523 results about "Hepatocellular carcinoma" patented technology

This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and / or secretion and / or abdominal disorders or diseases and / or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

Provided herein are methods and compositions for the diagnosis, prognosis and treatment of Hepatocellular carcinoma (HCC). Also provided are methods of identifying anti-HCC agents.

Certain biomarkers and biomarker combinations are useful in a qualifying hepatocellular carcinoma status in a patient. A diagnostic methodology employing these biomarkers and combinations can distinguish between hepatocellular carcinoma and chronic liver disease, for example.

A method for evaluating hepatocellular carcinoma in a subject is provided. In certain embodiments, the method comprises: a) obtaining a hepatocellular carcinoma protein marker profile for a sample obtained from the subject; and b) comparing the protein marker profile to a control profile.

Objective methods for detecting, diagnosing, treating and preventing hepatocellular carcinoma (HCC) are described herein. In particular, the present invention relates to two genes up-regulated in HCC cells as compared to normal cells, referred to herein as MGC47816 and HES6. In one embodiment, the diagnostic method involves the determining the expression level of MGC47816 or HES6 that discriminate between hepatocellular carcinoma cells and normal cells. The present invention further provides methods of screening for therapeutic agents useful in the treatment of HCC, methods of treating HCC, and methods for vaccinating a subject against HCC.

The present invention provides methods and compositions for treating hepatocellular carcinoma (HCC) by administering a composition comprising nanoparticles that comprise a taxane and an albumin. The invention also provides combination therapy methods of treating HCC comprising administering to an individual an effective amount of a composition comprising nanoparticles that comprise a taxane and an albumin and another agent, such as an agent that inhibits microtubule disassembly.

Elevated levels of GP73 in the sera is diagnostic for hepatocellular carcinoma. An increase in serum GP73 levels over time can also indicate the onset of hepatocellular carcinoma in subjects at risk for the disease.

This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and / or secretion and / or abdominal disorders or diseases and / or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

The invention relates to the technical field of genetic engineering, and particularly relates to a guide RNA (gRNA) sequence based on a CRISPR / Cas9 system and combinations thereof, as well as gRNA for a specific targeted knockout hepatitis B virus cccDNA P gene. In the invention, 30 gRNAs are designed according to design principles of CRISPR / Cas9, have a sequence table as shown in SEQ ID NO.1-30, and are constructed on a PX458 vector, to screen out four more efficient gRNAs. The CRISPR / Cas9 system guided by the four gRNAs and combinations thereof is utilized in a human hepatocellular carcinoma cell line (HepG2.2.15) to effectively knock out the human hepatitis B virus cccDNA P gene. The gRNA of the specific targeted hepatitis B virus cccDNA prepared in the invention can accurately target the hepatitis B virus cccDNA and realize gene knockout. The preparation method is simple in operation; the gRNA has a good targeting property; the CRISPR / Cas9 system is high in knockout efficiency.

The present invention is directed to methods, compositions and kits for treatment of cancer, e.g. heptacellular carcinoma. In some embodiments, the present invention discloses the use of a small-molecule compound of formulas (I)-(XXVI) as disclosed herein to inhibit transcription factor Late SV40 Factor (LSF) for treatment of cancer, e.g., HCC.

Quinoline derivatives showing anticancer activities against cancer cell lines of hepatocellular carcinoma (Hep3B), lung carcinoma (A549), esophageal squamous cell carcinoma (HKESC-1, HKESC-4 and KYSE150). The quinoline derivatives have a backbone structure of the following formulas:

The present invention is to provide a computer readable medium comprising a computer program for enabling a computer to carry out provision of information on hepatocellular carcinoma in a subject based on an analysis result on methylation status of a novel marker specific for hepatocellular carcinoma.The above object is achieved by obtaining the analysis result on methylation status of a CpG site located in a promoter region of at least one gene selected from CELF6 and RNF135 in a DNA sample derived from the subject and providing information on hepatocellular carcinoma in the subject based on the resulting analysis result.

The invention discloses a monoclonal antibody of GPC3, which is generated by the secretion of a human GPC3 resistant monoclonal antibody hybrid tumor cell strain with the preservation number of CGMCC No.3232. The monoclonal antibody can be used for an immunohistochemical test of hepatocellular carcinoma.

Methods for treating a human having heptocellular carcinoma comprising administering to the human a therapeutically effective amount of Compound A:or a pharmaceutically acceptable salt thereof, wherein the human has a complete response or partial response.

Disclosed are a method for early, sensitively and reliably detecting and distinguishing intrahepatic cholangiocarcinoma in a malignant tumor occurring primarily in the liver in a simple way, and a kit therefor. In the method, a glycan biomarker consisting of a lectin WFA (Wisteria floribunda Agglutinin)-binding glycoprotein derived from intrahepatic cholangiocarcinoma is used as a cancer marker to detect intrahepatic cholangiocarcinoma by detecting the cancer marker in a test specimen. The method for detecting intrahepatic cholangiocarcinoma can clearly differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma and enables early detection and determination with a performance clinically acceptable in terms of applicability, sensitivity and precision.

Protein transduction exploits the ability of some cell-penetrating peptide (CPP) sequences to enhance the uptake of proteins and other macromolecules by mammalian cells. Previously developed hydrophobic CPPs, named membrane translocating sequence (MTS), membrane translocating motif (MTM) and macromolecule transduction domain (MTD), are able to deliver biologically active proteins into a variety of cells and tissues. Various cargo proteins fused to these CPPs have been used to test the functional and / or therapeutic efficacy of protein transduction. For example, recombinant proteins consisting of suppressor of cytokine signaling 3 protein (CP-SOCS3) fused to the fibroblast growth factor (FGF) 4-derived MTM were developed to inhibit inflammation and apoptosis. However, CP-SOCS3 fusion proteins expressed in bacteria were hard to purify in soluble form. To address these critical limitations, CPP sequences called advanced MTDs (aMTD) have been developed in this art. This is accomplished by (i) analyzing previous developed hydrophobic CPP sequences to identify specific critical factors (CFs) that affect intracellular delivery potential and (ii) constructing artificial aMTD sequences satisfied for each critical factor. In addition, solubilization domains (SDs) have been incorporated into the aMTD-fused SOCS3 recombinant proteins to enhance solubility with corresponding increases in protein yield and cell- / tissue-permeability. These recombinant SOCS3 proteins fused to aMTD / SD having much higher solubility / yield and cell- / tissue-permeability have been named as improved cell-permeable SOCS3 (iCP-SOCS3) proteins. Previously developed CP-SOCS3 proteins fused to MTM were only tested or used as anti-inflammatory agents to treat acute liver injury. In the present art, iCP-SOCS3 proteins have been tested for use as anti-cancer agents in the treatment of hepatocellular carcinoma. Since SOCS3 is frequently deleted in and loss of SOCS3 in hepatocytes promotes resistance to apoptosis and proliferation, we reasoned that iCP-SOCS3 could be used as a protein-based intracellular replacement therapy for the treatment of hepatocellular carcinoma. The results support this reasoning: treatment of hepatocellular carcinoma cells with iCP-SOCS3 results in reduced cancer cell viability, enhanced apoptosis and loss of cell migration / invasion potential. Furthermore, iCP-SOCS3 inhibits the growth of hepatocellular carcinoma in a subcutaneous xenografts model. In the present invention with iCP-SOCS3 fused to an empirically determined combination of newly developed aMTD and customized SD, macromolecule intracellular transduction technology (MITT) enabled by the advanced MTD may provide novel protein therapy against hepatocellular carcinoma.

Pharmaceutical compositions are provided that are useful in treating or preventing neoplastic disease, such as cancer. The compositions comprise a pharmaceutically acceptable carrier, and an effective therapeutic or prophylactic amount of a nitroxide antioxidant that alters the expression of one or more genes related to the cancer. Methods are also provided for the use of the pharmaceutical compositions in the treatment or prevention of cancer. In a preferred embodiment, the nitroxide antioxidant is Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), and the cancer is esophageal cancer, hepatocellular carcinoma, colon cancer, prostate cancer, lung cancer, gastric carcinoma, renal cell carcinoma, bone cancer, breast cancer, cervical cancer, brain cancer, or a cancer associated with the tumor suppressor gene p53.

The present invention is directed to pharmaceutical compositions and methods of treatment that relate to the inhibition, resolution and / or prevention of an array of the manifestations of metabolic syndromes, including Type 2 diabetes, hyperlipidemia, weight gain, obesity, insulin resistance, hypertension, atherosclerosis, fatty liver diseases and certain chronic inflammatory states that lead to these manifestations, among others. In additional aspects, the present invention relates to compositions and methods which may be used to treat, inhibit or reduce the likelihood of hepatitis viral infections, including Hepatitis B and Hepatitis C viral infections, as well as the secondary disease states and / or conditions which are often associated with such viral infections, including hepatic steatosis (steatohepatitis), cirrhosis, fatty liver and hepatocellular cancer, among other disease states or conditions.

The invention relates to new therapeutic approaches for treating cancer, in particular hepatocellular carcinoma, with Nanoparticules loaded with a chemotherapeutic antitumoral agent. In particular, it relates to the treatment of cancer by administration of said Nanoparticules by intravenous infusion for at least 2 hours in order to prevent toxicological side effects and increase the benefit / risk ratio of the treatment.

The invention relates to the technical field of medicaments. Dimethyldiguanide belongs to a biguanides oral hypoglycemic medicament and is widely applied to pharmaceutical therapy of type 2 diabetes. The invention aims at providing a novel application of the dimethyldiguanide and particularly an application of the dimethyldiguanide in preparation of medicaments for preventing or treating the hepatocellular carcinoma. According to the application disclosed by the invention, the restriction effect of the dimethyldiguanide on the hepatocellular carcinoma is found by research from two aspects, namely, cell culture in vitro and animal experiment in vivo. Experiments find that the dimethyldiguanide has the capabilities of restricting proliferation and clone formation of a hepatocellular carcinoma cell line and causing the cell cycle arrest and apoptosis increase of the hepatocellular carcinoma cell line, and also has the capability of enhancing the hepatocellular carcinoma resisting effect of chemotherapeutics when combined with the chemotherapeutics, such as cis-platinum, doxorubicin and the like. The invention provides the novel application of the dimethyldiguanide and also provides a novel concept for prevention and treatment of the hepatocellular carcinoma.

A method for the treatment of hepatic fibrotic injuries caused by various diseases, viral infections or toxic agents which involves the use of glatiramer acetate as an immuno-modulatory agent. The diseases to be treated are hepatic fibrosis and hepatic cellular carcinomas. Also disclose is the use of glatiramer acetate in the treatment of inflammatory bowel diseases. Additionally, disclosed are methods for screening for immuno-modulatory agents which are useful in the treatment of hepatic fibrosis, hepatic cellular carcinomas and inflammatory bowel diseases.

By means of a proteomic approach, the markers of hepatocellular carcinoma (HCC) in the liver of a knockout mouse (MAT1A− / −) have been identified for the MAT1A gene (deficient in the synthesis of S-adenosylmethionine). 27 proteins have been detected the expression thereof is altered in, at least, 50% of the analysed tumours. Amongst them, 13 proteins have been validated in biopsies of patients with HCC of different etiology, and 7 of them have been validated in biopsies of patients with liver cirrhosis, a stage prior to the development of HCC, which makes it possible to differentiate between prior stages of the disease and even between different etiologies (viral and alcoholic). Having a panel of markers available may contribute to more accurately defining the alterations associated with the development of HCC and thus facilitate prognosis and diagnosis of this disease.

The present invention relates to methods of diagnosing, and methods of treating, hepatocellular carcinoma in a subject. The invention also relates to polypeptide antagonists of PLVAP proteins, including humanized and chimeric antibodies that specifically bind PLVAP proteins, as well as compositions and kits comprising such polypeptide antagonists.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. In particular, the present invention relates to several novel peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses or as targets for the development of pharmaceutically / immunologically active compounds and cells.

The present invention features a method for determining the methyltransferase activity of a polypeptide and screening for modulators of methyltransferase activity, more particularly for modulators of the methylation of retinoblastoma by SMYD3. The invention further provides a method or pharmaceutical composition for prevention or treating of colorectal cancer, hepatocellular carcinoma, bladder cancer and / or breast cancer using a modulator so identified. N-terminal truncated forms of SMYD3 (alias ZNFN3A1) have higher methylating activity. Lys 824 is a preferred methylation site on the RB1 protein for SMYD3.

The present invention provides methods and compositions for treating hepatocellular carcinoma (HCC) by administering a composition comprising nanoparticles that comprise a taxane and an albumin. The invention also provides combination therapy methods of treating HCC comprising administering to an individual an effective amount of a composition comprising nanoparticles that comprise a taxane and an albumin and another agent, such as an agent that inhibits microtubule disassembly.

The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are versatile vehicles for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. Any kind of compound, but in particular drugs, such as interferons, viral reverse transcriptase inhibitors or core assembly inhibitors, and / or labels can be specifically targeted to the liver and so be enriched in the liver. This liver targeting can further be used for the targeted diagnosis, prevention and / or treatment of liver diseases or disorders, such as hepatitis, malaria, hepatocellular carcinoma (HCC), as well as for the prevention of HAV, HBV, HCV and / or HDV infection. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified preS-derived peptide(s) and the compound(s) to be specifically delivered to the liver. The present invention furthermore relates to a method for the combined treatment of a liver disease and the prevention of HAV, HBV, HCV and / or HDV infection. The present invention relates also to the use of the preS-derived peptides in gene therapy and the delivery of immunogenic epitopes for hepatocyte-mediated antigen presentation to activate liver-directed immunological responses.