22 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.

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.

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

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.

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 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 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 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.

The invention discloses an application of ranunculaceol in preparation of anti-cancer drugs. The invention proposes and verifies that the ranunculool can induce ferroptosis by regulating a Dcp1a related pathway for the first time, remarkably inhibits the activity of cancer cells, and further inhibits the progress of drug-resistant breast cancer; meanwhile, the combined application of the ranunculate and the tamoxifen can effectively improve the treatment effect of the tamoxifen on the drug-resistant breast cancer, and a new direction is provided for the treatment of the tamoxifen drug-resistant breast cancer.

This invention discloses a method for constructing a spontaneous psoriasis mouse model and its application, which will be applied to fatty acid synthase. Basin Chimeric mice were obtained by injecting embryonic stem cell clones with the loxP site inserted into their genes into blastocysts. These chimeric mice were then mated to produce... Basin flox / flox Mice; and tool mice Krt14‑CreERT2 + / ‑ Pairing and grouping animals together to screen for genotypes that are suitable for breeding. Krt14‑CreERT2 + / ‑ ; Basin flox / flox Mouse models of spontaneous psoriasis were obtained by continuous induction with tamoxifen. The spontaneous psoriasis mouse model constructed in this invention is superior to acute models that require exogenous induction, facilitating long-term observation and intervention experiments, and providing a more ideal tool for studying the pathogenesis of psoriasis and screening and evaluating new drug candidates for psoriasis.

The application discloses a use of sildenafil in preparation of an anti-breast cancer drug in combination with tamoxifen, and sildenafil can promote the entry of GAPDH into a nucleus and inhibit the proliferation of tamoxifen-resistant cells (MCF-7TR). The application also discloses an anti-breast cancer drug composition which can inhibit the proliferation of breast cancer tamoxifen-resistant cells (MCF-7TR) and thus reverse the sensitivity of the drug-resistant cells to tamoxifen, and the composition comprises sildenafil and tamoxifen. The application utilizes the targeted reversing effect of sildenafil on breast cancer cells resistant to tamoxifen, so that the breast cancer tamoxifen-resistant cells can be restored to be sensitive to tamoxifen, and a more economical, convenient and effective treatment option is brought to tumor patients.