203 results about "Mouse tumor" patented technology

The invention discloses application of a crRNA mediated CRISPR/Cas13a gene editing system in tumor cells. According to the invention, in a U87 glioma cell system, a Cas13a protein can be mediated ontocomplementary target RNA by single-stranded crRNA and is cut. Meanwhile, the Cas13a protein can also trigger a joint shearing effect in eucaryotic cells, i.e., after starting to cut a first piece oftarget RNA, the Cas13a protein carries out aimless random cutting on other encountered RNA so as to take effects of inhibiting and killing tumors, such as effects of reducing a tumor cell index, inhibiting a mouse tumor formation rate and a tumor size. The invention provides a novel method for inhibiting or killing the tumor cells so as to lay a foundation for application of a random shearing effect of the CRISPR-Cas13 system in eukaryotic cells.

The invention discloses 14 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters shown in the general formula I. In the general formula I, AA represents L-Ser residue, L-Glu (OBzl) residue, L-Phe residue, L-Val residue, L-Arg residue, L-Tyr residue, L-Ala residue, L-Trp residue, L-Asn residue, L-Met residue, L-Ile residue, Gly residue, L-Asp (OBzl) residue or L-Leu residue. The invention discloses a preparation method of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters, discloses HT-29, K562, A549 and HL60 tumor cell growth inhibition effects of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters, further discloses S180-loading mice tumor growth inhibition effects of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters, and also discloses use of the 3H-imidazo[4,5-c]pyridine-6-formyl-amido acid benzyl esters as antitumor drugs.

The invention discloses a recombinant Ganoderma Lucidum immunomodulatory protein (rLZ-8) which has anti-tumor effect and is expressed by Pichia pastoris, and a pharmaceutical preparation thereof. The rLZ-8 has the effect of directly killing or damaging NB4 or K562 or HL-60 or S180 or H22 cells and not affecting normal cells; and the rLZ-8 can quickly and efficiently induce a plurality of tumor cells to apoptosize in vitro, can also effectively kill the tumor cells in a body of a mouse tumor model, has no obvious toxic side effect, and can keep or raise the level of leucocytes. In addition, the invention also provides an anti-tumor pharmaceutical preparation type taking the rLZ-8 as a core composition.

The invention discloses conjugates of beta-carboline-3-carboxylic acid and oligopeptides, preparation, a nano structure, and an application thereof as an antitumor agent. The invention discloses conjugates (8a-f) of beta-carboline-3-carboxylic acid and six oligopeptides, wherein the six oligopeptides are Leu-Pro-Asn-Ile-Ser-Lys-Pro (LPNISKP), Arg-Gly-Asp-Ser (RGDS), Arg-Gly-Asp-Phe (RGDF), Arg-Gly-Asp-Val (RGDV), Leu-Asp-Ser (LDV), and Lys-Glu (KE). The invention discloses a preparation method and nano structure of the conjugates, discloses an inhibition effect of the conjugates on five tumor cell strains namely HL60, HCT-8, HeLa, BEL-7402, and HepG2, and further discloses an inhibition effect on tumor growth of S180 tumor-bearing mice. The experiment results show that the provided conjugates of beta-carboline-3-carboxylic acid and six oligopeptides have an excellent antitumor effect, so that the conjugates is advantageous for being used as an antitumor drug in clinic.

The invention discloses application of A-nor-5 alpha-androstane compounds in preparation of malignant tumor resistant medicaments. The compounds have the following general formula I, and comprise Ia, Ib, Ic, Id, Ie and If. The growth inhibition rate of the A-nor-5 alpha-androstane compounds for in-vitro human liver cancer cell Hep 3B, human breast cancer MDA-MB-231, human lung adenocarcinoma A549 and mouse melanoma B16 is higher than 85% on average, and even up to 99.98% to the maximum. The in-vivo test proves that the inhibition rate of the A-nor-5 alpha-androstane compounds for mouse tumors, such as intestinal cancer C26, liver cancer H22, Lewis lung cancer, breast cancer, B16 melanoma and the like, is higher than 50% on average, and even up to 63.19% to the maximum. The result proves that the compounds disclosed by the invention have an obvious malignant tumor resistant action. The A-nor-5 alpha-androstane compounds disclosed by the invention have an obvious and broad-spectrum action on inhibiting growth of malignant tumor cells, and are novel targeted malignant tumor resistant medicaments with low drug toxicity and favorable treatment effect; and the A-nor-5 alpha-androstane compounds just specifically act on tumor cells, but not influence normal cells, thereby having a high clinical application value.

The invention provides a preparation method of organoid spheres. The preparation method comprises the steps that matrigel containing cells and fluorocarbon oil are introduced into a three-way device to obtain cell spheres, and after culture is performed, the organoid spheres are formed; according to the preparation method of the organoid spheres, the micro-fluid control method is adopted for generating mono-disperse biomaterial organs, high-throughput production is achieved, the sizes, shapes and structures of organoids are controllable and uniform, and compared with a 2D tumor sensitivity predicting model, the organoids are combined with tumor micro-environment factors, and the prediction result is more accurate; compared with a PDX mouse tumor sensitivity predicting model, the modeling period is shorter, and the cost is lower; compared with common gene sequencing, the clinic predicting rate is higher; the preparation method of organoid spheres has the important significance and valuefor clinic application, and the important basis is supplied to detection of related results.

The invention provides a bispecific antibody as well as a preparation method and an application thereof. Meanwhile, the invention also provides a mouse tumor cell line expressing human-derived HER2 protein and an application of the cell line. The bispecific antibody provided by the invention can set up a bridge between the target cell and the functional molecule (cell) to activate an oriented immunoreaction, and has a broad application prospect in tumor immunotherapy. A tumor cell in-vivo efficacy experiment of the bispecific antibody provided by the invention is developed in an animal model with a complete immune system, wherein the tumor is killed by the cells of the immune system, and the efficacy of the bispecific antibody mediating the immune cells to kill the tumor cells can be effectively reflected, and thus a perfect efficacy evaluation method is provided for developing a bispecific antibody drug targeting immune cells and tumor cells.

The invention belongs to the technical field of nanometer materials, and particularly relates to a zinc oxide-gadolinium-drug composite nanoparticle, and a preparation method and application thereof. The composite nanoparticle comprises a zinc oxide nanocrystal core, a polymer shell, gadolinium (III) ions modified by coordinate bonds and surface-loaded anti-cancer drug molecules, has high stability, luminescence property and magnetic relaxation rate and can be applied to cell and small animal fluorescence imaging, magnetic resonance imaging, mouse tumor treatment and the like. The preparation method includes coating a zinc oxide nanoparticle with a polymer through two copolymerization reactions, coordinating a large quantity of carboxyl groups carried by the polymer with the gadolinium (III) ions to magnetize the nanoparticle, and loading the drug molecules onto the surface of the nanoparticle. A nanoparticle drug loading platform has a good fluorescence-magnetic resonance imaging function, high drug loading rate and high release rate, is low in toxicity and is completely degraded in mouse bodies without residues, thereby having better biosecurity and medication specificity than anti-cancer drugs.

The invention discloses a technetium-99m labeled isocyanide-containing FAPI derivative with a structural general formula of [99mTc-(CN-FAPI) 6] < + > and a preparation method and an application thereof. The [99mTc (CNFAPI) 6] < + > complex is obtained through two steps of synthesis of a ligand CN-FAPI and preparation of [99mTc-(CNFAPI) 6] < + >. The complex is simple and convenient to prepare, high in radiochemical purity and good in stability, has relatively high uptake and good retention at tumor parts of tumor-bearing mice, has specificity in tumor uptake, and is a novel tumor imaging agentwith popularization and application values.

The invention provides a gene for encoding HPV (human papilloma virus) 6-type L2N120E7E6 fusion protein, expression vectors, a method, a bacteria strain and an application. The invention is characterized in that prokaryotic expression vectors are utilized to fuse HPV 6-type L2N-end 120 amino acids, E7 proteins and E6 proteins, and constructing the encoded gene according to the amino acid of the fusion protein. In the invention, the gene for encoding the HPV 6-type L2N120E7E6 fusion proteins is successfully designed and the expression vectors and the transformation bacteria strain of the high-expression HPV 6-type L2N120E7E6 fusion proteins are successfully constructed; and in the fusion proteins, the immunogenicity is strong, the immunoreaction of specific T cells can be induced, the tumor forming time of mice can be obviously delayed, and the growth of the tumors of 20% mice is completely restrained. The invention can be used for preventing and treating HPV 6-type infection and relevant diseases, such as genital wart.

The invention relates to a codon-optimized gene of a 16-type L2E7 recombinant protein of human papilloma virus (HPV), which can be expressed efficiently in colibacillus. The optimized gene can be expressed efficiently by being inserted in a prokaryotic expression vector pET9a, and the expression level accounts for 50% of all viruses; an expression protein is immune to mice after being purified. Proved by experiment results, the protein has the same immunogenicity with a protein which is not expressed by the optimized gene and can induce the release of specific gamma-1NF; proved by tumor growth inhibition animal experiments, protein immunity has evident inhibition effect on tumor growth and the growth of 90% of mouse tumor cells can be inhibited completely. The prokaryotic high-efficiency expression system of L2E7 recombinant protein, which is established by the optimized gene, can be used in the pilot scale production and drug discovery of preventive and curative vaccines of HPV16 infection and relevant cervical carcinoma.

The invention relates to an application of Trichoderma pseudokoningii extracellular polysaccharides having anticancer activities. The Trichoderma pseudokoningii extracellular polysaccharides having the anticancer activities can reduce the vitality of K562 cells in vitro when they are applied to tumor growth inhibition (auxiliary) medicines, so intracellular active oxygen and free calcium ion concentrations are improved, the expression abundance of mRNA of p53 and Bax genes is improved, the expression of the Bc1-2 transcription level is reduced, the ectropion of cell membrane phosphatidylserine of the human chronic granulocyte leukemia cells K562 is induced, and the nuclear polycondensation and the fragmentation of K562 are induced to generate apoptotic bodies and apoptosis; and in-vivo administration can increase weights of tumor bearing mice and alleviate growth speeds and weights of tumors of the tumor bearing mice, thereby tumor cell killing and tumor growth inhibiting purposes are reached.

The invention provides a human papilloma virus (HPV) 18 type L2NE7E6 fusion protein gene efficiently expressing in Escherichia coli, and an expression vector, a preparation method, a strain and a use thereof L2N protein, E7 protein and E6 protein amino acid sequences of 11th-200th amino acids of an HPV18 type L2 protein are fused, a codon optimization gene suitable for Escherichia coli expression is designed, the codon optimization gene is inserted into a prokaryotic expression vector pET9a to obtain a pET9a-HPV18L2NE7E6 expression vector and its conversion strain, the expression level accounts for 50% of all bacteria, an antibody generated by a pure fusion protein immune mouse can neutralize an HPV18 type pseudovirus in order to generate a specific T cell immune response and obviously postpone the tumor formation time of the mouse, and the growth of 20% of mouse tumors can be completely inhibited. The fusion protein can be used for developing vaccines for preventing and treating HPV18 type infection and relevant diseases.

The invention discloses a compound with a general formula of 99mTc (HYNIC-FAPI) (tricine/TPPTS) technetium-99 m labeled FAPI derivative containing hydrazino-nicotinamide, and a preparation method and application thereof. By two steps of synthesis of ligand HYNIC-FAPI and 99mtc (HYNIC-FAPI) (tricine/TPPTS) preparation, the 99mTc (HYNIC-FAPI) (tricine/TPPTS) complex is obtained. The complex has the advantages of simple preparation, high radiochemical purity and good stability, has high uptake and good detention at tumor parts of tumor-bearing mice, has specific uptake in tumors, and is a novel tumor radiopharmaceutical with clinical application value.

The invention discloses a camptothecin derivative, and a preparation method and application thereof to preparation of medicament for treating tumor. The camptothecin derivative has a following structural formula; and the derivative, salts and composition thereof can be applied to preparation of medicaments for treating mammalian cell proliferative diseases, such as cancer. Through its own medicament molecular design and further biological activity determinations in vitro and in vivo, the prepared and synthesized compound is proved to have obvious inhibitory activity on various cancers, and shows good results in models for inhibiting growth of mouse tumor.

Methods of identifying specific target molecules for design of anti-angiogenic and vascular targeting approaches are disclosed. Transcriptional profiles of tumor endothelial cells were compared with that of normal resting endothelial cells, normal but angiogenically activated placental endothelial cells, and cultured endothelial cells. Although the majority of transcripts were classified as general angiogenesis markers, 17 genes were identified that show specific overexpression in tumor endothelium. Antibody targeting of four cell-surface expressed or secreted products (vimentin, CD59, HMGB1 and IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. The results demonstrate the utility of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.

The invention discloses a near infrared conjugated polymer, a preparation method of the near infrared conjugated polymer, and application of the near infrared conjugated polymer to living body imagingand living body tumor treatment. The conjugated polymer is prepared from platinum complexes and alkyne monomers through polymerization. The Pt coupling effect is used for improving the photothermal treatment effect; the photophysical property of the polymers is regulated through a conjugated system, so that the conjugated polymer which has the near infrared ray absorption performance and the goodphotothermal imaging effect and can be used for living mouse tumor treatment is obtained. The conjugated polymer can be used in the technical fields of photodynamics therapy, photothermal therapy, biomarking and detection and the like under the photothermal imaging guidance. The preparation process is simple; the raw materials are cheap and rich; the industrial production is convenient. The structure general formula of the near infrared conjugated polymer is shown in the description.

The invention discloses a preparation and application of an oral tumor vaccine with attenuated salmonella typhimurium as a vector. The preparation of the vaccine comprises the following steps: (1) firstly, establishing a recombined vaccine vector integrating a micro gene with a self-transfer system through a molecular biological method; and (2) electrically transforming the recombined vaccine vector created in the step (1) into attenuated salmonella typhimurium SL7207 to establish the recombinant oral tumor vaccine. According to the preparation disclosed by the invention, the micro gene and the self-transfer system are integrated onto one vector for the first time, the salmonella typhimurium is electrically transformed to obtain the oral tumor vaccine, and the immune prevention effect of the vaccine on tumors is verified by a mouse tumor model, so that the oral tumor vaccine can be applied in the field of preparing immune preventive medicines for tumors.

The invention relates to a genetically modified cell of coexpression mouse membranous type interleukin 15 and retinoic acid early transcript 1 epsilon (Rae-1 epsilon) and a preparation method thereof. The genetically modified cell is a BaF3 cell which can stabilize the genetically modified cell of the coexpression membranous type IL-15 and Rae-1 epsilon protein. The genetically modified cell can be prepared by a method comprising the following steps: amplifying a mouse Rae-1 epsilon gene and a mouse membrane expression type IL-15 gene by a polymerase chain reaction (PCR) technology; respectively inserting the amplified mouse Rae-1 epsilon gene and the amplified mouse membrane expression type IL-15 gene into two polyclone sites of an eukaryotic expression vector pVITRO2-mcs to acquire a recombined vector; transfecting the recombined vector into a mouse tumor cell strain BaF3; and acquiring the genetically modified cell by antibiotics screening and flow cytometry sorting. The genetically modified cell can provide IFN-gamma producing killer dendritic cells (IKDC) with triple stimulating signals as an instrument for efficiently amplifying and activating the IKDC in vitro. In addition, the genetically modified cell can also be used for antineoplastic immunotherapy research.

The invention discloses medical applications of four buxus alkaloids compounds in the preparation of antitumor medicines. Experiment results show that the four compounds KBA01, KBA02, KBA03 and KBR18, under the condition of concentration without toxicity to wild normal mouse embryonic fibroblast cells, can selectively kill mouse tumor cells with tumor specific mutant genes p53 and Ras; accordingly, the compounds are very strong in killing activity to human colon cancer cell strains with p53 mutants, but not strong in killing activity to human wild colon cancer cell strains with p53 mutants; and as shown in a GFP (Green Fluorescence Protein) reporter vector screening system of a gene promoter, the compounds KBA02 and KBA03 can activate a promoter of a cancer suppressor gene p16. The characteristics indicate that the compounds from the four buxus plant origins have application potentials for preparing personalized treatment medicines aiming at the tumor mutant genes p53 and Ras as well as the cancer suppressor gene p16.

The invention relates to a recombined extrasin alpha 1 two-strand body protein and a preparation method thereof. Glycin and serine are connected in series with bimolecular extrasin alpha 1 (T alpha 1), a connection mode is as follows: T alpha 1-Gly-Ser=T alpha 1, and an extrasin alpha 1 two-strand body gene expression vector is constructed by synthesized extrasin alpha 1 two-strand body genes so that extrasin alpha 1 which can not be directly expressed in colon bacillus can be efficiently expressed in the colon bacillus in a two-strand body way. The purified extrasin alpha 1 two-strand body protein has biological activity and can promote lymphocytes of small mice to proliferate, restrain tumor cell strains from proliferating and obviously restrain the tumor growth of tumor-bearing mice, thereby establishing a base for the further research and the extensive application of the extrasin alpha 1.

The invention provides a method building a mice portable breast cancer tumor cell suspension orthotopic model. The method building the portable breast cancer tumor cell suspension orthotopic model comprises the following steps that a mice spontaneous breast cancer tumor is grinded in a mesh screen, centrifugation is conducted, tumor cell suspension with cell contraction of (0.7-1.9) * 106 cell/mL is manufactured by nutrient solution in a deployed mode, 0.2 to 0.4 mL of the tumor cell suspension is injected under the front limb armpit skin of each mouse, the mice are bred normally for 9 to 21 days, and the construction of the mice portable breast cancer tumor cell suspension orthotopic model is finished. An injected tumor cell is formed by real C3H mice tumor cells inside the body of the mouse by grinding, the growing process of the breast cancer cell inside the mouse body is simulated, and the mice are bred normally without a particular environment after the injection is finished. After transplantation, lesions are found to be formed by the C3H at the front limb armpit of the mice are found through detection, the method building the mice portable breast cancer tumor cell suspension has the advantages of being high in occurrence rate, short in time, high in tumor formation rate, low in cost and the like, and therefore the method building the mice portable breast cancer tumor cell suspension can be widely applied to experiments of breast cancer treatment.

The invention belongs to the technical field of medical bio-engineering, and particularly relates to new application of the signal adjusting protein alpha(SIRP alpha). The signal adjusting protein alpha(SIRP alpha) belongs to a member of the immunoglobulin super family(IGSF). In-vitro biological experiments and in-vivo animal experiments prove that in the application of the signal adjusting protein alpha(SIRP alpha) in the preparation of the DC vaccine for preventing and treating tumors of the invention, the SIRP alpha signal path negatively regulates the activity and antigen presentation functions of the DC. The invention further constructs a tumor DC vaccine which can interfere with the SIRP alpha expression by the mediation of a lentiviral vector, and the tumor DC vaccine can obviously improve the DC activation level and the antigen presentation function of the DC and be used for preventing and treating mouse tumors and is a novel tumor vaccine. The invention provides a new idea for clinical treatment application of the SIRP alpha.

The invention discloses a human and mice tumor suppressor and coded protein, wherein the gene relates to the regulation and control for encoded proteins and cell cycles, thus is closely related to the occurrence of tumors, the gene, the encoded protein and their derivatives can be used for diagnosis and treatment for tumor diseases caused by cell cycle control imbalance and medicament screening.

The invention discloses a preparation method of a near-infrared fluorescent compound which accurately targets tumor cells and is activated by beta-galactosidase, wherein the structure of the fluorescent compound is shown in a formula I. The probe compound combines a substrate alphaD-galactose (alphaD-gal) recognized by beta-galactosidase with cyanine near-infrared fluorophores to introduce an alphavbeta3-integrin receptor-targeted ligand c-RGD. The ability of the ligand c-RGD targeting tumor cells is utilized for near-infrared imaging of live mouse tumors overexpressing beta-galactosidase. Theprobe has the advantages that receptor-mediated cell uptake and molecular target activation are combined to realize real-time and non-invasive detection of beta-galactosidase in living tissues. The probe can be successfully applied to improve cancer imaging and promote effective cancer diagnosis.

Embodiments of the invention provide mouse tumor models involving either the B16 mouse melanoma or MXT mouse mammary tumor, untreated or treated with chemotherapy and/or anti-cachectic agents, for the study of tumor-generated or cancer therapy-generated cachexia-inducing signals and mechanisms. Other embodiments of the invention also provide additional models, including pre-treatment of mouse skin with anti-cachectic proteins prior to tumor implantation, for the study of anti-cachectic signals and mechanisms generated by the skin. To reduce or reverse tumor- and chemotherapy-induced cachexia, embodiments of the invention use the human proteins placental alkaline phosphatase, transferrin, α₁-antitrypsin preparations or combinations thereof as well as chemically synthesized CCDTHT or N,N-diethyl-N-methyl-2-[(9-oxo-9H-thioxanthen-2-yl)methoxy]-ethanaminium iodide or CCDTHT-like compounds.