38 results about "Metastasis model" patented technology

Provided is an anticancer agent which comprises an anti-PD-1 antibody or an anti-PD-L1 antibody as an active ingredient, functioning to reverse the unresponsiveness of iNKT cells in which anergy has been induced by administration with an iNKT cell ligand. The anti-PD-1 or anti-PD-L1 antibody blocks the PD-1 / PD-L1-mediated signaling pathway not only to prevent the iNKT cell ligand-induced iNKT cell anergy, but also to reverse the unresponsiveness of already anergic iNKT cells to produce cytokines. In addition, the anti-PD1 or anti-PD-L1 antibody ensures the potent anti-tumor activity of iNKT cells as demonstrated by a significant reduction in the number of metastatic nodules in B16F10 melanoma metastasis models in vivo. Collectively, the anticancer agent can be very useful in the treatment of cancer, particularly metastatic cancer.

Provided is an anticancer agent which comprises an anti-PD-1 antibody or an anti-PD-L1 antibody as an active ingredient, functioning to reverse the unresponsiveness of iNKT cells in which anergy has been induced by administration with an iNKT cell ligand. The anti-PD-1 or anti-PD-L1 antibody blocks the PD-1 / PD-L1-mediated signaling pathway not only to prevent the iNKT cell ligand-induced iNKT cell anergy, but also to reverse the unresponsiveness of already anergic iNKT cells to produce cytokines. In addition, the anti-PD1 or anti-PD-L1 antibody ensures the potent anti-tumor activity of iNKT cells as demonstrated by a significant reduction in the number of metastatic nodules in B16F10 melanoma metastasis models in vivo. Collectively, the anticancer agent can be very useful in the treatment of cancer, particularly metastatic cancer.

The invention discloses an in vitro model simulating human tumor metastasis. Cells in the model have a tumor high metastasis character. The model is constructed by building of a micro spherical hydrogel support frame by tumor high metastasis cells, building of a tumor cell in vitro metastasis model and identifying of the constructed tumor cell in vitro metastasis model. The model can grow in a three-dimensional culturing cell in a clustering mode, and tumor cell biological behaviors in metastasis can be detected. The model has important value in studying of a clinical tumor metastasis mechanism and controlling of screening of metastasis medicine and can be taken as a technical platform for manufacturing anti-tumor metastasis gene vaccines and building screening of anti-tumor metastasis medicine.

The invention relates to a lentivirus vector expression system of luciferase and an application thereof. Particularly speaking, in the invention a luciferase lentivirus expression system with FG12-Luc2 as core plasmid is successfully constructed, and a PVTT-1 cell line from tumor thrombus tissue of liver cancer patients is established by the system. Through the lentivirus expression system, liver cancer tissue is successfully marked; and by experimental methods such as subcutaneous transplantation and orthotopic liver cancer transplantation, a mouse orthotopic transplantation liver cancer metastasis model is established which is suitable for serial passage, is applicable to in-vivo imaging, and can realize real-time monitoring of the growth and metastasis conditions of tumors in the body.

The invention discloses a microfluidic chip, a tumor metastasis model based on the chip, a model construction method and application. The microfluidic chip comprises three layers of chip layers, two layers of porous membranes and two layers of fixed plates, wherein each chip layer is provided with one cell culture chamber with the diameter of 0.1 to 10mm and a micro-fluid channel with the width of0.1 to 10mm and the height of 10 to 500mum, the pore diameter of each porous membrane is 0.1 to 20mum and the porous membranes can be used for realizing cell wall attachment and mutual communication.The construction method of the tumor metastasis model comprises the following steps: 1) filling collagen into the chip by adopting the microfluidic chip and coating the porous membranes; 2) filling vascular endothelial cells into the second layer of the chip and constructing a blood vessel cavity model; and 3) filling tumor cells into the first layer of the chip. The model can be used for researches of different tumor cell metastasis and screening of anti-tumor medicines, and has the characteristics of stability, reliability and high integrated level.

The invention provides an application of blood exosome miR-1283 to preparation of liver cancer diagnosis products. The sequence of the blood exosome is as shown in SEQID No.1. According to the application disclosed by the invention, a mouse liver cancer metastasis model through liver cancer cell strains, and the situation that the PNC proportion of metastasis liver cancer cells is far higher thanthat of in situ site is found. Metastasis liver cancer tissue and in situ site liver cancer tissue are separated for cell culture, then exosome miRNA components of two cell culture supernatants are subjected to chip analysis, and exosomes significantly rise in liver cancer cells high in PNC proportion. The blood exosomes are novel biological markers. Prepared products are stable, minimally invasive, easy to detect, and quantitative and precise, sensibility and specificity of disease diagnosis can be increased, diagnosis and metastasis risk early warning are facilitated, reference is provided for developing other tumor similar biological markers, and a convenient noninvasive diagnosis manner is provided for metastasis early warning and prognosis assessment of liver cancer based on PNC.

The invention discloses a model in vitro which can simulate the metastasis of human liver cancer dynamically. The construction steps comprise the construction of an anti-cell adherence model by using human liver cancer cell line BEL7402 with high metastasis; the construction of metastasis model in vitro of liver cancer cell and the identification for the constructed in vitro metastasis model of liver cancer. The model of the invention can be used for the control research between the in situ cancer and the tumor in metastasis; the invention can further be used as a monitoring system for the biological behavior detection of the tumor cell in metastasis and the judgment of tumor prognosis. The model has important value for the research of clinical tumor metastasis mechanism and the screening of metastasis control drugs. The model can also be used as the screening technology platform for the preparation of anti-tumor transgenic vaccine and the construction of anti-tumor metastasis drugs.

The invention relates to a 4-aminopyrrolopyrimidine derivative and a preparation method and application thereof, and belongs to the field of medicines. The invention provides a compound shown as a formula I or pharmaceutically acceptable salt thereof. The compound can significantly inhibit the activity of RIPK1 kinase, has high selectivity and good safety, and is a potential therapeutic drug for RIPK1 kinase related diseases. TNF alpha induced SIRS model and mouse melanoma lung metastasis model experiments prove that the compound disclosed by the invention can play a role in inhibiting RIPK1 kinase in vivo and has remarkable anti-inflammatory and anti-tumor metastasis activity. The invention provides a new strategy and means for comprehensively treating tumor metastasis.

The invention provides a method for establishing an early metastasis model of esophageal squamous carcinoma, and belongs to the field of biomedicine. The method can effectively study the clinical regularity and characteristics of esophageal squamous carcinoma metastasis according to the early metastasis model of esophageal squamous carcinoma. The establishing method includes the steps of screening esophageal squamous carcinoma cells to obtain the subline cells of esophageal squamous carcinoma; inoculating the subline cells of esophageal squamous carcinoma to the inside of the renal capsule of a mouse to make the subline cells of esophageal squamous carcinoma grow under the renal capsule of the mouse, and obtaining the early metastasis model of esophageal squamous carcinoma. The method for establishing the early metastasis model of esophageal squamous carcinoma is used for studying the clinical regularity and characteristics of esophageal squamous carcinoma metastasis.

This invention provides a system and methods for modeling tumor metastasis in vitro where primary tumor tissue is cultivated in an orientation and an environment such that the natural composition, three-dimensional organization, and environmental conditions of the tumor can be adjusted. The invention further provides mechanism for inducing tumors to undergo metastatic processes resulting in production of tumor progenitor or stem cells that can be collected, characterized, or used to induce tumors in normal tissue constructs in vitro.

The invention discloses a method for constructing an in vitro model with dynamic simulation of hepatoma metastasis of human beings, comprising construction of a cell attachment resistant model, construction of the hepatoma cell in vitro metastasis model, identification of the constructed hepatoma in vitro metastasis model, etc. The method of the invention applies high metastasis tendency BEL7402 hepatoma cells to simulate and construct the in vitro model for hepatoma cell metastasis by constructing a model which makes the BEL7402 hepatoma cells deviated from attachment of extracellular matrixes and simulating a condition that transitional cells grows by means of anchorage dependence again when meeting adequate environment. By utilization of the model, control study of carcinoma in situ and tumor during the metastatic process can be performed, and the model can be further taken as a monitoring system for detecting biological behaviors of tumor cells during the metastatic process and judging tumor prognosis. The model has important value in researching a clinical tumor metastatic mechanism and controlling screening of metastasis drugs and also can be taken as a platform for preparing tumor metastasis resistant gene vaccine and establishing a tumor metastasis resistant drug screening technology.

The invention discloses a model in vitro which can simulate the metastasis of human neuroglioma dynamically. The construction steps comprise the construction of an anti-cell adherence model by using human neuroglioma cell line U251; the construction of in vitro metastasis model of human neuroglioma cell and the identification for the constructed metastasis model in vitro of human neuroglioma. The model of the invention can be used for the control research between the in situ cancer and the tumor in metastasis; the invention can further be used as a monitoring system for the biological behavior detection of the tumor cell in metastasis and the judgment of tumor prognosis. The model has important value for the research of neuroglioma metastasis mechanism and the screening for metastasis control drugs. The model can also be used as the screening technology platform for the preparation of anti-neuroglioma transgenic vaccine and the construction of anti-tumor metastasis drugs.

The invention provides a hepatoma extrahepatic metastasis prediction model based on radiomics and a construction method and application thereof, and can solve the technical problem that a mature and effective hepatoma extrahepatic metastasis prediction model based on a radiomics method is not developed in the prior art. The construction method comprises the following steps: acquiring an original medical image and clinical information; randomly dividing liver cancer patients into a training set and a verification set in proportion; extracting a preliminary image omics feature; the LASSO regression model carries out dimensionality reduction and screening on the preliminary image omics features in the training set to obtain first target image omics features, and the first target image omics features are utilized to construct various classifier models; using an SMOTE algorithm to amplify the first target image omics features to obtain amplified image omics feature data; carrying out dimensionality reduction by using an LASSO regression model and an RFC-RFE algorithm, screening the amplified image omics feature data, obtaining a second target image omics feature, constructing a plurality of classifier models by using the second target image omics feature, and calculating an image score; and evaluating the classifier models to select out the optimal classifier model through screening.

The invention discloses a colorectal cancer liver metastasis animal model construction method for multi-modal imaging research. The defect that an existing colorectal cancer liver metastasis implanting model is high in colorectal obstruction morbidity and short in model survival time and cannot adapt to long-term experiment is overcome. Adopted animals are 5-year-old BALB / C-nu-nu female nude mice, an adopted injection is human colorectal cancer cells (HT29), and the method comprises the construction steps that 0.1 ml of colorectal cancer cells with the concentration being 2.5*10<7> / ml prepared from 0.01 MPBS is injected into the spleen, the injection time is about 3 min, the spleen is placed into an enterocoelia after injection is finished, and a colorectal cancer liver metastasis nude mouse model can be obtained seven weeks after the model is manufactured. Due to the fact that the concentration of the colorectal cancer cells (HT29) is 25*10<7> / ml, the dosage of the colorectal cancer cells is 0.1 ml, the liver metastasis model can be obtained by only injecting a cell suspension into the spleen at a time, and therefore the method is easy to implement, high in molding success rate and worthy of popularization and has certain economic and practical value.

The invention relates to the field of tumor tissue engineering materials, and discloses a construction method of a three-dimensional engineering breast cancer lung metastasis model. The construction method includes construction of a primary diffuse leptomeningeal melanomatosis (PDLM)-collagen-chitosan scaffold, construction of a 3D breast cancer lung metastasis model of a single cell-composite scaffold, construction of a 3D breast cancer lung metastasis model of a multi-cell-composite scaffold and construction of a 3D breast cancer lung metastasis model of a multi-cell-composite scaffold-cytokine co-culture system. The invention further discloses the three-dimensional engineering breast cancer lung metastasis model and application. The model scaffold constructed by the invention is closer to components, mechanical strength and biochemical information of a lung extracellular matrix (ECM), the composite scaffold-based multi-cell co-culture system can better simulate a breast cancer lung metastasis microenvironment, constructed engineered tumor tissue is similar to biological characteristics of an in-vivo lung metastasis focus, and the model scaffold has important application value and prospect in research on the occurrence and development mechanism of breast cancer lung metastasis and an anti-tumor strategy.

The invention provides a carboline ruthenium complex as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The series of carboline ruthenium complexes provided by the invention not only can inhibit tumor metastasis, but also have an inhibition effect on primary tumors, and are high in biological activity. The complex provided by the invention has a selective killing effect on tumor cells, can form relatively stable spherical nano-molecules in vitro, and can interact with DNA and transferrin; in vivo experiments, an S180 mouse sarcoma model evaluates the inhibition effect of the complex on primary tumors, and the LLC anti-metastasis model evaluates the anti-metastasis effect of the complex on lung cancer; in addition, ICP-MS isutilized to determine the distribution of the complex 2b in a living body, immunohistochemistry and immunofluorescence analysis are carried out on tumor tissues at the same time, and results show thatthe complex 2b can inhibit the growth of primary tumors in the living body and can inhibit the metastasis of tumors on lungs.

The invention discloses a method for establishing a model of a large animal tumor lymph node high-metastasis model and rapidly detecting the lymph node containing tumor cells in real time. The methodcomprises the following steps: establishing a rabbit tongue tumor model, and establishing a rabbit cervical lymph node high-metastasis model based on the rabbit tongue tumor model; after successful establishment of the rabbit cervical high-metastasis model, an endogenous substance 5-aminolevulinic acid (5-ALA) is used, and the fluorescence of its metabolite protoporphyrin (PPIX) is used to rapidlyand accurately detect the rabbit cervical lymph node. The method has the advantages of simple operation and high reliability, fully and completely simulates the clinical characteristics and biological characteristics of human tongue cancer lymph node metastasis, provides a research model for the treatment and resection of lymph node metastasis of human tumors, provides a novel means for intraoperative visualization of real-time tumor lymph node dissection, and has broad application prospects in the fields of biomedical and photodynamic diagnosis.

The invention provides a microfluidic chip for constructing a bionic lung cancer brain metastasis model to solve the problem of the current difficulty in constructing a blood brain barrier for the lung cancer brain metastasis and incapability to achieve intuitive observation and the like. The microfluidic chip comprises a bionic lung portion and a bionic brain portion and is characterized in thatthe bionic lung portion is disposed on the upstream of the chip and comprises a three-layer structure including an upper substrate layer, an intermediate porous film layer and a lower substrate layer.The three-layer structure is provided with a gas channel, a liquid channel and a vacuum channel. The bionic brain portion is disposed on the downstream of the chip, and comprises a two-layer structure including an upper substrate layer and a lower substrate layer. The upper substrate layer is a cover layer. The lower substrate layer comprises a brain parenchyma chamber, and a blood brain barrierring is arranged outside the brain parenchyma chamber. A blood vessel cavity is arranged outside the blood brain barrier ring. The blood vessel cavity is connected with the liquid channel on the lowersubstrate layer of the bionic lung portion through a connecting channel. The blood brain barrier ring is provided with a micro gap structure communicated with the brain parenchyma chamber and the vascular chamber. The vascular chamber and the brain parenchyma chamber are provided with an inlet and an outlet for the liquid to flow in and out.

The invention discloses a highly metastatic model of human melanoma, a highly metastatic cell subline of the human melanoma, creation methods for the highly metastatic model and the highly metastatic cell subline, and the dynamic detection of metastasis. The subcutaneously-transplanted mouse highly metastatic model and the corresponding cell subline are established in an in-vivo screening way in a mouse with severe combined immune deficiency (SCID) by using mouse lung metastasis, namely human malignant melanoma cell strain A375 pulmonary metastasis, wherein the highly metastatic cell subline of the human melanoma is A375sci, and has a human tumor cell karyotype; and 60 to 75 hypo-triploid-dominated chromosomes are acrocentric and have a heteroploid karyotype. The cell subline has the two routes of metastasis of blood trails and lymph. The in-vivo screening of the highly-metastatic model is performed by using animals with severe immune deficiency, and is expressed and applied in nude mice. A method for detecting Alu genes by using a polymerase chain reaction (PCR) method is simple, highly sensitive and highly specific, and can be used for detecting organ metastasis, particularly micrometastasis, in a human tumor animal-xenotransplantation model.

The invention provides (6S)-3-acetyl base-6-methylol-4,6,7,12-tetrahydrofuran-4-oxyindole[2,3-alpha]quinolizine-alph-D-furan glucuronate, provides a preparation method thereof, discloses the anti-tumor activity thereof in a mice S180 transplanted sarcoma model, discloses the anti-tumor metastasis activity thereof in a mice Lewis lung cancer metastasis model, discloses an anti-inflammation role thereof in a mice ear swelling model, and further discloses an anti-thrombus role thereof in a rat common carotid artery-external jugular vein circulation bypath thread method anti-thrombus model. The invention discloses application of (6S)-3-acetyl base-4-oxo-4,6,7,12-tetraindole-[2,3-alpha]quinolizine-6-formyl-glucuronate in preparation of anti-tumor drugs, anti-lung cancer metastasis drugs, anti-inflammation drugs and anti-thrombus drugs.

The invention relates to a method for sieving tumor metastasis inhibiting genes by utilization of an RNA interference library, which is to utilize an in vivo transplantation tumor metastasis model of immunodeficient mouse cells to better simulate generation of tumor metastasis than a cell model, and utilize the RNA interference library to make various genes of a human genome randomly reduce expression in tumor cell strains respectively, so as to greatly strengthen the potency of cells of which the tumor metastasis inhibiting genes reduce expression to form tumor metastasis. Therefore, after cells treated by the RNA interference library are injected into the in vivo of an immunodeficient mouse, the cells of which the tumor metastasis inhibiting genes reduce expression can form a lung tumor in the condition that contrast cells can not form tumor metastasis, and novel tumor metastasis inhibiting genes can be determined and sieved by separating the lung tumor and cloning the expression reduction genes in the lung tumor. The tumor metastasis inhibiting genes are sieved in the whole genome level by the method, and are used: firstly, for further researching generation, development and an action mechanism of tumor metastasis; secondly, as biological markers of tumor for guiding formulation of a tumor treatment solution under the condition of diagnosis, and evaluating the treatment effect and detecting relapse after diagnosis; and thirdly, as a target of tumor targeting treatment to achieve the aim of preventing and treating tumor metastasis is achieved by strengthening the functions of the tumor metastasis genes.

The invention discloses a method for establishing a drosophila melanogaster model for inducing colon cancer high-frequency metastasis, and relates to the technical field of biogenetics. The invention aims to establish tumor migration which is obvious in migration, high in migration efficiency and stable in adult body. The method specifically comprises the following steps: adding lgl <- / -> UASRasV12 and FRT40A / Cyo into a reaction kettle; a TM3 / TM6B fruit fly strain and Sp / Cyo; the method comprises the following steps: hybridizing fruit fly strains of lgl <-> / -UASRasV12 and SnaOE / TM < 3 > / MKRS, and selecting FRT40A / Cyo with genotypes of lgl <-> / -UASRasV12 and FRT40A / Cyo from later generations; according to the method, a fruit fly strain capable of being subjected to passage preservation is built by using a single-cell culture medium, UASRasV12 and SnaOE / TM6B. According to the invention, fruit fly colon cancer is taken as a model, and an efficient tumor metastasis model is established through genetic manipulation of expression of tumor related factors such as Ras and lgl, Sna and the like.

The circRHOBTB3 targeting ASO drug is designed and synthesized, and the level of circRHOBTB3 in cells can be effectively improved; after the ASO is used for treating colorectal cancer cells and an animal tumor metastasis model, proliferation, migration and invasion of the colorectal cancer cells in vitro and metastasis of the colorectal cancer cells in vivo are effectively inhibited, and a way is provided for treatment of malignant tumors.

The invention discloses a method for constructing a luciferase high-expressed Huh7 cell line. A luciferase high-expressed Huh7 cell line is obtained by adopting a lentiviral vector. According to the method, firstly, a luciferase gene is transferred into a Huh7 cell line by utilizing a lentiviral infection technology, so that the luciferase gene can be expressed in the Huh7 cell; and then, a cell over-expressing luciferase is screened by adopting a method for selecting monoclonal cells, and mass amplification is performed to obtain the Huh7 cell line stably over-expressing the luciferase. The Huh7 cell line stably high expressing luciferase can be used as a specific marker to detect the part of a cell existing in an animal body and can be used for studying a tumor metastasis model.

The invention discloses a micromolecule non-encoding RNA (microRNA-210), a host gene (lncRNA MIR210HG) of the micromolecule non-coding RNA (microRNA-210) and application thereof. The microRNA-210 and the lncRNA MIR210HG disclosed by the invention can be used as specific markers of the gastric cancer. Besides, an in-vitro metastasis chamber and an in-vivo mouse tail intravenous injection tumor cell lung metastasis model are carried out, which shows that the microRNA-210 and the lncRNA MIR210HG can promote gastric cancer cell metastasis, and the gastric cancer cell metastasis can be inhibited by inhibiting a common transcription factor of the microRNA-210 and the lncRNA MIR210HG. Therefore, the microRNA-210, the lncRNA MIR210HG and the common transcription factor of the microRNA-210 and the lncRNA MIR210HG can be used for gastric cancer diagnosis, can also be used as targets for preparing drugs for inhibiting gastric cancer metastasis or anti-tumors, and can provide a new thought and a new way for gastric cancer treatment.

The invention discloses an expression up-regulator of LncRNA MALAT1. The up-regulator is thapsigargin. Thapsigargin can regulate the expression of MALAT1, solve the technical problem of high expression of MALAT1 in cells, reduce costs, and can promote the metastasis of tumor cells, thereby improving the success rate of cell metastasis models, which is beneficial to the study of tumor publishing mechanisms and The establishment of tumor metastasis model is of great significance.

The invention provides (6S)-3-acetyl base-4-oxo-4,6,7,12-tetraindole-[2,3-alpha]quinolizine-6-formyl-(3-glucosamine), provides a preparation method thereof, discloses the anti-tumor activity thereof in a mice S180 transplanted sarcoma model, discloses the anti-tumor metastasis activity thereof in a mice Lewis lung cancer metastasis model, discloses an anti-inflammation role thereof in a mice ear swelling model, and further discloses an anti-thrombus role thereof in a rat common carotid artery-external jugular vein circulation bypath thread method anti-thrombus model. The invention discloses application of (6S)-3-acetyl base-4-oxo-4,6,7,12-tetraindole-[2,3-alpha]quinolizine-6-formyl-(3-glucosamine) in preparation of anti-tumor drugs, anti-lung cancer metastasis drugs, anti-inflammation drugs and anti-thrombus drugs.