Paclitaxel: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Antineoplastic Combined Chemotherapy Protocols: The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.Carboplatin: An organoplatinum compound that possesses antineoplastic activity.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Tubulin Modulators: Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.Infusions, Intravenous: The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.Lung Neoplasms: Tumors or cancer of the LUNG.Taxoids: A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS.Breast Neoplasms: Tumors or cancer of the human BREAST.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Bridged Compounds: Cyclic hydrocarbons that contain multiple rings and share one or more atoms.Cell Line, Tumor: A cell line derived from cultured tumor cells.Carcinoma, Non-Small-Cell Lung: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.Neutropenia: A decrease in the number of NEUTROPHILS found in the blood.Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.Epothilones: A group of 16-member MACROLIDES which stabilize MICROTUBULES in a manner similar to PACLITAXEL. They were originally found in the myxobacterium Sorangium cellulosum, now renamed to Polyangium (MYXOCOCCALES).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Pharmaceutical Vehicles: A carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered. (Dictionary of Pharmacy, 1986)DeoxycytidineDrug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Maximum Tolerated Dose: The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.Epirubicin: An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.Fallopian Tube Neoplasms: Benign or malignant neoplasms of the FALLOPIAN TUBES. They are uncommon. If they develop, they may be located in the wall or within the lumen as a growth attached to the wall by a stalk.Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I.Vinblastine: Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)Combined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Drug Carriers: Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Kinetics: The rate dynamics in chemical or physical systems.Schilling Test: A diagnostic test in which vitamin B12 is tagged with radioactive cobalt, taken orally, and gastrointestinal absorption is determined via measurement of the amount of radioactivity in a 24-hour urine collection.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.Nanoparticles: Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.Peritoneal Neoplasms: Tumors or cancer of the PERITONEUM.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Time Factors: Elements of limited time intervals, contributing to particular results or situations.Ifosfamide: Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.Neoplasms, Glandular and Epithelial: Neoplasms composed of glandular tissue, an aggregation of epithelial cells that elaborate secretions, and of any type of epithelium itself. The concept does not refer to neoplasms located in the various glands or in epithelial tissue.LeukopeniaModels, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Albumins: Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Bacterial Proteins: Proteins found in any species of bacterium.Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.Hematologic Diseases: Disorders of the blood and blood forming tissues.Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.Thrombocytopenia: A subnormal level of BLOOD PLATELETS.Micelles: Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as EMULSIONS.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Platinum Compounds: Inorganic compounds which contain platinum as the central atom.Chemotherapy, Adjuvant: Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.Polyglutamic Acid: A peptide that is a homopolymer of glutamic acid.Molecular Weight: The sum of the weight of all the atoms in a molecule.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Chemistry, Pharmaceutical: Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use.Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project.Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cyclosporins: A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
". "Paclitaxel, Protein-Bound Suspension". Paclitaxel, Protein-Bound Suspension. Cancer.Org. January 6, 2015. Retrieved January ...
... evofosfamide and protein-bound paclitaxel (nab-paclitaxel) have been investigated in combination with gemcitabine in patients ... protein-bound paclitaxel (Abraxane), marketed by Celgene; and FOLFIRINOX, which is a combination of generic products that are ... The study CA046 compares gemcitabine with gemcitabine plus nab-paclitaxel. Gemcitabine is a generic product sold by many ... The indirect comparison of both studies shows comparable efficacy profiles of evofosfamide and nab-paclitaxel in combination ...
This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine ... "The human pathology proteome in pancreatic cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 28 September 2017 ... Borazanci E, Von Hoff DD; Von Hoff, DD (September 2014). "Nab-paclitaxel and gemcitabine for the treatment of people with ... in pancreas cancer.[77] By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices ...
In 2013, the U.S. Food and Drug Administration approved protein-bound paclitaxel (also known as nab-paclitaxel, sold as ... "The cost of nab-paclitaxel is not justified by its limited benefit, says NICE in draft guidance" (Press release). National ...
Another novel utilization of the EPR effect comes from Protein-bound paclitaxel (marketed under the trade name Abraxane) where ... fibroblast specific protein 1 (FSP-1) and fibroblast activation protein (FAP). None of these factors can be used to ... paclitaxel (a molecule which dysregulates cell division via stabilization of microtubules) is bound to albumin to add bulk and ... These efforts include protein capsids and liposomes. However, as some important, normal tissues, such as the liver and kidneys ...
". "Paclitaxel, Protein-Bound Suspension". Paclitaxel, Protein-Bound Suspension. Cancer.Org. January 6, 2015. Retrieved January ... Albumin-bound paclitaxel (trade name Abraxane, also called nab-paclitaxel) is an alternative formulation where paclitaxel is ... Paclitaxel binds to beta-tubulin subunits of microtubules. From 1967 to 1993, almost all paclitaxel produced was derived from ... Space-filling model of paclitaxel Rotating paclitaxel molecule model Crystal structure of paclitaxel Total charge surface of ...
... is known to bind many proteins, especially to angiomotin and endothelial cell surface ATP synthase but also ... Safety and Efficacy Study of rhAngiostatin Administered in Combination With Paclitaxel and Carboplatin to Patients With Non- ... Additionally, smaller fragments of angiostatin may bind several other proteins. There is still considerable uncertainty on its ... Angiostatin is a 38 kDa fragment of a larger protein, plasmin (itself a fragment of plasminogen) enclosing three to five ...
... , also known as nanoparticle albumin-bound paclitaxel or nab-paclitaxel, is an injectable formulation ... "Definition of "protein-bound paclitaxel"". National Cancer Institute Dictionary of Cancer Terms. "FDA approves Celgene's ... Stinchcombe, Thomas E (2007). "Nanoparticle albumin-bound paclitaxel: a novel Cremphor-EL®-free formulation of paclitaxel". ... Gradishar, William J (2006). "Albumin-bound paclitaxel: a next-generation taxane". Expert Opinion on Pharmacotherapy. 7 (8): ...
Microtubules are composed of polymers consisting of the protein tubulin. Therefore, paclitaxel binds at the site of β-tubulin ... Paclitaxel is generally prevented from reaching its target in the cell due to the presence of the efflux pump P-glycoprotein (P ... ANG1005 is a paclitaxel-Angiopep-2 conjugate. Various Angiopep vectors have been composed and differ by their anti-cancer ... This has then been shown to be a prospective cancer therapy drug that can not only be conjugated to paclitaxel but also ...
Even though numerous other spindle proteins exist that could be the target of novel chemotherapeutics, tubulin-binding agents ... Another type, Paclitaxel, acts by attaching to tubulin within existing microtubules. Next, it stabilizes the polymer. Normally ... A spindle poison, also known as a spindle toxin, is a poison that disrupts cell division by affecting the protein threads that ... Its origin stems from kinetochores, proteins that aid in joining DNA and microtubules on the chromatids. Only one unattached ...
... cells with expression of mutations in the paclitaxel binding site or expression of ABC transporter multidrug resistance protein ... Unlike other microtubule-stabilizing agents, most taccalonolides do not bind to the taxane-binding site of tubulin. The exact ... thermodynamics of binding to the Paclitaxel site predicts cytotoxicity. Chem. Biol. 12 (12) (2005), 1269-1279. Li, J., Risinger ... While taxanes like Paclitaxel and docetaxel have been used successfully against breast, ovarian, prostate, and non-small-cell ...
... binds the BH3 domain of other BAX or BCL-2 proteins in its active form. In the protein's inactive form, the groove binds its ... Strobel T, Tai YT, Korsmeyer S, Cannistra SA (November 1998). "BAD partly reverses paclitaxel resistance in human ovarian ... In addition, it can become activated by binding BCL-2, as well as non-BCL-2 proteins such as p53 and Bif-1. Conversely, BAX can ... "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. ...
Now it is clear that there is often a range of protein targets that the drug can bind. An example target for targeted therapy ... Paclitaxel prevents the cell cycle at the boundary of G2-M, whereas docetaxel exerts its effect during S-phase. Taxanes present ... They are so named because of their ability to alkylate many molecules, including proteins, RNA and DNA. This ability to bind ... Mutations in genes that produce drug target proteins, such as tubulin, can occur which prevent the drugs from binding to the ...
Classified as an orphan disease, there is currently no therapy for OPMD, caused by a mutation in the poly(A) binding protein ... The development of resistance to chemotherapies such as paclitaxel and cisplatin in non-small-cell lung cancer (NSCLC) is ... Nervana is an investigational ddRNAi construct that knocks down the expression of protein kinase C gamma (PKCγ) known to be ... McCarroll, J. A.; Gan, P. P.; Liu, M.; Kavallaris, M. (2010). "III-Tubulin is a Multifunctional Protein Involved in Drug ...
1999). "The polo-like protein kinases Fnk and Snk associate with a Ca(2+)- and integrin-binding protein and are regulated ... 2003). "Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells". Mol ... and integrin-binding protein CIB". Mol. Cancer Res. 1 (5): 376-84. PMID 12651910. Matsuda A, Suzuki Y, Honda G, et al. (2003 ... Serine/threonine-protein kinase PLK2 is an enzyme that in humans is encoded by the PLK2 gene. Serum-inducible kinase is a ...
Tubulin binding drugs have been classified on the basis of their mode of action and binding site as: a) Paclitaxel site ligands ... This protein is a product of multidrug resistance gene MDR1 and a member of family of ATP-dependent transporters (ATP-binding ... Binding site of different drugs on tubulin Taxol bound to tubulin. Vinblastine bound to tubulin. Colchicine bound to tubulin. ... The binding mechanism of the paclitaxel mimic that of the GTP nucleotide along with some important differences. GTP binds at ...
Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins". J. Biol. Chem. 272 (49): ... Strobel T, Tai YT, Korsmeyer S, Cannistra SA (1998). "BAD partly reverses paclitaxel resistance in human ovarian cancer cells ... Yang H, Masters SC, Wang H, Fu H (June 2001). "The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta". ... When BAD is phosphorylated by Akt/protein kinase B (triggered by PIP3), it forms the BAD-(14-3-3)protein heterodimer. This ...
... lipid binding domain of P120GAP mediates protein-protein interactions with Ca2+-dependent membrane-binding proteins. Evidence ... Han EK, Tahir SK, Cherian SP, Collins N, Ng SC (Jul 2000). "Modulation of paclitaxel resistance by annexin IV in human cancer ... Kojima K, Yamamoto K, Irimura T, Osawa T, Ogawa H, Matsumoto I (Mar 1996). "Characterization of carbohydrate-binding protein ... Annexin IV (ANX4) belongs to the annexin family of calcium-dependent phospholipid binding proteins. Although their functions ...
... which binds to ribonucleases in one of the tightest known protein-protein interactions.[1] Natural enzyme inhibitors can also ... For example, paclitaxel (taxol), an organic molecule found in the Pacific yew tree, binds tightly to tubulin dimers and ... An enzyme binding site that would normally bind substrate can alternatively bind a competitive inhibitor, preventing substrate ... fraction of the enzyme population bound by inhibitor [. I. ]. [. I. ]. +. K. i. {\displaystyle {\cfrac {{\ce {[I]}}}{[{{\ce {I ...
This protein localizes to the cytoplasm and nucleus and displays GTP-binding and GTPase activity. Alternative splicing results ... "Identification of a novel role of Septin 10 in paclitaxel-resistance in cancers through a functional genomics screen". Cancer ... Septin 10 is a protein that in humans is encoded by the SEPT10 gene. This gene encodes a member of the septin family of ...
These chromatin binding domains can span up to 3-4 nucleosomes. These large domains are scaffolds for further protein ... Drugs such as Paclitaxel, Imatinib, and doxorubicin which activate FoxO3a or its targets are being used. Modification to ... This is a common trait of fork head factors as they contain a winged helix DNA-binding domain that mimics the DNA-binding ... In the breast cancer cell line, MCF-7, it was found that FoxA1 was bound to 50% of estrogen receptor binding sites independent ...
... this acts as an assembly of different ECM proteins, including fibronectin, laminins, interstitial collagens, heparin-binding ... This has a higher response rate than solvent-based paclitaxel (15% vs 8%). Abraxane can also deliver a 49% higher dose of ... The ECM protein tenascin C (TNC) is up-regulated in metastatic breast cancer. TNC is an adhesion-modulating extracellular ... Some of these proteins are discussed here in relation to breast-cancer metastasis. Fibronectin is an extracellular glycoprotein ...
... protein-bound paclitaxel)(nab-paclitaxel),該藥與吉西他濱並用治療胰臟癌的療法於2013獲FDA核可[85]。截至2013年底,對於體能狀況較佳者,上述兩種療法是較佳的選擇。而對於體能狀況不
cIAP1 contains baculovirus IAP repeat domains that facilitate binding to caspases and other proteins. cIAP1 is recruited to TNF ... "LCL161 increases paclitaxel-induced apoptosis by degrading cIAP1 and cIAP2 in NSCLC". J Exp Clin Cancer Res. 35 (1): 158. doi: ... cIAP1 (also named BIRC2) is the abbreviation for a human protein, cellular inhibitor of apoptosis protein-1. It belongs to the ... The gene of cIAP1 resides on chromosome 11 and its protein has a quaternary structure. It has a unique protein chain, ...
Yoo, J.E.; Park, Y.N.; Oh, B.K. (January 2014). "PinX1, a Telomere Repeat-binding Factor 1 (TRF1)-interacting Protein, ... "The telomere/telomerase binding factor PinX1 regulates paclitaxel sensitivity depending on spindle assembly checkpoint in human ... PINX1 binds to N-terminus of hTERT and binds to hTR in the presence of hTERT. PINX1 binding to hTR "is correlated to the ... PINX1 differs from other proteins that regulate telomere length in that it acts on telomerase while other proteins adjust ...
In August 2009, during a major restructuring activity, BMS acquired the biotechnology firm Medarex as part of the company's "String of Pearls" strategy of alliances, partnerships and acquisitions.[28] In November, Bristol-Myers Squibb announced that it was "splitting off" Mead Johnson Nutrition by offering BMY shareholders the opportunity to exchange their stock for shares in Mead Johnson. According to Bristol-Myers Squibb, this move was expected to further sharpen the company's focus on biopharmaceuticals. In October 2010, the company acquired ZymoGenetics, securing an existing product as well as pipeline assets in hepatitis C, cancer and other therapeutic areas. Bristol-Myers Squibb agreed to pay around $2.5 billion in cash to buy Inhibitex Inc. in attempt to compete with Gilead/Pharmasset to produce Hepatitis C drugs. The settlement will be finished in 2 months for its Inhibitex's shareholders acceptance of 126 percent premium price of its price over the previous 20 trading days ended on ...
... in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol). This diterpenoid is an important drug in the treatment of cancer but, also expensive because the compound is harvested from a scarce resource, namely the Pacific yew (Taxus brevifolia). Not only is the synthetic reproduction of the compound itself of great commercial and scientific importance, but it also opens the way to paclitaxel derivatives not found in nature but with greater potential. The paclitaxel molecule consists of a tetracyclic core called baccatin III and an amide tail. The core rings are conveniently called (from left to right) ring A (a cyclohexene), ring B (a cyclooctane), ring C (a cyclohexane) and ring D (an oxetane). The paclitaxel drug development process took over 40 years. The anti-tumor activity of a bark extract of the Pacific yew tree was ...
... , sold under the brand name Onglyza, is an oral hypoglycemic (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Early development was solely by Bristol-Myers Squibb; in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug. In April 2016, the U.S. FDA added a warning about increased risk of heart failure. This was based on data in an article that concluded "DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes." Saxagliptin is used as monotherapy or in combination with other drugs for the treatment of type 2 diabetes. It does not appear to decrease the risk of heart attacks or strokes. It increases the risk of hospitalization for heart failure by ...
... , sold under the trade name Capoten, is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was discovered in 1977. It was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the revolutionary development process. Captopril was discovered and developed at E. R. Squibb & Sons Pharmaceuticals based on concepts pioneered by Nobel Laureate John Vane and is now marketed by Bristol-Myers Squibb. Captopril's main uses are based on its vasodilation and inhibition of some renal function activities. These benefits are most clearly seen in: 1) Hypertension 2) Cardiac conditions such as congestive heart failure and after myocardial infarction 3) Preservation of kidney function in diabetic nephropathy Additionally, it has shown mood-elevating properties in some patients. This is consistent with the observation that animal ...
... is an angiotensin converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphinate-containing ACE inhibitor marketed, by Bristol-Myers Squibb under the trade name Monopril. Fosinoprilat proved to have the same problem as enalaprilat and the other carboxylate-containing ACE inhibitors (namely poor oral bioavailability). Addition of a hydrophobic side-chain modulated the ionisation characteristics of the molecule, making it more bioavailable. Fosinopril is administered as a prodrug and is converted in vivo to the active form fosinoprilat. In congestive heart failure, the ability of the heart to pump enough blood to satisfy the physiological needs of the body is reduced. This condition has a variety of causes, including damaged heart valves, myocardial infarction, hypertension, vitamin B1 deficiency, and genetic mutations. When subsequent blood flow to the kidneys is reduced, the kidneys respond by ...
... (INN, USAN, trade name Farxiga /fɑːrˈsiːɡə/ far-SEE-gə in the U.S. and Forxiga in the EU and Russia) is a drug of the gliflozin class, used to treat type 2 diabetes. It was developed by Bristol-Myers Squibb in partnership with AstraZeneca. In July 2011 a U.S. Food and Drug Administration (FDA) endocrinologic and metabolic drugs advisory committee recommended against approval until more data were available. The FDA approved dapagliflozin on January 8, 2014 for glycemic control, along with diet and exercise, in adults with type 2 diabetes. In 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a positive opinion on the drug. It is now marketed in a number of European countries. The FDA approved the combination product dapagliflozin and metformin hydrochloride extended-release, called Xigduo XR, in November 2014. In Feb 2017 the FDA approved a once-daily combination of dapagliflozin 10 mg and saxagliptin 5 mg, as Qtern. Since ...
This multi-page article lists pharmaceutical drugs alphabetically by name. Many drugs have more than one name and, therefore, the same drug may be listed more than once. Brand names and generic names are differentiated by the use of capital initials for the former. See also the list of the top 100 bestselling branded drugs, ranked by sales. Abbreviations are used in the list as follows: INN = International Nonproprietary Name BAN = British Approved Name USAN = United States Adopted Name Two-letter codes for countries List of drugs 1-9 , A , B , C , D , E , F , G , H , I , J , K , L , M , N , O , P , Q , R , S , T , U , V , W , X , Y , Z K-Dur (Merck) K-Lease K-Pop K-Tab K+ redirects to potassium Kadian (Actavis) Kafocin Kainair kainic acid (INN) kalafungin (INN) Kaletra (Abbott Laboratories) kallidinogenase (INN) kanamycin (INN) Kantrex (Bristol-Myers Squibb) Kaon Cl Kappadione (Eli Lilly and Company) Kapidex Kariva Kayexalate (Sanofi Aventis) kebuzone (INN) Keflet Keflex (Eli Lilly and Company) ...
The epothilones are a class of potential cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials epothilones have better efficacy and milder adverse effects than taxanes. As of September 2008[update], epothilones A to F have been identified and characterised. Early studies in cancer cell lines and in human cancer patients indicate superior efficacy to the taxanes. Their mechanism of action is similar, but their chemical structure is simpler. Due to their better water solubility, cremophors (solubilizing agents used for paclitaxel which can affect cardiac function and cause severe hypersensitivity) are not needed. Endotoxin-like properties known from paclitaxel, like activation of macrophages synthesizing inflammatory cytokines and nitric oxide, are not observed for epothilone B. Epothilones were originally identified as metabolites produced by the soil-dwelling myxobacterium ...
... (CIPN) is a progressive, enduring, and often irreversible condition featuring pain, numbness, tingling and sensitivity to cold in the hands and feet (sometimes progressing to the arms and legs) that afflicts between 30% and 40% of patients undergoing chemotherapy. Chemotherapy drugs associated with CIPN include thalidomide, the epothilones such as ixabepilone, the vinca alkaloids vincristine and vinblastine, the taxanes paclitaxel and docetaxel, the proteasome inhibitors such as bortezomib, and the platinum-based drugs cisplatin, oxaliplatin and carboplatin. Whether CIPN arises, and to what degree, is determined by the choice of drug, duration of use, the total amount consumed and whether the patient already has peripheral neuropathy. Though the symptoms are mainly sensory - pain, tingling, numbness and temperature sensitivity - in some cases motor nerves are affected, and occasionally, also, the autonomic nervous system. CIPN often follows the first ...
En 1971, los quimistas Wani, Wall e Taylor isolan una molecula, lo paclitaxel o Taxòl. La rusca de Taxus brevifolia (tueis del Pacific) - que se trapa en America del Nòrd a l'escai de « mètge de las selvas » - foguèt utilizada per las seunas proprietats anticancerosas. I a dins los brots joves dels taxanes (moleculas toxicas) que contenon de substàncias anticancerosas. Sol inconvenient: es rare. 10 kg de rusca de tueis del Pacific donan sonque 1 grama de produch actiu[1]. Saven que levar la rusca d'aqueles arbres los tua. Mai tard se produguèt per emisintèsa, amb la DAB-III una molecula presenta dins las agulhas de Taxus baccata, le taxotèr, una substéncia vesina del taxòl, mas dos còps mai eficaç. Aquela molecula es al vam de la luta anticàncer, fòrça eficaç contra los càncers del sen, de l'ovari, del palmon. ...
Paul Robeson (* 1898 - † 1976), viacjazyčný herec, športovec, spevák, spisovateľ, aktivista za ľudské práva, nositeľ ocenenia Spingarn Medal a Leninovej ceny ...
Members of the combretastatin family possess varying ability to cause vascular disruption in tumors. Combretastatin binds to the β-subunit of tubulin at what is called the colchicine site, referring to the previously discovered vascular disrupting agent colchicine. Inhibition of tubulin polymerization prevents cancer cells from producing microtubules. Microtubules are essential to cytoskeleton production, intercellular movement, cell movement, and formation of the mitotic spindle used in chromosome segregation and cellular division. The anti-cancer activity from this action results from a change in shape in vasculature endothelial cells. Endothelial cells treated with combretastatin rapidly balloon in shape causing a variety of effects which result in necrosis of the tumor core. The tumor edge is supported by normal vasculature and remains, for the most part, unaffected. As a result it is likely that any therapeutic use will involve a combination of drugs or treatment options. ...
An etoposide-treated DU145 prostate cancer cell exploding into a cascade of apoptotic bodies. The sub images were extracted from a 61-hour time-lapse microscopy video, created using quantitative phase-contrast microscopy. The optical thickness is color-coded. With increasing thickness, color changes from gray to yellow, red, purple and finally black.[1] ...
Protein-bound paclitaxel, also known as nanoparticle albumin-bound paclitaxel or nab-paclitaxel, is an injectable formulation ... "Definition of "protein-bound paclitaxel"". National Cancer Institute Dictionary of Cancer Terms. "FDA approves Celgenes ... Stinchcombe, Thomas E (2007). "Nanoparticle albumin-bound paclitaxel: a novel Cremphor-EL®-free formulation of paclitaxel". ... Gradishar, William J (2006). "Albumin-bound paclitaxel: a next-generation taxane". Expert Opinion on Pharmacotherapy. 7 (8): ...
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  • Using a new proprietary CobaCyte paclitaxel nanoparticle formulation, named Cobraxane™, the company's scientists have observed significant tumor growth inhibition in preclinical tumor models. (nanowerk.com)
  • Paclitaxel is approved in the UK for ovarian, breast and lung, bladder, prostate, melanoma, esophageal, and other types of solid tumor cancers as well as Kaposi's sarcoma. (wikipedia.org)
  • In this study, we demonstrate that loss of GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2) inhibits breast tumor initiation, a finding that may lead to improved cancer treatments. (pnas.org)
  • G3BP2 regulates breast tumor initiation through the stabilization of Squamous cell carcinoma antigen recognized by T cells 3 (SART3) mRNA, which leads to increased expression of the pluripotency transcription factors Octamer-binding protein 4 (Oct-4) and Nanog Homeobox (Nanog). (pnas.org)
  • The epidermoid tumor line KB-3-1 was exposed to increasing concentrations of paclitaxel and 5 μmol/L CL-347099 for up to 1 year. (aacrjournals.org)
  • Thus, this protein family is likely to support cellular processes essential for tumor progression: survival and migration. (aacrjournals.org)
  • It is hypothesized that nab -paclitaxel utilizes receptor-mediated albumin transcytosis to internalize paclitaxel in the tumor interstitium [ 16 , 14 , 17 ]. (jcancer.org)
  • Recently, nab -paclitaxel has demonstrated activity in several SCC tumor types, such as non-small cell lung cancer (NSCLC), cervical cancer, and head and neck cancers, including cancer of the oropharynx, esophageal cancer, and nasopharyngeal cancer (NPC). (jcancer.org)
  • Here, we used a mouse model of PDA to show that the coadministration of nab -paclitaxel and gemcitabine uniquely demonstrates evidence of tumor regression. (aacrjournals.org)
  • Given that PDA is a stromal-rich tumor with abundant SPARC expression, in a series of clinical trials investigators are evaluating the combination of nab -paclitaxel and gemcitabine in patients with metastatic PDA. (aacrjournals.org)
  • A diagnosis of triple-negative breast cancer means that the three most common proteins associated with breast cancer growth - estrogen receptor, progesterone receptor and HER2/neu - are not expressed on the tumor. (globenewswire.com)
  • Paclitaxel belongs to a class of drugs known as chemotherapy drugs. (kaiserpermanente.org)
  • citation needed] A number of these side effects are associated with the excipient used, Cremophor EL, a polyoxyethylated castor oil, and allergies to cyclosporine, teniposide, and other drugs containing polyoxyethylated castor oil may indicate increased risk of adverse reactions to paclitaxel. (wikipedia.org)
  • Paclitaxel, one of the most effective chemotherapy drugs that stabilizes microtubules, has been widely used to treat various cancers [ 4 , 5 ]. (mdpi.com)
  • The report also observes that drugs used in the NSCLC treatment range from regular regimens to targeted therapies, and concurrently are based on simple chemistries to advanced complex protein. (sbwire.com)
  • The improved response rate demonstrated in the study supported the recent approval of nab-paclitaxel combined with carboplatin as first-line treatment of advanced NSCLC. (ascopost.com)
  • The predictive performance of the PBPK model was assessed by evaluating its utility in predicting pharmacokinetics of paclitaxel in rats and humans. (springer.com)
  • Because paclitaxel is metabolized by CYP2C8 and CYP3A4, the possibility of drug-drug interactions mediated by enzyme inhibition may exist between the combining agents. (aspetjournals.org)
  • Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. (globenewswire.com)
  • Because stathmin and SCLIP expression significantly correlated in NSCLC tissues, we searched for common upstream regulators and identified the far upstream sequence element-binding protein-1 (FBP-1) as a pivotal inducer of several stathmin family members. (aacrjournals.org)
  • Clinical studies suggest that nab -paclitaxel may be particularly effective in cancers with squamous histology, including NSCLC. (jcancer.org)
  • All responses were partial responses, except for one complete response in the conventional paclitaxel group. (ascopost.com)
  • There were no significant differences between the nab-paclitaxel and conventional paclitaxel groups in progression-free survival (median = 6.3 vs 5.8 months) or overall survival (median = 12.1 vs 11.2 months). (ascopost.com)
  • Second-line therapy was used in 53% of the nab-paclitaxel group and 54% of the conventional paclitaxel group. (ascopost.com)
  • For reversible inhibition, nilotinib was found to be the most potent inhibitor against both CYP2C8 and CYP3A4, and the inhibition potency could be explained by strong hydrogen binding based on molecular docking simulations and type II binding based on spectral analysis. (aspetjournals.org)
  • the large volume of distribution indicates extensive extravascular distribution and/or tissue binding of paclitaxel. (rxdrugsinfo.com)
  • locally delivered to the wall of the artery, a paclitaxel coating limits the growth of neointima (scar tissue) within stents. (wikipedia.org)
  • The model demonstrated reasonable predictions of plasma and tissue paclitaxel concentration-time profiles in rats and plasma profiles in humans. (springer.com)
  • In a population pharmacokinetic/pharmacodynamic study, nab -paclitaxel also demonstrated faster and deeper tissue penetration and slower elimination than its solvent-based counterpart in patients with advanced solid tumors [ 15 ]. (jcancer.org)