101 results about "Blastoma" 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 invention relates to a method for constructing a mouse orthotopic model of highly aggregated glioblastoma, belonging to the fields of biomedicine and experimental animal model technology. Glioblastoma cells are resuspended in a composite carrier of a specific ratio of matrix gel and serum-free culture medium, and a low-temperature injection technique is used. Utilizing the thermosensitivity of matrix gel in the mouse intracranial environment (i.e., its phase transition from liquid to gel at a certain temperature), precise colonization and physical locking of tumor cells at target coordinate points are achieved. This method improves upon existing glioblastoma mouse orthotopic model construction techniques that suffer from tumor cell diffusion and loss, low tumor formation rate, irregular tumor morphology, large intragroup variability, and needle reflux due to low viscosity of the inoculation carrier. It provides a good disease model for subsequent screening or evaluation of anti-glioblastoma drugs.

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

This invention discloses an engineered CAR-T cell targeting HIF-1α and its application in tumor immunotherapy. The CAR-T cell expresses a chimeric antigen receptor regulated by the hypoxia-responsive element HRE promoter, with its extracellular domain specifically binding to HIF-1α and its intracellular domain employing the 4-1BB+CD3ζ signaling module. Simultaneously, through immune checkpoint knockout and cytokine / chemokine modification, it achieves hypoxia-dependent activation, anti-exhaustion, high infiltration, and strong killing effects. The CAR-T cells of this invention significantly improve the adaptability to the solid tumor microenvironment and therapeutic efficacy, reduce off-target toxicity, and can be used to prepare drugs for treating malignant tumors such as lung cancer, liver cancer, pancreatic cancer, colorectal cancer, and glioblastoma, possessing significant clinical translational value.

Disclosed herein are methods and systems for treating cancer including glioblastoma, recurrent glioblastoma, or newly diagnosed glioblastoma, using the administration of ultra-low radio frequency energy (u / RFE®), either alone or in combination with one or more conventional cancer therapies. In some embodiments, the one or more conventional cancer therapies include chemotherapy or an anti-angiogenic therapy or other therapies.

This invention discloses a class of 2-(2-(quinolin-4-yloxy)ethyl)pyridazine-3(2H)-one compounds, their preparation methods, and applications. The structure of these compounds is shown in general formula (I). This invention also discloses that the above compounds have a significant inhibitory effect on interleukin-1 receptor-associated kinase 1 (IRAK1). These compounds can inhibit the proliferation of various tumor cells, including liver cancer, lung cancer, pancreatic cancer, gastric cancer, kidney cancer, colon cancer, esophageal cancer, glioblastoma, leukemia, multiple myeloma, and other solid tumors and hematological malignancies. This invention provides a new option for tumor treatment.

Disclosed herein are synthesis and use of covalent inhibitors selective for Transcriptional Enhancer Factor TEF-1 (TEAD1), which can be used for treatment of cancers such as glioblastoma, gastric cancer, colorectal cancer, pancreatic ductal adenocarcinoma (PDAC), and malignant pleural mesothelioma (MPM). Further disclosed herein are pharmaceutical compositions including the TEAD1 inhibitor and methods of treating cancers using the same.

A method and apparatus for detecting MGMT promoter methylation in glioblastoma, relating to the field of Raman spectroscopic detection. The method comprises: performing Raman spectral scanning on a glioma tissue sample to be detected to obtain Raman spectral data; preprocessing the Raman spectral data to obtain normalized Raman spectral data; extracting intensity values at characteristic shifts from the normalized Raman spectral data; and inputting the intensity values at the characteristic shifts into a classification model to calculate a classification prediction value, the classification prediction value being used for assisting in determining the MGMT promoter methylation state of said glioma tissue sample. The effect of the present application is that low-cost, non-destructive and accurate detection of the MGMT promoter methylation state of glioblastoma can be achieved.

The application provides application of MTA1 which is highly expressed in glioma stem cells (GSC) in treatment of glioblastoma (GBM). The application firstly proposes that GSC in GBM highly expresses MTA1 protein molecules, the highly expressed MTA1 is positively correlated with poor prognosis of GBM patients, and also promotes the stemness, cell proliferation and spheroid formation ability of GSC. Targeting the highly expressed MTA1 in GSC can inhibit the malignant progression of GBM. The application provides a new target and inhibitor for targeted treatment of GBM.

The present application relates to the technical field of biology, and relates to an siRNA targeting glioblastoma multiforme and a use thereof. Provided is an siRNA targeting glioblastoma multiforme. An antisense strand of this siRNA can specifically bind to a target nucleic acid to initiate degradation of the target nucleic acid, wherein the target nucleic acid comprises a pathogenic gene in glioblastoma multiforme, and the pathogenic gene in glioblastoma multiforme comprises a gene encoding ribonucleotide reductase subunit M2 and / or a gene encoding heat shock protein 47. Studies have shown that both the gene encoding the ribonucleotide reductase subunit M2 and the gene encoding the heat shock protein 47 have a significant correlation with the survival of patients with glioblastoma multiforme. The two genes can be used as therapeutic targets for glioblastoma multiforme. The siRNA capable of effectively knocking down the expression of the two genes in the patients with glioblastoma multiforme has great application prospects in the preparation of drugs for preventing and / or treating glioblastoma multiforme.

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 application discloses an intervention strategy for targeting CACNA2D2 protein and application thereof, and belongs to the technical field of medicine and biotechnology.The application discloses for the first time that abnormal high expression of CACNA2D2 is related to poor prognosis of neuroblastoma, especially malignant progression, and provides that CACNA2D2 gene is used as a drug target to prepare a drug for treating neuroblastoma, and further provides application of CACNA2D2 siRNA in preparation of a drug for treating neuroblastoma.After down-regulation of CACNA2D2 gene expression, cell proliferation and clone formation ability of neuroblastoma cells are significantly inhibited.Therefore, the application provides a new direction for development of a drug for treating neuroblastoma, and provides a possibility for preparing a new drug for treating neuroblastoma, improving curative effect of patients, improving prognosis and survival.

The application belongs to the technical field of biomedicine, and particularly relates to application of E33 region methylation level in evaluation of medulloblastoma prognosis. The nucleotide sequence of the E33 region is shown in SEQ ID NO:1; the medulloblastoma comprises G3 subtype medulloblastoma and / or G4 subtype medulloblastoma. The application finds that the low methylation state of the E33 region is directly related to the prognosis of the medulloblastoma Group 3 / 4 patient, the high / low methylation level of the E33 region can be detected to effectively predict the clinical result of the patient, and the methylation level of the E33 region is detected to lay a foundation for early prognosis evaluation and personalized treatment strategy of the medulloblastoma Group 3 / 4 patient.

The invention discloses an application of a flavonoid natural product Peruvianoside I in preparation of an anti-retinoblastoma drug, belongs to the field of medicinal chemistry, and has the following structure: the compound can selectively inhibit LSD1 enzyme activity and can be used as the anti-retinoblastoma drug. Experiments find that the anti-tumor action mechanism is related to inhibition of retinoblastoma cell migration. As a selective histone lysine specific demethylase LSD1 inhibitor, the compound has the potential of developing the retinoblastoma resisting medicine.

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.

Provided herein are methods of treating glioblastoma including administering to a subject having glioblastoma a therapeutically effective amount of a pharmaceutical composition comprising 4-1BBL, optionally in combination with recombinant IL-12. The 4-1BBL can be provided to the subject via an adeno-associated virus, for example AAV-F, and the IL-12 can be provided by intratumoral injection.

The invention discloses leech carbon dots and a preparation method and application thereof, the leech carbon dots are uniform in particle size and regular in morphology, and the leech carbon dots are obtained by taking leeches and pure water as raw materials through hydrothermal reaction, centrifugation, dialysis and freeze drying. The leech carbon dots disclosed by the invention can more easily penetrate through a blood brain barrier, and are low in toxicity, high in biological safety and good in anti-tumor effect. Compared with traditional chemotherapeutic drugs, the preparation cost is low, batch production is easy, and the action effect is strong. The traditional Chinese medicine composition can inhibit proliferation, migration and invasion of tumor cells, cross blood brain barrier and other tissue barriers, retard the cell cycle of glioblastoma, inhibit angiogenesis of glioblastoma, promote pyroptosis of glioblastoma and reverse lactic acid expression, and is combined with traditional chemotherapeutic drugs to enhance the curative effect.

The invention discloses application of MBD3 as an intervention target in preparation of a neuroblastoma treatment medicine, and belongs to the technical field of biological medicine. According to the application disclosed by the invention, a substance for reducing the expression level of the MBD3 gene or reducing the protein level of the MBD3 is applied to the development of a medicine for treating the neuroblastoma, and it is proved that interference on the expression of the MBD3 gene can induce the G0 / G1 phase cell cycle arrest of neuroblastoma cells and promote cell apoptosis, so that the in-vivo and in-vitro proliferation activity of the neuroblastoma cells is effectively inhibited; the small-molecule drug enbopiravidone can down-regulate the MBD3 protein level and significantly inhibit the growth of neuroblastoma cells. According to the invention, MBD3 is taken as a new target spot for treating neuroblastoma, a new direction is provided for overcoming the limitation of the existing therapy, a scientific basis is provided for developing a novel neuroblastoma treatment strategy based on MBD3 inhibition, and the application has important significance for improving the living quality and survival prognosis of high-risk children.

The invention provides application of OPC-like cell detection in prediction of glioblastoma with epilepsy. Specifically, the invention provides an application of a detection reagent of OPC-like cell markers PDGFRA and EGFRvIII in prediction of epilepsy of people with glioblastoma. The invention has an application prospect in the field of diagnosis and treatment of diseases of glioblastoma with epilepsy.

Provided relates to immune cells (e.g., T cells such as γδ T cells) modified to have no or reduced expression and / or function of Ariadne homolog 1 (ARIH1) and further optionally BCL11B, uses thereof (e.g., for treating glioblastoma), and methods of generating thereof. Also provided are methods of modifying γδ T cells using pseudotyped lentiviruses (e.g., BaEV-Rless glycoprotein or BaEV-TR glycoprotein pseudotyped lentiviruses).

This application relates to the field of biomedical technology, specifically disclosing a therapeutic probe targeting neuroblastoma GD2, adapted to the clinical needs of relapsed, refractory, and high-risk neuroblastoma. This therapeutic probe comprises paired diagnostic and therapeutic components, both using the humanized anti-GD2 monoclonal antibody hu3F8 as the sole targeting carrier; the diagnostic component is a zirconium-89-labeled deferoxamine-hu3F8 conjugate, and the therapeutic component is an actinium-225-labeled DOTA-hu3F8 conjugate. This application also discloses its preparation method, obtaining a high-purity product through three steps: antibody-chelating agent conjugation, radionuclide labeling, and purification. This probe system can be used to prepare a therapeutic drug composition for neuroblastoma, exhibiting strong targeting specificity, enabling imaging-guided precise radioimmunotherapy, and demonstrating good synergistic diagnostic and therapeutic effects.

The present invention provides a method for constructing brain glioma organoids capable of preserving an immune microenvironment. The culture medium, culture system and method provided by the present invention overcome the shortages that, with the prolonging of culture time, a large number of tumor immune cells are lost and the tumor immune microenvironment is greatly damaged in current glioblastoma organoid models, and can more completely preserve the tumor microenvironment of glioblastoma for a longer time, and greatly retain the heterogeneity of organoid tissue. The present invention is suitable for constructing a new generation of glioblastoma organoid models, and provides more reliable research tools for tumor microenvironment research of glioblastoma, tumorigenesis mechanism research, drug efficacy screening, and the development and application of disease models.

The invention provides application of an EGFR (epidermal growth factor receptor) inhibitor in preparation of a medicine for treating diseases mediated by the activity of a guanylate exchange factor (GEF) or jointly mediated by the activity of the guanylate exchange factor (GEF) and the activity of EGFR tyrosine kinase. The diseases are cancers selected from the following groups: lung cancer, colon cancer, breast cancer, endometrial cancer, thyroid cancer, glioma, squamous cell carcinoma, prostate cancer, melanoma, leukemia and glioblastoma. Specifically, the invention discovers that EGFR has a GEF function for promoting activation of Ras homologous protein (Rhb) besides traditional tyrosine kinase activity, the function does not depend on the tyrosine kinase activity and plays a key role by depending on a glutamic acid residue at the 804th site on an EGFR molecule, the Rhb-GEF activity of EGFR causes allosteric activation of a mammal rapamycin target protein complex 1 (mTORC1), and the activity of the EGFR causes allosteric activation of the mammal rapamycin target protein complex 1 (mTORC1). The tumor growth is finally promoted.

The invention provides an anti-tumor drug cell screening model establishment method based on a TBR1 site-directed mutant and application, and belongs to the technical field of biological medicine. By analyzing data of patients with medullary blastoma (MB) in children hospital of Nanjing Medical University and clinical patients with MB in EGA database, it is found that the proportion of Group 4 subtype MB is the highest, and TBR1 mutation specifically exists in Group 4 subtype MB; a mutation spectrum of TBR1 in Group 4 subtype MB clinical patient data is analyzed, a result shows that mutation is missense mutation, mutation sites are all concentrated in a T-box structural domain of TBR1, and a TBR1-G275 site is high-frequency mutation; the method comprises the following steps: designing a site 275 of a pegRNA targeted TBR1 T-box region by using a CRISPR-Cas9-based PE (Polyethylene) technology, carrying out site-directed mutagenesis on TBR1 in a Group 4 subtype D283 cell line on a genome level, and successfully constructing the Group 4 subtype MB cell model with TBR1-G275C mutation by using a method of drug screening, monoclonal culture and final sequencing verification.

The invention discloses an application of TCF7L2 (T cell factor 7L2) in treatment of glioblastoma. The research shows that the transcription factor TCF7L2 has an important tumor inhibition effect in glioblastoma cells (GBM), and the deletion of the transcription factor TCF7L2 can obviously accelerate the growth and malignant progression of tumor cells, so that the response capability of the GBM cells to exogenous neural signals is enhanced, and the tumor development is further promoted. In mechanism, the TCF7L2 regulates and controls the expression of various neurotransmitter receptors, and inhibitors applying the receptors can effectively reverse tumor promoting phenotypes caused by deletion of the TCF7L2, so that the TCF7L2 plays a key role in inhibiting GBM nerve dependence progression by maintaining the steady state of neural signal related receptors. The invention provides a new diagnostic and prognostic marker and a new therapeutic target for treatment of GBM, and provides a new thought and a new strategy for treatment of GBM.

The invention discloses a cerebrospinal fluid biomarker for monitoring glioma prognosis by a mass spectrometry technology and application of the cerebrospinal fluid biomarker. The biomarker comprises at least one of the following more than 30 proteins: AMBP, ATRN, ECM1, FCN2, HSPA8, NTM, PCDHGC5, PGLYRP2, PSMB1, RNH1, TMEM132A and the like. The invention also discloses application of the biomarker in preparation of a product for prognosis monitoring of tumors. The cerebrospinal fluid biomarker can be used for prognosis monitoring of CAR-T treatment of glioblastoma, has important significance on diagnosis and prognosis monitoring of high-grade glioblastoma, is earlier in early warning window phase, can realize long-term high-frequency monitoring, has good application value for individual follow-up visit of patients, and has wide application prospects. The CAR-T treatment prognosis monitoring of other types of tumors, especially nervous system solid tumors, can also be realized, and the application value is wide.

The description provides compositions and methods for treating ETBR-related cancer. In certain aspects, the description provides a delivery system for the controlled, systemic release of at least one of ETBR antagonists, caspase-8 inhibitors, or a combination thereof, optionally including an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide or a combination thereof. The compositions described are useful for the treatment of certain cancers, including, e.g., breast cancer, malignant melanoma, squamous cell carcinoma, glioblastoma, as well as others. In addition, the description provides a delivery system for the controlled release of at least one of ETBR antagonists, caspase-8 inhibitors or a combination thereof, optionally including at least one of an ETAR antagonist, an anti-PD-1 antibody, a bRAF inhibitor, niacinamide, or a combination thereof, to the central nervous system that are useful for treating cancers that have spread to the brain.

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 present disclosure provides methods of treating a medulloblastoma in a subject in need comprising administering T3 to the subject. The present disclosure also provides methods of inhibiting proliferation of medulloblastoma cells in a subject in need by administering T3 to the subject. Moreover, the present disclosure provides uses of T3 for treating medulloblastoma and the manufacture of a medicament for treating medulloblastoma.

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.