54 results about "Neuroendocrine tumors" patented technology

The present invention provides novel phthalazinone compounds and isomer thereof, pharmaceutically acceptable salts, solvates, chemically protected forms, and prodrugs; which can be used as PARP inhibitor and pharmaceutical compositions containing the novel phthalazinone compounds; wherein A, R1 and X are defined as shown. The medicine is used for the treatment of: vascular diseases, neurotoxicity, or diseases improved through the inhibition of PARP activity; or used as adjuvants for the treatment of cancers, or used for enhancing the therapeutic effect of radiation or chemotherapeutic agents on tumor cells, wherein the cancers includes breast cancer, ovarian cancer, colon cancer, melanoma, lung cancer, gastrointestinal stromal tumor, brain cancer, cervical cancer, pancreatic cancer, prostate cancer, gastric cancer, chronic myeloid leukocytes hypercytosis, liver canser, lymphoma, peritoneal cancer, soft tissue sarcoma, neuroendocrine tumors, advanced solid tumors, and glioblastoma.

The present invention is in the field of drug delivery, and specifically, cationic liposome-based drug delivery. In embodiments, this invention provides methods of making ligand-targeted (e.g., antibody- or antibody fragment-targeted) liposomes useful for the delivery of liposomes to tumors, including brain tumors. In embodiments, the liposomes deliver temozolomide across the blood-brain barrier for treatment of primary or metastatic brain tumors. Additional cancers that can be treated with the liposomes include neuroendocrine tumors, melanoma, prostate, head and neck, ovarian, lung, liver, kidney, breast, urogenital, gastric, colorectal, cervical, vaginal, angiosarcoma, liposarcoma, rhabdomyosarcoma, choriocarcinoma, pancreatic, retinoblastoma and other types of cancer. In another embodiment the liposomes deliver melphalan for the treatment of multiple myeloma, other tumors of the blood or other solid tumors. In still other embodiments the liposomes can deliver other drugs such as pemetrexed or irinotecan for treatment of cancer or drugs including atropine for treatment of organophosphate poisoning.

Methods and pharmaceutical compositions for treating or suppressing symptoms of neuroendocrine (NE) tumors comprising increasing the levels or activities of Notch1 protein or other components of the Notch1 signaling pathway of the cancer cells. Also disclosed are pharmaceutical compositions for the methods.

The disclosure provides methods for the use of gene expression measurements to classify or identify neuroendocrine cancer in samples obtained from a subject in a clinical setting, such as in cases of formalin fixed, paraffin embedded (FFPE) samples.

The present invention is concerned with deuterium-enriched pyrimidine compounds of formula I, their derivatives, enantiomers, diastereomers, solvates and pharmaceutical salts thereof,and their uses in the treatment, prevention and modulation of various diseases including chronic liver diseases, liver cirrhosis, liver fibrosis, hepatocellular carcinoma, liver cancer, renal cell carcinoma, kidney cancer, colorectal cancer, brain cancer, breast cancer, blood cancer, lung cancer, thyroid cancer, ovarian cancer, pancreas cancer, prostate cancer, stomach cancer, testicular cancer, uterus cancer, intestinal cancer, skin cancer, and other forms of cancer, carcinoid tumors, teratocarcinoma, tumor progression, metastasis and fibrosis in the neuroendocrine neoplasia, fibrotic processes as well as a disease state modulated directly or indirectly with 5-HT receptors, 5-HT1, 5-HT1A, 5-HT2 receptors, 5-HT2A and 5-HT2B receptors, dopamine receptors and multiple kinase pathways.

The invention relates to a medicament-tumor number 1 capable of killing cancer cells and curing various tumors and cancers and leukemia. The medicament comprises glossy ganoderma, ginseng, herba epimedii, astragalus membranaceus, giant knotweed rhizome, Chinese caterpillar fungus, heartleaf houttuynia herb and liquorice root. The medicament capable of killing cancer cells and curing various tumors and cancers and leukemia is prepared by pure traditional Chinese medicine, is good in treatment effects, less in side effects, short in treatment course and the like, is rapid in effect and high in cure rate, has effects of killing cancer cells and improving human body immunity, has functions of prolonging life and anti-aging and is capable of curing leukemia and various tumors and cancers, such as leukemia, bone cancer, lymphoma, intestinal cancer, liver cancer, renal carcinoma, gastric cancer, pelvic cancer, uterine cancer, cervical cancer, bladder cancer, prostatic cancer, pancreatic cancer, lung cancer, brain cancer, neuroendocrine tumor, mammary cancer and esophageal cancer.

Methods and pharmaceutical compostions for treating or suppressing symptoms of neuroendocrine (NE) tumors comprising inhibiting the activities of GSK-3β of the cancer cells. Also disclosed are pharmaceutical compositions for the methods. Preferably, the pharmaceutical composition comprises Li+, SB216763, SB415286, indirubins, Paullones, Hymenialdisine, Azakenpaullone, Thienyl and phenyl α-halomethyl ketones, CHR 99021, AR-A014418, Bis-7-azaindolylmaleimides, CHR 98023, CHR-98014, and ZM336372, or a pharmaceutically acceptable salt or derivative thereof.

There is provided a radiolabelled peptide-based compound for diagnostic imaging using positron emission tomography (PET). The compound may thus be used for diagnosis of malignant diseases. The compound is particularly useful for imaging of somatostatin overexpression in tumors, wherein the compound is capable of being imaged by PET when administered with a target dose in the range of 150-350 MBq, such as 150-250 MBq, preferable in the range of 191-210 MBq.

This invention relates to methods and compositions for treating carcinoid syndrome and other adverse symptoms associated with tumor-producing neuroendocrine tumors, said methods comprising administering a therapeutically effective amount of a vascular disrupting agent, or a pharmaceutically acceptable salt thereof, to a subject having a hormone producing neuroendocrine tumor. In preferred implementations, the vascular disrupting agent is combretastatin A-4 phosphate, combretastatin A-1 diphosphate, or a pharmaceutical acceptable salt thereof.

A bifunctional shRNA-based composition and methods for knocking down the expression of the PDX-1 oncogene in target cells is described herein. The invention also provides methods to deliver the shRNA-containing expression vectors to target tissues overexpressing the PDX-1 oncogene.

A bifunctional shRNA-based composition and methods for knocking down the expression of the PDX-1 oncogene in target cells is described herein. The invention also provides methods to deliver the shRNA-containing expression vectors to target tissues overexpressing the PDX-1 oncogene.

Methods and pharmaceutical compositions for treating or suppressing symptoms of neuroendocrine (NE) tumors comprising increasing the levels or activities of Notch1 protein or other components of the Notch1 signaling pathway of the cancer cells. Also disclosed are pharmaceutical compositions for the methods.

The method relates to novel application of PAK3 as a biological marker of a neuroendocrine tumor. Through protein expression level detection of PAK3 on thymic carcinoid, pheochromocytoma, parathyroid adenoma, pituitary tumor, adrenal adenoma, cell strains of islet cell tumor, cell strains of small cell lung cancer and other neuroendocrine tumor tissues and cells, the PAK3 highly expresses and covers neuroendocrine tumors common in clinics and relates to each tissue and gland of body; the novel application initially finds that the PAK3 is relevant to tumors, in particular to the neuroendocrine tumor; the novel application discloses that the PAK3 can obviously increase the transferring capacity of the cell and shows that the PAK3 plays an important role in the developing process of the neuroendocrine tumor; and the result shows that the PAK3 can be used as the biological marker of the neuroendocrine tumor.

Disclosed herein, are methods of treating a neuroendocrine tumor (NET) in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an agent that inhibits a tropomyosin receptor kinase (Trk) protein, wherein the NET is associated with a Trk protein that has undergone a genetic translocation or is an NTRK gene fusion protein. Also disclosed herein are methods of treating a neuroendocrine tumor (NET) in an individual in need thereof, comprising: (a) obtaining a sample of NET genetic material from the individual; (b) determining whether the NET tumor comprises a NTRK translocation or gene fusion; and (c) administering to the individual a therapeutically effective amount of an agent that inhibits a tropomyosin receptor kinase (Trk) protein.

Methods and compositions for treating neuroendocrine tumors are disclosed.

The invention provides a somatostatin precursor compound of octreotide, and belongs to the technical field of radioactive drugs and nuclear medicine.The precursor compound is NOTA-TATE, and the structure is shown in the following formula I (the formula is shown in the description). The invention also provides a somatostatin ligand compound of the octreotide, wherein the precursor compound NOTA-TATE is labeled by using radionuclide A to obtain A-NOTA-TATE.The invention also provides a method for preparing the somatostatin precursor compound and the somatostatin ligand compound of the octreotide.The ligand compound obtained by nuclide labeled NOTA-TATE is a colorless transparent liquid injection, has the advantages of simple preparation process, short time-consuming, high labeling rate, stable labeling, good affinity with somatostatin receptors, good targeting for tumor and good imaging effect,can be used for differential diagnosis, staging, accurate localization of focus, treatment andcurative effect monitoring of neuroendocrine tumors, and has good application prospects.

This invention relates to methods and compositions for the diagnosis of neuroendocrine lung cancers. In particular, the invention concerns the use of cDNA microarrays to facilitate the differential diagnosis of neuroendocrine tumor types.

The invention discloses a drug for neuroendocrine tumors and a process thereof, and specifically relates to the field of biopharmaceuticals, wherein the drug includes the following raw materials: cysteamine hydrochloride, Boc2O, TPE-NHS, Boc-SS-NH2, HOOC-PEG5k-NH2, BLG-NCA, NHS, octreotide, 3-aminophenylboric acid and ETO. With phenylborate bonds contained in the drug, micelles can maintain structural stability in blood circulation, thereby protecting an encapsulated drug, reducing drug leakage, and reducing systemic toxic and side effects. When the drug-loaded micelles are gathered in tumor tissues through the EPR effect, octreotide on the surface of the micelles can specifically bind to the overexpressed somatostatin acceptors of neuroendocrine tumor cells, so as to enhance the targetingability of the micelles.

The invention directed to compounds that are specific inhibitors of PKC delta, and methods and compositions for the treatment and prevent of cancers and other disorders. Compositions comprising compounds of the invention are used to treat cancers such as, for example, carcinoid and neuroendocrine tumors, malignant melanomas, pancreatic, gastrointestinal and lung cancers. Neuroendocrine tumor cell lines of pulmonary and gastrointestinal origin are surprisingly sensitive to PKC delta inhibition by the compounds of the invention. The invention is further directed to methods, compositions and kits containing compounds of the formulas (Ia), (Ib), (IIa), (IIb), (IIIa), (IIIb), (IVa), (IVb), and (V) as disclosed and described in FIGS. 11 and 12.

The present invention relates to the use for enhancing Notch signaling in an individual, of a compound showing the general formula (I) and / or a pharmaceutically acceptable salt or ester thereof, for the treatment of a disease selected from the group of dermatological disorders including atopic dermatitis, psoriasis, immune related disorders, cancer, squamous cell carcinoma, cutaneous and lung squamous cell carcinoma, head and neck cancer, non-melanoma skin cancer, basal cell carcinoma and actinic keratosis, neuroendocrine tumors, neuroendocrine small cell carcinoma and carcinoid tumors, thyroid carcinomas, muscular disorders muscular dystrophy and impaired regeneration capacity after injury; use in immunotherapy for cancer.

Disclosed herein, are methods of treating a neuroendocrine tumor (NET) in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an agent that inhibits a tropomyosin receptor kinase (Trk) protein, wherein the NET is associated with a Trk protein that has undergone a genetic translocation or is an NTRK gene fusion protein. Also disclosed herein are methods of treating a neuroendocrine tumor (NET) in an individual in need thereof, comprising: (a) obtaining a sample of NET genetic material from the individual; (b) determining whether the NET tumor comprises a NTRK translocation or gene fusion; and (c) administering to the individual a therapeutically effective amount of an agent that inhibits a tropomyosin receptor kinase (Trk) protein.

A modification of the existing INSM1 promoter region has been discovered that incorporated DNA elements that silence expression of neuronal genes in non-neuronal cells and that has increased the effectiveness and safety of using the INSM1 promoter for tumor treatment. One modification was addition of one or two tandem copies of neuronal restrictive silencer elements (NRSEs) derived either from the mouse nicotinic acetylcholine receptor (nAChR) or the rat superior cervical ganglion 10 (SCG10) promoters. These NRSEs were placed in the expression construct either directly upstream or downstream of the INSM1 promoter sequence. The most effective expression construct was the nAChR NRSE element positioned downstream of the INSM1 promoter. This expression construct increased the tissue specificity of the INSM1 promoter without a significant decrease in its activity. In addition, the modified INSM1 promoter was placed into a viral vector, adenovirus 5. Constructs with an insulator element, the chicken HS4 β-globin insulator element, with the INSM1 promoter was shown to decrease the interference of the viral genome on its expression. Constructs have been made that do not decrease the INSM1 promoter activity but significantly augment the tumor specificity of the promoter. Linking the construct to a reporter gene allowed for detection of the placement of the viral vector, and this detection can be used for diagnosing or locating neuroendocrine tumors.

Use of somatostatin or analogues thereof to enhance the effects of radiation on cellular proliferation and apoptosis, particularly use of somatostatin combined with externally applied radiation to treat neuroendocrine tumors and / or acromegaly.

There is provided a radiolabelled peptide-based compound for diagnostic imaging using positron emission tomography (PET). The compound may thus be used for diagnosis of malignant diseases. The compound is particularly useful for imaging of somatostatin overexpression in tumors, wherein the compound is capable of being imaged by PET when administered with a target dose in the range of 150-350 MBq, such as 150-250 MBq, preferable in the range of 191-210 MBq.

The invention discloses an electrochemical immunosensor for simultaneously detecting two neuroendocrine tumor markers and belongs to the technical field of electrochemical biosensing. According to thesensor, two parallel glassy carbon electrodes are used as working electrodes, and the surfaces of the electrodes are sequentially modified with a metal ion functionalized porous magnesium silicate / gold nanoparticle / polyethylene glycol / chitosan composite material and a recognition antibody. When specific binding occurs between the markers and the antibody, differentiable electric signals of the two metal ions are recorded through differential pulse voltammetry to realize simultaneous detection of CgA and CgB, and the more the markers react with the antibody, the lower the electric signals are.The electrochemical immunosensor is advantaged in that the electrochemical immunosensor is high in sensitivity and low in detection limit, the limitation of a single marker can be made up, and accuracy of neuroendocrine tumor diagnosis is improved.

The invention provides a somatostatin analogue and application thereof. The structure of the somatostatin analogue is as shown in formula I), a Phe-D-Trp-Lys-Thr motif with high affinity to a somatostatin receptor is reserved in the structure of the somatostatin analogue, the probe structure is modified through different chelating agents and different nuclides, and a broad-spectrum radiolabeled somatostatin molecular probe targeting a somatostatin receptor is designed. All subtypes of somatostatin receptors are targeted, and the probe is used as an early diagnosis probe for broad-spectrum neuroendocrine tumors. Therefore, precise medical treatment of early diagnosis, early discovery and early treatment of neuroendocrine tumors is realized.

The invention relates to a method of imaging pancreatic β-cells, endocrine gastroenteropancreatic tumors and bronchial and thyroid neuroendocrine tumors and a method of treating endocrine gastroenteropancreatic tumors and bronchial and thyroid neuroendocrine tumors by targeting of glucose-independent insulinotropic polypeptide receptors (GIP receptors). Compounds considered are GIP or a GIP analog, each carrying a radionuclide, optionally complexed through a chelator. Non-radioactive GIP receptor antagonists as such are also considered in the long-term treatment of the mentioned tumors. The invention also relates to the use of a combination of GIP or a GIP analog, each carrying a radionuclide, with a GLP-1 agonist and / or somatostatin analogs, also carrying a radionuclide.

The invention provides a hybridoma cell line for secreting a monoclonal antibody against chromogranin A and application of the hybridoma cell line and also provides an application method of secreted monoclonal antibody capable of specifically recognizing human chromogranin A for immunological diagnosis on multiple kinds of tumors. CgA protein is a soluble acidic protein with highest content in human adrenal medulla, has the molecular weight being 48kD and extensively exists in neurons as well as neuroendocrine cells and tumor cells thereof. CgA protein expression is related to neuroendocrine tumors, and is used for marking the neuroendocrine tumors, thus being used for diagnosing the neuroendocrine tumors. An antigen for preparing the antibody is a recombinant protein which is expressed by escherichia coli and has immunogenicity activity, and the finally obtained antibody belongs to an IgG2b subtype. Discovered by immunohistochemistry assay on multiple kinds of tumor tissues, the antibody can well identify tumor occurrence and can be used for immunological diagnosis of the tumors.

A method for treating a neuroendocrine tumor is disclosed, which includes administering a first dose of 111In-pentetreotide to a subject having the neuroendocrine tumor; and administering a second dose of 111In-pentetreotide to the subject after a selected duration has elapsed after the administering of the first dose, wherein the first dose and the second dose are each about 400 mCi or higher, and wherein the selected duration is at least a week. In another method, the first dose and the second dose are each about 500 mCi and the selected duration is between 10 and 12 weeks. The method may further include administration of a third dose. A composition for treating a neuroendocrine tumor includes 111In-pentetreotide having a radioactivity of about 400 mCi or higher in a single dose.