223 results about "Stage melanoma" patented technology

The invention belongs to the technical field of deep processing of agricultural products, and provides royal jelly protein zymolyte with melanin inhibition activity and preparation and application of the royal jelly protein zymolyte. Performing enzymolysis on the soluble royal jelly protein solution with pepsin to obtain enzymatic hydrolysate; and carrying out ultrafiltration separation on the enzymatic hydrolysate to obtain a polypeptide solution with the molecular weight of less than 3KDa, namely royal jelly protein hydrolysate. The royal jelly is used as a raw material, the royal jelly protein hydrolysate with low molecular weight is prepared by extracting royal jelly protein and utilizing a protease enzymolysis technology and an ultrafiltration separation technology, and the royal jelly protein hydrolysate has good melanogenesis inhibition activity and can reduce generation of mouse melanoma cells and zebra fish melanin. The inhibitor is derived from natural food royal jelly, is green and safe, is controllable in conditions in the preparation process, is convenient to extract, does not need artificial synthesis, and is expected to be applied to food, medicines or cosmetics with a whitening effect.

The present invention belongs to the technical field of cancer immunotherapy, and particularly relates to a cholesterol-modified cationic liposome tumor vaccine, a preparation method therefor, and use thereof. In order to solve the problems of poor targeting and strong side effects of TLR agonists in anti-tumor treatment, the present invention provides a cationic liposome prepared from a cholesterol-modified 1V209 molecule, a cationic lipid component, cholesterol, and DSPE-PEG2000, and then the cationic liposome and ovalbumin 5 form the tumor vaccine by electrostatic adsorption. Animal experiments show that the vaccine can induce antigen-specific CD8+ T cells, activate lymphocytes, and generate stronger antigen cross-presentation, more memory T cells, antibodies, and cytokines. Prophylactic inoculation with the vaccine can significantly delay the progression of mouse melanoma and lymphoma and prolong the survival of mice. The combination use of the vaccine and a PD-1 checkpoint inhibitor can further enhance the anti-tumor effect. Therefore, the vaccine is a promising cancer vaccine.

The invention discloses a zinc-selenium doped white calcium stone injectable hydrogel for treating melanoma and a preparation method of the zinc-selenium doped white calcium stone injectable hydrogel. The preparation method comprises the following steps: 1, preparing hydrophilic zinc-selenium doped white calcium stone; 2, preparing oxidized sodium alginate; and (3) dispersing the hydrophilic zinc-selenium-doped white phosphorus calcium stone into the oxidized sodium alginate solution, adding the carboxymethyl chitosan solution, and uniformly mixing to obtain the zinc-selenium-doped white phosphorus calcium stone injectable hydrogel for treating melanoma. The injectable hydrogel prepared by the invention has good injectability, self-healing property and biocompatibility, and is suitable for tumor wound models with any shape and depth; the composition has good effects of promoting normal cell proliferation and inhibiting tumor cell growth, and can be used for tumor postoperative treatment to inhibit tumor recurrence and promote surgical defective tissue repair.

The invention belongs to the field of probiotics and application thereof, and particularly relates to a humanized bifidobacterium animalis probiotic strain and application thereof in preparation of drugs for preventing or treating melanoma. The preservation number of the humanized bifidobacterium animalis is GDMCC No: 65044, the preservation unit is called GDMCC for short, and the active metabolite of the humanized bifidobacterium animalis contains mannose. The composition contains the bifidobacterium animalis probiotic strain, and contains / does not contain metabolites of the bifidobacterium animalis probiotic strain and one or more physiologically acceptable excipients or carriers. The method has the advantages that the protective strain lacked by the melanoma patient is screened and separated from the intestinal tract of a healthy person, the strain can normally survive in the intestinal tract of the human body and has no toxic or side effect, and a new way is provided for prevention and treatment of the melanoma patient by supplementing the lacked protective strain and active metabolites of the patient in a targeted manner; and an innovative solution is provided for auxiliary immunotherapy of melanoma.

The invention relates to the field of treatment of malignant melanoma, and discloses application of miR-18a and a downstream target thereof, and a composition for treating drug-resistant melanoma. The application finds the potential of miR-18a and downstream target thereof as malignant melanoma targeted therapy and immunotherapy biomarkers and the possibility of miR-18a and downstream target thereof as a therapeutic target for overcoming drug resistance. The application discovers that after the miR-18a is knocked out, melanoma targeted therapy drug resistance and CD8 + T cell tolerance can be simultaneously caused. Then, in a malignant melanoma patient receiving a BRAF inhibitor and immunotherapy, high expression prognosis of the miR-18a is relatively good, which prompts that the miR-18a can predict the curative effect of targeted therapy and immunotherapy and can be used as a biomarker of the curative effect of targeted therapy and immunotherapy. The invention further discloses a specific mechanism of miR-18a for causing targeted therapy or immunotherapy drug resistance.

The invention provides a melanoma segmentation method fusing a convolutional neural network and Transform. The method comprises the following specific steps: step 1, obtaining a melanoma training set; 2, expanding the data volume of the training set by adopting a data enhancement technology, and further enhancing the general applicability or generalization ability of the constructed model; and step 3, by innovatively introducing an SViT-C encoder, the excellent local feature extraction capability of a convolutional neural network (CNN), the excellent global dependence modeling advantage of Transform and the spatial pyramid pooling characteristic of PSP-Net are fused. The encoder ingeniously utilizes local features to guide global features, so that higher-level semantic association is accurately captured; 4, implementing a model training process to optimize and determine a training weight; and 5, implementing detailed performance evaluation and robustness test on the independent test set.

The invention discloses a glucan modified bionic nanoparticle as well as a preparation method and application thereof. Preparing nanoparticles based on PLGA as an inner core; the tumor cell membrane is extracted from B16F10 melanoma cells and is used as an outer capsid; glucan is coupled with a hydrophobic long chain through reductive amination and is modified on the surface of a biomimetic nanoparticle cell membrane through a hydrophobic effect. The dextran nano delivery system is successfully constructed, cell membrane specific antigens and dextran are efficiently and jointly delivered to lymph nodes, tumor cell membranes provide epitopes for immune activation of nanoparticles, and beta-dextran provides molecular support for nanoparticle targeting immune cells. In-vivo and in-vitro activity experiments prove that the glycolipid modified bionic nanoparticles can effectively activate innate immunity through macrophages and NK cells, can promote dendritic cell antigen presentation, and initiate potent adaptive immune response. The bionic nanoparticles have huge development potential of novel tumor vaccines, and a new thought is provided for immunotherapy of cancers.

The invention discloses miR-150-3p-loaded engineered extracellular vesicles with the surfaces modified with iRGD targeting peptides and application of the miR-150-3p-loaded engineered extracellular vesicles in melanoma treatment, and belongs to the technical field of biological medicines.The miR-150-3p is loaded in EVs, the surfaces of the miR-150-3p are modified with the iRGD targeting peptides, and iEV-150 is obtained; the preparation method of the iEV-150 comprises the following steps: S1, screening miR-150-3p; s2, constructing an HEK293T cell line capable of stably expressing the miR-150-3p; s3, introducing an ANXA2 protein; s4, culturing an HEK293T cell line; s5, separating the EVs; s6, coupling the iRGD targeting peptide to the surface of the extracellular vesicle membrane; the iEV-150 can effectively deliver miR-150-3p to melanoma cells, inhibit tumor cell proliferation, DNA damage repair and epithelial-mesenchymal transition, and promote melanoma cell death by inducing ferroptosis.

The application provides a radionuclide nanohydrogel microneedle and a preparation method and application thereof, and belongs to the field of nanobiomedicine. 32 P-labeled calcium phosphate, which is formed by a biomimetic reaction of Ag2S@Ca 32 P nanoparticles, and a base layer which is a base matrix and comprises hyaluronic acid 32 P nanohydrogel microneedle can release Ag2S nanoparticles in response to a weakly acidic tumor environment, and under the irradiation of near-infrared light, the photothermal conversion efficiency can effectively kill bacteria, effectively improve the tumor hypoxic environment, enhance the treatment effect of radionuclides, play an antibacterial and wound healing promoting role in melanoma defect repair, and maximize the inhibition of tumor growth and tumor recurrence.

The invention discloses an anti-tumor compound, a preparation method, a pharmaceutical composition containing the compound and application, and belongs to the technical field of biological medicine. The compound disclosed by the invention has a remarkable effect in an in-vitro anti-tumor activity test. In the design process, the N3-((4, 6-dimethyl-2-oxo-1, 2-dihydropyridine-3-yl) methyl)-N3 '-(R)-[1, 1'-biphenyl]-3, 3 '-dicarboxamide compound is designed and synthesized, the anti-tumor effect is improved, and it is found that the N3-((4, 6-dimethyl-2-oxo-1, 2-dihydropyridine-3-yl) methyl)-N3'-(R)-[1, 1 '-biphenyl]-3, 3'-dicarboxamide compound has good anti-proliferation capacity on human melanoma cells A375. In the synthesis process, the synthesis steps are optimized, and possibility is provided for future industrial production.

The invention provides an engineered bionic dendritic cell vesicle coupled antigen peptide tumor vaccine as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The engineered bionic dendritic cell vesicle provided by the invention is internally loaded with an agonist of an interferon gene stimulation receptor, and the surface of an outer membrane is coupled with a melanoma antigen peptide gp100. In the engineering bionic dendritic cell vesicle provided by the invention, the antigen peptide gp100 can trigger the hyperactivity of various immune cells such as DC at a lymph node part, the antigen presentation procedure of the DC is promoted, and the killing ability of effector T cells is enhanced; the interferon gene loaded in the vesicles stimulates agonists of receptors, so that immune cells can be promoted to be activated, the ability of the immune cells to recognize pathogens and abnormal cells is enhanced, meanwhile, various immune cells are induced to secrete I-type interferon, apoptosis of tumor cells is promoted, immune memory effects of the immune cells are promoted, and recurrence and metastasis of tumors are prevented.

The invention provides a method of treating a melanoma comprising (i) identifying a patient having a PD-L1-negative melanoma and (ii) administering to the patient a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof. The methods of the invention can extend progression-free survival for over 8 months and / or reduces the tumor size at least about 10%, about 20%, about 30%, about 40%, or about 50% compared to the tumor size prior to the administration.

The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors. These data suggest the generality of drug-mediated MEK kinase cleavage as a therapeutic strategy to prevent resistance to targeted anticancer therapies.

The invention discloses a tumor targeting boron-containing Fe3O4-based nano-enzyme and a preparation method and application thereof, and belongs to the technical field of tumor treatment.The tumor targeting boron-containing Fe3O4-based nano-enzyme takes boron-10 doped Fe3O4 nano-enzyme as a boron-containing drug group and an enzyme activity center, and the surface of the tumor targeting boron-containing Fe3O4-based nano-enzyme is modified with a targeting group; the targeting group is chitosan-folic acid-polyethylene glycol. The tumor targeting boron-containing Fe3O4-based nano-enzyme has relatively strong selective enrichment capacity on tumor cells such as melanoma, shows good biocompatibility and low toxicity, and has relatively strong apoptosis induction and killing effects on the melanoma cells in boron neutron capture therapy; meanwhile, active oxygen free radicals can be generated in boron neutron capture therapy to generate an oxidative damage effect.

A neutrophil loaded with attenuated salmonella and a preparation method therefor and a use thereof, relating to the technical field of biology. Vascular clearance by a neutrophil is a key factor affecting the tumor colonization rate of oncolytic bacteria, i.e., attenuated salmonella typhimurium. The neutrophil can be recruited to a tumor microenvironment after being loaded with the oncolytic bacteria, so that the tumor colonization rate and tumor targeting performance of the bacteria are effectively improved. The neutrophil can directly kill tumor cells and release intracellular oncolytic bacteria to induce an anti-tumor immune response, thereby effectively inhibiting the progression of pulmonary metastases from melanoma.

The invention provides an engineered bionic nano dendritic cell vesicle, a melanoma vaccine, a preparation method and application, and particularly belongs to the technical field of biological medicine. The engineering bionic nano dendritic cell vesicle is loaded with an interferon gene stimulating factor agonist and a holoantigen engineering vesicle which is derived from melanoma cells and is subjected to oxidation treatment. The engineered bionic nano dendritic cell vesicles can be used for preparing melanoma vaccines, are good in safety and strong in stability, and have a good anti-melanoma effect.

The invention discloses a spleen-targeted nano platform construction method suitable for tumor vaccination, and particularly relates to the field of vaccines.The spleen-targeted nano platform construction method comprises the steps that S1, CL15H6-DOPS LNPs, spherical polymer vesicles and erythrocyte membrane coated nano-particles are selected as spleen-targeted nano-carriers; s2, integrating an immunologic adjuvant; mn < 2 + > doped LNPs, ultrasonic response lipidosome and a CD3 antibody are selected to be coupled to serve as an integration material; s3, delivering in vivo; animal models are selected for in-vivo delivery and curative effect verification, and B16F10 melanoma mice, MC38 colon cancer mice and non-human primates are selected as the animal models respectively. By optimizing the chain length and the surface topological structure (such as spherical polymer vesicles) of the liposome, the spleen enrichment rate is remarkably increased, and the red marrow myeloid cell uptake efficiency is enhanced. By combining with common delivery of a manganese adjuvant, an STING channel is activated, secretion of type I interferon is promoted, and the proportion of antigen-specific CD8 + T cells and the tumor inhibition rate are increased.

The invention discloses a preparation method of drug-loaded membrane protein bionic vesicles based on a microfluidic technology and application of the drug-loaded membrane protein bionic vesicles to targeted melanocyte delivery drugs, and belongs to the technical field of pharmaceutical preparations. The method is easy and convenient to operate, assembly of the phospholipid bilayer and insertion of the membrane protein are accurately controlled through the laminar focusing technology, and the stable and efficient drug-loaded membrane protein bionic vesicle is formed. The drug-loaded membrane protein bionic vesicles can effectively target melanocytes, promote the uptake of the vesicles, significantly improve the accumulation of drugs in the melanocytes, and enhance the treatment effect on melanocyte related diseases (such as hyperpigmentation, melanoma, vitiligo and the like). Meanwhile, the drug-loaded bionic vesicles constructed by the invention have relatively low keratinocyte uptake rate, drug uptake of non-targeted tissues is effectively reduced, and side effects of drugs are reduced, so that the drug-loaded membrane protein bionic vesicle system constructed by the invention has great prospects in the aspect of treating melanocyte related diseases.

The application discloses a kind of elastin-like polypeptide V 20 K 40 L, mRNA vaccine and preparation method and application in preparation tumor prevention, mitigation or treating drug.The elastin-like polypeptide carrier V 20 K 40 L provided by the application has good biocompatibility, and has no adverse reaction in vivo.The elastin-like polypeptide V 20 K 40 L provided by the application has amphiphilic structure, can be loaded Melan-A mRNA by hydrophobic self-assembly and electrostatic adsorption, and is in the state of shrinkage when higher than Tt temperature, which can prevent the uncontrollable leakage of mRNA.Furthermore, V 20 K 40 L contains lysosome escape peptide, which can further improve the transfection efficiency of mRNA by promoting lysosome escape.The elastin-like polypeptide V 20 K 40 L in the application can deliver Melan-A mRNA efficiently and safely, and realize the prevention and treatment of melanoma.

A series of 1, 3, 5-triazine compounds that exhibit potent inhibition of endosomal trafficking and autophagy is provided. These compounds effectively suppress cancer cell proliferation, growth, and migration, induce cell cycle arrest at the G0 / G1 phase, promote cancer cell death via non-apoptotic pathways, and inhibit tumor sphere formation. Moreover, select compounds within this series demonstrate significant inhibition of tumor growth and metastasis in mouse models of lung cancer and melanoma. Additionally, they modulate macrophage polarization and the tumor microenvironment by regulating cytokine secretion. These findings highlight the potential of 1, 3, 5-triazine compounds as promising antitumor agents.

The invention discloses an application of an OH2 oncolytic virus combined with a PD-1 inhibitor in preparation of an antitumor drug. The OH2 oncolytic virus and the PD-1 inhibitor are jointly applied to tumor treatment, and through the synergistic effect of the OH2 oncolytic virus and the PD-1 inhibitor, the anti-tumor immune response is enhanced, and the treatment effect is improved. According to the combined treatment scheme, tumor cells can be directly killed, recurrence and metastasis of tumors can be inhibited by activating systemic immune response, and a new treatment choice is provided for tumor patients. In the application, the neutrophile granulocyte number level in the blood of a tumor patient is closely associated with the treatment effect of the anti-tumor medicine, the anti-tumor medicine can be used for evaluating the treatment effect, and the anti-tumor medicine is suitable for common tumor adaptations including colorectal cancer, esophageal cancer, head and neck tumor, gastric cancer, biliary tract system tumor, sarcoma, melanoma and other tumors.

The pharmaceutical composition for preventing and treating melanoma comprising K-ras-specific activated T cells according to the present invention uses, as an antigen composition, K-ras mutant (G12D, G12V, and G13D) recombinant overlapping peptides which are designed such that the peptides are sequentially divided into a total of 12 epitopes (n=1 to 12, wherein the last epitope (n=12) comprises 23 amino acids) in units of 30 amino acids in the amino acid sequence of K-ras with 15 amino acid sequences overlapping between the epitopes, and thus has the advantage of being more effective in recognizing and killing melanoma in which K-ras, K-ras mutant G12V, K-ras mutant G12D, or K-ras mutant G13D is detected. Therefore, the pharmaceutical composition for preventing and treating melanoma comprising K-ras-specific activated T cells according to the present invention has the advantage of being capable of effectively preventing and treating melanoma in which not only K-ras but also K-ras mutants are detected.

The invention provides compositions and methods for treatment of melanoma and other cancers. In particular, the invention provides a single or double-stranded nucleic acid that inhibits a certain group of long non-coding RNAs (lncRNAs) that have been discovered to be associated with melanoma. Inhibition of these lncRNAs in melanoma cells and xenograft mouse models leads to inhibition of cell proliferation, induction of apoptosis, and reduced cancer cell growth. The invention also relates to a method of inhibiting cancer cell growth with specific kinase inhibitors that have been found to show similar inhibition effects as the nucleic acids targeting the lncRNAs. The single or double-stranded nucleic acid and the specific kinase inhibitors constitute a novel therapeutic strategy in the treatment of melanoma and other cancers.

Here, the inventors have developed a spectral flow cytometry assay to measure heme biosynthesis. By using this new assay on melanoma cell lines, they observed a direct correlation between high PPIX levels in differentiated MITFhigh cells and a protection against ferroptosis. Conversely, cell lines with low PPIX levels were associated with a dedifferentiated MITFlow phenotype enriched in stem cell markers and more sensitive to ferroptosis inducers. They also found that inhibition of PPIX biosynthesis in differentiated melanoma cells synergizes with iron overload to induce lipid peroxidation and tumor cell death. Finally, they show that decreased levels of PPIX linked to increased ferroptosis sensitivity can be acquired in vivo in melanoma tumors that relapse after anti-MAPK targeted therapies. The present invention relates to a method of determining whether a subject has or is at risk of having melanoma ferroptosis sensitivity and targeted therapy resistance comprising i) determining the level of protoporphyrin IX (PPIX) in a biological sample obtained from the subject and ii) comparing the level determined at step i) with a predetermined reference value: wherein if the level of the PPIX determined at step (i) is lower than the predetermined reference value is indicative that the said patient is having melanoma ferroptosis sensitivity and targeted therapy resistance or wherein if the level of the PPIX determined at step (i) is higher than the predetermined reference value is indicative that the said patient is having melanoma ferroptosis resistance and targeted therapy sensitivity. The present invention also relates to a method for treating resistant melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of a ferroptosis inducer.

The invention discloses jellyfish polypeptide with tyrosinase inhibitory activity and application of the jellyfish polypeptide, and belongs to the technical field of biology. A jellyfish crude polypeptide is prepared, a jellyfish polypeptide GEPINPEAWLWYYKYVG is identified and optimized from the jellyfish crude polypeptide, and experiments prove that the jellyfish polypeptide provided by the invention can inhibit the activity of tyrosinase in vitro, can inhibit melanin secretion of B16-F10 mouse melanoma cells, and can inhibit the activity of tyrosinase in the cells. Therefore, the jellyfish polypeptide can be used as a tyrosinase inhibitor and an anti-melanin synthesis agent and is applied to the fields of cosmetics, medical treatment and the like. Experiments prove that the jellyfish polypeptide provided by the invention has no cytotoxicity, is derived from ocean, and has no disease risks and religious barriers of terrestrial animals.

The invention discloses a molecular mechanism research method regulated and controlled through metabolism reprogramming, and relates to the technical field of molecular biology. The method specifically comprises the following steps: S1, preparing an experimental cell material and an experimental reagent; the experimental cell material is melanoma cells, and the experimental reagent comprises a DMEM high glucose culture medium, PINK1 targeting lentivirus and the like. According to the application, cell infection, RNA (Ribonucleic Acid) extraction, RT-qPCR (Reverse Transcription-Quantitative Polymerase Chain Reaction) detection, Western blot experiment, cell activity detection and the like are carried out on lentivirus targeting PINK1, a molecular mechanism of melanoma caused by BRAF gene V600E mutation regulated by PINK1 through metabolic reprogramming is researched, and aerobic glycolysis caused by PINK1 down-regulation can be alleviated by inhibiting ENO2, so that PINK1 inhibits aerobic glycolysis of melanoma cells, and the application has the advantages that the application is simple, the application is convenient, and the application has a wide application prospect. The low-expression PINK1 promotes the growth of melanoma cells.

The invention discloses a sifA gene knockout attenuated salmonella recombinant engineering bacterium as well as a preparation method and application thereof, and belongs to the technical field of microbial biology. An intracellular vesicle (SCV) of the attenuated salmonella VNP20009 of the engineering bacterium forms a related gene sifA, and the related gene sifA is seamlessly knocked out. The engineering bacterium is named as VNP20009 [delta] sifA. The invention also discloses a preparation method of the engineering bacterium. The engineering bacterium has the characteristic of keeping the characteristic of specific colonization of a female parent strain VNP20009 in a tumor hypoxic region, and meanwhile, the biotoxicity of the strain is further reduced; meanwhile, the strain has a potential value of becoming a chassis strain for combined synthesis of biological tumor therapy due to relatively weak killing performance and higher intracellular load on immune cells. The invention also provides a construction method of the strain and application of the strain in treatment of mouse entity subcutaneous melanoma.

The present invention relates to the field of biomedicine, and in particular to immunogenic cell death-enhancing nanovesicle hydrogels and their applications. The present invention provides a 3D-printable, multifunctional, synergistic immunogenic cell death-enhancing nanovesicle hydrogel. The hydrogel uses SerMA hydrogel as a matrix and encapsulates cell membrane nanovesicles (N@ILO) loaded with the photothermal agent IR1061, the chemotherapy drug OXA, and the tumor acidic microenvironment regulator Lon. The hydrogel triggers initial tumor immunogenic cell death through the photothermal effect, further enhances the ICD effect through OXA, and modulates the acidic tumor microenvironment through Lon to increase T cell activity, achieving multimodal synergistic anti-tumor therapy after surgery. The hydrogel also possesses excellent photocurable 3D printing capabilities and can be used to construct personalized filling structures that match postoperative defect areas. The hydrogel has broad application prospects and provides a new strategy and theoretical basis for the comprehensive postoperative treatment of choroidal melanoma.

The application relates to a method for establishing a MASH and a related liver cancer model by using a liver stellate cell-specific Lonp1 knockout mouse. flox / flox Mice are crossed with Lrat-2A Cre Mice to obtain mice with specific Lonp1 gene deletion in liver stellate cells. The mice do not have obvious liver abnormalities at 2 weeks old, liver fibrosis and lipid accumulation appear at 6 weeks old, cirrhosis and inflammation foci formation appear at 6 months old, and liver cancer gradually appears at 10 months old. More importantly, the mice can form a large number of large liver cancer nodules within 16 weeks under the induction of GAN diet. In addition, when melanoma cells are injected into the spleen to establish a splenic liver metastasis model, the liver stellate cell Lonp1 deletion mice show a significantly increased number of metastatic tumors. The model can effectively simulate the pathological process of MASH progressing to liver cancer, and provides a reliable tool for related mechanism research and drug development.

Disclosed are neuronal nitric oxide synthase (nNOS) inhibitors and methods of using the same in treating a disease or disorder associated with nNOS activity, such as a neurological disease or disorder, or melanoma.