30 results about "Macroglobulinemia" patented technology

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

Disclosed are methods of treating Waldenstrom's Macroglobulinemia comprising administering to the animal, a therapeutically effective amount of a heterocyclic compound of Formula I.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease reduce tumor burden in multiple myeloma and to block bone disease.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

Methods for evaluating and treating Waldenstrom's macroglobulinemia are provided.

The present invention provides a fusion protein inhibiting TACI-BAFF complex formation and preparation method therefor and use thereof. Specifically, the fusion protein of the present invention is of high biological activity for blocking BAFF / APPRIL, and may significantly lower the serum IgM concentration in normal Balb / c mice as well as the serum IgM and IgE concentration in C57 / B6 mice with asthma. The TACI-Fc fusion protein of the present invention may be used in the treatment of autoimmune diseases, including asthma, systemic lupus eythematosus and rheumatoid arthritis, etc., and may also be used in the treatment of B cell enrichment-related diseases, including multiple myeloma, chronic lymphocytic leukemia, macroglobulinemia and plasmacytic leukemia, etc.

The invention discloses features, inter alia, immunogenic XBP1-, CD138-, and CS1-derived peptides (and pharmaceutical compositions thereof). The peptides can be used in a variety of methods such as methods for inducing an immune response, methods for producing an antibody, and methods for treating a cancer (e.g., a plasma cell disorder such as multiple myeloma or Waldenstrom's macroglobulinemia). The peptides can also be included in MHC molecule multimer compositions and used in, e.g., methods for detecting a T cell in a population of cells.

The invention relates to treatment of cancer. More specifically the invention relates to methods of treating cancer selected from the group consisting of squamous cell cancer, lung cancer including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer, as well as B-cell lymphoma including low grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade / follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom's Macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairy cell leukemia; chronic myeloblastic leukemia; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema such as that associated with brain tumors, Meigs' syndrome, melanoma, mesothelioma, multiple myeloma, fibrosarcoma, osteosarcoma and epidermoid carcinoma, by administering antibodies directed to α2β1 integrin.

The invention provides a fusion protein for inhibiting formation of a TACI-BAFF complex and a preparation method and application thereof. Specifically, the fusion protein provided by the invention has high biological activity for enclosing BAFF / APPRIL, can significantly reduce serum IgM concentration of the normal Balb / c mice, and serum IgM and IgE concentration of C57 / B6 of asthmatic mice. The TACI-Fc fusion protein provided by the invention can be used for the treatment of autoimmune diseases, including asthma, systemic lupus erythematosus and rheumatoid arthritis, also can be used for the treatment of diseases related to B cell increase, such as multiple myeloma, chronic lymphocytic leukemia, macroglobulinemia and plasma cell leukemia.

The present disclosure provides thiazolyl-containing compounds of Formula (I), (II), or (III). The compounds described herein may be able to inhibit protein kinases (e.g., Src family kinases (e.g., hemopoietic cell kinase (HCK)), Bruton's tyrosine kinase (BTK)) and may be useful in treating and / or preventing proliferative diseases (e.g., myelodysplasia, leukemia, lymphoma (e.g., Waldenstrom's macroglobulinemia)) and in inducing apoptosis in a cell (e.g., malignant blood cell). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

This invention provides methodologies and methods for measuring concentrations of higher molecular weight (HMW) transthyretin (TTR) species, or functional equivalents, in a biological sample that are useful as a clinically applicable biomarker (diagnostic, prognostic, predictive, treatment response, safety) for multiple diseases and conditions. Our discovery is immediately applicable and generally available for the general practitioner for use in diseases where currently few to no biomarkers available like light-chain amyloidosis (AL), a B-cell / plasma cell cancer / dyscrasia that is also associated with multiple myeloma, monoclonal gammopathy of undetermined significance (MUGS), B-cell lymphomas, and Waldenstrom macroglobulinemia. Methodologies and methods are disclosed.

The present disclosure provides a method for treating a subject afflicted with Waldenstrm's macroglobulinemia (WM) comprising administering to the subject a therapeutically effective amount of an antibody or an antigen-binding portion thereof that specifically binds to a CXCR4 receptor expressed on the surface of a WM cell. The disclosure also provides a therapeutic regimen for treating a patient afflicted with C1013G / CXCR4-associated WM.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to reduce tumor burden in multiple myeloma and to block bone disease.

Discussed herein are pharmaceutical compositions containing Ibrutinib and processes for preparing them. The compositions may be utilized in the treatment of a variety of conditions including, without limitation, B-cell proliferative disorders such as non-Hodgkin lymphoma (diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma or burkitt lymphoma), Waldenstrom macroglobulinemia, plasma cell myeloma, chronic lymphocytic leukemia, lymphoma, or leukemia. These compositions are designed for oral ingestion. The compositions are contained within a capsule such as a standard or sprinkle or in a liquid formulation such as a suspension. In one embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, and magnesium stearate. In another embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropylmethylcellulose, citric acid monohydrate, disodium hydrogen phosphate, sucralose, sodium methyl parahydroxybenzoate, sodium ethyl parahydroxybenzoate, concentrated hydrochloric acid, sodium hydroxide, and water.

The present disclosure provides a method for treating a subject afflicted with Waldenstrm's macroglobulinemia (WM) comprising administering to the subject a therapeutically effective amount of an antibody or an antigen-binding portion thereof that specifically binds to a CXCR4 receptor expressed on the surface of a WM cell. The disclosure also provides a therapeutic regimen for treating a patient afflicted with C1013G / CXCR4-associated WM.

The present invention provides a fusion protein inhibiting TACI-BAFF complex formation and preparation method therefor and use thereof. Specifically, the fusion protein of the present invention is of high biological activity for blocking BAFF / APPRIL, and may significantly lower the serum IgM concentration in normal Balb / c mice as well as the serum IgM and IgE concentration in C57 / B6 mice with asthma. The TACI-Fc fusion protein of the present invention may be used in the treatment of autoimmune diseases, including asthma, systemic lupus eythematosus and rheumatoid arthritis, etc., and may also be used in the treatment of B cell enrichment-related diseases, including multiple myeloma, chronic lymphocytic leukemia, macroglobulinemia and plasmacytic leukemia, etc.

The invention relates to treatment of cancer. More specifically the invention relates to methods of treating cancer selected from the group consisting of squamous cell cancer, lung cancer including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer, as well as B-cell lymphoma including low grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade / follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom's Macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairy cell leukemia; chronic myeloblastic leukemia; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema such as that associated with brain tumors, Meigs' syndrome, melanoma, mesothelioma, multiple myeloma, fibrosarcoma, osteosarcoma and epidermoid carcinoma, by administering antibodies directed to α2β1 integrin.

A method for treating B-cell lymphoma in a subject that has been diagnosed as having a B-cell lymphoma characterized by a mutation in MYD88 and is in need of such treatment is presented. The lymphoma is treated with an oligonucleotide having a sequence 5′-(CCT)n-3′. The B-cell lymphoma may be activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) or Waldenstrom's macroglobulinemia (WM).

Methods for evaluating and treating Waldenstrom's macroglobulinemia are provided.

The present invention provides methods and compositions for treatment of hyperproliferative disorders and cancers, including multiple myeloma and Waldenström's macroglobulinemia, comprising administering to a patient in need of the treatment a TACI-Ig fusion molecule in amount sufficient to suppress proliferation-inducing functions of BlyS and APRIL.

The invention relates to the field of biological detection, in particular to a digital PCR kit, a primer and probe for detecting WM (macroglobulinemia) related gene mutation. The kit contains the primer and the probe which are used for detecting the mutation of the CXCR4S338X site. According to the kit, a digital PCR technology is adopted, the human CXCR4S338X mutation site is quantitatively detected, and reference is provided for curative effect monitoring and clinical medication of clinical doctors on targeted medication of WM patients.

Various features are disclosed herein, including immunogenic XBP1-, CD138-, and CS1-derived peptides (and pharmaceutical compositions thereof), among others. The peptides can be used in a variety of methods, such as for inducing an immune response, for generating antibodies, and for treating cancer (e.g. plasma cell disorders such as multiple myeloma or Waldenstrom's macroglobulinemia) approach. The peptides can also be included in MHC molecule multimer compositions, and can also be used, for example, in methods for detecting T cells in a population of cells.

The invention provides a fusion protein for inhibiting formation of a TACI-BAFF complex and a preparation method and application thereof. Specifically, the fusion protein provided by the invention has high biological activity for enclosing BAFF / APPRIL, can significantly reduce serum IgM concentration of the normal Balb / c mice, and serum IgM and IgE concentration of C57 / B6 of asthmatic mice. The TACI-Fc fusion protein provided by the invention can be used for the treatment of autoimmune diseases, including asthma, systemic lupus erythematosus and rheumatoid arthritis, also can be used for the treatment of diseases related to B cell increase, such as multiple myeloma, chronic lymphocytic leukemia, macroglobulinemia and plasma cell leukemia.

A method for treating B-cell lymphoma in a subject that has been diagnosed as having a B-cell lymphoma characterized by a mutation in MYD88 and is in need of such treatment is presented. The lymphoma is treated with an oligonucleotide having a sequence 5'-(CCT)n-3'. The B-cell lymphoma may be activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) or Waldenstrom's macroglobulinemia (WM).

Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldanstrom macroglobulinemia.

Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldanstrom macroglobulinemia.

The present invention discloses a method for separating and purifying α2-macroglobulin from Cohn Fraction IV precipitation, in which Cohn Fraction IV precipitation is treated by ammonium sulfate precipitation, zinc ion affinity chromatography, gel filtration, and ultrafiltration and concentration sequentially and thereby α2-macroglobulin is obtained finally. With the method provided in the present invention, purified α2-macroglobulin plasma protein that has a clinical application value is obtained, the Cohn Fraction IV precipitation is changed from a discarded material into a valuable material, and plasma is utilized comprehensively. In addition, the method is easy and simple to use, easy to scale up, and suitable for separation and purification of α2-macroglobulin at a large scale.

The present invention relates to the field of medicines, and specifically relates to a 4-aminopyrimidine compound having a structural feature represented by formula (I), or pharmaceutically acceptable salts thereof, a preparation method for the compound, and a use of the compound and the salts as a Bruton tyrosine kinase (BTK) inhibitor. A result of experiments shows that the compound in the present invention has a significant inhibition effect on the BTK, and can be used for treating thromboembolism, inflammatory disorders, autoimmune diseases, Waldenstrom macroglobulinemia, B cell lymphomas, and other diseases.