49 results about "Neuroblastoma" patented technology

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.

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 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.

The invention discloses siRNA of a targeted FGF2 / TERT gene, a complex co-delivery system and application of the siRNA. According to the siRNA of the targeted FGF2 / TERT gene and the complex co-delivery system adopting the siRNA, the gene expression of FGF2 or TERT in cells can be remarkably inhibited; the delivery system disclosed by the invention can be used as an FGF2 or TERT inhibitor, remarkably overcomes chemotherapy drug resistance, can also enhance the sensitivity of tumor cells to chemical drugs, has an important clinical application value in the aspect of improving the treatment effect of tumors such as breast cancer and neuroblastoma, and has a great application prospect.

The application provides a kind of common solid tumor activity image evaluation method and medium in children abdomen, utilize 3D convolution neural network model, capture the change information of lesion on the image of plain scan and enhancement after intravenous period, carry out intelligentized silhouette generation lesion in the intensification area and intensification degree after chemotherapy, finally comprehensively all information is intelligently diagnosed, judge tumor activity, form abdominal solid tumor artificial intelligence auxiliary activity evaluation scheme after chemotherapy;The application utilizes the plain scan and enhanced CT image, realizes the automatic intensification degree quantitative evaluation of children hepatoblastoma, nephroblastoma and neuroblastoma by tumor automatic segmentation and registration subtraction image calculation, so as to extract lesion characteristics from multiple angles, fully excavate image information, which can significantly improve the accuracy and sensitivity of activity discrimination of children abdominal solid tumor after chemotherapy.

The invention provides a gene detection kit for neuroblastoma molecular typing and application. Specifically, the invention provides a group of gene groups for determining molecular typing of neuroblastoma and / or evaluating survival risk of neuroblastoma patients, the molecular typing based on tissue transcriptome sequencing performs subgroup division on clinical NB child patients from the perspective of full bulk RNA-seq, and the system is more comprehensive compared with a grading system formed by previous research; the probability of occurrence of adverse events such as metastasis, relapse and death of different individual child patients can be predicted during definite diagnosis of tumors, a current clinical risk level grading system is assisted, and accurate recognition of atypical high-risk child patients such as MYCN non-amplification and decision making of an early upgrading treatment strategy are achieved; the method is helpful for individualized selection of a novel immunotherapy scheme for recurrent refractory high-risk patients and improvement of treatment results.

A salt, crystal form, preparation method, and application of a nitrogen-containing heterocyclic derivative are disclosed. Specifically, the salt and crystal form of a compound of general formula (I), a preparation method thereof, and a pharmaceutical composition containing a therapeutically effective amount of the crystal form are disclosed, as well as their use as a KRAS G12C mutation inhibitor in the treatment of diseases or conditions such as leukemia, neuroblastoma, melanoma, breast cancer, lung cancer, and colon cancer, wherein each substituent in general formula (I) is as defined in the specification.

The application discloses a urine collection and analysis device for early diagnosis of neuroblastoma. The urine collection and analysis device comprises a collector for collecting instant urine of a patient, a valve pipe is installed through the collector, a centrifugal tank is clamped through the valve pipe, a negative pressure delivery pipe for absorbing centrifugal supernatant is connected through the centrifugal tank, a first negative pressure pump is installed on the negative pressure delivery pipe, the other side of the negative pressure delivery pipe is connected with a precipitation tank, and the precipitation tank is connected with a detection liquid storage tank through a negative pressure delivery hose. A sample distribution pipe is installed below the detection liquid storage tank, an automatic sampler is arranged below the sample distribution pipe, a plurality of samples prepared by the automatic sampler are sequentially conveyed to a chromatography control module and a mass spectrum detection module for rapid detection and analysis. The urine collection and analysis device can quickly collect, process and detect and analyze urine samples, so that neuroblastoma can be accurately diagnosed in a short time, and the diagnosis efficiency is improved.

The present invention provides methods and kits a) for preventing and / or treating neuroblastoma (e.g., high-risk neuroblastoma) that is linked, in part, to high levels of ODC activity and increased cellular polyamine content, b) for predicting cancer patient survival, especially cancer patients whose cancer is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and c) for selecting treatment options for such patients based on the allelic nucleotide sequence or SNP at positions +263 and / or +316 of the ODC1 gene. The invention also provides, cancer treatment methods comprising the determination of the ODC1 genotype at the +263 and / or +316 positions, as a means to guide treatment selection, which includes, in some aspects the administration of pharmaceutically effective amounts of α-difluoromethylornithine (DFMO), either as a monotherapy or in combination with one or more other drugs. In addition, the present invention provides methods for preventing and / or treating patients that have been determined to have cancer stem cells, such as patients in cancer remission that are at risk for relapse.

The invention belongs to the technical field of gene detection, and particularly relates to application of a reagent for improving the m6A modification level of a partial region of an FKBP4 gene in preparation of a medicine for treating neuroblastoma. MeRIP-seq is adopted to detect neuroblastoma tissue diseases with different risk levels in the early stage of the application, and GEO online database analysis and screening are combined to find that the expression of FK506 binding protein (FK506binding protein 4, FKBP4) in high-risk neuroblastoma is significantly higher than that in middle-low-risk neuroblastoma, and the m6A level in the high-risk neuroblastoma is significantly reduced. On the basis, it is found that a part of the FKBP4 gene region plays an important role in expression and functions of the neuroblastoma, the function of FKBP4m6A modification in the neuroblastoma is further determined, and a new target spot and a new strategy are provided for precise treatment of the neuroblastoma.

Provided herein, is a method for cancer therapy through the administration of pharmaceutical compositions comprising cannabis-specific flavonoids such as cannflavins. The flavonoids provided herein, inhibit Trk inhibitory activity therefore can be therapeutically effective for treating RTK / Trk-associated cancers. Also provided is a pharmaceutical or natural health product comprising cannflavin A and / or cannflavin B and / or cannflavin C for treating and / or preventing cancer. Such cancers are brain cancer, breast cancer, colorectal cancer, prostate cancer, pancreas cancer, ovarian cancer, lung cancer, bladder cancer, melanoma, thyroid cancer, head and neck cancers, uterine sarcoma, and / or neuroblastoma adrenocortical carcinoma.

The invention belongs to the technical field of biological medicines, and particularly relates to application of WP1066 in preparation of a medicine for treating and / or preventing neuroblastoma. The invention finds that the WP1066 specifically inhibits the proliferation of MYCN amplified NB cells, but basically has no influence on MYCN non-amplified NB cells and normal cells. In the mechanism level, the small molecule drug WP1066 inhibits the activity of the NB cells by inhibiting the SK-N-BE (2) p-STAT3 level of the MYCN amplified NB cells and the expression level of downstream anti-apoptosis molecules Bcl-2. Experimental results show that WP1066 has a specific killing effect on MYCN amplified NB cells, can become a novel therapeutic drug for MYCN amplified NB, and has significance in treatment of MYCN amplified high-risk NB.

The present application belongs to the technical field of molecular medicine, and relates to a probe, a marker combination and a prediction method for non-invasive risk grading of neuroblastoma. The probe UUU-DZ-tFNA can detect UDG in vitro, cells, living bodies and plasma exosomes, and it is proved that UDG in plasma exosomes is closely related to the risk grading of NB. The plasma exosomes of NB patients are collected MYCN Whether to amplify, whether the tumor is metastatic, neuron-specific enolase content, lactate dehydrogenase content and plasma exosome UDG content are integrated, and a NB non-invasive risk grading prediction model is established through a machine learning algorithm. The optimal risk grading model is a neural network model. The area under the receiver operating characteristic curve of the combined model is improved by 5.2% compared with the optimal prediction result of the combined prediction model of the single clinical index, and the sensitivity and specificity are significantly improved. The present application has key clinical values for accurate grading of NB children, individualized treatment plan formulation and efficacy monitoring.

The present invention provides a compound of Formula I, a salt thereof, or a solvate thereof, as described herein, the composition is used for treating MYC positive cancers including lung cancer, leukemia, breast cancer, myeloproliferative diseases, colorectal cancer, medulloblastoma, kidney cancer, hepatocellular cancer, melanoma, ovarian cancer, prostate cancer, esophageal adenocarcinoma, liposarcoma, esophageal squamous carcinoma, gastrointestinal stromal tumor, glioma, mucus fibrosarcoma, smooth muscle sarcoma, neuroblastoma, synovial sarcoma, mesothelioma, and the like. Gastric cancer, thyroid cancer, lymphoma, osteosarcoma, rhabdomyosarcoma, fibrosarcoma, epithelial cancer and neurological cancer.

The application discloses a small molecule degrading agent of aryl formamides and application thereof, and has a structure shown in general formula I or a pharmaceutically acceptable salt, an isotopically labeled compound thereof. The compound of the application has a targeted degradation activity on MYC protein, and has a significant proliferation inhibiting activity on various solid tumor cells such as neuroblastoma and rhabdomyosarcoma. The compound of the application can be used for preparing a degrading agent targeting MYC protein, and can also be used for preparing a drug for treating diseases related to MYC gene amplification, fusion, mutation, expression imbalance, conformational change and function abnormality.