54 results about "Sonic hedgehog" patented technology

The present invention relates to compounds, small interfering RNAs and compositions and methods of inhibiting tumorigenesis using agents that inhibit the sonic hedgehog and GLI signaling pathway, including agents that inhibit GLI expression, synthesis and/or function. The present invention also relates to particular biomarkers that can be used in the diagnosis and prognosis of cancer. Methods of treating cancer, including glioblastomas, medulloblastomas, basal cell carcinomas, prostate cancer and small cell and non-small cell lung cancer are also provided using small organic compounds, siRNAs and blocking antibodies that inhibit or block the SHH/GLI pathway.

The invention provides compositions and methods for increasing hair growth and decreasing hair loss. In one embodiment, the compositions comprise a plurality of hair growth agents. Optionally, the hair growth agents are selected from the group consisting of: IGF-1, FGF-2, FGF-10, PDGF-AA, Wnt-3a, noggin, ephrin-A3, sonic hedgehog (SHH), BMP-6 and hypoxanthine.

The invention relates to a method for inducing a human pluripotent stem cell to differentiate into an RPE cell. According to the method, an inhibitor is used for inducing the human pluripotent stem cell to differentiate into a neural precursor; after Shh, IGF1 and EGF growth factors are utilized to activate ERK 1/2, JNK, Sonic hedgehog signal routes, the cell is presented as the shape of neuroepithelium, Activen A and Chir99021 are added to activate TGFbeta and Wnt signal routes respectively to induce a neuro-epithelial cell into a retinal progenitor cell; adherent culture is conducted on theretinal progenitor cell to obtain an RPE cell at an underdeveloped state. The invention further studies the field of applying the underdeveloped RPE cell to treating retinal degenerative diseases. Compared with the prior art, the method firstly makes three stages of differentiating the human pluripotent stem cell to the underdeveloped RPE cell and related small molecular substances and growth factors used therein clear. Compared with a matured RPE, the underdeveloped RPE obtained through differentiation can treat the retinal degenerative diseases more effectively after being transplanted.

Methods and compositions for increasing trichogenicity of cells in culture are provided. One embodiment provides culturing dissociated mammalian dermal cells in vitro in the presence of an effective amount of one or more sonic hedgehog (Shh) pathway agonists to increase the trichogenicity of the dissociated mammalian dermal cells compared to untreated dissociated mammalian dermal cells. The cell culture optionally includes epidermal cells. Preferred Shh agonists include, but are not limited to CUR-0236715 and CUR-0201365 available from Curis, Inc. Trichogenicity is measured using the Aderans Hair Patch Assay™. The cultured dermal cells can be maintained in culture in the presence of the one or more Shh agonists for at least 1 to 7 or more days prior to harvest. The treated, cultured dermal cells can be used to treat hair loss in a mammalian subject, preferably a human, by implanting them in an effective amount to induce hair follicle formation.

The invention provides metastatic tumor deletion protein small-molecule cyclopeptide, derivatives or salts thereof, a preparation method for the metastatic tumor deletion protein small-molecule cyclopeptide, the derivatives or salts thereof and an application of the metastatic tumor deletion protein small-molecule cyclopeptide, the derivatives or salts thereof in preparation of antitumor medicaments. The metastatic tumor deletion protein small-molecule cyclopeptide is low in molecular weight, high in stability and very low in toxicity and can enter cells through cell membranes to inhibit endocytosis of tumor cells and interfere morphologic change of the cell membranes and conduction of relevant antitumor signals by inhibiting dimerization of Mtss1 protein, so that cell proliferation and growth caused by tumor stimulating factors such as epidermal growth factors EGF, platelet derived growth factor PDGF or sonic hedgehog (shh) factors are weakened, wherein the in-vitro inhibition activity of nanomole-scale inhibitor-protein can remarkably inhibit the endocytosis of the cells after the inhibitor-protein is directly added into cell culture fluid without being transfected or packaged by lipidosome.

The invention discloses a nerve regeneration gel as well as a preparation method and application thereof. The matrix of the nerve regeneration gel is formed by fibrinogen, thrombin, laminin and fibronectin; the nerve regeneration gel contains procyanidine, sonic hedgehog, an epidermal growth factor, neurenergen-3 and a vascular endothelial growth factor. In-vitro test and animal test show that thegel is capable of accelerating neuron regeneration and neurite extension and repairing the injured nerve tissue. The matrix of the gel comprises fibrin, laminin and fibronectin and is capable of reducing formation of cavities and accelerating adhesion and proliferation of endogenous neural stem cells; the procyanidine in the gel is capable of resisting oxidation and inhibiting inflammation; the sonic hedgehog, the epidermal growth factor and the neurenergen-3 are capable of accelerating proliferation of the stem cells and differentiation to neurons of the stem cells; the vascular endothelialgrowth factor is capable of accelerating generation of blood vessels. The gel can be formed in situ on injured parts and can be used for treating nervous system injury.

The invention belongs to the field of pharmacy, and relates to an application of a TCM monomer of apigenin to prepare a medicine for treating the pancreatic cancer. A CCK-8 method for evaluation, repeated screening and optimization, and a pharmacodynamic test for inhibiting proliferation of pancreatic cancer SW1990 cells are adopted to screen an effective monomer, having a strong anti-tumor effect, of apigenin. Moreover, an equipment of apigenin for interfering a Sonic Hedgehog signal channel of human pancreatic cancer SW1990 stem cells is carried out. The result shows that apigenin can obviously inhibit proliferation of pancreatic cancer stem cells, lower the ratio of pancreatic cancer stem cells, and reduce self-renewable ability of pancreatic cancer stem cells. The ratio of CD24+CD44+ cells is obviously lowered through flow cytometry; the amount of cancer stem cells cultured free of serum decreases; and expression of members in the Sonic Hedgehog signal channel at mRNA and protein levels is obviously lowered. The TCM monomer of apigenin can be taken as an individual unique active component for preparing the medicine for treating the pancreatic cancer.

Methods are provided in which a sterol-depleting agent such as β-cyclodextrin (βCD), is used to modulate signaling by a differentiation signaling protein such as Hedgehog protein or a BMP in vitro. As illustrated herein, the use of βCD in conjunction with Sonic Hedgehog N-terminal peptide (ShhN) causes substantially all of the cells in neural plate explants to differentiate as neurons, such as motor neurons. Also provided are cell therapy methods and screening methods that rely on the modulation of signaling of a differentiation signaling protein such as Hedgehog, by a sterol-depleting agent such as βCD.

This invention provides methods for determining whether an agent, known to upregulate the sonic hedgehog pathway, increases brain progenitor cell division in a subject. Furthermore, this invention provides methods for treating anxiety, depression, a cognitive disorder or a neuro-degenerative disorder or inhibiting the onset of anxiety, depression or a cognitive disorder by administering to an afflicted subject a therapeutically or prophylactically effective amount of the agent known to upregulate the sonic hedgehog pathway. Finally, this invention provides methods for treating anxiety, depression, a cognitive disorder or a neuro-degenerative disorder or inhibiting the onset of anxiety, depression or a cognitive disorder by administering to an afflicted subject a therapeutically or prophylactically effective amount of Hh-Ag 1.1, Hh-Ag 1.2, Hh-Ag 1.3, or a derivative of Hh-Ag 1.1, Hh-Ag 1.2 or Hh-Ag 1.3.

Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

The present invention relates to a method for preparing induced dopaminergic neuronal progenitors (iDPs) comprising inducing an expression of Oct4, Sox2, Klf4, and c-Myc genes in adult cells and direct reprogramming of the adult cells to the iDPs by treating the cells with sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF8); and a cell therapy product and a composition for treating or preventing Parkinson's Disease (PD) which comprises the iDPs as active ingredients. In addition to this, the present invention relates to a method for preparing midbrain dopaminergic neurons comprising isolating NSC-like colony by culturing the iDPs, dissociating the isolated NSC-like colony, and culturing the cells on the neural cell differentiation medium. Further, the present invention relates to a method for treating PD or a method for screening medicine for preventing or treating PD using the cells of the present invention. The progenitors prepared by the method for preparing the iDPs of the present invention can be widely used in the known art since the neuronal progenitors have significantly higher efficiency in differentiating to the dopaminergic neurons compared to conventional methods and lack side effects such as immunogenicity and ethical issues because patients' own somatic cells can be used.

The present invention generally relates to compositions, reagents and methods for detecting and treating a neural tube defect in a fetus. One aspect of the invention provides a method including administrating a composition containing noggin or LDN-193189 to the fetus in utero. In certain embodiments, the composition is administrated if the maternal blood or amniotic fluid contains an elevated amount of BMP4 and/or a reduced amount of noggin. In another aspect of the invention, the method includes administrating a composition containing GDC-0449 to the fetus in utero. In certain embodiments, the GDC-0449 is administrated if the maternal blood or amniotic fluid contains an elevated amount of sonic hedgehog.

The present invention relates to the field of stem cells. More specifically, the present invention provides methods and compositions useful for the highly efficient conversion of human stem cells to lineage-specific neurons. In a specific embodiment, a method of inducing differentiation of human stem cells into dopaminergic (DA) neurons comprises the steps of (a) transfecting human stem cells with a lentiviral vector encoding Atoh1, wherein the vector is Dox inducible; and (b) growing the transfected cells in culture in the presence of Dox, Sonic Hedgehog (SHH) and FGF-8b until DA neurons are induced.

Mechanisms nourish stem cells for organ regeneration and prevent alcohol related diseases such as Fetal Alcohol Syndrome (FAS) and Liver Sclerosis. These stem cell nutrients have been found to positively affect the skin, liver, brain neurons, pancreas, and the GI tract. Cholesterol supplementation prevents fetal alcohol spectrum defects (FASD) in alcohol-exposed zebra fish embryos. Using the zebra fish model, alcohol was found to interfere with embryonic development by disrupting cholesterol-dependent activation of a critical signaling molecule, sonic hedgehog (Shh). Cholesterol supplementation of the alcohol-exposed embryos restored the functionality of the molecular pathway and prevented development of FASD-like defects. Novel biomarkers were identified for diagnosing alcohol related diseases by lipid chemical analysis and Raman Spectroscope.

The invention relates to the technical field of stem cell culture, in particular to cell culture fluid, application of the cell culture fluid and a method of inducting DPSCs (Dental Pulp Stem Cells) to differentiate into neuron-like cells. The cell culture fluid provided by the invention comprises basic culture fluid, GDNFs (Glial Cell-Derived Neurotrophic Factors), Shh (Sonic hedgehog), EGFs (Epidermal Growth Factors) and cAMP (Cyclic Adenosine monophosphate). The culture fluid provided by the invention can be used for inducting the DPSCs to differentiate into the neuron-like cells. When the culture fluid is used for inducing the DPSCs, the form of the DPSCs starts to change from 12h; after the 24h from the induction, the form of the DPSCs is obviously changed; the cell refractivity starts to be enhanced; cell processes increase and grows and differentiate into the form of the neuron-like cells. Through western bolt detection, after 24h from the induction, the expression amounts of Nestin and MAP2 (Microtubule-Associated Protein 2) in the DPSCs are obviously increased. Therefore the culture fluid has the advantages of short period and high efficiency when being used for inducing the DPSCs to differentiate into the neuron-like cells.

The present invention relates to compounds for modulating sonic hedgehog signaling and preventing or treating cancer.