Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Fungal: The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation.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.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.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.Disease Resistance: The capacity of an organism to defend itself against pathological processes or the agents of those processes. This most often involves innate immunity whereby the organism responds to pathogens in a generic way. The term disease resistance is used most frequently when referring to plants.Drug Resistance, Multiple, Viral: The ability of viruses to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutation.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).Vascular Resistance: The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.Antitubercular Agents: Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Tuberculosis, Multidrug-Resistant: Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.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.Antimalarials: Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)HIV Protease: Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Cell Line, Tumor: A cell line derived from cultured tumor cells.Multidrug Resistance-Associated Proteins: A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.Neoplasms, Cystic, Mucinous, and Serous: Neoplasms containing cyst-like formations or producing mucin or serum.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).HIV Reverse Transcriptase: A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.Mycobacterium tuberculosis: A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.R Factors: A class of plasmids that transfer antibiotic resistance from one bacterium to another by conjugation.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Genes, MDR: Genes for MEMBRANE TRANSPORT PROTEINS that confer resistance to toxic compounds. Several superfamilies of these multidrug export proteins are known and found in both prokaryotes and eukaryotes.Tetracycline Resistance: Nonsusceptibility of bacteria to the action of TETRACYCLINE which inhibits aminoacyl-tRNA binding to the 30S ribosomal subunit during protein synthesis.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Drug Resistance, Multiple, Fungal: The ability of fungi to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutations.Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins.Streptomycin: An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Tetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.Skin Neoplasms: Tumors or cancer of the SKIN.Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Bacterial Proteins: Proteins found in any species of bacterium.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Plant Diseases: Diseases of plants.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Lung Neoplasms: Tumors or cancer of the LUNG.Parasitic Sensitivity Tests: Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Plasmodium falciparum: A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Neoplasms, Multiple Primary: Two or more abnormal growths of tissue occurring simultaneously and presumed to be of separate origin. The neoplasms may be histologically the same or different, and may be found in the same or different sites.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.Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.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.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Kidney Neoplasms: Tumors or cancers of the KIDNEY.Conjugation, Genetic: A parasexual process in BACTERIA; ALGAE; FUNGI; and ciliate EUKARYOTA for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a uni-directional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes.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.Pyrimethamine: One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.DNA, Neoplasm: DNA present in neoplastic tissue.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.Neoplasms, Second Primary: Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.beta-Lactam Resistance: Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets.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.HIV Protease Inhibitors: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series.Resistance Training: A type of strength-building exercise program that requires the body muscle to exert a force against some form of resistance, such as weight, stretch bands, water, or immovable objects. Resistance exercise is a combination of static and dynamic contractions involving shortening and lengthening of skeletal muscles.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Chloramphenicol Resistance: Nonsusceptibility of bacteria to the action of CHLORAMPHENICOL, a potent inhibitor of protein synthesis in the 50S ribosomal subunit where amino acids are added to nascent bacterial polypeptides.Breast Neoplasms: Tumors or cancer of the human BREAST.Liver Neoplasms: Tumors or cancer of the LIVER.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.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Malaria, Falciparum: Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.Thyroid Neoplasms: Tumors or cancer of the THYROID GLAND.Genes, Bacterial: The functional hereditary units of BACTERIA.Adenocarcinoma, Mucinous: An adenocarcinoma producing mucin in significant amounts. (From Dorland, 27th ed)Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Sulfadoxine: A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.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.Ampicillin Resistance: Nonsusceptibility of a microbe to the action of ampicillin, a penicillin derivative that interferes with cell wall synthesis.Myeloproliferative Disorders: Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.Tetrahydrofolate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.pol Gene Products, Human Immunodeficiency Virus: Proteins encoded by the POL GENE of the HUMAN IMMUNODEFICIENCY VIRUS.Antiviral Agents: Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.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.Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Colonic Neoplasms: Tumors or cancer of the COLON.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.Erythromycin: A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.P-Glycoproteins: A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.Azoles: Five membered rings containing a NITROGEN atom.Parotid Neoplasms: Tumors or cancer of the PAROTID GLAND.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.Anti-Retroviral Agents: Agents used to treat RETROVIRIDAE INFECTIONS.Dihydropteroate Synthase: An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. EC 2.5.1.15.Chloramphenicol: An antibiotic first isolated from cultures of Streptomyces venequelae in 1947 but now produced synthetically. It has a relatively simple structure and was the first broad-spectrum antibiotic to be discovered. It acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. (From Martindale, The Extra Pharmacopoeia, 29th ed, p106)RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cystadenoma: A benign neoplasm derived from glandular epithelium, in which cystic accumulations of retained secretions are formed. In some instances, considerable portions of the neoplasm, or even the entire mass, may be cystic. (Stedman, 25th ed)Neoplasms, Connective and Soft Tissue: Neoplasms developing from some structure of the connective and subcutaneous tissue. The concept does not refer to neoplasms located in connective or soft tissue.Neoplasms, Plasma Cell: Neoplasms associated with a proliferation of a single clone of PLASMA CELLS and characterized by the secretion of PARAPROTEINS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Appendiceal Neoplasms: Tumors or cancer of the APPENDIX.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Protozoan Proteins: Proteins found in any species of protozoan.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Candida albicans: A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis).Methicillin Resistance: Non-susceptibility of a microbe to the action of METHICILLIN, a semi-synthetic penicillin derivative.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Cystadenoma, Mucinous: A multilocular tumor with mucin secreting epithelium. They are most often found in the ovary, but are also found in the pancreas, appendix, and rarely, retroperitoneal and in the urinary bladder. They are considered to have low-grade malignant potential.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.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Carcinoma, Pancreatic Ductal: Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.Endocrine Gland Neoplasms: Tumors or cancer of the ENDOCRINE GLANDS.Gastrointestinal Neoplasms: Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Artemisinins: A group of SESQUITERPENES and their analogs that contain a peroxide group (PEROXIDES) within an oxepin ring (OXEPINS).Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.Vault Ribonucleoprotein Particles: Large cytoplasmic ribonucleoprotein particles that have an eight-fold symmetry with a central pore and petal-like structure giving the appearance of an octagonal dome. (The Dictionary of Cell Biology, Lackie and Dow, 2nd ed.)Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Tuberculosis, Pulmonary: MYCOBACTERIUM infections of the lung.Tuberculosis: Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.Bone Neoplasms: Tumors or cancer located in bone tissue or specific BONES.beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins.Extrachromosomal Inheritance: Vertical transmission of hereditary characters by DNA from cytoplasmic organelles such as MITOCHONDRIA; CHLOROPLASTS; and PLASTIDS, or from PLASMIDS or viral episomal DNA.Vancomycin Resistance: Nonsusceptibility of bacteria to the action of VANCOMYCIN, an inhibitor of cell wall synthesis.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Uterine Neoplasms: Tumors or cancer of the UTERUS.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.Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.Eye Neoplasms: Tumors or cancer of the EYE.DNA Gyrase: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.Genetic Variation: Genotypic differences observed among individuals in a population.Macrolides: A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Neoplasms, Vascular Tissue: Neoplasms composed of vascular tissue. This concept does not refer to neoplasms located in blood vessels.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Viral Load: The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a SURROGATE MARKER in disease progression.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Nose Neoplasms: Tumors or cancer of the NOSE.Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.Neoplasms, Radiation-Induced: Tumors, cancer or other neoplasms produced by exposure to ionizing or non-ionizing radiation.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Neoplastic Stem Cells: Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.Malaria: A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cephalosporin Resistance: Non-susceptibility of an organism to the action of the cephalosporins.Antiretroviral Therapy, Highly Active: Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Salivary Gland Neoplasms: Tumors or cancer of the SALIVARY GLANDS.Testicular Neoplasms: Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Carcinoma, Papillary: A malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. (Stedman, 25th ed)Adenocarcinoma, Papillary: An adenocarcinoma containing finger-like processes of vascular connective tissue covered by neoplastic epithelium, projecting into cysts or the cavity of glands or follicles. It occurs most frequently in the ovary and thyroid gland. (Stedman, 25th ed)Vincristine: An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)DNA Transposable Elements: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.Adenoma: A benign epithelial tumor with a glandular organization.Extensively Drug-Resistant Tuberculosis: Tuberculosis resistant to ISONIAZID and RIFAMPIN and at least three of the six main classes of second-line drugs (AMINOGLYCOSIDES; polypeptide agents; FLUOROQUINOLONES; THIOAMIDES; CYCLOSERINE; and PARA-AMINOSALICYLIC ACID) as defined by the CDC.Kanamycin Resistance: Nonsusceptibility of bacteria to the antibiotic KANAMYCIN, which can bind to their 70S ribosomes and cause misreading of messenger RNA.Herbicide Resistance: Diminished or failed response of PLANTS to HERBICIDES.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Neoplasms, Muscle Tissue: Neoplasms composed of muscle tissue: skeletal, cardiac, or smooth. The concept does not refer to neoplasms located in muscles.Dog Diseases: Diseases of the domestic dog (Canis familiaris). This term does not include diseases of wild dogs, WOLVES; FOXES; and other Canidae for which the heading CARNIVORA is used.PiperazinesGene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.Antiprotozoal Agents: Substances that are destructive to protozoans.HIV: Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.Sulfonamides: A group of compounds that contain the structure SO2NH2.Folic Acid Antagonists: Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)

Interleukin-6 dependent induction of the cyclin dependent kinase inhibitor p21WAF1/CIP1 is lost during progression of human malignant melanoma. (1/9539)

Human melanoma cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 (IL-6). This response is lost in cell lines derived from advanced lesions, a phenomenon which may contribute to tumor aggressiveness. We sought to determine whether resistance to growth inhibition by IL-6 can be explained by oncogenic alterations in cell cycle regulators or relevant components of intracellular signaling. Our results show that IL-6 treatment of early stage melanoma cell lines caused G1 arrest, which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex formation. Instead, IL-6 caused a marked induction of the cdk inhibitor p21WAF1/CIP1 in three different IL-6 sensitive cell lines, two of which also showed a marked accumulation of the cdk inhibitor p27Kip1. In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the resistant lines. In fact, of five IL-6 resistant cell lines, only two expressed detectable levels of p21WAF1/CIP1 mRNA and protein, while in three other lines, p21WAF1/CIP1 was undetectable. IL-6 dependent upregulation of p21WAF1/CIP1 was associated with binding of both STAT3 and STAT1 to the p21WAF1/CIP1 promoter. Surprisingly, however, IL-6 stimulated STAT binding to this promoter in both sensitive and resistant cell lines (with one exception), suggesting that gross deregulation of this event is not the unifying cause of the defect in p21WAF1/CIP1 induction in IL-6 resistant cells. In somatic cell hybrids of IL-6 sensitive and resistant cell lines, the resistant phenotype was dominant and IL-6 failed to induce p21WAF1/CIP1. Thus, our results suggest that in early stage human melanoma cells, IL-6 induced growth inhibition involves induction of p21WAF1/CIP1 which is lost in the course of tumor progression presumably as a result of a dominant oncogenic event.  (+info)

Retinoic acid, but not arsenic trioxide, degrades the PLZF/RARalpha fusion protein, without inducing terminal differentiation or apoptosis, in a RA-therapy resistant t(11;17)(q23;q21) APL patient. (2/9539)

Primary blasts of a t(11;17)(q23;q21) acute promyelocytic leukaemia (APL) patient were analysed with respect to retinoic acid (RA) and arsenic trioxide (As2O3) sensitivity as well as PLZF/RARalpha status. Although RA induced partial monocytic differentiation ex vivo, but not in vivo, As203 failed to induce apoptosis in culture, contrasting with t(15;17) APL and arguing against the clinical use of As203 in t(11;17)(q23;q21) APL. Prior to cell culture, PLZF/RARalpha was found to exactly co-localize with PML onto PML nuclear bodies. However upon cell culture, it quickly shifted towards microspeckles, its localization found in transfection experiments. Arsenic trioxide, known to induce aggregation of PML nuclear bodies, left the microspeckled PLZF/RARalpha localization completely unaffected. RA treatment led to PLZF/RARalpha degradation. However, this complete PLZF/RARalpha degradation was not accompanied by differentiation or apoptosis, which could suggest a contribution of the reciprocal RARalpha/PLZF fusion product in leukaemogenesis or the existence of irreversible changes induced by the chimera.  (+info)

Overexpression of the multidrug resistance-associated protein (MRP1) in human heavy metal-selected tumor cells. (3/9539)

Cellular and molecular mechanisms involved in the resistance to cytotoxic heavy metals remain largely to be characterized in mammalian cells. To this end, we have analyzed a metal-resistant variant of the human lung cancer GLC4 cell line that we have selected by a step-wise procedure in potassium antimony tartrate. Antimony-selected cells, termed GLC4/Sb30 cells, poorly accumulated antimony through an enhanced cellular efflux of metal, thus suggesting up-regulation of a membrane export system in these cells. Indeed, GLC4/Sb30 cells were found to display a functional overexpression of the multidrug resistance-associated protein MRP1, a drug export pump, as demonstrated by Western blotting, reverse transcriptase-polymerase chain reaction and calcein accumulation assays. Moreover, MK571, a potent inhibitor of MRP1 activity, was found to markedly down-modulate resistance of GLC4/Sb30 cells to antimony and to decrease cellular export of the metal. Taken together, our data support the conclusion that overexpression of functional MRP1 likely represents one major mechanism by which human cells can escape the cytotoxic effects of heavy metals.  (+info)

Differential regulation of specific genes in MCF-7 and the ICI 182780-resistant cell line MCF-7/182R-6. (4/9539)

To elucidate the mechanisms involved in anti-oestrogen resistance, two human breast cancer cell lines MCF-7 and the ICI 182780-resistant cell line, MCF-7/182R-6, have been compared with regard to oestrogen receptor (ER) expression, ER function, ER regulation, growth requirements and differentially expressed gene products. MCF-7/182R-6 cells express a reduced level of ER protein. The ER protein is functional with respect to binding of oestradiol and the anti-oestrogens tamoxifen, 4-hydroxy-tamoxifen and ICI 182780, whereas expression and oestrogen induction of the progesterone receptor is lost in MCF-7/182R-6 cells. The ER protein and the ER mRNA are regulated similarly in the two cell lines when subjected to treatment with oestradiol or ICI 182780. Oestradiol down-regulates ER mRNA and ER protein expression. ICI 182780 has no initial effect on ER mRNA expression whereas the ER protein level decreases rapidly in cells treated with ICI 182780, indicating a severely decreased stability of the ER protein when bound to ICI 182780. In vitro growth experiments revealed that the ICI 182780-resistant cell line had evolved to an oestradiol-independent phenotype, able to grow with close to maximal growth rate both in the absence of oestradiol and in the presence of ICI 182780. Comparison of gene expression between the two cell lines revealed relatively few differences, indicating that a limited number of changes is involved in the development of anti-oestrogen resistance. Identification of the differentially expressed gene products are currently in progress.  (+info)

p53 status of newly established acute myeloid leukaemia cell lines. (5/9539)

We analysed the status of the p53 gene and protein in eight newly established acute myeloid leukaemia (AML) cell lines representing blast cells of either de novo leukaemia patients in first remission or patients with relapsed and chemotherapy-resistant disease causing their death. There were no mutations in the p53 gene in any of the cell lines as analysed by single-strand conformation polymorphism of amplified exons 5-8. However, the p53 protein was clearly and consistently expressed in all of these cell lines, as shown by immunohistochemistry, Western blotting and flow cytometry. The consistently expressed p53 protein was located in both the nucleus and the cytoplasm of all the cell lines and, as shown by flow cytometry, it was mostly in a conformation typical of the mutated protein. These AML cell lines offer a tool for studying the production and function of the p53 protein and its possible role in cell cycle regulation and chemoresistance as well as in the regulation of apoptosis in AML.  (+info)

Profound variation in dihydropyrimidine dehydrogenase activity in human blood cells: major implications for the detection of partly deficient patients. (6/9539)

Dihydropyrimidine dehydrogenase (DPD) is responsible for the breakdown of the widely used antineoplastic agent 5-fluorouracil (5FU), thereby limiting the efficacy of the therapy. To identify patients suffering from a complete or partial DPD deficiency, the activity of DPD is usually determined in peripheral blood mononuclear cells (PBM cells). In this study, we demonstrated that the highest activity of DPD was found in monocytes followed by that of lymphocytes, granulocytes and platelets, whereas no significant activity of DPD could be detected in erythrocytes. The activity of DPD in PBM cells proved to be intermediate compared with the DPD activity observed in monocytes and lymphocytes. The mean percentage of monocytes in the PBM cells obtained from cancer patients proved to be significantly higher than that observed in PBM cells obtained from healthy volunteers. Moreover, a profound positive correlation was observed between the DPD activity of PBM cells and the percentage of monocytes, thus introducing a large inter- and intrapatient variability in the activity of DPD and hindering the detection of patients with a partial DPD deficiency.  (+info)

SDZ PSC 833, the cyclosporine A analogue and multidrug resistance modulator, activates ceramide synthesis and increases vinblastine sensitivity in drug-sensitive and drug-resistant cancer cells. (7/9539)

Resistance to chemotherapy is the major cause of cancer treatment failure. Insight into the mechanism of action of agents that modulate multidrug resistance (MDR) is instrumental for the design of more effective treatment modalities. Here we show, using KB-V-1 MDR human epidermoid carcinoma cells and [3H]palmitic acid as metabolic tracer, that the MDR modulator SDZ PSC 833 (PSC 833) activates ceramide synthesis. In a short time course experiment, ceramide was generated as early as 15 min (40% increase) after the addition of PSC 833 (5.0 microM), and by 3 h, [3H]ceramide was >3-fold that of control cells. A 24-h dose-response experiment showed that at 1.0 and 10 microM PSC 833, ceramide levels were 2.5- and 13.6-fold higher, respectively, than in untreated cells. Concomitant with the increase in cellular ceramide was a progressive decrease in cell survival, suggesting that ceramide elicited a cytotoxic response. Analysis of DNA in cells treated with PSC 833 showed oligonucleosomal DNA fragmentation, characteristic of apoptosis. The inclusion of fumonisin B1, a ceramide synthase inhibitor, blocked PSC 833-induced ceramide generation. Assessment of ceramide mass by TLC lipid charring confirmed that PSC 833 markedly enhanced ceramide synthesis, not only in KB-V-1 cells but also in wild-type KB-3-1 cells. The capacity of PSC 833 to reverse drug resistance was demonstrated with vinblastine. Whereas each agent at a concentration of 1.0 microM reduced cell survival by approximately 20%, when PSC 833 and vinblastine were coadministered, cell viability fell to zero. In parallel experiments measuring ceramide metabolism, it was shown that the PSC 833/vinblastine combination synergistically increased cellular ceramide levels. Vinblastine toxicity, also intensified by PSC 833 in wild-type KB-3-1 cells, was as well accompanied by enhanced ceramide formation. These data demonstrate that PSC 833 has mechanisms of action in addition to P-glycoprotein chemotherapy efflux pumping.  (+info)

Modulation of the cytotoxicity of 3'-azido-3'-deoxythymidine and methotrexate after transduction of folate receptor cDNA into human cervical carcinoma: identification of a correlation between folate receptor expression and thymidine kinase activity. (8/9539)

Cervical carcinoma is an AIDS-defining illness. The expression of folate receptors (FRs) in cervical carcinoma (HeLa-IU1) cells was modulated by stable transduction of FR cDNA encapsidated in recombinant adeno-associated virus-2 in the sense and antisense orientation (sense and antisense cells, respectively). Although sense cells proliferated slower than antisense or untransduced cells in vivo and in vitro in 2% (but not 10%) FCS, [methyl-3H]thymidine incorporation into DNA was significantly increased in sense cells in 10% serum; therefore, the basis for this discrepancy was investigated. The activity of thymidine kinase (TK) was subsequently directly correlated with the extent of FR expression in single cell-derived clones of transduced cells. This elevated TK activity was not a result of recruitment of the salvage pathway based on the presence of adequate dTTP pools, normal thymidylate synthase (TS) activity, persistence of increased thymidine incorporation despite the exogenous provision of excess 5,10-methylene-tetrahydrofolate, and documentation of adequate folates in sense cells. The increase in TK activity conferred significant biological properties to sense cells (but not antisense or untransduced cells) as demonstrated by augmented phosphorylation of 3'-azido-3'-deoxythymidine (AZT) and concomitantly greater sensitivity to the cytotoxic effects of AZT. Conversely, sense cells were highly resistant to methotrexate, but this was reversed by the addition of AZT. The direct correlation of FR expression and TK activity indicates a previously unrecognized consequence of FR overexpression.  (+info)

Role of the Drug Transporter ABCC3 in Breast Cancer Chemoresistance. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
How to deal with cancer drug resistance - posted in Research Idea, Design and Collaboration: Anybody has a good idea on how to solve cancer drug resistance issues. Many new drugs are designed to block one or more signal transduction pathways in order to block cancer cell proliferation. But cancer cell can bypass the blocked pathway and survives later in the treatment cycles. Combination or coktail of multiple drugs can have serious side-effects. What other general ideas can provide better...
Free Online Library: Research and Markets: This Essential Report on Cancer Drug Resistance is Available Now. by Business Wire; Business, international Antimitotic agents Market research Reports Antineoplastic agents Care and treatment Drug therapy Cancer research Cancer treatment Drug resistance in microorganisms Microbial drug resistance Oncology, Experimental Pharmaceutical industry
Drug resistance remains a great challenge in the treatment of gastric cancer. The goal of this study was to explore the anti-tumor effects and mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP) in human oxaliplatin-resistant gastric cancer cells. After producing oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling time were observed, followed by detection of cell cycle distribution and apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT assay, in vivo pharmacodynamics and pathomorphology experiments were used to detect killing activities of CIK combined with L-OHP. Compared with parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S phase were reduced and cell apoptosis rate was increased (P < 0.05), the inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer cells was significantly lower and the expression of P-gp was significantly higher (P < 0.05). However, there was
The dose-limiting toxicity of chemotherapeutics, heterogeneity and drug resistance of cancer cells, and difficulties of targeted delivery to tumors all pose daunting challenges to effective cancer therapy. We report that small interfering RNA (siRNA) duplexes readily penetrate intact bacterially derived minicells previously shown to cause tumor stabilization and regression when packaged with chemotherapeutics. When targeted via antibodies to tumor-cell-surface receptors, minicells can specifically and sequentially deliver to tumor xenografts first siRNAs or short hairpin RNA (shRNA)-encoding plasmids to compromise drug resistance by knocking down a multidrug resistance protein. Subsequent administration of targeted minicells containing cytotoxic drugs eliminate formerly drug-resistant tumors. The two waves of treatment, involving minicells loaded with both types of payload, enable complete survival without toxicity in mice with tumor xenografts, while involving several thousandfold less drug, ...
Drug resistance is a major obstacle in curing ovarian cancer but new research from the Centenary Institute has discovered a treatment that kills ovarian cancer cells in a new way that
The molecular mechanism by which cancer-associated fibroblasts (CAFs) confer chemoresistance in ovarian cancer is poorly understood. The purpose of the present study was to evaluate the roles of CAFs in modulating tumor vasculature, chemoresistance, and disease progression. Here, we found that CAFs upregulated the lipoma-preferred partner (LPP) gene in microvascular endothelial cells (MECs) and that LPP expression levels in intratumoral MECs correlated with survival and chemoresistance in patients with ovarian cancer. Mechanistically, LPP increased focal adhesion and stress fiber formation to promote endothelial cell motility and permeability. siRNA-mediated LPP silencing in ovarian tumor-bearing mice improved paclitaxel delivery to cancer cells by decreasing intratumoral microvessel leakiness. Further studies showed that CAFs regulate endothelial LPP via a calcium-dependent signaling pathway involving microfibrillar-associated protein 5 (MFAP5), focal adhesion kinase (FAK), ERK, and LPP. Thus, ...
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Read up on the latest developments in several important areas of cancer research emerging from the 2019 American Association for Cancer Research annual meeting.
Drug resistance may emerge de novo when beneficial peptides are expressed by bacteria using completely random, noncoding DNA sequences
Hello: We have a drug resistant cell (murine) line that routinely is grown in presence of the drug. When these cell were grown in absence of the drug the phenotype changed to sensible after 90 passages (we compare levels of accumulation of drug in WT and resistant cell, the resistant accumulate less). Can we conclude that there may be single mutation event involved in the generation of resistance and that after 90 passages in absence of selection pressure reverted? Or is it just matter of regulation of expression of genes under that stress? And that in absence of drug everything goes back to normal levels? Is 90 passages too long to restore normal levels of expressions and actually it is a mutation? How to calculate the mutation frequency and number of passages necessary for the expression of a mutation? Thanks for your help! Nancy ...
Bacteria in tumors make cancer resistant to chemotherapy. Wait, what? That’s right. According to Ravid Straussman at the Weizmann Institute, Gammapro
{loadposition article-preamble} Hi Everyone, Lauren Miller had spectacular success using EFT for her stage 3 cancer. She shares her story (and EFT methods) in this article. Please note that while only one successful EFT session launched this remarkab...
The findings presented here support a model linking Pgrmc1 to cancer progression. Pgrmc1 is overexpressed in breast tumors (Crudden et al., 2005), is induced by chemotherapy (Mallory et al., 2005b), and promotes chemotherapy resistance in breast cancer cells (Crudden et al., 2006). In separate papers, Peluso et al. subsequently showed that Pgrmc1 is overexpressed in ovarian cancer, where it contributes to chemotherapy resistance (Peluso et al., 2008a) and suppresses apoptosis (Peluso et al., 2008b). However, many tumors express Pgrmc1 before chemotherapy, suggesting a function for Pgrmc1 other than drug resistance. Indeed, Pgrmc1 is induced by carcinogens in vivo, suggesting a role in the early stages of tumorigenesis (Selmin et al., 1996). In the present study, we present evidence that Pgrmc1 promotes tumor growth in vivo. We inhibited Pgrmc1 expression by using a sequence-specific shRNA that had been previously characterized in human kidney cells (Hughes et al., 2007) and used two separate in ...
Researchers now able to use a 3D computer model to helps screen millions of chemo drugs, giving researchers a view of the structure of a protein believed played a crucial role in chemotherapy failure.
In cancer chemotherapy, multidrug resistance (MDR) is a major clinical problem which occurs by an influential mechanism and which leads to the failure of cancer chemotherapy and/or a relapse of the cancer. In this study ...
A protein that enables cancer cells to grow, invade tissues and eventually resist chemotherapy and has lethal consequences for patients was found by researchers.
Active drug efflux by the adenosine triphosphate-binding cassette (ABC) transporter ABCG2 is one of the common mechanisms causing multiple drug resistance in various human cancers. In the intrinsic drug resistance of hepatocellular carcinoma (HCC), the role of ABCG2 is closely associated with side population (SP), a minor subset of cancer stem-like cells with unique capacity to extrude lipophilic dye Hoechst 33342 and many chemotherapeutic agents. In this study, we showed that ABCG2 was intrinsically expressed in a subgroup of HCC tissues and its expression pattern significantly influenced the levels of drug efflux from HCC cell lines. In MHCC-97L HCC cell line with intrinsic ABCG2 expression, we confirmed the importance of SP cells to the drug efflux-related chemotherapy resistance and found that the SP analysis provided an efficient method to evaluate the functional activity of ABCG2 transporter. In this cell line, we discovered that the SP proportion was modulated by the treatments of Akt ...
Therapy resistance can arise within tumor cells because of genetic or phenotypic changes (intrinsic resistance), or it can be the result of an interaction with the tumor microenvironment (extrinsic resistance). Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and mediate cell-to-cell communication by transferring mRNAs, miRNAs, DNAs and proteins causing extrinsic therapy resistance. They transfer therapy resistance by anti-apoptotic signalling, increased DNA-repair or delivering ABC transporters to drug sensitive cells. As functional mediators of tumor-stroma interaction and of epithelial to mesenchymal transition, exosomes also promote environment-mediated therapy resistance. Exosomes may be used in anticancer therapy exploiting their delivery function. They may effectively transfer anticancer drugs or RNAs in the context of gene therapy reducing immune stimulatory effects of these drugs and hydrophilic qualities facilitating crossing of cell
The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In general, for these patients anti-hormonal therapy is the therapy of first choice. Despite good responses in 50-60% of the patients, unfortunately all patients develop (acquired) resistance. Patients with acquired anti-hormonal resistance can be subdivided into three different groups: (1) patients that have lost ER-expression (~25%), (2) patients with preserved ER-expression (~55%) and (3) patients with enhanced ER-expression (~30%). Several studies suggest different treatment strategies for these three different ER-phenotypes in antihormonal resistant breast cancer. In patients with acquired anti-hormonal resistance, ~30% of the patients still respond to hormone-additive therapy with estrogens. In vitro studies have shown estrogen-induced apoptosis in long-treated estrogen deprived cells (simulating aromatase inhibitor resistance). It is suggested that this estrogen-hypersensitivity is accompanied by ...
For decades, natural products represent a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR). Multidrug resistant cells overexpressing BCRP, ABCB5 and mutated ∆EGFR were not cross-resistant towards sanguinarine. Interestingly, P-gp overexpressing cells were hypersensitive to sanguinarine. Doxorubicin uptake assay carried by flow
Defining the molecular transcriptomic profile for predicting the clinical outcome of anthracycline resistant breast cancers. Defining metastases in relation with the primary tumor. BREAST-OMICS
Two recent in vitro studies conducted in the U.S. and Europe raise a provocative question: Can FDA-approved human immunodeficiency virus (HIV) drugs be used to treat chemoresistant ovarian cancer? Both studies were based upon the fact that HIV patients taking antiretroviral inhibitors have a lower incidence of infection-associated malignancies. Based upon that fact, the researchers…
Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of only 9%. Acquired drug resistance is a major factor that limits the effectiveness of chemotherapy. Exosomes, secreted
Italian and German scientists have designed peptides to target the protein-protein interface of a key enzyme in DNA synthesis crucial for cancer growth. The peptides act by a novel inhibitory mechanism and curb cancer cell growth in drug resistant ovarian cancer cells. The interdisciplinary research project was led by the University of Modena and Reggio Emilia (UNIMORE) and the Heidelberg Institute for Theoretical Studies (HITS).
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This cisplatin-resistant cell line has been developed by chronic exposure of the parent cisplatin-sensitive A2780 cell line (ECACC No. 93112519) to increasing concentrations of cisplatin. A2780cis is cross-resistant to melphalan, adriamycin and irradiation. An increased ability to repair DNA damage as well as cytogenetic abnormalities has been observed. In order to retain resistance cisplatinum has to be added to the media every 2-3 passages. In addition to this matched pair of drug-sensitive/resistant cell lines an adriamycin-resistant cell line, A2780adr (ECACC No. 93112520), has been isolated from the same parental line A2780 ...
Osimertinib binds tightly to a protein, epidermal growth factor receptor (EGFR), which is overexpressed in many tumours.. EGFR is involved in a pathway that signals for cell proliferation, and so is a target for drugs. Blocking the action of EGFR (inhibiting it) can switch it off, and so is a good way to treat the disease.. Osimertinib is an effective anticancer drug that works in this way. It is used to treat non-small-cell lung cancer (NSCLC), in cases where the cancer cells have a particular (T790M) mutant form of EGFR.. It is a so-called third-generation EGFR inhibitor, which was approved as a cancer treatment in 2017. Osimertinib is a covalent inhibitor: as such, it binds irreversibly to EGFR by forming a chemical bond with it.. Although patients generally respond well to osimertinib, most acquire drug resistance within one year of treatment, so the drug stops working.. Drug resistance arises because the EGFR protein mutates, so that the drug binds less tightly.. One such mutation, called ...
Chemoresistant tumor cells pose a threat to the efficacy of treatment and severely worsen the prognosis for the treated animal due to relapse. Understanding the mechanism of resistance is the first step leading to circumvention of the resistance and development of more efficient therapies. The chemotherapeutic doxorubicin was used to ... read more treat canine MelT4 melanoma, and POS and HMPOS osteosarcoma cells. The survival of cells was determined by cell count as well as MTT essay, and the mRNA of surviving cells isolated. PCR and electrophoresis were used to visualize the presence of mRNA coding for drug efflux pumps MDR, ABCB5 and ABCG2 as well as transcription factors NANOG, Oct-4 and SOX-2. The presence of cell surface marker CD-133 was also determined. Western Blots were performed for ABCB5 and ABCG2 to determine eventual translation of the results on an mRNA level to a protein level. A non-treated cell population equal to the surviving population was used as reference in all ...
Model of tumor cell resistance to antineoplastic therapy through angiopoietin-like protein 2 (ANGPTL2) expression. Tumor cell-secreted ANGPTL2 induces spleen ty
The Ras/MEK/ERK and PI3K/Akt/mTor pathways play a central role in the regulation of normal cell growth, division and differentiation. Dysregulation of these signaling pathways driven by oncogenic mutations/activation leading to elevated kinase activity has been demonstrated in many human cancers. Strong evidence suggests the existence of a feedback loop with crosstalk between these two signaling cascades leading to redundancy in survival pathways. Consequently, monotherapy targeting a single cascade may be insufficient to induce tumor cell death due to drug resistance mechanisms. Initial biological results are presented from a series of novel small molecule kinase inhibitors specifically designed to simultaneously target both MEK1 and PI3K. Structural analogs of the ATP-competitive PI3K inhibitor ZSTK474 and the ATP-noncompetitive class of MEK inhibitors PD0325901, respectively, were covalently combined to provide single compound dual inhibitors. Inhibitors showed potent MEK1 inhibition (0.015 , ...
Health, ...German researchers have identified an unexpected molecular marker that...Triple-negative breast cancers --which do not express the genes for es...At the IMPAKT Breast Cancer Conference in Brussels PhD student Caroli...The researchers undertook their study in three steps. First they condu...,Gene,expression,predicts,chemotherapy,sensitivity,,of,triple-negative,breast,cancer,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Background: Among several chemotherapeutic agents, 5-Fluorouracil (5-FU) has been widely used as a key drug in adjuvant chemotherapy for gastric cancer. However, no reliable marker, which predicts the response to 5-FU in an adjuvant setting, has been identified. Hypoxia-induced drug resistance, via up-regulation of hypoxia-inducible factor (HIF) -1α, is a major obstacle in the development of effective cancer therapy. Despite the numerous investigations, few clinical studies have so far assessed the relationship between the HIF-1α expression and the chemo-resistance of gastric cancer patients in an adjuvant setting.. Objective: To determine whether the expression of HIF-1α predicts the relapse of gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy.. Materials and Methods: Two HIF-1α knockdown gastric cancer cell lines were established in order to clarify the role of HIF-1α in chemo-resistance against 5-FU. The sensitivity to 5-FU was evaluated by MTT ...
The development of targeted therapies has provided new options for the personalized management of patients with advanced solid tumors. mAbs directed against the EGFR, such as cetuximab and panitumumab, have emerged as important therapeutic agents in the treatment of metastatic colorectal cancer patients. However, their use is substantially limited by intrinsic and acquired cancer cell resistance. Several hypotheses have been developed to explain why resistant cancer cell arises and how it is possible to overcome it. One possibility is cancer intrinsic genetic heterogeneity, which could be more prominent in the metastatic setting (28, 29). Heterogeneous genetic alterations in genes involved in the EGFR pathways have been hypothesized to play a role in resistance to anti-EGFR drugs in colorectal cancer, including activating mutations in KRAS, NRAS, B-RAF, and PIK3CA, and loss of expression of PTEN (13). The overall scenario is complicated by presence of additional genetic mechanisms able to ...
TY - JOUR. T1 - Molecular determinants of chemotherapy resistance in ovarian cancer. AU - Cooley, Megan. AU - Fang, Pingping. AU - Fang, Fang. AU - Nephew, Kenneth. AU - Chien, Jeremy. PY - 2015/11/1. Y1 - 2015/11/1. KW - cancer genomics. KW - chemotherapy. KW - functional genomics. KW - heterogeneity. KW - intra-tumor. KW - ovarian cancer. KW - resistance. UR - http://www.scopus.com/inward/record.url?scp=84947967812&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84947967812&partnerID=8YFLogxK. U2 - 10.2217/pgs.15.130. DO - 10.2217/pgs.15.130. M3 - Article. C2 - 26554863. AN - SCOPUS:84947967812. VL - 16. SP - 1763. EP - 1767. JO - Pharmacogenomics. JF - Pharmacogenomics. SN - 1462-2416. IS - 16. ER - ...
New research using mathematical models of different types of cancer-including melanoma, pancreatic, and colorectal-to determine the evolutionary dynamics of lesions in response to treatment is revealing why and how cancer cells resist targeted therapies. The study by Ivana Bozic, PhD, from the Department of Mathematics at Harvard University, and colleagues was published online in eLife.. Study Details. The investigators, a team of mathematicians and oncologists from a variety of academic centers, designed a mathematical model to predict the effects of combination targeted therapies on tumors based on data obtained from 20 melanoma patients receiving vemurafenib (Zelboraf). They then applied their model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. Their findings showed that when dual therapy is used, most patients experience longer-term disease control as long as there were no single cell mutations that caused cross-resistance to both ...
Background] Most NSCLC patients harboring activating EGFR mutations benefit from treatment with EGFR-TKIs, but the final clinical efficacy of EGFR-TKIs varies because of development of tumor resistant to EGFR-TKIs. Multiple kinase-targeted 2nd generation TKIs such as afatinib have been developed to overcome drug resistance to the 1st generation TKIs. Afatinib is an irreversible multitargeted TKI targeting EGFR including T790M, HER2 and HER4. To develop further personalized therapeutics and drug resistance modifiers, we should understand the molecular based mechanism of drug resistance to 2nd as well as 3rd generation TKIs. In our present study, we present a novel finding that acquisition of cancer stem-like cells properties accompanying with activation of residual Src family kinase (SFK)/focal adhesion kinase (FAK) is responsible for the survival of afatinib-resistant lung cancer cells when expression of targeted EGFR, HER2 and HER4 is abraded.. [Materials and methods] We have established ...
They will use the funds to develop software tools for designing and testing site-specific CRISPR systems that target drug resistance mechanisms in cancer cells.
Affiliation (Current):東北大学,農学研究科,教授, Research Field:Applied microbiology,Biological Sciences,Science and Engineering,Applied molecular and cellular biology,応用微生物学・応用生物化学, Keywords:糸状菌,転写因子,トランスポーター,シグナル伝達,麹菌,菌類,発現制御,アミラーゼ生産,ヒスチジンキナーゼ,転写制御因子, # of Research Projects:19, # of Research Products:127, Ongoing Project:Elucidation of drug resistance mechanisms in filamentous fungi by functional analyses of transcription factors
PerProGlio Project aims to identify individual parameters that determine recurrence and therapy resistance in Glioblastoma (GBM) with possible therapeutic implications.
The drug resistant cell line MOR/0.2R has been derived from the parent line, MOR, by continuous exposure to increasing concentrations of doxorubicin (also known as adriamycin). MOR/0.2R accumulate lower levels of doxorubicin than the parent line and have been shown to overexpress multi drug resistance associated protein (MRP). Expression of a 190kDa membrane protein associated with the degree of drug-resistance has been indicated. Cells grow as easily detaching aggregates ...
The expanding spectrum of both established and candidate oncogenic driver mutations identified in non-small-cell lung cancer (NSCLC), coupled with the increasing number of clinically available signal transduction pathway inhibitors targeting these driver mutations, offers a tremendous opportunity to enhance patient outcomes. Despite these molecular advances, advanced-stage NSCLC remains largely incurable due to therapeutic resistance. In this Review, we discuss alterations in the targeted oncogene (on-target resistance) and in other downstream and parallel pathways (off-target resistance) leading to resistance to targeted therapies in NSCLC, and we provide an overview of the current understanding of the bidirectional interactions with the tumour microenvironment that promote therapeutic resistance. We highlight common mechanistic themes underpinning resistance to targeted therapies that are shared by NSCLC subtypes, including those with oncogenic alterations in epidermal growth factor ...
Our observations identify NM23-H1 as the archetype of a metastasis suppressor gene acting as repressor of the early stages of the invasive program in primary tumors. We propose that NM23-H1 functions as a barrier against the conversion of in situ carcinoma into invasive carcinoma. Our data support the notion that NM23-H1 silencing induces an invasive phenotype linked to partial EMT associated with the β-catenin nuclear translocation and upregulation of TCF/LEF-1-mediated transcription, a molecular signature of the Wnt pathway (32). EMT is a major switch to exacerbate the metastatic behavior by generating migratory and invasive signals, as well as anticancer drug resistance phenotypes (33). We found that NM23-H1 is reduced at the invasive front of human primary tumors concomitantly with reduced membrane-bound E-cadherin, further supporting the biological significance of our experimental data. Collectively, our data identify NM23-H1 as a critical regulator of E-cadherin-mediated intercellular ...
During the third situation, we were unable to make a definitive determination. Other cases with acquired mutations of uncertain significance integrated two cancers with ,-catenin mutations, the two of which occurred concomitantly with the EGFR T790M mutation. Fifteen posttreatment biopsies did not reveal any new mutations as assessed from the SNaPshot assay, nor MET or EGFR amplification. Two sufferers on this group had inadequate posttreatment tissue for EGFR and MET gene copy amount analyses. Between the 15 individuals without having an recognized genetic resistance mechanism, only 2 patients had stopped EGFR TKI treatment for more than two weeks in the time of biopsy. Each of the drug-resistant tumor specimens underwent routine pathological analyses, and in some instances, sizeable alterations from the predominant histology of the resistant tumors have been observed. To our surprise, 5 patients were found to have a diagnosis of smaller cell lung cancer inside their drug-resistant tumor ...
The failure of chemotherapeutic drugs in treatment of various cancers is attributed to the acquisition of drug resistance. However, the migration mechanisms of drug-resistant cancer cells remain incom...
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We have recently received and uploaded many new electronic-books into our catalog. Access these titles through our Full Text Finder, or by clicking on the links below. Have questions? Contact us at x68497 or [email protected] Basic Science and Oncology Bacterial Therapy of Cancer: Methods and Protocols. Breast Cancer: Methods and Protocols. Cancer Drug Resistance: Overviews…
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This proposal outlines a 5 year program designed to develop the principal investigator into an independent translational researcher and investigate the role of...
Colorectal cancer is the third most common cancer among men and women. It is a major clinical problem worldwide, considering a high number of positive-diagnosed patients and death rate among them....
Initial response to multiagent chemotherapy is seen in about 80-90% cases, but relapses with subsequent resistance to drugs is ... Kaur V (2016). "A rare case of blastic plasmacytoid dendritic cell neoplasm with deletion 7q.31, in the setting of heavy pre- ... 2016). "A rare case of blastic plasmacytoid dendritic cell neoplasm with deletion 7q.31, in the setting of heavy pre-treatment ... A few cases of therapy related blastic plasmacytoid dendritic cell neoplasm (BPDCN) have also been reported. The clinical ...
Primary or acquired drug resistance to this drug is very rare. Additional adjuvant chemotherapy may be necessary if a patients ... This continuous signaling, it is presumed, leads to the development of myeloid and/or lymphoid neoplasms that commonly include ... The drug often causes long-term complete hematological and cytogenic remissions as doses well below those used to treat chronic ... The disease is treated with a chemotherapy drug, lenalidomide. Human chromosome translocations between the PDGFRB gene and at ...
"Trials to overcome drug resistance to EGFR and ALK targeted therapies-past, present, and future". Frontiers in Oncology. 4 (233 ... Horn, L; Lovly, CM; Johnson, DH (2015). "Chapter 107: Neoplasms of the lung". In Kasper, DL; Hauser, SL; Jameson, JL; Fauci, AS ... Clinical trials are underway to evaluate how well these drugs kill lung cancer cells in humans.[184] Several drugs that target ... Targeting these tags with drugs can kill cancer cells. Early-stage research in NSCLC using drugs aimed at epigenetic ...
... lymphoid neoplasms, or features of both types of neoplasms. Most commonly, the present with features of myeloid neoplasms with ... This resistance is linked to the occurrence of a S601P mutation in PDGFRA. Acquired resistance to imatinib have in most cases ... That is, many types of these disorders are remarkably susceptible to relatively non-toxic drugs. Hematopoietic stem cells give ... Like the latter neoplasm, hematologic neoplasms cause by ETV6-JAK2 and BCR-JAK2 are aggressive and progress rapidly. Too few ...
Sequential application of drugs can lead to the sequential evolution of resistance mutations to each drug in turn.[102] ... which may be benign neoplasms) or else a malignant neoplasm (cancer). These neoplasms are also indicated, in the diagram below ... Resistance to BCR-ABL targeting drugs[edit]. In the case of Gleevec (Imatinib), which targets the BCR-ABL fusion gene in ... Resistance to selective estrogen receptor modulator drugs[edit]. Selective estrogen receptor modulators (SERMs) are a commonly ...
... drug resistance, multiple, viral MeSH G12.392.395 --- drug resistance, neoplasm MeSH G12.392.491 --- insecticide resistance ... drug resistance, fungal MeSH G12.392.269.383.500 --- drug resistance, multiple, fungal MeSH G12.392.269.420 --- drug resistance ... drug resistance, multiple, viral MeSH G12.392.300 --- drug resistance, multiple MeSH G12.392.300.500 --- drug resistance, ... herb-drug interactions MeSH G12.392.269 --- drug resistance, microbial MeSH G12.392.269.347 --- drug resistance, bacterial MeSH ...
Inactivation is the rarest type of resistance, where an acetyl group is added to the molecule, causing inactivation of the drug ... diabetes and various types of neoplasms. Incyclinide was announced to be ineffective for rosacea in September 2007. Several ... Expert Opinion on Drug Safety. 7 (5): 571-577. doi:10.1517/14740338.7.5.571. ISSN 1744-764X. PMID 18759709. Resistance,, WHO ... although drug-resistance is mounting and their effect on overall mortality is questioned. Tetracycline derivatives are ...
Creative Peptides, Eli Lilly, and Cebix all had drug development programs for a C-peptide product. Cebix had the only ongoing ... C-peptide may be used for determining the possibility of gastrinomas associated with Multiple Endocrine Neoplasm syndromes (MEN ... to help determine degree of insulin resistance. Therapeutic use of C-peptide has been explored in small clinical trials in ... Bigelow, Bruce V. (23 February 2015). "Cebix Shuts Down Following Mid-Stage Trial of C-Peptide Drug". Xconomy. Garde, Damian ( ...
Metastasis and drug resistance are distinguishable. Access to methylation profiling is important to cancer research because: ... caused by accumulation of DNA mutations and epigenetic alterations leading to unrestrained cell proliferation and neoplasm ... Drug therapies can inhibit PIK3CA. Another example is the BRAF gene, one of the first to be implicated in melanomas. BRAF ... Some anticancer drugs target mtDNA and have shown positive results in killing tumor cells. Research has used mitochondrial ...
Dou QP, Li B (August 1999). "Proteasome inhibitors as potential novel anticancer agents". Drug Resistance Updates. 2 (4): 215- ... Kales SC, Ryan PE, Nau MM, Lipkowitz S (June 2010). "Cbl and human myeloid neoplasms: the Cbl oncogene comes of age". Cancer ... Vries EG, Verweij J (2000). "Clinical Cancer Research 2000: New Agents and Therapies". Drug Resistance Updates. 3 (4): 197-201 ... Drug Resistance Updates. 5 (6): 249-58. doi:10.1016/s1368-7646(02)00121-8. PMID 12531181. Clifford SC, Cockman ME, Smallwood AC ...
Chen HY, Shao CJ, Chen FR, Kwan AL, Chen ZP (2010). "Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in ... Such mutations and epigenetic alterations can give rise to cancer (see malignant neoplasms). Thus, CpG island hyper/hypo- ...
... indicative of prolonged drug action The indenoisoquinolines are seldom or not used as substrates for the multidrug resistance ... Use of topoisomerase inhibitors for antineoplastic treatments may lead to secondary neoplasms because of DNA damaging ... rapid reversal of the trapped cleavable complex after drug removal, requiring prolonged infusions, 3) resistance of cancer ... These drugs are anti-cancer therapies. bacterial type II topoisomerase inhibitors (gyrase and topo IV): fluoroquinolones. These ...
... drug resistance, fungal MeSH G04.185.515.286.383.500 --- drug resistance, multiple, fungal MeSH G04.185.515.286.420 --- drug ... neoplasm regression, spontaneous MeSH G04.335.119.260 --- erythrocyte aging MeSH G04.335.122.100 --- autocrine communication ... drug resistance, multiple MeSH G04.185.515.329.500 --- drug resistance, multiple, bacterial MeSH G04.185.515.329.625 --- drug ... drug resistance, microbial MeSH G04.185.515.286.347 --- drug resistance, bacterial MeSH G04.185.515.286.347.500 --- beta-lactam ...
Trial results released in June 2012 show that bendamustine, a drug first developed in East Germany in the 1960s, more than ... ISBN 0-7817-5007-5. Frequency of lymphoid neoplasms. (Source: Modified from WHO Blue Book on Tumour of Hematopoietic and ... clinical evidence suggests that rituximab could be also used in combination with integrin inhibitors to overcome the resistance ... This combination therapy also left patients with fewer side effects than the older treatment (a combination of five drugs- ...
... can occur which prevent the drugs from binding to the protein, leading to resistance to these types of drugs.[117] Drugs used ... Secondary neoplasm[edit]. Development of secondary neoplasia after successful chemotherapy or radiotherapy treatment can occur ... Resistance[edit]. Resistance is a major cause of treatment failure in chemotherapeutic drugs. There are a few possible causes ... Antibody-drug conjugates[edit]. Antibody-drug conjugates (ADCs) comprise an antibody, drug and a linker between them. The ...
... lymphoproliferative neoplasms, malnutrition, and use of immunosuppressive drugs.. People with recurrent boils are as well more ... It may occur following antibiotic use due to the development of resistance to the antibiotics used. An associated skin disease ... Knowledge of the antimicrobial resistance of S. aureus is important in the selection of antimicrobials for treatment. Nodule ( ... Laube S, Farrell M (2002). "Bacterial skin infection in the elderly: diagnosis and treatment". Drugs and Aging. 19 (5): 331-42 ...
Curiously, mutant revertant MCF-7/AdrVp cells that lost their multidrug resistance and became drug-sensitive also lost H19 ... In contrast to most other cancers, adrenocortical neoplasms appear to have decreased expression of H19. To determine a possible ... Drug-resistant MCF-AdrVp cells do not overexpress P-glycoprotein, a cell membrane efflux pump commonly found in multidrug ... p95, or NCA-90, is related to carcinoembryonic antigens, which have been found to reduce drug toxicity by Kawaharata et al. NCI ...
"Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance". Nature. 494 (7436): 251-256. ... a benign but locally infiltrative odontogenic neoplasm. The V600E mutation may also be linked, as a single-driver mutation (a ... In spite of the drug's high efficacy, 20% of tumors still develop resistance to the treatment. In mice, 20% of tumors become ... Drugs that treat cancers driven by BRAF mutations have been developed. Two of these drugs, vemurafenib and dabrafenib are ...
KIT-D816V point mutations in c-KIT exon 17 are responsible for resistance to targeted therapy drugs like imatinib mesylate, a ... Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in ... Imatinib (Glivec/Gleevec), an orally administered drug initially marketed for chronic myelogenous leukemia based on bcr-abl ...
... in P-450 metabolism should be considered when patients exhibit unusual sensitivity or resistance to drug effects at normal ... Neoplasm. Neoplasms have been described with prolonged exposure to some medications or toxins. Hepatocellular carcinoma, ... Drug induced hepatitis. Drug-induced hepatic necrosis. Drug induced hepatic fibrosis. Drug induced hepatic granuloma. Toxic ... Drug induced liver disease. Drug induced liver damage. Drug induced liver injury. Hepatogenous poisoning ...
Acquired resistance to Gleevec is uncommon but has been observed in patients whose mutated cells develop a T674I or D842V ... This drug, also known as Gleevec, has been a FDA-approved and most successful treatment for Philadelphia chromosome-positive ... While the success of Gleevec in treating the myeloproliferative neoplasm/myeloblastic leukemia or T-lymphoblastic leukemia/ ... "Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1". American Journal of Clinical Pathology. ...
... can occur which prevent the drugs from binding to the protein, leading to resistance to these types of drugs. Drugs used in ... Survivors of childhood cancer are more than 13 times as likely to get a secondary neoplasm during the 30 years after treatment ... Resistance is a major cause of treatment failure in chemotherapeutic drugs. There are a few possible causes of resistance in ... drug-to-drug interactions, genetics, and obesity, which has a major impact on the actual concentration of the drug in the ...
... in P-450 metabolism should be considered when patients exhibit unusual sensitivity or resistance to drug effects at normal ... Oral contraceptives Neoplasm Neoplasms have been described with prolonged exposure to some medications or toxins. ... Drug metabolism is usually divided into two phases: phase 1 and phase 2. Phase 1 reaction is thought to prepare a drug for ... Drugs interact with the enzyme family in several ways. Drugs that modify cytochrome P-450 enzyme are referred to as either ...
... and colon neoplasms. PELP1 signaling contributes to hormonal therapy resistance. Altered localization of PLP1 contributes to ... Since PELP1 lacks known enzymatic activity, drugs that target PELP1 interactions with other proteins should have clinical ... AR, PELP1 and Src form constitutive complexes in prostate neoplasms model cells that exhibit androgen independence. Cytoplasmic ... Since PELP1 interacts with histone modifications and epigenetic enzymes, drugs targeting epigenetic modifier enzymes may be ...
... drug resistance - drug-drug interaction - DSMB - Duffy antigen system - dysplasia - dyspnea efficacy - empirical - encephalitis ... New Drug Application - nebulized - Nef - neonata infectionl - neoplasm - nephrotoxic - neuralgia - neurological complications ... antiretroviral drugs - antisense drugs - antitoxins - Antiviral drug - aphasia - aphthous ulcer - apoptosis - approved drugs - ... multi-drug rescue therapy - multiple drug-resistant tuberculosis (MDR-TB) - mutation - myalgia - mycobacterium - mycobacterium ...
... drug resistance - drug-drug interaction - DSMB - Duffy antigen system - dysplasia - dyspnea ... New Drug Application - nebulized - Nef - neoplasm - nephrotoxic - neuralgia - neurological complications of AIDS - neuropathy ... antiretroviral drugs - antisense drugs - antitoxins - Antiviral drug - aphasia - aphthous ulcer - apoptosis - approved drugs - ... multi-drug rescue therapy - multiple drug-resistant tuberculosis (MDR-TB) - mutation - myalgia - mycobacterium - mycobacterium ...
Interactions between myeloma cells and the marrow microenvironment affect the survival, proliferation, and drug resistance of ... Plasma cell neoplasms are tumors derived from an expansion of mutated mature B-cells and their precursors. These neoplasms ... has been identified and is the most likely site of drug resistance, which almost invariably develops during treatment; such ... "Plasma Cell Neoplasms: General Considerations." Williams Hematology, 9e Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW ...
"Drug Resistance, Neoplasm" by people in this website by year, and whether "Drug Resistance, Neoplasm" was a major or minor ... "Drug Resistance, Neoplasm" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "Drug Resistance, Neoplasm" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Drug Resistance, Neoplasm". ...
Breast Neoplasms. Neoplasms by Site. Neoplasms. Breast Diseases. Skin Diseases. Paclitaxel. Albumin-Bound Paclitaxel. ... and low drug resistance to paclitaxel using the Extreme Drug Resistance (EDR) Assay in patients with previously treated ... then tested by the Extreme Drug Resistance (EDR) Assay to determine probability of drug resistance to paclitaxel. After ... Evaluation of Drug Resistance in Patients With Metastatic Breast Cancer. The recruitment status of this study is unknown. The ...
Pages that link to "Drug resistance neoplasm". ← Drug resistance neoplasm. What links here. Page:. Namespace:. all. (Main). ... The following pages link to Drug resistance neoplasm: View (previous 50 , next 50) (20 , 50 , 100 , 250 , 500)*Drug ‎ (← links) ...
Drug Resistance. *Humanized. *Humanized: therapeutic use. *Humans. *Kidney Neoplasms. *Kidney Neoplasms: drug therapy ...
Drug Resistance, Neoplasm* * Etoposide / administration & dosage * Female * Follow-Up Studies * Humans * Hyperthermia, Induced ...
Cell Proliferation / drug effects * Disease Models, Animal * Drug Resistance, Neoplasm * ErbB Receptors / antagonists & ...
Keywords: Pooled shRNA screen; MYC; JAK2; PIM; drug combination; myeloproliferative neoplasms. Received: March 27, 2014 ... Therefore, effective drug combinations are urgently needed to combat such resistance. We set out to generate JAK2 inhibitor- ... Effective drug combination is one way to enhance therapeutic efficacy and combat resistance against JAK2 inhibitors. To ... JAK2 inhibitor-resistant clones are sensitive to JAK2/PIM drug combination. Rapidly emerging resistance to targeted kinase ...
BACKGROUND: As an important stress-response mechanism, autophagy plays crucial role in the tumor formation and drug resistance ... Pharmacogenomics of genes involved in antifolate drug response and toxicity in osteosarcoma.. Expert Opin Drug Metab Toxicol. ... drug resistance and tumor recurrence. However, the relationship between autophagy and OS CSCs still remains unclear.. METHODS: ... The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line ...
Induction of multidrug resistance by doxorubicin (DOX), together with non-specific toxicities, has restricted DOX-based ... Drug Delivery Systems. Drug Resistance, Multiple. Drug Resistance, Neoplasm. Endocytosis. Humans. Mice. Mice, Nude. Neoplasm ... Colonic Neoplasms / drug therapy, metabolism, pathology. Doxorubicin / chemistry, pharmacology*. ... Here we investigated whether DOX-EBP is able to overcome drug resistance and the underlying molecular mechanisms.. EXPERIMENTAL ...
Drug resistance in the treatment of cancer still remains a major clinical concern. Resistance to tamoxifen is seen in half of ... and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been ... PAK1-mediated phosphorylation of serine 305 (S305) of ERα leads to resistance to tamoxifen. In our study, PAK1-induced ... suggestive tamoxifen resistance was designed. According to our hypothesis, phosphorylation of ERα-S305 by PAK1 may be reversed ...
Cell Growth Processes / drug effects. Dose-Response Relationship, Drug. Drug Resistance, Neoplasm. Humans. K562 Cells. Leukemia ... Myelogenous, Chronic, BCR-ABL Positive / drug therapy*, pathology. Membrane Potential, Mitochondrial / drug effects. ... as well as in patients with primary and/or acquired resistance to imatinib.. ...
Kidney Neoplasms. *Neoplasm Metastasis. *Cytochrome P 450. *Multi-Drug Resistance. *P-Glycoprotein ...
Distinct Receptor Tyrosine Kinase Subsets Mediate Anti-HER2 Drug Resistance in Breast Cancer.  Alexander, Peter; Chen, Rui; ...
Survivin expression and cancer cell drug resistance. Fengzhi Li; Fiscal Year: 2008 ... neoplasm metastasis*lung neoplasms*inbred c3h mice*anticarcinogenic agents*pathologic neovascularization*inbred f344 rats* ... experimental mammary neoplasms. Summary. Summary: Experimentally induced mammary neoplasms in animals to provide a model for ... neoplasm transplantation*breast neoplasms*methylnitrosourea*carcinogens*adenocarcinoma*nude mice*transgenic mice*antineoplastic ...
Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma. - Diana Seidel, ... Drug Resistance, Neoplasm. *Female. *Gangliosides (genetics, immunology) *Genetic Engineering. *Humans. *Immunotherapy, ... Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma.. Abstract. The ... Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find ...
Drug Design Drug Resistance, Neoplasm Enhancer of Zeste Homolog 2 Protein Gene Expression Regulation, Neoplastic Humans ... such as drug resistance and the importance of selectivity over EZH1 or somatic EZH2 mutants. ... Areas covered: This review summarizes recent efforts in the drug development of EZH2 inhibitors reported in the patent ...
Discovery of a novel B-Raf fusion protein related to c-Met drug resistance Dillon, Roslyn; Nilsson, Carol L LU ; Shi, Stone D-H ... iframe src="https://lup.lub.lu.se/search/publication?embed=1&q=keywords+exact+%22Drug+Resistance%2C+Neoplasm%22&hide_pagination ... MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells Husted, Susanne; ... Adaptive mitochondrial reprogramming and resistance to PI3K therapy Ghosh, Jagadish C; Siegelin, Markus D; Vaira, Valentina; ...
Drug Resistance, Multiple Gene Expression Regulation Humans Methotrexate Multidrug Resistance-Associated Proteins Neoplasms ... Multidrug resistance protein (MRP)7, MRP8, and MRP9 (gene symbols ABCC10, ABCC11, and ABCC12) are recently identified members ... MRP7 and MRP8 are lipophilic anion pumps that are able to confer resistance to chemotherapeutic agents. MRP7 is competent in ... MRP8 is a cyclic nucleotide efflux pump that is able to confer resistance to nucleoside-based agents, such as PMEA and 5FU. The ...
Chapter 4. Multiple Mechanisms of Drug Resistance in Glioblastoma and Novel Therapeutic Opportunities. (Caleb Yelton and Swapan ... Chapter 5. TNF- α and Its Receptors in Gynecological and Breast Neoplasms. (Rosekeila Simões Nomelini, Cid Almeida de Lima, ... of all tumors recur due to therapy resistance. The most challenging aspect in the treatment of glioblastomas is the invasive ... the immunological mechanisms in these neoplasms, and the role as possible future targets in the treatment. ...
Our previous studies exploring melphalan resistance in the human rhabdomyosarcoma xenograft TE-671 MR revealed elevation of DNA ... Key words Melphalan Drug resistance Antineoplastic agents DNA polymerases Neoplasm transplantation Received: 19 June 1995 / ... Our previous studies exploring melphalan resistance in the human rhabdomyosarcoma xenograft TE-671 MR revealed elevation of DNA ...
Drug Resistance, Neoplasm. en. dc.subject. Embryo, Mammalian. en. dc.subject. Fibroblasts. en. ... the potential mechanisms underlying resistance to this targeted drug in MPM are still unknown. Functional genetic analyses were ... However, MPM tissues from patients who failed to respond to bortezomib and MPM cell lines selected for resistance to bortezomib ... and the observed loss of BAK expression or NOXA transactivation may be relevant mechanisms of resistance in the clinic.. en. ...
Mentions: Hypoxia has been shown to promote resistance to cytotoxic drugs in other human OS cell lines [12]. Thus we asked ... Mentions: Hypoxia has been shown to promote resistance to cytotoxic drugs in other human OS cell lines [12]. Thus we asked ... we show that hypoxia results in resistance of human OS cells to doxorubicin-mediated toxicity (6-13 fold increase, p,0.01). ... we show that hypoxia results in resistance of human OS cells to doxorubicin-mediated toxicity (6-13 fold increase, p,0.01). ...
Drug Resistance, Multiple. *Drug Resistance, Neoplasm. *Gene Expression Regulation, Neoplastic. *HT29 Cells ... Background: The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters ... Background: The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters ... restored the antitumor effects of different chemotherapeutic drugs, restored a proper tumor-immune system recognition in ...
... to drug resistance in ovarian cancer were reviewed to determine the relationship of TSGs with ovarian cancer drug resistance. ... It has been demonstrated that TSGs contribute to drug resistance in several types of solid tumors. However, an overview of the ... We observed that the 15 TSGs had close interactions with each other, suggesting that they may contribute to drug resistance in ... The main limitation to a successful treatment for ovarian cancer is the development of drug resistance to combined chemotherapy ...
  • Epithelial tumor cells that have undergone epithelial-to-mesenchymal transition (EMT) are typically prone to metastasis and drug resistance and contribute to a poor clinical outcome. (elsevier.com)
  • Comprehensive co-detecting observable aneuploid CTCs and CECs by SE-iFISH, along with applicable genomic and/or proteomic single cell molecular profiling, are anticipated to facilitate elucidating how those disparate categories of aneuploid CTCs and CECs cross-talk and functionally interplay with tumor angiogenesis, therapeutic drug resistance, tumor progression, and cancer metastasis. (mdpi.com)
  • Using a Topo I-deficient murine B lymphoma-derived subclone (P388-45/C) selected for its resistance to high dosage of the antitumor drug camptothecin, we show that Topo I depletion results in the hypophosphorylation of SR proteins and impairs exonic splicing enhancer (ESE)-dependent but not constitutive splicing. (cnrs.fr)
  • The contents of this volume include reviews on dendrimers for anti-cancer drug delivery, treatment methods for advanced cutaneous squamous cell carcinoma, targeting heat shock proteins for cancer treatment, Bayesian systems for optimizing treatment protocols in oncology and much more. (eurekaselect.com)
  • Additionally, the bone marrow microenvironment, where MM cells preferentially home and grow, plays a crucial role in MM cell growth and survival and in developing resistance to conventional and novel therapies for MM. It has been shown that angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, are expressed and secreted by MM cells and contribute to myeloma-bone marrow neovascularization ( 8 ). (aacrjournals.org)
  • In this review, we discuss the various BCR-ABL-dependent and-independent mechanisms of resistance observed in CML, and the range of therapeutic solutions available to overcome such resistance and to ultimately improve the survival of patients with CML. (drugdiscoverytoday.com)
  • Inhibition of the drug extrusion activity of MDR1/P-gp by low-molecular weight pharmacologically active compounds as a method to reverse MDR in patients suffering on malignant diseases has been studied capaciously, but the clinical results have generally been disappointing. (nih.gov)
  • antibiotic resistance (AR) cassettes, which we found associated with mobile genetic elements such as Tn3, Tn7, and Tn10. (bioportfolio.com)
  • The potential induction of antibiotic resistance represents a highly undesirable side‐effect of chemical cleaning, as MDR pathogens have been constantly and rapidly growing in the recent decades and a high proportion of HAIs is caused by MDR bacteria (Caini et al . (pubmedcentralcanada.ca)
  • The association between tumor drug resistance and the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K-AKT-mTOR) pathway was measured by western blot, assessing the changes in protein kinase B (AKT), phosphor-AKT (p-AKT), P70, and p-P70 protein levels. (elsevierpure.com)
  • Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer. (ouhsc.edu)
  • Distinct Receptor Tyrosine Kinase Subsets Mediate Anti-HER2 Drug Resistance in Breast Cancer. (duke.edu)
  • Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer. (semanticscholar.org)
  • The incidence of HER2 receptor expression, evaluated by IHC in different neoplasms is reported in Table 1 . (jcancer.org)
  • This progress is reflected in the 2016 update of the World Health Organization classification of lymphoid neoplasms, which lists as many as 41 mature B-cell neoplasms (including provisional categories). (cdc.gov)
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, Waldenström macroglobulinemia, hairy cell leukemia, and marginal zone lymphomas of splenic, nodal, and extranodal types represent examples of B-cell neoplasms in which novel molecular biomarkers have been discovered in recent years. (cdc.gov)
  • As the results, the tumor uptake of drug-loaded nanoparticles as well as their interstitial penetration within the tumor would be greatly increased for mice pre-treated with erlotinib at the oral feeding dose of 50 mg/kg, leading to remarkably improved chemotherapeutic efficacy of nanomedicine. (bioportfolio.com)
  • Cancer scientists and oncologists have worked together for some time to find ways of understanding anticancer drug resistance and also to develop pharmacological strategies to overcome that resistance. (surrey.ac.uk)
  • The results from a number of these trials are eagerly awaited and there are many in the cancer research community who remain committed to this area of anticancer drug discovery. (surrey.ac.uk)
  • Therefore, the use of cell lines for drug testing in future studies may aid the progress of anticancer drug research. (spandidos-publications.com)
  • In the present study, the genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia (T-ALL) cell line, is analyzed in depth, and the usefulness of cell lines in anticancer drug research is debated ( 5 - 7 ). (spandidos-publications.com)
  • The Food and Drug Administration (FDA) has granted de novo authorization to Vela Diagnostics USA for its Sentosa SQ HIV Genotyping assay, making this the first FDA-authorized test that detects HIV type-1 drug resistance mutations using next-generation sequencing (NGS). (aacc.org)
  • Our findings elucidate the mechanism of driver gene mutations-independent mechanism of acquired resistance to cetuximab in HNSCC and also provide potential strategies for combating cetuximab resistance. (zfin.org)
  • On the basis of these observations we sought to determine whether drug resistance in neuroblastoma cell lines was associated with a lack of p53 function and/or p53 mutations. (aacrjournals.org)
  • The "classical" MDR phenotype is the result from decreased cellular drug accumulation mediated by the adenosine triphosphate binding cassette (ABC)-transporter MDR1/P-glycoprotein (MDR1/P-gp, ABCB1) encoded by the human MDR1 gene. (nih.gov)
  • Loss of p53 function was selectively achieved by transduction of human papillomavirus 16 E6 (which degrades p53) into two drug-sensitive neuroblastoma cell lines with intact p53, causing high-level drug resistance to L-PAM, carboplatin, and etoposide. (aacrjournals.org)
  • 2016 ), and also, more importantly, against antibiotics, as recently reported for chlorhexidine induction of resistance against Colistin (Wand et al . (pubmedcentralcanada.ca)