21 results about "Medulloblastoma" patented technology

Bioadhesive and biodegradable polymeric nanoparticles can be administered intrathecally, for example, via the cisterna magna, into the spinal column to allow widespread distribution for the treatment of tumors such as leptomeningeal metastases. The nanoparticles rapidly spread to all cerebrospinal fluid (CSF) compartments, including the brain parenchyma and spinal column. The bioadhesive nanoparticles penetrate and are retained for long periods of time, during which time they can continue to release drugs. These nanoparticles can be loaded with different therapeutic, preventive, or diagnostic agents, most preferably DNA repair inhibitors, to enhance the killing of leptomeningeal tumors, such as leptomeningeal metastases, and disseminated tumors, such as medulloblastoma. In a preferred embodiment, patients are treated with a combination of a PARP inhibitor and temozolomide.

The invention relates to a biomarker combination for treating SHH subtype medulloblastoma, and aims to solve the problems that existing treatment targets are deficient, the curative effect is limited and precise treatment is insufficient. The invention reveals that an m6A-YTHDF2 signal axis is a novel treatment target of SHH-MB for the first time, the YTHDF2 regulates and controls the expression of a downstream target gene DENND2A through an m6A dependency mode, the high expression of the YTHDF2 is related to poor prognosis of a patient, and knock-down of the YTHDF2 can significantly inhibit the proliferation and balling ability of SHH-MB cells. According to the invention, the TET-ON regulated SHH-MB cell line capable of inducing to knock down YTHDF2 is constructed, and a tool is provided for drug screening; it is clear that a YTHDF2 inhibitor (such as DC-Y13-27 and the like) can achieve the anti-tumor effect by down-regulating DENND2A expression, and the drug sensitivity of SHH-MB tumor cells to a Hedgehog signal channel small molecule inhibitor Vismodegib (GDC-0449) is improved.

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.

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 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.

In one aspect, the disclosure relates to compounds that behave as molecular glue degraders (MGDs) and methods of making and using same. In various aspects, the disclosed compounds are useful for modulating PPIL4 activity through targeted degradation. In various aspects, the compounds are useful for treating medulloblastoma and / or acute lymphoblastic leukemia (ALL). In further aspects, the present disclosure relates to methods of making the disclosed compounds, pharmaceutical compositions comprising the disclosed compounds, and methods of treating various clinical conditions and disorders using the same, such as T-cell acute lymphoblastic leukemia. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Disclosed are methods, compositions, and kits for treating pediatric cancers using hydroxyureamethyl acylfulvene (LP-184) or pharmaceutically acceptable salts / solvates thereof. The methods include monotherapy and combination regimens for pediatric sarcoma, medulloblastoma, glioma (including DIPG), hepatoblastoma, Wilms tumor, and related malignancies. Combination therapies include LP-184 with vincristine, topoisomerase I poisons (topotecan or irinotecan), PARP inhibitors (e.g., rucaparib), or spironolactone, yielding additive or greater-than-additive reductions in tumor growth or cell viability.

Methods of treatment of medulloblastoma by administering thyroid hormone (T3) to a subject are provided herein.

In accordance with the purpose(s) of the present disclosure, described herein are pyruvate dehydrogenase kinase 1 (PDK1) inhibitors and methods for treating cancer in a subject. In one aspect, the compounds having a formula represented by structure I or the pharmaceutically acceptable salt thereof as provided herein can be used to treat cancer associated with an elevated level of PDK1 in the subject such as, for example, glioblastoma, medulloblastoma, or breast cancer. Pharmaceutical compositions composed of the PDK1 inhibitors described herein are also provided.

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 invention discloses a sample typing method, system and equipment for medulloblastoma, and a medium. The method comprises the following steps: acquiring gene expression data and clinical subtype information of a patient with medulloblastoma; constructing a plurality of co-expression modules through a weighted gene co-expression network on the basis of the gene expression data, calculating feature genes of the co-expression modules, screening out target co-expression modules related to the to-be-typed sample on the basis of the feature genes and related scores, and extracting target module genes from the target co-expression modules; carrying out differential expression gene analysis on the to-be-typed sample to screen out differential expression genes meeting a first preset condition, determining subtype candidate genes based on the target module genes and the differential expression genes, and typing the to-be-typed sample of the medulloblastoma based on the state of the FHDC1 gene in the subtype candidate genes to obtain the to-be-typed sample of the medulloblastoma. Therefore, the invention can improve the accuracy of sample typing of myeloblastoma.

The invention provides a treatment device for treating medullary blastoma based on a radiation method, which comprises a supporting plate, an arc-shaped shell is arranged on the supporting plate, an arc-shaped track is arranged on the inner side of the shell, two groups of fixing plates capable of relatively sliding are further arranged on one side of the shell, arc-shaped blocks are slidably clamped in the arc-shaped track, and the two groups of arc-shaped blocks are connected through a fixing band. The arc-shaped block drives the fixing plate to slide through the transmission mechanism when sliding, a driving mechanism connected with the shell is arranged on the arc-shaped block, the arc-shaped block is driven to slide through the driving mechanism, power of the arc-shaped block is switched to winding of the end of the fixing belt when movement of the fixing plate is blocked, and a locking mechanism is further arranged on the arc-shaped block. And when the fixing belt is tensioned, the positions of the wound fixing belt and the arc-shaped block are fixed. The device can rapidly complete automatic fixation of different head types, the whole process does not need any adjustment, the forehead and cheeks of a patient can be fixed at the same time, operation is convenient and rapid, the structure is ingenious, and the treatment efficiency is effectively improved.

The invention belongs to the technical field of biological medicines, and relates to a tetrahydropyridine [4, 3-d] pyrimidine derivative as a Hedgehog signaling pathway inhibitor and a preparation method thereof. The tetrahydropyridine [4, 3-d] pyrimidine derivative serving as a Hedgehog signal channel inhibitor is prepared by creatively adjusting the reaction temperature and the ratio of reactants to a catalyst, the reaction yield is greatly increased, the reaction conditions are mild, and the derivative serving as the Hedgehog signal channel inhibitor has good activity on pancreatic cancer cells and medulloblastoma.

The present invention relates to the field of cancer. More specifically, the present invention provides compositions and methods useful for detecting long non-coding RNAs (lncRNA) in medulloblastoma. In one embodiment, the present invention provides a method comprising detecting lnc RNA HLX2-7 in a biological sample obtained from a patient having or suspected of having medulloblastoma. In certain embodiments, detecting step is performed using RNA fluorescence in situ hybridization (FISH) assay. In specific embodiments, the biological sample is a tissue sample. In particular embodiments, the tissue sample is a formalin-fixed paraffin-embedded (FFPE) sample. In a specific embodiment, the FISH assay comprises oligonucleotide probes that hybridize to lncHLX2-7 (SEQ ID NO:200) and branched DNA signal amplification.

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a α5-containing GABAA receptor agonist (e.g., a α5-containing GABAA receptor positive allosteric modulator) as described herein in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of a α5-containing GABAA receptor agonist (e.g., a α5-containing GABAA receptor positive allosteric modulator) as described herein in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

Brain tumors remain the leading cause of cancer-related deaths in children and often are associated with long-term sequelae among survivors of current therapies. Telomerase and telomeres play important roles in cancer, representing attractive therapeutic targets to treat children with poor-prognosis brain tumors such as diffuse intrinsic pontine glioma (DIPG), high-grade glioma (HGG) and high-risk medulloblastoma (MB). It has shown that DIPG, HGG and MB frequently express telomerase activity. It is now shown that the telomerase-dependent incorporation of 6-thio-2′deoxyguanosine (6-thio-dG), a telomerase substrate precursor analog, into telomeres leads to telomere dysfunction-induced foci (TIFs) along with extensive genomic DNA damage, cell growth inhibition and cell death of primary stem-like cells derived from patients with DIPG, HGG and MB. Importantly, the effect of 6-thio-dG is persistent even after drug withdrawal. Treatment with 6-thio-dG elicits a sequential activation of ATR and ATM pathways and induces G2 / M arrest. In vivo, treatment of mice bearing MB xenografts with 6-thio-dG delays tumor growth, increases in-tumor TIFs and apoptosis. Furthermore, 6-thio-dG crosses the blood-brain barrier and specifically targets tumor cells in an orthotopic mouse model of DIPG. Together, these findings suggest that 6-thio-dG is a promising approach to treat therapy-resistant telomerase-positive pediatric brain tumors.

The invention provides a salt form and a crystal form of a chiral heterocyclic compound with hedgehog pathway antagonist activity. The compound is (R)-1-(6-(5 '-chloro-3, 5-dimethyl-[2, 4'-bipyridyl]-2 '-yl)-5-methyl-5, 6, 7, 8-tetrahydropyrido [4, 3-d] pyrimidine-2-yl) piperidine-4-alcohol, the pharmaceutically acceptable salt of the compound has a high-temperature endothermic peak, so that the compound has good thermal stability, and the crystal form is basically not changed when the compound is heated. Particularly, the fumarate anhydrous crystal form F shows optimal thermodynamic stability, good physical and chemical stability and myeloblastoma resistance, better hygroscopicity, solubility and bioavailability compared with a free alkali amorphous form, better pharmacokinetic characteristics compared with GDC-0449, a better tumor inhibition effect and higher hedgehog signal channel inhibition activity.

An orally active, brain penetrant first-in-class small molecule midkine inhibitor for use in the treatment of triple-negative breast cancer, brain tumors (including glioblastoma, medulloblastoma, and NF1-mutant optic pathway gliomas), ovarian and endometrial cancers, lung cancer, as well as gynecologic non-malignant conditions such as endometriosis, uterine fibroids, and preterm birth, in which tumor cells and / or pathological cells exhibit heightened midkine signaling and express multiple midkine receptors.

The application discloses a medulloblastoma cell line. The medulloblastoma cell line provided by the application is identified by STR and karyotype analysis, no human cell cross contamination is found in the cell, and no cell with more than 80% matching degree of STR typing data is found in the Cellosaurus database. The cell line is also proved to be a neural tumor by HE staining, kki67 staining and synaptophysin staining. The cell can be stably passaged and can be used for drug sensitivity test. The cell line provided by the application provides a new direction for the research on the related mechanism and treatment method of medulloblastoma.

The invention provides an innovative method for methylation detection of medulloblastoma, and high-sensitivity and non-invasive methylation detection can be realized by combining a liquid biopsy technology and a novel methylation marker LINC00511 gene. According to the method, quantum dot labeling and surface enhanced Raman scattering technologies are utilized, so that the detection sensitivity and specificity of the methylation marker are remarkably improved, and the method is suitable for real-time monitoring of the low-abundance methylation marker. Compared with a traditional methylation detection method, the method provided by the invention can realize rapid and accurate detection in biological samples such as blood, urine and the like. The detection technology can be used for early diagnosis of medulloblastoma, can also effectively monitor the treatment reaction, has a wide clinical application prospect, and is especially suitable for the fields of non-invasive diagnosis and personalized treatment.