31 results about "Brain metastasis" patented technology

The invention discloses a substituted 2-amino-9-(3, 3-difluoropiperidine-4-yl)-7, 9-dihydro-8H-purine-8-ketone compound with a structural formula as shown in formula (I): (I) The substituted 2-amino-9-(3, 3-difluoropiperidine-4-yl)-7, 9-dihydro-8H-purine-8-ketone compound disclosed by the invention as well as a derivative and pharmaceutically acceptable salt thereof, and a preparation method of the substituted 2-amino-9-(3, 3-difluoropiperidine-4-yl)-7, 9-dihydro-8H-purine-8-ketone compound. The compound can be used as a protein kinase inhibitor drug to play a role, especially can inhibit protein expression induced by DNA-PK, and can be used for treating or preventing diseases related to abnormal protein kinase activity. The compound can be used for treating cancer, such as cancer, cancer accompanied with brain metastasis, cancer accompanied with meningeal metastasis, glioma, glioblastoma, diffuse endogenous bridge glioma (DIPG) and the like, and can be independently applied or combined with other treatment modes (such as radiation therapy or chemotherapy).

The present disclosure provides compositions and methods comprising amrannekast, or a pharmaceutically acceptable salt thereof, for the treatment and prevention of brain metastases. The present disclosure provides treatment and / or prevention of brain metastases in a subject suffering from ER + breast cancer within such compositions and methods.

The invention belongs to the technical field of biological medicine, and particularly relates to application of CST6 as a lung cancer brain metastasis early diagnosis marker. The core of the invention is to confirm that CST6 is used as a marker for early diagnosis and prediction of brain metastasis of lung cancer for the first time. In experimental verification, the CST6 protein expression quantity of the lung cancer cell strain H1975-BrM with high brain metastasis potential is remarkably higher than that of a common cell strain, an animal model further shows that overexpression of CST6 can promote formation of brain metastasis, and knock-down expression can inhibit metastasis capacity; clinical sample analysis shows that the serum CST6 concentration of brain metastasis patients is far higher than that of non-metastasis patients and healthy people, and the diagnostic value of CST6 is supported. In the aspect of diagnosis efficiency, the area under the ROC curve of the serum CST6 reaches 0.848, and high accuracy is shown. On the whole, the clinical blank is filled, and a reliable tool is provided for non-invasive lung cancer brain metastasis risk management.

This invention discloses a wasp venom peptide-M nanocomposite, its preparation method, and its applications, belonging to the field of medicinal chemistry. Using indocyanine green as a morphology mediator, this invention prepares an ultra-small particle size dendritic tetrasulfide by reacting it with triethylamine, hexadecyltrimethylammonium bromide, tetraethyl orthosilicate, and bis[3-(triethoxysilyl)propyl]tetrasulfide in water. Wasp venom peptide-M is then loaded onto this nanocomposite to obtain the wasp venom peptide-M nanocomposite. In vitro experiments have confirmed that this composite can significantly kill 4T1 breast cancer cells. Furthermore, thanks to its ultra-small particle size, it also exhibits good targeting and enrichment, significant anti-tumor efficacy, and excellent safety in a breast cancer brain metastasis model, providing a novel and efficient nanomedicine delivery system for brain tumor treatment and the development of related therapeutic drugs.

This invention belongs to the field of pharmaceutical formulation technology, specifically disclosing a gastrodin transdermal patch and its preparation method. The patch consists of a backing layer, a drug-containing matrix layer, and an anti-adhesive layer, using gastrodin as the active ingredient. It employs HP-β-CD inclusion technology, combined with an HPMC and PVP polymer backbone and an oleic acid-menthol composite transdermal enhancement system. The preparation utilizes solvent casting and low-temperature vacuum drying processes, which are mild and controllable. This invention effectively solves the problems of difficult transdermal absorption, easy recrystallization, and low bioavailability of gastrodin. The resulting patch has excellent adhesion, no skin irritation, high transdermal penetration, and good skin biocompatibility. It can efficiently cross the blood-brain barrier, regulate the neuroinflammatory microenvironment in the brain, significantly inhibit the colonization and progression of non-small cell lung cancer brain metastases, and strongly reverse tumor-related anxiety and depression-like mood disorders. It provides a novel drug delivery regimen with great clinical translational potential for the non-invasive synergistic treatment of brain tumors and their associated mood disorders.

The present invention relates to the treatment of cancer with metastases in the central nervous system (CNS), in particular in the brain, using the HER2 tyrosine kinase inhibitor zongertinib. Accordingly, compounds for use, methods of prevention and / or treatment and uses related to said treatment are herewith provided.

The utility model relates to the technical field of tumor cell metastasis models, in particular to a breast cancer circulating tumor cell remote metastasis model which comprises a base and a fixing rod, the fixing rod is fixedly connected to the base, the fixing rod is fixedly connected with a brain metastasis model, a placing component is installed on the brain metastasis model, and the placing component is fixedly connected with the brain metastasis model. The placing part comprises an inclined plate, a fixed plate, a movable plate, a pressed plate, a straight spring and a collecting box, the inclined plate is fixedly connected in the brain metastasis model, the clamping plate clamps small balls with different colors through the matching effect of the extrusion rod, the movable plate, the collecting box and other parts, the small balls can be taken out by pulling the clamping plate, and the small balls can be conveniently taken out. And residual water is left in the collecting box, so that the small balls can be quickly taken out, meanwhile, no water drips on the outer surface of the model, the situation that the transparency of the model is affected by water marks generated on the outer surface of the model due to water dripping is avoided, and the transparency of the organ model and the cleanliness of a placement environment are guaranteed.

This invention relates to the field of biomedical technology, providing the application of a combination of diagnostic biomarkers for lung adenocarcinoma brain metastases based on BNIP3, CD74, and LYZ. Specifically, it relates to the application of this combination of diagnostic biomarkers in the preparation of reagents for predicting the prognosis of lung adenocarcinoma brain metastases. These reagents predict the prognosis of lung adenocarcinoma brain metastases by detecting the expression levels of BNIP3, CD74, and LYZ in the brain metastatic tissues of patients with lung adenocarcinoma brain metastases. This invention, based on a combination of diagnostic biomarkers for lung adenocarcinoma brain metastases based on BNIP3, CD74, and LYZ, can accurately assess the progression and risk level of a patient's disease in predicting prognosis and risk stratification of lung adenocarcinoma brain metastases. This provides precise reference for subsequent individualized treatment plans and rehabilitation programs, thus optimizing patient management.

The invention relates to the technical field of biology, in particular to a construction method of a novel lung cancer brain transfer model. The method comprises the following steps: carrying out induction culture on stem cells to obtain an embryoid organ, and carrying out differentiation culture on the embryoid organ to obtain a midbrain ventral organ; the method comprises the following steps: shearing and digesting small cell lung cancer (SCLC) tissue blocks to obtain SCLC cells, and carrying out suspension culture to obtain small cell lung cancer (SCLC) organs; and placing the midbrain ventral organ and the small cell lung cancer organ in the same culture container, and carrying out co-culture to obtain the novel lung cancer brain transfer model. Compared with a human-derived tumor tissue xenograft technology with a low success rate, the novel lung cancer brain transfer model provided by the embodiment of the invention has high fusion efficiency and batch stability, and interference of other heterologous animal components can be reduced. In addition, the organoid fusion model established by using the technology of the invention is easier to observe, deliver drugs and sample.

This invention provides a nucleic acid aptamer that targets and binds to the IGF2BP2 protein and its application, belonging to the field of pharmaceutical technology. This invention is the first to design a highly specific nucleic acid aptamer targeting the RNA recognition protein IGF2BP2, obtaining a nucleic acid aptamer that can target and specifically bind to the IGF2BP2 protein (see SEQ ID No. 1-2). This nucleic acid aptamer can effectively inhibit the activity of tumor cells, tumor stem cells, and breast cancer brain metastases, breast cancer lung metastases, breast cancer liver metastases, breast cancer kidney metastases, and breast cancer bone metastases, providing a new drug component for the treatment of malignant and refractory tumors (especially glioblastoma and distant metastatic breast cancer). Furthermore, it was discovered that modification with N6-methyldeoxyadenosine monophosphate can further enhance the specificity of the nucleic acid aptamer and strengthen its efficacy in inhibiting tumor cell activity.

The present disclosure is directed to a method that involves selecting a subject having a primary tumor and obtaining, from the selected subject, a sample containing exosomes derived from primary tumor cells. The exosomes are isolated from the sample and expression levels of cell migration-inducing and hyaluronan-binding protein (CEMIP) are detected in the isolated exosomes.

The present invention relates to a method for predicting survival of non-small cell lung cancer patients with brain metastasis. More specifically, it proposes a method that is useful for predicting the survival of the patients by comparing TMTrg of the patients with cut off value for predicting long term survival.

The application belongs to the technical field of pharmaceutical preparations, and specifically discloses an acetyl gastrodin transdermal patch and a preparation method thereof. The transdermal patch takes acetyl gastrodin as an effective component, is encapsulated in cubic phase liposomes composed of glycerol monostearate, cholesterol and Pluronic F127, is dispersed in a complex matrix of hydroxypropyl methyl cellulose and ethyl cellulose, and is matched with a complex transdermal enhancer of glyceryl caprylate / caprate and ethanol. In the preparation, the liposome material is first melted to load the drug, and then drug-loaded cubic phase liposomes are formed through ice water bath ultrasonic treatment. Then, the drug-loaded cubic phase liposomes are mixed with the polymer matrix and excipients, are defoamed, are coated, and are dried in two steps to be shaped. The cubic phase liposomes are used to significantly improve the drug penetration rate and stability, realize 24-hour smooth drug release, efficiently penetrate the skin and the blood-brain barrier, significantly inhibit non-small cell lung cancer brain metastases, improve tumor secondary anxiety and depression, have excellent skin compatibility, and provide a new non-invasive synergistic treatment scheme for brain tumors and concurrent emotional disorders.

The invention provides a curcuma zedoary ethanol extract as well as a preparation method and application thereof in resisting brain metastatic tumor. The curcuma zedoary ethanol extract disclosed by the invention has remarkable cytotoxicity inhibition activity, and the inhibition effect of the curcuma zedoary ethanol extract is time-dependent and dose-dependent. The curcuma zedoary ethanol extract can inhibit the growth of brain metastases of breast cancer and lung cancer.

The application discloses a small cell lung cancer brain metastasis risk prediction method based on cfDNA methylation map and belongs to the technical field of biomedical detection. The application solves the technical problems of the lag of the small cell lung cancer brain metastasis imaging diagnosis in the prior art, the insufficient sensitivity and specificity of traditional tumor markers, and the lack of systematic background noise correction. The application extracts cfDNA from peripheral blood samples of patients and healthy people, quantifies the methylation signals of brain tissue cells in the plasma by using a whole U fragment ratio method, removes tumor background noise by using a multi-dimensional Marker filtering strategy including primary focus filtering, intra-sample dynamic rejection and background database filtering, combines a random forest algorithm to construct a prediction model and outputs a risk score. The application can accurately identify high-risk patients several months before imaging diagnosis, and realizes early warning.

The application discloses a marker tiRNA-Gln-TTG-001 and application thereof, and belongs to the technical field of biotechnology and molecular diagnosis. The applicant finds that, compared with lung cancer patients without brain metastasis, tiRNA-Gln-TTG-001 is significantly highly expressed in the peripheral blood circulation of lung cancer patients with brain metastasis, which provides an important basis for the marker as a specific plasma marker for predicting, monitoring or diagnosing lung cancer brain metastasis. The new clinical cases are selected for verification, and the results show that tiRNA-Gln-TTG-001 can be used as a specific metastasis marker for lung cancer brain metastasis, which opens up a new non-invasive, convenient and specific detection way for early prediction, dynamic monitoring, diagnosis and efficacy evaluation of lung cancer brain metastasis.

The invention discloses an application of LOX in plasma exosome as a lung adenocarcinoma brain metastasis early warning marker, and the content difference of LOX in plasma exosome samples of patients with lung adenocarcinoma brain metastasis and non-brain metastasis is verified. The fact that early warning or diagnosis of the lung adenocarcinoma brain metastasis by detecting the LOX content change in the plasma exosome has high specificity and accuracy is proved, it is affirmed that LOX can serve as a marker to provide new guidance for early warning or diagnosis of the lung adenocarcinoma brain metastasis, and convenience is provided for clinical diagnosis in a liquid biopsy mode; the obvious clinical application value is realized.

In one aspect, antibodies that bind to subdomain II of human HER2 are provided. In another aspect, antibodies comprising a light chain polypeptide that pairs with both a heavy chain polypeptide for binding to subdomain II of human HER2 and a heavy chain polypeptide for binding to subdomain IV of human HER2 are provided. In a further aspect, antibodies that bind to both subdomain II and subdomain IV of human HER2 comprising a common light chain polypeptide are provided. Methods of treating a cancer or treating brain metastasis of a cancer using these antibodies are also provided.

The invention discloses a small-molecule inhibitor ratenshu and application thereof, and belongs to the technical field of biological pharmacy. On the basis of mostly retaining the immunosuppressive activity of triptolide, the small-molecule inhibitor ratenshu disclosed by the invention has the advantages that the toxicity is greatly reduced, the solubility is improved, and the druggability is better. Besides, the small-molecule inhibitor ratenshu is small in side effect and high in targeting performance, the small-molecule compound capable of smoothly passing through the blood-brain barrier can treat or reduce growth of non-small cell lung cancer brain metastatic cells, and the small-molecule inhibitor ratenshu has wide application prospects when being applied to preparation of drugs for treating non-small cell lung cancer brain metastatic growth.

The invention discloses a bionic nano-carrier capable of reversibly regulating and controlling a blood brain barrier and application of the bionic nano-carrier. The bionic nano-carrier is of a core-shell structure, a lecithin surface modified inorganic nano-material serves as a core, a cell membrane of brain metastatic cancer cells coats the surface of the core to serve as a shell, and an A2A adenosine receptor agonist is loaded in a cell membrane coating layer. The blood brain barrier crossing efficiency is further improved; wherein the lecithin surface modified inorganic nano-material is obtained by using an oleic acid modified inorganic nano-material as a matrix and carrying out surface modification through amphiphilic ligand lecithin. The bionic nano-carrier regulates and controls the blood-brain barrier permeability in a reversible mode, the problems that the brain transfer efficiency of a brain metastatic cell membrane bionic carrier through a cell bypass path is limited, potential safety hazards exist in a traditional blood-brain barrier permeability regulation and control open means and the like are solved, and a new strategy is provided for efficient brain delivery.

The invention relates to the field of tumor diagnosis and treatment, and provides application of CDKN2A and ISG15 proteins in diagnosis or treatment of brain metastasis of lung cancer. The invention particularly relates to application in preparation of products for diagnosing or inhibiting lung cancer brain metastasis, tumor immune escape, tumor epithelial-mesenchymal transition, tumor cell invasion and migration ability, tumor cell matrix metalloproteinase expression quantity and tumor cell PD-L1 level. The invention provides a more effective way for diagnosis or treatment of brain metastasis of lung cancer, and has important clinical application value.

This invention provides therapeutic drugs and methods for treating brain metastases from cancer. [Solution] In one embodiment, a bispecific protein having the ability to specifically bind to both subdomain II and subdomain IV of human HER2 is provided. In another embodiment, a method is provided for treating cancer or brain metastases of cancer using a bispecific protein that specifically binds to subdomains II and IV of human HER2.

In alternative embodiments, provided are methods comprising use of orthotopic and organoid models to better characterize ADAR1 activity in breast cancer (BC) metastatic niches, with a special focus on the less studied brain metastasis (BM). Methods as provided herein provide new insights into the mechanistic role of ADAR1 in breast metastatic disease and provide novel models for developing or discovering new therapeutics, such as as drugs, effective against BC and BM.

The application belongs to the technical field of biological medicine, and relates to an SLC15A1 targeted protein degradation agent, a construction method thereof and application of the agent in preparation of a drug for treating brain metastasis of lung adenocarcinoma. The application constructs an SLC15A1 targeted PROTAC protein degradation agent IL-PROTAC. The degradation agent couples ibuprofen with a ligand of an E3 ubiquitin ligase, lenalidomide, through a linker, so as to form a bifunctional molecule capable of targeting SLC15A1 and inducing protein degradation of SLC15A1. The IL-PROTAC drug constructed by the application has been proved to be capable of significantly inhibiting tumor growth of a LUAD brain metastasis model and prolonging the survival cycle of an animal model.

The application provides a tumor treatment system and application of an alternating electric field in preparation of a drug for treating non-small cell lung cancer brain metastasis. The system comprises a tumor electric field treatment device for applying an alternating electric field to a lesion site of a patient's head, and a radiotherapy device for irradiating the patient's head with radioactive rays, wherein the alternating electric field has a frequency of 100-300 kHz and an electric field strength of at least 0.1 V / cm, and the patient has unresectable non-small cell lung cancer brain metastasis and has not received antitumor treatment for non-small cell lung cancer brain metastasis.

The invention discloses an antisense oligonucleotide of a targeted hsacirc0004807 gene and application of the antisense oligonucleotide in inhibition of brain metastasis of breast cancer. The application of the annular RNA gene-hsacirc0004807 serving as a regulation target or a regulation marker in prevention or treatment of cancer brain metastasis is provided for the first time, meanwhile, a series of designed ASO is provided, expression of the hsacirc0004807 gene can be remarkably inhibited through the synthesized ASO or ASO expressed based on a carrier, the brain metastasis inhibiting effect is obvious, and the application of the annular RNA gene-hsacirc0004807 in prevention or treatment of cancer brain metastasis is achieved. The invention provides the application of the method for inhibiting the expression of the annular RNA gene-hsacirc0004807 gene in preparation of drugs for inhibiting or treating cancer brain metastasis, and the method has a definite clinical application prospect.

The application discloses a kind of risk stratification model construction method and system for EGFR mutant non-small cell lung cancer meningeal metastasis patient, belong to tumor prognosis evaluation technical field.The multicenter retrospective clinical database is first constructed and data preprocessing is completed, then the predictor is screened by LASSO Cox regression, and the five core prognostic factors of ECOG PS score, brain metastasis, MRI meningeal enhancement, CSFC result and intracranial pressure are determined by multi-factor Cox proportional risk regression and linear predictor is constructed, then it is converted into integer type weighted risk score, finally the best cutoff value is determined based on survival function, and the patient is divided into low-risk group and high-risk group.The application can clearly distinguish the patient group with significant difference in prognosis, the required indicators are all clinical routine items, the operation is simple, the accessibility is high, can accurately guide individualized treatment decision and clinical trial stratification, and has important clinical application value.

The invention relates to the technical field of vaccines, and particularly discloses a preparation method and application of a tumor cell vaccine, the preparation method comprises the steps of collecting breast cancer cells in a growth index phase, preparing a cell suspension, performing radiation treatment, uniformly mixing the cells and the like, and single-time high-dose (40Gy) radiation is adopted as an inactivation mode; the completeness of a cell structure and the diversity of antigens can be kept to the greatest extent while the proliferation capacity of tumor cells is thoroughly destroyed. The prepared vaccine can strongly activate organism specific T cell immunity and significantly increase the number of IFN gamma < + > CD8 < + > T cells in peripheral blood and tumor local microenvironments, so that an immunosuppressive'cold tumor 'microenvironment is reversed to an immunoactivated'hot tumor' microenvironment, and resistance of breast cancer brain metastasis to immunotherapy is overcome.

This invention discloses a brain delivery nanocarrier via a transcellular transport pathway. It uses a lecithin-modified inorganic nanomaterial as its core and a membrane-fused liposome-cell membrane as its shell. The membrane-fused liposome-cell membrane coats the surface of the lecithin-modified inorganic nanomaterial, forming a core-shell structure. The membrane-fused liposome-cell membrane is formed by the hybridization and fusion of membrane-fused liposomes with the cell membranes of metastatic brain cancer cells. This brain delivery nanocarrier can efficiently cross the blood-brain barrier via a membrane fusion pathway, bypassing the classic endocytosis-lysosome pathway to enter brain microvascular endothelial cells, thus solving the problems of low delivery efficiency and easy retention and degradation in lysosomes of existing nanomaterials.

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to scaffold molecules that inhibit epidermal growth factor receptor (EGFR), the methods of making same, the pharmaceutical compositions comprising same, and the methods of treating cancers involving aberrant EGFR activity.