An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I.
Compounds that inhibit the activity of DNA TOPOISOMERASES.
A plant genus of the family NYSSACEAE (sometimes classified in the CORNACEAE family). It is a source of CAMPTOTHECIN.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.
Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.
Organic compounds that contain silicon as an integral part of the molecule.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The Madder plant family of the order Rubiales, subclass Asteridae, class Magnoliopsida includes important medicinal plants that provide QUININE; IPECAC; and COFFEE. They have opposite leaves and interpetiolar stipules.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
The conformation, properties, reaction processes, and the properties of the reactions of carbon compounds.
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.
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.
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.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
This line KB is now known to be a subline of the ubiquitous KERATIN-forming tumor cell line HeLa. It was originally thought to be derived from an epidermal carcinoma of the mouth, but was subsequently found, based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting, to have been established via contamination by HELA CELLS. The cells are positive for keratin by immunoperoxidase staining. KB cells have been reported to contain human papillomavirus18 (HPV-18) sequences.
DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.
A cell line derived from cultured tumor cells.
Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.
An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
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.
A reaction that severs one of the covalent sugar-phosphate linkages between NUCLEOTIDES that compose the sugar phosphate backbone of DNA. It is catalyzed enzymatically, chemically or by radiation. Cleavage may be exonucleolytic - removing the end nucleotide, or endonucleolytic - splitting the strand in two.
The process by which a DNA molecule is duplicated.
A subclass of iridoid compounds that include a glucoside moiety, usually found at the C-1 position.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
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.
Leukemia L1210 is a designation for a specific murine (mouse) leukemia cell line that was originally isolated from a female mouse with an induced acute myeloid leukemia, which is widely used as a model in cancer research, particularly for in vivo studies of drug efficacy and resistance.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Pyrido-CARBAZOLES originally discovered in the bark of OCHROSIA ELLIPTICA. They inhibit DNA and RNA synthesis and have immunosuppressive properties.
A physiochemical process which occurs in a wide range of organisms which unlike BASAL METABOLISM is not required for or essential to short-term survivability but to long-term general well-being of the organism.
Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
The study of the structure, preparation, properties, and reactions of carbon compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
DNA present in neoplastic tissue.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
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.
Established cell cultures that have the potential to propagate indefinitely.
A family of fused-ring hydrocarbons isolated from coal tar that act as intermediates in various chemical reactions and are used in the production of coumarone-indene resins.
Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A type of MONOTERPENES, derived from geraniol. They have the general form of cyclopentanopyran, but in some cases, one of the rings is broken as in the case of secoiridoid. They are different from the similarly named iridals (TRITERPENES).
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
Compounds that inhibit cell production of DNA or RNA.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals and causes visceral leishmaniasis (LEISHMANIASIS, VISCERAL). The sandfly genera Phlebotomus and Lutzomyia are the vectors.
Colorless, odorless crystals that are used extensively in research laboratories for the preparation of polyacrylamide gels for electrophoresis and in organic synthesis, and polymerization. Some of its polymers are used in sewage and wastewater treatment, permanent press fabrics, and as soil conditioning agents.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.
The action of a drug in promoting or enhancing the effectiveness of another drug.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A plant genus of the family CELASTRACEAE. The leafy stems of khat are chewed by some individuals for stimulating effect. Members contain ((+)-norpseudoephedrine), cathionine, cathedulin, cathinine & cathidine.
Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
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.
Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Tumors or cancer of the COLON.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
An RNA polymerase II transcriptional inhibitor. This compound terminates transcription prematurely by selective inhibition of RNA synthesis. It is used in research to study underlying mechanisms of cellular regulation.
An anthracenedione-derived antineoplastic agent.
A group of FLAVONOIDS characterized with a 4-ketone.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
The cells in the granulocytic series that give rise to mature granulocytes (NEUTROPHILS; EOSINOPHILS; and BASOPHILS). These precursor cells include myeloblasts, promyelocytes, myelocytes and metamyelocytes.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
The rate dynamics in chemical or physical systems.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.

Novel selective inhibitors for human topoisomerase I, BM2419-1 and -2 derived from saintopin. (1/2758)

Compounds BM2419-1 and -2 were isolated from a culture broth of a fungus Paecilomyces sp. BM2419. It was shown that these novel compounds were artifacts derived from saintopin, a dual inhibitor of topoisomerase I and II by independent processes. In the human topoisomerase I inhibition assay using the recombinant Saccharomyces cerevisiae, BM2419-1 and -2 inhibited selectively the yeast growth dependent on human topoisomerase I induction with IC50 values of 0.3 ng/ml and 6.0 ng/ml, respectively.  (+info)

Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes. (2/2758)

Replication protein A (RPA) is a DNA single-strand binding protein essential for DNA replication, recombination and repair. In human cells treated with the topoisomerase inhibitors camptothecin or etoposide (VP-16), we find that RPA2, the middle-sized subunit of RPA, becomes rapidly phosphorylated. This response appears to be due to DNA-dependent protein kinase (DNA-PK) and to be independent of p53 or the ataxia telangiectasia mutated (ATM) protein. RPA2 phosphorylation in response to camptothecin required ongoing DNA replication. Camptothecin itself partially inhibited DNA synthesis, and this inhibition followed the same kinetics as DNA-PK activation and RPA2 phosphorylation. DNA-PK activation and RPA2 phosphorylation were prevented by the cell-cycle checkpoint abrogator 7-hydroxystaurosporine (UCN-01), which markedly potentiates camptothecin cytotoxicity. The DNA-PK catalytic subunit (DNA-PKcs) was found to bind RPA which was replaced by the Ku autoantigen upon camptothecin treatment. DNA-PKcs interacted directly with RPA1 in vitro. We propose that the encounter of a replication fork with a topoisomerase-DNA cleavage complex could lead to a juxtaposition of replication fork-associated RPA and DNA double-strand end-associated DNA-PK, leading to RPA2 phosphorylation which may signal the presence of DNA damage to an S-phase checkpoint mechanism. KEYWORDS: camptothecin/DNA damage/DNA-dependent protein kinase/RPA2 phosphorylation  (+info)

The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin. (3/2758)

Camptothecin is an antitumor agent that kills cells by converting DNA topoisomerase I into a DNA-damaging poison. Although camptothecin derivatives are now being used to treat tumors in a variety of clinical protocols, the cellular factors that influence sensitivity to the drug are only beginning to be understood. We report here that two genes required for sister chromatid cohesion, TRF4 and MCD1/SCC1, are also required to repair camptothecin-mediated damage to DNA. The hypersensitivity to camptothecin in the trf4 mutant does not result from elevated expression of DNA topoisomerase I. We show that Trf4 is a nuclear protein whose expression is cell cycle-regulated at a post-transcriptional level. Suppression of camptothecin hypersensitivity in the trf4 mutant by gene overexpression resulted in the isolation of three genes: another member of the TRF4 gene family, TRF5, and two genes that may influence higher order chromosome structure, ZDS1 and ZDS2. We have isolated and sequenced two human TRF4 family members, hTRF4-1 and hTRF4-2. The hTRF4-1 gene maps to chromosome 5p15, a region of frequent copy number alteration in several tumor types. The evolutionary conservation of TRF4 suggests that it may also influence mammalian cell sensitivity to camptothecin.  (+info)

Fractionated administration of irinotecan and cisplatin for treatment of lung cancer: a phase I study. (4/2758)

A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose escalation of CPT-11 to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CPT-11 at escalated dose was feasible and could improve the treatment outcome. Twenty-four previously untreated patients with unresectable non-small-cell lung cancer (NSCLC) or extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP was fixed at 60 mg m(-2) and given by 1-h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an increase of 10 mg m(-2). The maximally tolerated dose of CPT-11 was determined as 60 mg m(-2) because grade 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limiting toxicity. The objective response rates were 76% for NSCLC and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m(-2) and 60 mg m(-2) respectively.  (+info)

Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model. (5/2758)

6-Hydroxymethylacylfulvene (MGI-114) is a semisynthetic analogue of the toxin illudin S, a product of the Omphalotus mushroom. MGI-114 induces cytotoxicity in a variety of solid tumors in vivo, including the refractory HT29 human colon cancer xenograft. In this study, the potential application of MGI-114 in the treatment of colon cancer was further explored by evaluating the activity of MGI-114 in combination with irinotecan (CPT-11) and 5-fluorouracil (5FU). Groups of 9 nude mice bearing HT29 xenografts were treated with either single agent MGI-114, CPT-11, or 5FU, or MGI-114 in combination with CPT-11 or 5FU. MGI-114 was administered at doses of 3.5 and 7 mg/kg i.p. daily on days 1 through 5, and CPT-11 and 5FU were administered at doses of 50 and 100 mg/kg i.p. on days 1, 12, and 19. In the single agent studies, MGI-114, CPT-11, and 5FU all resulted in decreased final tumor weights compared with vehicle-treated controls (P<0.05), but only MGI-114 at 7 mg/kg produced partial responses. When MGI-114 at 3.5 mg/kg was combined with CPT-11, significant decrements in final tumor weights occurred compared with monotherapy with the same doses of MGI-114 and CPT-11 (P< or =0.001). Also, administration of the low-dose combination (MGI-114 at 35 mg/kg and CPT-11 at 50 mg/kg) resulted in final tumor weights similar to those achieved after administration of high-dose MGI-114 as a single agent. Moreover, the combination of MGI-114 and CPT-11 produced partial responses in nearly all of the animals, with some animals achieving complete responses. The outcome with the combination of MGI-114 and 5FU was less striking, with fewer partial responses and no complete responses. These results suggest enhanced activity when MGI-114 is combined with CPT-11, and clinical trials to further evaluate this combination regimen are planned.  (+info)

Combined irinotecan and oxaliplatin plus granulocyte colony-stimulating factor in patients with advanced fluoropyrimidine/leucovorin-pretreated colorectal cancer. (6/2758)

PURPOSE: To evaluate the efficacy and tolerance of combined irinotecan and oxaliplatin in patients with advanced colorectal cancer pretreated with leucovorin-modulated fluoropyrimidines. PATIENTS AND METHODS: Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after discontinuing palliative chemotherapy with fluoropyrimidines/leucovorin, were enrolled onto this study. Treatment consisted of oxaliplatin 85 mg/m2 on days 1 + 15 and irinotecan 80 mg/m2 on days 1 + 8 + 15 every 4 weeks. Depending on the absolute neutrophil counts (ANC) on the day of scheduled chemotherapeutic drug administration, a 5-day course of granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d was given. RESULTS: The overall response rate was 42% for all 36 assessable patients (95% confidence interval, 26% to 59%), including two complete remissions (6%). Thirteen additional patients (36%) had stable disease, and only eight (22%) progressed. The median time to treatment failure was 7.5 months (range, 1 to 13.5+ months). After a median follow-up time of 14 months, 19 patients (53%) are still alive. Hematologic toxicity was commonly observed, although according to the ANC-adapted use of G-CSF (in 31 patients during 81 of 174 courses), it was generally mild: grade 3 and 4 granulocytopenia occurred in only five and two cases, respectively. The most frequent nonhematologic adverse reactions were nausea/emesis and diarrhea, which were rated severe in 17% and 19%, respectively. CONCLUSION: Our data suggest that the combination of irinotecan and oxaliplatin with or without G-CSF has substantial antitumor activity in patients with progressive fluoropyrimidine/leucovorin-pretreated colorectal cancer. Overall toxicity was modest, with gastrointestinal symptoms constituting the dose-limiting side effects. Further evaluation of this regimen seems warranted.  (+info)

Phase I study of a weekly schedule of irinotecan, high-dose leucovorin, and infusional fluorouracil as first-line chemotherapy in patients with advanced colorectal cancer. (7/2758)

PURPOSE: To determine the maximum-tolerated dose (MTD) of a weekly schedule of irinotecan (CPT-11), leucovorin (LV), and a 24-hour infusion of fluorouracil (5-FU24h) as first-line chemotherapy in advanced colorectal cancer and to assess preliminary data on the antitumor activity. PATIENTS AND METHODS: Twenty-six patients with measurable metastatic colorectal cancer were entered onto this phase I study. In the first six dose levels, fixed doses of CPT-11 (80 mg/m2) and LV (500 mg/m2) in combination with escalated doses of 5-FU24h ranging from 1.8 to 2.6 g/m2 were administered on a weekly-times-four (dose levels 1 to 4) or weekly-times-six (dose levels 5 to 6) schedule. The dose of CPT-11 was then increased to 100 mg/m2 (dose level 7). RESULTS: Seventy-nine cycles of 5-FU24h/LV with CPT-11 were administered in an outpatient setting. No dose-limiting toxicities were observed during the first cycle at dose levels 1 to 6, but diarrhea of grade 4 (National Cancer Institute common toxicity criteria) was observed in three patients after multiple treatment cycles. Other nonhematologic and hematologic side effects, specifically alopecia and neutropenia, did not exceed grade 2. With the escalation of CPT-11 to 100 mg/m2 (dose level 7), diarrhea of grade 3 or higher was observed in four of six patients during the first cycle; thus, the MTD was achieved. Sixteen of 25 response-assessable patients (64%; 95% confidence interval, 45% to 83%) achieved an objective response. CONCLUSION: The recommended doses for further studies are CPT-11 80 mg/m2, LV 500 mg/m2, and 5-FU24h 2.6 g/m2 given on a weekly-times-six schedule followed by a 1-week rest period. The addition of CPT-11 to 5-FU24h/LV seems to improve the therapeutic efficacy in terms of tumor response with manageable toxicity.  (+info)

Cyclosporine inhibited calcium-mediated apoptosis of HL-60 cells. (8/2758)

AIM: To study the effects of cyclosporine (Cyc) on apoptosis of HL-60 cells. METHODS: Apoptotic cells induced by harringtonine (Har), camptothecin (Cam), or calcimycin (Cal), thapsigargin (Tha) were identified with DNA electrophoresis, morphology, and flow cytometry. Relative [Ca2+]i alteration of apoptotic HL-60 cells were determined with flow cytometry. RESULTS: Cal 1 mg.L-1 or Tha 0.5 mg.L-1 induced apoptosis of HL-60 cells. This effect was inhibited by nontoxic concentration of Cyc 1 mg.L-1. Cyc did not inhibit Har- or Cam-induced apoptosis of HL-60 cells. Both Cal and Tha increased intracellular calcium, whereas Har or Cam did not. CONCLUSION: Cyc inhibited apoptosis only induced by calcium increasement in HL-60 cells. The mechanism of apoptosis induced by Cal or Tha was different from that by Har or Cam.  (+info)

Camptothecin is a topoisomerase I inhibitor, which is a type of chemotherapeutic agent used in cancer treatment. It works by interfering with the function of an enzyme called topoisomerase I, which helps to uncoil DNA during cell division. By inhibiting this enzyme, camptothecin prevents the cancer cells from dividing and growing, ultimately leading to their death.

Camptothecin is found naturally in the bark and stem of the Camptotheca acuminata tree, also known as the "happy tree," which is native to China. It was first isolated in 1966 and has since been developed into several synthetic derivatives, including irinotecan and topotecan, which are used clinically to treat various types of cancer, such as colon, lung, and ovarian cancers.

Like other chemotherapeutic agents, camptothecin can have significant side effects, including nausea, vomiting, diarrhea, and myelosuppression (suppression of bone marrow function). It is important for patients receiving camptothecin-based therapies to be closely monitored by their healthcare team to manage these side effects effectively.

Topoisomerase I inhibitors are a class of anticancer drugs that work by inhibiting the function of topoisomerase I, an enzyme that plays a crucial role in the relaxation and replication of DNA. By inhibiting this enzyme's activity, these drugs interfere with the normal unwinding and separation of DNA strands, leading to DNA damage and ultimately cell death. Topoisomerase I inhibitors are used in the treatment of various types of cancer, including colon, small cell lung, ovarian, and cervical cancers. Examples of topoisomerase I inhibitors include camptothecin, irinotecan, and topotecan.

DNA topoisomerases are enzymes that modify the topological structure of DNA by regulating the number of twists or supercoils in the double helix. There are two main types of DNA topoisomerases: type I and type II.

Type I DNA topoisomerases function by cutting one strand of the DNA duplex, allowing the uncut strand to rotate around the break, and then resealing the break. This process can relieve both positive and negative supercoiling in DNA, as well as introduce single-stranded breaks into the DNA molecule.

Type I topoisomerases are further divided into three subtypes: type IA, type IB, and type IC. These subtypes differ in their mechanism of action and the structure of the active site tyrosine residue that makes the transient break in the DNA strand.

Overall, DNA topoisomerases play a crucial role in many cellular processes involving DNA, including replication, transcription, recombination, and chromosome segregation. Dysregulation of these enzymes has been implicated in various human diseases, including cancer and genetic disorders.

Antineoplastic agents, phytogenic, also known as plant-derived anticancer drugs, are medications that are derived from plants and used to treat cancer. These agents have natural origins and work by interfering with the growth and multiplication of cancer cells, helping to slow or stop the spread of the disease. Some examples of antineoplastic agents, phytogenic include paclitaxel (Taxol), vincristine, vinblastine, and etoposide. These drugs are often used in combination with other treatments such as surgery, radiation therapy, and other medications to provide a comprehensive approach to cancer care.

Topotecan is a chemotherapeutic agent, specifically a topoisomerase I inhibitor. It is a semi-synthetic derivative of camptothecin and works by interfering with the function of topoisomerase I, an enzyme that helps to relax supercoiled DNA during transcription and replication. By inhibiting this enzyme, topotecan causes DNA damage and apoptosis (programmed cell death) in rapidly dividing cells, such as cancer cells. It is used in the treatment of various types of cancer, including small cell lung cancer and ovarian cancer.

Topoisomerase inhibitors are a class of anticancer drugs that work by interfering with the function of topoisomerases, which are enzymes responsible for relaxing supercoiled DNA during processes such as replication and transcription. Topoisomerase I inhibitors selectively bind to and stabilize the cleavage complex formed between topoisomerase I and DNA, preventing the relegation of the broken DNA strand and resulting in DNA damage and cell death. Examples include irinotecan and topotecan. Topoisomerase II inhibitors, on the other hand, bind to and stabilize the cleavage complex formed between topoisomerase II and DNA, leading to double-stranded DNA breaks and cell death. Examples include doxorubicin, etoposide, and mitoxantrone. These drugs are used in the treatment of various types of cancer.

Camptotheca is a genus of trees in the family Nyssaceae, native to China and Tibet. It is also known as "camptotheca acuminata" or "the Chinese happy tree." The bark and leaves of this tree contain camptothecin, a compound that has been studied for its potential anti-cancer properties. Camptothecin and its derivatives are used in the treatment of various types of cancer, including colon, ovarian, and small cell lung cancer.

DNA damage refers to any alteration in the structure or composition of deoxyribonucleic acid (DNA), which is the genetic material present in cells. DNA damage can result from various internal and external factors, including environmental exposures such as ultraviolet radiation, tobacco smoke, and certain chemicals, as well as normal cellular processes such as replication and oxidative metabolism.

Examples of DNA damage include base modifications, base deletions or insertions, single-strand breaks, double-strand breaks, and crosslinks between the two strands of the DNA helix. These types of damage can lead to mutations, genomic instability, and chromosomal aberrations, which can contribute to the development of diseases such as cancer, neurodegenerative disorders, and aging-related conditions.

The body has several mechanisms for repairing DNA damage, including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. However, if the damage is too extensive or the repair mechanisms are impaired, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of potentially harmful mutations.

Teniposide is a synthetic podophyllotoxin derivative, which is an antineoplastic agent. It works by interfering with the DNA synthesis and function of cancer cells, leading to cell cycle arrest and apoptosis (programmed cell death). Teniposide is primarily used in the treatment of acute lymphoblastic leukemia (ALL) and other malignancies in children. It is often administered through intravenous infusion and is typically used in combination with other chemotherapeutic agents.

The medical definition of Teniposide can be stated as:

Teniposide, chemically known as (4'-demethylepipodophyllotoxin 9-[4,6-O-(R)-benzylidene-α-L-glucopyranoside]), is a semi-synthetic podophyllotoxin derivative with antineoplastic activity. It inhibits DNA topoisomerase II, leading to the formation of DNA-topoisomerase II cleavable complexes, G2 arrest, and apoptosis in cancer cells. Teniposide is primarily used in the treatment of acute lymphoblastic leukemia (ALL) and other malignancies in children, often administered through intravenous infusion and typically used in combination with other chemotherapeutic agents.

Topoisomerase II inhibitors are a class of anticancer drugs that work by interfering with the enzyme topoisomerase II, which is essential for DNA replication and transcription. These inhibitors bind to the enzyme-DNA complex, preventing the relaxation of supercoiled DNA and causing DNA strand breaks. This results in the accumulation of double-stranded DNA breaks, which can lead to apoptosis (programmed cell death) in rapidly dividing cells, such as cancer cells. Examples of topoisomerase II inhibitors include etoposide, doxorubicin, and mitoxantrone.

Organosilicon compounds are a class of chemical compounds that contain at least one organic group (a group of atoms composed mainly of carbon and hydrogen) bonded to a silicon atom. The organic group can be an alkyl group, aryl group, or any other group that is derived from a hydrocarbon.

The term "organosilicon" is used to describe the covalent bond between carbon and silicon atoms, which is a type of bond known as a "sigma bond." This bond is formed by the overlap of atomic orbitals between the carbon and silicon atoms. The resulting organosilicon compound can have a wide range of physical and chemical properties, depending on the nature of the organic group and the number of such groups attached to the silicon atom.

Organosilicon compounds are widely used in various industries, including electronics, coatings, adhesives, and pharmaceuticals. They are also used as intermediates in the synthesis of other chemical compounds. Some common examples of organosilicon compounds include silicones, which are polymers that contain repeating units of siloxane (Si-O-Si) bonds, and organofunctional silanes, which are used as coupling agents to improve the adhesion of materials to surfaces.

Antineoplastic agents are a class of drugs used to treat malignant neoplasms or cancer. These agents work by inhibiting the growth and proliferation of cancer cells, either by killing them or preventing their division and replication. Antineoplastic agents can be classified based on their mechanism of action, such as alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapy agents.

Alkylating agents work by adding alkyl groups to DNA, which can cause cross-linking of DNA strands and ultimately lead to cell death. Antimetabolites interfere with the metabolic processes necessary for DNA synthesis and replication, while topoisomerase inhibitors prevent the relaxation of supercoiled DNA during replication. Mitotic inhibitors disrupt the normal functioning of the mitotic spindle, which is essential for cell division. Targeted therapy agents are designed to target specific molecular abnormalities in cancer cells, such as mutated oncogenes or dysregulated signaling pathways.

It's important to note that antineoplastic agents can also affect normal cells and tissues, leading to various side effects such as nausea, vomiting, hair loss, and myelosuppression (suppression of bone marrow function). Therefore, the use of these drugs requires careful monitoring and management of their potential adverse effects.

Rubiaceae is not a medical term, but a taxonomic category in botany. It refers to the family of flowering plants that includes more than 13,500 species, distributed across approximately 600 genera. Some well-known members of this family include coffee (Coffea arabica), gardenias (Gardenia jasminoides), and madder (Rubia tinctorum).

In a medical context, certain plants from the Rubiaceae family have been used in traditional medicine for various purposes. For example:

* Coffee (Coffea arabica) beans are used to prepare caffeinated beverages that can help with alertness and concentration.
* Gardenia fruits and flowers have been used in traditional Chinese medicine to treat anxiety, insomnia, and inflammation.
* Madder root (Rubia tinctorum) has been used as a dye and in traditional medicine to treat skin conditions and digestive disorders.

However, it's important to note that the medicinal use of plants from this family should be based on scientific evidence and under the guidance of healthcare professionals, as some of these plants can have side effects or interact with medications.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

Aphidicolin is an antimicrotubule agent that is specifically a inhibitor of DNA polymerase alpha. It is an antibiotic that is produced by the fungus Cephalosporium aphidicola and is used in research to study the cell cycle and DNA replication. In clinical medicine, it has been explored as a potential anticancer agent, although its use is not currently approved for this indication.

I believe there may be some confusion in your question as "Organic chemistry phenomena" is a broad term and not a medical definition. However, I can provide you with an explanation of organic chemistry phenomena in a general context.

Organic chemistry is the study of carbon-containing compounds, their synthesis, reactions, properties, and structures. The term "organic" was originally used to describe biological materials, but now it refers to any compound that contains carbon atoms bonded to hydrogen atoms, except for some simple oxides, sulfides, and halides.

Organic chemistry phenomena encompass a wide range of processes and events related to organic compounds. These can include:

1. Structural properties: Understanding the arrangement of atoms in organic molecules and how they influence chemical behavior and reactivity.
2. Stereochemistry: The study of three-dimensional spatial arrangements of atoms in organic molecules, which can significantly impact their properties and biological activity.
3. Functional groups: Recognizing and understanding the behavior of specific groupings of atoms within organic molecules that determine their chemical reactivity.
4. Reaction mechanisms: Investigating and describing the step-by-step processes by which organic reactions occur, including the movement of electrons, formation and breaking of bonds, and energy changes.
5. Synthetic methodologies: Developing strategies and techniques for creating complex organic molecules from simpler precursors, often involving multiple steps and protecting group strategies.
6. Physical properties: Examining how factors such as molecular weight, polarity, solubility, and melting/boiling points affect the behavior of organic compounds in various conditions.
7. Spectroscopic analysis: Utilizing techniques like NMR (Nuclear Magnetic Resonance), IR (Infrared) spectroscopy, and mass spectrometry to analyze the structure and composition of organic molecules.
8. Biochemistry and medicinal chemistry: Exploring how organic compounds interact with biological systems, including drug design, development, and delivery.

While not a medical definition per se, understanding organic chemistry phenomena is crucial for many areas within medicine, such as pharmaceutical research, toxicology, and biochemistry.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

Drug screening assays for antitumor agents are laboratory tests used to identify and evaluate the effectiveness of potential drugs or compounds that can inhibit the growth of tumor cells or induce their death. These assays are typically performed in vitro (in a test tube or petri dish) using cell cultures of various types of cancer cells.

The assays measure different parameters such as cell viability, proliferation, apoptosis (programmed cell death), and cytotoxicity to determine the ability of the drug to kill or inhibit the growth of tumor cells. The results of these assays can help researchers identify promising antitumor agents that can be further developed for clinical use in cancer treatment.

There are different types of drug screening assays for antitumor agents, including high-throughput screening (HTS) assays, which allow for the rapid and automated testing of a large number of compounds against various cancer cell lines. Other types of assays include phenotypic screening assays, target-based screening assays, and functional screening assays, each with its own advantages and limitations.

Overall, drug screening assays for antitumor agents play a critical role in the development of new cancer therapies by providing valuable information on the activity and safety of potential drugs, helping to identify effective treatments and reduce the time and cost associated with bringing new drugs to market.

Etoposide is a chemotherapy medication used to treat various types of cancer, including lung cancer, testicular cancer, and certain types of leukemia. It works by inhibiting the activity of an enzyme called topoisomerase II, which is involved in DNA replication and transcription. By doing so, etoposide can interfere with the growth and multiplication of cancer cells.

Etoposide is often administered intravenously in a hospital or clinic setting, although it may also be given orally in some cases. The medication can cause a range of side effects, including nausea, vomiting, hair loss, and an increased risk of infection. It can also have more serious side effects, such as bone marrow suppression, which can lead to anemia, bleeding, and a weakened immune system.

Like all chemotherapy drugs, etoposide is not without risks and should only be used under the close supervision of a qualified healthcare provider. It is important for patients to discuss the potential benefits and risks of this medication with their doctor before starting treatment.

I'm sorry for any confusion, but "KB cells" is not a widely recognized or established term in medical or scientific communities. It's possible that "KB cells" may refer to a specific cell line used in scientific research. KB cells are a type of cell line derived from a human carcinoma (a type of cancer) of the nasopharynx (the upper part of the throat behind the nose). They are often used in studies related to cancer, virology, and other areas of biomedical research.

However, without more context or information, it's difficult to provide a more precise definition of "KB cells." If you have more information about where you encountered this term or what specific context it was used in, I may be able to give a more accurate answer.

DNA topoisomerases are enzymes that regulate the topological state of DNA during various cellular processes such as replication, transcription, and repair. They do this by introducing temporary breaks in the DNA strands and allowing the strands to rotate around each other, thereby relieving torsional stress and supercoiling. Topoisomerases are classified into two types: type I and type II.

Type II topoisomerases are further divided into two subtypes: type IIA and type IIB. These enzymes function by forming a covalent bond with the DNA strands, cleaving them, and then passing another segment of DNA through the break before resealing the original strands. This process allows for the removal of both positive and negative supercoils from DNA as well as the separation of interlinked circular DNA molecules (catenanes) or knotted DNA structures.

Type II topoisomerases are essential for cell viability, and their dysfunction has been linked to various human diseases, including cancer and neurodegenerative disorders. They have also emerged as important targets for the development of anticancer drugs that inhibit their activity and induce DNA damage leading to cell death. Examples of type II topoisomerase inhibitors include etoposide, doxorubicin, and mitoxantrone.

A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.

Superhelical DNA refers to a type of DNA structure that is formed when the double helix is twisted around itself. This occurs due to the presence of negative supercoiling, which results in an overtwisted state that can be described as having a greater number of helical turns than a relaxed circular DNA molecule.

Superhelical DNA is often found in bacterial and viral genomes, where it plays important roles in compacting the genome into a smaller volume and facilitating processes such as replication and transcription. The degree of supercoiling can affect the structure and function of DNA, with varying levels of supercoiling influencing the accessibility of specific regions of the genome to proteins and other regulatory factors.

Superhelical DNA is typically maintained in a stable state by topoisomerase enzymes, which introduce or remove twists in the double helix to regulate its supercoiling level. Changes in supercoiling can have significant consequences for cellular processes, as they can impact the expression of genes and the regulation of chromosome structure and function.

Amsacrine is a chemotherapeutic agent, which means it is a medication used to treat cancer. It is classified as an antineoplastic drug, and more specifically, as an intercalating agent and a topoisomerase II inhibitor. Amsacrine works by intercalating, or inserting itself, into the DNA of cancer cells, which prevents the DNA from replicating and ultimately leads to the death of the cancer cell. It is primarily used in the treatment of acute myeloid leukemia (AML) and other hematologic malignancies.

The chemical name for Amsacrine is 5-[3-amino-1-(3-aminopropyl)-2-hydroxybut-1-yloxy]-8-chloro-1,4-naphthoquinone. It has a molecular formula of C16H17ClNO5 and a molecular weight of 359.8 g/mol.

Amsacrine is typically administered intravenously, and its use is usually reserved for patients who have not responded to other forms of chemotherapy. It may be used in combination with other anticancer drugs as part of a treatment regimen. As with any chemotherapeutic agent, Amsacrine can have significant side effects, including nausea, vomiting, and hair loss. It can also cause damage to the heart and other organs, so it is important for patients to be closely monitored during treatment.

It's worth noting that while Amsacrine can be an effective treatment for some types of cancer, it is not a cure-all, and its use must be carefully considered in the context of each individual patient's medical history and current health status.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

Drug resistance, also known as antimicrobial resistance, is the ability of a microorganism (such as bacteria, viruses, fungi, or parasites) to withstand the effects of a drug that was originally designed to inhibit or kill it. This occurs when the microorganism undergoes genetic changes that allow it to survive in the presence of the drug. As a result, the drug becomes less effective or even completely ineffective at treating infections caused by these resistant organisms.

Drug resistance can develop through various mechanisms, including mutations in the genes responsible for producing the target protein of the drug, alteration of the drug's target site, modification or destruction of the drug by enzymes produced by the microorganism, and active efflux of the drug from the cell.

The emergence and spread of drug-resistant microorganisms pose significant challenges in medical treatment, as they can lead to increased morbidity, mortality, and healthcare costs. The overuse and misuse of antimicrobial agents, as well as poor infection control practices, contribute to the development and dissemination of drug-resistant strains. To address this issue, it is crucial to promote prudent use of antimicrobials, enhance surveillance and monitoring of resistance patterns, invest in research and development of new antimicrobial agents, and strengthen infection prevention and control measures.

DNA cleavage is the breaking of the phosphodiester bonds in the DNA molecule, resulting in the separation of the two strands of the double helix. This process can occur through chemical or enzymatic reactions and can result in various types of damage to the DNA molecule, including single-strand breaks, double-strand breaks, and base modifications.

Enzymatic DNA cleavage is typically carried out by endonucleases, which are enzymes that cut DNA molecules at specific sequences or structures. There are two main types of endonucleases: restriction endonucleases and repair endonucleases. Restriction endonucleases recognize and cleave specific DNA sequences, often used in molecular biology techniques such as genetic engineering and cloning. Repair endonucleases, on the other hand, are involved in DNA repair processes and recognize and cleave damaged or abnormal DNA structures.

Chemical DNA cleavage can occur through various mechanisms, including oxidation, alkylation, or hydrolysis of the phosphodiester bonds. Chemical agents such as hydrogen peroxide, formaldehyde, or hydrazine can induce chemical DNA cleavage and are often used in laboratory settings for various purposes, such as DNA fragmentation or labeling.

Overall, DNA cleavage is an essential process in many biological functions, including DNA replication, repair, and recombination. However, excessive or improper DNA cleavage can lead to genomic instability, mutations, and cell death.

DNA replication is the biological process by which DNA makes an identical copy of itself during cell division. It is a fundamental mechanism that allows genetic information to be passed down from one generation of cells to the next. During DNA replication, each strand of the double helix serves as a template for the synthesis of a new complementary strand. This results in the creation of two identical DNA molecules. The enzymes responsible for DNA replication include helicase, which unwinds the double helix, and polymerase, which adds nucleotides to the growing strands.

Iridoid glucosides are a type of plant-based compounds that are characterized by their iridoid structure, which is a cyclic organic compound containing a cyclopentane ring fused to a six-membered unsaturated carbocycle. These compounds are often found in plants as glycosides, meaning they are combined with a sugar molecule such as glucose.

Iridoid glucosides have been identified in a variety of plant families, including the Lamiaceae (mint family), Scrophulariaceae (figwort family), and Rubiaceae (coffee family). Some examples of iridoid glucosides include geniposide, which is found in the fruit of the gardenia plant, and aucubin, which is found in the leaves of the eucommia tree.

Iridoid glucosides have been studied for their potential medicinal properties, including anti-inflammatory, antioxidant, and antimicrobial effects. However, more research is needed to fully understand their mechanisms of action and potential therapeutic uses.

DNA repair is the process by which cells identify and correct damage to the DNA molecules that encode their genome. DNA can be damaged by a variety of internal and external factors, such as radiation, chemicals, and metabolic byproducts. If left unrepaired, this damage can lead to mutations, which may in turn lead to cancer and other diseases.

There are several different mechanisms for repairing DNA damage, including:

1. Base excision repair (BER): This process repairs damage to a single base in the DNA molecule. An enzyme called a glycosylase removes the damaged base, leaving a gap that is then filled in by other enzymes.
2. Nucleotide excision repair (NER): This process repairs more severe damage, such as bulky adducts or crosslinks between the two strands of the DNA molecule. An enzyme cuts out a section of the damaged DNA, and the gap is then filled in by other enzymes.
3. Mismatch repair (MMR): This process repairs errors that occur during DNA replication, such as mismatched bases or small insertions or deletions. Specialized enzymes recognize the error and remove a section of the newly synthesized strand, which is then replaced by new nucleotides.
4. Double-strand break repair (DSBR): This process repairs breaks in both strands of the DNA molecule. There are two main pathways for DSBR: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly rejoins the broken ends, while HR uses a template from a sister chromatid to repair the break.

Overall, DNA repair is a crucial process that helps maintain genome stability and prevent the development of diseases caused by genetic mutations.

Cell survival refers to the ability of a cell to continue living and functioning normally, despite being exposed to potentially harmful conditions or treatments. This can include exposure to toxins, radiation, chemotherapeutic drugs, or other stressors that can damage cells or interfere with their normal processes.

In scientific research, measures of cell survival are often used to evaluate the effectiveness of various therapies or treatments. For example, researchers may expose cells to a particular drug or treatment and then measure the percentage of cells that survive to assess its potential therapeutic value. Similarly, in toxicology studies, measures of cell survival can help to determine the safety of various chemicals or substances.

It's important to note that cell survival is not the same as cell proliferation, which refers to the ability of cells to divide and multiply. While some treatments may promote cell survival, they may also inhibit cell proliferation, making them useful for treating diseases such as cancer. Conversely, other treatments may be designed to specifically target and kill cancer cells, even if it means sacrificing some healthy cells in the process.

Leukemia L1210 is not a medical definition itself, but it refers to a specific mouse leukemia cell line that was established in 1948. These cells are a type of acute myeloid leukemia (AML) and have been widely used in cancer research as a model for studying the disease, testing new therapies, and understanding the biology of leukemia. The L1210 cell line has contributed significantly to the development of various chemotherapeutic agents and treatment strategies for leukemia and other cancers.

Drug resistance in neoplasms (also known as cancer drug resistance) refers to the ability of cancer cells to withstand the effects of chemotherapeutic agents or medications designed to kill or inhibit the growth of cancer cells. This can occur due to various mechanisms, including changes in the cancer cell's genetic makeup, alterations in drug targets, increased activity of drug efflux pumps, and activation of survival pathways.

Drug resistance can be intrinsic (present at the beginning of treatment) or acquired (developed during the course of treatment). It is a significant challenge in cancer therapy as it often leads to reduced treatment effectiveness, disease progression, and poor patient outcomes. Strategies to overcome drug resistance include the use of combination therapies, development of new drugs that target different mechanisms, and personalized medicine approaches that consider individual patient and tumor characteristics.

Intercalating agents are chemical substances that can be inserted between the stacked bases of DNA, creating a separation or "intercalation" of the base pairs. This property is often exploited in cancer chemotherapy, where intercalating agents like doxorubicin and daunorubicin are used to inhibit the replication and transcription of cancer cells by preventing the normal functioning of their DNA. However, these agents can also have toxic effects on normal cells, particularly those that divide rapidly, such as bone marrow and gut epithelial cells. Therefore, their use must be carefully monitored and balanced against their therapeutic benefits.

The cell cycle is a series of events that take place in a cell leading to its division and duplication. It consists of four main phases: G1 phase, S phase, G2 phase, and M phase.

During the G1 phase, the cell grows in size and synthesizes mRNA and proteins in preparation for DNA replication. In the S phase, the cell's DNA is copied, resulting in two complete sets of chromosomes. During the G2 phase, the cell continues to grow and produces more proteins and organelles necessary for cell division.

The M phase is the final stage of the cell cycle and consists of mitosis (nuclear division) and cytokinesis (cytoplasmic division). Mitosis results in two genetically identical daughter nuclei, while cytokinesis divides the cytoplasm and creates two separate daughter cells.

The cell cycle is regulated by various checkpoints that ensure the proper completion of each phase before progressing to the next. These checkpoints help prevent errors in DNA replication and division, which can lead to mutations and cancer.

Ellipticines are a class of naturally occurring alkaloids that have been isolated from various plants, including those in the family Apocynaceae. These compounds have been found to exhibit various biological activities, including anti-cancer and anti-microbial properties.

Ellipticines have a unique chemical structure, characterized by a planar, aromatic core with two side chains that contain nitrogen atoms. This structure allows ellipticines to intercalate into DNA, disrupting its normal function and leading to cell death. As a result, ellipticines have been studied as potential anti-cancer agents, particularly for the treatment of drug-resistant cancers.

In addition to their anti-cancer properties, ellipticines have also been found to exhibit antibacterial, antifungal, and antiparasitic activities. However, further research is needed to fully understand the mechanisms behind these effects and to determine the safety and efficacy of ellipticines as therapeutic agents.

Secondary metabolism in the context of microbiology and plant biology refers to the metabolic pathways that produce secondary metabolites. These are compounds that are not directly involved in the growth, development, or reproduction of an organism but have other functions, such as defense against predators or competitors, or in ecological interactions with other organisms.

Examples of secondary metabolites include antibiotics, toxins, pigments, and various signaling molecules. The production of these compounds is often induced under specific environmental conditions or developmental stages, and they can play important roles in the survival and fitness of the producing organism.

In contrast, primary metabolism refers to the metabolic pathways that produce compounds essential for growth, development, and reproduction, such as amino acids, nucleotides, and carbohydrates.

Lactones are not a medical term per se, but they are important in the field of pharmaceuticals and medicinal chemistry. Lactones are cyclic esters derived from hydroxy acids. They can be found naturally in various plants, fruits, and some insects. In medicine, lactones have been used in the synthesis of drugs, including certain antibiotics and antifungal agents. For instance, the penicillin family of antibiotics contains a beta-lactone ring in their structure, which is essential for their antibacterial activity.

I'm sorry for any confusion, but "Leukemia P388" is not a widely recognized medical term or a specific type of leukemia. The term "P388" is often used to refer to a particular type of mouse leukemia that is commonly used in laboratory research for testing potential anti-cancer drugs.

Leukemia, in general, is a type of cancer that originates in the bone marrow and results in an overproduction of abnormal white blood cells (leukocytes). These abnormal cells crowd out the healthy cells in the bone marrow, leading to a weakened immune system and various complications.

There are many different types of leukemia, classified based on the type of white blood cell affected (myeloid or lymphocytic) and the speed of progression (acute or chronic). If you're looking for information about a specific type of leukemia, I would be happy to help if you could provide more details.

Organic chemistry is a branch of chemistry that deals with the study of carbon-containing compounds, their synthesis, reactions, properties, and structures. These compounds can include both naturally occurring substances (such as sugars, proteins, and nucleic acids) and synthetic materials (such as plastics, dyes, and pharmaceuticals). A key characteristic of organic molecules is the presence of covalent bonds between carbon atoms or between carbon and other elements like hydrogen, oxygen, nitrogen, sulfur, and halogens. The field of organic chemistry has played a crucial role in advancing our understanding of chemical processes and has led to numerous technological and medical innovations.

The term "DNA, neoplasm" is not a standard medical term or concept. DNA refers to deoxyribonucleic acid, which is the genetic material present in the cells of living organisms. A neoplasm, on the other hand, is a tumor or growth of abnormal tissue that can be benign (non-cancerous) or malignant (cancerous).

In some contexts, "DNA, neoplasm" may refer to genetic alterations found in cancer cells. These genetic changes can include mutations, amplifications, deletions, or rearrangements of DNA sequences that contribute to the development and progression of cancer. Identifying these genetic abnormalities can help doctors diagnose and treat certain types of cancer more effectively.

However, it's important to note that "DNA, neoplasm" is not a term that would typically be used in medical reports or research papers without further clarification. If you have any specific questions about DNA changes in cancer cells or neoplasms, I would recommend consulting with a healthcare professional or conducting further research on the topic.

Tumor suppressor protein p53, also known as p53 or tumor protein p53, is a nuclear phosphoprotein that plays a crucial role in preventing cancer development and maintaining genomic stability. It does so by regulating the cell cycle and acting as a transcription factor for various genes involved in apoptosis (programmed cell death), DNA repair, and cell senescence (permanent cell growth arrest).

In response to cellular stress, such as DNA damage or oncogene activation, p53 becomes activated and accumulates in the nucleus. Activated p53 can then bind to specific DNA sequences and promote the transcription of target genes that help prevent the proliferation of potentially cancerous cells. These targets include genes involved in cell cycle arrest (e.g., CDKN1A/p21), apoptosis (e.g., BAX, PUMA), and DNA repair (e.g., GADD45).

Mutations in the TP53 gene, which encodes p53, are among the most common genetic alterations found in human cancers. These mutations often lead to a loss or reduction of p53's tumor suppressive functions, allowing cancer cells to proliferate uncontrollably and evade apoptosis. As a result, p53 has been referred to as "the guardian of the genome" due to its essential role in preventing tumorigenesis.

Neoplasms are abnormal growths of cells or tissues in the body that serve no physiological function. They can be benign (non-cancerous) or malignant (cancerous). Benign neoplasms are typically slow growing and do not spread to other parts of the body, while malignant neoplasms are aggressive, invasive, and can metastasize to distant sites.

Neoplasms occur when there is a dysregulation in the normal process of cell division and differentiation, leading to uncontrolled growth and accumulation of cells. This can result from genetic mutations or other factors such as viral infections, environmental exposures, or hormonal imbalances.

Neoplasms can develop in any organ or tissue of the body and can cause various symptoms depending on their size, location, and type. Treatment options for neoplasms include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy, among others.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

I'm sorry for any confusion, but "Indenes" is not a recognized medical term or concept in the field of medicine or healthcare. It may be that there is a spelling mistake or typo in your question. If you are referring to "Indenes" as a chemical compound, it is a polycyclic aromatic hydrocarbon (PAH) with the molecular formula C9H8. However, I would recommend consulting a chemistry or toxicology resource for information on its non-medical uses and properties.

Naphthoquinones are a type of organic compound that consists of a naphthalene ring (two benzene rings fused together) with two ketone functional groups (=O) at the 1 and 2 positions. They exist in several forms, including natural and synthetic compounds. Some well-known naphthoquinones include vitamin K1 (phylloquinone) and K2 (menaquinone), which are important for blood clotting and bone metabolism. Other naphthoquinones have been studied for their potential medicinal properties, including anticancer, antibacterial, and anti-inflammatory activities. However, some naphthoquinones can also be toxic or harmful to living organisms, so they must be used with caution.

In the context of cell biology, "S phase" refers to the part of the cell cycle during which DNA replication occurs. The "S" stands for synthesis, reflecting the active DNA synthesis that takes place during this phase. It is preceded by G1 phase (gap 1) and followed by G2 phase (gap 2), with mitosis (M phase) being the final stage of the cell cycle.

During S phase, the cell's DNA content effectively doubles as each chromosome is replicated to ensure that the two resulting daughter cells will have the same genetic material as the parent cell. This process is carefully regulated and coordinated with other events in the cell cycle to maintain genomic stability.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Iridoids are a type of naturally occurring compounds that are widely distributed in the plant kingdom. They are characterized by the presence of a cyclopentanoid structure fused to a monoterpene unit. Iridoids have a wide range of biological activities, including anti-inflammatory, analgesic, and antioxidant effects. Some iridoids also have potential therapeutic benefits in the treatment of various diseases, such as cancer and neurodegenerative disorders.

In a medical context, iridoids may be mentioned in relation to their presence in certain medicinal plants or herbs used in traditional medicine, or in research investigating their potential pharmacological properties. However, it is important to note that the use of iridoid-containing plants or supplements should only be done under the guidance of a qualified healthcare professional, as with any medical treatment.

A prodrug is a pharmacologically inactive substance that, once administered, is metabolized into a drug that is active. Prodrugs are designed to improve the bioavailability or delivery of a drug, to minimize adverse effects, or to target the drug to specific sites in the body. The conversion of a prodrug to its active form typically occurs through enzymatic reactions in the liver or other tissues.

Prodrugs can offer several advantages over traditional drugs, including:

* Improved absorption: Some drugs have poor bioavailability due to their chemical properties, which make them difficult to absorb from the gastrointestinal tract. Prodrugs can be designed with improved absorption characteristics, allowing for more efficient delivery of the active drug to the body.
* Reduced toxicity: By masking the active drug's chemical structure, prodrugs can reduce its interactions with sensitive tissues and organs, thereby minimizing adverse effects.
* Targeted delivery: Prodrugs can be designed to selectively release the active drug in specific areas of the body, such as tumors or sites of infection, allowing for more precise and effective therapy.

Examples of prodrugs include:

* Aspirin (acetylsalicylic acid), which is metabolized to salicylic acid in the liver.
* Enalapril, an angiotensin-converting enzyme (ACE) inhibitor used to treat hypertension and heart failure, which is metabolized to enalaprilat in the liver.
* Codeine, an opioid analgesic, which is metabolized to morphine in the liver by the enzyme CYP2D6.

It's important to note that not all prodrugs are successful, and some may even have unintended consequences. For example, if a patient has a genetic variation that affects the activity of the enzyme responsible for converting the prodrug to its active form, the drug may not be effective or may produce adverse effects. Therefore, it's essential to consider individual genetic factors when prescribing prodrugs.

Alkaloids are a type of naturally occurring organic compounds that contain mostly basic nitrogen atoms. They are often found in plants, and are known for their complex ring structures and diverse pharmacological activities. Many alkaloids have been used in medicine for their analgesic, anti-inflammatory, and therapeutic properties. Examples of alkaloids include morphine, quinine, nicotine, and caffeine.

Nucleic acid synthesis inhibitors are a class of antimicrobial, antiviral, or antitumor agents that block the synthesis of nucleic acids (DNA or RNA) by interfering with enzymes involved in their replication. These drugs can target various stages of nucleic acid synthesis, including DNA transcription, replication, and repair, as well as RNA transcription and processing.

Examples of nucleic acid synthesis inhibitors include:

1. Antibiotics like quinolones (e.g., ciprofloxacin), rifamycins (e.g., rifampin), and trimethoprim, which target bacterial DNA gyrase, RNA polymerase, or dihydrofolate reductase, respectively.
2. Antiviral drugs like reverse transcriptase inhibitors (e.g., zidovudine, lamivudine) and integrase strand transfer inhibitors (e.g., raltegravir), which target HIV replication by interfering with viral enzymes required for DNA synthesis.
3. Antitumor drugs like antimetabolites (e.g., methotrexate, 5-fluorouracil) and topoisomerase inhibitors (e.g., etoposide, doxorubicin), which interfere with DNA replication and repair in cancer cells.

These drugs have been widely used for treating various bacterial and viral infections, as well as cancers, due to their ability to selectively inhibit the growth of target cells without affecting normal cellular functions significantly. However, they may also cause side effects related to their mechanism of action or off-target effects on non-target cells.

HeLa cells are a type of immortalized cell line used in scientific research. They are derived from a cancer that developed in the cervical tissue of Henrietta Lacks, an African-American woman, in 1951. After her death, cells taken from her tumor were found to be capable of continuous division and growth in a laboratory setting, making them an invaluable resource for medical research.

HeLa cells have been used in a wide range of scientific studies, including research on cancer, viruses, genetics, and drug development. They were the first human cell line to be successfully cloned and are able to grow rapidly in culture, doubling their population every 20-24 hours. This has made them an essential tool for many areas of biomedical research.

It is important to note that while HeLa cells have been instrumental in numerous scientific breakthroughs, the story of their origin raises ethical questions about informed consent and the use of human tissue in research.

'Leishmania donovani' is a species of protozoan parasite that causes a severe form of visceral leishmaniasis, also known as kala-azar. This disease primarily affects the spleen, liver, and bone marrow, leading to symptoms such as fever, weight loss, anemia, and enlargement of the spleen and liver. The parasite is transmitted to humans through the bite of infected female sandflies. It's worth noting that this organism can also affect dogs and other animals, causing a disease known as canine leishmaniasis.

Acrylamides are a type of chemical that can form in some foods during high-temperature cooking processes, such as frying, roasting, and baking. They are created when certain amino acids (asparagine) and sugars in the food react together at temperatures above 120°C (248°F). This reaction is known as the Maillard reaction.

Acrylamides have been classified as a probable human carcinogen by the International Agency for Research on Cancer (IARC), based on studies in animals. However, more research is needed to fully understand the potential health risks associated with acrylamide exposure from food.

Public health organizations recommend limiting acrylamide intake by following some cooking practices such as:

* Avoiding overcooking or burning foods
* Soaking potatoes (which are high in asparagine) in water before frying to reduce the formation of acrylamides
* Choosing raw, unprocessed, or minimally processed foods when possible.

HT-29 is a human colon adenocarcinoma cell line that is commonly used in research. These cells are derived from a colorectal cancer tumor and have the ability to differentiate into various cell types found in the intestinal mucosa, such as absorptive enterocytes and mucus-secreting goblet cells. HT-29 cells are often used to study the biology of colon cancer, including the effects of drugs on cancer cell growth and survival, as well as the role of various genes and signaling pathways in colorectal tumorigenesis.

It is important to note that when working with cell lines like HT-29, it is essential to use proper laboratory techniques and follow established protocols to ensure the integrity and reproducibility of experimental results. Additionally, researchers should regularly authenticate their cell lines to confirm their identity and verify that they are free from contamination with other cell types.

Drug synergism is a pharmacological concept that refers to the interaction between two or more drugs, where the combined effect of the drugs is greater than the sum of their individual effects. This means that when these drugs are administered together, they produce an enhanced therapeutic response compared to when they are given separately.

Drug synergism can occur through various mechanisms, such as:

1. Pharmacodynamic synergism - When two or more drugs interact with the same target site in the body and enhance each other's effects.
2. Pharmacokinetic synergism - When one drug affects the metabolism, absorption, distribution, or excretion of another drug, leading to an increased concentration of the second drug in the body and enhanced therapeutic effect.
3. Physiochemical synergism - When two drugs interact physically, such as when one drug enhances the solubility or permeability of another drug, leading to improved absorption and bioavailability.

It is important to note that while drug synergism can result in enhanced therapeutic effects, it can also increase the risk of adverse reactions and toxicity. Therefore, healthcare providers must carefully consider the potential benefits and risks when prescribing combinations of drugs with known or potential synergistic effects.

DNA fragmentation is the breaking of DNA strands into smaller pieces. This process can occur naturally during apoptosis, or programmed cell death, where the DNA is broken down and packaged into apoptotic bodies to be safely eliminated from the body. However, excessive or abnormal DNA fragmentation can also occur due to various factors such as oxidative stress, exposure to genotoxic agents, or certain medical conditions. This can lead to genetic instability, cellular dysfunction, and increased risk of diseases such as cancer. In the context of reproductive medicine, high levels of DNA fragmentation in sperm cells have been linked to male infertility and poor assisted reproductive technology outcomes.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

'Catha' is a plant species also known as Khat, Kat, or Qat. It contains psychoactive compounds that can cause stimulant-like effects when chewed, brewed into tea, or taken in other forms. The main active compound in Catha is cathinone, which is similar in structure and effects to amphetamines.

The use of Catha can produce feelings of euphoria, increased alertness, and talkativeness, but it can also cause side effects such as increased heart rate, blood pressure, and anxiety. Long-term use of Catha has been associated with a number of health problems, including tooth decay, gastrointestinal issues, and mental health disorders.

It's worth noting that the legal status of Catha varies by country and region. In some places, it is legal and widely used, while in others, it is considered a controlled substance and its use is restricted or prohibited.

A drug carrier, also known as a drug delivery system or vector, is a vehicle that transports a pharmaceutical compound to a specific site in the body. The main purpose of using drug carriers is to improve the efficacy and safety of drugs by enhancing their solubility, stability, bioavailability, and targeted delivery, while minimizing unwanted side effects.

Drug carriers can be made up of various materials, including natural or synthetic polymers, lipids, inorganic nanoparticles, or even cells and viruses. They can encapsulate, adsorb, or conjugate drugs through different mechanisms, such as physical entrapment, electrostatic interaction, or covalent bonding.

Some common types of drug carriers include:

1. Liposomes: spherical vesicles composed of one or more lipid bilayers that can encapsulate hydrophilic and hydrophobic drugs.
2. Polymeric nanoparticles: tiny particles made of biodegradable polymers that can protect drugs from degradation and enhance their accumulation in target tissues.
3. Dendrimers: highly branched macromolecules with a well-defined structure and size that can carry multiple drug molecules and facilitate their release.
4. Micelles: self-assembled structures formed by amphiphilic block copolymers that can solubilize hydrophobic drugs in water.
5. Inorganic nanoparticles: such as gold, silver, or iron oxide nanoparticles, that can be functionalized with drugs and targeting ligands for diagnostic and therapeutic applications.
6. Cell-based carriers: living cells, such as red blood cells, stem cells, or immune cells, that can be loaded with drugs and used to deliver them to specific sites in the body.
7. Viral vectors: modified viruses that can infect cells and introduce genetic material encoding therapeutic proteins or RNA interference molecules.

The choice of drug carrier depends on various factors, such as the physicochemical properties of the drug, the route of administration, the target site, and the desired pharmacokinetics and biodistribution. Therefore, selecting an appropriate drug carrier is crucial for achieving optimal therapeutic outcomes and minimizing side effects.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Diterpenes are a class of naturally occurring compounds that are composed of four isoprene units, which is a type of hydrocarbon. They are synthesized by a wide variety of plants and animals, and are found in many different types of organisms, including fungi, insects, and marine organisms.

Diterpenes have a variety of biological activities and are used in medicine for their therapeutic effects. Some diterpenes have anti-inflammatory, antimicrobial, and antiviral properties, and are used to treat a range of conditions, including respiratory infections, skin disorders, and cancer.

Diterpenes can be further classified into different subgroups based on their chemical structure and biological activity. Some examples of diterpenes include the phytocannabinoids found in cannabis plants, such as THC and CBD, and the paclitaxel, a diterpene found in the bark of the Pacific yew tree that is used to treat cancer.

It's important to note that while some diterpenes have therapeutic potential, others may be toxic or have adverse effects, so it is essential to use them under the guidance and supervision of a healthcare professional.

HL-60 cells are a type of human promyelocytic leukemia cell line that is commonly used in scientific research. They are named after the hospital where they were first isolated, the Hospital of the University of Pennsylvania (HUP) and the 60th culture attempt to grow these cells.

HL-60 cells have the ability to differentiate into various types of blood cells, such as granulocytes, monocytes, and macrophages, when exposed to certain chemical compounds or under specific culturing conditions. This makes them a valuable tool for studying the mechanisms of cell differentiation, proliferation, and apoptosis (programmed cell death).

HL-60 cells are also often used in toxicity studies, drug discovery and development, and research on cancer, inflammation, and infectious diseases. They can be easily grown in the lab and have a stable genotype, making them ideal for use in standardized experiments and comparisons between different studies.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

Colonic neoplasms refer to abnormal growths in the large intestine, also known as the colon. These growths can be benign (non-cancerous) or malignant (cancerous). The two most common types of colonic neoplasms are adenomas and carcinomas.

Adenomas are benign tumors that can develop into cancer over time if left untreated. They are often found during routine colonoscopies and can be removed during the procedure.

Carcinomas, on the other hand, are malignant tumors that invade surrounding tissues and can spread to other parts of the body. Colorectal cancer is the third leading cause of cancer-related deaths in the United States, and colonic neoplasms are a significant risk factor for developing this type of cancer.

Regular screenings for colonic neoplasms are recommended for individuals over the age of 50 or those with a family history of colorectal cancer or other risk factors. Early detection and removal of colonic neoplasms can significantly reduce the risk of developing colorectal cancer.

Caspases are a family of protease enzymes that play essential roles in programmed cell death, also known as apoptosis. These enzymes are produced as inactive precursors and are activated when cells receive signals to undergo apoptosis. Once activated, caspases cleave specific protein substrates, leading to the characteristic morphological changes and DNA fragmentation associated with apoptotic cell death. Caspases also play roles in other cellular processes, including inflammation and differentiation. There are two types of caspases: initiator caspases (caspase-2, -8, -9, and -10) and effector caspases (caspase-3, -6, and -7). Initiator caspases are activated in response to various apoptotic signals and then activate the effector caspases, which carry out the proteolytic cleavage of cellular proteins. Dysregulation of caspase activity has been implicated in a variety of diseases, including neurodegenerative disorders, ischemic injury, and cancer.

Dichlororibofuranosylbenzimidazole is not a medical term, but it is a chemical compound with the formula C6H5Cl2N2O4. It is also known as tribuzole or 1-(2'-deoxy-2'-fluoro-β-D-erythro-pentofuranosyl)-2,2-dichlorobenzimidazole.

Tribuzole is an antiviral drug that has been studied for the treatment of HIV infection. It works by inhibiting the reverse transcriptase enzyme of the virus, which is necessary for the replication of the viral RNA into DNA. However, tribuzole has not been approved for clinical use due to its limited efficacy and unfavorable side effects profile.

Therefore, there is no medical definition for 'dichlororibofuranosylbenzimidazole' as it is not a term used in medical practice or literature.

Mitoxantrone is a synthetic antineoplastic anthracenedione drug, which means it is used to treat cancer. Its medical definition can be found in various authoritative sources such as the Merck Manual or Stedman's Medical Dictionary. Here's a brief version of the definition from MedlinePlus, a service of the US National Library of Medicine:

"Mitoxantrone is used to treat certain types of cancer (e.g., breast cancer, leukemia, non-Hodgkin's lymphoma). It works by slowing or stopping the growth of cancer cells. Mitoxantrone belongs to a class of drugs known as antitumor antibiotics."

Please note that this is a simplified definition meant for general information purposes and does not include all the details that might be present in a comprehensive medical definition. Always consult a healthcare professional or refer to authoritative resources for accurate, detailed, and up-to-date information.

Flavanones are a type of flavonoid, which is a class of plant pigments widely found in fruits, vegetables, and other plants. Flavanones are known for their antioxidant properties and potential health benefits. They are typically found in citrus fruits such as oranges, lemons, and grapefruits. Some common flavanones include hesperetin, naringenin, and eriodictyol. These compounds have been studied for their potential effects on cardiovascular health, cancer prevention, and neuroprotection, although more research is needed to fully understand their mechanisms of action and therapeutic potential.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.

Inhibitory Concentration 50 (IC50) is a measure used in pharmacology, toxicology, and virology to describe the potency of a drug or chemical compound. It refers to the concentration needed to reduce the biological or biochemical activity of a given substance by half. Specifically, it is most commonly used in reference to the inhibition of an enzyme or receptor.

In the context of infectious diseases, IC50 values are often used to compare the effectiveness of antiviral drugs against a particular virus. A lower IC50 value indicates that less of the drug is needed to achieve the desired effect, suggesting greater potency and potentially fewer side effects. Conversely, a higher IC50 value suggests that more of the drug is required to achieve the same effect, indicating lower potency.

It's important to note that IC50 values can vary depending on the specific assay or experimental conditions used, so they should be interpreted with caution and in conjunction with other measures of drug efficacy.

RecQ helicases are a group of enzymes that belong to the RecQ family, which are named after the E. coli RecQ protein. These helicases play crucial roles in maintaining genomic stability by participating in various DNA metabolic processes such as DNA replication, repair, recombination, and transcription. They are highly conserved across different species, including bacteria, yeast, plants, and mammals.

In humans, there are five RecQ helicases: RECQL1, RECQL4, RECQL5, BLM (RecQ-like helicase), and WRN (Werner syndrome ATP-dependent helicase). Defects in these proteins have been linked to various genetic disorders. For instance, mutations in the BLM gene cause Bloom's syndrome, while mutations in the WRN gene lead to Werner syndrome, both of which are characterized by genomic instability and increased cancer predisposition.

RecQ helicases possess 3'-5' DNA helicase activity, unwinding double-stranded DNA into single strands, and can also perform other functions like branch migration, strand annealing, and removal of protein-DNA crosslinks. Their roles in DNA metabolism help prevent and resolve DNA damage, maintain proper chromosome segregation during cell division, and ensure the integrity of the genome.

Granulocyte precursor cells, also known as myeloid precursors or myeloblasts, are early-stage cells found in the bone marrow. These cells are part of the production process for granulocytes, a type of white blood cell that plays a crucial role in fighting off infections.

Granulocyte precursor cells differentiate and mature into three main types of granulocytes: neutrophils, eosinophils, and basophils. These cells have distinct functions in the immune response, such as neutralizing and destroying invading pathogens (neutrophils), regulating inflammation and fighting parasitic infections (eosinophils), and mediating allergic reactions and inflammation (basophils).

Abnormalities in granulocyte precursor cells can lead to various medical conditions, such as leukemia, where these cells become cancerous and multiply uncontrollably. Monitoring granulocyte precursor cells is essential for diagnosing and managing hematological disorders.

Staurosporine is an alkaloid compound that is derived from the bacterium Streptomyces staurosporeus. It is a potent and broad-spectrum protein kinase inhibitor, which means it can bind to and inhibit various types of protein kinases, including protein kinase C (PKC), cyclin-dependent kinases (CDKs), and tyrosine kinases.

Protein kinases are enzymes that play a crucial role in cell signaling by adding phosphate groups to other proteins, thereby modulating their activity. The inhibition of protein kinases by staurosporine can disrupt these signaling pathways and lead to various biological effects, such as the induction of apoptosis (programmed cell death) and the inhibition of cell proliferation.

Staurosporine has been widely used in research as a tool to study the roles of protein kinases in various cellular processes and diseases, including cancer, neurodegenerative disorders, and inflammation. However, its use as a therapeutic agent is limited due to its lack of specificity and high toxicity.

Molecular structure, in the context of biochemistry and molecular biology, refers to the arrangement and organization of atoms and chemical bonds within a molecule. It describes the three-dimensional layout of the constituent elements, including their spatial relationships, bond lengths, and angles. Understanding molecular structure is crucial for elucidating the functions and reactivities of biological macromolecules such as proteins, nucleic acids, lipids, and carbohydrates. Various experimental techniques, like X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM), are employed to determine molecular structures at atomic resolution, providing valuable insights into their biological roles and potential therapeutic targets.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Doxorubicin is a type of chemotherapy medication known as an anthracycline. It works by interfering with the DNA in cancer cells, which prevents them from growing and multiplying. Doxorubicin is used to treat a wide variety of cancers, including leukemia, lymphoma, breast cancer, lung cancer, ovarian cancer, and many others. It may be given alone or in combination with other chemotherapy drugs.

Doxorubicin is usually administered through a vein (intravenously) and can cause side effects such as nausea, vomiting, hair loss, mouth sores, and increased risk of infection. It can also cause damage to the heart muscle, which can lead to heart failure in some cases. For this reason, doctors may monitor patients' heart function closely while they are receiving doxorubicin treatment.

It is important for patients to discuss the potential risks and benefits of doxorubicin therapy with their healthcare provider before starting treatment.

"Nude mice" is a term used in the field of laboratory research to describe a strain of mice that have been genetically engineered to lack a functional immune system. Specifically, nude mice lack a thymus gland and have a mutation in the FOXN1 gene, which results in a failure to develop a mature T-cell population. This means that they are unable to mount an effective immune response against foreign substances or organisms.

The name "nude" refers to the fact that these mice also have a lack of functional hair follicles, resulting in a hairless or partially hairless phenotype. This feature is actually a secondary consequence of the same genetic mutation that causes their immune deficiency.

Nude mice are commonly used in research because their weakened immune system makes them an ideal host for transplanted tumors, tissues, and cells from other species, including humans. This allows researchers to study the behavior of these foreign substances in a living organism without the complication of an immune response. However, it's important to note that because nude mice lack a functional immune system, they must be kept in sterile conditions and are more susceptible to infection than normal mice.

Caspase-3 is a type of protease enzyme that plays a central role in the execution-phase of cell apoptosis, or programmed cell death. It's also known as CPP32 (CPP for ced-3 protease precursor) or apopain. Caspase-3 is produced as an inactive protein that is activated when cleaved by other caspases during the early stages of apoptosis. Once activated, it cleaves a variety of cellular proteins, including structural proteins, enzymes, and signal transduction proteins, leading to the characteristic morphological and biochemical changes associated with apoptotic cell death. Caspase-3 is often referred to as the "death protease" because of its crucial role in executing the cell death program.

"Curran Synthesis of Camptothecin". Archived from the original on 2009-09-05. Reich HJ. "Comins Synthesis of Camptothecin". ... Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening ... "Camptothecin". Chemnetbase - Dictionary of Drugs. Wang XH, Huang M, Zhao CK, Li C, Xu L (June 2019). "Design, synthesis, and ... "Camptothecin". DrugBank. Retrieved 9 October 2016. Adams DJ, Wahl ML, Flowers JL, Sen B, Colvin M, Dewhirst MW, et al. (January ...
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Camptothecin · Topotecan · Irinotecan · Rubitecan · Belotecan); 2. Podophyllum (Etoposide · Teniposide); 3a. Anthracyclines ( ...
The article Camptothecin lists other analogues of camptothecin and the article Topoisomerase inhibitor lists other compounds ... Camptothecin analogues irinotecan and topotecan, which inhibit TOP1, are among the most effective FDA-approved anticancer ... Irinotecan is an analogue of the cytotoxic natural alkaloid camptothecin, obtained from the Chinese tree Camptotheca acuminata ... "A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity". Proc. Natl. Acad. Sci. ...
... is a semi-synthetic derivative of camptothecin. Camptothecin is a natural product extracted from the bark of the tree ... It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its ... Pommier Y (October 2006). "Topoisomerase I inhibitors: camptothecins and beyond". Nature Reviews. Cancer. 6 (10): 789-802. doi: ... "The mechanism of topoisomerase I poisoning by a camptothecin analog". Proceedings of the National Academy of Sciences of the ...
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He discovered Taxol and camptothecin with Monroe Eliot Wall. Chetan E. Chitnis - worked on molecular parasitology and ...
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The direct nitration of camptothecin results in regioselectivity problems. One way that has been used to synthesize Rubitecan ...
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Li, S.; Zhang, Z.; Cain, A.; Wang, B.; Long, M.; Taylor, J. (2005). "Antifungal Activity of Camptothecin, Trifolin, and ...
"Antifungal Activity of Camptothecin, Trifolin, and Hyperoside Isolated from Camptotheca acuminata". Journal of Agricultural and ...
Albihn A, Mo H, Yang Y, Henriksson M (2007). "Camptothecin-induced apoptosis is enhanced by Myc and involves PKCdelta signaling ...
... lowreyana S.Y.Li The bark and stems of C. acuminata contain the alkaloid camptothecin. Several chemical derivatives ... Li, S.; Zhang, Z.; Cain, A.; Wang, B.; Long, M.; Taylor, J. (2005). "Antifungal Activity of Camptothecin, Trifolin, and ... of camptothecin are under investigation for or used as drugs for cancer treatment, including irinotecan, topotecan, rubitecan. ...
Type 1 topoisomerase is inhibited by irinotecan, topotecan, hexylresorcinol and camptothecin. The human topoisomerase type IB ...
... "p21-activated kinase 5 inhibits camptothecin-induced apoptosis in colorectal carcinoma cells". Tumour Biology. 31 (6): 575-82. ...
Effect of Camptothecin on Collagen Synthesis in Fibroblasts From Patients With Keloid. Annals of Plastic Surgery July 2009 - ... However, the findings related to the role of camptothecin and its potential therapeutical use were reaffirmed in the study by ... Czuwara-Ladykowska J, Makiela B, Smith EA, Trojanowska M, Rudnicka L.: The inhibitory effects of camptothecin, a topoisomerase ... Makiela, B; Barusińska, A; Czuwara, J; Majewski, S; Jablonska, S; Rudnicka, L. (1995) "The effect of camptothecin, an apoptosis ...
Fungi can synthesize podophyllotoxin and camptothecin, precursors to etoposide, teniposide, topotecan, and irinotecan. Lentinan ...
His group conjugated cyclodextrin to the anti-cancer compound camptothecin to improve the bio-availability and exhibit efficacy ... Schluep, T. (1 March 2006). "Preclinical Efficacy of the Camptothecin-Polymer Conjugate IT-101 in Multiple Cancer Models". ...
2010). Correlation of camptothecin-producing ability and phylogenetic relationship in the genus Ophiorrhiza. Planta Med. in pub ... 2004). Camptothecin production by in vitro cultures of Ophiorrhiza liukiuensis and O. kuroiwai. Plant Biotechnology 21:4 275. ... Ophiorrhiza is a genus of flowering plants in the coffee family (Rubiaceae). Species of the genus contain camptothecin, an ... 2007). Organogenesis from leaf and internode explants of Ophiorrhiza prostrata, an anticancer drug (camptothecin) producing ...
Several groups have encapsulated anti-cancer medications such as: Camptothecin, Methotrexate, and Doxorubicin. Results from ... December 2006). "Dendrimer-encapsulated camptothecins: increased solubility, cellular uptake, and cellular retention affords ...
Curran, D. P.; Liu, H., New 4+1 radical annulations - a formal total synthesis of (+/-)-camptothecin. J. Am. Chem. Soc. 1992, ... A 1991 synthesis of the important anti-cancer agent camptothecin illustrates many of these features. The synthesis takes place ...
sfn error: no target: CITEREFGoodmanWalsh2001 (help) Wall ME, Wani MC (February 1995). "Camptothecin and taxol: discovery to ... sfn error: no target: CITEREFGoodmanWalsh2001 (help) Wall ME, Wani MC (February 1995). "Camptothecin and taxol: discovery to ...
"Aspirin inhibits camptothecin-induced p21CIP1 levels and potentiates apoptosis in human breast cancer cells". International ...
... is a drug which is a structural analog of camptothecin with antineoplastic activity. A derivative is used in ...
... and Camptothecin: Base Sequence Analysis and Activity against Camptothecin- Resistant Topoisomerases I". Cancer Research. 63 ( ... a twist around the camptothecins". Oncotarget. 9 (99): 37286-37288. doi:10.18632/oncotarget.26466. ISSN 1949-2553. PMC 6324668 ...
"Comparison of In Vitro Activities of Camptothecin and Nitidine Derivatives against Fungal and Cancer Cells". Antimicrobial ...
"Curran Synthesis of Camptothecin". Archived from the original on 2009-09-05. Reich HJ. "Comins Synthesis of Camptothecin". ... Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening ... "Camptothecin". Chemnetbase - Dictionary of Drugs. Wang XH, Huang M, Zhao CK, Li C, Xu L (June 2019). "Design, synthesis, and ... "Camptothecin". DrugBank. Retrieved 9 October 2016. Adams DJ, Wahl ML, Flowers JL, Sen B, Colvin M, Dewhirst MW, et al. (January ...
Water-soluble esters of camptothecin compounds. Wall, M., & Wani, M. (1999). Water-soluble esters of camptothecin compounds. (U ... Non-toxic camptothecin prodrugs are prepared by esterifying the 20-position hydroxyl group of camptothecin derivatives. ...
... camptothecin. We have examined the following antigens by immunocytochemical techniques: (i) the 180-kDa n … ... Behavior of nuclear matrix proteins during camptothecin-induced apoptosis in HL-60 human leukemia cells Exp Cell Res. 1995 Nov; ... camptothecin. We have examined the following antigens by immunocytochemical techniques: (i) the 180-kDa nucleolar isoform of ... in the nucleolus and precisely within certain granules which are known to appear in the nucleolar area after camptothecin ...
Synthesis and Evaluation of Indenoisoquinoline Non-Camptothecin Topoisomerase I Inhibitors (NIH-Only) ... Synthesis and Evaluation of Indenoisoquinoline Non-Camptothecin Topoisomerase I Inhibitors (NIH-Only) ...
Camptothecin is an alkaloid compound used as an anti-cancer agent. It is a topoisomerase I inhibitor in DNA synthesis. ... Camptothecin has been shown to bind and stabilize a topoisomerase I-DNA complex in vitro, preventing the enzyme from ... Camptothecin is found in Mappia foetida (Nothapodytes foetida), a plant native to eastern India. The compound itself is ... Camptothecin (Camptotheca acuminata), (GoldBio Catalog # C-705) has also been produced by endosymbiotic fungi present in ...
Camptothecin (CPT) analogues and derivatives serve as a novel class of effective anticancer agents that exert their action ... Organogenesis from leaf and internode explants of Ophiorrhiza prostrata, an anticancer drug (camptothecin) producing plant. A. ... against DNA topoisomerase I. This paper presents procedures for the rapid, high frequency regeneration of a camptothecin ...
Adult, Antineoplastic Agents/*radiation effects, Camptothecin/analogs & derivatives/*chemistry/isolation & purification/* ... Structural identification and biological activity of 7-methyl-10,11-ethylenedioxy-20(S)-camptothecin, a photodegradant of ... camptothecin (MEC). Tests of the growth inhibition potential of MEC in seven human tumor cell lines showed that the compound ... was approximately 2-18-fold more cytotoxic than lurtotecan, topotecan, and 7-ethyl-10-hydroxy-20(S)-camptothecin (SN-38). ...
DMH+ standard camptothecin. Administration of conjugated CPT significantly ameliorated the toxicity caused by DMH as indicated ... Camptothecin is an important chemotherapeutic agent used in the treatment of several cancers and most commonly used as first ... IN VIVO TOXICITY COMPARISON STUDIES BETWEEN CAMPTOTHECIN AND DISULFIDE LINKED BIOTIN CONJUGATED CAMPTOTHECIN IN COLON TUMOR ... 2023). IN VIVO TOXICITY COMPARISON STUDIES BETWEEN CAMPTOTHECIN AND DISULFIDE LINKED BIOTIN CONJUGATED CAMPTOTHECIN IN COLON ...
Camptothecin. Journal of Materials Chemistry B. This article can be cited before page numbers have been issued, to do this ... 43 U. Swami, S. Goel and S. Mani, Camptothecin Curr. Drug Targetes, 2013, 14, 777-797.. 44 C. Y. Sun, S. Shen, C. F. Xu, H. J. ... In the current study, we demonstrate a strategy to coordinate the release of camptothecin (CPT) and α-tocopherylsuccinate (TOS ... camptothecin and doxorubicin were covalently conjugated to polymers and released by hydrolysis of ester and amide bonds, and ...
Camptothecin (CPT), a plant alkaloid with antitumor activity, is a specific inhibitor of eukaryotic DNA topoisomerase I. We ... Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites.. ... "Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites." ... "Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites." ...
DESCRIPTION (provided by applicant): Based on the extensive data generated during the phase I portion of our studies, there is sufficient and compelling information to support the further development of the highly lipophilic and blood-stable topoisomerase inhibitor, DB-67. In part, the pre-clinical and clinical evaluation of DB-67 is currently being supported by the NCI through the RAID program; the RAID program studies focus on the non-targeted, liposomal delivery of DB-67, in which DB-67 is formulated in the bilayer of the liposome vesicle. This phase II STTR proposal focuses on the liposomal delivery of core-loaded DB-67 prodrug esters. Liposomal core-loading is a feature of FDA-approved liposomal products such as Doxil and DaunoXome and tumor-targeting has been documented for these formulations. The phase II studies proposed below focus on a novel approach allowing for the liposomal delivery of core-loaded DB-67 prodrug esters, which will permit tumor targeting and, accordingly, effect lower ...
Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique. In: Annals of the New York Academy ... Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique. / Lowe, J.E.; Sheerin, Angela; ... Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique. Annals of the New York Academy of ... Lowe, JE, Sheerin, A, Jennert-Burston, K, Burton, D, Ostler, E, Bird, J, Green, MHL & Faragher, R 2004, Camptothecin ...
TOP1 is the molecular target of camptothecin and related drugs such as irinotecan and SN38 (irinotecans active metabolite). ... TOP1 is the molecular target of camptothecin and related drugs such as irinotecan and SN38 (irinotecans active metabolite). ... New Topoisomerase I mutations are associated with resistance to camptothecin.. Molecular Cancer, 2011, 10 (1), pp.64. ⟨10.1186/ ...
... Pharmaceutical Crops, 2014, 5: 146-162. Shiyou Li, ... Our experiments showed that camptothecins (CPTs) are primarily accumulated in glandular trichomes in Camptotheca. We found that ...
This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA ... Li, F.; Jiang, T.; Li, Q.; Ling, X. Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their ... This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA ... Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human ...
Producing high quality China Largest Factory Manufacturer Camptothecin CAS 7689-3-4 For stock delivery. ... High quality China Largest Factory Manufacturer Camptothecin CAS 7689-3-4 For stock delivery from China, Chinas leading Plant ... Camptothecin. Synonyms. 2,2-dichloro-N-{1-(fluoromethyl)-2-hydroxy-2-[4-(methylsulfanyl)phenyl]ethyl}acetamide; Florfeniol; ... China Largest Factory Manufacturer Camptothecin CAS 7689-3-4 For stock delivery Products - Plant Extract Ingredients ...
The proposed tumor-cell targeted formulation was shown to be able to simultaneously host the model anticancer drug camptothecin ... The proposed tumor-cell targeted formulation was shown to be able to simultaneously host the model anticancer drug camptothecin ... Solvatochromic fluorescent BODIPY derivative as imaging agent in camptothecin loaded hexosomes for possible theranostic ...
Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti. Molecules. 26 (20) 6226. https ... Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti. Partridge, F.A., Poulton, B., ... Preprint: Actions of camptothecin derivatives on larvae and adults of the arboviral vector Aedes aegypti. Partridge, F.A., ... Camptothecin and its derivatives are inhibitors of topoisomerase I, have known activity against several agricultural pests, and ...
Grant helps fund research into camptothecin analogues. Feb. 10, 1997. No Comments ...
The ability of a panel of camptothecin derivatives to access the tumor compartment was evaluated to determine the mechanisms by ... Microregional localization and activity of members of the camptothecin class of topoisomerase I targeting agents, including ... Supplemental Figure S3 from Tissue Penetration and Activity of Camptothecins in Solid Tumor Xenografts. ...
Topical delivery of camptothecin alleviates the side effects caused by systemic chemotherapy; hence, the developed herbal gel ... Anticancer activity results indicate that camptothecin gel induce cell death in A-439 cells having IC50 48.03 μg and % ... Mass and Infrared Spectra respectively conforms molecular weight and functional groups present in camptothecin. All the ... The objective of present research work is to design and characterize camptothecin gel using Carbopol-934 for the treatment of ...
Camptothecin / administration & dosage * Camptothecin / adverse effects * Camptothecin / analogs & derivatives * Carcinoma, ...
A simple computer model of camptothecin-loaded dodecyldimethylamine oxide micelle provided the diameter of the structure cross ... The values of the packing parameter of camptothecin-loaded dodecyldimethylamine oxide micelles indicate their spherical shape ... The solubilisation of poorly soluble antineoplastic drug camptothecin by nonionic surfactants (polysorbates and octylphenol ... From the dynamic light scattering measurements, the hydrodynamic diameter values of camptothecin-loaded alkyldimethylamine ...
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive condition of chromosomal instability that is clinically characterized by microcephaly, a distinct facial appearance, short stature, immunodeficiency, radiation sensitivity, and a strong predisposition to lymphoid malignancy. Mutations in the NBN (NBS1) gene located in band 8q21 ar...
深入研究「Ubiquitin-dependent destruction of topoisomerase I is stimulated by the antitumor drug camptothecin」主題。共同形成了獨特的指紋。 ... The antitumor drug camptothecin (CPT) and its analogs inhibit the rejoining step of the breakage/rejoining reaction, which ... The antitumor drug camptothecin (CPT) and its analogs inhibit the rejoining step of the breakage/rejoining reaction, which ... The antitumor drug camptothecin (CPT) and its analogs inhibit the rejoining step of the breakage/rejoining reaction, which ...
Camptothecin Effectively Regulates Germline Differentiation through Bam-Cyclin A Axis in , Camptothecin Effectively Regulates ... Camptothecin (CPT), first isolated from Chinese tree Camptotheca acuminate, produces rapid and prolonged inhibition of DNA ...
... camptothecin-武汉科斯坦生物科技有限公司 ...
Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. Studies using a ... N2 - Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. Studies ... AB - Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. Studies ... abstract = "Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. ...
Camptothecin, metho. xy- CAMPTOTHECIN,10-MET. HOXY More... Camptothecine, 10-m. ethoxy- ...
  • In this study we focused our attention on the behavior of four nuclear matrix proteins during the various stages of apoptosis in the HL-60 cell line exposed to the DNA topoisomerase I inhibitor, camptothecin. (nih.gov)
  • The presentation, "VIVACITAS ONCOLOGY PRESENTS OUR LEAD COMPOUND, AR-67, A NOVEL 3RD GENERATION CAMPTOTHECIN IN RECURRENT GLIOBLASTOMA," details AR-67 (Topoisomerase I Inhibitor) as a highly potent and novel lipophilic small molecule compound in a Phase II recurrent Glioblastoma Multiforme (reGBM) trial. (globenewswire.com)
  • TOP1 is the molecular target of camptothecin and related drugs such as irinotecan and SN38 (irinotecan's active metabolite). (hal.science)
  • Several derivatives of camptothecin, such as irinotecan and topotecan, have been developed and approved for the treatment of various cancers, including colorectal, lung, and ovarian cancers. (selfgrowth.com)
  • The antitumor drug camptothecin (CPT) and its analogs inhibit the rejoining step of the breakage/rejoining reaction, which traps the enzyme in covalent linkage with DNA (the cleavable complex). (tmu.edu.tw)
  • BN80927 belongs to a novel family of camptothecin analogs, the homocamptothecins, developed on the concept of topoisomerase I (Topo I) inhibition and characterized by a stable seven-membered β-hydroxylactone ring. (aacrjournals.org)
  • Camptothecin (CPT) is a topoisomerase inhibitor. (wikipedia.org)
  • Camptothecin (CPT), a plant alkaloid with antitumor activity, is a specific inhibitor of eukaryotic DNA topoisomerase I. We have previously isolated and characterized a CPT-resistant topoisomerase I isolated from a CPT-resistant human leukemia cell line, CPT-K5. (duke.edu)
  • However, WS cells have been reported to show abnormal sensitivity to the drug camptothecin (an inhibitor of topoisomerase type I). A rapid assay for this sensitivity would be a useful marker of loss of wrn function. (brighton.ac.uk)
  • However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. (wikipedia.org)
  • Non-toxic camptothecin prodrugs are prepared by esterifying the 20-position hydroxyl group of camptothecin derivatives. (rti.org)
  • Camptothecin (CPT) analogues and derivatives serve as a novel class of effective anticancer agents that exert their action against DNA topoisomerase I. This paper presents procedures for the rapid, high frequency regeneration of a camptothecin producing plant, Ophiorrhiza prostrata D. Don from leaf and internode explants via shoot organogenesis. (ejbiotechnology.info)
  • Camptothecin and its derivatives are inhibitors of topoisomerase I, have known activity against several agricultural pests, and are also approved for the treatment of several cancers. (westminster.ac.uk)
  • Camptothecin (Camptotheca acuminata), (GoldBio Catalog # C-705) has also been produced by endosymbiotic fungi present in Camptotheca acuminata, which is a tree predominantly found in southern China. (goldbio.com)
  • Our experiments showed that camptothecins (CPTs) are primarily accumulated in glandular trichomes in Camptotheca. (benthamopen.com)
  • Camptothecin (CPT), first isolated from Chinese tree Camptotheca acuminate, produces rapid and prolonged inhibition of DNA synthesis and induction of DNA damage by targeting topoisomerase I (top1), which is highly activated in cancer cells . (bvsalud.org)
  • Semisynthetic derivative of camptothecin, an alkaloid extract from the Camptotheca acuminate tree. (medscape.com)
  • The proposed tumor-cell targeted formulation was shown to be able to simultaneously host the model anticancer drug camptothecin and a pyrene-modified BODIPY fluorophore, based on dynamic light scattering, small-angle X-ray scattering, and cryogenic transmission electron microscopy. (unica.it)
  • Scholars@Duke publication: Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites. (duke.edu)
  • Camptothecin is an alkaloid compound used as an anti-cancer agent. (goldbio.com)
  • In these patients, as well as in patients from the Phase I trial, no Grade 3 or 4 diarrhea was observed, which is one of the challenges of the earlier generation Camptothecin-based compounds. (globenewswire.com)
  • Tests of the growth inhibition potential of MEC in seven human tumor cell lines showed that the compound was approximately 2-18-fold more cytotoxic than lurtotecan, topotecan, and 7-ethyl-10-hydroxy-20(S)-camptothecin (SN-38). (eur.nl)
  • We identified rubitecan (a synthetic derivative of camptothecin) as a hit compound that reduced A. aegypti larval motility. (westminster.ac.uk)
  • Camptothecin has been found to inhibit an enzyme called topoisomerase I, which plays a critical role in DNA replication and repair. (selfgrowth.com)
  • We extended our investigation to adult mosquitoes and found that camptothecin increased lethality when delivered in a blood meal to A. aegypti adults at 100 µM and 10 µM, and completely blocked egg laying when fed at 100 µM. (westminster.ac.uk)
  • In the current study, we demonstrate a strategy to coordinate the release of camptothecin (CPT) and α-tocopherylsuccinate (TOS) from hybrid micelles for nucleus and mitochondrion interferences. (statsignals.com)
  • From the dynamic light scattering measurements, the hydrodynamic diameter values of camptothecin-loaded alkyldimethylamine oxide and nonionic micelles were found in the range of 4-42 nm and 5-120 nm, respectively. (edu.pl)
  • The values of the packing parameter of camptothecin-loaded dodecyldimethylamine oxide micelles indicate their spherical shape at all the investigated surfactant concentrations. (edu.pl)
  • The 125- and 160-kDa proteins localized in the nucleolus and precisely within certain granules which are known to appear in the nucleolar area after camptothecin administration. (nih.gov)
  • This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA strand and forming a transient protein-DNA covalent complex. (mdpi.com)
  • Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. (tmu.edu.tw)
  • New Topoisomerase I mutations are associated with resistance to camptothecin. (hal.science)
  • Camptothecin is an important chemotherapeutic agent used in the treatment of several cancers and most commonly used as first line drug in treatment of colon cancer. (jptcp.com)
  • The solubilisation of poorly soluble antineoplastic drug camptothecin by nonionic surfactants (polysorbates and octylphenol ethoxylates) and alkyldimethylamine oxide surfactants with the alkyl chain length 8 to 16 carbon atoms was investigated. (edu.pl)
  • Camptothecin has also been found in other plants including Chonemorpha fragrans. (wikipedia.org)
  • Camptothecin is found in Mappia foetida ( Nothapodytes foetida ), a plant native to eastern India. (goldbio.com)
  • Using this assay, we have found that a significantly increased level of strand breaks can be demonstrated in WS cells treated with camptothecin compared with normal controls. (brighton.ac.uk)
  • By inhibiting this enzyme, camptothecin prevents cancer cells from dividing and can induce cell death . (selfgrowth.com)
  • The decreasing number of oxyethylene units and the extension of the hydrophobic part of nonionic surfactant molecule resulted in the increase of camptothecin solubility. (edu.pl)
  • We are excited to present at this year's 5th Meridian Clinical Trials conference and share perspectives on developing new therapies in various disease areas to improve the lives of patients and to demonstrate AR-67's therapeutic potential in reGBM, as well as in other difficult-to-treat cancers for which Camptothecins are administered in combination therapies," said Tina Runk, EVP of Clinical Operations, Co-Founder, and Director of Vivacitas. (globenewswire.com)
  • Animals were divided into four groups: Group I: normal control, Group II: DMH treated, Group III: DMH+ CPT-SS-Biotin treated and Group IV: DMH+ standard camptothecin. (jptcp.com)