS: Jejunoileitis might be a severe form of Crohn's disease (CD). The aim of the study was to evaluate clinical characteristics, therapeutics modalities and long-term outcome in CD patients with jejunoileitis (CDJI). METHODS: All patients with CDJI followed in the department of Gastroenterology from 1963 to 1999 were included and compared to matched (on Year of CD diagnosis) CD controls without jejunoileitis. Data were obtained from retrospective review of medical charts. RESULTS: Eighteen patients with CDJI were compared to 36 matched CD controls. Median follow-up was 7.65 Years in both groups. At time of CDJI diagnosis the following signs were significantly more frequent in patients with jejunoileal CD than in controls: malnutrition (39% vs 3%), pain suggesting obstruction (33% vs 8%), vomiting (28% vs 5%). Patients with CDJI were more frequently male: M/F ratio=2.0/1.1 (P=0.33). Upper digestive involvement (esophagus, stomach and duodenum) (67% vs 36%, P=0.04) and small intestine strictures (61% vs 19%, P=0.06) were more frequent in CDJI. Initial management was more "aggressive" in CDJI than in controls: steroids in 62% vs 30%, azathioprine in 39% vs 3%, total parenteral nutrition in 28% vs 8% and surgery in 33% vs 17%. During follow-up, the need for azathioprine therapy and surgery were more frequent in CDJI than in controls (extensive small bowel resection in two patients). In 10 of 18 patients, jejunoileitis involvement was diagnosed with a median delay of 3.6 Years (range: 0.5-14.5) after CD diagnosis and at time of CD diagnosis in the 8 others; outcome after CDJI diagnosis was similar in these 2 groups. CONCLUSION: The main revealing signs of jejunoileitis in CD patients are obstruction and malnutrition. Patients with CDJI require more often azathioprine and surgery than CD patients without jejunoileitis. Jejunoileitis is a severe form of CD more frequently complicated by extensive small bowel resection