59 results about "Positive Estrogen Receptor" patented technology

The present invention relates to quantitative molecular indicators that can guide clinical decisions in breast cancer, such as estrogen receptor (ESR1)-positive, lymph node-negative breast cancer. In particular, the invention concerns certain genes, the varied expression of which indicates the likelihood of recurrence of surgically resected breast cancer in patients who are not treated with a therapeutic agent in the adjuvant setting. In addition, the invention concerns the use of quantitative measurement of the expression of certain genes, including the ESR1 gene, that measure as a continuous variable, to determine (a) the likelihood of a beneficial response to the anti-estrogen therapeutic agent, such as tamoxifen; and (b) the potential magnitude of beneficial response to chemotherapy.

Described herein are methods and compositions for treating an ER-related disease condition characterized by a mutation in the ESR1 gene by administering an estrogen receptor modulator. Also described herein are methods of treating hormone resistant-estrogen receptor (ER) positive breast cancers characterized by a mutation in the ESR1 gene by administering an estrogen receptor modulator.

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.

Estrogenic compositions comprising calycosin and analogs thereof are provided. Also provided are methods of using said extracts to achieve an estrogenic effect, especially in a human, e.g. a female human. In some embodiments, the methods include treatment of climacteric symptoms. In some embodiments, the methods include treatment of estrogen receptor positive cancer, such as estrogen responsive breast cancer. In some embodiments, the methods include treatment or prevention of osteoporosis.

The present application demonstrates that HDAC inhibitors can be used in combination with hormonal therapy to treat and prevent estrogen receptor positive breast cancer. HDAC inhibitors can also be combined with IGF-1R inhibitors, mTOR inhibitors, and EGFR inhibitors to treat breast cancer, optionally in combination with hormonal therapy if indicated. Combinations of the compounds, with or without HDAC inhibitors, and with or without hormonal therapy, can also be used. The invention therefore provides methods of treatment and pharmaceutical compositions.

Estrogenic compositions comprising nyasol and analogs thereof are provided. Also provided are methods of using said extracts to achieve an estrogenic effect, especially in a human, e.g. a female human. In some embodiments, the methods include treatment of climacteric symptoms. In some embodiments, the methods include treatment of estrogen receptor positive cancer, such as estrogen responsive breast cancer. In some embodiments, the methods include treatment or prevention of osteoporosis.

Estrogenic extracts of Asparagus conchinchinensis (Lour.) Merr of the Liliaceae Family are provided. Also provided are methods of using said extracts to achieve an estrogenic effect, especially in a human, e.g. a female human. In some embodiments, the methods include treatment of climacteric symptoms. In some embodiments, the methods include treatment of estrogen receptor positive cancer, such as estrogen responsive breast cancer. In some embodiments, the methods include treatment or prevention of osteoporosis.

A method for selecting a breast cancer patient for therapy with an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor, comprises (a) determining whether the cancer comprises a tumor that is estrogen receptor positive (ER+) and (b) selecting the patient for such therapy only if the cancer is determined to comprise an ER+ tumor. A method for treating breast cancer in a patient further comprises (c) administering to the patient, if so selected, an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor. A method for treating a breast tumor in a patient having SERM-resistant ER+ breast cancer comprises administering to the patient an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor. A therapeutic combination useful in treatment of a breast tumor comprises an agent that reduces production of angiotensin II, for example an ACE inhibitor or renin inhibitor, and a second agent that comprises (a) an aromatase inhibitor or (b) an estrogen receptor modulator or antagonist.

The invention provides a selective inhibitor of CDK8 / 19 for use in a method of treating a patient having estrogen receptor positive (ER+) breast cancer, including breast cancer that is resistant to antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8 / 19 is administered in combination with antiestrogen therapy. In some embodiments, the selective inhibitor of CDK8 / 19 is administered to ER+HER2+ breast cancer patients in combination with HER2-targeting drugs.

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.

The present invention provides methods for increasing sensitivity of cancer cells to an antiestrogen agent, such as a selective estrogen receptor modulator (SERM). The methods include administering to the subject a polynucleotide in an amount effective to increase the antiestrogen agent sensitivity of the cancer cells. The cancer cells may be estrogen receptor positive, such as ER-α66 positive or ER-α36 positive, prior to the administering. Also provided are methods for decreasing the amount of estrogen receptor present in a cancer cell, methods for determining whether antiestrogen agent sensitivity of cancer cells in a subject can be increased, methods for diagnosing whether a subject has, or is at risk for developing, cancer, and methods for identifying an agent that increases the amount of let-7 miRNA in a cell.

The invention provides a 3-substituted acrylic acid compound as well as a preparation method and application thereof and in particular relates to a 3-substituted acrylic acid compound, a stereoisomer,a pro-drug, a hydrate or pharmaceutically acceptable salt or ester thereof, and a pharmaceutical composition thereof as well as a preparation method and application thereof. The compound provided bythe invention can inhibit activity of an estrogen receptor, regulate expression level of the estrogen receptor down or induce degradation of the estrogen receptor and can be used for preventing or treating diseases related to overactivity of the estrogen receptor, especially estrogen receptor positive (ER+) drug-resistant diseases (such as breast cancer producing drug resistance to anti-estrogen therapy).

The present invention relates to the treatment of breast cancer which is estrogen receptor positive (ER+) and / or human epidermal growth factor receptor 2 positive (HER2) and / or progesterone receptor positive (PR) and / or facilitates chromatin transcription positive (FACT+) with a curaxin, including curaxin 137. The present invention also pertains to a method of identifying a subject who has a breast cancer tumor and is likely to respond to treatment with a curaxin.

The invention discloses a receptor molecularly-targeted imaging agent and a preparation method and application thereof. The receptor molecularly-targeted imaging agent comprises a polyethylene glycol short chain which is linked with 17alpha-ethinyloestradiol of a target estrogen receptor through 'click' reaction. The receptor molecularly-targeted imaging agent is shown as a concrete general molecular formula in the description, wherein the 17alpha-ethinyloestradiol serves as a targeting group, polyethylene glycol serves as a hydrophilic group, and <18>F serves as a radioactive group. The receptor molecularly-targeted imaging agent has excellent biological properties and high specificity, is high in uptake when used in positive breast cancer tumors of the estrogen receptor and capable of distinguishing between estrogen positive receptors and estrogen negative receptors, and meets the conditions as a breast cancer receptor imaging agent.

The disclosure provides methods for treating estrogen receptor positive (ER+) cancer in women with an effective amount of lasofoxifene, a pharmaceutically acceptable salt thereof, or a prodrug thereof. The disclosure also includes the detection of the Estrogen Receptor 1 (ESR1) gene mutations that lead to endocrine resistance and treatment of endocrine resistant ER+ cancers.

Herein disclosed are methods that are predictive of resistance to endocrine therapy in an estrogen receptor-positive (ER-positive) breast cancer patient. An exemplary method comprises detecting the overexpression of MN / CA9 gene expression product(s) in a sample from an affected subject, wherein if MN / CA9 is overexpressed, then the subject is considered to have a greater probability of resistance to endocrine therapy, particularly tamoxifen, and a corresponding poorer prognosis if undergoing endocrine therapy, than if MN / CA9 is not overexpressed. MN / CA9 gene expression products useful in the predictive / prognostic methods include MN / CA IX, MN proteins / polypeptides, MN nucleic acids and soluble MN / CA IX antigen (s-CA IX). The methods are useful as an aid in the selection of treatment for a patient with an ER-positive breast tumor. The methods of the invention can be used, for example, to identify those patients requiring additional / alternative therapies, preferably, but not necessarily, therapies that are not affected by acidic pH. The methods also comprise the use of diagnostic / prognostic imaging to detect MN / CA IX in a patient tumor, wherein the presence of MN / CA IX in one or more tumors is indicative of probable resistance to antiestrogen therapy, particularly to tamoxifen.

Acquired and de novo endocrine resistance are major clinical problems in the management of breast cancer patients. Though the antiestrogen tamoxifen prolongs disease-free and overall survival in the adjuvant setting, and induces remissions in over half of the patients with estrogen receptor positive metastatic disease, all patients eventually acquire tamoxifen resistance. Furthermore, many of the resistant tumors actually appear to be stimulated by tamoxifen just as they are by estrogens. The present invention provides methods of predicting endocrine resistance comprising detecting the biological activity and / or expression of p38 MAPK and / or AIB1. The invention further provides methods of reducing, reversing, or preventing endocrine resistance comprising contacting a breast or prostate tumor with a p38 MAPK pathway inhibitor.

Disclosed is an accelerated progression relapse test for use in the prognosis of disease states. According to the test disclosed herein, it can be determined whether a patient would benefit from treatment for a disease state or whether the patient's prognosis would not have a high probability of benefit with additional treatment. In particular, the test is useful in determining a patient's prognosis for cancer (breast, colon, lung, etc). For example, the test of the invention can be used to determine the prognosis for estrogen receptor positive (ER+) breast cancer patients. In the test for ER+ breast cancer patients, four genetic probes are employed that target MK167, CDC6, and SPAG5 gene products. The ER+ breast cancer test stratifies a patient population into two groups, with the low gene expression group identifying a group that is less likely to benefit from additional treatment measures, and a high gene expression group, identifying a group more likely to benefit from additional treatment measures.

Estrogenic extracts of Anemarrhena asphodeloides Bge. from the Liliaceae Family are provided. Also provided are methods of using said extracts to achieve an estrogenic effect, especially in a human, e.g. a female human. In some embodiments, the methods include treatment of climacteric symptoms. In some embodiments, the methods include treatment of estrogen receptor positive cancer, such as estrogen responsive breast cancer. In some embodiments, the methods include treatment or prevention of osteoporosis.

The present invention provides a novel series of cationic, lipid-based, 17α-substituted-estradiol derivatives. The present invention further provides a process for the preparation of a novel series of 17α-substituted-estradiol derivatives. The invention also provides information about highly selective anticancer activities of these molecules in estrogen responsive cell lines. The compound elicits high level of toxicity to gynecological cancer cell lines such as MCF-7, T47D (estrogen receptor positive cell lines), MDA-MB-468 (estrogen receptor knock-out cell line), HeIa (cervical cancer). The present class of cationic lipid-based, estradiol derivatives is likely to find specific use in developing target specifically deliverable anticancer drugs for the treatment of gynecological cancers that are most prevalent in women population irrespective of ethnicity.

The present invention describes methods for long-term culturing of ERpos cells, cell lines, and / or cell strains with exetended lifespan and / or cell strain as well as culture medium compositions. The invention further describes methods for isolating cells which may be used as starting point for long-term culturing of ERpos cells, cell lines, and / or cell strains with extended lifespan and / or cell strain. The invention further discloses various methods for generating ERpos tumorigenic cells, cell lines, and / or cell strains with extended lifespan and / or cell strain as well as various assays for their use.

The present invention relates to a nucleic acid aptamer molecule that includes a domain that binds to an estrogen receptor, molecular complexes that include the nucleic acid aptamer molecule and an estrogen receptor, and constructed DMA molecules and expression systems, as well as host cells, that the contain an RNA aptamer molecule of the invention. Use of these aptamers and encoding constructs to inhibiting estrogen receptor activity in a cell and to treat estrogen receptor-positive cancers is also described.

The invention relates to cancer, and more specifically to breast cancer, and particularly to estrogen receptor positive breast cancer that is resistant to endocrine therapy. The invention provides methods for selecting subgroups of subjects for treatment, and methods of treatment of a subgroup of subjects.

The invention provides a method of screening for a compound that modulates RIZ histone methyltransferase (HMT) activity, by contacting a RIZ or RIZ fragment having HMT activity with one or more candidate compounds, and determining histone methyltransferase activity of the contacted RIZ or RIZ fragment. Also provided is a method of screening for a compound that modulates progesterone receptor (PR) activity, by providing a RIZ1 modulatory compound, and determining the ability of the RIZ1 modulatory compound to modulate PR activity. Further provided is a method of identifying an individual with an estrogen receptor positive (ER+) tumor having a reduced likelihood of responding to endocrine therapy. The method involves determining the RIZ1 status of the tumor, wherein an abnormal RIZ1 status identifies the individual as an individual with a reduced likelihood of responding to endocrine therapy.

The invention discloses an estrogen receptor targeting radioactive tracer, and a preparation method and application thereof. The tracer is of an ethinylestradiol dimer structure, molecules of the tracer comprise two same 17 alpha-ethinylestradiol groups, and the tracer is prepared by marking radioactive signal groups in one step through a polyethylene glycol short chain by applying a click chemical reaction. The tracer has high uptake in uterus, ovary, breast cancer cells and tumors with positive estrogen receptors, can distinguish estrogen positive receptors from estrogen negative receptors in vitro and vivo, has strong specificity, and meets the condition of being used as a breast cancer estrogen receptor imaging agent. The structural formula of the tracer is shown as follows.

The present invention relates to a cow milk protein fatty acid modifier capable of inducing human breast cancer cell apoptosis, and a preparation method thereof, and belongs to the technical field of medicine or function food preparation. According to the method, cow milk albumin is subjected to a decalcification treatment to form the unfolded state, and then an unsaturated fatty acid is adopted to carry out appropriate molecule modification on the lactoalbumin component through the anion exchange chromatography technology to form the milk protein fatty acid modifier, wherein the in vitro cell model test results of the modifier prove that the modifier can significantly induce the human breast cancer cell (including estrogen receptor positive cells and estrogen receptor negative cells) apoptosis and does not significantly affect the normal human breast cells. According to the present invention, the support can be provided for development of the breast cancer prevention and treatment drug and the anti-breast cancer function food, the new reference is provided for the high value utilization of the whey protein and the optimization of the formula milk powder, and the positive significance is provided for promotion of the fine and deep processing of the milk product.