158 results about "Tamoxifen" patented technology

This invention relates, e.g., to a method for predicting the response of a subject having estrogen-receptor-positive breast cancer to an inhibitor of the estrogen signaling pathway (e.g. tamoxifen), comprising measuring in a cancer sample from the subject the level of phosphorylation, compared to a baseline value, of one or more of the following members of an interconnected intracellular signaling pathway: (a) 4EBP1, and / or (b) p70S6, and / or (c) STAT3, and / or (d) FAK, wherein a significantly elevated level of phosphorylation of 4EBP1, and / or p70S6 and / or STAT3, and / or a significantly decreased level of phosphorylation of FAK, compared to the baseline value, indicates that the subject is likely to be a non-responder to the inhibitor and / or has a poor prognosis. Additional members of the intracellular signaling pathway whose phosphorylation can be measured are also described. Also described is a method for treating breast cancer in a subject in need thereof, wherein the subject exhibits an elevated level of phosphorylation of these markers, comprising administering to the subject an effective amount of one or more inhibitors of members of the interconnected intracellular signaling pathway.

The invention is directed to an improved drug delivery system that includes a micelle, comprising polyethylene glycol and a lipid component, and a pharmaceutical agent dispersed in the lipid component. The delivery system may also include a targeting ligand. The micelle delivery system of the invention is capable of stabilizing, inter alia, poorly soluble pharmaceutical agents and increasing their delivery efficacy. Appropriate pharmaceutical agents useful in the system of the invention include anti-inflammatory agents, agents for photodynamic therapy, anti-tumor agents, anti-neoplastic agents, anti-metastatic agents, and imaging agents, as well as hydrophobized derivatives thereof. Specifically, the pharmaceutical agent can be porphyrin, chlorine-6-trimethyl ester, tamoxifen, paclitaxel, 1,3-bis(2-chloroethyl)-1-nitrosourea, camptothecin, ellipticine, rhodamine, dequalinium, diphenylhexatriene, vitamin K3, diethylene triamine pentaacetic acid, or a functional derivative thereof. The micelles in the system of the invention have low critical micellar concentration and high kinetic stability, which provides great advantages in biodistribution, for example, accumulation at the site of a tumor.

An encapsulated delivery system, and, in particular, a nanoparticulate delivery system representing a qualitatively different approach to overcoming multi-drug resistance while simultaneously administering the chosen drug treatment to a patient, e.g., in a site-specific manner, is disclosed. A composition according to the invention includes a therapeutically effective amount of one or more multi-drug resistance reversing agents selected from the group consisting of ceramide and ceramide modulators; and a therapeutically effective amount of a therapeutic agent, wherein the therapeutic agent is different from the one or more multi-drug resistance reversing agents, and the one or more multi-drug resistance reversing agents and the therapeutic agent are encapsulated, preferably co-encapsulated, in a biocompatible, biodegradable delivery vehicle for delivery to a patient in need of treatment, for example, for specific localization at, or higher probability of delivery to, a treatment site in a patient administered the composition. Preferably, the one or more multi-drug resistance reversing agents are ceramide, paclitaxel or tamoxifen.

The various embodiments of the present disclosure relate generally to compositions and methods for the targeted cellular delivery of nanoparticles. More particularly, the various embodiments of the present invention are directed to the cellular delivery of nanoparticles tethered to a ligand by way of a poly(ethylene glycol) linkage, wherein the ligand demonstrates a binding specificity for a cellular target. In an exemplary embodiment, the ligand is tamoxifen and the cellular target is the estrogen receptor, which is upregulated in many breast cancer cells.

Acridine containing cisplatin compounds have been disclosed that show greater efficacy against cancer than other cisplatin compounds. Methods of delivery of those more effective cisplatin compounds to the nucleus in cancer cells is disclosed using one or more amino acids, one or more sugars, one or more polymeric ethers, C1-6alkylene-phenyl-NH—C(O)—R15, folic acid, αvβ3 integrin RGD binding peptide, tamoxifen, endoxifen, epidermal growth factor receptor, antibody conjugates, kinase inhibitors, diazoles, triazoles, oxazoles, erlotinib, and / or mixtures thereof; wherein R15 is a peptide.

A method for determining the likelihood that a therapy involving administration of tamoxifen to a patient afflicted with an estrogen receptor positive breast cancer will provide a therapeutic benefit to the patient which comprises determining the level of expression of epidermal growth factor receptor present within a non-nuclear compartment in cells present in a breast tissue sample from the patient; and comparing the level of expression so obtained to a predetermined level of expression wherein the likelihood the therapy will provide a therapeutic benefit to the patient is greater if the level of expression in step a) is less than the predetermined level of expression.

Provided are methods and compositions for reducing the toxicity of certain hydrophobic therapeutic agents, especially polyene antibiotics, in particular, Amphotericin B (AmB), and therapeutics such as paclitaxel, tamoxifen, an acylated prodrug or an acylated cis-platin, by incorporating these agents within micelles comprising an amphiphilic block-forming copolymer. Where the polyene is amphotericin B, desirably the spacer is an alkyl molecule of aabout 2 to about 8 carbon atoms, desirably 6 carbon atoms, and the core is an N-alkyl molecule of about 8 to about 28 carbon atoms, desirably 12 to 22 carbon atoms, advantageously, 12 to 18 carbon atoms, and as specifically embodied, 18 carbon atoms (stearate moiety). For the formulation of a larger polyene, the spacer and core are proportionately larger than those for amphotericin B. As specifically exemplified herein, the polymer backbone is a PEO of about 270 units with about 10-30 core-forming PLAA subunits, and advantageously about 14-24. Desirably the stearate moiety has a substitution level on the copolymer from about 35 percent to about 70 percent.

Provided are cosolvent evaporation methods and compositions for improving the solubility of hydrophobic compounds, including therapeutic agents such as anticancer drugs, polyene antibiotics, antilipidemic agents, and hydrophobic compounds used in various industries, and / or for reducing the toxicity of certain hydrophobic therapeutic agents, especially polyene antibiotics, in particular, Amphotericin B (AmB), and therapeutics such as paclitaxel, tamoxifen, an acylated prodrug or an acylated cis-platin, by incorporating these agents within micelles comprising an amphiphilic block-forming copolymer.

The flavonoid family of phytochemicals, particularly those derived from soy, has received attention regarding their hormonal activity and their effects on human health and disease. The types and amounts of these compounds in soy and other plants are controlled by both constitutive expression and stress-induced biosynthesis. The health benefits of soy may therefore be dependent upon the amounts of the various hormonally active phytochemicals present. We have identified increased biosynthesis of the isoflavonoid phytoalexin compounds, Glyceollins I, II and III, in soy plants grown under stressed conditions (elicited soy), which exhibit marked anti-estrogenic effects on ER function. Here we demonstrate that specific glyceollins, isolated from elicited soy, displayed anti-estrogenic activity, suppressing basal and estrogen stimulated colony formation of ER-positive estrogen dependent breast cancer cells and inhibiting ER-dependent gene expression of progesterone receptor (PgR) and stromal derived factor-1 (SDF1 / CXCL12). Examining the effects of glyceollin on in vivo tumor formation / growth we demonstrate the ability of glyceollins to significantly suppress basal and estrogen-stimulated tumor growth of ER-positive MCF-7 breast and BG-1 ovarian carcinoma cells in ovariectomized female nude mice. We further demonstrate that the effects of glyceollins on suppression of tumor growth correlate with inhibition of estrogen stimulated PgR expression. In contrast to the uterotropic activity of tamoxifen the glyceollins displayed no uterine agonist activity. The Glyceollin (I-III) compounds may represent an important component of the health effects of soy as well as represent novel anti-estrogens useful in the prevention or treatment of breast and ovarian carcinoma.

Pharmaceutical composition comprising a chemotherapeutic agent and a TGF-beta antisense oligonucleotide, wherein the antisense oligonucleotide reduces the sensitivity and IC50, respectively, of the cytotoxicity of the chemotherapeutic agent. Preferably, the antisense oligonucleotide is a TGF-beta 1, 2, and / or 3 antisense oligonucleotide and the chemotherapeutic agent is preferably gemcitabine, 5-fluorouracil, temozolomide, dacarbacine, docetaxel, cisplatin, oxaliplatin, tamoxifen, or irinotecan.

The disclosed method rapidly identifies with desired accuracy AML patients, including elderly AML patients, likely to respond to treatment with a combination of a farnesyltransferase inhibitor and one or more of etoposide, teniposide, tamoxifen, sorafenib, paclitaxel, temozolomide, topotecan, trastuzumab and cisplatinum. In an embodiment, the improvements include the use of whole blood rather than the customary bone marrow sample, thus making the assay more accurate, rapid, less intrusive, less expensive as well as less painful. The method includes evaluation of a two-gene expression ratio (RASGRP1:APTX), which with a corresponding threshold, provides sufficient accuracy for predicting the response to the combination treatment. In the preferred embodiment the combination treatment combines tipifarnib (R115777, ZARNESTRA®) with etoposide. Further, the elderly AML patients identified as being likely responsive to the combination treatment with tipinifarb and etoposide have a complete recovery rate comparable to the best therapy available for younger patients.

The invention relates to the technical field of animal models and concretely, relates to a method for building an animal model with PHF 14 gene knockout-based acute kidney injury and renal fibrosis after injury. The invention builds a model of renal fibrosis after kidney injury under the genetic background of PHF 14 gene knockout under adult conditions and provides essential conditions for researching a use of a PHF 14 gene in fibrotic diseases. Compared with the existing PHF 14 knockout model, the PHF 14 gene knockout provided by the invention does not cause embryonic lethal. A test on adult-stage tamoxifen induced knockout of PHF 14 proves that the PHF 14 gene knockout does not cause embryonic lethal. Compared with a group without knockout, the group subjected to knockout has no substantial pathology of lung, liver and kidney. The method prevents systemic disease state-caused interference on following-up acute kidney injury model making and realizes individual research on use of the gene defect in renal fibrosis pathogenesis.

The invention discloses a kit and method for detecting the tamoxifen personalized medicine genetic polymorphism by use of the pyrosequencing technique. The genetic polymorphism specifically refers to the single nucleotide polymorphism of CYP2D6*10(rs1065852) and (SULT1A1*2) (rs9282861). The kit comprises the primer shown by SEQ ID NO.3-8. The kit disclosed by the invention can realize accurate, quick and high-flux detection on CYP2D6*10(rs1065852) and (SULT1A1*2) (rs9282861) so as to realize safe, reasonable and effective personalized administration of the tamoxifen medicine.

The present invention relates to methods and compositions for inhibiting cell survival and / or promoting cell death following exposure to cytotoxic agents and stress such as radiation or chemotherapy exposure through inhibition of V-H+-ATPase. In particular, the formation and / or acidification of acidic vesicular organelles (AVOs) may be prevented or decreased by inhibiting the activity of vacuolar proton ATPase (“V-H+-ATPase”). The methods and compositions of the invention are based on the observation that (i) following irradiation surviving cancer cells accumulate AVOs and that their acidification is mediated by V-H+-ATPase; (ii) surviving colonies of cells contain higher levels of AVOs; and (iii) inhibition of V-H+-ATPase decreases the clonogenic survival of cells irradiated or exposed to chemotherapeutic agents. These observations led to the conclusion that V-H+-ATPase activity and AVO function serve to protect cells from radiation and chemotherapy damage. In addition, agents such as bFGF, TNF-α, PMA, rapamycin and tamoxifen were shown to be inducers of acidic organelle formation. Therefore signal transduction pathways mediated by these agents provide targets for drug screening assays designed to identify inhibitors of V-H+-ATPase activity and AVO formation / acidification. The present invention may be used to treat cancer subjects through sensitization of neoplastic cells to the toxic effects of radiation and chemotherapy.

The invention discloses a novel use of formononetin in pharmacy, and in particular discloses an application of formononetin in preparing a medicine for treating breast cancer. The applicants discover that formononetin can remarkably inhibit cell proliferation of breast cancer for the first time and discover through experiments that formononetin retards cell cycle by way of inactivating IGF1 / IGF1R-PI3K / AKT, so that formononetin generates good activity of inhibiting cell proliferation of breast cancer, and can be used as a cell cycle retardant to replace tamoxifen to inhibit cell proliferation of breast cancer so as to prevent and treat breast cancer. In addition, the applicants in experiments further discover that formononetin can be used as the cycle retardant for cancer cells and has specific targeting to normal cells as an agonist, so that formononetin has very high development value and real application value.

The invention belongs to technical field of medicines and specifically relates to an oxygen bridge bis-heptylene sulfonamide compound containing a suberic acid monoanilide group as well as a synthesizing method, application and an anti-breast cancer drug composition of the oxygen bridge bis-heptylene sulfonamide compound. The oxygen bridge bis-heptylene sulfonamide compound containing the suberic acid monoanilide group is prepared by one-step reaction of the following raw materials: 3-(4-hydroxyphenyl)-4-suberic acid monoanilino-furan and an ethenyl sulfonamide derivative at the temperature of 90 DEG C for 3 without a solvent or a catalyst. The oxygen bridge bis-heptylene sulfonamide compound is different from the existing anti-breast cancer drug tamoxifen in action modes and is an anti-breast cancer compound acting on an estrogen receptor and histone histone deacetylase dual target sites.

The invention discloses a tamoxifen flexible nano-liposome gel and a preparation method thereof. The gel is prepared from the following raw materials at a certain ratio: tamoxifen, cholesterol, phospholipid material, water-soluble gel substrate, transdermal penetration enhancer, surface active agent, preservative, humectants, pbs buffer solution, ammonia water, distilled water and ethyl alcohol. The preparation method comprises the following steps: 1) preparing a tamoxifen flexible nano-liposome suspension; 2) preparing a blank gel substrate; and 3) uniformly mixing the tamoxifen flexible nano-liposome suspension with the blank gel substrate, thereby acquiring the tamoxifen flexible nano-liposome gel. The gel has higher drug-carrying capacity and encapsulating effect to tamoxifen and has higher stability and transdermal permeability. The preparation method is simple, the operation is convenient and the preparation cost is low.

The invention relates to protecting functions and applications of FSTL1 in anti-fibrosis steady-state regulation of tissues such as livers, and particularly relates to uses of FSTL1 protein or an FSTL1 regulating compound in preparation of medicines treating tissue fibrosis diseases. The invention also relates to a conditional FSTL1 gene knockout non-human animal model closely related to the degree of tissue fibrosis pathological changes, a preparing method thereof and uses of the model in tissue-fibrosis-preventing medicine screening. Treatment is performed by combining different tamoxifen dosages and different animal growth stages, the systemic or vascular endothelial cell FSTL1 gene knockout non-human animal model is obtained and the model is used for simulating different tissue fibrosis pathological changes.

The invention discloses an exogenous-gene removable slow virus controlled expression carrier system and an application. The system comprises a reaction / regulation plasmid and a packaging plasmid; a construction method is as follows: a loxP sequence is inserted into a pSMPUW 3'LTR through site-specific mutagenesis, an original promoter is replaced by a TRE and a simplest CMV promoter, and an exogenous reporter gene is inserted into an MCS to obtain the reaction plasmid; a CMV-rtTA2S-M2 sequence, an EMCV sequence and a Cre-ER sequence are inserted into the pSMPUW subjected to site-specific mutagenesis to obtain the regulation plasmid. The application is as follows: packaging is conducted to obtain a reaction / regulation slow virus; both the reaction slow virus and the regulation slow virus are cotransfected to a target stem cell, a Dox induction exogenous reporter gene is used for expressing and tracing the image, and finally a 4-OH-tamoxifen is used for inducing and excising the exogenous reporter gene. According to the invention, the exogenous reporter gene is expressed in a controlled manner in vivo and can also be removed immediately to avoid disturbing the normal physiological function of a target cell.

The invention discloses a tamoxifen drug resistance related microRNA molecule MiR-200a and application thereof, and belongs to the field of tumor biotherapy. The nucleotide sequence of the tamoxifen drug resistance related microRNA molecule MiR-200a disclosed by the invention is as shown in SEQ ID NO. 1. The MiR-200a, as a novel breast cancer tamoxifen drug-resistance marker, has the characteristics of low expression in ER positive breast cancer tamoxifen drug-resistance cells and high expression in ER positive breast cancer tamoxifen sensitive cells. Therefore, the invention provides a new target for designing breast cancer tamoxifen drug-resistance drugs, and subsequently, new drugs, directly corresponding to breast cancer tamoxifen drug resistance, are designed and developed. The MiR-200a disclosed by the invention has a biological function and an action mechanism of promoting breast cancer cell drug resistance; therefore, an effective way is provided for the effective reversal of breast cancer tamoxifen drug resistance and for the improvement of clinical chemotherapeutic effect on the breast cancer.

The invention relates to a 1, 1, 2-triaryl-1, 3-butadiene compound one-step synthesized from raw materials simple and easy to obtain by applying classical Suzuki-Miyaura coupling reaction and can also obtain anticancer substance Tamoxifen by using simple and known converting steps. In structure, the obtained compound contains a triaryl tetra-substituted ethylene unit similar to Tamoxifen, therefore it possibly has a certain clinical medicinal application value and has the value of screening and applying anticancer drugs of a kind.

The invention discloses an oxo-bridged bicyclo-heptylene sulfonamides compound containing different alkyl chain lengths, as well as a preparation method and application thereof, and belongs to the technical field of medicines. 3-(4-hydroxycyclohexyl phenyl)-4-(4-alkoxy phenyl)-furan and a phenylethylene sulfonamide derivative are adopted as raw materials, no catalyst is needed, the raw materials are reacted at 90 DEG C for 8 hours, and the oxo-bridged bicyclo-heptylene sulfonamides compound containing the different alkyl chain lengths is obtained through one-step preparation. The action mode of the oxo-bridged bicyclo-heptylene sulfonamides compound is different from the action mode of existing anti-breast cancer drug tamoxifen, and the compound not only can be used for effectively inhibiting the growth of a breast cancer cell MCF-7, but also has favorable estrogen receptor alpha down-regulation activity equivalent to fulvestrant, and shows an application prospect of the compound in breast cancer therapy.

The invention relates to a transcription activator like effector (TALE)-functional group-estrogen receptor (ER) function protein and an application thereof, wherein the TALE-functional group-ER function protein is formed by sequentially linking TALE, ER and a functional group or sequentially linking TALE, a functional group and ER, wherein the functional group is a combination comprising one or more than two materials selected from activation domain (AD), nuclease, methylase, demethylase and recombinase. During practical application, tamoxifen (TAM) or 4-OH-tamoxifen (4-OH-TAM) are introduced into cytoplasm so as to control the function protein to enter nucleus at the specific time.

The invention discloses an application of ligustilide as an adjuvant drug of antitumor drugs. The research found that ligustilide can directly inhibit autophagy and then can perform combined effects with the antitumor drugs such as tamoxifen, cis-platinum and the like, the antitumor effect is improved, and the drug resistance of tumor cells to the antitumor drugs can be improved.

The invention relates to a construction method of an STAT3 mitochondrial localization conditional gene knock-in mouse model. The method comprises the following steps: firstly, constructing an STAT3 mitochondrial localization conditional gene knock-in recombinant targeting vector, transfecting the recombinant targeting vector to fertilized ova of a donor mouse, and then transplanting the donor mouse fertilized ova into the uterus of a fake pregnant mother mouse to produce a chimeric mouse; mating the chimeric mouse with a C57BL / 6J mouse to obtain an F1 generation; mating the F1 generation witha mouse of tissue-specific expression Cre recombinase to obtain a double-hybrid mouse; and are intercrossing the double-hybrid mouse and an STAT3<f / +> or STAT3<f / f> mouse, and inducing the obtained offspring by tamoxifen to obtain the STAT3 mitochondrial localization conditional gene knock-in mouse model. According to the mouse model disclosed by the invention, the STAT3 gene is expressed in specific tissues and cell types, and an ideal model is provided for researching the action mechanism of STAT3 in specific cell development and differentiation, body metabolism and tumor occurrence and development.

The invention discloses a method for preparing a pyrazole derivative and a tetra-substituted olefin (Z)-Tamoxifen which is a clinical drug for treating the breast cancer from a polysubstituted sulfo-olefin. The pyrazole derivative is prepared by carrying out a condensation cyclization reaction on a raw material alpha-oxoketone monothioacetal which is easy to prepare and has a structure diversity and various reaction centers and a nucleophilic reagent hydrazine at a reflux temperature; and the tetra-substituted olefin (Z)-Tamoxifen is prepared by carrying out a coupling reaction on the raw material alpha-oxoketone monothioacetal and arylboric acid at 50DEG under the catalysis of Pd. Compared with reported preparation methods of the pyrazole derivative and (Z)-Tamoxifen, the preparation method makes products have the advantages of good regioselectivity and stereoselectivity, easily available raw material, simple operation, mild preparation reaction conditions, and high efficiency.

The invention relates to a medicine for treating lobular hyperplasia of galactophore, which aims at solving the technical problems that the prior medicine for treating lobular hyperplasia of galactophore fails to address both the symptoms and root causes. The medicine comprises the following compositions in weight portion: 5 to 30 portions of angelica, 10 to 60 portions of radices paeoniae alba, 10 to 30 portions of dandelion, 5 to 25 portions of bistortae, 5 to 35 portions of herba violae, 15 to 45 portions of spreading hedyotis herb, 15 to 45 portions of barbat skullcap and 0.6 to 5 portions of tamoxifen. The medicine contains compositions of traditional Chinese medicines and western medicines which are synergic to take effect; the compositions of traditional Chinese medicines soothe liver, invigorate spleen, nourish blood and regulate menstruation; and the compositions of western medicines can competitively obstruct an estrogen receptor, thereby completely removing pathogeny and address the disease both symptoms and root causes.

The invention discloses a method to make medicine using Chitin-fiber used for prevent hyperplasia of mammary glands and the application. It contains Chitin, medicine and medicine adsorbing accelerant. The medicine includes one or more from Tamoxifen, isoflavone, bromocriptine and Danazol. The medicine adsorbing accelerant is one or the compound from azone, oleic acid, N-methyl-2- pyrrolidone, propylene glycol, and borneol. The Chitin contains weight proportion of A, medicine contains weight proportion of B and medicine adsorbing accelerant contains weight proportion of C, and 60 D01F 9 / 00 D01F 1 / 10 D01D 5 / 00 A61L 15 / 28 A41C 3 / 00 A41B 9 / 12 0 6 1 2006 / 8 / 17 1936128 2007 / 3 / 28 100447320 2008 / 12 / 31 2008 / 12 / 31 2008 / 12 / 31 Lifangjian Medical Sci. & Tech. Consulting (Shanghai) Co., Ltd. Shanghai 201108 Zhu Limin Fan Zaixia dongmei 31208