A lipophilic copper(II)bis(thiosemicarbazone) labeled with the positron-emitting isotope (61)Cu with hypoxia-selective and radioisotopic activities. With a high membrane permeability and redox potential, (61)Cu-ATSM easily enters and selectively resides in hypoxic cells. The extent of (61)Cu-ATSM retention in tissue is inversely related to the state of tissue oxygenation allowing the quantitation of tissue hypoxia with positron emission tomography (PET).
A methylated tryptophan with anti-immunosuppressive activity. 1-methyl-d-tryptophan inhibits the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades the essential amino acid tryptophan, and may increase or maintain tryptophan levels important to T cell function. Tryptophan depletion is associated with immunosuppression involving T cell arrest and anergy.
A semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata radiolabeled with carbon 11 (11C) with antineoplastic and radiotracer properties. During the S phase of the cell cycle, topotecan inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Quantitation of 11C topotecan accumulated in tumor tissues by positron emission tomography (PET) may help predict responses to topotecan therapy.
An iodine 123-radiolabled small molecule that exhibits high affinity for prostate-specific membrane antigen (PSMA) with potential use in molecular imaging. 123-I-MIP-1095, a radiolabeled glutamate-urea-lysine analogue, selectively binds PSMA, which allows imaging of PSMA-expressing prostate cancer cells with gamma scintigraph. PSMA is a transmembrane glycoprotein highly expressed by malignant prostate epithelial cells and vascular endothelial cells of various solid tumors.
An iodine 131-radiolabeled small-molecule benzamide compound with potential antineoplastic activity. The benzamide moiety of 131-I-MIP-1145 binds to melanin, selectively delivering a cyotoxic dose of gamma and beta radiation to melanin-expressing tumor cells. Melanin pigments, polymer derivatives of the amino acid tyrosine, are over-expressed in approximately 40% of melanomas.
An iodine 131 (I 131) radioconjugate of the synthetic chlorotoxin (CTX) TM-601 with potential antiangiogenic and antineoplastic activities. CTX is a 36 amino acid neurotoxin found in the venom of the giant yellow scorpion Leiurus quinquestriatus that preferentially binds malignant cells of neuroectodermal origin. The recombinant version of this peptide, TM-601, is expressed in and purified from E. coli and then covalently linked to I 131 to produce 131I-TM-601. 131I-TM-601 binds to tumor cells of neuroectodermal origin and is internalized; administered once, it may be used as a radioimaging agent; repeated administration may result in a tumor-specific, cumulative radiocytotoxic dose of I 131. In addition, TM-601 alone, similar to native CTX, may inhibit angiogenesis due to its ability to bind to and inhibit matrix metalloproteinase 2 (MMP-2), an endopeptidase involved in tissue remodeling processes such as angiogenesis.
The orally bioavailable C-4 methyl carbonate analogue of paclitaxel, labeled with radioactive carbon 14, with radioisotope and potential antineoplastic activities. 14C BMS-275183 binds to tubulin and inhibits microtubule disassembly, which may result in cell cycle arrest at the G2/M phase and inhibition of cell division, and subsequently cell death. This agent may be useful for treating multi-drug resistant (MDR) tumors because it does not appear to be a substrate for P-glycoprotein.
16, 16-dimethyl prostaglandin E2
A stable derivative of prostaglandin E2 (PGE2) with potential hematopoietic activity. Administration of 16,16 dimethyl-prostaglandin E2 (dmPGE2) appears to lead to increased formation of hematopoietic stem and progenitor cells. Even though the exact mechanism of action has yet to be fully elucidated, this agent may stimulate hematopoiesis by activating the Wnt signaling pathway, which increases cellular levels of beta-catenin, a subunit of the cadherin protein complex.
A radioconjugate and an acetate analog labeled with fluorine F 18 ((18)F-FAC), a positron-emitting isotope, with potential prostate tumor tracer property using positron emission tomography (PET). Although the mechanism of action is unclear, fluorine F 18 acetate preferentially accumulates in tumor tissue, serving as a tracer for imaging tumors with PET. Fluorine 18 has a longer radioactive half-life (110 min) vs. the half-life of carbon-11 acetate (20.4 min). Furthermore, (18)F-FAC showed a rapid clearance from liver and extensive excretion to bile and urine in comparison with carbon-11 acetate, therefore this tracer may be a useful alternative to C-11 acetate for the detection of prostate tumors by PET.
A fluorine-18-labeled acycloguanosine derivative substrate for herpes simplex virus type-1 thymidine kinase (HSV1-tk). 18F-FHBG is used as a reporter probe to image the expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene in gene transfer therapy. HSV1-tk and and HSV1-tk-metabolized 18F-FHBG co-localize, allowing positron emission tomography (PET) localization of HSV1-tk gene-transfected tissue and the assessment of gene transfer efficiency.
A radiofluorinated 2-nitroimidazole derivative with hypoxia-specific tracer activity. 18F-fluoroazomycin arabinoside is reduced under hypoxic conditions and is often seen in various malignant tumors, forming highly reactive intermediates. In its reduced form, 18F-fluoroazomycin arabinoside covalently binds to macromolecules, thereby accumulating in hypoxic cells and allowing radioisotopic imaging of these particular cells. Compared to 18F-misonidazole, 18F-fluoroazomycin arabinoside has a lower octanol:water partition coefficient; it therefore has less tendency to accumulate in lipophilic tissues and exhibits a faster renal clearance, leading to an improved imaging ability of hypoxic tissue.
A radiotracer consisting of methylcholine labeled with the positron-emitting radioisotope fluorine F 18 (18F-FMCH) with potential imaging use. Upon administration, 18F-fluoromethylcholine incorporates into tumor cells through an active, carrier-mediated transport mechanism for choline and then is phosphorylated intracellularly by choline kinase, an enzyme frequently upregulated in human tumors, yielding phosphoryl 18F-fluoromethylcholine. In turn, phosphoryl 18F-fluoromethylcholine is integrated into phospholipids in the cell membrane as part of phosphatidylcholine. As the proliferation of cancer cells is much higher than normal cells, tumor cells exhibit an increased rate of 18F-FMCH uptake and incorporation, allowing tumor imaging with positron emission tomography (PET).
A radiofluorinated 2-nitroimidazole derivate with hypoxia-specific tracer activity. Misonidazole is reduced under hypoxic conditions and in reduced form covalently binds to macromolecules in hypoxic cells. 18F (fluorine-18) radiofluorination of misonidazole to form 18F-fluoromisonidazole allows radioisotopic imaging of reduced misonidazole bound to macromolecules in hypoxic cells.
A deoxyuridine prodrug with potential antineoplastic activity. Upon cellular uptake, 2’-F-ara-deoxyuridine (FAU) is phosphorylated by thymidine kinase to FAU monophosphate and subsequently methylated in the 5'-position by thymidylate synthase (TS) to its activated form, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) 5-methyluracil monophosphate (FMAUMP). FMAUMP is incorporated into DNA leading to an inhibition of DNA synthesis and so cell growth. The catalytic activity of TS is critical to activation of FAU and subsequent incorporation into DNA. FAU may be beneficial in the case of tumors with high TS activity that are resistant to TS inhibitors.
A depot formulation containing a bioresorbable, controlled-release, calcium sulphate-based paste of the nonsteroidal antiandrogen 2-hydroxyflutamide (2-HOF) with potential antineoplastic activity. Upon injection into the tumor site in the prostate, 2-hydroxyflutamide depot slowly releases 2-HOF, which competitively binds to androgen receptors (ARs), blocking the binding of dihydrotestosterone (DHT). This may inhibit androgen-dependent DNA and protein synthesis, resulting in tumor cell growth arrest and decreased cellular proliferation. In addition, 2-HOF inhibits nuclear uptake of androgen in androgen-responsive tissues.
An orally bioavailable estradiol metabolite with potential antineoplastic activity. 2-Methoxyestradiol inhibits angiogenesis by reducing endothelial cell proliferation and inducing endothelial cell apoptosis. This agent also inhibits tumor cell growth by binding to tubulin, resulting in antimitotic activity, and by inducing caspase activation, resulting in cell cycle arrest in the G2 phase, DNA fragmentation, and apoptosis.
2G-1 TCR retroviral vector-transduced lymphocytes
A preparation of autologous human T-lymphocytes isolated from renal cell cancer (RCC) patient and transduced with 2G-1 TCR, a retroviral vector encoding the alpha and beta chains of a T-cell receptor that recognizes TNF-related apoptosis inducing ligand (TRAIL) bound to death receptor 4 (DR4), with potential immunostimulating and antineoplastic activities. After transduction, expansion in culture, and introduction into the RCC patient, 2G-1 TCR retroviral vector-transduced lymphocytes may stimulate a cytotoxic T lymphocyte (CTL) response against RCC cells with TRAIL bound to DR4 on their surfaces. TRAIL, a member of the TNF superfamily, is a homotrimeric type II membrane protein that rapidly induces oligomerization of receptor intracellular death domains and apoptosis in a variety of tumor cells when bound to its receptors; DR4 (TRAIL receptor 1), a member of the TNF receptor family, is overexpressed by a variety of malignant cell types.
3'-aminomethyl nicotine-P. aeruginosa r-exoprotein A conjugate vaccine
A hapten-carrier immunoconjugate composed of the hapten trans-3?-aminomethyl nicotine conjugated to a recombinant P. aeruginosa exoprotein A, rendered nontoxic through amino acid depletion, with potential immunostimulating activity. Upon vaccination with 3'-aminomethyl nicotine-P. aeruginosa r-exoprotein A conjugate vaccine, the immune system may produce anti-nicotine antibodies. Antibody-bound nicotine cannot pass the blood brain barrier (BBB) to activate brain nicotine receptors. Nicotine, a small organic molecule that is not
immunogenic, must be haptenized and conjugated to a carrier
protein, such as nontoxic recombinant P. aeruginosa exoprotein A, to induce an antibody response. Aluminium
hydroxide may be used as an adjuvant for this vaccine.
A synthetic cytidine nucleoside containing a covalently bound ethynyl group with potential antineoplastic and radiosensitizing activities. 3'-C-ethynylcytidine is metabolized in tumor cells to ethynylcytidine triphosphate (ECTP), which inhibits RNA synthesis by competitive inhibition of RNA polymerases I, II and III; subsequently, RNase L is activated, resulting in apoptosis. RNase L is a potent antiviral and antiproliferative endoribonuclease that cleaves singled stranded RNA, causes 28s rRNA fragmentation, and activates Janus Kinase (JAK), a mitochondrial-dependent apoptosis signaling molecule.
A radioconjugate consisting of a thymidine analogue radiolabeled with fluorine F 18, a positron emitting isotope. Phosphorylated by S-phase-specific thymidine kinase 1, 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) is trapped intracellularly by entering the salvage pathway of DNA synthesis without incorporation into DNA. 18F-FLT serves a marker of tumor cell proliferation for imaging with positron emission tomography (PET); as a marker of proliferation rather than metabolism, it is more specific to tumor tissue than 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG). This agent is metabolically stable, accumulates in the normal bone marrow and the liver, and does not cross the blood-brain barrier.
A ring-substituted amphetamine derivative, structurally related to the hallucinogen mescaline, with entactogenic, neurotoxic, and motor-stimulatory activities. 3,4-methylenedioxymethamphetamine (MDMA) produces an acute, rapid enhancement in both the release of serotonin from and the inhibition of serotonin reuptake by serotonergic nerve endings in the brain. Once within the cell, MDMA depletes stores of tryptophan hydroxylase (TPH) via acute oxidative inactivation; in turn, depleted stores of TPH leave cell terminals open to damage from oxidative stress, possibly a source of MDMA neurotoxicity. This agent also induces norepinephrine, dopamine, and acetylcholine release and can act directly on a number of receptors, including alpha 2-adrenergic and 5-hydroxytryptamine (5-HT) 2A receptors. MDMA may suppress the dyskinesia associated with long-term use of L-dopamine (L-DOPA) without affecting the efficacy of L-DOPA treatment.
A synthetic analogue of nucleoside uridine lacking a ring nitrogen in the 3-position. 3-deazauridine inhibits cytidine synthase, thereby reducing intracellular levels of cytidine and deoxycytidine and disrupting DNA and RNA synthesis. This agent may trigger apoptosis and enhance differentiation of neoplastic cells..
An iodinated doxorubicin analogue with antiamyloid activity. 4'-Iodo-4'-deoxydoxorubicin (IDOX) binds with high affinity to five types of natural amyloid fibrils including immunoglobulin light chains, amyloid A, transthyretin (methionine-30 variant), ß-protein (Alzheimer), and ß2-microglobulin. This agent may inhibit fibril growth, increasing the solubility of amyloid tissue deposits and facilitating their clearance. IDOX has also been shown to insulin amyloid fibrillogenesis in vitro.
4-nitroestrone 3-methyl ether
A synthetic derivative of estradiol. 4-nitroestrone 3-methyl ether inhibits estrogen sulfotransferase (EST), a progesterone-induced secretory endometrial enzyme which affects estrogen receptor levels. This agent has been shown to be an effective growth inhibitor of some chemically induced animal mammary tumors.
4-peptide melanoma vaccine
An emulsion of 4 melanoma peptides with potential immunomodulating and antineoplastic activities. Upon vaccination, 4-peptide melanoma vaccine may stimulate an immune response against 4 different melanoma associated antigens. This may lead to a reduction in tumor cell proliferation of cancer cells expressing these antigens.
A folate-based biomodulator with potential antineoplastic activity. 5,10-methylenetetrahydrofolate (MTHF) stabilizes the covalent binding of the fluorouracil metabolite 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP) to its target enzyme, thymidylate synthase, which results in inhibition of thymidylate synthase, depletion of thymidine triphosphate (TTP), a necessary constituent of DNA, and tumor cell death. Unlike leucovorin, MTHF, as the active form of folate, does not require metabolic activation and may increase the chemotherapeutic effects of fluorouracil with lower toxicity.
A fluorinated pyrimidine analogue antimetabolite with potential antineoplastic activity. As a prodrug, 5-fluoro-2-deoxycytidine is converted by intracellular deaminases to the cytotoxic agent 5-fluorouracil (5-FU). 5-FU is subsequently metabolized to active metabolites including 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP binds to and inhibits thymidylate synthase, thereby reducing the production of thymidine monophosphate, which leads to depletion of thymidine triphosphate and the inhibition of DNA synthesis and cell division. FUTP competes with uridine triphosphate (UTP) for incorporation into the RNA strand, which results in the inhibition of RNA and protein synthesis and cell proliferation. Other fluorouracil metabolites also get incorporated into both DNA and RNA, with further inhibition of cellular growth.
5-fluorouracil/salicylic acid topical solution
A topical formulation containing 0.5 % of antimetabolite 5-fluorouracil (5-FU) and 10% of salicylic acid, with potential antimitotic and keratolytic activity. Upon cutaneous application, 5-FU in the 5-fluorouracil/salicylic acid topical solution impedes pyrimidine metabolism thereby inhibiting cell growth, while the salicylic acid induces anti-inflammatory response and results in keratolytic effect. This may result in the breakdown of keratinocytes and prevent proliferation of keratinocytes locally.
The fluorine-18 (18F)-radiolabeled pyrimidine analog 5-fluorouracil (5-FU) with positron-emitting activity. Upon administration, 5-[18F]fluorouracil distribution in tumor tissue may be measured with positron emission tomography (PET). The degree of 5-[18F]fluorouracil uptake in tumor tissue may help to predict the response to 5-fluorouracil-based chemotherapy or to determine the response to other therapeutic agents used to treat 5-FU-sensitive tumors.
50% oxygen/50% nitrous oxide premix
An equimolar gas mixture of oxygen (O2) and nitrous oxide (N2O) with potential analgesic activity. Upon inhalation, 50% oxygen/50% nitrous oxide premix produces rapidly reversible analgesia. The exact mechanism through which nitrous oxide exerts its analgesic effect has yet to be fully elucidated, but it appears to be associated with the neuronal release of endogenous opioid peptides.
A synthetic triazine analogue of uridine with antimetabolite activity. 6-azauridine inhibits de novo pyrimidine synthesis and DNA synthesis and is converted intracellularly into mono, di-, and triphosphate derivatives, which incorporate into RNA and inhibit protein synthesis.
A semisynthetic analogue of the Streptomyces melanovinaceus-derived tetracyclic antitumor antibiotic quinocarmycin with potential antineoplastic activity. Quinocarmycin belongs to the naphthyridinomycin/saframycin class of antitumor antibiotics. These antibiotics appear to act through DNA alkylation.
A synthetic derivative of staurosporine with antineoplastic activity. 7-hydroxystaurosporine inhibits many phosphokinases, including the serine/threonine kinase AKT, calcium-dependent protein kinase C, and cyclin-dependent kinases. This agent arrests tumor cells in the G1/S of the cell cycle and prevents nucleotide excision repair by inhibiting the G2 checkpoint kinase chk1, resulting in apoptosis.
8-hydroxyquinoline sulfate ointment
An ointment formulation containing the sulfate salt of 8-hydroxyquinoline in a petrolatum and lanolin base with skin-protecting activity. Upon topical application, 8-hydroxyquinoline sulfate exhibits antiseptic activity while lanolin moisturizes and softens skin.
A topical gel containing a peptide derived from the human papillomavirus (HPV). Application of 851B gel may stimulate the host immune system to trigger a cytotoxic T-lymphocyte response to cells that express HPV.
A synthetic imidazoquinoline Toll-like receptor 7 (TLR7) agonist with immunostimulating and potential antitumor activities. TLR7 agonist 852A binds to and activates TLR7, thereby stimulating plasmacytoid dendritic cells (pDC) through the TLR7-MyD88-dependent signaling pathway. Activation of pDC results in secretion of interferon alpha, the production of proimflammatory cytokines, the upregulation of co-stimulatory molecules, and enhanced T and B-cell stimulatory responses.
A radiolabeled macromolecule consisting of the chelating agent diethylenetriamine pentaacetic acid (DTPA) and mannose each attached to a dextran backbone and labeled with metastable technetiumTc-99 (Tc-99m), with mannose binding and radioisotopic activities. Upon injection, the mannose moiety of 99mTc-DTPA-mannosyl-dextran binds to mannose-binding protein (MBP). As MBPs reside on the surface of dendritic cells and macrophages, this gamma-emitting macromolecule tends to accumulate in lymphatic tissue where it may be imaged using gamma scintigraphy. This agent exhibits rapid clearance from the injection site, rapid uptake and high retention within the first draining lymph node, and low uptake by the remaining lymph nodes. MBP is a C-type lectin that binds mannose or fucose carbohydrate residues, such as those found on the surfaces of many pathiogens, and once bound activates the complement system.
(Other name for: hydrocortisone sodium succinate)
A murine IgG1 monoclonal anti-idiotype antibody, containing a variable antigen-binding region that functionally mimics the three-dimensional structure of a specific epitope on the ovarian cancer tumor-associated antigen CA-125, with potential antineoplastic activity. With a variable antigen-binding region that acts as a surrogate antigen for CA-125, abagovomab may stimulate the host immune system to elicit humoral and cellular immune responses against CA-125-positive tumor cells, resulting in inhibition of tumor cell proliferation.
A synthetic decapeptide and antagonist of naturally occurring gonadotropin-releasing hormone (GnRH). Abarelix directly and competitively binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. As a result, this may relieve symptoms associated with prostate hypertrophy or prostate cancer, since testosterone is required to sustain prostate growth.
A soluble fusion protein consisting of the extracellular
domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to
a modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1
(IgG1) with immunosuppressive activity. Abatacept binds CD80 and CD86 on antigen presenting cells (APCs), blocking interaction with CD28 on T lymphocytes, which initiates a co-stimulatory signal required for full activation of T lymphocytes.
(Other name for: etaracizumab)
(Other name for: liposomal amphotericin B)
(Other name for: tretinoin)
A novel, broad-spectrum hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. Abexinostat inhibits several isoforms of HDAC, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling; the selective transcription of tumor suppressor genes; and the tumor suppressor protein-mediated inhibition of tumor cell division and induction of tumor cell apoptosis.
HDAC, upregulated in many tumor types, is an an enzyme that is responsible for the deacetylation of chromatin histone proteins.
An orally active acetate salt of the steroidal compound abiraterone with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels.
(Other name for: methotrexate)
(Other name for: paclitaxel albumin-stabilized nanoparticle formulation)
absorbable gelatin sponge
A sterile hemostatic agent composed of purified porcine-derived gelatin. In regional chemotherapy, absorbable gelatin sponge may be used to embolize arteries in the region of a tumor in order to block or retard blood flow; this blockage results in a locally increased concentration of chemotherapeutic agents delivered to the tumor when chemotherapeutic agents are infused into the embolized arterial circulation upstream of the blockage.
A synthetic peptide that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). ABT-510 inhibits the actions of several pro-angiogenic growth factors important to tumor neovascularization; these pro-angiogenic growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)), hepatocyte growth factor (HGF), and interleukin 8 (IL-8).
An orally bioavailable antimitotic sulfonamide. ABT-751 binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, thereby preventing tumor cell replication. This agent also disrupts tumor neovascularization, reducing tumor blood flow and so inducing a cytotoxic effect.
A chemotherapy regimen consisting of doxorubicin hydrochloride (Adriamycin), bleomycin, vinblastine and dacarbazine, used alone or in combination with radiation therapy, for the primary treatment of Hodgkin lymphoma. (NCI Thesaurus)
A regimen containing doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate and etoposide used in combination with radiation therapy for the treatment of low-risk, childhood Hodgkin lymphoma. (NCI Thesaurus)
A regimen consisting of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide, given in combination with radiation therapy and used for the treatment of high-risk, childhood Hodgkin's lymphoma. (NCI Thesaurus)
A chemotherapy regimen consisting of doxorubicin hydrochloride (Adriamycin) and cyclophosphamide used in the adjuvant setting for the primary treatment of breast cancer. This regimen is also used for the treatment of recurrent and metastatic breast cancer. (NCI Thesaurus)
A chemotherapy regimen consisting of doxorubucin hydrochloride (Adriamycin) and cyclophosphamide, followed by paclitaxel (Taxol), administered on either a dose-dense or sequential schedule and used as an adjuvant treatment for breast cancer. (NCI Thesaurus)
A 5-aminoimidazole-4-carboxamide (AICA) riboside, a purine nucleoside analog, and a nucleotide biosynthesis precursor with B cell pro-apoptotic activity. Following cellular uptake, acadesine is phosphorylated to AICA ribotide (ZMP), which mimics 5'-adenosine monophosphate (AMP). Both AMP-activated protein kinase (AMPK) and AMPK kinase (AMPKK) are activated by ZMP, which appears to be necessary for the induction of apoptosis. Acadesine-induced apoptosis also appears to require cytochrome c release from mitochondria and caspase activation and is p53-independent. However, the exact mechanism of acadesine-induced apoptosis is unknown. T cells are significantly less susceptible than B cells to acadesine-induced apoptosis. AMPK regulates several cellular systems including the cellular uptake of glucose, the beta-oxidation of fatty acids, protein synthesis, and the biogenesis of glucose transporter 4 (GLUT4) and mitochondria.
A complex oligosaccharide used as a hypoglycemic agent in diabetes management. Acarbose inhibits enzymes required in catabolism of carbohydrates, specifically pancreatic alpha-amylase, which hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, and the membrane-bound intestinal alpha-glucosidases, which hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. When acarbose is orally administered, less digestion of complex carbohydrates occur and less glucose is absorbed in the small intestine, thereby producing a smaller rise in postprandial blood glucose levels after a carbohydrate load.
(Other name for: isotretinoin)
acelullar cadaveric dermal matrix
A human dermis-derived allograft material. Acellular cadaveric dermal matrix (ACDM) is derived from human cadaveric dermis from which the epidermis, all viable cells and major histocompatibility class (MHC) II antigens have been removed to minimize alloimmunogenicity, while the dermal collagen matrix is preserved. ACDM may placed over wounds to aid as a substitute for skin when necessary such as for surgical reconstruction or for protection against wound exposure and breakdown and wound infection.
(Other name for: perindopril erbumine)
A p-aminophenol derivative with analgesic and antipyretic activities. Although the exact mechanism through which acetaminophen exert its effects has yet to be fully determined, acetaminophen may inhibit the nitric oxide (NO) pathway mediated by a variety of neurotransmitter receptors including N-methyl-D-aspartate (NMDA) and substance P, resulting in elevation of the pain threshold. The antipyretic activity may result from inhibition of prostaglandin synthesis and release in the central nervous system (CNS) and prostaglandin-mediated effects on the heat-regulating center in the anterior hypothalamus.
A synthetic N-acetyl derivative of the endogenous amino acid L-cysteine, a precursor of the antioxidant enzyme glutathione. Acetylcysteine regenerates liver stores of glutathione. This agent also reduces disulfide bonds in mucoproteins, resulting in liquification of mucus. Some evidence suggests that acetylcysteine may exert an anti-apoptotic effect due to its antioxidant activity, possibly preventing cancer cell development or growth. In addition, acetylcysteine has inhibited viral stimulation by reactive oxygen intermediates, thereby producing antiviral activity in HIV patients.
An orally administered non-steroidal antiinflammatory agent. Acetylsalicylic acid binds to and acetylates serine residues in cyclooxygenases, resulting in decreased synthesis of prostaglandin, platelet aggregation, and inflammation. This agent exhibits analgesic, antipyretic, and anticoagulant properties.
(Other name for: tetracycline hydrochloride)
(Other name for: rabeprazole sodium)
An orally-active metabolite of the synthetic aromatic retinoic acid agent etretinate with potential antineoplastic, chemopreventive, anti-psoratic, and embryotoxic properties. Acitretin activates nuclear retinoic acid receptors (RAR), resulting in induction of cell differentiation, inhibition of cell proliferation, and inhibition of tissue infiltration by inflammatory cells. This agent may also inhibit tumor angiogenesis.
A modified amino acid and structural analog of glutamine. Acivicin inhibits glutamine amidotransferases in the purine and pyrimidine biosynthetic pathways, thereby inhibiting tumor growth in cell lines dependent on glutamine metabolism.
An oligosaccharide anthracycline antineoplastic antibiotic isolated from the bacterium Streptomyces galilaeus. Aclarubicin intercalates into DNA and interacts with topoisomerases I and II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. Aclarubicin is antagonistic to other agents that inhibit topoisomerase II, such as etoposide, teniposide and amsacrine. This agent is less cardiotoxic than doxorubicin and daunorubicin.
(Other name for: diethylstilbestrol)
(Other name for: nimustine)
A synthetic imidazoquinoline with antineoplastic activity. Acodazole intercalates into DNA, resulting in disruption of DNA replication. Use of this agent has been associated with significant cardiotoxicity.
A tricyclic acridine-based (or carboxamide-based) drug with dual topoisomerase inhibitor and potential antineoplastic activities. Acridine carboxamide inhibits both topoisomerases I and II and intercalates into DNA, resulting in DNA damage, the disruption of DNA repair and replication, the inhibition of RNA and protein synthesis, and cell death.
(Other name for: Haemophilus influenzae b vaccine)
(Other name for: ursodiol)
(Other name for: recombinant interferon gamma)
(Other name for: masoprocol)
actinium Ac 225 lintuzumab
A radioimmunoconjugate consisting of the humanized monoclonal antibody lintuzumab conjugated to the alpha-emitting radioisotope actinium Ac 225 with potential antineoplastic activity. The monoclonal antibody moiety of actinium Ac 225 lintuzumab specifically binds to the cell surface antigen CD33 antigen, delivering a cytotoxic dose of alpha radiation to cells expressing CD33. CD33 is a cell surface antigen expressed on normal non-pluripotent hematopoietic stem cells and overexpressed on myeloid leukemia cells.
(Other name for: fentanyl citrate)
(Other name for: alteplase)
(Other name for: estradiol/norethindrone acetate tablet)
(Other name for: IH636 grape seed proanthocyanidin extract)
(Other name for: risedronate sodium)
(Other name for: pioglitazone hydrochloride)
A synthetic analog of the purine nucleoside, guanosine, with potent antiviral activity against herpes simplex viruses type 1 and 2, varicella-zoster virus and other viruses. After conversion in vivo to the active metabolite acyclovir triphosphate, acyclovir competitively inhibits viral DNA polymerase, incorporates into and terminates the growing viral DNA chain, and inactivates viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the thymidine kinase of HSV.
The sodium salt form of acyclovir, a synthetic analog of the purine nucleoside, guanosine, with potent antiviral activity against herpes simplex viruses type 1 and 2, varicella-zoster virus and other viruses. After conversion in vivo to the active metabolite acyclovir triphosphate, acyclovir competitively inhibits viral DNA polymerase, incorporates into and terminates the growing viral DNA chain, and inactivates viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the thymidine kinase of HSV.
(Other name for: dapsone gel, 5%)
A replication incompetent adenoviral vector encoding the full-length tumor suppressor gene Reduced Expression in Immortalized Cells (REIC or DKK3) (ad-REIC/DKK3), with potential antineoplastic activity. Upon intratumoral injection, tumor cells express REIC/DKK3 protein. This may result in the activation of c-Jun-NH2-kinase (JNK) and ultimately apoptosis via Bcl2 suppression and caspase-3 activation. Expression of REIC/DKK3 is normal in healthy cells but reduced or absent in many cancer cells; Forced overexpression of REIC/DKK3 in cancer cells may lead to an induction of tumor cell apoptosis and reduction of tumor cell growth while sparing normal, healthy cells naturally expressing endogenous REIC/DKK3.
A cancer vaccine consisting of a recombinant adenoviral vector encoding the tumor-associated antigen (TAA) human MUC-1 (hMUC-1) linked to the extracellular domain (ecd) of the co-stimulatory molecule CD40 ligand (CD40L) and an adenovirus signal sequence that encodes a secretory signal peptide (Ad-sig) with potential immunostimulating and antineoplastic activities. Due to the presence of the secretory signal peptide expressed by Ad-sig in the vaccine construct, transfected cells may secrete a fusion protein composed of hMUC-1 and the CD40L ecd. The CD40L moiety part of the fusion protein binds to CD40 receptors on dendritic cells (DCs). Subsequently, DCs may be activated and migrate, T-cells may expand, and a cytotoxic T lymphocyte (CTL) response against tumor cells that overexpress hMUC-1 may follow. MUC-1 is a hypoglycosylated TAA overexpressed by epithelial cancer cells.
A recombinant type 5 adenovirus (Ad5), encoding the gene for the human sodium-iodide symporter (NIS) linked to the cytomegalovirus (CMV) promoter, with potential gene transfection activity. Upon intratumoral injection, Ad5-CMV-NIS is taken up by tumor cells, resulting in the cellular expression of NIS. Subsequently, orally administered iodine 131 is taken up by NIS-expressing tumor cells, which may result in the selective accumulation of a cytotoxic dose of beta and gamma radiation in non-thyroidal tumor cells, sparing adjacent normal tissue. NIS, an intrinsic membrane glycoprotein, is an ion pump that actively transports iodide into cells which concentrate iodine; in addition to thyroid epithelial cells, it is found in non-thyroidal tissues including the salivary glands, the gastric mucosa, and lactating mammary glands.
A second generation, replication-competent adenovirus type 5 containing a yeast cytosine deaminase(yCD)/mutant sr39 herpes simplex virus thymidine kinase fusion (yCD/mutTKsr39) gene and the 11.6 kDa adenovirus death protein (ADP) gene with potential oncolytic activity. Upon intratumoral administration and transduction of Ad5-yCD/mutTK(SR39)rep-ADP into tumor cells and subsequent expression of cytosine deaminase and viral thymidine kinase, administered prodrugs 5-fluorocytosine (5-FC) and ganciclovir are converted into their respective metabolites 5-fluorouracil (5-FU) and ganciclovir-5-monophosphate (ganciclovir-MP); 5-FU is subsequently metabolized to cytotoxic active metabolites 5-fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (F-dUMP); ganciclovir-TP subsequently is converted by mammalian thymidine kinase to cytotoxic ganciclovir-triphosphate (ganciclovir -TP). Tumor cells adjacent to tumor cells transduced with this agent may be killed through a "bystander effect". ADP may enhance spread and oncolytic activity of replication-competent adenoviruses. In addition to its oncolytic activity, Ad5-yCD/mutTK(SR39)rep-ADP may exhibit radiosensitizing activity.
An RGD-4C–modified, infectivity-enhanced, bicistronic type 5 adenovirus expressing herpes simplex virus thymidine kinase (HSV-tk) gene, a therapeutic suicide gene, and the somatostatin receptor type 2 (SSTR2) gene with potential antineoplastic activity. Modification with the double cyclic peptide RGD-4C allows the virus to bind to cellular integrins, frequently expressed on the surfaces of ovarian cancer cells, instead of the coxsackie and adenovirus (CAR) receptor, which is often nonfunctional in ovarian cancer cells. Upon intratumoral administration, Ad5.SSTR/TK.RGD transfects tumor cells and expresses the HSV-tk gene. After subsequent administration of a synthetic acyclic guanosine analogue prodrug like ganciclovir (GCV), expressed HSV-tk phosphorylates and activates the prodrug, which may result in inhibition of DNA synthesis and apoptosis in HSV-tk-expressing cancer cells. Additionally, as a bystander effect, adjacent non-transfected cells may be killed by the activated antiviral drug. SSTR2 expression allows imaging of gene transfer into tumor cells using a radiolabeled somatostatin analogue.
A replication-defective adenoviral-CMV vector that encodes a wild-type p53 gene. Ad5CMV-p53 induces tumor cells that have been transfected with the vector to produce wild-type p53, a tumor suppressor gene that is deleted or mutated in a significant number of cancers. In transfected tumor cells, the wild-type p-53 gene product exerts an antitumor effect by blocking cell cycle progression at the G1/S regulation point, activating DNA repair proteins in the presence of DNA damage, and initiating apoptosis when DNA damage is irreparable.
Ad5F35-LMP1/LMP2-transduced autologous dendritic cells
Autologous dendritic cells (DCs) transduced with the replication-deficient adenoviral vector Ad5F53 encoding the Epstein-Barr virus (EBV) transmembrane latent membrane proteins 1 and 2 (LMP1/LMP2) with potential immunostimulatory activity. Vaccination with Ad5F35-LMP1/LMP2-transduced autologous dendritic cells may stimulate a specific cytotoxic T-lymphocyte (CTL) response against LMP1- and LMP2-expressing tumor positive cells, resulting in tumor cell lysis and inhibition of tumor cell proliferation. LMP1 and LMP2 are expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkin disease.
(Other name for: methadone hydrochloride)
(Other name for: doxepin hydrochloride)
(Other name for: dextroamphetamine-amphetamine)
(Other name for: dextroamphetamine-amphetamine)
An induction chemotherapy regimen consisting of cytarabine (Ara-C), daunorubicin and etoposide used for the treatment of childhood acute myeloid leukemia. (NCI Thesaurus)
A recombinant human IgG1 monoclonal antibody (MoAb) directed against the tumor associated antigen (TAA) epithelial cell adhesion molecule (EpCAM) with potential antitumor activity. Adecatumumab binds to EpCAM, which may result in antibody-dependent cellular cytotoxicity (ADCC) directed against EpCAM-expressing tumor cells. EpCAM (CD326), a cell surface protein upregulated on many tumor cell types, promotes the proliferation, migration and invasiveness of tumor cells; for some cancers, overexpression has been correlated with decreased survival.