摘要:
Soluble recombinant CD44 hyaluronic acid binding domain (CD44HABD) inhibits angiogenesis in vivo in chick and mouse and thereby inhibits human tumor growth of various origins. The anti-angiogenic effect of CD44-HABD is independent of hyaluronic acid (HA) binding, since non-HA-binding mutants of CD44HABD still maintain anti-angiogenic properties. The invention discloses soluble non glycosylated CD44 recombinant proteins as a novel class of angiogenesis inhibitors based on targeting of vascular cell surface receptor. A method of block of angiogenesis and treatment of human tumors using recombinant CD44 proteins as well as their analogues is disclosed. As a further embodiment of the invention, methods for screening for new drug targets using CD44 recombinant proteins and their analogues are presented.
摘要:
The present invention relates to proteins, polypeptides and nucleotides related to the human homologue of the Drosophila suppressor of fused gene, which is involved in the transduction of signals in the HH-PTC pathway. The invention also relates to antibodies raised against the polypeptides according to the invention. The molecules according to the present invention are useful in diagnostic and therapeutic methods relating to conditions associated with defects in said pathway, especially certain malformations and cancer. Other fields of application of the molecules according to the invention are e.g. studies of embryonic development, gene transcription and tissue repair.
摘要:
The invention relates to a method of treatment for states related to inhibition of angiogenesis and endothelial cell proliferation comprising administering an effective amount of vimentin or its derivatives or its fragments, to a subject in need thereof. Further, the invention relates to a pharmaceutical composition and a medicament comprising vimentin, as well as the use of vimentin in the manufacture of a medicament. Hereby, angiogenesis and endothelial cell proliferation can be controlled, and therapeutic treatment for related states is provided.
摘要:
The invention relates to a method of treatment for states related to inhibition of angiogenesis and endothelial cell proliferation comprising administering an effective amount of vimentin or its derivatives or its fragments, to a subject in need thereof. Further, the invention relates to a pharmaceutical composition and a medicament comprising vimentin, as well as the use of vimentin in the manufacture of a medicament. Hereby, angiogenesis and endothelial cell proliferation can be controlled, and therapeutic treatment for related states is provided.
摘要:
The present invention relates to a method for predicting or designing, detecting, and/or verifying a novel cell-penetrating peptide (CPP) and to a method for using said new CPP and/or a novel usage of a known CPP for an improved cellular uptake of a cellular effector, coupled to said CPP. Furthermore, the present invention also relates to a method for predicting or designing, detecting and/or verifying a novel cell-penetrating peptide (CPP) that mimics cellular effector activity and/or inhibits cellular effector activity. The present invention additionally relates to the use of said CPP for treating and/or preventing a medical condition and to the use of said CPP for the manufacture of a pharmaceutical composition for treating a medical condition.
摘要:
The present invention relates to human serine/threonine kinase ULK3 and its ability to regulate GLI transcription factors; mediators of SHH signaling. This disclosure demonstrates that ULK3 enhances endogenous and over-expressed GLI1 and GLI2 transcriptional activity in cultured cells, and ULK3 alters subcellular localization of GLI1. According to this disclosure ULK3 is an autophosphorylated kinase and phosphorylates GLI proteins in vitro. A peptide sequence in GLI1 C-terminus that is phosphorylated by ULK3 is provided in this disclosure. ULK3 catalytical activity is shown to be crucial for its function in SHH pathway. This disclosure shows that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins. Furthermore, a therapeutic method in SHH dependent human disorders is disclosed by pharmacological inhibition of ULK3 kinase activity. Identification of ULK3 substrate sequence in GLI1 allows the design of peptide-based modulators of its kinase activity.
摘要:
Soluble recombinant CD44 hyaluronic acid binding domain (CD44HABD) inhibits angiogenesis in vivo in chick and mouse and thereby inhibits human tumor growth of various origins. The anti-angiogenic effect of CD44-HABD is independent of hyaluronic acid (HA) binding, since non-HA-binding mutants of CD44HABD still maintain anti-angiogenic properties. The invention discloses soluble non glycosylated CD44 recombinant proteins as a novel class of angiogenesis inhibitors based on targeting of vascular cell surface receptor. A method of block of angiogenesis and treatment of human tumors using recombinant CD44 proteins as well as their analogues is disclosed. As a further embodiment of the invention, methods for screening for new drug targets using CD44 recombinant proteins and their analogues are presented.
摘要:
CD44, the receptor for hyaluronic acid, has complex functions in cellular physiology, cell migration and tumour metastasis. The inventors have previously found that human CD44 receptor overexpression in mouse fibrosarcoma cells inhibits subcutaneous tumour growth in mice [Kogerman et al., Oncogene 1997; 15:1407-16; Kogerman et al., Clin Exp Metastasis 1998; 16:83-93]. Here it is demonstrated that a tumour growth inhibitory effect of CD44 is caused by block of angiogenesis. Furthermore, the inventors have found that soluble recombinant CD44 hyaluronic acid binding domain (CD44HABD) inhibits angiogenesis in vivo in cLick and mouse and thereby inhibits human tumour growth of various origins. The anti-angiogenic effect of CD44-HABD is independent of hyaluronic acid (HA) binding, since non-HA-binding mutants of CD44HABD still maintain anti-angiogenic properties. The invention discloses soluble CD44 recombinant proteins as a novel class of angiogenesis inhibitors based on targeting of vascular cell surface receptor. A method of block of angiogenesis and treatment of human tumours using recombinant CD44 proteins as well as their analogues is disclosed. As a further embodiment of the invention, methods for screening for new drug targets using CD44 recombinant proteins and their analogues is presented.