21 results about "Metastasis model" patented technology

This invention relates to the application of β-sitosterol glycoside in the preparation of products for treating lung cancer. This invention creatively provides a new use for the active monomer β-sitosterol glycoside, demonstrating that β-sitosterol glycoside can significantly inhibit the migration ability of lung cancer cells at doses without cell proliferation inhibitors, clarifying the specificity of its anti-metastatic effect, and laying the foundation for further new drug development of this monomer component. Through an in vivo mouse lung metastasis model, this invention demonstrates that β-sitosterol glycoside effectively inhibits the formation of lung metastases while exhibiting no significant toxic side effects in experimental animals, demonstrating high safety, and providing a new candidate molecule for the development of low-toxicity, highly effective anti-lung cancer metastasis drugs.

The application specifically relates to a breast cancer invasion and metastasis model based on anisotropic collagen hydrogel and a construction method thereof, and belongs to the technical field of biomedical materials and tumor microenvironment. The anisotropic hydrogel with highly parallel arrangement of collagen fibers is prepared by adopting a PDMS mold pre-tensioning-stress rebound process, and the orientation index is 0.62+ / -0.05. The hydrogel has high matching of mechanical properties with the breast cancer microenvironment in vivo and good biocompatibility. The model can induce mature adipocytes to dedifferentiate and fibroblasts to transdifferentiate, and drive the breast cancer cells to have enhanced invasion and migration ability and EMT phenotype, and reproduce a pathological axis of "collagen orientation→adipocyte dedifferentiation→breast cancer invasion and metastasis". The process depends on the activation of a DDR1-integrin beta1-FAK-YAP signal path, and a DDR1 inhibitor can effectively reverse the above effects. The application can be used for breast cancer metastasis mechanism research and drug screening targeting the DDR1 path.

The invention belongs to the technical field of new applications of medicines, and particularly relates to an aniline pyridine TEAD degradation agent, a preparation method thereof and an application of the degradation agent in preparation of antitumor drugs. According to the research, a novel aniline pyridine TEAD degradation agent with a clear structure is designed and synthesized by coupling a TEAD palmitoylation inhibitor niflumic acid serving as a lead compound with a CRBN type E3 ligase ligand through connecting chains with different lengths and different types by virtue of a computer-aided drug design means. The influence of the optimal compound (XY-3L) on cancer cell proliferation and cell functions is detected in an in-vitro cell experiment, and the curative effect of the optimal compound (XY-3L) in a melanoma lung metastasis model is explored in vivo.

The application discloses application of pachymic acid B in preparation of a medicine for preventing peritoneal metastasis of gastric cancer and a medicine composition thereof. The pachymic acid B is chemically named as 3-O-acetyl-16alpha-hydroxydehydrotrametenolic acid. The in-situ transplantation peritoneal metastasis model of the gastric cancer proves that intraperitoneal injection of the pachymic acid B can significantly reduce the number of peritoneal metastasis nodules and tumor load, the prevention effect is equivalent to that of oxaliplatin, and there is no obvious organ toxicity. Further experiments prove that the pachymic acid B can up-regulate the mRNA and protein expression levels of SPRED2 genes in peritoneal tissues of the gastric cancer, and plays a role in a time-dose dependent manner. The pachymic acid B provided by the application is administered by intraperitoneal injection, can be prepared into a suspension containing sodium carboxymethyl cellulose, and is especially suitable for perioperative administration of gastric cancer primary focus resection. Compared with the prior art, the application has the advantages of clear composition, novel action mechanism, high safety, simple operation, strong accessibility and the like.

The invention relates to the technical field of biological medicines, in particular to application of four micro RNAs (Ribonucleic Acid) of miR-92a, miR-25, miR-30d and miR-30c and inhibitors targeting the four micro RNAs to preparation of medicines for resisting metastasis of multiple cancer species such as breast cancer, colorectal cancer and melanoma. When the nucleic acid inhibitor anti-agomirs targeting at least one of a set consisting of miR-92a, miR-25, miR-30d and miR-30c is used for treating metastasis of multiple cancer species, the anti-metastasis effect is remarkable, the universality is high, and the nucleic acid inhibitor anti-agomirs can show a strong inhibition effect in three different tumor metastasis models of breast cancer, colorectal cancer and melanoma; especially, when the four inhibitors are combined for use, the synergistic effect is prominent, the colorectal cancer liver metastasis load can be reduced by 90% or above, the breast cancer metastasis rate is reduced by 80% or above, the melanoma metastasis inhibition rate is 65% or above, and the composition is suitable for treatment of multi-cancer metastasis.

The present application relates to the field of animal model construction, and in particular to a melanoma liver metastasis model construction method, which uses a spleen injection method to construct a human melanoma A375-M1 cell line liver metastasis model, and is identified in vivo by PET-CT and MRI, and is identified ex vivo by Bouin's and H&E.The human melanoma liver metastasis tumor model constructed by the present application has the advantages of short construction time, simple method and 100% modeling success rate.This metastasis model simulates the development process and pathological characteristics of melanoma liver metastasis, solves the problem of the lack of an ideal animal model for human melanoma during liver metastasis, and helps to explore and screen the development of anti-liver metastasis drugs for human melanoma, and plays a positive promoting role in new strategies for anti-melanoma liver metastasis.

The invention discloses application of an IGF2BP2-m6A-VCAN-TLR2 (Insulin-like Growth Factor 2BP2-m6A-VCAN-TLR2) signal axis in preparation of a medicine for treating lymphatic metastasis of intrahepatic cholangiocarcinoma. Aiming at the problems of unknown lymphatic metastasis mechanism and lack of effective targets of intrahepatic cholangiocarcinoma, the invention discovers and verifies that mRNA binding protein 2 of insulin-like growth factor 2 is modified by m6A to regulate and control the expression of pluripotent proteoglycan so as to activate a Toll-like receptor 2 signal, promote macrophages to secrete vascular endothelial growth factor C and drive a brand new pathway of lymphatic metastasis. Based on this, the invention provides an inhibitor targeting the signal axis, especially a small molecule compound 8010-8498. Experiments show that the compound can significantly inhibit migration, invasion and epithelial-mesenchymal transition of bile duct cancer cells, reduce macrophage secretion of vascular endothelial growth factors C, effectively inhibit tumor growth and lymphatic metastasis in a nude mouse popliteal lymph node metastasis model and a spontaneous bile duct cancer model, and present a synergistic effect when combined with gemcitabine and cis-platinum.

This invention discloses a wasp venom peptide-M nanocomposite, its preparation method, and its applications, belonging to the field of medicinal chemistry. Using indocyanine green as a morphology mediator, this invention prepares an ultra-small particle size dendritic tetrasulfide by reacting it with triethylamine, hexadecyltrimethylammonium bromide, tetraethyl orthosilicate, and bis[3-(triethoxysilyl)propyl]tetrasulfide in water. Wasp venom peptide-M is then loaded onto this nanocomposite to obtain the wasp venom peptide-M nanocomposite. In vitro experiments have confirmed that this composite can significantly kill 4T1 breast cancer cells. Furthermore, thanks to its ultra-small particle size, it also exhibits good targeting and enrichment, significant anti-tumor efficacy, and excellent safety in a breast cancer brain metastasis model, providing a novel and efficient nanomedicine delivery system for brain tumor treatment and the development of related therapeutic drugs.

The utility model relates to the technical field of tumor cell metastasis models, in particular to a breast cancer circulating tumor cell remote metastasis model which comprises a base and a fixing rod, the fixing rod is fixedly connected to the base, the fixing rod is fixedly connected with a brain metastasis model, a placing component is installed on the brain metastasis model, and the placing component is fixedly connected with the brain metastasis model. The placing part comprises an inclined plate, a fixed plate, a movable plate, a pressed plate, a straight spring and a collecting box, the inclined plate is fixedly connected in the brain metastasis model, the clamping plate clamps small balls with different colors through the matching effect of the extrusion rod, the movable plate, the collecting box and other parts, the small balls can be taken out by pulling the clamping plate, and the small balls can be conveniently taken out. And residual water is left in the collecting box, so that the small balls can be quickly taken out, meanwhile, no water drips on the outer surface of the model, the situation that the transparency of the model is affected by water marks generated on the outer surface of the model due to water dripping is avoided, and the transparency of the organ model and the cleanliness of a placement environment are guaranteed.

The application discloses an IGF2BP2-m6A-VCAN-TLR2 signal axis in the preparation of a drug for treating intrahepatic cholangiocarcinoma lymphatic metastasis. In view of the problems of unknown intrahepatic cholangiocarcinoma lymphatic metastasis mechanism and lack of effective target, the application finds and verifies a new pathway that from insulin-like growth factor 2 mRNA binding protein 2, m6A modification regulates the expression of multi-functional proteoglycan, and then activates Toll-like receptor 2 signal, promotes macrophage secretion of vascular endothelial growth factor C and drives lymphatic metastasis. Based on this, the application provides an inhibitor targeting the signal axis, in particular, a small molecule compound 8010-8498. Experiments show that the compound can significantly inhibit cholangiocarcinoma cell migration, invasion and epithelial mesenchymal transition, reduce macrophage secretion of vascular endothelial growth factor C, and effectively inhibit tumor growth and lymphatic metastasis in a naked mouse popliteal lymph node metastasis model and a spontaneous cholangiocarcinoma model. The compound presents a synergistic effect in combination with gemcitabine and cisplatin.

The invention provides a lung cancer cell LLC-ML2 as well as an establishment method and application thereof. The lung cancer cells are used for highly expressing CD18 molecules, Strc molecules, Cd79a molecules, Amigo2 molecules, Plet1 molecules, Angptl4 molecules and Plac1 molecules; ddx3y, Cbr3, Sox11, Pid1, Kdm5d, Eif2s3y and Capn6 molecules are not expressed or are subjected to low expression. The LLC cell strain is obtained by inoculating common LLC cells to a C57BL / 6 mouse, taking a lung metastatic focus for culture, inoculating primarily cultured metastatic focus cells to the C57BL / 6 again, taking the lung metastatic focus for different clone culture, and screening. Through two times of lung metastatic focus tumorigenesis and screening, compared with LLC cells, the lung cancer cells are shorter in use time for constructing a metastasis model, and the metastasis rate of main organs is higher; an efficient cell model is provided for better researching a tumor invasion and metastasis mechanism.

This invention relates to the field of animal model construction, specifically a method for constructing a lung metastasis model of the human melanoma A375-M1 cell line. The human melanoma A375-M1 cell line lung metastasis model was constructed using tail vein injection, and in vivo identification was performed using PET-CT and MRI, while in vitro identification was performed using Bouin's and H&E assays. The human melanoma lung metastasis model constructed by this invention has the advantages of short construction time, simple method, and 100% modeling success rate. This metastasis model simulates the development process and pathological characteristics of melanoma lung metastasis, solving the problem of the lack of ideal animal models for human melanoma lung metastasis. It contributes to the exploration and screening of anti-lung metastasis drugs for human melanoma and plays a positive role in promoting new strategies for combating melanoma lung metastasis.

The present application relates to the field of biotechnology, in particular, the application of E4BP4 in hematological diseases such as multiple myeloma. The present application proves that E4BP4 can be used as a potential biomarker and prognostic indicator for predicting the development of multiple myeloma, which is helpful for the treatment of multiple myeloma. Moreover, the E4BP4 protein can be used in the preparation of MM promoting reagents, which can be further used in the amplification of MM cells, the preparation of MM tumor metastasis models, the screening of MM treatment drugs and the like. After knocking down E4BP4, autophagy is induced and MM cell apoptosis is promoted, thereby enhancing the anti-myeloma effect of dexamethasone on MM. E4BP4 inhibitory drugs can be used as anti-myeloma drugs together with dexamethasone.

The invention discloses a cell strain A375-H for constructing a melanoma liver metastasis model as well as a construction method and application of the cell strain A375-H, and relates to the technical field of biology, and the preservation number of the cell strain A375-H is CGMCC No.46344. The cell strain is classified and named as an A375 high metastatic melanoma cell strain. The A375-H cell strain with high metastatic property and liver metastatic potential is efficiently and conveniently obtained by adopting a continuous 10-round Transwell screening combined monoclonal cell selection method. The A375-H cell strain has high liver metastasis invasion potential, and a unique seed cell model is provided for researching the liver metastasis mechanism of melanoma.

The application belongs to the field of biological medicine, and relates to application of chondroitin acid protein 1 in preparation of a reagent for diagnosing lung adenocarcinoma or evaluating lung adenocarcinoma prognosis. The application screens CRTAC1 from a GEO database through bioinformatics analysis and a machine learning algorithm, and the CRTAC1 is significantly lowly expressed in lung adenocarcinoma tissues, and an AUC reaches 0.972. Verification of a GEPIA database shows that low expression of the CRTAC1 is significantly related to poor prognosis such as advanced pathological stages, and a patient with high expression has better prognosis. The CRTAC1 blocks epithelial-mesenchymal transition through inhibition of an EGF / ErbB signal path, and remodels a tumor immune microenvironment through inhibition of M2 type macrophage polarization. A mouse lung metastasis model proves that overexpression of the CRTAC1 significantly reduces lung metastasis nodules. The application provides a new molecular marker and a drug target for early diagnosis, prognosis evaluation and precise treatment of lung adenocarcinoma.

The application belongs to the technical field of biological pharmacy, discloses application of RING1 in inhibition of esophageal squamous cell carcinoma metastasis through ubiquitination degradation of Integrin alpha 5, and provides application of a RING1 activator in preparation of a drug for treating metastatic esophageal squamous cell carcinoma. The application systematically evaluates the inhibiting effect of RING1 on esophageal squamous cell carcinoma metastasis through in-vitro cell experiments and a mouse in-vivo metastasis model; the results show that RING1 inhibits the activation of the FAK signal pathway by mediating K11 type ubiquitination degradation of Integrin alpha 5, and then inhibits the adhesion, migration ability and in-vivo metastasis ability of ESCC cells.

The application belongs to the technical field of biological medicine, and relates to an SLC15A1 targeted protein degradation agent, a construction method thereof and application of the agent in preparation of a drug for treating brain metastasis of lung adenocarcinoma. The application constructs an SLC15A1 targeted PROTAC protein degradation agent IL-PROTAC. The degradation agent couples ibuprofen with a ligand of an E3 ubiquitin ligase, lenalidomide, through a linker, so as to form a bifunctional molecule capable of targeting SLC15A1 and inducing protein degradation of SLC15A1. The IL-PROTAC drug constructed by the application has been proved to be capable of significantly inhibiting tumor growth of a LUAD brain metastasis model and prolonging the survival cycle of an animal model.

The application discloses a cell strain A375-H for constructing a melanoma liver metastasis model and a construction method and application thereof, relates to the technical field of biology, and has a preservation number of CGMCC No.46344; and a classification name of A375 high-metastasis melanoma cell strain. A375-H cell strain with high metastasis and liver metastasis potential is efficiently and conveniently obtained by using a continuous 10-round Transwell screening combined with a single clone cell picking method. The A375-H cell strain has high liver metastasis potential, and provides a unique "seed cell" model for studying a liver metastasis mechanism of melanoma.

The invention relates to a method for establishing MASH and a related liver cancer model by using a hepatic stellate cell specific Lonp1 knockout mouse, conditional gene knockout is realized by using a Cre-loxP system, a Lonp1flox / flox mouse and an Lrat-2ACre mouse are hybridized, and the mouse of which the Lonp1 gene is specifically deleted in hepatic stellate cells is obtained. The mouse does not have obvious liver abnormality at the age of 2 weeks, has liver fibrosis and lipid accumulation at the age of 6 weeks, has liver cirrhosis with inflammatory focus formation at the age of 6 months or above, and gradually has liver cancer at the age of 10 months. More importantly, the mouse can form a large number of liver cancer nodules with large volume within 16 weeks under the induction of GAN diet. In addition, when melanoma cells are injected into the spleen to establish a spleen-liver metastasis model, the hepatic stellate cell Lonp1-deficient mouse shows significantly increased number of metastatic tumors. The model can effectively simulate the pathological process from MASH to liver cancer, and provides a reliable tool for related mechanism research and drug development.

The invention discloses application of hyodeoxycholic acid in preparation of a medicine for relieving obesity-related subcutaneous metastatic colorectal cancer symptoms, and belongs to the technical field of medical bioengineering. After hyodeoxycholic acid is applied to a constructed obese mouse colorectal cancer subcutaneous metastasis model and intervened by hyodeoxycholic acid, compared with a high-fat diet control group, the volume of subcutaneous transplanted tumor of a mouse is obviously reduced, the damage degree of terminal colon tissue is obviously relieved, and inflammation infiltration and epithelial damage are effectively inhibited. Meanwhile, the intestinal flora structure of the mice in the intervention group is obviously changed, the relative abundance of 9 bacteria genus is obviously increased, and the relative abundance of 18 bacteria genus is obviously reduced. The results show that the hyodeoxycholic acid can relieve tumor load and tissue pathological damage of obesity-related colorectal cancer by adjusting the homeostasis of intestinal flora, so that the treatment effect is achieved. The application of the secondary bile acid in the field of tumor treatment is expanded.

Method for producing a spontaneous metastasis model is disclosed herein. The models, according to various embodiments herein, achieve a higher metastasis incidence rate, in an instance about 100% for mesenteric lymph node (mLN) invasion and about 80 to 90% for secondary organs. The models are kinetic model having a luciferase-based expression system that provide more statistically significant and robust data. The embodiments herein further include a method for producing the model for metastasis, comprising transplanting recombinant carcinoma cells having increased invasiveness and decreased tumorigenic properties and luciferase gene expression system, in one or more orthotopic positions in an animal.