308 results about "Tumor vessel" patented technology

Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.

A conjugate is disclosed herein, wherein the conjugate includes a ligand having the ability to specifically and stably bind to an external receptor or binding site on a tumor vasculature endothelial cell, wherein the external receptor or binding site is specific for tumor vasculature endothelial cells. The conjugate also includes an anticancer agent that is selectively toxic to cancer cells operatively attached to the ligand. The anticancer agent may be L-methioninase. Pharmaceutical compositions comprising the conjugate are also disclosed, as well as methods of treating a cancer tumor or cancer cells with a therapeutically effective amount of the conjugate.

Provided are methods of generating an immune response to an antigen specifically associated with tumor vascular endothelial cells (TVECA). The method comprises administering to an individual an expression vector encoding the TVECA. The vector comprises a transcription unit encoding a secretable fusion protein, the fusion protein containing a TVECA and CD40 ligand. In other methods, administration of a fusion protein containing the TVECA and CD40 ligand is used to enhance the immune response above that obtained by vector administration alone. Further methods comprise the combination therapy using an expression vector encoding a secretable TVECA fusion protein and a tumor antigen vaccine.

The invention discloses an application of metal fullerene monocrystal nanoparticles in preparation of a tumor vascular disrupting agent. The monocrystal nanoparticles are water-soluble metal fullerene nanoparticles with the surface charged with negative electricity, and have the particle size range of 50-250 nm; the nanomaterial can absorb and convert outside world radiation energy into heat energy, and the volume is expanded sharply when a temperature reaches a phase transition point. During treatment, a tumor-carried living organism is injected and given with the metal fullerene monocrystal nanoparticles; the metal fullerene monocrystal nanoparticles reach a tumor part through blood circulation, and are stranded at tumor pores and defective parts; under the action of the outside world radiation energy, the metal fullerene monocrystal nanoparticles accumulate heat, the temperature rises, and the volume is expanded sharply when the temperature exceeds the phase transformation critical point, so that morphological structures or functions of tumor vascular endothelial cells are changed, and tumor vessels are interdicted so as to make the tumor cells starved to death.

The present invention relates to conjugates of water-soluble polymers and o-(chloracetyl-carbamoyl) fumagillol (TNP-470) and use of those conjugates as specific intracellular carriers of the TNP-470 into tumor vessels. The present invention further relates to use of those conjugates to lower the neurotoxicity of TNP-470. Preferably, the polymer has a molecular weight in the range of 100 Da to 800 kDa. More preferably, the polymer has a molecular weight no greater than 60 kDa. Most preferably, the polymer has a molecular weight in the range of 15 kDa to 40 kDa.

The invention discloses an ethoxy diphenylethane derivative and a preparation method and application thereof. The 4, position of a B aromatic ring of phenylethane is chemically modified by an ethoxyl group, and simultaneously, a hydroxyl group at the 3, position of the B aromatic ring of the phenylethane is modified into water-soluble pro-drugs such as phosphate and the like, and likewise, an amino acid side chain is introduced into an amino group at the 3, position to form an amino acid amide water-soluble pre-drug having a structure as shown by a structural formula (I). An ethoxy phenylethane derivative and a pre-drug thereof have strong capacity of inhibiting tubulin aggregation, have obvious targeted destructive functions to tumor vessels, selectively cause the tumor vessels to have dysfunctions and structural damages, induce the apoptosis of vascular endothelial cells so that tumor cells lose the support of nutrition and oxygen gas, and give play to the functions of killing and wounding the tumor cells or inhibiting the tumor metastasis.

The invention relates to an anticancer slow-release gel injection which contains slow-release microspheres containing an angiogenesis inhibitor, an amphiphilic block polymer, a solvent and a slow-release agent, wherein the composition of the amphiphilic block polymer and the non-organic solvent exhibit the property of temperature-sensitive gelation. After the in vivo injection, the injection turns into a stagnant and biodegradable water-insoluble gel and the gel slowly releases the drug contained therein for a plurality of weeks to a plurality of months. After the intratumoral or peritumoral injection, the anticancer slow-release gel injection can significantly reduce the general drug reactions and is used for treating tumors of different stages. The angiogenesis inhibitor is selected from SU5416, SU6668, bosutinib, sprycel, erlotinib, vandetanib, gefitnib, canertinib, lapatinib, lestaurtinib, masitinib, vatalanib, mubritinib, tandutinib, nilotinib, marimastat, nilotinib, pelitinib, telatinib, sunitinib, sorafenib, zarnestra, sirolimus, imatinfb, lenalidomide and thalidomide.

The invention relates to a tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system, as well as a preparation method and application thereof. The tumor vessel-tumor cell membrane-cell nucleus continuous targeted drug delivery system comprises mesoporous silica nano-particles, RGD polypeptide which is linked to the surfaces of the mesoporous silica nano-particles in a covalent manner and serves as a tumor vessel / tumor cell membrane targeting ligand, and a nuclear localization signal polypeptide sequence serving as a cell nucleus targeting ligand. Under the condition of intravenous injection, the drug-loaded system can be enriched in a tumor tissue by means of the targeting effect of the tumor vessel to reduce the uptake of normal tissues and reduce toxic and side effect, is capable of increasing the phagocytosis amount of tumor cells by means of the identification effect on the tumor cell membrane, and can be used for directly delivering anti-cancer drugs into a cell nucleus by means of the delivery performance of the cell nucleus to increase the concentration of effective drugs, so that an optimal treatment effect can be achieved.

The instant invention provides methods for treating a solid tumor in a subject comprising modulating nitric oxide production in the tumor to normalize tumor vasculature and administering an anti-tumor therapy to the subject. The invention further provides methods of treating a solid tumor in a subject comprising selectively increasing cyclic guanosine monophosphate (cGMP) or cGMP dependent protein kinase G production in the tumor vasculature to an amount effective to normalize tumor vasculature and administering an anti-tumor therapy to the subject.

A liver cancer blood vessel specific target polypeptide LCI-X7 able to specific binding with liver cancer blood vessel is extracted from the naked mouse model of human liver cancer by the showing technique of phage random peptide library in body and microscopic laser cutting technique. It provides important theory and practical basis for the diagnosis to liver cancer transfer recurrence and target therapy.

The present invention provides a system presenting site-specific accumulation through a ligand that specifically targets a receptor overexpressed on the surface of specific cells within a target organ, like, for example, tumor cells and / or vascular cells of tumor blood vessels. Moreover, this invention provides a method where, upon internalization of the previous-mentioned system by the target cells, triggered release at a high rate of the associated agent takes place, permitting efficient intracellular delivery and, thus, increased concentration of the transported cargo at the target site. Overall, this invention provides a method for the diagnosis, prevention and treatment of human diseases and disorders.

Disclosed are various compositions and methods for use in achieving specific blood coagulation. This is exemplified by the specific in vivo coagulation of tumor vasculature, causing tumor regression, through the site-specific delivery of a coagulant using a bispecific antibody.

The invention discloses an ethoxydiphenylethane derivative and a synthetic method and uses thereof 4′ position of phenylethane B aromatic ring is chemically modified by ethoxy and hydroxy at position 3′ thereof is simultaneously modified to water soluble prodrug such as phosphate, and similarly, amino acid side chain is introduced to amino at position 3′ to form amino acid amide water soluble prodrug having the structure shown as formula (I)the ethoxydiphenylethane derivative and the prodrug thereof include strong tubulin aggregation inhibiting ability and obvious target damage effect for tumor vessels, selectively cause dysfunction and structural damage of tumor vessels and induce apoptosis of vascular endothelial cells in order to play the role of killing tumor cells or inhibiting tumor metastasis in case that the tumor cells are free from the support of nutrition and oxygen.

The invention relates to a gene transfer system binding to a growth factor receptor, comprising 4-element complex gene transfer system consisting of ligand oligopeptide / polycationic polypeptide / endosome release oligopeptide / exogenous DNA or 3-element complex consisting of ligand oligopeptide / polycationic polypeptide / exogenous DNA. The invention exemplifies E5, GE7, GV1 and GV2 systems and they can be targeted for the introduction of exogenous genes into malignant tumor cells or tumor vascular endotheliocytes. They are also able to highly inhibit the growth of tumor cells in animals while p15, p16 or p21WAF-1 was used as exogenous genes. The system according to the invention is a new introduction system in tumor gene therapy.

Robust classification methods analyze magnetic resonance spectroscopy (MRS) data (spectra) of fine needle aspirates taken from breast tumors. The resultant data when compared with the histopathology and clinical criteria provide computerized classification-based diagnosis and prognosis with a very high degree of accuracy and reliability. Diagnostic correlation performed between the spectra and standard synoptic pathology findings contain detail regarding the pathology (malignant versus benign), vascular invasion by the primary cancer and lymph node involvement of the excised axillary lymph nodes. The classification strategy consisted of three stages: pre-processing of MR magnitude spectra to identify optimal spectral regions, cross-validated Linear Discriminant Analysis, and classification aggregation via Computerised Consensus Diagnosis. Malignant tissue was distinguished from benign lesions with an overall accuracy of 93%. From the same spectrum, lymph node involvement was predicted with an accuracy of 95% and tumor vascularisation with an overall accuracy of 92%.

Cytokine derivatives capable of homing the tumoral vessels and the antigen presenting cells and the use thereof as antitumoral agents.

The invention discloses a water-soluble fullerene nano-material as well as a preparation method and an application thereof. A general structural formula of the water-soluble fullerene nano-material is shown as C2n(OH)x(Amino Acid)y, wherein n is less than or equal to 60 and is greater than or equal to 20, x is less than or equal to 50 and is greater than or equal to 0, y is less than or equal to 20 and is greater than or equal to 0 and Amino Acid is water-soluble amino acid. The nano-material provided by the invention is applied to preparation of medicines for treating tumors, wherein the tumors include at least one of liver cancer, lung cancer, colorectal cancer, renal cancer, pancreatic cancer, cancer in bones, breast cancer, ovarian cancer, prostatic cancer, esophagus cancer, gastric cancer, oral cancer, nose cancer, laryngeal cancer, cancer of biliary duct, cervical cancer, uterine cancer, testicle cancer, meningeoma, skin cancer, melanoma and sarcoma. The nano-material profvided by the invention is good in water solubility, good in affinity with organisms and low in preparation cost, and the nano-material can obviously block off tumor vessels and rapidly cut off nutrition supply to tumor tissues.

The invention discloses an application of miltirone in preparation of antitumor drugs. The miltirone has a structure of formula I; the miltirone serves as an inhibitor of STAT3 (Signal Transducer and Activator of Transcription 3) and is capable of inhibiting growth and proliferation of tumor cells which are abnormally activated by STAT3 so as to cause the apoptosis of the tumor cells and also capable of improving sensibility of cytotoxic drugs and inhibiting formation of tumor vessels. The miltirone with the structure of formula I can inhibit STAT3 kinase Tyr705 phosphorylation level to achieve the functions of accelerating the apoptosis of the tumor cells, improving the sensibility of chemotherapy drugs and inhibiting formation of new vessels; and the proliferation of tumor cells can be significantly inhibited due to the combined combination of the miltirone with low toxicity or non-toxic concentration and adriacin doxorubicin with low toxicity or non-toxic concentration and the combined application of the miltirone and cis-platinum with low toxicity or non-toxic concentration. The functions of the miltirone with the structure of formula I have positive significance to prevention and treatment of tumors.

The invention discloses a magnetic resonance imaging detectable in-situ liquid crystal precursor embolism composition which comprises the following components: an MRI water-soluble or water-insoluble contrast medium, a liquid crystal material, a physiological acceptable water-soluble organic solvent and water. The following components can be added according to the treatment goal and the clinical demand: an X ray-impermeable water-soluble or water-insoluble contrast medium and / or drugs. The MRI detectable liquid embolism composition disclosed by the invention has the characteristics of low viscosity, no toxicity, low cost and fast curing, can be injected, and is mainly used in local embolism treatment and relevant imageological examination of tumors, vascular malformation and hemostasis.

The invention discloses a human single chain antibody and application of an antitumor vascular endothelium marker molecule 8-cell outer region. The amino acid sequence of the single chain antibody is SEQ ID NO:1. The amino acid sequence of a heavy chain variable region of the antibody is SEQ ID NO:2, and the amino acid sequence of a light chain variable region of the antibody is SEQ ID NO:3. The human single chain antibody of the antitumor vascular endothelium marker molecule 8-cell outer region can be applied to early diagnosis and target treatment of tumor.

The invention discloses phenylpiperazine derivatives and pharmaceutically acceptable salts thereof. The invention is characterized in that: the derivatives have the structure shown as a formula I; and in the formula, R1 refers to -H, -R, -OR, -COOR, halogen or -CN group, R refers to alkyl, the substitution position of R1 on a benzene ring is a para-position, ortho-position or meta-position of piperazine, m is a natural number ranging from 0 to 2, and R2 refers to a substituted or unsubstituted carboxyl group or sulfonic acid group. The phenylpiperazine derivatives and pharmaceutically acceptable salts thereof can be prepared into medicines for inhibiting tumor cell metastasis and tumor angiogenesis, medicines for treating liver cancer, breast cancer, ovarian cancer, gastric cancer, colon cancer, lung cancer or melanoma, tumor chemotherapy medicines and auxiliary medicines in surgical therapy.

The invention discloses a VR operation simulation system based on a human organ 3D model. The system comprises a CT data importing unit, a CT image segmentation unit, a 3D modeling unit and a VR operation simulation unit, wherein the CT data importing unit is used for importing the CT data; the CT image segmentation unit is used for segmenting soft tissue organs, tumors, blood vessels and hard tissues on the CT image and sectioning the soft tissue organs according to the blood vessels; the 3D modeling unit is used for establishing the 3D models of soft tissue organs, tumors, blood vessels and hard tissues in all sections and fusing to form the human organ 3D model; the VR operation simulation unit comprises a VR operation simulation excision module, an excision result analysis module, an operation simulation measuring module and an operation simulating risk assessment module. The invention also discloses a VR operation simulation method based on the human organ 3D model. According to the invention, the section of the organ with the tumor is directly acquired and the positioning for the tumor is more accurate, so that the operation difficulty and risk are reduced; the preoperative simulation excision and operation risk assessment can be realized; a virtual reality technology is adopted for simulating the operation; the authenticity of the analog simulation and the accuracy of the simulation result are increased.

The invention discloses a multi-parameter tumor blood vessel normalization detection system and detection method. The system comprises a light source module, an imaging module, a blood flow detectionand analysis module, a blood oxygen detection and analysis module, a blood vessel normalization judgment module and a display module. According to the method, a two-dimensional blood flow image is reconstructed through an algorithm, blood vessel morphology characteristics are extracted through an image processing method, a two-dimensional tumor blood oxygen image is calculated through a laser image and a narrow-band green light image, tumor tissue hypoxia degree information is provided, and through a deep neural network discrimination method and combination with blood flow image characteristics and blood oxygen image characteristics whether tumor vessels are normalized or not can be judged. The method has the advantages of being multi-parameter, non-invasive, non-radiative, intelligent indiagnosis and the like, whether tumor blood vessels are in a normal window period or not is intelligently judged by monitoring tumor blood supply, oxygen supply and blood vessel forms, and a basis isprovided for making a more reasonable anti-tumor combined treatment scheme.

The invention relates to a co-culture model of microencapsulated tumor cells and endothelial cells. The preparation method comprises the steps: first, tumor cells are mixed into 2 percent of sodium alginate solution to lead cells suspension which is injected with 100mmol / L of calcium chloride solution to be colloidized through a microcapsule generator then; normal saline is used for washing the obtained material which then reacts with 0.1 percent of polylysine solution and is washed by normal saline; next, 0.15 percent of sodium alginate solution is added and washed by normal saline; the 55mmol / L sodium citrate solution is employed to liquefy microcapsule core and cultured in a CO2 of culture box; the microencapsulated tumor cells are directly used for being cultured or frozen reserved; the endothelial cells are employed to be adherently cultured or led to three dimensional growth; the microencapsulated tumor cells are added into the same culture solution; co-culture is done; tumor cells and endothelial cells are separated; finally, travelling gene detection, protein detection and culture liquid cytokine detection are done. The invention overcomes the limitation of Matrigel method and the defect of Transwell method, has an imitated micro-environment for microencapsulated tumor cells and endothelial cells to interact, and has long service life for one-time making and decreases research personnel and financial resources.

The present invention provides methods of immunizing a subject against a tumor, inhibiting tumor growth, inhibiting tumor recurrence, treating, suppressing the growth of, or decreasing the incidence of a tumor, overcoming tolerance to a tumor vasculature marker (TVM) in a subject comprising the step of administering a vaccine comprising a TVM or a nucleic acid encoding a TVM and related vaccines. The present invention also provides a method of targeting a tumor vasculature in a subject having a tumor comprising the step of contacting said subject with a labeled compound that binds a) a tumor vasculature marker (TVM) or b) a nucleic acid molecule encoding said TVM.

The invention provides the expression and the purification of a recombinant fusion protein, particularly a fusion protein of the tumor blood vessel targeted polypeptide and tissue factor and a preparation method and application thereof. The preparation method of the fusion protein of the tumor blood vessel targeted polypeptide and tissue factor comprises the following steps: designing primers, carrying out PCR (polymerase chain reaction) to amplify an recombinant gene of the fusion protein EG3287-tTF, guiding the recombinant gene of the fusion protein EG3287-tTF into a carrier, guiding a recombinant carrier into a host cell, constructing a recombinant engineering bacteria for expressing the fusion protein EG3287-tTF, fermenting to culture, and separating and purifying fermentation liquor to obtain the fusion protein of the tumor blood vessel targeted polypeptide and tissue factor. The targeted antitumor fusion protein EG3287-tTF is constructed, a novel tTF derivative with the antitumor advantage of the tTF and the targeting effect is obtained, the antitumor effect of the tTF is improved, and a foundation is laid to the development of a novel medicament for the targeted therapy of the tumor blood vessel.

The invention belongs to the fields of radiopharmaceuticals and nuclear medicine and provides an imaging drug <68>Ga-NOTA-IF7 targeting Anxa1 in tumor blood vessels and a preparation method thereof. The drug <68>Ga-NOTA-IF7 is used for differential diagnosis and periodization of tumors, accurate positioning of focuses and curative effect monitoring. According to the invention, the tumor imaging drug <68>Ga-NOTA-IF7 is prepared through leaching of <68>Ga and <68>Ga-NOTA-IF7 labeling. The preparation method has the advantages of simple preparation technology, convenient operation, small consumption of time, a high labeling rate and a stable marker and facilitates further application of the drug in clinical practice, scientific research and medicinal development. The invention also provides a novel positive electron tumor imaging agent. The novel positive electron tumor imaging agent has good targeting to tumors, so tumor imaging effects are improved, and a visual tool is provided for differential diagnosis and periodization of tumors, accurate positioning of focuses and curative effect monitoring. <68>Ga-NOTA-IF7 is a labeled compound belonging to polypeptide and has the advantages of small molecular weight, low immunogenicity, good tissue penetrability, high tumor tissue affinity and good application prospects.

The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with at least one S hemoglobin allele which are capable of selectively localizing in tumor vasculature resulting in vaso-occlusion, hemolysis and heme release. A tumoricidal effect is achieved when these cells are administered in before during or after administration of (i) an agent(s) that interferes with degradation of reactive oxygen species, (ii) impairs glucose uptake and / or (iii) chemotherapy. These cells also carry oncolytic viruses, antitumor proteins, multidrug resistant proteins, chemotherapy, monoclonal antibodies, superantigens, superantigen conjugates and fusion proteins, siRNAs, plasmids and non-protein toxins and attenuated tumoricidal bacterial cells specifically into the tumors and induce a tumoricidal effect.