91 results about "Large-cell lymphoma" patented technology

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound.

The invention is directed to a method of prognosing in an individual a transformation from follicular lymphoma to diffuse large B-cell lymphoma (DLBCL) by measuring changes and / or lack of changes in certain groups of related clonotypes, referred to herein as “clans,” in successive clonotype profiles of the individual. A clan may arise from a single lymphocyte progenitor that gives rise to many related lymphocyte progeny, each possessing and / or expressing a slightly different immunoglobulin receptor due to somatic mutation(s), such as base substitutions, inversions, related rearrangements resulting in common V(D)J gene segment usage, or the like. A higher likelihood of transformation from follicular lymphoma to DLBCL is correlated with the persistence of clans in successive clonotype profiles whose clonotype membership fails to undergo diversification over time.

Differential Methylation Hybridization (DMH) was used to identify novel methylation markers and methylation profiles for hematopoieetic malignancies, leukemia, lymphomas, etc. (e.g., non-Hodgkin's lymphomas (NHL), small B-cell lymphomas (SBCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma (B-CLL / SLL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), etc.). Particular aspects provide novel biomarkers for NHL and subtypes thereof (e.g., MCL, B-CLL / SLL, FL, DLBCL, etc.), AML, ALL and MM, and further provide non-invasive tests (e.g. blood tests) for lymphomas and leukemias. Additional aspects provide markers for diagnosis, prognosis, monitoring responses to therapies, relapse, etc., and further provide targets and methods for therapeutic demethylating treatments. Further aspects provide cancer staging markers, and expression assays and approaches comprising idealized methylation and / or patterns” (IMP and / or IEP) and fusion of gene rankings.

The present disclosure provides a compound of formula (I) and the use thereof for the therapeutic treatment of human cancers including B-cell lymphoma and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.

The invention discloses chimeric antigen receptor T cells targeting CD19, and application of the chimeric antigen receptor T cells. A chimeric antigen receptor for preparing the chimeric antigen receptor T cells comprises interleukin 2 signal peptide, an anti-CD19 single chain antibody, a CD8 protein molecular hinge region, a transmembrane region, an intracellular signal structural domain, and anintracellular signal transduction structural domain of CD3 zeta protein molecules which are sequentially connected in series. The chimeric antigen receptor T cells are used for preparing medicines orpreparations for treating hematological malignancies, wherein the hematological malignancies comprise CD19-positive acute B-lymphocytic leukemia, diffuse large B-cell lymphoma and non-Hodgkin lymphoma.

The invention discloses a CAR-T (chimeric antigen receptor T cell) for targeting CD19 and an application of the CAR-T. A CAR for preparing the CAR-T comprises interleukin 2 signal peptides, an anti-CD19 single-chain antibody, a CD8 protein molecule hinge region, a transmembrane region, an intracellular signal structure region and a CD3 zeta protein molecule intracellular signal conduction structure region which are connected in series sequentially and has the amino acid sequence shown in SEQ ID NO:9. The CAR-T is applied to preparation of a medicine or a preparation for treating hematologicalmalignancy, wherein the hematological malignancy comprises CD19-positive B-cell acute lymphocytic leukemia, diffuse large B cell lymphoma and non-hodgkin's lymphoma.

The present invention provides a BTK inhibitor compound (having s structure represented by a formula (I)) and uses of the BTK inhibitor compound in medicines. According to the present invention, the compound and the pharmaceutical composition can be used for treatment of diffuse large B-cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia. The formula (I) is defined in the specification.

A method of treating diffuse large B-cell lymphoma comprising administering to a patient a pharmaceutically acceptable amount of a composition comprising a thienotriazolodiazepine compound, said thienotriazolodiazepine compound being represented by Formula (I), wherein R1 is alkyl having a carbon number of 1-4, R2 is a hydrogen atom; a halogen atom; or alkyl having a carbon number of 1-4 optionally substituted by a halogen atom or a hydroxyl group, R3 is a halogen atom; phenyl optionally substituted by a halogen atom, alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4 or cyano; --NR5--(CH2)m--R6 wherein R5 is a hydrogen atom or alkyl having a carbon number of 1-4, m is an integer of 0-4, and R6 is phenyl or pyridyl optionally substituted by a halogen atom; or --NR7--CO--(CH2)n-- R8 wherein R7 is a hydrogen atom or alkyl having a carbon number of 1-4, n is an integer of 0-2, and R8 is phenyl or pyridyl optionally substituted by a halogen atom, and R4 is --(CH2)a--CO--NH--R9 wherein a is an integer of 1-4, and R9 is alkyl having a carbon number of 1-4; hydroxyalkyl having a carbon number of 1-4; alkoxy having a carbon number of 1-4; or phenyl or pyridyl optionally substituted by alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4, amino or a hydroxyl group or --(CH2)b--COOR10 wherein b is an integer of 1-4, and R10 is alkyl having a carbon number of 1-4, or a pharmaceutically acceptable salt thereof or a hydrate or solvate thereof, wherein the patient has activated B-cell diffuse large B-cell lymphoma.

The invention relates to a molecular mark (p-Akt and / or YB-1) for selecting treatment scheme and / or prognostic evaluation of diffuse large b-cell lymphomas and an application therefore, and relates to a method for selecting treatment scheme and / or prognostic evaluation of diffuse large b-cell lymphomas. The molecular mark p-Akt and / or YB-1 can simply and correctly judge the prognosis of diffuse large b-cell lymphomas, to select objective treatment scheme for patients, thereby improving the prognosis effect of treatment scheme and saving medical cost.

The present invention is directed to pharmaceutical compositions and methods of using combination therapies containing a SYK inhibitor, or a pharmaceutically acceptable salt thereof, and a antineoplastic or antiinflammatory agent for the treatment of inflammatory, autoimmune and cell proliferative diseases, such as allergic reaction, transplant rejection, rheumatoid arthritis (RA), lupus, multiple sclerosis (MS) or psoriasis undesired acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL) (including diffuse large B cell lymphoma (DLBCL)), mantle cell lymphoma, acute lymphocytic leukemia (ALL), follicular lymphoma, Burkitt's lymphoma, small Lymphocytic (SLL), Lymphoma, multiple myeloma, asthma, vasculitis, Idiopathic thrombocytopenic purpura (ITP), Heparin Induced Thrombocytopenia (HIT) and hemolytic anemia.

The invention relates to the field of anti-tumor, and discloses a purpose of a mitoxantrone liposome preparation for preparation of medicine for treating a lymphoma, wherein the lymphoma is preferablya non-hodgkin lymphoma, is further preferably an invasive non-hodgkin lymphoma, is more further preferably a recurrent and refractory invasive lymphoma, and is more further preferably a diffuse largeB cell lymphoma or a peripheral T-cell lymphoma. The mitoxantrone liposome preparation is singly used, and is not applied in a way of being combined with other anti-tumor medicine.

The invention aims to provide an application of chlorogenic acid in preparing drugs for prevention and treatment of primary cutaneous T-cell lymphoma. Experiments show that the chlorogenic acid can activate CD4 T-lymphocytes and CD8 T-lymphocytes, and prevent and treat primary cutaneous T-cell lymphoma by taking the CD4 T-lymphocytes and the CD8 T-lymphocytes as targets. According to the invention, the chlorogenic acid is adopted for promoting the proliferation of T-lymphocytes of a body and activating the T-lymphocytes so as to achieve the purpose of treating primary cutaneous T-cell lymphoma. Meanwhile, the chlorogenic acid also can inhibit the proliferation of primary cutaneous T-cell lymphoma cells, and the inhibition effect of the chlorogenic acid is similar to the inhibition effect of interferon.

The invention discloses a molecular pathological classification method of diffuse large B-cell lymphomata, which use three quantum dot markers of different wavelengths as fluorescent probes to detect the expression of CD10, Bcl-6 and MUM1 proteins in a biological sample. The invention also discloses a kit for the molecular pathological classification of diffuse large B-cell lymphomata and an application thereof. The molecular pathological classification method of diffuse large B-cell lymphomata obviously improves the working efficiency, and can provide a rational regimen for patients with diffuse large B-cell lymphomata, thereby being beneficial to saving medical expenses.

Patients having a disease associated with high level of thioredoxin system activity or a requirement for nitric oxide, e.g. large cell lymphoma or restenosis, are treated with a thioredoxin reductase inhibitor, e.g. auranofin or arsenic trioxide, and a nitric oxide donating compound, e.g. isosorbide mononitrite or isosorbide dinitrite or nitroglycerin or S-nittrosothiol. Patients having a disease associated with nitric oxide synthase overexpression or increased activity, e.g. Parkinson's disease or septic shock or pancreatic cancer, are treated with Trx / Trx reductase upregulator, e.g. aptamer that binds to thioredoxin reductase inhibitor, and agent causing depletion of nitric oxide (or adduct thereof), e.g. L-NMMA or L-NAME or minocycline or ascorbate or N-acetylcysteine.

The invention discloses a reagent kit for detecting lymphoma genovariation and an application of the reagent kit, and particularly discloses the reagent kit for detection or auxiliary detection of variation of a lymphoma related gene. The reagent kit comprises a substance for detecting BCL2,BCL6, MYC and / or gene IGH fusion, the substance is a complete set of DNA probes, and the complete set of theDNA probes comprises 376 probes as shown in SEQID NO:1 to SEQ ID NO:376. The reagent kit can be used for detection or auxiliary detection of the variation of the lymphoma related gene, substyping ofcells of origin (cell of origin, COO) of patients suffering from diffuse large B-cell lymphoma, and auxiliary diagnosis, prognostication judging and / or targeted drug prediction of the patients suffering from lymphoma.

The invention provides a BTK (bruton tyrosine kinase) inhibitor compound (compound shown as a formula (I)) and a purpose of the BTK inhibitor compound in medicine. The compound provided by the invention and a medicine composition of the compound can be used for treating diffuse large B cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia.

A method for diagnosing a lymphoid proliferative disorder (such as lymphoma, T-cell lymphoma or leukemia) in a subject or determining the risk of a subject for a lymphoid proliferative disorder recurrence after transient remission, which includes high throughput T-Cell Receptor β (TCRβ) sequencing tests to identify dominant oncogenic clones in the subject suffering from the lymphoid proliferative disorder. Oligonucleotides primer compositions and kits associated with the above-described methods are also provided herein. Said subject includes living organisms, such as mammals (e.g., dogs, cats, pigs, cows, horses, goats, rabbits, humans), non-mammalian vertebrates, such as birds (e.g., chicken, ducks), fish (e.g., sharks), or frogs, and transgenic species thereof.

The invention relates to microRNA-34a and related microRNAs for use in the treatment of B-cell lymphoma. Likewise it relates to microRNA-34a for use in the preparation of a medicament for the treatment of B-cell lymphoma, and for a method of treatment of B-cell lymphoma comprising administering microRNA-34a. These claims are based on the observation that microRNA-34a shows strong anti-proliferative effects when overexpressed in diffuse large B-cell lymphoma (gDLBCL) cell lines, or when delivered intratumorally or systemically in xenograft models of DLBCL.

The invention relates to microRNA-34a and related microRNAs for use in the treatment of B-cell lymphoma. Likewise it relates to microRNA-34a for use in the preparation of a medicament for the treatment of B-cell lymphoma, and for a method of treatment of B-cell lymphoma comprising administering microRNA-34a. These claims are based on the observation that microRNA-34a shows strong anti-proliferative effects when overexpressed in diffuse large B-cell lymphoma (gDLBCL) cell lines, or when delivered intratumorally or systemically in xenograft models of DLBCL.

A method of treating diffuse large B-cell lymphoma comprising administering to a patient a pharmaceutically acceptable amount of a composition comprising a thienotriazolodiazepine compound, said thienotriazolodiazepine compound being represented by Formula (I), wherein R1 is alkyl having a carbon number of 1-4, R2 is a hydrogen atom; a halogen atom; or alkyl having a carbon number of 1-4 optionally substituted by a halogen atom or a hydroxyl group, R3 is a halogen atom; phenyl optionally substituted by a halogen atom, alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4 or cyano; —NR5—(CH2)m—R6 wherein R5 is a hydrogen atom or alkyl having a carbon number of 1-4, m is an integer of 0-4, and R6 is phenyl or pyridyl optionally substituted by a halogen atom; or —NR7—CO—(CH2)n—R8 wherein R7 is a hydrogen atom or alkyl having a carbon number of 1-4, n is an integer of 0-2, and R8 is phenyl or pyridyl optionally substituted by a halogen atom, and R4 is —(CH2)a—CO—NH—R9 wherein a is an integer of 1-4, and R9 is alkyl having a carbon number of 1-4; hydroxyalkyl having a carbon number of 1-4; alkoxy having a carbon number of 1-4; or phenyl or pyridyl optionally substituted by alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4, amino or a hydroxyl group or —(CH2)b—COOR10 wherein b is an integer of 1-4, and R10 is alkyl having a carbon number of 1-4, or a pharmaceutically acceptable salt thereof or a hydrate or solvate thereof, wherein the patient has activated B-cell diffuse large B-cell lymphoma.

To provide a medicament which shows more remarkable effect in treatment of activated B-cell like diffuse large B-cell lymphoma (ABC-CLBCL) than the existing Btk inhibitor, and is excellent in safety. The present compound exhibits more remarkable effect in treatment of activated B-cell like diffuse large B-cell lymphoma (ABC-DLBCL) patients, inter alia, ABC-DLBCL patients having CD79B wild-type gene background than the existing Btk inhibitor, and therefore, it can attain the object of the present invention.

The invention belongs to the field of biological and medical examination, and relates to a detection method of a molecular tying marker of a diffuse large B-cell lymphoma, and a kit related to the detection method. The invention firstly provides the detection method of the molecular marker of the diffuse large B-cell lymphoma, which comprises the steps as follows: 1) a biomacromolecule combined with the specificity of the molecular marker is contacted with a biological sample taken from a diffuse large B-cell lymphoma patient; 2) the expression level of the molecular marker in the biological sample is determined; and 3) a judgment model is established according to a detection result of the molecular marker. The invention further provides the application of the method to molecular tying of the diffuse large B-cell lymphoma, and the corresponding kit. The method provided by the invention can be used for judging a molecular subtype of the diffuse large B-cell lymphoma, estimating the prognosis of the patient and providing a basis for early intervention treatment and the implementation of individualized treatment.

The invention discloses a peripheral blood TCR marker of diffuse large B-cell lymphoma as well as a detection kit and application of the peripheral blood TCR marker. The marker comprises at least one of proteins of which the sequences are as shown in SEQ ID NO.1-100. On the basis of a high-throughput sequencing method, only a small amount of peripheral blood needs to be adopted, RNA is extracted, an immune map library is established by treating a sample, then through high-throughput sequencing and TCR data analysis, firstly, a characteristic TCR sequence in the peripheral blood of the diffuse large B-cell lymphoma is determined, and then a test result of a sample to be tested is compared with the characteristic TCR sequence, and therefore, whether the patient suffers from the diffuse large B-cell lymphoma or not is determined. According to the invention, a huge number of diffuse large B-cell lymphoma specific TCR sequences can be compared at the same time, and compared with single detection of one or more markers, the kit has higher specificity and accuracy, and the diagnosis efficiency is improved.

The invention discloses a kit for detecting gene mutation of diffuse large B-cell lymphoma and belongs to the field of gene detection and disease diagnosis. It is found that a certain connection exists between KCNG1 gene and diffuse large B cell lymphoma (DLBCL), and the kit can be used for auxiliary diagnosis of DLBCL by detecting whether G185A mutation exists in KCNG1 gene or not. The genes detected by the kit for detecting DLBCL gene mutation include a KCNG1 gene and MYD88, CD79B, EZH2, B2M, NOTCH2, STAT6 and TP53 genes which are determined to be related to DLBCL generation in the prior art. The invention provides a new material for auxiliary diagnosis of DLBCL; the kit can detect the mutation condition of the gene at one time, and provides a basis for early diagnosis, typing judgment,prognosis stratification and medication guidance of DLBCL.

The present invention is based, in part, on the discovery that galectin-1 (Gal1) plays a role in immune disorders, including Hodgkin lymphoma, anaplastic large cell lymphoma, or MLL+ pre B-cell ALL. Accordingly, the invention relates to compositions, kits, and methods for diagnosing, prognosing, and monitoring immune disorders, e.g., Hodgkin lymphoma, anaplastic large cell lymphoma, or MLL+ pre B-cell ALL.

The present disclosure provides a compound of formula (I) and the use thereof for the therapeutic treatment of human cancers including B-cell lymphoma and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.

The invention discloses a drug composition for treating B cell lymphoma. The drug composition comprises a PI3K / AKT signal pathway inhibitor and a chemotherapeutic drug, and further comprises targetedCD20 infliximab, such as rituximab. The drug composition provided by the invention is especially suitable for treating relapsed or refractory B cell lymphoma. In view of the key effect of a CSC (cancer stem cell) in the transferring and drug resisting process, the invention provides a new pro-differentiation therapy strategy for the CSC, that is, a decisive signal conduction pathway for maintaining the dryness of the stem cell is determined, and then the pathway is interfered to promote CSC differentiation. The differentiation cell is finally sensitive to a routine treatment method (such as chemotherapy). Under the condition, the PI3K / AKT signal pathway inhibitor is combined with an R-CHOP scheme to exert a good effect of treating drug-resisting DLBCL (diffuse large B cell lymphoma).