59 results about "G1/S checkpoint" patented technology

The present invention refers to steroid derivatives for use as medicaments. More specifically, the invention also relates to the use of a steroid derivative of 5-androstene-, 5-pregnenolone or corresponding saturated derivatives (androstane- or pregnane-) in the manufacture of a medicament for the treatment of a benign and/or malignant tumour, which medicament is capable of interrupting disturbances in Wnt-signaling, such as cell-cycle arrest in G1-phase, and/or providing an angiostatic effect. Examples of such steroid derivatives are -5-androstene-17-ol, androstane-17-ol-pregnane-17-ol or pregnane-17-ol derivatives. In a further aspect, the invention relates to a method of producing a medicament for the treatment of a benign and/or malignant tumour and/or an inflammatory condition comprising the steps of contacting 5-androstane-3β,17-diol or androstane-3β-diol, an enzyme and a sulfotransferase to provide 5-androstene-17-ol-3β-sulfate or corresponding andros tane derivative (17-AEDS or 17-AADS); and mixing the 17-AEDS or 17-AADS so produced with a suitable carrier; whereby a medicament which is capable of acting as a ligand to peroxisome proliferators-activated receptor-(PPAR) is produced.

The present invention relates to the downregulation of surface receptor CCR5 expression through manipulation of the cell cycle in activated lymphocytes by administering a composition that arrests the G1 phase of the cell cycle, thereby reducing receptor sites for entry of HIV into T cells, and thus, the effects of HIV. Further, compositions are disclosed that include at least one G1 phase arresting agent and at least one antiviral agent, wherein the combination of agents synergistically enhances the activity of the antiviral agent.

The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest. Economical reutilization of protein coding sequences in this manner is without precedent in mammalian genomes, and the unitary inheritance of INK4a-p16 and ARF-p19 may reflect a dual requirement for both proteins in cell cycle control.

The invention belongs to the field of radiation sensitizing agents, in particular to an application of BTG2 (B cell translocation gene 2) in preparing a tumor radiation sensitizing agent for ionizing radiation including X-rays. The invention discloses an application of liposome mediated eukaryotic expression plasmid pcDNA3-BTG2 in preparing the radiation sensitizing agent, wherein the liposome mediated eukaryotic expression plasmid pcDNA3-BTG2 is transfected to MCF-7 (macrophage chemotactic factor-7) breast cancer cells and MDA-MB-231 breast cancer cells and expressed successfully, and the BTG2 protein can up-regulate the proapoptosis Bax protein and down-regulate the cell cycle regulatory protein Cyclin D1, and by promoting the cell apoptosis, G0/G1 phase arrest of the cells is promoted, thereby increasing the sensitivity of the breast cancer cells to ionizing radiation including the X-rays.

The present invention provides methods of producing a cloned non-human mammalian nuclear transfer (NT) embryo and methods for producing a cloned non-human mammal. Embodiments of the methods include introducing donor genetic material into a metaphase I oocyte; introducing donor genetic material into a non-enucleated oocyte; introducing donor genetic material obtained from a donor cell that is at metaphase into an oocyte; introducing donor genetic material into an oocyte, and naturally activating the oocyte or the NT embryo; and introducing donor genetic material obtained from a donor cell that is at late G1 phase into an oocyte.

The present invention relates to compositions and methods for inducing increased levels and availability of β-chemokines by administering to a subject at least one G1 phase arresting compound, wherein the increased levels and availability of β-chemokines block chemokine/viral receptors thereby preventing or treating viral infections.

The invention relates to application of demethylzeylasteral to preparation of a medicine for treating pancreatic cancer. The application proves that the compound demethylzeylasteral has a significant killing effect on human pancreatic cancer cells, can induce tumor cell cycle arrest in a G0/G1 phase and achieves a pancreatic cancer resisting effect through induction of autophagic death and Caspase-3-dependent apoptosis of the cells; in combination with gemcitabine, the demethylzeylasteral can significantly reduce the IC50 of the gemcitabine, and through combined drug administration, a better inhibitory effect on the human pancreatic cancer cells is achieved; at low concentration, the demethylzeylasteral can induce the autophagic death of the cells so as to improve the antitumor effect of the gemcitabine, while at high concentration, the demethylzeylasteral improves the chemotherapeutic effect of the gemcitabine mainly through promotion of the apoptosis. On the basis of the application, the demethylzeylasteral can be applied to preparation of the medicine for treating the pancreatic cancer, and the prepared medicine is combined with the gemcitabine for use, or the demethylzeylasteral can be used for researching a cell autophagy or apoptosis mechanism.

The invention relates to an application of long-chain non-coding RNA lncLCIR-1 as a lung cancer molecular marker. According to the invention, stable high expression of the lncLCIR-1 in lung cancer tissues is found for the first time, and the level of the lncLCIR-1 is reduced after radiotherapy, so that the lncLCIR-1 in the lung cancer is a potential index for predicting the curative effect of theradiotherapy, and is a novel lung cancer molecular marker. The application of the lncLCIR-1 detection reagent in preparing a reagent for diagnosing the prognosis of a lung cancer patient mainly uses the lncLCIR-1 as a detection marker to prepare a corresponding fluorescence quantitative PCR detection kit for detecting the prognosis of the lung cancer patient in radiotherapy. In addition, the siRNAcan inhibit the expression of lncLCIR-1, so that the cell cycle of the lung cancer is regulated, the G1 phase block of the lung cancer cell is caused, the proliferation of the lung cancer cell is inhibited, and the siRNA has important significance in the preparation of a medicament for treating the lung cancer.

The invention relates to application of miR-486-5p in a non-small cell lung carcinoma cell line. The miR-486-5p performs specific low-expression in a non-small cell lung carcinoma cell and a series of lung carcinoma tissue clinical specimen; in an H1299 cell, the over-expressed miR-486a-5p can inhibit cell proliferation of H1299 and inhibit G1/S conversion to block the cell in the G1 phase. Experiments based on bioinformatics analysis discovers that the miR-486a-5p is complementary with 3'-UTR () of a target gene mRNA (messenger ribonucleic acid), so that translation of the mRNA of the target gene can be inhibited or the mRNA of the target gene can be directly degraded; furthermore, western blotting and other experiments prove that the CDK4 gene is the target gene of the miR-486a-5p. The experiment first proves that the CDK4 gene is the garget gene of miR-486a-5p, and the miRNA is utilized to diagnose and treat non-small cell lung carcinoma in clinical application, and a certain application value is created for providing the aspect of drug targets.

The invention discloses a preparation method and application of a dual-targeting DNA nano drug-loaded complex. DNA single chains S1, S2, S4, S5, S7 and S8, a nucleic acid aptamer 1, a natural nucleic acid aptamer AS1411 and chemically modified nucleic acid four ligands AS1411-1, AS1411-2 and AS1411-3 are mixed in a TM buffer solution, the mixture is placed in a PCR instrument to be constructed, and a DNA tetrahedral Aptamer 1-AS1411, a DNA tetrahedral Aptamer 1-AS1411-1, a DNA tetrahedral Aptamer 1-AS1411-2 and a DNA tetrahedral Aptamer 1-AS1411-3 are obtained through construction respectively. According to the preparation method and application of the dual-targeting DNA nano drug-loaded complex, four dual-targeting DNA nano drug-loading systems based on CD44 and nucleolin nucleic acid aptamers are constructed, and compared with a single-targeting drug-loading complex and a negative control group, four dual-targeting drug-loaded complexes have stronger nuclease degradation resistance, capability of targeting melanoma A375 cells, capability of inhibiting proliferation of the A375 cells and capability of inducing the A375 cells to generate G1 phase retardation.

The invention discloses a composition for inhibiting glioma growth and an application thereof. The composition comprises a substance for improving the expression of protein (PTEN) as shown in sequence 1 of the sequence table, and a substance for inhibiting the expression of protein (B) as shown in sequence 3 of the sequence table. Experiments demonstrate that when the combination of recovering the expression of protein PTEN with inhibiting the expression of protein B is compared with only recovery of the expression of protein PTEN or only inhibition of expression of protein B, the AKT phosphorylation level of recombinant glioma cell lines is significantly decreased, cell proliferation and colony formation are significantly inhibited, and the proportion of cells stopping at the G0/G1 phase and the cell apoptosis rate are significantly increased; Glioma in transplanted mouse body has no increase in size at 20-48 days after treatment by recovering the expression of protein PTEN combined with inhibiting the expression of protein B, and the tumor weight is almost zero at the 48th day after the treatment. The invention provides a new and effective combination therapy scheme for glioma, and has wide application prospects.

The p53 messenger RNA nanoparticles, a preparation method thereof and an application thereof in preparing a drug for treating tumors belong to the technical field of genetic engineering. The p53 messenger RNA nanoparticles are prepared by the following method: 1, chemically modified p53mRNA is synthesized in vitro; and 2, a nano-system is prepared by a self-assembly method to deliver the p53 messenger RNA in vivo. The p53 messenger RNA nanoparticles play an anti-tumor and chemosensitivity-enhancing therapeutic role by restoring the anti-tumor function of p53. The advantages of the invention are as follows: 1, the p53 messenger RNA in the invention is successfully delivered to the p53 inactivated liver cancer and lung cancer tumor cells through the nano-system to effectively and rapidly induce cell apoptosis and G1 phase cell cycle arrest in vivo and in vitro, thus significantly inhibiting the growth of tumor cells; and 2, the p53 messenger RNA delivered by the nanoparticles can enhancethe anti-tumor effect of a mTOR inhibitor everolimus by supplementing the tumor suppressor p53 deleted in the tumor.

The invention relates to an anti-tumor medicine for treating glioblastoma, wherein the medicine is avasimibe. The medicine provided by the invention induces apoptosis through a mitochondrial pathway to realize the activity against the glioblastoma; the medicine provided by the invention induces the apoptosis by non-specifically blocking a cell cycle; and the medicine provided by the invention induces the cell cycle to be blocked in a G0/G1 phase and a G2/M phase through a p53-dependent pathway.

The invention discloses application of isoliensinine in preparation of drugs for targeted inhibition of AKT activation. Studies show that the AKT activation is obviously inhibited after cervical cancer cells are treated by the isoliensinine; the isoliensinine inhibits AKT activation passages, up-regulates p21 expression, and down-regulates expression of cyclin E1 and cyclin-dependent kinase CDK2,so that the cervical cancer cells are arrested in the G1 phase, the proliferation and migration of the cervical cancer cells are inhibited, and apoptosis is induced. A new medial use of the isoliensinine is provided, a new alternate drug is provided for treatment of cervical cancer, and the application is of great clinical significance.

The invention relates to an application of NOB1 gene in treating a brain glioma disease. NOB1 gene can regulate and control cell cycle of human glioma to reduce G1 phase stagnation in the cell cycle caused by NBO1 level; in addition, the NOB1 gene can regulate and control proliferation of human glioma cells to inhibit growth retardation of the glioma cells caused by the NOB1; moreover, the reduction of the NOB1 can prevent occurrence of the human glioma cell tumor. The study finds the NOB1 of the invention is necessary to inhibiting the occurrence of brain glioma in vivo or in vitro; in addition, according to the expression result of the NOB1 gene in the brain glioma tissue, the NOB1 gene provides powerful means for biological targeted therapy of the glioma in the future.

The invention discloses an establishment and synthesis method of a dual-targeting DNA (deoxyribonucleic acid) nano drug-loaded complex. The drug-loaded complex is prepared by the following steps: simultaneously connecting an Aptamer 1 and a natural AS1411 or a chemically modified AS1411 to a DNA tetrahedron in a manner of complementary base pairing, so as to respectively obtain a DNA tetrahedral Aptamer 1-AS1411, a DNA tetrahedral Aptamer 1-AS1411-1, a DNA tetrahedral Aptamer 1-AS1411-2 and a DNA tetrahedral Aptamer 1-AS1411-3. The drug-loaded complex is applied to preparation of drugs for treating melanoma. According to the invention, four dual-targeting DNA nano drug-loaded systems based on CD44 and nucleolin nucleic acid aptamers are constructed, and compared with a single-targeting drug-loaded complex and a negative control group, the four dual-targeting drug-loaded complexes have stronger nuclease degradation resistance, capability of targeting melanoma A375 cells, capability of inhibiting proliferation of the A375 cells and capability of inducing the A375 cells to generate G1 phase retardation.

Novel synthetic bis(benzylidene-benzenamine)disulfides and the preparation method are disclosed in the present invention. These compounds are afforded with the oxidizing reagent at low temperature and short time period via intra-molecular coupling reaction. In vitro experiments have been revealed that bis-disulfides are cytotoxic to cancer cells, especially human breast cancer cells MCF-7. Additionally, bis-disulfides arrest the cell cycle at sub-G1 phase and increase p38 phosphorylation to result in apoptosis. Bis-disulfides also inhibit growth of murine melanoma B16 cells but have no cytotoxicity to human fibroblasts. Bis-disulfides also can reduce murine melanoma size in the mouse model. The prepared compounds of the invention would be applicable in anti-cancer and anti-tumor therapies.

The invention relates to the field of virology, in particular to novel application of doublecortin-like kinase 1 (DCLK1), wherein the application is to prepare a J subgroup avian leukosis virus replication enhancer. According to the invention, it is found that the DCLK1 can interact with ALV-J SU protein and promote a cell cycle to be converted from the G1 phase to the S phase so as to remarkably increase the ALV-J replication amount, and on this basis, the ALV-J replication amount is remarkably increased. a DCLK1 overexpression plasmid pcDNA3.1-DCLK1 transfected DF-1 cell is constructed, so that the DCLK1 is highly expressed in the cell, ALV-J replication is remarkably promoted, the virus yield is improved, the DCLK1 has no toxic or side effect on the cell, and the DCLK1 can be used as a virus replication enhancer to be applied to culture of ALV-J.

Methods for collecting cells in M phase or G₁ phase, by which the percentage of M phase or G₁ phase cells is higher than that attained by the conventional methods are disclosed.