62 results about "Growth arrest" patented technology

The present invention discloses novel mechanisms in the aging process and describes novel methods for high-throughput screening to identify, detect, and purify agents to be used for improving mitochondrial function, maintaining the cell cycle-arrested state in senescent and post mitotic cells, and thus preventing or treating age-related diseases or disorders associated with accelerated mitochondrial function loss, telomere dysfunction, and / or deterioration of the growth-arrested state. The present invention also discloses a number of compounds or compositions identified from this method. The present invention further provides the use of low doses of rapamycin or its analogs as a mimic of caloric restriction in preventing age-related diseases or disorders.

Provided herein are methods for inducing growth arrest or apoptosis in cancer cells in a subject. Further provided are methods of inhibiting or treating metastasis of a cancer cell in a subject. The methods involve administering to the subject an antibody conjugate containing an antibody, variant thereof, or functional fragment thereof having binding specificity of the antibody as produced by the hybridoma having ATCC accession number PTA 2439 and a biologically active molecule. The antibody (e.g., mAb 3E10) variant or functional fragment thereof provides for the in vivo transduction of the conjugate to the nucleus of mammalian cells, where the conjugated biologically active molecule may exert its effect. In particular embodiments, the antibody conjugate comprises a single chain Fv fragment of an antibody having the binding specificity of mAb 3E10 produced by ATCC PTA 2439, conjugated to p53.

Provided herein are methods to suppress specificity protein (Sp) activity in a cell associated with a cell proliferative disease. The methods are effective to inhibit a microRNA in the cell using an antisense microRNA oligonucleotide which results in an increase in expression of a specificity protein (Sp) suppressor gene thereby inducing Sp degradation, apoptosis or growth arrest by releasing inhibitors of G2 / M (Myt-1) or inhibition. Also provided are methods of treating a cancer using the antisense microRNA oligonucleotide. In addition the present invention provides antisense microRNA-27a oligonucleotides useful in the methods described herein.

The present invention provides novel proteins and peptides from the receptor binding region of human Growth Arrest Specific Gene 6 (Gas6) and antibodies, including specified portions or variants, specific for at least one such Gas6 peptide or fragment thereof. The aforesaid peptides can be used to generate human, primate, rodent, mammalian, chimeric, humanized and / or CDR-grafted anti-Gas6 antibodies. The invention also provides for the nucleic acids encoding such peptides and anti-Gas6 antibodies, complementary nucleic acids, vectors, host cells, and methods of making and using thereof, including therapeutic formulations, administration and devices. Fifteen novel peptide sequences from the Gas6 G domain that are implicated in Gas6 interactions with its receptors are identified, isolated, and synthesized so as to allow generation of anti-Gas6 antibodies. The peptide sequences include three ESTs that encompass regions predicted to contribute to receptor binding or that can raise anti-Gas6 antibodies. This invention provides for such antibodies to be used in modulating or treating at least one Gas6-related disease in a cell, tissue, organ, animal, or patient. Such diseases may include, but are not limited to, thromboembolic disease, ischemic disease, venous thromboembolism, arterial or venous thrombosis, pulmonary embolism, restenosis, diabetic angiopathy and allograft atherosclerosis.

The present invention provides novel proteins and peptides from the receptor binding region of human Growth Arrest Specific Gene 6 (Gas6) and antibodies, including specified portions or variants, specific for at least one such Gas6 peptide or fragment thereof. The aforesaid peptides can be used to generate human, primate, rodent, mammalian, chimeric, humanized and / or CDR-grafted anti-Gas6 antibodies. The invention also provides for the nucleic acids encoding such peptides and anti-Gas6 antibodies, complementary nucleic acids, vectors, host cells, and methods of making and using thereof, including therapeutic formulations, administration and devices. Fifteen novel peptide sequences from the Gas6 G domain that are implicated in Gas6 interactions with its receptors are identified, isolated, and synthesized so as to allow generation of anti-Gas6 antibodies. The peptide sequences include three ESTs that encompass regions predicted to contribute to receptor binding or that can raise anti-Gas6 antibodies. This invention provides for such antibodies to be used in modulating or treating at least one Gas6-related disease in a cell, tissue, organ, animal, or patient. Such diseases may include, but are not limited to, thromboembolic disease, ischemic disease, venous thromboembolism, arterial or venous thrombosis, pulmonary embolism, restenosis, diabetic angiopathy and allograft atherosclerosis.

The present invention provides epitope-tagged mammalian recombinant Growth Arrest Specific Gene 6 (Gas6) proteins or polypeptides that retain their biological activity of Gas6, including a novel method of generating and purifying the aforesaid proteins or polypeptides. Such biolgically active eptitope-tagged Gas6 proteins or polypeptides can be used when the presence of Gas6 is required and / or when Gas6 antagonists and receptors need to be identified. Prior to being expressed from a mammalian cell, the recombinant Gas6 protein or polypeptide is tagged with either Flag or polyhistidine to the C-terminus. After expression, the protein or polypeptide is purified in a single step affinity purification using either anti-Flag antibody resin or nickle resin. The purified epitope-tagged mammalian recombinant Gas6 protein or polypeptide maintains its biological activity and can be used thereafter.

The invention discloses a method for enhancing the anti-cervical cancer activity of glutaminase enzyme inhibitor by taking TIGA1 (Transcript Induced by Growth Arrest 1) as a target spot, and provides application of a substance for inhibiting or reducing TIGA1 expression in tumor cells in preparing a product for treating tumor, or the application of the substance for inhibiting or reducing the TIGA1 expression in the tumor cells in preparing a product for inhibiting tumor cell growth. According to the method disclosed by the invention, an experiment verifies that by using a TIGA1 gene as an effective target spot and combining an RNA (Ribonucleic Acid) interference technology and the glutaminase enzyme inhibitor, the drug resistance of cancer cells is remarkably reduced, and the anti-cancer activity of the glutaminase enzyme inhibitor is increased the method can be used for treating cervical cancer. Combination of the target spots and chemotherapy drugs such as the glutaminase enzyme inhibitor may be a means for increasing the curative effect of the chemotherapy drugs and reducing the death rate of the cervical cancer, and the anti-tumor effect of the glutaminase enzyme inhibitor is greatly increased.

This invention discloses monoclonal antibodies (MAbs) which have little or no signaling activity as monomers become potent anti-tumor agents when they are converted into homoconjugates. The homoconjugates exert anti-growth activity by signaling G0 / G1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and does not require an Fc portion. These conjugates are potent, anti-tumor agents.

The invention is based in part on the discovery that uncoupling proteins (UCPs) are expressed in the plasma membrane of rapidly dividing cells but not of growth arrested, chemotherapy resistant cells. It has also been found according to the invention that UCP is expressed in the lysosomal membrane under certain metabolic conditions. Thus the invention is methods, products, screening assays and kits relating to the manipulation of UCP expression within cellular and intracellular membranes.

In a method of arresting fatigue crack growth in a metal member, a hole is formed beside a tip portion of a fatigue crack with respect to a crack extension direction, in a metal member body, in which the fatigue crack occurs due to an action of applied cyclic tensile stress. Then, a press-fit object being higher in stiffness than the metal member body and larger in external size than the hole is press-fitted into the hole. Compressive stress is made to act on the tip portion of the fatigue crack from directions lateral to the crack extension direction.

The invention is based in part on the discovery that uncoupling proteins (UCPs) are expressed in the plasma membrane of rapidly dividing cells but not of growth arrested, chemotherapy resistant cells. It has also been found according to the invention that UCP is expressed in the lysosomal membrane under certain metabolic conditions. Thus the invention is methods, products, screening assays and kits relating to the manipulation of UCP expression within cellular and intracellular membranes.

The present invention describes a single-protein production (SPP) system in living E. coli cells that exploits the unique properties of an mRNA interferase, for example, MazF, a bacterial toxin that is a single stranded RNA- and ACA-specific endoribonuclease, which efficiently and selectively degrades all cellular mRNAs in vivo, resulting in a precipitous drop in total protein synthesis. Concomitant expression of MazF and a target gene engineered to encode an ACA-less mRNA results in sustained and high-level (up to 90%) target expression in the virtual absence of background cellular protein synthesis. Remarkably, target synthesis continues for at least 4 days, indicating that cells retain transcriptional and translational competence despite their growth arrest. SPP technology works well for yeast and human proteins, even a bacterial integral membrane protein. This novel system enables unparalleled signal to noise ratios that should dramatically simplify structural and functional studies of previously intractable but biologically important proteins. The present invention also provides an optimized condensed single protein production system.

The invention relates to application of lncRNAGAS5 as an early stage age-related macular degeneration (AMD) diagnostic marker. Expression difference of lncRNAs between an early stage AMD patient and apatient in a control group is detected by virtue of a gene chip, growth arrest specific transcripts 5 (GAS5) are selected from all the differentially expressed lncRNAs for further verification, clinical sample capacity is expanded, circular lncRNA expression is carried out by adopting a fluorescent quantitative PCR method, contents of lncRNA in the AMD patient and the control group are compared,and feasibility of lncRNAGAS5 as the diagnostic marker is verified. ROC curve analysis indicates that area under the curve of GAS5 is 89.6%, so that GAS5 can be taken as the early stage age-related macular degeneration diagnostic marker.

The present invention provides for a genetically modified host cell in a growth-arrested state producing an antibiotic.

Provided herein are methods to suppress specificity protein (Sp) activity in a cell associated with a cell proliferative disease. The methods are effective to inhibit a microRNA in the cell using an antisense microRNA oligonucleotide which results in an increase in expression of a specificity protein (Sp) suppressor gene thereby inducing Sp degradation, apoptosis or growth arrest by releasing inhibitors of G2 / M (Myt-1) or inhibition. Also provided are methods of treating a cancer using the antisense microRNA oligonucleotide. In addition the present invention provides antisense microRNA-27a oligonucleotides useful in the methods described herein.

The use of modulators of Mre 11, tankyrase, the DNA damage pathway and MRN complex formation of the protection of mammals from failure of growth arrest, apoptosis or proliferative senescence.

A method of inducing cytostasis in a population of HIV-infected cells is disclosed which comprises applying to a population of HIV-infected cells a cytostatically effective amount of an inhibitor comprising an isolated peptide having the amino acid sequence FCRFLLCPSRTSD or SQCEQEGGRCRFLLCPSRTSNIGKLGCEPLWKC CKRWGG, or a conservative variant thereof, whereby cell growth in at least a portion of the HIV-infected cells is arrested, rendering the growth-arrested cells non-HIV producing. The peptide may be conjugated with an agent that is capable of selectively targeting HIV-infected cells.

The present method has anti-aging properties against high-glucose. The present invention reveals the anti-aging properties of antcin M (ANM) and elucidates the molecular mechanism underlying the effects. It is found that exposure of human normal dermal fibroblasts (HNDFs) to high-glucose (HG) for 3 days, cell phase arrest and senescence are accelerated. As confirmed through experiments, co-treatment with ANM significantly attenuates HG-induced growth arrest and promotes cell proliferation. In addition, treatment with ANM eliminates HG-induced reactive oxygen species through the induction of anti-oxidant genes via transcriptional activation of NF-E2 related factor-2 (Nrf2). Treatment with ANM abolishes HG-induced stress-induced premature senescence as evidenced by reduced senescence-associated β-galactosidase activity. Also, the HG-induced decline in aging-related marker protein, senescence marker protein-30, is rescued by ANM. Furthermore, treatment with ANM increases expression of silent mating type information regulation 2 homologs 1 (SIRT-1), and prevents SIRT-1 depletion.

A system and method for optimizing the systemic delivery of growth-arresting lipid-derived bioactive drugs or gene therapy agents to an animal or human in need of such agents utilizing nanoscale assembly systems, such as liposomes, resorbable and non-aggregating nanoparticle dispersions, metal or semiconductor nanoparticles, or polymeric materials such as dendrimers or hydrogels, each of which exhibit improved lipid solubility, cell permeability, an increased circulation half life and pharmacokinetic profile with improved tumor or vascular targeting.

The invention discloses a composition for promoting a therapeutic effect of a retina degenerative disease gene and an application thereof. A research proves that the long-term C-MER proto-oncogene tyrosine kinase (MerTK) mutation can cause the serious reconstruction of a retina micro-environment, the growth arrest specific gene 6 (Gas6) necessary for MerTK exerting function is extremely reduced and the relative component of phagocytosis path is influenced, so that the joint overexpression of exogenous tyrosine kinase family receptor MerTK and ligand Gas6 is adopted for inducing retina pigment epithelial cell phagocytic ability, the retinitis pigmentosa pathology course caused by the cell phagocytic function disorder can be relieved and the theory and technical base are established for the treatment of such diseases.

A use of a compound in obtaining cytoskeleton and cell elongation is disclosed, the compound is 7-chloro-6-piperidin-1-yl-quinoline-5,8-dione with a chemical formula of C14H13CIN2O2, is designated as PT-262. The PT-262 can induce cell elongation by stabilization of the F-actin and induction of the abnormal actin polymerization in cancer cells, further, the PT-262 possesses antitumor activity and can block survival pathway of the cancer cells, resulting in cancer cells apoptosis, and the PT-262 can induce growth arrest and inhibition of cell cycle. PT-262 stabilizes cancer cells cytoskeleton that results in an irreversible cell elongation, decreases the levels of cyclin B1 and phospho-cdc2 proteins, and inhibits the survival signal pathway of Ras-ERK proteins. The PT-262 also inhibits the mitochondrial membrane potential and induces the caspase-3 activation and apoptosis in the cancer cells.

Genomic analysis of ovarian cancers demonstrated a regional chromosomal increase in expression and gene duplication. TGF-β stimulation indicated a link between SnoN RNA and TGF-β. In TIOSE, SnoN protein levels were reduced 15 min post TGF-β-stimulation, likely by proteosome-mediated degradation. SnoN inhibition decreased cell growth between 20 and 50% concurrent with increased p21 levels. Stable expression of SnoN led to growth arrest through induction of senescence. Collectively, these results implicate SnoN levels in multiple roles during ovarian carcinogenesis: promoting cellular proliferation in ovarian cancer cells and as a positive mediator of cell cycle arrest and senescence in non-transformed ovarian epithelial cells.

The purpose of the present invention is to provide a cell culture medium, particularly a serum-free cell culture medium, that makes it possible to raise cell growth efficiency without using feeder cells. The present invention provides a serum-free cell culture medium containing growth arrest-specific 6 (GAS6).

The invention discloses a molecular marker for detecting susceptibility of ovarian cancer. Nucleotide sequences of the molecular marker are shown in SEQ ID NO.1, and mononucleotide polymorphism, namely T>C is present at 1506th site. A kit for detecting susceptibility of ovarian cancer comprises a pair of specific primers having sequences in SEQ ID NO.2 and SEQ ID NO.3. A method for detecting presence of mononucleotide polymorphism in GADD45A (growth arrest and DNA-damage-inducible protein 45 alpha) gene in a sample in vitro includes: firstly, amplifying the GADD45A gene in the sample by the specific primers to obtain an amplification product; secondly, subjecting the amplification product to sequence determination, and detecting presence of mononucleotide polymorphism, namely 1506T>C, in the amplification product. The method is simple, accurate and fast in detection and high in specificity, and is important to effectively implementing early diagnosis, early treatment and individual prevention and treatment to high risk groups or susceptible individuals and patients with ovarian cancer.

The present invention relates to a method for the treatment of anemia based on the administration of the product of growth arrest-specific gene 6 (Gas6), its mutants, variants, active derivatives and the physiological tolerated salts of said Gas6 derivatives or of a group of biologically active substances inducing a GAS6 expression or releasing action or of a group of compounds that activate the Sky, AxI or Mer receptor tyrosine kinases. Furthermore the invention relates to a pharmaceutically effective composition to treat anemia. The composition comprises a pharmaceutically effective amount of a product of growth arrestspecific gene 6 (Gas6), or its mutant, variant, active derivative or the physiological tolerated salts of said Gas6 derivative or a biologically active substance that induces GAS6 expression or GAS6 release or a substance that activates the Sky, AxI or Mer receptor tyrosine kinases.

In a method of arresting fatigue crack growth in a metal member, a hole is formed beside a tip portion of a fatigue crack with respect to a crack extension direction, in a metal member body, in which the fatigue crack occurs due to an action of applied cyclic tensile stress. Then, a press-fit object being higher in stiffness than the metal member body and larger in external size than the hole is press-fitted into the hole. Compressive stress is made to act on the tip portion of the fatigue crack from directions lateral to the crack extension direction.

The present invention describes a single-protein production (SPP) system in living E. coli cells that exploits the unique properties of an mRNA interferase, for example, MazF, a bacterial toxin that is a single stranded RNA- and ACA-specific endoribonuclease, which efficiently and selectively degrades all cellular mRNAs in vivo, resulting in a precipitous drop in total protein synthesis. Concomitant expression of MazF and a target gene engineered to encode an ACA-less mRNA results in sustained and high-level (up to 90%) target expression in the virtual absence of background cellular protein synthesis. Remarkably, target synthesis continues for at least 4 days, indicating that cells retain transcriptional and translational competence despite their growth arrest. SPP technology works well for yeast and human proteins, even a bacterial integral membrane protein. This novel system enables unparalleled signal to noise ratios that should dramatically simplify structural and functional studies of previously intractable but biologically important proteins.