50 results about "Tamoxifen" patented technology

Disclosed is an anticancer composition using a flavone derivative. In the present invention, the flavone derivative exhibits cytotoxicity against: H827, H1299, H522, and A549, which are human non-small cell lung cancer cell lines; MCF-7, which is a human breast cancer cell line; and PANC-1, which is a human pancreatic cancer cell line, in a time-dependent manner and in a treatment concentration-dependent manner, and not only exhibits a synergistic effect when used in combination with other conventional anticancer agents, such as osimertinib, which is an anticancer agent targeting for lung cancer, tamoxifen, which is a hormone agent against breast cancer, and gemcitabine, which is a cytotoxic anticancer agent against pancreatic cancer, but also exhibits the effect of synergistically inhibiting the expression of HIF-1α when used alone or in combination with an existing anticancer agent.

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

Most of therapeutic failures in chemotherapy during cancer invasion and metastasis are attributed to drug resistance. The inventors aimed to investigate the potential of targeting the secreted protein, eAGR2 as a novel adjuvant strategy to enhance the effectiveness of chemotherapy and overcoming chemoresistance in cancer therapy. Remarkably, extracellular AGR2 (eAGR2) demonstrated the ability to enhance resistance to both (doxorubicin and tamoxifen) treatments. Furthermore, even in the case of drug-resistant cancer cells that exhibited inherent resistance to chemotherapy, supplementation with an AGR2-blocking antibody restored sensitivity to tamoxifen in vitro. Thus, the inventor shed light on previously unknown chemotherapy resistance in resistant breast cancer cells, which can be effectively overcome by blocking eAGR2. Consequently, the inhibition of eAGR2 emerges as a promising adjunctive approach for concurrent administration alongside existing first- and second-line cancer therapies. This not only has the potential to bolster the efficacy of chemotherapy but also to prevent tumour chemoresistance.

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 invention aims to provide a novel application of a ferroptosis inhibitor, and the ferroptosis inhibitor is Liproxstatin-1. Research is carried out on the ferroptosis phenomenon in the follicle atresia process of egg laying poultry, it is found that the ferroptosis inhibitor Liproxstatin-1 can save follicle particle cell death induced by tamoxifen (TMX), can inhibit the oxidative stress level and intracellular iron ion overload caused by TMX treatment, effectively inhibits the follicle ferroptosis phenomenon induced by TMX, and can be used for preparing the follicle atresia inhibitor Liproxstatin-1 and the follicle atresia inhibitor Liproxstatin-1 in the follicle atresia process of egg laying poultry. And finally, the egg laying function of livestock and poultry is recovered, and the traditional Chinese medicine composition can be developed into a medicine for treating follicular atresia of livestock and poultry for treating follicular atresia.

The present invention discloses a 3,3-diaryl-phenyl acrylate derivative and a synthesis method thereof. Using o-bromostilbene as a raw material, under the catalysis of a palladium salt, a coupling reaction is carried out with phenyl formate to stereospecifically synthesize a series of 3,3-diaryl-phenyl acrylate derivatives with different structures, and the product can be further converted into the (Z)-Tamoxifen drug molecule. This method has easily available raw materials, simple operation, mild reaction conditions, and the functional groups have diversity.

The invention discloses application of alpha spiral polypeptide combined with tamoxifen to preparation of an anti-breast cancer pharmaceutical composition, and belongs to the technical field of biological medicine. A large number of experimental studies show that the alpha spiral polypeptide 6w and tamoxifen are combined for medication, the killing ability of the ERalpha high-expression breast cancer cell line can be obviously improved, the phenomena of apoptosis, cell cycle arrest in the G0 / G1 phase and the like of the ERalpha high-expression breast cancer cell line can be obviously improved, an estrogen receptor signal channel can be inhibited, and the ERalpha high-expression breast cancer cell line can be used for treating the ERalpha high-expression breast cancer cell line. The expression level of related genes such as pS2 at the downstream of a signal is obviously reduced, and the proliferation of tamoxifen drug-resistant cells can be better inhibited.

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.

Described herein are compounds of Formula I, or their pharmaceutically acceptable salts thereof, compositions comprising the same, and methods of using such compounds or compositions in inducing Cdc20 degradation in a cell, blocking mitotic progression, inhibiting tumor proliferation, treating cancer, and / or re-sensitizing a subject to cancer treatment with tamoxifen.

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.

To provide a novel production technique applicable to the production of Z-tamoxifen through the use of low-cost and easily available chemicals as starting materials, and also to establish a stereoselective synthesis technique of E-tamoxifen, which is the other isomer.SOLUTION: The present invention provides a method for producing a tamoxifen precursor, the method comprising a step of reacting (A) dihalodiphenylethylene with a boron compound having a 4-(2-dimethylaminoethoxy)phenyl group to produce a tamoxifen precursor represented by the following formula (in the formula, R represents a 2-dimethylaminoethoxy group, and X represents a halogen atom).SELECTED DRAWING: None

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 belongs to the technical field of tumor treatment, and particularly discloses a copper silicate-based nano targeting drug delivery system for synergistically treating breast cancer, which comprises CuSiO3, tamoxifen, narcissus-derived carbon quantum dots, polyethylene glycol and hyaluronic acid. The preparation method comprises the following steps: loading tamoxifen and narcissus-derived carbon quantum dots on CuSiO3 through electrostatic interaction, carrying out polyethylene glycol covalent modification, and coating with hyaluronic acid with targeting ability to prepare the CuSiO3 (at) TAF (at) CDs-PEG-HA nano targeting drug delivery system. According to the copper silicate-based nano-targeting drug delivery system for synergistically treating breast cancer, intracellular redox steady-state imbalance is caused based on oxidative stress and weakened antioxidant capacity, so that the copper silicate-based nano-targeting drug delivery system shows an efficient tumor treatment effect on human breast cancer cells and tumor-bearing mouse models.

The present invention relates to a specific Cul7 gene knockout mouse model and a method and application for establishing the same based on the Cre / LoxP system. Specifically, parental Cul7<supgt;fl / fl< / supgt; mice are crossed with Col2a1-CreERT2 mice to obtain offspring with the genotype Cul7<supgt;fl / +< / supgt>; Col2a1-CreERT2 mice. The obtained Cul7<supgt;fl / +< / supgt>; Col2a1-CreERT2 mice are then crossed with Cul7<supgt;fl / fl< / supgt> mice, and Cul7<supgt;fl / fl< / supgt>; Col2a1-CreERT2 mice are obtained through genotyping of the offspring mice. The Cul7<supgt;fl / fl< / supgt>; Col2a1-CreERT2 mice are intraperitoneally injected with tamoxifen after birth, and a Cul7 cKO mouse model is successfully constructed, which shows obvious growth retardation and short limbs, consistent with the clinical manifestations of patients with 3M syndrome. The successful establishment of the model in the present invention provides a reliable experimental model for further studying the Cul7 gene signaling pathway and the pathogenic mechanism of 3M syndrome in the future.

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.

The present invention relates to a method for constructing a transgenic lung adenocarcinoma mouse model with overexpression of MR-1, and the method comprises the following steps: Step 1, constructing a PNKD gene knock-in model mouse; Step 2, obtaining cKP mice; Step 3, mating the cKP mice obtained in Step 2 with the PNKD gene knock-in mice obtained in Step 1; Step 4, inducing genotype change with tamoxifen; Step 5, detecting.

The invention discloses a bone marrow mesenchymal stem cell exosome and application thereof. The mesenchymal stem cell exosome disclosed by the invention is prepared by treating mesenchymal stem cells through serum containing tamoxifen-resistant traditional Chinese medicine compound active ingredients and a breast cancer drug-resistant cell exosome. The mesenchymal stem cell exosome can be used for treating endocrine drug-resistant breast cancer, especially tamoxifen drug-resistant breast cancer, and the curative effect of the mesenchymal stem cell exosome is superior to that of a traditional Chinese medicine compound administration mode.

The present invention provides a system for drug-inducible expression of a polynucleotide comprising a) a first nucleic acid sequence comprising a first promoter inducible by said drug, wherein the first promoter is operably linked to said polynucleotide, wherein said first promotor comprises a binding site for a DNA binding domain, wherein said binding site comprises at least one responsive element that is recognized by said DNA binding domain (DBD), and b) a second nucleic acid sequence comprising a second promoter, wherein the second promoter is operably linked to a nucleic acid sequence encoding a synthetic transcription factor, wherein said synthetic transcription factor comprises i) an activation domain (AD), wherein said AD comprises the p65 activation domain of the human transcription factor NFκB or a functional variant thereof, ii) said DNA binding domain (DBD), wherein said DBD comprises or consists of 3 zinc finger domains, iii) a ligand-binding domain (LBD), wherein said LBD is a modified human estrogen receptor which is able to bind said drug, and wherein said ligand-binding domain (LBD) is positioned at the C-terminus of said synthetic transcription factor, and c) said drug, wherein said drug is tamoxifen or a metabolite of tamoxifen.