47 results about "Osseous metastasis" patented technology

The present invention describes methods of treating cancer, cancer metastasis, and drug resistant cancers using miRNA inhibitors; for example, inhibitors of miR-409-5p. Also described are methods of using the miRNA as biomarkers; for example, to predict responsiveness to a cancer drug, to detect a disease state of cancer.

The invention relates to methods and pharmaceutical compositions for the treatment of bone density related diseases. More particularly, the present invention relates to a ROBO1 modulator for use in a method for the treatment of a bone mineral density related disease in a subject. In a particular embodiment the ROBO1 modulator is selected from the group consisting of small organic molecules, antibodies, aptamers or polypeptides. In another particular embodiment said bone mineral density related disease is selected from the group consisting of ghosal hematodiaphyseal dysplasia syndrome (GHDD), osteoporosis, osteoporosis associated to pseudoglioma, osteoporosis and oculocutaneous hypopigmentation syndrome, osteoporosis due to endocrinological dysfunction, osteogenesis imperfecta osteopenia, Paget's disease, osteomyelitis, hypercalcemia, osteonecrosis, hyperparathyroidism, lytic bone metastases, periodontitis, bone loss due to immobilization and osteoporosis associated with a disease selected from the group consisting of cachexia, anorexia, alopecia, rheumatoid arthritis, psoriatic arthritis, psoriasis, and inflammatory bowel disease.

The invention discloses a novel adenine bisphosphonate, a preparation method and the application in the preparation of pharmaceutical preparations for the treatment of the metabolic bone diseases. A compound is (2-(6-amino-purine-9-yl)-1-hydroxy-phosphono-ethyl)phosphonate and 3-((6-amino-purine-9-yl)-1-hydroxy-phosphono-propyl)phosphonate. The compound can be used for the treatment of hypercalcemia, bone pains and other metabolic bone diseases caused by osteoporosis, osteitis deformans and bone metastasis of the malignant tumor, and the invention has an anti-cancer effect at the same time.

The invention provides a fluorescence labeled human triple-negative breast cancer osseous metastasis cell line. The fluorescence labeled human triple-negative breast cancer osseous metastasis cell line is prepared with a method as follows: a human triple-negative breast cancer cell MDA-MB-231 is cultured; a lentivirus carrier containing RFP (red fluorescence protein) is amplified, and an RFP labelled MDA-MB-231 cell is prepared; the RFP-MDA-MB-231 cell is transplanted to the fourth pair breast fat pad position of a nude mouse and grows into tumor; shin bone of a hind limb is taken after 4-6 weeks, bone marrow is flushed with a buffer solution and digested with collagenase, a single cell from the bone marrow is obtained, in-vitro culture amplification is performed, and red fluorescence cells are sorted with a flow cytometry; through tumor formation screening in a body of the nude mouse, the red fluorescence labelled MDA-MB-231 human triple-negative breast cancer osseous metastasis cellline is obtained. The human triple-negative breast cancer osseous metastasis cell line has the characteristics of osseous metastasis, is labelled by fluorescent protein and realizes visualization andtraceability.

Compounds of the formulaare useful in the treatment of various disorders including, but not limited to, cancer (tumor metathesis, tumorgenesis / tumor growth), angiogenesis (as in cancer, diabetic retinopathy, rheumatoid arthritis), restenosis (following balloon angioplasty or stent implantation), inflammation (as in rheumatoid arthritis, psoriasis), bone diseases (osteopenia induced by bone metastases, immobilization and glucocortocoid treatment, periodontal disease, hyperparathyroidism and rheumatoid arthritis), and as antiviral agents. Novel method of making compounds of formula I are also provided.

The invention discloses an isotopic tracing method for monitoring cancer cell osseous metastasis. The method refers to a measurement method by taking 41Ca as a tracer agent and taking accelerator mass spectrometry (AMS) as a tracer agent and is used for monitoring the occurrence, development and resolution processes of the cancer cell osseous metastasis, and belongs to the technical field of nuclear technologies. The method disclosed by the invention comprises the following steps: (1) generating a 41Ca marked tracer agent; (2) marking an experimental nude mouse by using the 41Ca marked tracer agent; (3) collecting a urine sample of the nude mouse in the step (2), and separating the element Ca; (4) measuring the 41Ca / 40Ca isotope abundance ratio in the calcium fluoride powder obtained in the step (3); and (5) drawing a standard curve; and (6) analyzing the difference, so as to obtain the cancer cell osseous metastasis degree. According to the method disclosed by the invention, the problems that the sensitivity of a conventional monitoring means is relatively low and the early monitoring of the cancer cell osseous metastasis is difficultly realized are solved, and the method has high clinical application values and social benefits.

The present invention relates to fully humanized antibodies, specifically to a fully human anti-RANKL antibody, a nucleic acid molecule encoding the antibody, and a composition containing the antibody. The present invention further relates to uses of the antibody in preparation of drugs for prevention and treatment of bone loss related diseases, especially osteoporosis, arthritis osteolysis damage or tumor bone metastasis and other diseases. According to the present invention, the antibody is specifically bound with human RANKL and blocks the activity of the human RANKL while the potential immunesuppression of the human RANKL on human body is reduced, the antibody has good stability, and the defect of the non-uniformity (heterogeneity) of the IgG2 antibody production on the batch quality identification is avoided.

The invention provides a method for diagnosing bone metastases in nuclide bone imaging based on deep learning. The method relates to a bone scanning diagnosis classification model, a bone metastasis tumor region segmentation model and a bone metastasis tumor load evaluation and automatic report generation model. By the adoption of the method, the bone metastasis tumor can be judged, automatic region segmentation can be conducted, the recognition accuracy is high, and full-automatic analysis from original image input to report generation is preliminarily achieved.

The invention discloses an application of miR-133b in diagnosing, forecasting and treating prostate cancer with osseous metastasis. The invention researches and finds that the miR-133b has low expression in prostate cancer and has lower expression in osseous metastasis of prostate cancer; a further research proves that the low expression of miR-133b is related to the osseous metastasis of prostate cancer and indicates shorter osseous metastasis-free survival period; besides, over-expression miR-133b is capable of in vitro restraining migration and invasion of prostate cancer and in vivo restraining osseous metastasis of prostate cancer; the miR-133b mimics also can in vitro restrain the osseous metastasis of prostate cancer; the above results prove that miR-133b can be used for preparing diagnostic reagent, forecasting reagent and osseous metastasis restraining drug for the prostate cancer with osseous metastasis.

The invention discloses an application of TSPAN1 in diagnosis, prognosis and treatment of breast cancer metastasis. The invention finds the high expression of TSPAN1 in tissues and cells of breast cancer metastasis and the high expression indicates shorter survival time without osseous metastasis; in vivo and in vitro experiments prove that the down-regulated expression of TSPAN1 genes can restrain the breast cancer metastasis and invasion so as to restrain the osseous metastasis of breast cancer; on the basis of the finding, the invention provides application of a reagent for detecting the expression level of the TSPAN1 gene in preparing a kit for detecting if breast cancer metastasis occurs and / or a prognosis kit for forecasting the breast cancer metastasis trend; a TSPAN1 inhibiting reagent is used for preparing the drug for preventing and / or treating breast cancer metastasis, and a new thought is supplied for diagnosis, prognosis and treatment of breast cancer metastasis.

The invention discloses a fluorescent quantitative polymerase chain reaction (PCR) assay kit for bone metastasis of lung cancer. The kit comprises the following components: a specific primer, a specific probe, a standard DNA template and a fluorescent quantitative PCR reaction solution. The invention further discloses a using method of the fluorescent quantitative PCR assay kit for the bone metastasis of the lung cancer. The kit can detect the expression quantity of novel_mir_89 quickly and quantitatively by the kit so as to detect the occurrence of the bone metastasis of the lung cancer. The invention is simple, convenient and quick in operation, stable in result and high in sensitivity and specificity.

A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof,wherein: one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; orR1 and R2 are both H;one of R3 and R4 is H, and the other is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; orR3 and R4 are joined together with the adjacent backbone carbon atom to form a spiro-C5-C6 cycloalkyl group;R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl; orR6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached;R8 is C1-8-alkyl or C3-8-cycloalkyl;R9 is a para-substituted 6-membered monocyclic aryl or heteroaryl ring which includes up to five heteroatoms.The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

The invention provides a bifunctional stent with anti-tumor and tissue defect repair effects and a preparation method thereof, and relates to the technical field of biomedical materials. The bifunctional stent is prepared by the following steps that nano-particles are prepared, specifically, iron salt, magnesium salt, dopamine and / or dopamine hydrochloride are uniformly mixed to obtain nano-particles of polydopamine complexed iron ions and magnesium ions; emulsion paste is prepared, specifically, polylactic acid-glycolic acid, an organic solvent, tricalcium phosphate, a surfactant and the nanoparticles are uniformly mixed to obtain composite emulsion paste; and printing and forming are carried out, specifically, the composite emulsion paste is used as printing ink, and printing is carried out to form a stent. The bifunctional stent with the anti-tumor and tissue defect repair effects has the effects of killing tumor cells and promoting osteoblast differentiation in cooperation with CDT / PTT, and can be applied to resisting postoperative recurrence of bone metastatic tumors and tissue defects.

The invention discloses application of miR-582 in preparing a prostatic cancer osseous metastasis diagnosis and prognosis kit and medicine. It is unexpectedly found that miR-582-3p and miR-582-5p havea low expression in prostatic cancer tissue of osseous metastasis, and the low expression of miR-582-3p or miR-582-5p predicts a lower bone-free metastasis survival rate; besides, an in-vivo experiment and an in-vitro experiment both prove that the overexpression of pri-miR-583 can up-regulate miR-582-3p and miR-582-5p, and through a TGF-beta signal access, prostatic cancer osseous metastasis andmigration and invasion of prostatic cancer osseous metastasis cell lines are inhibited. Thus, based on the findings, miR-582 can be applied to preparing the prostatic cancer osseous metastasis diagnosis and prognosis kit, and the medicine inhibiting prostatic cancer osseous metastasis is expected to be developed.

The present invention describes methods of treating cancer, cancer metastasis, and drug resistant cancers using miRNA inhibitors; for example, inhibitors of miR-409-5p, miR-409-3p, miR-154*. Also described are methods of using the miRNA as biomarkers; for example, to predict responsiveness to a cancer drug, to detect a disease state of cancer.

The invention relates to a mark product of <89>Zr marked denosumab. The mark product is [<89>Zr]-Df-Bz-NCS-denosumab; and Df-Bz-NCS-denosumab is marked by adopting <89>Zr. The mark product disclosed by the invention is accurate and reliable in development result, proper in half-life period, good in specificity, targeting property and in-vitro stability and higher in radioactive chemical purity; a good imaging effect can be realized; for bone imaging, the mark product is capable of responding internal metabolism conditions of drugs objectively and accurately; and therefore, osteoporosis and solid tumour osseous metastasis can be diagnosed earlier.

The invention discloses the application of an inhibitor GSK-J4 of histone demethylase to preparation of a therapeutic drug for osteosarcoma. That histone deemthylase KDM5B is associated with the treatment of the osteosarcoma is proved for the first time. GSK-J4 acts on the histone demethylase KDM5B to significantly inhibit proliferation of osteosarcoma cells, and therefore, can be used as a new breakthrough for preparing a drug for treating the osteosarcoma. Besides, the invention also discloses the ability of the GSK-J4 for inhibiting transfer of the osteosarcoma cells by targeting the KDM5Bfor the first time, and provides a novel idea for researching and developing a drug for treating lung metastasis and osseous metastasis of the osteosarcoma.

The invention discloses an antitumor combined medicine. The combined medicine comprises a diphosphonate compound serving as an active ingredient and CIK cells, wherein the diphosphonate compound is at least one of clinical medication etidronate disodium, clodronate disodium, pamidronate disodium, tiludronate disodium, alendronate sodium, neridronate sodium, olpadronate sodium, risedronate sodium, sodium ibandronate, incadronate disodium and zoledronic acid. The method for greatly improving the tumor cell killing capability of CIK cells by utilizing combination of anti-tumor-osseous-metastasis diphosphonate medicines and the CIK cells, so that the number of CIK cells for achieving the treatment effect the same as a conventional method is greatly reduced; and compared with biological treatment of single CIK cells, the combined medicine has the advantages that the relatively high safety of CIK cells can be maintained, and the treatment effect can be remarkably improved.

The invention relates to urine protein markers for tumor bone metastasis and application thereof. The invention relates to the application of a urine protein marker selected from a group consisting ofatrial natriuretic peptide receptor 2, galectin-3 binding protein, hepcidin, osteopontin, growth differentiation factor 15, hydroxy acid oxidase 2, NKG2-DII type integrated membrane protein, fatty acid binding protein, brain and complement component C6, alpha1 acidic glycoprotein, thioredoxin, mitochondria, beta-2-microglobulin, uridine and the like in the prediction of the risk of tumor bone metastasis and / or the diagnosis of tumor bone metastasis. According to the application, an animal model for screening the urine protein markers related to tumor bone metastasis is established, the urineprotein markers related to tumor bone metastasis are obtained by using the established animal model, and application of a detection reagent of the markers in preparation of a kit for diagnosing tumorbone metastasis of a subject is also established.

Provided is an anticancer compound including a cleavable linker specifically activated in a tumor microenvironment, and use thereof. The anticancer compound is represented by the following formula, wherein, R1 is a normal functional group or a protection group; R2 is Ala, Thr, Val or Ile; R3 is Ala, Val or Asn; R4 is a drug group linked via a hydroxyl group or an amino group; and the general formula of the drug is R4H. The anticancer compound is only activated at a local portion of a tumor, thus avoiding the defect of immune system damage of a traditional chemotherapeutic drug, and promoting tumor immunization by removing a tumor immunosuppression cell. The anticancer compound or pharmaceutical composition thereof is jointly used with immunotherapy, thus improving the effect of treating the tumor, and effectively inhibiting tumor metastasis and osseous metastasis.

The invention provides an external-use drug for treating osseous metastasis cancer pain and a preparation method of the external-use drug. The external-use drug comprises scutellaria barbata, black nightshade, cantharides, rhizoma corydalis, curcuma zedoary, pericarpium citri reticulatae viride, long-noded pit vipers, centipedes, scorpions, rhizoma sparganii, borneol and asarum. The contents of the scutellaria barbata, the black nightshade, the cantharides, the rhizoma sparganii and the curcuma zedoary are the same and are highest. The contents of the pericarpium citri reticulatae viride and the rhizoma sparganii are the same. The contents of the borneol and the asarum are the same and are lowest. The external-use drug has the advantages that multiple proper amounts of Chinese herbs are matched mutually and used jointly for treatment coordination, and accordingly, the curative effect of obviously relieving the osseous metastasis cancer pain can be achieved; the preparation method is simple, the external-use drug can be made into liquid, the liquid can be also made into a plaster for external application, the dosage form of the drug can be flexible and changeable, and accordingly, needs of different patients can be met.

The invention discloses an application of miR-19a-3p in preparing a diagnostic reagent and a therapeutic drug for prostate cancer with osseous metastasis. The invention researches and finds that the miR-19a-3p has low expression in prostate cancer with osseous metastasis, the miR-19a-3p low expression is related to the prostate cancer with osseous metastasis, the over-expression miR-19a-3p is capable of in vitro restraining migration and invasion of prostate cancer with osseous metastasis and in vivo restraining osseous metastasis of prostate cancer, so that the miR-19a-3p can be used for preparing diagnostic reagent and the therapeutic drug for prostate cancer with osseous metastasis.

The present invention relates to a composition comprising osmundacetone or a pharmaceutically acceptable salt thereof for preventing or treating bone diseases. More specifically, the present invention relates to: a composition comprising osmundacetone, a pharmaceutically acceptable salt thereof, or an Osmunda japonica extract as an effective ingredient, for preventing or treating osteoporosis, rheumatoid arthritis, arthralgia, Paget disease, bone metastatic cancer, or fracture; a food composition for improvement; a use of a salt; and a treatment method. The composition according to the present invention shows a strong inhibitory activity against proliferation and differentiation of osteoclast which causes bone loss, and activation of differentiation of osteoblast, and thus can be usefully utilized in developing medicines for safe and effective treatment of bone diseases or functional foods for improving symptoms of bone diseases

The invention belongs to the technical field of osteoclast activation mechanism measurement, and discloses a measurement method for regulating an osteoclast activation mechanism in osseous metastasis.The method includes the steps of collecting data information of the lungs by a lung detection instrument; regulating osteoclast activation in osseous metastasis by RANK-RANKL; extracting myelomoncytes and differentiating the myelomoncytes to osteoclasts; judging whether a patient suffers from osseous metastasis or not by screening. The method can realize identification of osseous metastasis and healthy osseous metastasis bone tissue samples directly without sample pretreatment or normal temperature and pressure conditions, and has the advantages of simple operation, high precision and the like; myelomoncytes and mesenchymal stem cells are separated out at the same time, and primary myelomoncytes obtained by separation and purification can be successfully changed into osteoclasts by induced differentiation; meanwhile, data obtained after pretreatment and feature extraction is subjected to classification training by screening, and whether the patient suffers from osseous metastasis or not can be more conveniently and quickly judged.

The invention discloses a metastatic bone tumor special disease database construction method and system. The method comprises the following steps: respectively establishing a first set, a second set and a third set; retrieving the first part of the medical record according to a preset field; retrieving a second part, a third part and a fourth part of the medical record in the second set according to a preset field; traversing the full-text texts of the medical records in the first set, and intercepting evidence fragments; and judging whether the medical record is positive or not according to the evidence fragment, and if so, storing the medical record into a positive database. By the adoption of the metastatic bone tumor special disease database construction method and system, clinical data of patients with metastatic bone tumors can be automatically collected in a full-period and full-dimension mode, and structured processing and storage of the clinical data of the patients with metastatic bone tumors are achieved.