51 results about "Hepatocellular Cancers" patented technology

The invention provides a multi-modal large language model for generating a hepatocellular carcinoma key pathological diagnosis report, a framework main body is a visual coding module, and a multi-modal feature alignment module, a multi-head low-rank attention mechanism, an enhanced medical MoE mechanism and a structured output decoding layer are also introduced. The visual coding module is constructed on the basis of a Swin Transform architecture, visual pre-training is completed on hepatocellular carcinoma MRI data, and after a task specific classification head is stripped, a trunk feature extraction network is reserved to serve as an image modal representation encoder. The multi-modal feature alignment module guides the model to learn a cross-modal semantic mapping relation between a hepatocellular carcinoma MRI image and a key pathological diagnosis report language, image modal input is a visual feature sequence, and text modal output is a structured description text; and the structured output decoding layer generates six types of liver cancer focus attributes. According to the method, the pre-operative multi-parameter and multi-stage enhanced MRI image is utilized, and the open-source large model is finely adjusted to generate a matched liver cancer postoperative pathology report.

The invention relates to the technical field of hepatocellular carcinoma, in particular to a hepatocellular carcinoma prognosis model construction method based on immunogen cell death related genes and application, and an accurate prognosis prediction model is constructed by integrating the immunogen cell death related genes (IRGs) and molecular characteristics of hepatocellular carcinoma. A training set and a verification set provided by TCGA and ICGC databases are utilized, so that the model can perform effective sample analysis under a large-scale data background. Through consistency clustering analysis, the optimal clustering number is determined, the samples are orderly divided into different molecular subtypes, and it is ensured that the samples in each subtype have similar molecular characteristics. According to the invention, the capability of capturing liver cancer heterogeneity on the molecular level of the model is increased, so that the accuracy of prognosis prediction is improved.

Aspects of this invention are related to the use of N-desmethyl ruboxistaurin and pharmaceutically acceptable formulations thereof to modulate RSK signaling. Some aspects of the invention relate to the use of N-desmethyl ruboxistaurin to inhibit RSK. Some aspects of the invention provide methods of using N-desmethyl ruboxistaurin in the treatment of subjects with cancer, including breast cancer, ovarian cancer, prostate cancer, lung cancer, hepatocellular carcinoma, colorectal cancer, melanoma, osteosarcoma, myeloproliferative neoplasms, leukemia, and bladder cancer. The disclosed methods extend beyond disease treatment, including supportive care during radiation chemotherapy and prevention of cancer relapse. N-desmethyl ruboxistaurin administration, alone or in combination with other cancer therapies, inhibits RSK and shows a safety profile that supports its long-term use.

The present disclosure provides a new therapeutic target and marker, circBCO2, for inhibiting the progression of liver cancer, especially hepatocellular carcinoma. Inhibition of the expression of circBCO2 or destruction of the signal pathway regulated thereby can serve as a potential therapeutic target for inhibiting the progression of liver cancer. Meanwhile, circBCO2 can also serve as a marker, especially a prognostic marker, for HCC.

A method of inhibiting a cancer cell growth includes contacting the cancer cell with a Cu2(OH)3NO3 / CaSiO3@g-C3N4 nanocomposite material containing graphitic carbon nitride (g-C3N4), copper hydroxide nitrate (Cu2(OH)3NO3) and calcium silicate (CaSiO3), achieving an inhibition efficiency on human breast carcinoma (MCF-7) and human hepatocellular carcinoma (HepG-2) cell growth of greater than 95% in an in-vitro cellular viability assay.

The invention discloses application of a copper carrier in a medicine for enhancing drug resistance of copper death reversing liver cancer cells, and relates to the technical field of medicines. The copper carrier provided by the invention can activate copper death in cisplatin-resistant liver cancer cells in a manner of'three-arrow simultaneous shooting '. The method mainly comprises the following steps: increasing the number of copper ions entering cells (a first'arrow '), consuming GSH to reduce the loss of copper ions in the cells (a second'arrow'), and down-regulating the expression of ATP7B to inhibit the outflow of copper ions (a third'arrow '). Besides, the copper carrier down-regulates copper death related proteins (FDX1, DLAT, ATP7B and LIAS), also down-regulates drug resistance related proteins (ATP7B and P-gp), and shows a remarkable anti-liver cancer curative effect. Particularly, the bCCM can target mitochondria, improve the mitochondrial copper ion level, consume mitochondrial GSH and cause mitochondrial dysfunction mediated by copper death, and the bCCM and the cis-platinum have a remarkable synergistic effect and can reverse the drug resistance of the cis-platinum.

This invention discloses a prognostic and therapeutic suitability assessment model for hepatocellular carcinoma (HCC) based on mRNA vaccine antigens, and its construction method. First, the differences in gene expression between normal tissues and HCC tumors are analyzed to understand the mutations and genomic structural changes in HCC patients. Then, genes related to the level of antigen-presenting cell infiltration, as well as genes significantly related to overall survival and disease-free survival, are further selected from anomalously expressed and mutated genes to obtain candidate mRNA vaccine neoantigen targets. Based on the expression levels of these targets, patients are immunophenotyped to assess the patient population suitable for mRNA vaccines. Simultaneously, the relationship between target expression levels and patient prognosis is quantified to predict the probability of HCC patients achieving 3-year and 5-year overall survival. This invention can objectively and accurately assess treatment resistance and tumor immune status in HCC, improving the predictive accuracy of HCC treatment prognosis.

The present invention relates to systems and methods of processing CT scan images comprising a liver of a subject to detect and / or predict hepatocellular carcinoma (HCC) in the subject.

The disclosure provides binding agents (e.g., antibodies) against a human Hepatitis A virus cellular receptor 2 protein (TIM3), as well as kits and methods for using the same (e.g., immunoassays) as part of a companion diagnostic and for other applications. In some aspects, the binding agents described herein may be used in assays for detecting Non-Small Cell Lung Cancer (NSCLC) and / or other types of lung cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), Hepatocellular Carcinoma (HCC) or other types of liver cancer, Renal cell carcinoma, malignant melanoma, gastro-intestinal cancer, colorectal cancer, urothelial carcinoma and other types of bladder cancer, mamma carcinoma and / or other types of breast cancer, ovarian cancer, cervical cancer, prostate cancer, pancreatic cancer, lymphoma / leukemia, malignant mesothelioma, or a cancer in another organ or cell type.

The invention belongs to the technical field of biological medicines, and particularly relates to a membrane-coated oncolytic virus as well as a preparation method and application thereof. The oncolytic virus contains a GSDMD N-terminal expression cassette regulated and controlled by a heated shock promoter, and pyroptosis can be induced under exogenous mild thermal stimulation, so that the virus is promoted to be quickly released, and reinfection and amplification of adjacent tumor cells are realized. A bionic nano-vesicle (iNV) formed by a donor cell membrane modified by genetic engineering is used as an outer layer to coat a genetically engineered oncolytic virus (GOV) to obtain a membrane-coated oncolytic virus iNV-GOV, so that the membrane-coated oncolytic virus iNV-GOV simultaneously has immunocompatibility and active tumor recognition capability, is suitable for solid tumors such as pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHCC) and the like, and can be used for preparing an anti-tumor drug. And the tumor volume can be obviously reduced in mouse in-vivo model experiments.

This invention discloses a nanoparticle-based drug delivery system, MPL@ICC, its synthesis method, and its applications. The MPL@ICC system consists of hollow, porous nano-MnO2, a hydrophilic targeting complex on its surface, and an acid-responsive drug, INH-CA, and a photosensitizer loaded internally. It possesses both targeted transport and controlled release capabilities against human hepatocellular carcinoma cells (HepG2), allowing it to accumulate within these cells and achieve photodynamic therapy (PDT) and free radical-induced immune killing within the tumor. Simultaneously, it directly kills tumor cells and transforms them from non-immunogenic to immunogenic, mediating an anti-tumor immune response and achieving immunogenic cell death (ICD). This overcomes the shortcomings of ICD-induced cancer treatment strategies, which often fail to produce strong and durable therapeutic effects, and does not induce normal cell apoptosis, thus possessing controllability, effectiveness, and safety.

The invention relates to application of theaflavin as a UGP2 inhibitor and application of theaflavin in preparation of a medicine for preventing and / or treating hepatocellular carcinoma, and belongs to the technical field of biology. According to the invention, the monomeric compound theaflavin derived from a natural product can be used as a UGP2 direct targeting inhibitor for the first time, and is used for preparing a liver cancer treatment medicine for regulating and controlling glucose metabolism reprogramming. The theaflavin can be specifically and directly combined at a UGP2 active site in a targeting manner through high activity to inhibit the activity of the UGP2, is the first specific inhibitor which takes the UGP2 as a target spot and is reported at present, and can be used for remarkably inhibiting tumor phenotypes such as proliferation, migration and invasion of liver cancer cells by inhibiting UGP2-mediated UDPG synthesis and intracellular glycogen accumulation.

The present technology relates to the field of cancer treatment. In particular, the present technology relates to polypeptides targeting phosphatidylinositolprotein-3 (GPC3) and T cell receptor (TCR) for use in the treatment of phosphatidylinositolprotein-3 positive (GPC3 +) solid tumors, such as hepatocellular carcinoma (HCC) or non-small cell lung cancer (NSCLC). In addition, the technology relates to the dosage of said polypeptide when used as therapy.

The disclosure relates to peptide conjugates specific for Epithelial cell adhesion molecule (EpCAM) and the use thereof to detect and treat epithelial cell-derived cancers such as intrahepatic cholangiocarcinoma (ICC), hepatocellular carcinoma (HCC), breast cancer, colon cancer and basal cell carcinoma of the skin. The disclosure also relates to methods to monitor the therapeutic response of treated patients by detecting expression of EpCAM.

The present invention relates to 1,2-dicarboxamide compounds of Formula (I); pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, N-oxides or combination thereof, wherein 'X', 'Y', 'Z', ring A, ring B, R1, R2, R3, R4, R5, R6, 'm' and 'n' are as defined herein. The present invention also relates to 1,2-dicarboxamide compounds that modulate cellular activities like proliferation, differentiation, adhesion, migration and apoptosis by modulating protein kinase enzymatic activity. In particular the invention relates to compounds which inhibit, regulate, and / or modulate tyrosine kinases such as FLT1 (VEGFR1), FLT4 (VEGFR3), KDR (VEGFR2), MET (C-Met), MERTK (c-Mer), RET, AXL, TEK (TIE 2) and EGFR. The present disclosure relates to 1,2-dicarboxamide compounds for use in modulating kinase enzymatic activity and accordingly modulating kinase-dependent associated diseases and conditions such as cancers like Thyroid carcinoma, Ovarian carcinoma, Pancreatic carcinoma, Prostatic carcinoma, Renal cell carcinoma, Hepatocellular carcinoma, Breast carcinoma, Colorectal carcinoma, Oral squamous cell carcinoma, Colorectal, Lung adenocarcinoma or Endometrial cancer.

A kudzuvine flower terpine derivative, a preparation method and application thereof, a structure formula is shown as follows: wherein R1, R2 are H, CH3, CH2F, CHF2, CF3, t-Bu, MOM, EE, THP, a straight chain or branched alkane with carbon atom number being 1-5, an ester group, a silyl ether, a trifluoro or polyfluorinated alkane straight chain terminal alkyne alkane n=1, 2, 3, 4 or 5, m=1, 2, 3, 4, 5 or 6, when one group is a terminal alkyne, the other two groups are alkane or fluorinated alkane. The kudzuvine flower terpine derivative can inhibit the proliferation growth of liver cancer cells, induce liver cancer cell apoptosis and G2 / M cycle arrest, inhibit the migration and invasion of liver cancer cells, achieve the effect of resisting tumors, and provide a new leading drug for clinical treatment of hepatocellular carcinoma.

This invention provides an IR820-GPC3-Gd compound and its nanomaterials (IGD NPs) for phototherapy and magnetic resonance imaging of liver cancer, along with their preparation method and applications, belonging to the field of medicinal chemistry. The IR820-GPC3-Gd compound exhibits strong targeting, good phototherapy performance, and stable imaging. The IGD NPs demonstrate excellent active targeting ability for hepatocellular carcinoma (HCC); under 808nm laser irradiation, they exhibit outstanding photothermal and photodynamic properties, making them suitable for treating unresectable HCC. The combined fluorescence imaging and magnetic resonance imaging capabilities of the IGD NPs can precisely locate residual tumor boundaries and provide real-time surgical navigation, improving the conversion therapy efficiency of HCC and ultimately significantly reducing postoperative recurrence rates, providing an effective strategy for tumor downstaging and surgical navigation.

This invention belongs to the field of biomedical technology and provides the application of 16'-DEC in the preparation of anti-hepatocellular carcinoma drugs. This bisindole alkaloid compound can inhibit the proliferation and migration of hepatocellular carcinoma cells and can produce a synergistic anti-tumor effect with lenvatinib, solving the problems of limited efficacy and insufficient patient survival benefit of existing targeted drugs in hepatocellular carcinoma treatment. Experiments have confirmed that 16'-DEC exerts its anti-tumor effect by directly inhibiting mTOR kinase activity. This compound can specifically bind to mTOR protein, significantly upregulate the expression of autophagy-related genes by blocking the mTOR signaling pathway, and induce autophagic cell death in tumor cells. In vitro and in vivo experiments have demonstrated that inhibiting autophagy can reverse the anti-cancer effect of 16'-DEC, indicating that its pharmacodynamic mechanism mainly depends on the activation of the autophagy pathway. This invention is applicable to the development of novel targeted therapies for hepatocellular carcinoma, especially specific inhibitors of the mTOR signaling pathway.

The invention belongs to the technical field of biological medicines, and provides a porphyrin coupled ruthenium (II) complex as well as a preparation method and application thereof. The porphyrin coupled ruthenium (II) complex (PorRu, as shown in the following formula) can be selectively enriched in tumor tissues and is highly specifically combined with G quadruplex (G4) DNA (deoxyribonucleic acid) in a double-lock mode. The dual-binding configuration of PorRu enhances the stability of the structure interacting with DNA, so that more efficient photodynamic activation is realized. When PorRu is combined with G4 DNA and exposed to near-infrared light, high-level active oxygen can be generated, guanine bases are directly oxidized to form 8-oxoguanosine damage, the oxidative damage causes mitochondrial dysfunction and induces pyroptosis, and efficient tumor inhibition is achieved through a synergistic mechanism. The PorRu provides a promising strategy for breaking through the tumor hypoxia barrier, and has huge clinical transformation potential in the field of hepatocellular carcinoma treatment.

The application belongs to the technical field of immunobiology, and particularly relates to a hepatocellular carcinoma antigen peptide and application thereof. The hepatocellular carcinoma antigen peptide provided by the application is a group of shared neoantigens derived from splicing abnormalities, long fragment insertion and deletion or gene fusion mutations, and has the advantages of good safety, high sharing, strong immunogenicity and high tumor specificity. The number of spots produced by the hepatocellular carcinoma antigen peptide has a statistical difference through immunological enzyme-linked immunospot assay, which indicates that the hepatocellular carcinoma antigen peptide has strong immunogenicity. The hepatocellular carcinoma antigen peptide can specifically activate the killing efficiency of induced expanded T cells on tumor cells to be greater than or equal to 30% through tumor cell killing experiment verification, and has a significant tumor killing effect. The hepatocellular carcinoma antigen peptide has great market value when used for preparing a vaccine for preventing and / or treating hepatocellular carcinoma.

The present disclosure relates to novel antibodies or antigen-binding fragments thereof that bind to GPC3. These anti-GPC3 antibodies or fragments thereof preferably comprise no lysine residues in their CDRs, and thus are particularly suitable for conjugation. The present disclosure also relates to targeted radionuclide conjugates, such as targeted actinide 225 conjugate (TAC). Preferably a TAC of formula (I) comprising an anti-GPC3 antibody or fragment thereof of the present disclosure. The antibody or antigen-binding fragment thereof, and / or the antibody conjugate, and / or the TAC can be used in diagnosis and / or therapy, preferably in therapy, more preferably in the treatment of cancer, most preferably in the treatment of hepatocellular carcinoma (HCC). Pharmaceutical compositions comprising these antibodies, functional fragments and conjugates and kits with instructions are provided. The disclosure also provides methods and tools for making these antibodies, functional fragments and conjugates.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an MFN1 expression promoter in preparation of a medicine for treating mixed liver cancer. The MFN1 expression promoter provided by the invention is a recombinant expression vector containing MFN1. It is proved for the first time that MFN1 is highly expressed in hepatocellular carcinoma-like components of mixed liver cancer and is lowly expressed in cholangiocellular carcinoma-like components, and the MFN1 expression promoter can eliminate phenotypes of the mixed liver cancer by inhibiting cholangiocellular carcinoma-like tumor components in the mixed liver cancer, so that prognosis of tumor-bearing mice is improved. Theoretical basis and potential targets can be provided for treatment of the mixed type liver cancer, and certain guiding significance is achieved for research and development of targeted drugs for the mixed type liver cancer.

Compositions containing cannabinoids and kinase inhibitors are useful for the treatment of hepatocellular carcinoma (HCC). Compositions containing cannabinolic acid (CBNA) and sorafenib act synergistically on HepG2 cells, an in vitro liver cancer model, and on ex vivo patient-derived xenograft (PDX) HCC models. The effects of all of the disclosed compositions are superior to sorafenib alone, which is the first- and second-line chemotherapeutic agent for the treatment of HCC.

The invention provides a method for establishing a multi-group biomarker system based on lenvatinib, and relates to the technical field of biomedicine. The method comprises the following steps: collecting a sample and treating the sample to obtain a blood concentration threshold value of lenvatinib; processing the sample to obtain a to-be-detected sample, and processing the to-be-detected sample to obtain original mass spectrum data; carrying out preprocessing and multivariate statistical analysis on the original mass spectrum data, and screening differential metabolites; extracting an exosome in the sample; paraffin sections of tumor tissues, para-carcinoma tissues and normal components are obtained, and immune cell subpopulation differences between different tissues and different lenvatinib concentration groups are compared; and a plurality of groups of biomarker systems of lenvatinib in liver cancer cell cancer quality are established. According to the present invention, the plasma concentration, the plasma metabolite, the exosome miRNA and the tumor immune microenvironment of the lenvatinib are subjected to integrated analysis to construct the multi-dimensional treatment effect evaluation system, and the limitation of the single biomarker is exceeded;

The invention discloses a multi-phase CT image-based early recurrence risk prediction method and system after hepatocellular carcinoma liver transplantation, and belongs to the technical field of medical image processing and artificial intelligence. The method comprises the following steps: S1, multi-phase CT image acquisition and standardization preprocessing; s2, sketching a tumor area and a peritumor area to form a target volume; s3, extracting radiomics features and deep learning features; s4, performing multiple rounds of feature screening, and combining clinical risk factors to construct a deep learning radiomics column graph prediction model; s5, risk prediction and layering; and S6, combining with the traditional clinical standard to realize increment value integration. The system comprises an image access and preprocessing module, a feature calculation engine, a model management module, a risk assessment module and a clinical decision support module. The problems of insufficient information utilization, difficulty in clinical integration and the like in the prior art are solved by jointly analyzing the tumor and the peritumoral region and fusing multi-dimensional features, the early recurrence prediction precision is improved, and support is provided for clinical decision making.

The invention relates to novel crystalline solid forms of the chemical compound N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Compound 1), and solvates thereof, including hydrates, that are useful for the treatment of cancer. Also disclosed are pharmaceutical compositions comprising the crystalline solid forms and processes for making the crystalline solid forms, as well as methods of using them for the treatment of cancer, particularly thyroid cancer, prostate cancer, hepatocellular cancer, renal cancer, and non-small cell lung carcinoma. The crystalline solid forms can be used to make the L-malate salt of cabozantinib.

The invention relates to the field of biological medicine and immunotherapy, and particularly provides a liver cancer neoantigen vaccine based on immunopeptidomics and immunotherapy application of the liver cancer neoantigen vaccine. According to the invention, an MHC-I immunoprecipitation technology is combined with high-throughput mass spectrometry, a neoantigen short peptide group with excellent immunogenicity is identified from a liver cancer sample, and a long peptide group is obtained by extension on the basis of short peptides. The oligopeptide antigen and the long peptide antigen are respectively mixed with an adjuvant Poly (I: C) to prepare a vaccine, and a mouse liver cancer model proves that the vaccine can effectively inhibit tumor progression and induce a tumor microenvironment to be converted into an immune activation state. The invention provides a new antigen source and a vaccine form for individualized liver cancer immunotherapy, and has remarkable clinical application potential and industrialization prospect.

The invention discloses a capillary SERS (Surface Enhanced Raman Scattering) sensor based on CRISPR / Cas13a (Clustered Regularly Interspaced Short Palindromic Repeats / CRISPR associated 13a), a preparation method of the capillary SERS sensor and application of the capillary SERS sensor to detection of a hepatocellular carcinoma marker miR-221, the method comprises the following steps: 1) adopting a seed growth method, firstly synthesizing a decahedral gold nano seed, and on the basis, continuing to react and grow to obtain dumbbell-shaped gold and silver nano rods (DS Au-AgNRs); (2) dispersing the DS Au-AgNRs prepared in the step (1) into a PVP ethanol solution, and assembling the DS Au-AgNRs onto an aminated capillary tube by utilizing the interaction of PVP groups on the surfaces of nano-particles and amino groups on the inner wall of the capillary tube, so as to obtain a capillary tube SERS (Surface Enhanced Raman Scattering) substrate; and 3) modifying the surface of the capillary SERS substrate prepared in the step 2) with a single-stranded DNA modified with sulfydryl and Raman signal molecules (Cy5) through a gold-sulfur bond to construct the SERS sensor.The capillary SERS sensor provided by the invention has the advantages of high sensitivity, high specificity, convenience in sampling, low cost and the like, and is expected to provide a novel method with a prospect for early diagnosis of HCC.

This invention belongs to the fields of disease diagnosis, prognosis, and molecular biology, specifically relating to the application of spermine synthase (SMS) in the diagnosis, prognosis, and prediction of response to immune checkpoint blockade (ICB) therapy in hepatocellular carcinoma (HCC). Research revealed that, compared to normal liver tissue, the expression of spermine synthase (SMS) is significantly upregulated in HCC; and high SMS expression is associated with poor clinicopathological features of prognosis. Furthermore, compared to the low SMS expression group, HCC patients in the high SMS expression group had significantly shorter overall survival, disease-specific survival, and progression-free survival, thus SMS overexpression predicts unfavorable outcomes. Simultaneously, SMS overexpression affects immune cell infiltration in HCC patients, leading to poor immune checkpoint blockade (ICB) responses and poor treatment efficacy for HCC. In conclusion, SMS can serve as a biomarker for the diagnosis and prediction of clinical outcomes in HCC, and also as a biomarker for predicting ICB treatment response.

The invention provides an adeno-associated virus-mediated recombinant virus system for targeting liver cancer stem cells and application of the adeno-associated virus-mediated recombinant virus system. The invention provides a recombinant virus system rAAV2 / 8-Prom1-GFP-T2A-DTR of a targeted liver cancer stem cell, an rAAV2 / 8 virus formed by recombination of an AAV2 type genome and an AAV8 type capsid protein is used as a carrier, and polynucleotide for coding a CD133 promoter, a green fluorescent protein and a diphtheria toxin receptor is inserted into the carrier. The invention further provides application of the compound in preparation of a medicine for treating hepatocellular carcinoma, and also provides a medicine composition for targeting liver cancer stem cells. The virus vector constructed by the invention can effectively mark stem cells after occurrence of liver cancer, and is closer to a clinical practical application scene. The method not only can simulate the actual treatment process, but also has more significant significance for guiding the clinical treatment strategy. Through the AAV vector, the liver cancer stem cells can be targeted and marked after tumors occur, and the treatment purposes of effectively controlling the progress of liver cancer and prolonging the life cycle can be achieved by removing the targeted liver cancer stem cells and using chemotherapeutic drugs in a combined mode.