34 results about "Tamoxifen" patented technology

The invention discloses a construction method of a conditional knock-down dynactin animal model of astrocytes and an application of the animal model of the conditional knock-down dynactin animal model of the astrocytes. According to the method, a Dctn1LoxP gene knock-in mouse is hybridized with an Aldh1l1-Cre / ERT2 transgenic mouse, a target genotype mouse is obtained through three rounds of breeding, 100mg / kg Tamoxifen is continuously injected into the intraperitoneal cavity of the 2-month-old mouse for 5 days, and specific knock-down of dynactin in brain and spinal astrocytes is realized, including knockout of p150Glue and reduction of DCTN4, p50 and Arp1alpha protein levels. The model has the advantages of being high in specificity, permanent in intervention aging and capable of covering multiple life stages, the defects of a traditional model are overcome, the model can be used for researching the influence of dynactin on astrocyte neurobiological functions, a reliable tool is provided for screening related targets of nervous system diseases, and the model has important application value.

This invention relates to drug-resistant breast cancer cells and their applications, belonging to the field of tumor cell technology. The drug-resistant breast cancer cells of this invention are human mammary ductal carcinoma cells T47DR and / or human breast cancer cells MCF7R. The human mammary ductal carcinoma cells T47DR were deposited at the Guangdong Provincial Microbial Culture Collection Center on October 25, 2024, with accession number GDMCC No: 65348; the human breast cancer cells MCF7R were deposited at the same center on October 25, 2024, with accession number GDMCC No: 65347. This invention demonstrates that the clonogenic ability, migration ability, anti-apoptotic ability, and spheroidization ability of drug-resistant breast cancer cells are significantly enhanced. They can form tumors independently of estrogen and metastasize throughout the body in a short period of time. The tumor stemness of the drug-resistant cells is enhanced, and they exhibit resistance to apelexifen and / or tamoxifen.

The invention provides a pharmaceutical composition and application thereof in preparation of medicines for treating tumors. The pharmaceutical composition comprises the orbitrazine fumarate, a second active agent and pharmaceutically acceptable auxiliary materials. The second active agent comprises at least one of tamoxifen, irinotecan hydrochloride, sorafenib, cis-platinum, doxorubicin hydrochloride, paclitaxel and etoposide. The scheme provided by the invention has a remarkable synergistic anti-tumor effect, and a combined medication scheme is expected to provide a safer and more effective treatment choice for tumor patients, so that the pharmaceutical composition has an important clinical application value.

The invention belongs to the technical field of medical biological research, and particularly relates to a construction method of a spontaneous emphysema mouse model. The invention relates to a method for constructing a spontaneous emphysema mouse model, which comprises the following steps: when a Muc1 gene whole body knockout mouse naturally senility for 3-18 months to form spontaneous emphysema and / or a Muc1 type 2 alveolar epithelial cell knockout mouse is 6-8 weeks old, injecting tamoxifen into the intraperitoneal cavity of the mouse to induce knockout. According to the invention, the Muc1 gene knockout mouse is used for constructing a spontaneous emphysema mouse model product for the first time; the related products comprise construction schemes, application transformation and the like of a spontaneous emphysema model generated by Muc1 whole body knockout mouse (Muc1- / -) along with age increase and a spontaneous emphysema model generated by Muc1 type 2 alveolar epithelial cell knockout (Muc1AT2- / -) mouse induced by intraperitoneal injection tamoxifen along with age increase. The invention proves that the spontaneous emphysema model is successfully constructed.

Disclosed are methods of treating cancer with a tri-agent therapy. The methods include a cancer treatment regimen with two or three different antineoplastic medications, including tamoxifen, gefitinib, and vinorelbine (TGV). The cancer treatment regimen can include sequential and / or concurrent administration of tamoxifen, gefitinib, and vinorelbine. The cancer treatment regimen can include sequential and / or concurrent administration of tamoxifen and gefitinib as adjuvants to a prescribed treatment. The cancer treatment regimen can be cyclical or can be a continuous metronomic treatment with metronomic dosing. The cancer treatment regimen can be cyclical and then can be followed by a continuous metronomic treatment with metronomic dosing.

The invention discloses a construction method of an endothelial cell knockout Cdc42 gene aggravated bleomycin induced pulmonary fibrosis mouse model, which comprises the following steps of: mating a Cdc42 gene conditional knockout mouse with a mouse (Tie2-CreER) of which the endothelial cell specifically expresses tamoxifen induced Cre recombinase to obtain a double-transgenic mouse (Cdc42fl / fl-Tie2-CreER); the Cdc42 gene is specifically knocked out in vascular endothelial cells under the induction of tamoxifen, and then pulmonary fibrosis is induced by subcutaneous injection of bleomycin. The model shows aggravated pulmonary fibrosis phenotypes, including collagen deposition increase, alveolar structure damage and fibrosis-related protein expression up-regulation, and is high in construction success rate and good in repeatability. The invention also provides an application of the model in research of systemic sclerosis related interstitial lung disease pathogenesis and screening of anti-pulmonary fibrosis drugs, and an application of the Cdc42 gene as a drug target, and provides an accurate and reliable tool for pulmonary fibrosis research.

To provide methods for quantitation of tamoxifen and its metabolites in a sample by mass spectrometry, including tandem mass spectrometry.SOLUTION: In one aspect, methods are provided for determining the amount of tamoxifen and metabolites thereof in a sample in a single mass spectrometry assay, the methods comprising: (a) ionizing the tamoxifen and metabolites to produce one or more ions detectable by mass spectrometry; and (b) detecting the amount of the ions from the step by mass spectrometry; where the amount of the ions detected is related to the amount of each of tamoxifen and metabolites in the sample.SELECTED DRAWING: None

A mouse model with conditional knockout of a vitamin D-binding protein gene, and the use thereof. A method comprises the following steps: S1, performing flox modification on the mouse vitamin D-binding protein gene to obtain F0-generation positive mice having undergone the flox modification; S2, mating said F0-generation positive mice with wild type mice to obtain F1-generation positive mice with preserved flox modification; S3, hybridizing the F1-generation positive mice with tissue-specific Cre tool mice to obtain heterozygous mice, and mutually mating the heterozygous mice to obtain homozygous mice; and S4, selecting the obtained homozygous mice to undergo tamoxifen injection, so as to obtain mice with conditional knockout of the vitamin D-binding protein gene.

The application provides a method for constructing a mouse model of mitochondrial myopathy with a Lars2 gene deletion and application thereof, a first Lars2 flox / flox mouse is obtained by crossing an Acta1 ER‑Cre mouse with an Acta1 ER‑Cre -Lars2 flox / flox mouse; in the second step, the above mouse reaches 4 weeks of age, and tamoxifen 70-80 mg / kg is used for continuous intraperitoneal injection for 5 days; in the third step, 4 weeks later, tamoxifen 45-55 mg / kg is used for continuous intraperitoneal injection for 5 days; in the fourth step, the Acta1 ER‑Cre -Lars2 flox / flox mouse reaches 12-13 weeks of age, and skeletal muscle Lars2 protein deletion occurs, and skeletal muscle atrophy occurs obviously at 16 weeks of age, thereby obtaining a mouse model of mitochondrial myopathy with a Lars2 gene deletion.

The application discloses a construction method of a spontaneous psoriasis mouse model and application thereof, and inserts a loxP site into an embryonic stem cell clone in a fatty acid synthase gene Fasn Chimeric mice are obtained through blastocyst injection, and through mating, a Fasn flox / flox Mouse; and a tool mouse Krt14-CreERT2 + / ‑ The tool mouse is mated with the tool mouse, and a mouse with a genotype of Krt14-CreERT2 + / ‑ ; Fasn flox / flox is screened, and the mouse model is obtained through continuous induction of tamoxifen. The spontaneous psoriasis mouse model constructed by the application is superior to an acute model which needs external induction, is convenient for long-term observation and intervention experiments, and provides a more ideal tool for researching a pathogenesis of psoriasis, screening and evaluating new drug candidate compounds for psoriasis.

The invention discloses a construction method and application of an animal model for in-vivo ubiquitination enzyme screening, and belongs to the technical field of animal model construction. The traditional in-vitro screening of ubiquitination modification enzyme genes has the defects of unreal simulation environment, poor repeatability, narrow application range and the like, 150 SgRNAs are designed to construct library plasmids, loxP TC9 sequences and filling sequences are introduced to prepare transgenic Sanyang mice, and the transgenic Sanyang mice are used for in-vivo screening after being induced by tamoxifen. The mouse model constructed by the invention can realize gene screening in 29 tissues and organs, the success rate of target verification is more than 80%, the coefficient of variation is lower than 10%, the model can be stably passed, and the screening cost and technical threshold are greatly reduced.

The invention provides a nano-drug delivery platform of a metal organic framework based on Zn / Co-MOF as well as a preparation method and application of the nano-drug delivery platform, and belongs to the technical field of biology and new medicine. The nano-drug delivery platform based on the Zn / Co-MOF metal organic framework comprises a Zn / Co-MOF metal organic framework core, an organic drug composition loaded on the surface of the core and in micropores, and a homologous tumor cell membrane wrapping the outermost layer, wherein the organic pharmaceutical composition is prepared from a tamoxifen-cis-platinum dimer prodrug, a photo-thermal therapeutic agent IR-820 and an immunomodulator metformin. The nano-drug delivery platform provided by the invention visually monitors tumor development and treatment processes in vivo through fluorescence luminescence, integrates chemotherapy-photothermal-endocrine three modes into a whole, has good safety and biocompatibility, shows a remarkable anti-tumor effect in a tumor-bearing nude mouse model, and has good application prospects. And a brand new strategy is provided for treatment of ER + breast cancer.

The invention relates to a construction method and application of a mouse model with spontaneous gastric precancerous lesions. The construction method comprises the following steps: constructing a Pgc-Cre gene mouse only carrying an inducible Cre gene (tamoxifen can be injected in a rich manner to induce Cre nucleation); the method comprises the following steps: constructing a Rosa26-Zeb2 gene mouse which only carries a Zeb2 gene; the method comprises the following steps: taking Cre and Zeb2 genes as raw materials, mating to obtain a mouse carrying the Cre and Zeb2 genes at the same time, then administering a drug to the mouse, inducing Cre to enter a nucleus and promoting expression of the Zeb2 genes to obtain the mouse model with the spontaneous precancerous lesion of the gastric cancer; the medicine is tamoxifen. The mouse model constructed by the invention is driven by the specific inducible Cre of the stomach main cells, is limited to the stomach main cells, avoids gene disturbance of non-target cells, is simple and convenient to mate, low in cost and short in experimental period, and can be used for screening gastric precancerous lesion drugs.

The application discloses a kind of construction methods of mouse model for studying vascular endothelial senescence, belong to genetic engineering technical field, utilize 6030442E23Rik conditional gene knockout mouse and Tek-CreERT2 mouse (utilize CRISPR gene editing technology, Cre is inserted into mouse Tek gene stop codon, is the tool mouse of endothelial cell conditional knockout, currently, this kind of strain mouse has on market), cross, obtain 6030442E23Rik- / -Tek-CreERT2 mouse.Tamoxifen is dissolved in corn oil later, so that its final concentration is 20 mg / ml.Tamoxifen dose is 120mg / kg mouse weight later, intraperitoneal injection 5 times, once every other day, and the mouse model of endothelial cell 6030442E23Rik specificity knockout can be obtained 7 days after the end of last injection.The mouse model of endothelial cell 6030442E23Rik specificity knockout is an important mouse model for studying vascular endothelial senescence.

The invention relates to the technical field of animal model construction, in particular to a construction method and application of a gene editing mouse model for studying calcium library function and low fertility in mature sperms.The model is characterized in that tamoxifen is used for inducing, a Ddx4ERT2 promoter is used for driving Cre recombinase expression, three subtypes of IP3R are specifically knocked out in sperms at the same time, and the mouse model is obtained. The method is used for researching the action and mechanism of the subtype in male fertility. After the model mouse is subjected to two rounds of induced knockout, the fertility is severely damaged, the sperm quantity and movement level are reduced, and the acrosome reaction is abnormal, so that the model is a good model for evaluating the sperm dysfunction, and is expected to be used for screening treatment drugs for improving the sperm dysfunction, especially male sterility diseases caused by advanced acrosome reaction in the future. In addition, through screening optimization of an IP3R agonist and a calcium signal detection platform, it is further confirmed that the mouse model is a good model for studying sperm calcium library mediated calcium signals.

The invention discloses a construction method and application of a transgenic mouse model for in-vivo screening of immunotherapy target genes for regulating and controlling T cell metabolism, and belongs to the technical field of animal model construction. The technical problems to be solved are that in-vitro screening target spots for regulating and controlling T cell metabolism immunotherapy target genes in the prior art are poor in authenticity, complex in operation and high in cost, and corresponding in-vivo screening tools are lacked. According to the key points of the technical scheme, the construction method of the transgenic mouse model for in-vivo screening of the immunotherapy target genes for regulating and controlling T cell metabolism is provided, sgRNA (SEQ ID NO.1-150) of 140 immunotherapy target genes for regulating and controlling T cell metabolism and 10 control genes are designed, 150mer library plasmids are constructed step by step, and then model mice are constructed; target spots are screened through tamoxifen induction in combination with a tumor model, flow sorting and NGS analysis, 150 immunotherapy target genes for regulating and controlling T cell metabolism can be covered, operation is easy and efficient, and the screening cost is remarkably reduced.

The invention discloses a construction method and application of a KPCDK mouse model originated from inflammatory senescence cells induced by inflammation and senescence, the construction method of the model comprises the following steps: hybridizing a mouse expressing a Cdkn2a-CreER2 gene with a mouse in which both KrasLSL-G12D and Trp53R172H are mutated to obtain a KPCDK mouse, and the genotypes of the KPCDK mouse are KrasLSL-G12D / +, Trp53R172H / + and Cdkn2a-CreER2 / +; the KPCDK mouse model is obtained by carrying out injection induction on a KPCDK mouse by using rain frog element and tamoxifen. According to the application, through the combined action of the leifrotin and the tamoxifen, the spontaneous tumorigenesis experiment period can be shortened, the experiment efficiency can be improved, the experiment cost can be saved, and a basis is better provided for the research of an aging tumorigenesis mechanism caused by pancreatic cancer and inflammation and the research and development of medicines.

The application aims to provide a new application of an iron death inhibitor, Liproxstatin-1. The application studies the iron death phenomenon in the process of follicle atresia of laying poultry, finds that the iron death inhibitor Liproxstatin-1 can rescue the follicular granulosa cell death induced by tamoxifen (TMX), can inhibit the oxidative stress level and intracellular iron ion overload caused by TTMX treatment, can effectively inhibit the follicular iron death phenomenon induced by TTMX, and finally can restore the egg production function of livestock and poultry, and has the development into a drug for treating follicle atresia and used for treating follicle atresia of livestock and poultry.

Provided are methods for determining the amount of tamoxifen and its metabolites in a sample by mass spectrometry. In some aspects, the methods provided herein determine the amount of N-Desmethyl Tamoxifen. In some aspects, the methods provided herein determine the amount of N-Desmethyl Tamoxifen and other tamoxifen metabolites. In some aspects, the methods provided herein determine the amount of tamoxifen, N-Desmethyl Tamoxifen, and other tamoxifen metabolites.

To induce cancer cell death, cancer cells are selected that express estrogen-receptor β (ERβ) and mutant tumor protein 53 (TP53). An agent that increases ERβ protein expression is administered to the cells to induce cell death. To treat a subject having a cancer that is characterized by cancer cells expressing ERβ and mutant TP53, an agent that increases ERβ protein expression is administered to induce cell death in the cancer cells. To increase estrogen receptor β (ERβ) expression levels in a subject having low ERβ expression levels, tamoxifen is administered to increase ERβ protein levels in the subject. To treat a subject having cancer cells expressing estrogen-receptor β (ERβ) and wildtype tumor protein 53 (TP53), an agent that inhibits ERβ and TP53 binding interaction is administered to induce cell death in the cancer cells of the subject.

The present application provides a kind of estrogen receptor positive breast cancer fluorescent probe by parent nucleus dye nile blue derivative, estrogen receptor (ER) recognition group tamoxifen and alkane chain three parts constitute, the probe has the structure of general formula 1.The probe shows folded conformation in water environment, there is photoinduced electron transfer effect between nile blue derivative and tamoxifen, no obvious fluorescence signal;When the probe recognizes ER protein, the recognition group is combined with the binding site, the conformation of the probe changes into unfolded conformation, and strong fluorescence signal is shown.The excitation wavelength of the probe is about 630 nm, the emission wavelength is about 640-700nm, has stronger tissue penetration ability, lower tissue self-absorption and light scattering, can be targeted to breast cancer cell overexpressed ER protein, and specifically highlights estrogen receptor positive breast cancer.

The invention relates to the technical field of biological medicines, in particular to a construction method and application of a tool mouse for specifically knocking out cre by germ cell genes, and the construction method is characterized in that a Cre recombinant sequence carrying a Ddx4 promoter sequence is knocked into a mouse genome safety site Hipp11 by virtue of a CRISPR-CAS9 technology so as to construct a Ddx4 Promoter-Kozak-CreERT2-rBGpA gene knock-in mouse model. The model mouse realizes the characteristic of specific expression of CreERT2 recombinase under the driving of a germ cell specific promoter Ddx4, the expressed CreERT2 protein is inactivated after the cell cytoplasm is combined with the HSP90 protein, the CreERT2 is dissociated after being induced by tamoxifen and enters a cell nucleus, and an Loxp sequence is cut to realize gene recombination. According to the invention, the exogenous sequence is inserted into the safe site of the genome, so that the expression and function of the original endogenous gene of the mouse are not influenced, the fertility of the male and female mice is not influenced, and the method has the advantages of high efficiency and convenience in subsequent gene knockout. The model mouse is expected to accelerate the analysis of the action mechanism for regulating the gametogenesis gene of the mouse.

The invention relates to the technical field of neuroscience, in particular to a construction method and application of an animal model for specifically marking a central nervous system myelin sheath. The preparation method comprises the following steps: preparing Mog-DreERT The mT (loxp) / mG (rox) experimental substance can be used for simultaneously marking OPCs, OLs and myelin sheaths which are differentiated and mature by the OPCs, and existing myelin sheaths before induction; the method comprises the following steps: constructing NG2-CreERT by using a Cre-loxP and Dre-rox double recombinase system; the preparation method comprises the following steps: preparing Mog-DreERT The mT (loxp) / mG (rox) transgenic experimental object model can simultaneously mark formed and newly formed myelin sheaths after being induced by tamoxifen, and a novel research tool is provided for realizing multi-dimensional oligodendrocyte lineage tracking and stage-specific gene manipulation.

The present application belongs to the technical field of tumor treatment, and specifically discloses a copper silicate-based nano-targeted drug delivery system for synergistically treating breast cancer, which comprises CuSiO3, tamoxifen, narcissus-derived carbon quantum dots, polyethylene glycol and hyaluronic acid; tamoxifen and narcissus-derived carbon quantum dots are loaded on CuSiO3 through electrostatic interaction, and then polyethylene glycol is covalently modified, and then hyaluronic acid with targeting ability is coated to prepare a CuSiO3@TAF@CDs-PEG-HA nano-targeted drug delivery system. The copper silicate-based nano-targeted drug delivery system for synergistically treating breast cancer is used, and based on the imbalance of intracellular redox homeostasis caused by oxidative stress and weakened antioxidant capacity, the copper silicate-based nano-targeted drug delivery system exhibits high tumor treatment effect on human breast cancer cells and tumor-bearing mouse models.

The invention provides a mouse model of gastric poorly differentiated adenocarcinoma accompanied with signet ring cell carcinoma as well as a construction method, a cell strain and application of the mouse model. The invention relates to a construction method of a mouse model of gastric hypodifferentiation adenocarcinoma accompanied with signet ring cell carcinoma. The construction method comprises the following steps: constructing a mouse M3 of which a Trp53 gene is conditionally knocked out; the method comprises the following steps: hybridizing a mouse M3 with a mouse M1 with a genotype of Anxa10CreERT2 / + to obtain a mouse M13, and carrying out interaction on the mouse M13 to obtain a mouse M4; the method comprises the following steps: hybridizing a mouse M4 with a mouse M2 of which the genotype is KRASLSL-G12D / + to obtain a mouse M42, and hybridizing the mouse M42 with the mouse M4 to obtain a mouse M5; chemical induction is carried out on the mouse M5 by administration of drugs, and the mouse model with hypogastric differentiation adenocarcinoma accompanied by signet-ring cell carcinoma is obtained; wherein the medicine is prepared from tamoxifen. By means of the construction method, the mouse model and the cell strain of gastric hypodifferentiation adenocarcinoma accompanied with signet-ring cell carcinoma can be obtained, the tumor formation rate of mouse gastric cancer can be increased, the tumor formation time can be shortened, and the tumor formation condition is stable.

The invention relates to the technical field of gastric cancer mouse model construction, and provides a construction method and application of a gastric neuroendocrine cancer mouse model, and the construction method comprises the following steps: constructing an AMK gene mouse, then performing chemical induction on an AMK gene mouse drug, and performing pathological staining analysis to obtain the gastric neuroendocrine cancer mouse model. Wherein the genotype of the mouse with the AMK gene is Atp4bCreERT2 / +; mYCLSL / +; kRASLSL-G12D / < + >; the medicine contains tamoxifen. The gastric cancer mouse model containing the neuroendocrine cancer component, which is constructed by the invention, is high in invasion ability, high in malignancy degree and metastasis, conforms to clinical characterization of the gastric neuroendocrine cancer, can stably form tumors within a short time, and is high in repeatability. The gastric neuroendocrine cancer mouse model constructed by using the method provided by the invention can be applied to related researches of gastric neuroendocrine cancer etiology and drug development, screening and verification.

The invention discloses an application of a C3aR1 targeted inhibitor in preparation of a medicine for preventing or treating abnormal acne. According to the invention, tamoxifen is injected in the intraperitoneal cavity to induce Ncstn conditional knockout mice, and an abnormal acne model with typical inflammatory characteristics is constructed; after the model is established, intradermal administration of a C3aR1 inhibitor SB290157 is carried out on a mouse, so that a C3a-C3aR1 signal channel is blocked, and skin inflammation is improved. The results show that the C3aR1 inhibitor SB290157 can obviously relieve dermatitis symptoms of mice, and the C3aR1 inhibitor SB290157 is proved to have obvious prevention and treatment effects on abnormal acne.

The present application relates to the technical field of pharmaceutical preparation, in particular to a nanoemulsion containing tamoxifen and ginsenoside and a preparation method thereof. The present application prepares the nanoemulsion by citric acid tamoxifen, ginsenoside, glyceryl tributyrate, isopropyl myristate, tragacanth, poloxamer and glycerol, the prepared nanoemulsion has smaller particle size, good stability, can significantly improve the solubility, and further improve the targeting and therapeutic effect of the nanoemulsion.

The invention relates to the technical field of neuroscience, in particular to a method for marking a new myelin sheath in a central nervous system, which comprises the following steps: constructing an ENPP6-P2A-CreERT2-T2A-CFP gene segment, and obtaining an ENPP6-CreERT2 knock-in mouse through a gene editing technology; the ENPP6-CreERT2 mouse and the mT / mG report mouse are subjected to mating, and ENPP6-CreERT is obtained; an mT / mG double transgenic mouse; carrying out tamoxifen induction treatment on the double transgenic mice in a target time period, and activating Cre recombinase; brain tissues are collected after induction, and marked middle-stage oligodendroglia cells and myelin sheath structures formed by the middle-stage oligodendroglia cells are observed through a fluorescence report system. According to the invention, the purpose of specifically marking new myelin sheath during tamoxifen induction is achieved. And a new research tool is provided for controlling new myelin sheath in a specific time period. The problems that all new myelin sheaths after induction start can be marked in an existing method, and the new myelin sheaths in the induction period cannot be specifically marked are solved.

The invention belongs to the technical field of medical biological research, and particularly relates to construction and evaluation of a chronic obstructive pulmonary epithelial cell senescence model. A method for constructing a chronic obstructive pulmonary epithelial cell senescence model comprises the following steps: exposing tobacco smoke after 6-8 weeks of Muc1 gene whole-body knockout mice and / or exposing tobacco smoke after 6-8 weeks of Muc1 whole-body knockout rats and / or injecting tamoxifen into abdominal cavities of the mice when the Muc1 type II alveolar epithelial cell knockout mice are 6-8 weeks old, and then exposing tobacco smoke every one week. According to the invention, a series of evaluations are carried out on lung tissue pathological changes, lung epithelial cell changes and other indexes of the constructed model product, and the success of the construction of the chronic obstructive pulmonary pulmonary epithelial cell senescence model is jointly proved.