Showing papers by "Steffen Goletz published in 2011"

Expression of CD176 (Thomsen‐Friedenreich antigen) on lung, breast and liver cancer‐initiating cells

Abstract: The cancer-initiating capacity of most malignant tumours is considered to reside in a small subpopulation of cells. Therapeutical interventions should target these cells rather than the tumour mass. Numerous studies have shown that the carbohydrate antigen structure CD176 (Thomsen-Friedenreich antigen, core-1) is present in many types of cancer and absent in normal adult human tissues. In this study, we assessed whether CD176 is co-expressed with CD44 or CD133 [markers of cancer-initiating cells (CIC)] in human lung, breast and liver carcinoma. A variety of human cancer cell lines and surgical specimens of these malignancies were examined. It was found that in most cases the majority of tumour cells stained strongly for CD44 by immunohistochemistry and flow cytometry, whereas CD133 expression was found on a smaller, but varying proportion of cells. Co-expression of CD176 with CD44 was found at a surprisingly high percentage of cancer cells in vitro and in vivo. Co-expression of CD176 with CD133 was also detected, although at a lower rate. Tamoxifen treatment of MDA-435 breast cancer cells enhanced the CD44(+) /CD176(+) phenotype. Evidence is provided through a new sandwich solid-phase enzyme-linked immunosorbent assay (ELISA) suggesting that CD44 is a carrier molecule for CD176 not only in colorectal cancer as previously reported, but also in lung, breast and liver cancer. The expression of CD176 in CIC suggests that it may represent an effective target for tumour therapies.

Cancer stem cell markers and uses thereof

Abstract: The present invention inter alia pertains to therapeutic methods which are based on the use of an agent specifically binding a tumor-associated carbohydrate antigen for the treatment of cancer stem cells and related diseases. Also provided are diagnostic and prognostic methods using a tumor- associated carbohydrate antigen as marker for cancer stem cells.

Occurrence of the human tumor-specific antigen structure Galβ1-3GalNAcα- (Thomsen–Friedenreich) and related structures on gut bacteria: Prevalence, immunochemical analysis and structural confirmation

Abstract: The Thomsen-Friedenreich antigen (TF; CD176, Galβ1-3GalNAcα-) is a tumor-specific carbohydrate antigen and a promising therapeutic target. Antibodies that react with this antigen are frequently found in the sera of healthy adults and are assumed to play a role in cancer immunosurveillance. In this study, we examined the occurrence of α-anomeric TF (TFα) on a large variety of gastrointestinal bacteria using a novel panel of well-characterized monoclonal antibodies. Reactivity with at least one anti-TF antibody was found in 13% (16 of 122) of strains analyzed. A more in-depth analysis, using monoclonal antibodies specific for α- and β-anomeric TF in combination with periodate oxidation, revealed that only two novel Bacteroides ovatus strains (D-6 and F-1), isolated from the faeces of healthy persons by TF-immunoaffinity enrichment, possessed structures that are immunochemically identical to the true TFα antigen. The TF-positive capsular polysaccharide structure of strain D-6 was characterized by mass spectrometry, monosaccharide composition analysis, glycosidase treatments and immunoblot staining with TFα- and TFβ-specific antibodies. The active antigen was identified as Galβ1-3GalNAc-, which was α-anomerically linked as a branching structure within a heptasaccharide repeating unit. We conclude that structures immunochemically identical to TFα are extremely rare on the surface of human intestinal bacteria and may only be identifiable by binding of both antibodies, NM-TF1 and NM-TF2, which recognize a complete immunomolecular imprint of the TFα structure. The two novel B. ovatus strains isolated in this study may provide a basis for the development of TF-based anti-tumor vaccines.

Humanized egfr antibodies

Abstract: The present invention pertains to humanized anti-EGFR antibodies having antigen binding properties similar to those of the murine or chimeric anti-EGFR antibody from which they are derived. In particular, the present invention is directed to humanized anti-EGFR antibodies which are useful in the treatment of cancer.

Carbohydrate Antigens as Cancer-Initiating Cell Markers

Abstract: The hypothesis that cancer-initiating cells are a prerequisite for cancer ontogenesis is now widely accepted. The existence of cancer-initiating cells is well documented in brain, lung, and breast cancers (Boman et al., 2008; Takaishi et al., 2009), as well as in other malignancies. Cancer-initiating cells (CIC) exhibit low proliferative rates, self-renewing capacity, a propensity to differentiate into actively proliferating tumour cells, and show resistance to chemotherapy or radiation (Vander Griend et al., 2008; Sell & Leffert, 2008). Since cancerinitiating cells clearly differ from the majority of cells of the tumour mass, studying the expression and function of surface molecules on cancer-initiating cells is an important aspect of tumor biology. A great number of more or less specific surface molecules of cancer-initiating cells have been described during recent years. Among the markers most widely accepted is CD44 (Shipitsin et al., 2007; Ponnusamy & Batra, 2008). CD44 is a cell surface type I transmembrane glycoprotein involved in cell-cell interactions, cell adhesion, and migration. It is a receptor for hyaluronic acid, but can also interact with other ligands (Marhaba & Zoller, 2004). CD44 was found to be expressed on cancer-initiating cells in gastric cancer (Takaishi et al., 2009). A single CD44+ cell from a colorectal tumour could form a sphere in vitro and was able to generate a xenograft tumour resembling the properties of the primary tumour (Du et al., 2008). CD133 is also a widely recognized marker of cancer-initiating cells. CD133 was initially described as a surface antigen specific for human haematopoietic stem cells and as a marker for murine neuroepithelial and several other embryonic epithelia (Singh et al., 2004). In a number of recent studies, CD133 alone or in combination with other markers was used for the isolation of CIC from malignant tumours of colon, lung and liver (Haraguchi et al., 2008). CD133+ tumour cells repair radiation-induced DNA damage more effectively than CD133 tumour cells (Bao et al., 2006). CD133 is an independent prognostic marker that correlates with poor overall survival in patients with malignancies (Horst et al., 2008).

Folliculostimuline (fsh) recombinante humaine améliorée

Abstract: La presente invention concerne des preparations ameliorees de FSH permettant de stimuler la liberation des steroides sexuels a une concentration plus inferieure que la FSH urinaire generalement utilisee ou la FSH recombinante obtenue a partir des cellules CHO (cellules ovariennes de hamster chinois) et qui agissent independamment de la signalisation cAMP. Ces preparations ameliorees de FSH peuvent etre utilisees dans le traitement de la sterilite.

Anticorps anti-egfr humanisés

Abstract: La presente invention concerne des anticorps anti-EGFR humanises presentant des proprietes de liaison antigenique semblables a celles de l'anticorps anti-EGFR murin ou chimerique dont ils sont derives. En particulier, la presente invention concerne des anticorps anti-EGFR humanises qui sont utiles dans le traitement du cancer.

Anticorps à fragment fab glycosylé

Abstract: La presente invention concerne un procede permettant le controle de la demi-vie dans la circulation d'anticorps par l'ajustement de la quantite de l'acide sialique dans les glucides lies a la partie Fab des anticorps. La presente invention concerne egalement des anticorps ayant une demi-vie accrue dans la circulation.