68 results about "Neuroblastoma" patented technology

The invention discloses a neuroblastoma pathological image classification method based on a CMSwinKAN neural network, and the method comprises the steps: firstly building a neuroblastoma pathological image data set, and dividing the data set into a training set and a test set; a CMSwinKAN neural network model is constructed, wherein the CMSwinKAN neural network model comprises a SwinKANsform feature extraction module, a comparison driving multi-scale aggregation module and a kernel activation network classification head; performing feature classification on the slices through an SVM classifier to obtain classification confidence; dynamically weighting the output of the CMSwinKAN neural network model according to the classification confidence, and outputting a final classification result; and taking the training set as input, training the CMSwinKAN model and the SVM classifier, and adjusting and optimizing parameters of the CMSwinKAN neural network model and the SVM classifier.

The present disclosure relates, inter alia, to the combination therapy of an oncolytic adenovirus for the treatment of retinoblastoma, Ewing's sarcoma or neuroblastoma with a topoisomerase I inhibitor or a prodrug thereof, such as topotecan or SN-38, or a prodrug of a topoisomerase inhibitor, such as irinotecan.

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for an HLA-A11-restricted epitope of mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) (KRAS7-16), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (NRAS), or Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS). Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

The present invention provides a GD2-targeting CAR-T cell and its preparation and application. Specifically, the present invention provides a GD2-targeting CAR construct, which comprises the scFv fragment of the humanized GD2 antibody 3F8, the human Fc fragment, the ICOS transmembrane region, the ICOS and 4-1BB intracellular regions (co-stimulatory signals), and CD3ζ. The present invention also provides a CAR-T cell based on the above CAR, its preparation method and application. The CAR-T cell of the present invention can significantly inhibit the proliferation of tumor cells in a subcutaneous model of neuroblastoma, has a significant in vivo anti-tumor effect, and can be used for the targeted treatment of neuroblastoma.

The invention belongs to the field of neuroblastoma tissue analysis, and particularly discloses a child neuroblastoma tissue microarray chip and a preparation method thereof.The child neuroblastoma tissue microarray chip comprises a glass slide base material, and a plurality of neuroblastoma tissue samples arranged in a dot-matrix mode are arranged on the glass slide base material; by integrating a plurality of neuroblastoma samples including various pathological typing, grading and clinical staging types of neuroblastoma in a tissue block, efficient sample processing and analysis are achieved, comprehensiveness and representativeness of research are ensured, a large number of samples are analyzed simultaneously through a microarray technology, and the accuracy and accuracy of analysis are improved. The requirements for high-throughput screening of specific genes and expression proteins thereof in scientific research activities are met, the prediction capacity for tumor prognosis and the guidance accuracy for treatment schemes are improved, and neuroblastoma tissues are analyzed more efficiently and comprehensively.

Methods, compositions, and systems for treating various cancers are disclosed. The disclosed compositions may include a poly peptide with affinity for a CD99 cell surface protein. Disclosed polypeptides may comprise a sequence selected from GYYMH, RINPYTGATTYNQIFKD, YYYGNNYNVYLDY, SASQGISNYLS, YTSTLHIS, and QQYSNLPWT, and may include mouse, human, or humanized peptide sequences. In many embodiments, the polypeptides may be immunoglobulins, for example IgG3 or IgG4. The disclosed polypeptides may be administered to a subject having a cancer cell with elevated expression of CD99. In some embodiments, the subject may be suffering from cancer, including diffuse intrinsic pontine glioma (DIPG). Ewing Sarcoma, acute myeloid leukemia (AML), ependymoma, or neuroblastoma. Treatment methods include administering the disclosed polypeptides to a subject that may also be treated with radiation. Disclosed herein are systems for treating one or more cancers. The systems may comprise a radiation source, for example a medical fractionated radiation source.

GD2 specific chimeric antigen receptor effector cells for the treatment of solid tumors, possibly in combination with an enhancer of a Zeste homolog 2 (EZH2) inhibitor. The invention relates to a GD2-specific chimeric antigen receptor (GD2. CAR) effector cell for use in the treatment of solid tumors, in particular in the treatment of extracranial GD2 + tumors, such as soft tissue sarcoma and osteosarcoma, neuroblastoma, melanoma, lung cancer, bladder cancer and retinoblastoma, and brain tumors. In addition, the present invention also relates to the use of the GD2. CAR genetically modified effector cell in combination with an enhancer of a Zeste homolog 2 (EZH2) inhibitor for the treatment of solid tumors.

This disclosure provides compounds of formula (I) or pharmaceutically acceptable salts thereof, methods for preparing the same, and their use in the treatment and / or diagnosis of cancers such as neuroblastoma, prostate cancer, pancreatic cancer, leukemia, osteosarcoma, hepatoblastoma, lung cancer, colon cancer, breast cancer, skin cancer, thyroid cancer, and / or rhabdoid cancer. JPEG2026522940000099.jpg50170

The invention relates to a tricyclic heterocyclic compound as well as a preparation method and medical application thereof. Specifically, the invention relates to a compound shown in a general formula (I), a preparation method of the compound, a pharmaceutical composition containing the compound and application of the compound as an MAT2A inhibitor. The compound and the pharmaceutical composition containing the compound can be used for treating and / or preventing diseases related to MAT2A activity, such as mesothelioma, neuroblastoma, rectal cancer, colon cancer, esophageal cancer and the like. Wherein the definition of each group in the general formula (I) is the same as that in the specification.

This invention discloses a polycyclic pyrimidine compound and its uses. The invention provides a polycyclic pyrimidine compound of formula (I), its solvate, a pharmaceutically acceptable salt thereof, a solvate of its pharmaceutically acceptable salt, its tautomer, or its stereoisomer. The compound provided by this invention exhibits good degradation activity against CDK9 and good inhibitory activity against neuroblastoma.

The present invention relates to a combination therapy for treating metastasis of a GD2-positive cancer, such as relapsed or refractory neuroblastoma. In particular, the combination therapy comprises administration of stereotactic body radiotherapy (SBRT) at one or more metastatic sites in combination with administration of an anti-GD2 antibody or fragment thereof.

The MYC and NMYC transcription factors (TFs) play a key role in cell proliferation and are overexpressed in most cancer cells. However, in normal cells their overexpression triggers safeguard mechanisms promoting cell death and cellular senescence, which are bypassed in cancer cells. Here, the inventors reveal that in normal cells MYC binds to the Inositol 1,4,5-Trisphosphate Receptor type 1 (ITPR1) gene and upregulates its expression, triggering an ER-mitochondria calcium (Ca2+) transfer, which is involved in MYC-induced cell death and senescence. Supporting a tumor suppressive role of MYC / ITPR1 axis, ITPR1 expression is generally decreased in cancer and reactivation of this pathway induces cancer cell death. Nevertheless, some cancer cells, generally expressing high levels of MYCN and / or MYC, also express high level of ITPR1, which correlates with high expression of BCL2, encoding an inhibitor of ITPR1. Strikingly, in high-risk MYCN-amplified neuroblastoma, ITPR1 expression is controlled by NMYC and its level correlates with worse patient survival. In these cells, blocking the interaction between BCL2 and ITPR1, via an BCL2-BH4 domain inhibitor induces mitochondrial Ca2+ accumulation and cell death, and decreases tumor size. Thus, the present invention relates to a method for treating MYChigh cancer, and in particular NMYC--amplified neuroblastoma in a subject by administering an BCL2-BH4 domain inhibitor.

The invention provides a guide RNA (Ribonucleic Acid), the guide RNA is targeted to SFPQ (Small Form-Factor Pluggable Quantitative), and the primer sequence of the guide RNA is as follows: SFPQ sgRNA-FWD: 5 '-CGTACAAACGTGCCATG-3'; and SFPQ sgRNA-REV: 5 '-CATGGCACGTTTGAGTACG-3', and SFPQ sgRNA-REV: 5 '- The invention further provides an adeno-associated virus targeting the SFPQ, and the adeno-associated virus contains the guide RNA. The invention also provides an application of the adeno-associated virus targeting SFPQ in preparation of a medicine for treating neuroblastoma. The adeno-associated virus targeting SFPQ provided by the invention not only can inhibit tumor growth, but also can provide a new strategy for NB treatment by promoting NB cell differentiation.

An epigenetic silencer factor (ESF) for use in the treatment of cancer, or a polynucleotide encoding the same, wherein the ESF comprises a transcription factor DNA-binding domain functionally linked to at least one epigenetic effector domain, the transcription factor is an oncogenic transcription factor or a cancer-related transcription factor, and the cancer is selected from the group consisting of glioma, glioblastoma, medulloblastoma, astrocytoma, neuroblastoma, epithelioma, meningioma, retinoblastoma, rhabdomyosarcoma, lung cancer, prostate cancer, breast cancer, liver cancer, pancreatic cancer (e.g., human pancreatic ductal adenocarcinoma), bladder cancer, oropharyngeal cancer, kidney cancer, colon cancer (e.g., colon adenocarcinoma), colorectal cancer (CRC), or metastases of any of the foregoing.

The present disclosure relates to anti-GD2 and / or famesyltransferase inhibitor compositions for use in methods for treating a cancer, for example, neuroblastoma. Also provided is a method of preventing neuroblastoma metastasis, comprising administering to a subject a therapeutically effective amount of an anti-GD2 immunotherapy and a farnesyltransferase inhibitor. Further provided are compositions comprising tipifarnib and / or dinutuximab and methods of use thereof.

Described herein are methods and compositions for treating a disease, e.g. cancer (including solid tumors), using glial cells (e.g. microglia cells and / or astrocytes) and / or macrophages (e.g., CNS-associated macrophages) infected with an oncolytic virus (e.g., vaccinia virus). The methods and compositions provided herein demonstrate a synergistic anti-cancer effect.

The invention relates to a novel medical application of cinobufagin, and the cinobufagin is used as an N-myc protein inhibition / degradation agent and can be used for anti-tumor treatment of neuroblastoma and retinoblastoma.

The application provides a guide RNA which targets SFPQ, primer sequences of the guide RNA are as follows: SFPQ sgRNA-FWD: 5'-CGTACTCAAACGTGCCATG-3'; SFPQ sgRNA-REV: 5'-CATGGCACGTTTGAGTACG-3'. The application also provides an adeno-associated virus which targets SFPQ and contains the guide RNA. The application also provides use of the adeno-associated virus which targets SFPQ in preparation of a drug for treating neuroblastoma. The adeno-associated virus which targets SFPQ provided by the application can not only inhibit tumor growth, but also promote NB cell differentiation, thereby providing a new strategy for NB treatment.

The invention belongs to the field of biomedicine, and particularly relates to application of a reagent for detecting the m6A modification level of an FKBP4 gene in preparation of a neuroblastoma diagnostic product. The invention provides a primer pair for detecting the m6A modification level of a partial region of the FKBP4 gene. High-risk neuroblastoma and medium-low-risk neuroblastoma are distinguished by detecting the m6A modification level of the FKBP4 gene, wherein the m6A modification level of the FKBP4 gene in the high-risk neuroblastoma is remarkably lower than that in the medium-low-risk neuroblastoma. Through MeRIP-seq and RNA-seq combined analysis and in combination with GEO database screening, it is determined that the m6A modification level of the FKBP4 gene is closely related to the risk degree of neuroblastoma. By detecting the m6A modification level of the FKBP4 gene, high-risk neuroblastoma and medium-low-risk neuroblastoma can be accurately distinguished.

Disclosed is a single-domain antibody specifically binding to ganglioside GD2, which can specifically bind to GD2 glycan. The present application provides a single-domain antibody that can be used for targeting and / or treating several cancers (such as neuroblastoma, glioma, etc.) associated with GD2-overexpressing cells. The present application also relates to a recombinant nucleic acid sequence encoding the above-mentioned single-domain antibody, as well as an expression vector and a host cell.

The present application relates to the field of clinical laboratory medicine technology, in particular to a neuroblastoma and catecholamine-related tumor diagnosis kit and its application. The kit contains key components for detecting high vanillylmandelic acid and vanillylmandelic acid in urine, including isotope internal standard, specific chromatographic column, optimized mobile phase and sample pretreatment material. The detection method using the kit optimizes the collection, preservation and pretreatment process of instant urine samples, and combines the liquid chromatography-tandem mass spectrometry (LC-MS / MS) analysis conditions designed for low concentration and complex matrix samples to realize the rapid and accurate quantification of trace HVA and VMA in urine. It overcomes the shortcomings of traditional 24-hour urine detection method such as large trauma, long cycle and poor accuracy, and provides an efficient and reliable solution for non-invasive, early diagnosis and postoperative efficacy monitoring of neuroblastoma and other catecholamine-related tumors, which has important clinical application value.

The invention belongs to the technical field of bioinformatics and medical detection, and particularly relates to a marker combination for neuroblastoma (NB) noninvasive risk level grading, a prediction model, a prediction method and application thereof. The marker combination is used for determining the sex, determining whether the month age is greater than 18 months, determining whether plasma MYCN is amplified, determining whether tumors are metastatic, and determining the content of neuron-specific enolase and lactic dehydrogenase; a machine learning algorithm is used for constructing an NB noninvasive risk degree grading prediction model, the comprehensive performance of the random forest model is optimal, the area value under a subject working characteristic curve reaches 0.956, the sensitivity is 92.9%, the specificity is 82.1%, the accuracy rate is 87.5%, the Kappa value is 0.75, the F1 score is 0.881, and NB middle and low risk patients and NB high risk patients can be effectively distinguished; the NB non-invasive risk level grading prediction model constructed by the invention can quickly, accurately and non-invasively perform NB risk level grading, and has a relatively good clinical application value.

The invention discloses application of a GJC1 gene as a target spot in resisting neuroblastoma, and relates to the field of biological medicines. In-vitro and in-vivo experiments show that the GJC1 gene can be used as a therapeutic target of neuroblastoma, and growth of the tumor can be obviously inhibited by inhibiting, interfering or silencing gene expression. The invention provides a new treatment thought or means for the treatment of neuroblastoma.

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

The application relates to a dihydropyridine small-molecule compound and a preparation method and application thereof in preparing a drug for treating neuroblastoma, and belongs to the technical field of drug preparation. The application discloses a dihydropyridine small-molecule compound, a structural formula of which is as shown in the description, which can be used for preparing a drug for treating neuroblastoma with high ALDH18A1 expression, can effectively solve the problems of poor water solubility of YG1702, low inhibition rate of neuroblastoma and other drug application problems, and has a good application prospect.

The present invention belongs to the field of neuroblastoma treatment, and specifically relates to the use of an Aurora A inhibitor and a LUBAC inhibitor in combination in the preparation of a drug for treating neuroblastoma. The present invention has found that the combination of a small molecule inhibitor targeting LUBAC and an Aurora A inhibitor can significantly inhibit MYCN The activity of expanded NB cells was enhanced, and the effect of drug combination was better than that of drug alone, but it had no significant effect on normal cells and MYCN The inhibitory effect on the viability of non-expanded NB cells is not significant and can be used as MYCN Targeted drugs for expanded NB.

The invention relates to a co-culture of salivary gland organs and neuroblastoma as well as a preparation method and application of the co-culture. In the present disclosure, organoids based on human salivary gland tissue epithelial cells are cultured and co-cultured with neuroblastoma to construct a cell-cell direct interaction environment, thereby providing a neurological salivary gland hyperplasia model. In addition, the neurological salivary gland hyperplasia model can also be used to screen new therapeutic drugs and identify responses to botulinum toxin drugs, and thus the present disclosure helps to provide customized treatments for patients.

The invention relates to a selection of verified targets for T-cell receptors (TCR) against mutated human rat sarcoma (RAS) peptides as well as to several new T-cell receptors (TCR), which are isolated and / or expressed in an engineered cell, and which specifically recognize a G12V mutated human rat sarcoma (RAS) peptide, wherein the peptide is a mutated human Kirsten RAS (KRAS) peptide, a mutated human Harvey RAS (HRAS) peptide, or a human neuroblastoma RAS (NRAS) peptide, which consists of VVVGAVGVGK (SEQ ID NO: 1) or VVGAVGVGK (SEQ ID NO:2) presented in a HLA- A*11 complex, and wherein the individual TCR comprises a paired TCR alpha- and TCR beta-chain. The invention further relates to engineered cells and vectors expressing said TCRs and medical uses of the same for treating cancer patients.

The invention discloses application of FADS1 as a target spot in treatment of neuroblastoma, and relates to the technical field of biological medicine. The invention discloses an application of an FADS1 inhibitor in preparation of drugs for resisting tumors such as neuroblastoma. According to the application disclosed by the invention, by knocking down the expression of the FADS1 gene, the invasion and migration of neuroblastoma drug cells are remarkably inhibited, and a new target spot and a new choice are provided for the treatment of neuroblastoma drugs.

Heterocyclic compounds, their stereoisomers and their pharmaceutically acceptable salts are useful in the treatment of many types of cancers, such as cancers of the breast, prostate, pancreatic, gastric, lung, colon, rectum, esophagus cancer, duodenum, tongue, pharynx, liver, kidney, bile duct, uterine body, cervix, ovaries, urinary bladder, and skin. Other cancers to be treated include brain tumor, neurinoma, clear cell carcinoma, non-small cell lung cancer, small cell lung cancer, hemangioma, malignant lymphoma, malignant melanoma, thyroid cancer, bone tumor, vascular fibroma, glioblastoma, Neuroblastoma, sarcoma, neuroendocrine tumors, retinoblastoma, penile cancer, pediatric solid cancer, renal cell carcinoma, lymphoma, myeloma, leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, cutaneous T-cell lymphoma (CTCL), multiple myeloma (MM), myeloproliferative neoplasms (MPN), Myelodysplastic syndrome (MDS), polycythemia vera (PV), essential thrombocythemia, essential thrombocytosis (ET), and myelofibrosis (MF), and also including their metastases.