149 results about "Apoptosis induction" patented technology

An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

The present invention belongs to the field of medicine, and particularly relates to a novel curcumin pharmaceutical preparation, which comprises a solid dispersion, a micellar preparation, SMEDDS and a nanometer emulsion. According to the present invention, by increasing the solubility and the bioavailability of curcumin, the curcumin pharmaceutical preparation can effectively utilize the pharmacological effects of anti-oxidation, anti-inflammation, anti-cancer, apoptosis induction, antiangiogenesis, neuroprotection, anti-microorganism, liver and kidney protection, vascular formation inhibition, myocardial infarction prevention, blood glucose lowering, anti-rheumatism and the like of the curcumin.

Novel humanized immunoglobulins and active fragments thereof which are specifically reactive to Fas ligand are provided, and a site on Fas ligand which is important to inhibit apoptosis induced by the Fas-Fas ligand interaction against Fas-expressing cells is demonstrated. The novel humanized immunoglobulins and active fragments thereof which are specifically reactive to Fas ligand are prepared from hybridomas which produce monoclonal antibodies specifically reactive to Fas ligand, via recombinant DNA techniques. The humanized immunoglobulins can inhibit the physiological reactions between Fas ligand and Fas such as apoptosis. Further, identification of the site which is on Fas ligand and responsible for apoptosis induction allows creation of recombinant proteins or peptides which are specifically reactive to the amino acids within the site so as to inhibit apoptosis, and to find new therapeutic or diagnostic agents.

A preparation method for an ethanol extract of the fruiting body of Antrodia camphorata (EEAC) is provided. The preparation method includes steps of: (a) providing the fruiting body of A. camphorata (AC); (b) extracting the fruiting bodies with a first ethanol solution; and (c) obtaining EEAC. EEAC further can be sequentially extracted or fractioned by n-hexane, ethyl acetate and ethanol, and an n-hexane fraction (FC), an ethyl acetate fraction (FA) and an ethanol fraction (FB) respectively are generated. The growth inhibition and apoptosis induction of leukemia cell line HL 60 are effectively mediated by FA product, in which zhankuic acid A is the bioactive marker. The amount of triterpenoid in the fruiting body of AC can be determined by NMR and HPLC analysis.

The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5′-(MeCx)(Tx)MeCxAsAstscscsastsgsgsMeCxAx(Gx)(c)-3′, and preferably of the general formula 5′-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3′, wherein capital letters designate an LNA nucleotide analogue selected from β-D-oxy-LNA, β-D-thio-LNA, β-D-amino-LNA and α-L-oxy-LNA, small letters designate a deoxynucleotide, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumour development in vivo. The LNA oligonucleotides are superior to other LNA oligonucletides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down-regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.

The present invention discloses recombinant soluble human tumore necrosis factor related death inducing ligand and its preparation process and application in preparing antitumor medicine. The present invention adopts human tonsil tissue mRNA as template to amplify TRAIL coding sequence, constitute engineering colibacillus for expressing rhsTRAIL and engineering saccharomycete, establish the rhsTRAIL engineering colibacillus fermentation, occlusion body washing and destination protein purification process and the engineering saccharomycete and destination protein purification process separately, and obtain pure rhsTRAIL product, which has molecular weight of 19.6-24 KD and exists in both monomer and dimmer. The rhsTRAIL can induce death of several kinds of cancer cells outside body, inhibit amplification of liver cancer cell in tumor loading mouse obviously and kill tumor cell selectively, so that it may be used in preparing effective antitumor medicine.

The invention relates to fusion proteins useful as therapeutics against cancer. The fusion protein comprises of cell-targeting moiety and apoptosis-inducing moiety. Cell-targeting moiety and apoptosis-inducing moiety are linked by a flexible linker, which are specifically recognized by cancer specific protease and cleaved in situ to release the apoptotic domain. In particular, the invention is illustrated by a recombinant fusion protein between human Vasoactive Intestinal Peptide (VIP) and BH3 domain of Bcl2 family protein, linked by a linker that has site for cancer specific proteases. The fusion protein specifically targets VIP receptor over-expressing cancer cells and induces cell-specific apoptosis after cleavage at the linker site by cancer specific proteases. Such fusion proteins are useful for the delivery of therapeutic / apoptotic moiety (peptides) to specific cells with perturbed expression of, but not limited to neuropeptide receptors.

Recombinant galectin 8 (rGal 8), produced in host Escherichia coli, exerts hemagglutinating activity, neutrophil adhesion inducing activity, integrin αM-binding activity, proMMP-9 binding activity, active form MMP-9 production promoting activity, superoxide production promoting activity, apoptosis inducing activity for a particular cell, suppressive or inhibitory activity against the metastasis / invasion of tumor cells, etc. In the rGal 8, however, a link domain linking two CRDs is highly susceptible to protease and, therefore, is very easily digestible with the enzyme, thereby losing the above activities. Thus, there is a need for a more stabilized molecule in view of further studies. Modification of the link domain linking two CRDs in galectin 8 provides a modified molecule having an elevated activity without any undesirable effects on the above activities.

The invention relates to an extraction method of high cell apoptosis induction active lycium barbarum polysaccharide. The extraction method comprises using the fruit of Chinese wolfberry to serve as a raw material, obtaining lycium barbarum coarse polysaccharide through extraction, adopting an ultrafiltration membrane with 30K of molecular weight cutoff to separate the lycium barbarum polysaccharide, collecting percolate, using an ultrafiltration membrane with 10K of molecular weight cutoff to separate, collecting cutoff liquid 1, using an ultrafiltration membrane with 40K of molecular weight cutoff to separate, collecting percolate 1, conducting vacuum concentration and freeze drying on the cutoff liquid 1 and the percolate 1, and obtaining the high cell apoptosis induction active lycium barbarum polysaccharide. The extraction method uses a water extraction method to extract the lycium barbarum polysaccharide, removes protein, then adopts an ultrafiltration technique to grade and separate the polysaccharide, adopts the ultrafiltration membrane with a plurality of molecular weight cutoffs to repeatedly separate, overcomes shortcomings of being complex in column chromatography operation and unfavorable for industry or production and the like, is high in efficiency, low in cost, simple in operation, soft in condition, short in production phase and the like and provides a new thought for development of an active compound and industrialized application.

The invention provides a TNF (Tumor Necrosis Factor)-related apoptosis-inducing ligand fusion protein of extracellular parts and an XVIII type collagen NC1 domain or a trimerization domain, wherein the peptide adapter is [GlyGlyGlyGlySer]n, wherein the n is an integer of 0-4. The fusion protein is constructed and recombined; and the fusion protein is expressed for annealing, wherein the fusion protein after the annealing is expressed into relatively strong induced tumor cell apoptosis activity. According to the invention, the design of the fusion protein VXIII type collagen NC1 domain fusion TRAIL (Tnf Related Apoptosis Inducing Ligand) is adopted so that the half-life period of the related fusion protein in an experimental animal body can be prolonged and the defect that the half-life period of the TRAIL is just a little number of minutes can be overcome; the NC1 or trimerization domain has very strong trimerization characteristics and can stabilize a trimer thereof after the TRAIL is infused so as to keep to induce the tumor cell apoptosis activity; the endostatin domain contained in the NC1 domain has the effect of inhibiting the production of new vessels, and the effect can be cooperated with the apoptosis effect of the TRAIL so as to strengthen the anti-tumor effect of the infusion protein. The method disclosed by the invention can efficiently reduce the cost of the infusion protein production in a laboratory or in industry.

The invention provides binding molecules, including antibody molecules which selectively bind to a cell surface antigen of a target cell, and wherein the binding molecules, on binding the cell surface antigen, induce apoptosis of the target cell. There is also provided methods of and pharmaceutical compositions for apoptosis induction and uses thereof.

The invention provides an antibody in an extracellular region of a death receptor-5 of a tumor necrosis factor-related apoptosis inducing ligand. By a death receptor-5 agitated polyvalent antibody, a single-chain antibody of the death receptor-5 forms a polyvalent antibody through an oligomerization structural domain, and the amino acid sequence is shown as SEQIDNO.1. The single-chain antibody of the death receptor-5 forms a tetravalent antibody through a p53 structural domain, and the amino acid sequence is shown as SEQIDNO.2. After multimerization, the antibody can induce apoptosis of tumor cells, and is nontoxic to normal cells. The invention also provides an application of the death receptor-5 agitated polyvalent antibody in preparation of anti-tumor medicines.

The invention belongs to the field of genetic engineering and in particular relates to an application of long non-coding RNA (lncRNA) DUXAP8 to prognosis of gastric cancers and target drug treatment. With up-regulation of IncRNA DUXAP8 in gastric cancer cells, prognosis of patients with IncRNA DUXAP8 with high expression level is relatively poor. Effects are exerted on invasion, migration, and the like of the gastric cancer cells by changing expression of IncRNA DUXAP8. Gastric cancer cell proliferation and apoptosis induction can be inhibited by knocking down IncRNA DUXAP8 expression.

The invention, relating to the field of biotechnology, provides TRAIL fusion protein, a DNA sequence encoding the fusion protein, a vector containing the DNA sequence, a host cell or a transgenic animal containing the vector, a preparation method of the fusion protein and applications of the fusion protein. The TRAIL fusion protein from N-terminal to C-terminal comprises crosslinking region, humanized leucine zipper sequence and humanized TRAIL protein, humanized TRAIL extracellular region or fragments of humanized TRAIL extracellular region, can observably increase stability, prolong the half life in animal body and improve treatment effect, and has extensive application prospect.

A process for preparing the wither inducing ligand (TRAIL) associated with recombinant human soluble tumor necrosis factor includes such steps as providing thue engizzeered bacterium rsTRAIL96-281-pET156-BL21 (DE3) (CGMCC No.0659), fermenting culture, washing, ultrasonic breaking, salting-out, chromatography and exchanging in buffering liquid system.

A novel fusion protein, comprising a receptor-antagonizing domain and an angiogensis inhibiting domain, characterized, for example, by its ability to block apoptosis and / or inhibit endocrine response, is useful in treating cancer. For example, a human prolactin antagonist-endostatin fusion protein combines apoptosis induction and angiogenesis inhibition to combat cancer.

Galectin 9 exerts various functions depending on its localizations. On the other hand, galectin 9 is expected as participating in various biological functions. Thus, it has been required to clarify the detailed biological activities of galectin 9 and develop galectin 9-related techniques including development of drugs. Human galectin 9 shows a cytotoxic activity and an apoptosis-inducing activity on tumor cells but shows neither cytotoxic activity nor apoptosis-inducing activity on normal cells. Therefore, it is possible to employ galectin 9 proteins, galectin 9 agonists, galectin 9 antagonists, anti-galectin 9 binding protein antibodies, anti-galectin 9 binding sugar chain antibodies, galectin 9-producing, releasing or inducing substances, etc. as antitumor, antiallergic, immunosuppressive agents, drugs for autoimmune diseases, anti-inflammatory agents and active ingredients for adrenocortical steroid hormone alternatives.

Glucose deprivation is an attractive strategy in cancer research and treatment. Cancer cells upregulate glucose uptake and metabolism for maintaining accelerated growth and proliferation rates. Specifically blocking these processes is likely to provide new insights to the role of glucose transport and metabolism in tumorigenesis, as well as in apoptosis. As solid tumors outgrow the surrounding vasculature, they encounter microenvironments with a limited supply of nutrients leading to a glucose deprived environment in some regions of the tumor. Cancer cells living in the glucose deprived environment undergo changes to prevent glucose deprivation-induced apoptosis. Knowing how cancer cells evade apoptosis induction is also likely to yield valuable information and knowledge of how to overcome the resistance to apoptosis induction in cancer cells. Disclosed herein are novel anticancer compounds that inhibit basal glucose transport, resulting in tumor suppression and new methods for the study of glucose deprivation in animal cancer research.

The invention relates to water caltrops polysaccharide, the extraction method and the usage, belonging to field of Chinese herbal medicine, which is characterized in comprising following preparation methods: crude polysaccharide is prepared and purified and dissolved and produced into 5% of sugar solution; volume ratio of chloroform and normal butyl alcohol solution is 1 to 0.2; crude polysaccharide solution, chloroform and normal butyl alcohol solution are mixed according to volume ratio of 2 to 5 : 1 and are added into a vessel for oscillating about 30 min and centrifuging 15 min; the aqueous phase at the upper layer is taken for storing; the chloroform phase and protein solution are thrown away; protein can be removed three times according to the above method before the polysaccharide is dried and decolored through adopting active carbon method. The water caltrops polysaccharide has the advantages of anti-tumor, obvious proliferation inhibition and apoptosis induction upon Hela and U251 through pharmacodynamics experiment showing.

The invention discloses an application of an artemisinin compound artemisinin B having a structure shown in the specification in the preparation of antitumor drugs. Pharmacological and pharmacodynamic experiments in the invention prove that the artemisinin B has effects of specific propagation inhibition, apoptosis induction, cell cycle affection and the like on in vitro cultured human tumor cells. The artemisinin B is a low-toxicity unique-effect compound obtained from a natural component Artemisia annua, and provides a new drug selection for the clinical tumor treatment.

The invention discloses a broad-spectrum antiviral medicament as well as a preparation method and application thereof and relates to a creative medicament in the technical field of biology. The broad-spectrum antiviral medicament consists of a protein transduction label, a double-stranded RNA (Ribonucleic Acid) detection domain and an apoptosis induction domain. The preparation method comprises the steps of construction, expression and purification of a gene recombinant protein. The application comprises a cell model experiment, an animal model experiment and antiviral action for DNA (Deoxyribonucleic Acid) or RNA virus of dsRNA generated during infection cell. The broad-spectrum antiviral medicament is designed according to a pure cell antiviral natural mechanism and has the advantages of high reliability, broad-spectrum virus resistance, high specificity, no toxic or side effect, high safety, favorable repeatability of experiment result, easiness in popularization, simpleness and convenience in research and production and low cost.

The invention provides construction of TRAIL (Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand) recombinant bacille calmette guerin (rBCG), and relates to a shuttle expression vector comprising a signal peptide fragment of a major secretory antigen Ag85B of BCG and a gene fragment of a TRAIL and a construction method thereof. The obtained shuttle expression vector pMV261-Ag85B-TRAIL is used for constructing rBCGTRAIL, and can be applied to preparation of TRAIL rBCG for treating superficial bladder tumors, preventing postoperative recurrence thereof and preventing tuberculosis. The rBCG has dual functions of TRAIL and BCG, so that cooperative and synergistic actions of the TRAIL and BCG can be better brought into play; rBCG-TRAIL can secrete TRAIL, and the using amount of the rBCG-TRAIL can be lower than that of the BCG under the condition that the same or better immune effect is achieved, so that the toxic or side effect is reduced; and the rBCG-TRAIL can directly secrete TRAIL efficiently on a certain part, so that tumor cells can be killed in cooperation with the rBCG-TRAIL, and high cost caused by the use of a foreign cell factor is avoided.

A preparation method for an ethanol extract of the fruiting body of Antrodia camphorata (EEAC) is provided. The preparation method includes steps of: (a) providing the fruiting body of A. camphorata (AC); (b) extracting the fruiting bodies with a first ethanol solution; and (c) obtaining EEAC. EEAC further can be sequentially extracted or fractioned by n-hexane, ethyl acetate and ethanol, and an n-hexane fraction (FC), an ethyl acetate fraction (FA) and an ethanol fraction (FB) respectively are generated. The growth inhibition and apoptosis induction of leukemia cell line HL 60 are effectively mediated by FA product, in which zhankuic acid A is the bioactive marker. The amount of triterpenoid in the fruiting body of AC can be determined by NMR and HPLC analysis.

Disclosed is a method for improving cancer therapy that relies on induction of apoptosis in malignant cells. It has been found that docking of protease inhibitors PAI-1 and TIMP-1 renders malignant cells expressing these inhibitors more sensitive to apoptosis, whereas non-malignant cells do not change their sensitivity to apoptosis induction. It is therefore possible to increase the effect of various anti-cancer treatments in a rational manner and to predict whether or not an apoptosis-inducing cancer treatment will be effective in a patient or not. The invention also provides for methods of identifying agents that inhibit the apoptosis sensitivity modulating effects of protease inhibitors and to methods of identifying anti-cancer compounds that are not dependent on an apoptosis inducing mechanism which can be modulated by protease inhibitors.

The present invention provides a dye lignin derivative containing nitrogen monoxide donor, and in particular relates to a compound which is produced by ester bond connection of dye lignin (Genistein, Gen) and nitric acid ester NO (nitrogen monoxide) donor. The precursor derivative of nitrogen monoxide donor dye lignin (NO-G) with connected ester bonds is produced through chemical reaction between dye lignin (genistein) and a corresponding nitric acid ester NO donor. The ester bonds are broken in the structure through biological changes and drift out of the original drug Gen and the NO donor; NO can be slowly released to coordinate with the Gen, and the dual coordinated anti-tumor mechanism demonstrates excellent effects on apoptosis inhibition for ovary cancer and apoptosis induction of the ovary cancer.

The invention relates to a serum marker for detecting pulmonary embolism and an application thereof. The serum marker can be used for distinguishing patients with pulmonary embolism and normal people,the serum marker is a protein factor, and the protein factor is TRAIL: a tumor necrosis factor-related apoptosis-inducing ligand.

The invention discloses a malaria serum with an anti-tumor function and a preparation method and application of the malaria serum with the anti-tumor function.According to long-term arduous scientific experiments, the serum of patients with malaria has a certain anti-tumor function, and particularly the serum of patients with a syndrome of malaria and thrombocytopenia is effective in treatment or prevention of tumors, especially liver cancers, under specific concentration conditions.According to experiments, the serum has an evident apoptosis induction function on hepatoma cell strains (7721) cultured in vitro, and the hepatoma cell apoptosis induction ratio is increased along with increase of serum concentration.The malaria serum with the anti-tumor function and the preparation method and application of the malaria serum with the anti-tumor function provide theoretical and experimental bases for further researches on tumor cell apoptosis induction factors generated by plasmodia, breaks a new path for rediscovery pathogenesis of critical and cerebral malaria cases and epidemiologic researches of various plasmodium species and strains, and make new effort in application of the malaria serum or preparations thereof to preparation of medicines for treatment or prevention of the tumors, thereby having great scientific research values and significances.