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.
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)

RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and ramucirumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and ramucirumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet know whether giving cetuximab and irinotecan hydrochloride together is more effective with or without ramucirumab in treating colorectal cancer.. PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab and irinotecan hydrochloride with or without ramucirumab work in treating patients with advanced colorectal cancer with progressive disease after treatment with bevacizumab-containing chemotherapy. ...
Title: Transport Mechanism-Based Drug Molecular Design: Novel Camptothecin Analogues to Circumvent ABCG2-associated Drug Resistance of Human Tumor Cells. VOLUME: 12 ISSUE: 3. Author(s):Toshihisa Ishikawa, Yoji Ikegami, Kazumi Sano, Hiroshi Nakagawa and Seigo Sawada. Affiliation:Professor, Department ofBiomolecular Engineering, Graduate School of Bioscience and Biotechnology,Tokyo Institute of Technology, 4259-B-60 Nagatsuta, Midori-ku,Yokohama, 226-8501, Japan;. Keywords:ABCG2 gene, Camptothecin, antitumor, membrance vesicle, intracellular accumulation, drug development. Abstract: Acquired and intrinsic drug resistance in cancer is the major obstacle to long-term, sustained patient response to chemotherapy. Irinotecan (CPT-11) is a widely-used potent antitumor drug that inhibits mammalian DNA topoisomerase I (Topo I). However, overexpression of ABCG2 (BCRP/MXR/ABCP) reportedly confers cancer cells resistance to SN-38, the active form of CPT-11. To circumvent the ABCG2-associated drug resistance, ...
RATIONALE: Drugs used in chemotherapy, such as capecitabine and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy, cetuximab, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.. PURPOSE: This phase I/II trial is studying the side effects of giving capecitabine and irinotecan hydrochloride together with cetuximab and radiation therapy and to see how well it works in treating patients undergoing surgery for locally advanced rectal cancer. ...
Camptothecin analogues showing more potent anti-tumor activity than a naturally occurring alkaloid camptothecin, which also exhibit an immunosuppressive activity, in which the 1-ethyl of camptothecin is replaced by various members of substitutents such as alkyls (except ethyl), alkenyls, alkynyls, aralkyls or aryloylalkyls; being produced from readily accessible starting materials on totally synthetic method newly developed by the present inventor.
Advanced small cell lung cancer (SCLC) has a dismal prognosis. Modulation of the camptothecin topotecan, approved for second-line therapy, may improve response. Our recent finding of synergistic enhancement of the cytotoxic activity of camptothecin (CPT) by cyclin-dependent kinase 4 inhibitors is extended here to a panel of camptothecin analogs comprising 10-hydroxy-CPT (HOCPT), topotecan (TPT; 9-[(dimethylamino)-methyl]-10-hydroxy-CPT), 9-amino-CPT (9AC), 9-nitrocamptothecin (rubitecan), SN38 (7-ethyl-10-hydroxycamptothecin) and 10-hydroxy-9-nitrocamptothecin (CPT109) in combination with PD0332991, CDK4I, roscovitine and olomoucine. SCLC cell lines employed are chemoresistant NCI-H417 and DMS153 and the chemosensitive SCLC26A line established at our institution. The CPT analogs exhibiting highest cytotoxicity towards the three SCLC lines tested were SN38 and 9AC, followed by rubitecan, HOCPT, TPT and CPT109. NCI-H417 and DMS153 revealed an approximately 25-fold and 7-fold higher resistance compared to
Irinotecan Hydrochloride Trihydrate for Injection by Sandoz Canada Inc.: Irinotecan belongs to the group of cancer-fighting medications known as antineoplastics. It kills cancer cells by interfering with the genetic material DNA, which is necessary for their growth and reproduction. Irinotecan is usually used in combination with other medications to treat colon or rectal cancer.
Exatecan Mesylate is a synthetic analog of CPT, which is synthesized to increase solubility and enhance anti-tumor efficacy. The anhydrous, alkali-free form of the drug is called DX-8951. In vitro studies have shown that Exatecan Mesylate is more active than SN-38 and Topotecan on cell lines of various types of human tumors (including breast cancer, lung cancer, gastric cancer, and colon cancer). In the human tumor cloning test, Exatecan Mesylatef showed a dose-dependent inhibitory effect on clonal cells from head and neck, liver, non-small cell lung cancer, breast cancer, colon cancer, ovarian cancer, and prostate cancer. Exatecan Mesylate also has broad activity in human tumor xenografts of breast, lung, gastric, pancreatic, esophageal, and colon cancer, CPT-11-resistant non-small cell lung cancer and pancreatic tumor implanted in nude mice.. Although Exatecan Mesylate has high potency and potential bystander lethality, so far, its relatively challenging biophysical properties may limit ...
TY - JOUR. T1 - Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives. AU - Zhu,Gao Xiang. AU - Cheng,Pi Le. AU - Goto,Masuo. AU - Zhang,Na. AU - Morris-Natschke,Susan L.. AU - Hsieh,Kan Yen. AU - Yang,Guan Zhou. AU - Yang,Qian Ru. AU - Liu,Ying Qian. AU - Chen,Hai Le. AU - Zhang,Xiao Shuai. AU - Lee,Kuo Hsiung. PY - 2017. Y1 - 2017. N2 - In an effort to discover potent camptothecin-derived antitumor agents, novel camptothecin analogues with sulfonylpiperazinyl motifs at position-7 were designed and synthesized. They were evaluated for in vitro cytotoxicity with the sulforhodamine-B (SRB) method in five types of human tumor cell lines, A-549, MDA-MB-231, KB, KB-VIN and MCF-7. With IC50 values in the low μM to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan. Furthermore, compounds 12l (IC50, 1.2 nM) and 12k (IC50, 20.2 nM) displayed the ...
Irinotecan Hydrochloride, Temozolomide, and Dinutuximab with or without Eflornithine in Treating Patients with Relapsed or Refractory Neuroblastoma - NCT03794349
Find a comprehensive guide to possible side effects including common and rare side effects when taking Camptosar Injection (Irinotecan Hydrochloride) for healthcare professionals and consumers.
TY - JOUR. T1 - aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer. AU - Fujita, Yoshihiko. AU - Taguri, Masataka. AU - Yamazaki, Kentaro. AU - Tsurutani, Junji. AU - Sakai, Kazuko. AU - Tsushima, Takahiro. AU - Nagase, Michitaka. AU - Tamagawa, Hiroshi. AU - Ueda, Shinya. AU - Tamura, Takao. AU - Tsuji, Yasushi. AU - Murata, Kohei. AU - Taira, Koichi. AU - Denda, Tadamichi. AU - Moriwaki, Toshikazu. AU - Funai, Sadao. AU - Nakajima, Takako Eguchi. AU - Muro, Kei. AU - Tsuji, Akihito. AU - Yoshida, Motoki. AU - Suyama, Koichi. AU - Kurimoto, Takuya. AU - Sugimoto, Naotoshi. AU - Baba, Eishi. AU - Seki, Nobuhiko. AU - Sato, Mikio. AU - Shimura, Takaya. AU - Boku, Narikazu. AU - Hyodo, Ichinosuke. AU - Yamanaka, Takeharu. AU - Nishio, Kazuto. N1 - Funding Information: We thank Okumoto K. and Kitayama T. for technical support and Marco A. De Velasco for critically reading the manuscript. ...
Background The main toxicity of irinotecan in advanced colorectal cancer (CRC) is delayed diarrhoea. Intestinal SN-38, released by deconjugation of the parent glucuronide excreted into the bile or produced in situ by intestinal carboxylesterase, is toxic to the intestinal epithelium. The canalicular transport of irinotecan and SN-38G is mediated by ABCC2 (MRP2) and ABCB1 (MDR1) which are both inhibited by ciclosporin. We tested whether irinotecan and ciclosporin was non-inferior for anti-cancer efficacy and superior for toxicity compared with single-agent irinotecan. Methods Six hundred and seventy-two patients with advanced, measurable CRC following prior fluoropyrimidine- containing chemotherapy were randomised to either irinotecan 3-weekly 350 mg/m 2 (or 300 mg/m 2 if age | 70 or performance status (PS) = 2) or 3-weekly irinotecan at 140 mg/m 2 (120 mg/m 2 if age | 70 or PS = 2) with ciclosporin 3 mg/kg t.d.s. for three days by mouth starting on the morning before irinotecan. The primary end
TY - JOUR. T1 - Seeing the forest through the trees. T2 - A systematic review of the safety and efficacy of combination chemotherapies used in the treatment of metastatic colorectal cancer. AU - Bekaii-Saab, Tanios. AU - Wu, Christina. PY - 2014/7. Y1 - 2014/7. N2 - Combinations of fluoropyrimidines with oxaliplatin or irinotecan plus a biologic agent are standard treatments for metastatic colorectal cancer (mCRC). Recent approvals of first-line cetuximab, second-line ziv-aflibercept, and regorafenib as salvage therapy have increased the complexity of the treatment armamentarium. To define optimal regimens, we systematically reviewed combination chemotherapy trials (N= 83). Descriptive analyses focusing on fluoropyrimidine formulation, oxaliplatin vs irinotecan combinations, and compatibility with biologics indicated the following: infusional 5-fluorouracil (5-FU) yielded better efficacy and safety than bolus 5-FU. Capecitabine had similar outcomes and better safety than 5-FU with oxaliplatin ...
In the intent-to-treat analysis of the pooled data across all three studies, 193 of the 304 patients began therapy at the recommended starting dose of 125 mg/m2. Among these 193 patients, 2 complete and 27 partial responses were observed, for an overall response rate of 15.0% (95% Confidence Interval [CI], 10.0% to 20.1%) at this starting dose. A considerably lower response rate was seen with a starting dose of 100 mg/m2. The majority of responses were observed within the first two cycles of therapy, but responses did occur in later cycles of treatment (one response was observed after the eighth cycle). The median response duration for patients beginning therapy at 125 mg/m2 was 5.8 months (range, 2.6 to 15.1 months). Of the 304 patients treated in the three studies, response rates to Irinotecan were similar in males and females and among patients older and younger than 65 years. Rates were also similar in patients with cancer of the colon or cancer of the rectum and in patients with single and ...
Camptothecin analogues have become mainstays of chemotherapy for numerous malignancies (11). The mechanisms of action and resistance to camptothecins have extensively been investigated (12-14). The parent camptothecin molecule has several disadvantages: it is highly insoluble, and it is in the inactive carboxylate form at physiologic pH and, additionally, the inactive carboxylate form binds preferentially to human serum albumin, further shifting the equilibrium to this form (15, 16).. Clinical trials with the parent camptothecin (NSC 10880) in solid tumors, melanoma, and gastrointestinal malignancies (6, 7, 17, 18) were conducted by the National Cancer Institute more than 30 years ago. This compound was handicapped by dose limiting hemorrhagic cystitis (occurring in 5 of 15 patients) and severe bone marrow suppression (7, 18). Further investigation showed that a large fraction of camptothecin was excreted in urine where an acidic environment favors closing of the lactone and a reactivation of ...
Sequence-specific camptothecins are useful tools to inhibit specifically gene expression. The camptothecins are attached to the 3 end of triplex-forming
The next step was: The efficacy 5-FU/LV in combination with irinotecan or oxaliplatin in patients with metastatic CRC has been well documented in various phase II trials. To determine the most effective sequence of therapy, researchers randomized patients receive either a 2-hour infusion of leucovorin (200 mg/m2 or 400 mg/m2) on day 1 and irinotecan (180 mg/m2) followed by bolus 5-FU (400 mg/m2) and a 46-hour infusion of 5-FU (2400-3000 mg/m2) every 2 weeks (FOLFIRI) or the same regimen with oxaliplatin (100 mg/m2) replacing irinotecan on day 1 (FOLFOX6). Patients received the assigned therapeutic regimen until progression or unacceptable toxicity, at which time they crossed over and received the alternate regimen. Patients in the FOLFIRI group were crossed over to receive FOLFOX6 and those in the FOLFOX6 group were crossed over to the FOLFIRI arm. Of 109 patients randomized to FOLFIRI treatment, 81 (74%) were switched to FOLFOX6. Of 111 patients randomized to FOLFOX6, 69 (62%) switched to ...
Cetuximab. Cetuximab is a recombinant chimeric human:murine immunoglobulin G1 antibody that binds to the extracellular domain of the EGFR (81), promoting receptor internalization and degradation without receptor phosphorylation and activation (82-84). Several studies have shown that cetuximab is capable of inhibiting growth of EGFR-expressing tumor cells in vitro, and treatment with cetuximab results in marked inhibition of tumor growth in nude mice bearing xenografts of human cancer cell lines. Additionally, treatment with cetuximab in combination with chemotherapeutic drugs or radiotherapy is effective in eradicating well-established tumors in nude mice (81, 85, 86) and may even be able to reverse the resistance to some cytotoxic agents in these xenografts (86).. Cetuximab is approved for use in patients with EGFR-expressing metastatic colorectal cancer refractory to irinotecan-based chemotherapy, either in combination with irinotecan (for irinotecan-refractory patients) or as monotherapy (for ...
Background: Poly (ADP-ribose) polymerase (PARP) is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitormediated DNA damage. This Phase I study determined the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK) and pharmacodynamics (PD) of veliparib, an orally-bioavailable PARP 1/2 inhibitor, in combination with irinotecan. Methods: Patients with advanced solid tumors were treated with 100 mg/m2 irinotecan on days 1 and 8 of a 21-day cycle. Twice-daily (BID) oral dosing of veliparib (10-50 mg) occurred days 3- 14 (Cycle 1) and days -1-14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Paired tumor biopsies were obtained after irinotecan alone and veliparib/irinotecan to evaluate PARP1/2 inhibition and explore DNA damage signals (nuclear gamma-H2AX and pNBS1). Results: Thirty-five patients were treated. DLTs included fatigue, ...
TY - JOUR. T1 - Novel 20(S)-sulfonylamidine derivatives of camptothecin and the use thereof as a potent antitumor agent. T2 - A patent evaluation of WO2015048365 (A1). AU - Beretta, Giovanni Luca. AU - Zaffaroni, Nadia. AU - Varchi, Greta. PY - 2016/5/3. Y1 - 2016/5/3. N2 - A series of camptothecin (CPT) derivatives featuring acyl-esterification of the 20(S)-hydroxyl group with a residue containing a sulfonylamidine moiety is synthesized via a Cu catalyzed three-component reaction. The compounds show remarkable cytotoxicity against a panel of tumor cells, including a cell line exhibiting Multi-Drug Resistant (MDR) phenotype. The patent develops 9a, the best derivative of the series, that i) selectively poisons DNA Topoisomerase I (TopoI); ii) induces cell-cycle S-phase arrest with activation of the DNA damage response pathway and apoptosis induction and iii) shows considerable in vivo antitumor potency. We envision that the peculiar modification of the 20(S)-hydroxyl group of CPT with a ...
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Although the prognosis of childhood cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these DNA-topo …
The plant alkaloid camptothecin (CPT) has demonstrated the ability to inhibit replication of the equine anemia virus (E1AV) and the human immunodeficiency virus (HIV) in infected cells in culture....
The present study describes camptothecin resistance and the potential for drug glucuronidation in two cell lines overexpressing the ABC half-transporter, MXR. These sublines, S1-M1-80 and MCF-7 AdVp3000, show high levels of cross-resistance toward mitoxantrone, epirubicin, the CPT-11 metabolite SN-38, topotecan, and several other camptothecins (32) . This cross-resistance is associated with reduced drug accumulation and increased drug efflux. Using TLC, we investigated the ability of the sensitive and resistant cell lines to glucuronidate different compounds. Lysates from both S1-M1-80 resistant cells and S1 parental cells were able to glucuronidate 4-MU and epirubicin with no evidence of increased capacity in the resistant cells. In contrast, enzymatic assays indicated an up-regulation of glucuronidating capacity in the resistant breast cancer cells, and quantitative PCR demonstrated an increase in UGT1A mRNA. These results are consistent with a role for MXR in resistance to the camptothecins ...
This study determined the disposition of irinotecan hydrochloride trihydrate (CPT-11) after i.v. infusion of 125 mg/m2 (100 μCi) [14C]CPT-11 in eight patients with solid tumors. Mean ± S.D. recovery of radioactivity in urine and feces was 95.8 ± 2.7% (range 92.2-100.3%, n = 7) of dose. Radioactivity in blood, plasma, urine, and feces was determined for at least 168 h after dosing. Fecal excretion accounted for 63.7 ± 6.8 (range 54.2-74.9%, n = 7) of dose, whereas urinary excretion accounted for 32.1 ± 6.9% (range 21.7-43.8%; n = 7) of dose. One patient with a biliary T-tube excreted 30.1% of dose in bile, 14.2% in feces, and 48.2% in urine. Quantitative radiometric HPLC revealed that CPT-11 was the major excretion product in urine, bile, and feces. Aminopentane carboxylic acid (APC) and SN-38 glucuronide (SN-38G) were the most significant metabolites in urine and bile, whereas SN-38 and NPC, a primary amine metabolite, were relatively minor excretion products. SN-38 and APC were the most ...
3566 Background: Phase I/II data showed that ciclosporin (Cs) profoundly reduces the hepatobiliary clearance of irinotecan (Ir), and suggested that 40% standard dose Ir with concurrent Cs (IrCs) may give equal efficacy to standard Ir, with less diarrhoea. PICCOLO is a multicentre randomized controlled trial in which patients (pts) with aCRC, progressing after prior therapy, were randomised to Ir or IrCs. It was designed to detect non-inferior efficacy with reduced toxicity. METHODS: Eligible pts had: measurable aCRC, progressive during/after ≥1 prior regimen with fluoropyrimidines ± other drugs; no prior Ir; WHO PS 0-2. Before summer 2008, pts were allocated 1:1:1 (without prospective KRAS analysis) to Ir, IrCs or Ir/panitumumab. Thereafter, KRAS was analysed prospectively and pts with mutated or undetermined KRAS were allocated 1:1 to Ir (irinotecan 350 mg/m(2) [300 mg/m(2) if ≥70 yrs or PS2], q3w), or IrCs (irinotecan 140 mg/m(2) [120 mg/m(2) if ≥70 yrs or PS2] d1, Cs 3 mg/kg tds d0-2, q3w).
7-Ethyl-10-HydroxyCamptothecin (SN-38) - Browse to find 7-Ethyl-10-HydroxyCamptothecin (SN-38) sellers, suppliers, wholesalers, companies, manufacturers, exporters, factories.
A crystalline form of 5(S)-(2-hydroxyethoxy)-20(S)-camptothecin diastereoisomer of 5(RS)-(2-hydroxyethoxy)-20(S)-camptothecin is described that is characterized by having an X-ray powder diffraction pattern comprising one or more peak intensities expressed in degrees 2.theta. that are selected from the group consisting of 7.2.+-.0.1, 9.4.+-.0.1, 11.02.+-.0.1, 12.00.+-.0.1, 14.54.+-.0.1, 15.2.+-.0.1, 18.92.+-.0.1, 21.86.+-.0.1, 22.74.+-.0.1 and 26.42.+-.0.1. Methods of making and using the compound are also described.
Guidchem offer qualified suppliers for 7-Ethyl-10-hydroxycamptothecin (CAS NO.86639-52-3) ,Find latest products of 7-Ethyl-10-hydroxycamptothecin manufacturers, suppliers, exporters and producers on
Irinotecan liposomal is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Irinotecan liposomal is used to treat pancreatic cancer that has spread to other parts of the body. Irinotecan liposomal is usually given in combination with other cancer medicines. Irinotecan liposomal may...
Irinotecan liposomal is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Irinotecan liposomal is used to treat pancreatic cancer that has spread to other parts of the body. Irinotecan liposomal is usually given in combination with other cancer medicines. Irinotecan liposomal may...
This study will compare the efficacy of bevacizumab + oxaliplatin + capecitabine versus untreated control in patients with metastatic colorectal cancer,
This observational trial is investigating irinotecan-based regimens (folinic acid + fluorouracil + irinotecan, irinotecan + gimeracil/oteracil/tegafur, and
Differential involvement of the Mre11/Rad50/NBS (M/R/N) complex, BRCA1 and MLH1 in NF-kappaB activation by camptothecin and X- ...
Research Agreement for Camptothecin - Clayton Foundation for Research, Research Development Foundation and SuperGen Inc. and Other Business Contracts, Forms and Agreeements. Competitive Intelligence for Investors.
TY - JOUR. T1 - Camptothecin analogues. T2 - studies from The Johns Hopkins Oncology Center. AU - Slichenmyer, William J.. AU - Rowinsky, Eric K.. AU - Grochow, Louise B.. AU - Kaufmann, Scott H.. AU - Donehower, Ross C.. PY - 1994/1/1. Y1 - 1994/1/1. N2 - The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily ×5 schedule has been developed further with dose escalation using granulocytecolony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous ...
Brain tumor news: Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial.
We report here a tumor-targeting masked phototherapeutic agent 1 (PT-1). This system contains SN-38-a prodrug of the topoisomerase I inhibitor irinotecan. Topoisomerase I is a vital enzyme that controls DNA topology during replication, transcription, and recombination. An elevated level of topoisomerase I is found in many carcinomas, making it an attractive target for the development of effective anticancer drugs. In addition, PT-1 contains both a photo-triggered moiety (nitrovanillin) and a cancer targeting unit (biotin). Upon light activation in cancer cells, PT-1 interferes with DNA re-ligation, diminishes the expression of topoisomerase I, and enhances the expression of inter alia mitochondrial apoptotic genes, death receptors, and caspase enzymes, inducing DNA damage and eventually leading to apoptosis. In vitro andin vivo studies showed significant inhibition of cancer growth and the hybrid system PT-1 thus shows promise as a programmed photo-therapeutic (phototheranostic).. ...
We developed previously a resistant cell line, CEM/C2, from the human leukemia cell line CCRF-CEM by stepwise selection in camptothecin. This cell line is 974-fold more resistant to camptothecin than parental cells. Resistance is only partially explained by 2-fold reductions in topoisomerase I protein and mRNA levels. We further investigated biochemical and molecular features of topoisomerase I in the resistant cell line. Sequence analyses of the top1 cDNA from CEM/C2 identified mutations corresponding to two amino acid substitutions, Met370Thr and Asn722Ser. Asn722Ser is next to the catalytic Tyr723 in a region highly conserved among type I eukaryotic DNA topoisomerases. Recombinant top1 with the corresponding substitution was found to be catalytically active and resistant to camptothecin. These results indicate that camptothecin resistance of CEM/C2 is due to the mutation Asn722Ser and strongly suggest that the asparagine immediately flanking the catalytic tyrosine is important for the ...
TY - JOUR. T1 - Determination of the glucuronide metabolites of the topoisomerase I inhibitors, 7-ethyl-10-hydroxy-camptothecin (SN-38) and NU-ICRF 505 by high performance liquid chromatography. AU - Cummings, J.. AU - Ethell, B T.. AU - Boyd, Gary. AU - Burchell, B.. AU - Smyth, J F.. AU - Jodrell, D I.. PY - 2002. Y1 - 2002. N2 - HPLC methods are presented for the determination of the topoisomerase I inhibitors 7-ethyl 10-hydroxycamptothecin (SN-38) and NU/ICRF 505, their chemical/enzymatic hydrolysis products and glucuronide metabolites in both aqueous media and biological specimens. Chromatographic conditions were optimised for baseline resolution of the water-soluble metabolites from their non-water soluble parent compounds while eetaining compatibility with both atmospheric pressure electrospray ionisation and electron impact ionisation mass spectrometric detection. Solid phase extraction sample preparation utilising a C2-bonded silica sorbent enabled simultaneous recovery of parent ...
FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival
Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20(S)-camptothecin, SN-38 [7-ethyl-10-hydroxy-20(S)-camptothecin], topotecan, and 7-chloromethyl-10,11-methylenedioxy-20(S)camptothecin (CMMDC). The greatest potentiation was observed with the alkylating camptothecin CMMDC. Buthionine sulfoximine pretreatment also increased the number of camptothecin-induced DNA-protein crosslinks, indicating that GSH affects the mechanism of action of camptothecin.
Irinotecan serves as a water-soluble precursor of the lipophilic metabolite SN-38. SN-38 is formed from irinotecan by carboxylesterase-mediated cleavage of the carbamate bond between the camptothecin moiety and the dipiperidino side chain. SN-38 is approximately 1000 times as potent as irinotecan as an inhibitor of topoisomerase I purified from human and rodent tumor cell lines. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold; however, the plasma area under the concentration versus time curve (AUC) values for SN-38 are 2% to 8% of irinotecan and SN-38 is 95% bound to plasma proteins compared to approximately 50% bound to plasma proteins for irinotecan [see Clinical Pharmacology (12.3)]. The precise contribution of SN-38 to the activity of CAMPTOSAR is thus unknown. Both irinotecan and SN-38 exist in an active lactone form and an inactive hydroxy acid anion form. A pH-dependent equilibrium exists between the two forms such that an ...
Cells maintain genomic stability by the coordination of DNA-damage repair and cell-cycle checkpoint control. In replicating cells, DNA damage usually activates intra-S-phase checkpoint controls, which are characterized by delayed S-phase progression and increased Rad53 phosphorylation. We show that in budding yeast, the intra-S-phase checkpoint controls, although functional, are not activated by the topoisomerase I inhibitor camptothecin (CPT). In a CPT-hypersensitive mutant strain that lacks the histone 2A (H2A) phosphatidylinositol-3-OH kinase (PI(3) K) motif at Ser 129 (h2a-s129a), the hypersensitivity was found to result from a failure to process full-length chromosomal DNA molecules during ongoing replication. H2A Ser 129 is not epistatic to the RAD24 and RAD9 checkpoint genes, suggesting a non-checkpoint role for the H2A PI(3) K site. These results suggest that H2A Ser 129 is an essential component for the efficient repair of DNA double-stranded breaks (DSBs) during replication in yeast, ...
Genotype-directed Phase II Study of Irinotecan Dosing in Metastatic Colorectal Cancer (mCRC) Patients Receiving FOLFIRI + Bevacizumab study is currently recruiting healthy volunteers at Indiana CTSI, IN
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BACKGROUND: The identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Childrens Oncology Group study AHEP0731 included a HR stratum to explore the efficacy of novel agents. Herein, the authors report the response rate to the combination of vincristine (V) and irinotecan (I) and the outcome of patients with high-risk hepatoblastoma. METHODS: Patients with newly diagnosed metastatic hepatoblastoma or those with a serum alpha-fetoprotein (AFP) level /mL were eligible. Patients received 2 cycles of V at a dose of 1.5 mg/m2 /day intravenously on days 1 and 8 and I at a dose of 50 mg/m2 /day intravenously on days 1 to 5. Patients were defined as responders if they had either a 30% decrease in tumor burden according to Response Evaluation Criteria In Solid Tumors (RECIST) or a 90% ( | 1 log10 ) decline in their AFP level. Responders were to receive 2 additional cycles of VI intermixed with 6 cycles of the combination of cisplatin, doxorubicin, 5-fluorouracil, and vincristine (C5VD)
A phase II study was conducted to assess the response rate and toxicity profile of the combination of irinotecan (CPT-11, Camptosar) and cisplatin (Platinol) administered weekly to patients with untreated advanced 1
In vivo neuroblastoma (NB) xenograft model, resistant to the DNA-topoisomerase I inhibitor irinotecan (CPT-11), has been established to study resistance mechanisms acquired in a therapeutic setting. Common mechanisms of resistance were not involved in this resistance. Thus, we compared the gene expression profiles of sensitive, resistant, and reverted tumors using cDNA expression arrays. Expression of selected transcripts was confirmed by quantitative real-time PCR. We found that pleiotrophin (PTN), a heparin-binding growth factor, was the only gene significantly affected: PTN gene expression was downregulated in all resistant tumors (8-14-fold) as compared to sensitive tumors, and was increased (2-4-fold) in all reverted tumors as compared to resistant tumors. PTN thus appeared to be a likely candidate gene associated with resistance to CPT-11 in this in vivo model. To investigate the direct implication of PTN in NB, we transfected two NB cell lines with RNA interferences in order to silence PTN. PTN
TY - JOUR. T1 - 11H-Isoquino[4,3-c]cinnolin-12-ones. T2 - Novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity. AU - Ruchelman, Alexander L.. AU - Singh, Sudhir K.. AU - Ray, Abhijit. AU - Wu, Xiaohua. AU - Yang, Jin Ming. AU - Zhou, Nai. AU - Liu, Angela. AU - Liu, Leroy-Fong. AU - LaVoie, Edmond J.. PY - 2004/2/15. Y1 - 2004/2/15. N2 - Recent studies have identified 2,3-dimethoxy-8,9-methylenedioxy-11-[(2- dimethylamino)ethyl]-11H-isoquino[4,3-c]cinnolin-12-one (1a) as a novel topoisomerase I-targeting agent with potent cytotoxic activity. The effect of varied substituents at the 11-position of 2,3-dimethoxy-8,9-methylenedioxy-11H- isoquino[4,3-c]cinnolin-12-ones on topoisomerase I-targeting activity and cytotoxicity was evaluated. Potent TOP1-targeting activity was observed when the 11-position was substituted with either a 2-(N,N-dimethylamino)ethyl, a 2-(N,N-diethylamino)ethyl, a n-butyl, or a 2-(pyrrolidin-1-yl)ethyl group. The addition of a β-methyl ...
There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy. Our PDO test predicted response of the biopsied lesion in more than 80% of patients treated with irinotecan-based therapies without misclassifying patients who would have benefited from treatment. This correlation was specific to irinotecan-based chemotherapy, however, and the PDOs failed to predict outcome for treatment with 5-fluorouracil plus oxaliplatin. Our data suggest that PDOs could be used to prevent cancer patients from undergoing ineffective irinotecan-based chemotherapy.. ...
In southern China, where Camptotheca acuminata is native, people call these big-leafed trees Happy Trees. Chinese herbalists have been prescribing medicine from the leaves for centuries to treat various ailments, including leukemia. In the 1950s, National Cancer Institute researchers in the U.S. isolated the alkaloid camptothecin from the leaves, and today, several drugs derived from camptothecin help treat ovarian and colon cancer.. (Podcast: The Plant Detective, 8/16/14). ...
MeSH-minor] Aged. Aged, 80 and over. Area Under Curve. Camptothecin / administration & dosage. Camptothecin / adverse effects. Camptothecin / analogs & derivatives. Camptothecin / pharmacokinetics. Carcinoma, Small Cell / drug therapy. Cholangiocarcinoma / drug therapy. Deoxycytidine / administration & dosage. Deoxycytidine / adverse effects. Deoxycytidine / analogs & derivatives. Deoxycytidine / pharmacokinetics. Diarrhea / chemically induced. Dose-Response Relationship, Drug. Drug Interactions. Female. Gastrointestinal Hemorrhage / chemically induced. Half-Life. Humans. Infusions, Intravenous. Lung Neoplasms / drug therapy. Male. Middle ...
The present invention provides generally a compound having the following general formula (1): wherein R1 and R2 are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxyl group, an aryloxy group, an acyloxy group, -OC(O)ORd, wherein Rd is an alkyl group, a carbamoyloxy group, a halogen, a hydroxyl group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, -SRc, wherein, Rc is hydrogen, an acyl group, an alkyl group, or an aryl group, or R1 and R2 together form a group of the formula -O(CH2)nO- wherein n represents the integer 1 or 2; R3 is H, F, a halogen atom, a nitro group, an amino group, a hydroxyl group, or a cyano group; or R2 and R3 together form a group of the formula -O(CH2)nO- wherein n represents the integer 1 or 2; R4 is H, F, a C1-3 alkyl group, a C2-3 alkenyl group, a C2-3 alkynyl group, or a C1-3 alkoxyl group; R5 is a C1-10 alkyl group, or a propargyl
The objective of this study is to evaluate the safety and efficacy of Irinotecan Bead in the neoadjuvant treatment (i.e. the Irinotecan Bead is administ
Tumor profiling and response data were available for 12 patients. No difference in clinical activity was seen between the classical and basal-like subtypes, but the numbers were very small, commented Dr. Wainberg.. Safety Overview. Treatment-related adverse events grade ≥ 3 were observed in 69% of patients. The most common toxicity grade ≥ 3 was neutropenia, occurring in 31%; febrile neutropenia developed in 12% of patients, but none discontinued treatment, reported Dr. Wainberg. Of note, granulocyte colony-stimulating factors were not given prophylactically or mandated. This was left up to the institution.. Our findings suggest that NALIRIFOX is tolerable in newly diagnosed metastatic pancreatic cancer. No new safety signals were identified, and its antitumor activity is promising, Dr. Wainberg concluded.. The regimen is now being evaluated in the global randomized phase III NAPOLI-3 trial of previously untreated metastatic pancreatic adenocarcinoma. In NAPOLI-3, NALIRIFOX is being ...
Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer.[3] For colon cancer it is used either alone or with fluorouracil.[3] For small cell lung cancer it is used with cisplatin.[3] It is given by slow injection into a vein.[3] Common side effects include diarrhea, vomiting, bone marrow suppression, hair loss, shortness of breath, and fever.[3] Other severe side effects include blood clots, colon inflammation, and allergic reactions.[3] Those with two copies of the UGT1A1*28 gene variant are at higher risk for side effects.[3] Use during pregnancy can result in harm to the baby.[3] Irinotecan is in topoisomerase inhibitor family of medication.[4] It works by blocking topoisomerase 1 which results in DNA damage and cell death.[3] Irinotecan was approved for medical use in the United States in 1996.[3] It is on the World Health Organizations List of Essential Medicines, the safest and most effective medicines needed in ...
RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the
Kessel, D, Effects of camptothecin on rna synthesis in leukemia l1210 cells. (1971). Subject Strain Bibliography 1971. 891 ...
Patients with elevated bilirubin treated with irinotecan have an increased risk of toxicity, and a dose reduction is recommended. Patients with elevated AST, creatinine or prior pelvic radiation do not appear to have increased sensitivity to irinotecan, but the data are not adequate to support a specific dosing recommendation.
Health,... - Offers Unique Formulation of Important Cancer Medication -...LAKE FOREST Ill. Feb. 27 /- Hospira Inc.(NY... We are continuing to grow our leading portfolio of generic medication...Hospiras irinotecan product portfolio extends beyond the formulations...,Hospira,Launches,Generic,Irinotecan,Injection,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Anwendungsgebiete Panitumumab Vectibix ist indiziert zur Behandlung von erwachsenen Patienten mit metastasiertem kolorektalem Karzinom (mCRC, metastatic colorectal cancer) mit RAS-Wildtyp in der Erstlinientherapie in Kombination mit FOLFOX oder FOLFIRI. in der Zweitlinientherapie in Kombination mit FOLFIRI bei Patienten, die in der Erstlinientherapie eine Fluoropyrimidin-haltige Chemotherapie erhalten haben (ausgenommen Irinotecan). als Monotherapie nach Versagen von Fluoropyrimidin-, Oxaliplatin- und Irinotecan-haltigen Chemotherapieregimen. Fachinformation Vectibix, Stand März 2015 Zulassungserweiterung März 2015
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DSpace-CRIS consists of a data model describing objects of interest to Research and Development and a set of tools to manage the data. Standard DSpace is used to deal with publications and data sets, whereas DSpace-CRIS involves other CRIS entities: Researcher Pages, Projects, Organization Units and Second Level Dynamic Objects (single entities specialized by a profile, such as Journal, Prize, Event etc; because any profile can define its own set of properties and nested objects ...
OConnell BC, Adamson B, Lydeard JR, Sowa ME, Ciccia A, Bredemeyer AL, et al. A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability. Mol Cell. 2010 ;40(4):645-57. ...
inproceedings{318597, author = {MONSAERT, ELS and De Vos, Martine and Peeters, Marc}, booktitle = {ACTA GASTRO-ENTEROLOGICA BELGICA}, issn = {0001-5644}, pages = {D59-D59}, title = {A retrospective analysis of the efficacy and toxicity of irinotecan and 5FU/FA in patients with advanced carcinoma of the stomach or oesophagogastric junction}, volume = {66}, year = {2003 ...
Projekt „Repozytorium otwartego dostępu do dorobku naukowego i dydaktycznego UJ współfinansowany w ramach poddziałania 2.3.1 „Cyfrowe udostępnianie zasobów nauki Programu Operacyjnego Polska Cyfrowa z Europejskiego Funduszu Rozwoju Regionalnego i budżetu państwa na podstawie umowy o dofinansowanie nr POPC.02.03.01-00-0030/17-00 ...
... and camptothecin: base sequence analysis and activity against camptothecin-resistant topoisomerases I.". Cancer Res. 63 (21): ... Camptothecin-derived TopI inhibitors function by forming a ternary complex with TopI-DNA and are able to stack between the base ... Camptothecin (CPT) was first derived from the tree Camptotheca acuminata, native to southern China. It was isolated in a United ... Pommier Y (2004). "Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with ...
"Discovery of Camptothecin and Taxol". National Historic Chemical Landmarks. American Chemical Society. Retrieved 2012-10-28. " ... of frozen foods conducted at the USDA-ARS Western Regional Research Center between 1948 and 1965 The discovery of Camptothecin ...
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 ...
... is a semi-synthetic analog of camptothecin with antineoplastic activity. Liposomal lurtotecan was in clinical trials ... "Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C". Tetrahedron. 53 (32): 10953. doi:10.1016/S0040- ...
Alfonso LF, Srivenugopal KS, Arumugam TV, Abbruscato TJ, Weidanz JA, Bhat GJ (March 2009). "Aspirin inhibits camptothecin- ...
He discovered Taxol and camptothecin with Monroe Eliot Wall. Chetan E. Chitnis - worked on molecular parasitology and ...
The direct nitration of camptothecin results in regioselectivity problems. One way that has been used to synthesize Rubitecan ...
"Antifungal Activity of Camptothecin, Trifolin, and Hyperoside Isolated fromCamptotheca acuminata". Journal of Agricultural and ...
... camptothecin". Biochemistry. 25 (6): 1216-21. doi:10.1021/bi00354a004. PMID 3008823. Vasudevachari, M; Antony, A (1982). " ...
... the first established anticancer agent as camptothecin derivatives. 2014 - Hiroshi Nagase [ja]. Design and synthesis of opioid ...
Type 1 topoisomerase is inhibited by irinotecan, topotecan and camptothecin. The human topoisomerase type IB enzyme forms a ...
Li, S.; Zhang, Z.; Cain, A.; Wang, B.; Long, M.; Taylor, J. (2005). "Antifungal Activity of Camptothecin, Trifolin, 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. ...
... "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 ...
... contains alkaloids, such as 'camptothecin' (or CPT), 'chonemorphine', and 'funtumafrine'. 'Camptothecin' ... Anuradha Camptothecin and Camptothecin Producing Plants: Botany, Chemistry, Anticancer Activity, and Biotechnology (2020), p. ...
Aspirin inhibits camptothecin-induced p21CIP1 levels and potentiates apoptosis in human breast cancer cells. International ...
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". ...
Several groups have encapsulated anti-cancer medications such as: Camptothecin, Methotrexate, and Doxorubicin. Results from ...
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 ...
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 ...
Wall ME, Wani MC (February 1995). "Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture ... Wall ME, Wani MC (February 1995). "Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture ...
"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 ...
Futami K, Takagi M, Shimamoto A, Sugimoto M, Furuichi Y (2007). "Increased chemotherapeutic activity of camptothecin in cancer ... "Recapitulation of Werner syndrome sensitivity to camptothecin by limited knockdown of the WRN helicase/exonuclease". ...
Camptothecin-encapsulated BSA-PMMA nanoparticles revealed enhanced anti-tumor activity both in vitro and in animals. Beyond the ... conjugated denatured bovine serum albumin micelles for effective delivery of camptothecin". Polymer Chemistry. 3 (8): 1958. doi ... composed of BSA-PMMA with diameters of around 100 nm were obtained and the water insoluble chemotherapeutic drug camptothecin ...
CheckOrphan is a non-profit organization located in Basel, Switzerland and Santa Cruz, California that is dedicated to rare, orphan and neglected diseases. CheckOrphan offers users an interactive and dynamic platform for all these diseases. This strategy allows visitors to be updated daily on all the latest news and interact with people internationally. This is essential, because due to the nature of these diseases, there is not a large concentration of individuals within any given proximity ...
COMINS, DANIEL LEE, "THE SYNTHESIS OF ANALOGS OF CAMPTOTHECIN" (1977). Doctoral Dissertations. 1139. ...
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... and the chemistry of the camptothecins, together with the mechanism of topoisomerase and the way camptothecins poison this ... Additional resources for Camptothecins in Cancer Therapy (Cancer Drug Discovery and Development) ... Read Online or Download Camptothecins in Cancer Therapy (Cancer Drug Discovery and Development) PDF ... Camptothecins in Cancer Therapy (Cancer Drug Discovery and by Val R. Adams. Posted by admin ...
Namitecan: a Hydrophilic Camptothecin with a Promising Preclinical Profile. Current Medicinal Chemistry ...
Topotecan, a water-soluble camptothecin analog, exists at physiological pH as an equilibrium between the lactone form and the ... The mechanism of topoisomerase I poisoning by a camptothecin analog. PNAS. 2002, 99(24): 15387-15392. ... hydroxy-camptothecin hydrochloride]. J Pharmacol Exp Ther. 2007, 322(3): 1246-1252. ...
S)-(+)-Camptothecin. £42.50 - £42.50 Contact. (S)-(+)-Clopidogrel hydrogen sulfate. Call us for pricing Contact. ...
Biopharma Hypothesis: Design and computational analysis of a derivative of camptothecin. Page 1-10. ...
Nakagawa et al., 2006, Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer ... Yoshikawa et al., 2004, Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells., ... Ishikawa et al., 2006, Transport mechanism-based drug molecular design: novel camptothecin analogues to circumvent ABCG2- ... sulfonylamidine derivatives of camptothecin as potent antitumor agents., J Med Chem ...
Marlene WatkinsJune 15, 2019MainCamptothecin price, DAN15. Supplementary Materials? CAS-110-334-s001. 2 (CCL2), and C\X\C motif ... We also analyzed the effects of CnP alone or in combination with Camptothecin price gemcitabine in the SUIT\2?+?hPSC5 group. ... Cytokine array and ELISA Cytokine Camptothecin price information were likened between CAF\CM and CnP\treated CAF\CM using the ... L PBS Camptothecin price were s.c. injected bilaterally into the flanks of 7\week\aged female NOD\SCID mice (CLEA Japan, Inc., ...
He is co-discoverer of Taxol® and camptothecin™, two anti-cancer drugs considered standard in the treatment to fight ovarian, ...
Looking for Canaan? Find out information about Canaan. 1 According to biblical ethnography, Canaan was the son of Ham and the ancestor for whom the Canaanites were named. 2 Territory, the same as ancient... Explanation of Canaan
185delag 5677insa adriamycin brca1 breaks camptothecin cip1 clones confer doubling du germ insbrca1 mdm obvious parental ... 185delag 5677insa adriamycin brca1 breaks camptothecin cip1 clones confer doubling du germ insbrca1 mdm obvious parental ...
Effects ofover-expression of allene oxide cyclase on camptothecin production by cellcultures of Camptotheca acuminate,African ...
camptothecin essay. *dissertation collective action. *death with interruptions essays. *veterans speech. *essays on competitive ...
We will always work hard to provide our customers with high quality products and considerate services! You are welcome to cooperate with us, Join us and come to win-win!. ...
Cellular Response To Camptothecin. *Cellular Response To Hydroxyurea. *Cellular Macromolecule Catabolic Process ...
br Ethyl hydroxy camptothecin SN is an active metabolite of * br To confirm the level of miR in each ...
Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin. Arch Biochem ...
Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin. Arch Biochem ...
Camptothecin, proposed sprinkler waiver, blog, home, Brefeldin A, channel drains, street furniture, floor grate, VX-809, 17- ...
Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin. Arch Biochem ...
Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin. Arch Biochem ...
Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin. Arch Biochem ...
Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin. Arch Biochem ...
Conjugated eicosapentaenoic acid inhibits human topoisomerase IB with a mechanism different from camptothecin. Arch Biochem ...
  • Hsiang Y-H, Liu LF, Wall ME, Wani MC, Kirshenbaum S, Silber R, Potmesil M. DNA topoisomerase I-mediated DNA cleavage and cytotoxicity of camptothecin analogs. (
  • 3D-QSAR study of 20 ( S)-camptothecin analogs. (
  • Aim: To build up a quantitative structure-activity relationship (QSAR) model of 20 ( S)-camptothecin (CPT) analogs for the prediction of the activity of new CPT analogs for drug design. (
  • Its in vivo antitumor effects were superior to those of current camptothecin analogs against certain tumors. (
  • Camptothecin (CPT) and analogs exhibited additives to synergistic interactions with l -OddC by isobologram analysis. (
  • A practical and concise total synthesis of tricyclic ketone 7 (CDE ring), a valuable intermediate for the synthesis of racemic camptothecin and analogs, was described (8 chemical steps and 29% overall yield). (
  • This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. (
  • Camptothecin has poor water solubility and several camptothecin analogs and derivatives have been synthesized in an attempt to improve water solubility, bioavailability, and lactone stability. (
  • 2: Huang Q, Wang L, Lu W. Evolution in medicinal chemistry of E-ring-modified Camptothecin analogs as anticancer agents. (
  • Both cell lines were 400- to 1000-fold more resistant to topotecan, 9-amino-20( S )-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. (
  • Over the past decade, camptothecin agents such as topotecan and irinotecan have demonstrated activity against Ewing sarcoma, especially in combination with alkylating agents. (
  • The discovery of Camptothecin spurred the development of many derivatives with superior activity and solubility, including Irinotecan (sc-202186) and Topotecan (sc-204919). (
  • It is the only known target of the alkaloid camptothecin, from which the potent anticancer agents irinotecan and topotecan are derived. (
  • Received a prior camptothecin analog (e.g., topotecan, irinotecan). (
  • 6: Mollica A, Stefanucci A, Feliciani F, Cacciatore I, Cornacchia C, Pinnen F. Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer. (
  • The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. (
  • TOP1 is the molecular target of camptothecin and related drugs such as irinotecan and SN38 (irinotecan's active metabolite). (
  • Currently, topoisomerase inhibitors hold a prominent place among antibiotics and anticancer drugs in active medical use, as inhibitors like doxorubicin (anthracycline, TopII inhibitor), etoposide (TopII inhibitor), ciprofloxaxin (fluoroquinolone, TopII inhibitor), and irinotecan (camptothecin derivative, TopI inhibitor) were all included in the 2019 WHO Model List for Essential Medicines. (
  • Camptothecin analogues showing more potent anti-tumor activity than a naturally occurring alkaloid camptothecin, which also exhibit an immunosuppressive activity, in which the 1-ethyl of camptothecin is replaced by various members of substitutents such as alkyls (except ethyl), alkenyls, alkynyls, aralkyls. (
  • The present invention relates to camptothecin analogues. (
  • More particularly, it relates to novel camptothecin analogues showing potent anti-tumor and immunosuppressive activities, and to a process for producing them. (
  • Said camptothecin analogues may be represented by the following general formula (I): ##STR1## (wherein R is a lower alkyl of 3 - 6 carbon atoms, a lower alkenyl of 3 - 5 carbon atoms, a lower alkynyl of 2 - 3 carbon atoms, an aralkyl of 7 - 8 carbon atoms, or an aryloylalkyl of 8 - 10 carbon atoms). (
  • The present inventor has succeeded in developing a new process by which various kinds of camptothecin analogues can be produced in good yield, in which the 1-ethyl of camptothecin is replaced by a wide variety of substituents. (
  • Moreover, it has been elucidated that the resultant camptothecin analogues show more potent anti-tumor action than camptothecin itself. (
  • The cell lines demonstrated much less resistance to camptothecin and to several camptothecin analogues. (
  • The current status of camptothecin analogues as antitumor agents. (
  • These results suggest that 7-peptidyl derivatives represent a new class of camptothecin analogues. (
  • We found that GSH depletion increases the growth-inhibitory activity and the amount of DPCs formed by a number of camptothecin analogues. (
  • We also report the structure-activity relationship of camptothecin-peptide conjugates CGMMDC, ECMMDC, and CysMMDC and propose that 7-peptidyl camptothecins may be an important new class of camptothecin analogues. (
  • To circumvent the ABCG2-associated drug resistance, we have synthesized and characterized a total of fourteen new camptothecin (CPT) analogues with respect to both the inhibition of Topo I and the substrate specificity of ABCG2. (
  • Toshihisa Ishikawa, Yoji Ikegami, Kazumi Sano, Hiroshi Nakagawa and Seigo Sawada, " Transport Mechanism-Based Drug Molecular Design: Novel Camptothecin Analogues to Circumvent ABCG2-associated Drug Resistance of Human Tumor Cells", Current Pharmaceutical Design (2006) 12: 313. (
  • 7. Sriram D, Yogeeswari P, Thirumurugan R, and Ratan Bal T. Camptothecin and its analogues: a review on their chemotherapeutic potential. (
  • 20(S)-Camptothecin, the 20(S)-camptothecin sodium salt, and 12 analogues with substituents on the A ring differ widely in their effectiveness in the treatment of murine L1210 lymphoblastic leukemia in vivo. (
  • Potmesil, M. / DNA topoisomerase I-mediated DNA cleavage and cytotoxicity of camptothecin analogues . (
  • We nasally administered the anti-tumor drug camptothecin (CPT) in solution and in methoxy poly(ethylene glycol) (MPEG)/poly(e-caprolactone) (PCL) amphiphilic block copolymers (MPEG-PCL) and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat) MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. (
  • In contrast, the anticancer drug, camptothecin (CPT) induced a steady accumulation of p21CIP1 protein. (
  • The novel supramolecular complexes were prepared with a water-insoluble anticancer drug camptothecin (CPT) loading onto functionalized multiwalled carbon nanotubes via π-stacking, in order to improve their solubility and antitumor activity. (
  • Cleavable complexes, the covalent Topo1-DNA intermediates, become DNA damaged when the catalytic cycles are inhibited by the anti-tumor drug camptothecin (CPT). (
  • Camptothecin (CPT) is a potent DNA enzyme topoisomerase I (topo I) inhibitor with an IC50 and IC70 of 50 nM and 0.225 μM for breast cancer cell line MDA-MB-231. (
  • Metabolism of camptothecin, a potent topoisomerase I inhibitor, in the isolated perfused rat liver. (
  • CRLX101 is a nanoparticle drug conjugate composed of 20 (S)-camptothecin (a potent and highly selective topoisomerase I inhibitor) conjugated to a linear, cyclodextrinpolyethylene glycol-based polymer. (
  • I. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor fromCamptotheca acuminata, Journal of the American Chemical Society, (1966), pp. 3888-3890, Volume-Issue 88:16, ACS Publications, Washington, DC. (
  • CKD-602 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan) is a synthetic water-soluble camptothecin derivative and topoisomerase inhibitor that has been shown to have clinical anticancer effect against ovarian and lung cancer. (
  • Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20( S )-camptothecin, SN-38 [7-ethyl-10-hydroxy-20( S )-camptothecin], topotecan, and 7-chloromethyl-10,11-methylenedioxy-20( S )-camptothecin (CMMDC). (
  • We selected camptothecin for downstream studies and found that it is a limited spectrum enterovirus inhibitor that inhibits coxsackievirus A16 but not ECHOvirus 7. (
  • Camptothecin, a DNA topoisomerase 1 (TOP1) inhibitor, inhibits both viral RNA replication and translation based on luciferase replicon studies. (
  • Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of eukaryotic topoisomerase I (Top 1). (
  • Camptothecin is an alkaloid topoisomerase l (topo l) inhibitor with anticancer properties. (
  • S)-10-hydroxy-Camptothecin is an inhibitor of topoisomerase I originally isolated from the Chinese tree C. acuminata. (
  • Topoisomerase inhibitor classes have been derived from a wide variety of disparate sources, with some being natural products first extracted from plants (camptothecin, etoposide) or bacterial samples (doxorubicin, indolocarbazole), while others possess purely synthetic, and often accidental, origins (quinolone, indenoisoquinoline). (
  • Camptothecin and its derivatives are topoisomerase I inhibitors. (
  • As camptothecins bind at the interface of the TOP1â€"DNA complex, they represent a paradigm for interfacial inhibitors that reversibly trap macromolecular complexes. (
  • Metabolic and transcriptional analyses in response to potent inhibitors establish MEP pathway as major route for camptothecin biosynthesis in Nothapodytes nimmoniana (Graham) Mabb. (
  • Despite their highly synergistic activity in preclinical models, human studies combining PARP inhibitors and camptothecins have not translated into clinical benefit due to enhanced toxicity with the combination. (
  • One approach to improve ability to combine camptothecins with agents that sensitize their activity like PARP inhibitors is to use alternative formulations that minimize toxicity to the normal tissues. (
  • 4: Tomicic MT, Kaina B. Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors. (
  • 8: Sheng C, Miao Z, Zhang W. New strategies in the discovery of novel non-camptothecin topoisomerase I inhibitors. (
  • Manzo, Stefano Giustino (2015) Natural compounds Camptothecin and Triptolide: highly specific enzyme inhibitors and tools to dissect transcriptional functions , [Dissertation thesis], Alma Mater Studiorum Università di Bologna. (
  • Studies searching for antibiotic and anticancer agents in the mid to late 20th century have illuminated the existence of numerous unique families of both TopI and TopII inhibitors, with the 1960s alone resulting in the discovery of the camptothecin, anthracycline and epipodophyllotoxin classes. (
  • Camptothecin-derived TopI inhibitors function by forming a ternary complex with TopI-DNA and are able to stack between the base pairs that flank the cleavage site due to their planar structure. (
  • The starting compounds (II) used in this invention, i.e. 5-formyl-8-hydroxymethyl-9-oxo-5,5a,9,11,11a,12-hexahydroindolizino[1,2-b]quinoline-7-malonic acid alkyl esters (hereinafter referred to as malonic acid derivatives) are known compounds which serve as intermediates in the total synthesis of camptothecin disclosed in the specification of Japanese Unexamined publication No. 49/117499. (
  • Abelson HT, Penman S. Selective interruption of high molecular weight RNA synthesis in HeLa cells by camptothecin. (
  • Synthesis and biological activity in the camptothecin series. (
  • One of the primary cellular responses to camptothecin exposure is rapid cessation of RNA synthesis. (
  • TY - JOUR T1 - Synthesis and cytotoxic activity of new 9-substituted camptothecins. (
  • It is worth mentioning that the reported protecting group-free synthesis, with advantages of a short route, would be helpful for the future development of industry scale syntheses of camptothecin-family alkaloids. (
  • Pingxuan Shao, Wei Lu and Lei Wang*, "Short Protecting Group-free Syntheses of CDE Synthon of Racemic Camptothecin", Current Organic Synthesis (2020) 17: 1. (
  • The present invention relates to camptothecin-skeleton alkaloids isolated from Mappia foetida or obtained by semi-synthesis from said alkaloids. (
  • Li DZ, Li Y, Chen XG, Zhu CG, Yang J, Liu HY, Pan XD (2007) Synthesis and antitumor activity of heterocyclic acid ester derivatives of 20 S -camptothecins. (
  • Effects of camptothecin on rna synthesis in leukemia l1210 cells. (
  • To examine the effects of camptothecin on RNA synthesis genome-wide we used Bru-Seq and show that camptothecin treatment affected transcription initiation, elongation, termination, splicing and enhancer activity. (
  • abstract = "We have used an Aspergillus nidulans macroarray carrying sequences of 2,787 genes from this fungus to monitor gene expression of both wild-type and uvsBATR (the homologue of the ATR gene) deletion mutant strains in a time course exposure to camptothecin (CPT). (
  • Camptothecin inhibits DNA religation in the cleavage/religation step by binding to DNA topoisomerase I (topo I) and DNA which forms a DNA topoisomerase I - camptothecin - DNA complex. (
  • Camptothecin (CPT) is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme topoisomerase I (topo I). It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. (
  • Camptothecin (CPT), derived from the plant Camptotheca acuminata, specifically inhibits topoisomerase 1 (Top1). (
  • Ubiquitin, SUMO-1, and UCRP in camptothecin sensitivity and resistance. (
  • We show that these patient-derived cells exhibit sensitivity to camptothecin (CPT), impaired CPT-induced topoisomerase I (Topo I) degradation and ubiquitination, thereby suggesting Topo I to be a novel Cul4-dependent substrate. (
  • Other investigators have reported that GSH may also play a role in sensitivity to other nonalkylating camptothecins ( 8-10 ). (
  • This investigation sought to further define the role of GSH in camptothecin sensitivity. (
  • Because p125 focal adhesion kinase (FAK) is a transducer in the b1-integrin signaling pathway, it is essential to cell adhesion and it is overexpressed in metastatic breast cancer, we hypothesized that attenuation of FAK might enhance the sensitivity of breast cancer cells to camptothecins. (
  • sws-1 mutants exhibit sensitivity to DSB-inducing agents and fail to form mitotic RAD-51 foci following treatment with camptothecin. (
  • Through synthetic viability screening, we discovered that histone H4 K16 deacetylation drives the sensitivity of yeast cells to camptothecin and that inactivation of this pathway by mutating H4 K16 or the genes $\textit{SIR1-4}$ suppresses much of the hypersensitivity of $\textit{tof1}$∆ strains towards this agent. (
  • We show that disruption of rDNA or telomeric silencing does not mediate camptothecin resistance but that disruption of Sir1-dependent chromatin domains is sufficient to suppress camptothecin sensitivity in wild-type and $\textit{tof1}$∆ cells. (
  • The yeast Saccharomyces cerevisiae has been useful in establishing the phenotypic effects of specific mutations on the enzymatic activity and camptothecin sensitivity of yeast and human DNA topoisomerase I. To determine whether these phenotypes were faithfully reiterated in higher eukaryotic cells, wild-type and mutant yeast Top1 proteins were epitope-tagged at the amino terminus and transiently overexpressed in mammalian COS cells. (
  • We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells and MCF-7 AdVp3000 isolated from parental MCF-7 breast cancer cells. (
  • The lack of selection for higher levels of UGT capacity in the colon cells suggests that high levels of expression of MXR alone are sufficient to confer resistance to the camptothecins. (
  • Resistance to the camptothecins has been explored in model systems, and several putative mechanisms have been identified. (
  • Whereas camptothecins are active against a wide range of solid tumors, resistance can be a significant hindrance to therapy. (
  • Reported mechanisms of camptothecin resistance include down-regulation or mutation of topo I, reduced drug uptake, and defects in apoptotic response ( 3 ). (
  • Mechanism of Resistance to Camptothecin, a Cytotoxic Plant Secondary Metabolite, by Lymantria sp. (
  • 1999 Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. (
  • This study shows a strong association between cell attachment to substratum and activation of b1-integrin-signaling with resistance to the camptothecin derivative topotecan (TPT) in breast cancer cells. (
  • 3: Beretta GL, Gatti L, Perego P, Zaffaroni N. Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug. (
  • Non-camptothecins, such as indenoisoquinolines and indolocarbazoles, also associate with TopI itself, forming hydrogen bonds with residues that typically confer resistance to camptothecin. (
  • Camptothecin shows high activity against various tumor cells. (
  • CT-2106, a poly- l -glutamic acid-glycine-camptothecin conjugate, has the potential to deliver higher active camptothecin doses to tumor tissue compared with normal tissues, thereby reducing toxicity due to the enhanced permeability and retention effect of the poly-glutamate backbone. (
  • Camptothecin and its derivatives are monoterpenoid indole alkaloids exhibiting significant anti-tumor actions. (
  • S)-10-hydroxy-Camptothecin has strong anti-tumor activity against a wide range of experimental tumors including L1210 leukemia cells (IC50 = 1.15 μM). (
  • Camptothecin is an alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata Decsne. (
  • Camptothecin was originally isolated from the stem wood of the Camptotheca acuminata tree and was shown to exhibit antileukemic/antitumour activity, and reversibly inhibit Mitochondrial Topo I (nuclear Topo I (topoisomerase I)) by binding to and stabilizing the topoisomerase-DNA covalent complex. (
  • Camptothecin (CPT), a plant alkaloid originally isolated from the native Chinese tree, Camptotheca acuminate, exerts the toxic effect by targeting eukaryotic DNA topoisomerase 1 (DNA Topo1). (
  • Camptothecin (CPT), an extract of the plant Camptotheca acuminate , has been reported to have anti-inflammation and antitumor effects. (
  • With the aim of improving the production of these pharmaceuticals, the contents of camptothecin and 10-hydroxycamptothecin in different tissues including roots, stems, leaves, young flower buds, opening flowers, fading flowers and seeds from Camptotheca acuminata, were investigated. (
  • In the present study, the growth rate of Camptotheca acuminata cells in culture did not correlate with contents of camptothecin and 10-hydroxycamptothecin. (
  • 20-(S)-camptothecin (CPT) is a cytotoxic alkaloid extracted from the Chinese tree Camptotheca acuminata . (
  • Camptothecin, a pentacyclic alkaloid isolated from the Chinese tree Camptotheca acuminata (Hertzberg et al . (
  • Camptothecin is isolated from Camptotheca acuminata, a deciduous tree. (
  • Camptothecin is a natural alkaloid product first extracted from the stem wood of the Chinese tree Camptotheca acuminata . (
  • Camptothecin (CPT) was first derived from the tree Camptotheca acuminata, native to southern China. (
  • The antitumor agent camptothecin stabilizes type I topoisomerase-DNA complexes. (
  • The STING agonist was electrostatically complexed with nanotubes comprising a peptide-drug conjugate (a peptide that binds to the protein neuropilin-1, which is highly expressed in tumours, and the chemotherapeutic agent camptothecin) that self-assemble in situ into a supramolecular hydrogel. (
  • The camptothecins (CPT) are potent radiation sensitizers and are in their infancy in clinical studies. (
  • Camptothecins are a potent class of anticancer drugs that inhibit DNA Topoisomerase I. While seen strictly as cytotoxic compounds, camptothecins are actually also targeted agents, inhibiting DNA-Topoisomerase I (Topo I) cleavable complex. (
  • Antitumor activity of 7-ethyl-l0-[4-(1-piperidino)-1piperidinolcarbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors. (
  • The camptothecin analog CPT-11 has recently been approved for the treatment of 5-fluorouracil (5-FU)-resistant colorectal cancer (1) , thus opening a new chapter in chemotherapeutic radiation sensitization. (
  • The enzyme is often upregulated in cancer cells, and it is a target for chemotherapeutic drugs of the camptothecin (CPT) family. (
  • The camptothecins ( Fig. 1 ) are a class of chemotherapeutic agents that act by inhibiting topo 3 I ( 1 , 2 ). (
  • To find a more effective and less toxic chemotherapeutic agent, we have successfully prepared crystalline camptothecin-20( S )-O-propionate hydrate (CZ48) by reacting camptothecin with propionic anhydride using concentrated sulfuric acid as catalyst. (
  • Determine the maximum tolerated dose of polyglutamate camptothecin (CT-2106) in patients with advanced malignancies. (
  • This paper highlights important issues related to drug dosing, schedule of administration, pharmacokinetics, toxicity, and activity of commonly used camptothecin-based regimens. (
  • Pharmacokinetics of conjugated and unconjugated camptothecin were dose and time independent in the tested dose range. (
  • Conclusions: This study demonstrates clinical safety, favourable pharmacokinetics and preliminary antitumor activity of the novel hydrophilic camptothecin analogue namitecan in patients with heavily pretreated solid malignancies, when given either on a 2 out of 3 weeks or 3-weekly regimen. (
  • Modification of the hydroxy lactone ring of camptothecin: Inhibition of mammalian topoisomerase I and biology activity. (
  • Dependence of anticancer activity of camptothecins on maintaining their lactone function. (
  • This linkage stabilizes the active lactone form of camptothecin and enhances aqueous solubility. (
  • Covalent binding through the hydroxyl group of camptothecin to poly-glutamate (a biodegradable polymer of glutamic acid) via a glycine linker enhances the aqueous solubility of camptothecin and prevents opening of the lactone ring and subsequent camptothecin binding to albumin with decrease in free camptothecin fraction and inactivation ( 8 , 9 ). (
  • Indenosioquinolines and indolocarbazoles also lack the lactone ring present in camptothecin, making them more chemically stable and less prone to hydrolysis at biological pH. (
  • In this study, we designed and synthesized the conjugates TAT-CPT and TAT-2CPT by attaching camptothecin (CPT) to the N-terminus of the cell penetrating peptide TAT. (
  • 10. Kang C, Sun Y, Wang M, and Cheng X. Nanosized camptothecin conjugates for single and combined drug delivery. (
  • Camptothecin: Roles of the D and E Rings in Binding to the Topoisomerase I-DNA Covalent Binary Complex. (
  • Camptothecins stabilize this covalent intermediate by preventing topo I-mediated religation of the DNA strand ( 1 ). (
  • Interestingly, the mutant eSctop1T722A, which mimics camptothecin-induced cytotoxicity in yeast through stabilization of the covalent enzyme-DNA intermediate, induced apoptosis in COS cells in the absence of camptothecin. (
  • In the current study, we show that treatment of mammalian cells or yeast cells expressing human DNA TOP1 with camptothecin (CPT) induces covalent modification of the TOP1 by SUMO-1/Smt3p, a ubiquitin-like protein. (
  • The copolymer-coated multiwalled carbon nanotubes can effectively form non-covalent supramolecular complexes with camptothecin. (
  • 1. Hsiang Y-H, Hertzberg R, Hecht S, and Liu L. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. Journal of Biological Chemistry. (
  • Fingerprint Dive into the research topics of 'Increased camptothecin toxicity induced in mammalian cells expressing Saccharomyces cerevisiae DNA topoisomerase I'. Together they form a unique fingerprint. (
  • Increased camptothecin toxicity induced in mammalian cells expressing Saccharomyces cerevisiae DNA topoisomerase I . Journal of Biological Chemistry , 273 (14), 8425-8433. (
  • Phase I clinical trial of weekly and daily treatment with camptothecin (NSC-100880): correlation with preclinical studies. (
  • 5: Beretta GL, Zuco V, De Cesare M, Perego P, Zaffaroni N. Namitecan: a hydrophilic camptothecin with a promising preclinical profile. (
  • Like other camptothecin derivatives, SN38 exerts its cytotoxic activity through inhibition of Topoisomerase 1 (TOP1). (
  • Cao ZS, Giovanella BC (2003) Halo-alkyl esters of camptothecin and methods of treating cancer using these compounds. (
  • These findings of the effects of camptothecin on transcription have important implications for its anti-cancer activities and may aid in the design of improved combinatorial treatments involving Top1 poisons. (
  • All the formulations were designed firstly to increase the solubility of camptothecin in aqueous environment and secondly to reduce the toxicity problems related to the administration of this drug. (
  • In conclusion, the preliminary results of the paediatric evaluation of camptothecin derivatives show very encouraging results in childhood malignancies. (
  • Characterization of DNA Topoisomerase-1 in Spodoptera exigua for Toxicity Evaluation of Camptothecin and Hydoxy-Camptothecin. (
  • The present invention is directed to water-soluble derivatives of camptothecin. (
  • Depletion of TOP1 using siRNA was then able to rescue EV71 infection from camptothecin inhibition. (
  • Our findings reveal camptothecin to be a limited spectrum antiviral against enteroviruses that functions in a TOP1-dependent but cytotoxicity-independent manner. (
  • In this study, we have shown that camptothecin (CPT), a TOP1-specific poison, can induce rapid and extensive conjugation of SUMO-1/Smt3p to human DNA TOP1. (
  • In contrast, assays of growth in the presence of the Top1 poison camptothecin (CPT) indicate that the structure-specific nucleases dependent on RAD1 and MUS81 can contribute independently of TDP1 to repair, presumably by cutting off a segment of DNA along with the topoisomerase. (
  • Eukaryotic Top1s are the cellular target of the plant-derived anticancer indole alkaloid camptothecin (CPT), which reversibly stabilizes the Top1-dsDNA complex. (
  • Vishnuvajjala BR, Garzon-Aburbeh A (1990) Water soluble prodrugs of camptothecin. (
  • A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment but not after camptothecin treatment. (
  • Results obtained by using an in vitro transcription system supplemented with eukaryotic topoisomerase I show that this inhibition can be attributed to physical blockage of the RNA polymerase by camptothecin-stabilized topoisomerase I-DNA complexes on the DNA template. (
  • Differential stabilization of eukaryotic DNA topoisomerase I cleavable complexes by camptothecin derivatives. (
  • CMMDC is an interesting hybrid that combines the ability to bind and stabilize the topo I-DNA complexes typical of the camptothecins with a DNA-alkylating capacity characteristic of the nitrogen mustards or nitrosoureas ( 5 , 6 ). (
  • CT-2106 has a more manageable toxicity profile compared with unconjugated camptothecin. (
  • The sodium salt of camptothecin was relatively inactive with significant toxicity in clinical trials ( 6 , 7 ). (
  • It is a member of the camptothecin family that demonstrates less toxicity than its parent compound. (
  • Although most noted for its anticancer activity, Camptothecin and derivatives have shown other pertinent biochemical actions, including: antiprotozoal, antimalarial, inhibition of HIV, upregulation of p53, and induction of apoptosis. (
  • Camptothecin (CPT) has been known to induce apoptosis in various cancer cell lines. (
  • Camptothecin preferentially induced apoptosis in cells expressing wild-type eSctop1p yet did not appreciably increase the cytotoxic response of cells expressing a catalytically inactive (eSctop1Y727F) or a catalytically active, camptothecin-resistant eSctop1vac mutant. (
  • This study aims to explore the role of MPTP in the process of apoptosis induced by camptothecin (CPT) in Spodoptera exigua so as to further reveal the mechanisms of CPT-induced apoptosis in insects. (
  • MPTP dependency in mitochondrion-mediated apoptosis induced by camptothecin in Spodopetera exigua (Lepidoptera: Noctuidae)[J]. ACTA ENTOMOLOGICA SINICA, 2017, 60(10): 1105-1113. (
  • Several camptothecin and non-camptothecin derivatives are being developed to further increase anti-tumour activity and reduce side effects. (
  • Several camptothecin derivatives have been explored in clinical trials. (
  • 9,10] The original preparation (camptothecin sodium) was evaluated in clinical trials in the late 1960s and early 1970s. (
  • Subsequent phase II trials in advanced gastrointestinal cancer and malignant melanoma failed to demonstrate significant clinical activity of camptothecin sodium. (
  • Giovanella BC, Hinz HR, Kozielski AJ, Stehlin JS, Silber R, Potmesil M. Complete growth inhibition of human cancer xenografts in nude mice by treatment with 20(S)-camptothecin. (
  • Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. (
  • Furthermore, leukemia cells are known to have a distinctive propensity to undergo PCD following treatment with camptothecins compared to the relatively lower response of colon cancer cell lines (Darzynkiewicz et al . (
  • This essay has discussed various ways by which two or more than two drugs have been combined with Camptothecin through nanoparticles in order to yield anti-cancer therapy effectiveness. (
  • Venditto, Vincent J. "Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature. (
  • In a previous study, we established camptothecin (CPT)-resistant cell lines, A549/CPT and HT-29/CPT, from human lung cancer A549 and human colon cancer HT-29. (
  • 1: Bala V, Rao S, Boyd BJ, Prestidge CA. Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38. (
  • Taken together, the data suggest that part of the cytotoxicity of camptothecin is mediated through adduct formation on transcribed DNA, resulting in interference with transcriptional elongation. (
  • The plant alkaloid camptothecin (CPT) has demonstrated the ability to inhibit replication of the equine anemia virus (E1AV) and the human immunodeficiency virus (HIV) in infected cells in culture. (
  • Background: Camptothecin is a plant alkaloid that specifically binds topoisomerase I, inhibiting its activity and inducing double stranded breaks in DNA, activating the cell responses to DNA damage and, in response to severe treatments, triggering cell death. (
  • We have previously reported that DX-8951f, a water-soluble and nonprodrug camptothecin (CPT) derivative, exhibits both high in vitro potency against a series of 32 malignant cell lines and significant topoisomerase I inhibition. (
  • In probing the mechanism of inhibition of hypoxia inducible factor (HIF-1) by campothecins, we investigated the ability of human topoisomerase I to bind and cleave HIF-1 response element (HRE), which contains the known camptothecin-mediated topoisomerase I cleavage site 5′-TG. (
  • It has been used clinically more recently in China for the treatment of gastrointestinal tumors.CPT showed remarkable anticancer activity in preliminary clinical trials especially against breast, ovarian, colon, lung, and stomach cancers 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. (
  • Modelling suggested the possibility of a favourable interaction of small and polar 9-substituents with the topoisomerase I-DNA complex, which is consistent with the higher activity of these derivatives with respect to the corresponding 7-substituted camptothecins. (
  • All three derivatives [7-(γ-glutamylcysteinylmethyl)-10,11-methylenedioxy-20( S )-camptothecin, 7-(cysteinylglycylmethyl)-10,11-methylenedioxy-20( S )-camptothecin, and 7-(cysteinylmethyl)-10,11-methylenedioxy-20( S )-camptothecin] displayed topo I and cell growth-inhibitory activity. (
  • Recent work from this laboratory with cultured MCF-7 and MDA-MB-231 cells showed that a decrease in the pH of the extracellular medium potentiated camptothecin activity. (
  • Camptothecins are cell cycle specific, demonstrating greatest activity in the S-phase. (
  • The analysis of their in vitro antiproliferative activity on cultured human leukemic K562 cells demonstrated that liposomes, micellar solutions and microemulsion containing camptothecin exert similar or slightly enhanced effect as compared to that shown by the free drug. (
  • Finally, expression of dominant-negative versions of DP1, known to compromise E2F transcriptional activity, protects cortical neurons from death induced by camptothecin and sympathetic neurons from death evoked by UV treatment. (
  • Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. (
  • Camptothecin is one of the most promising anticancer drugs of the twenty first century. (
  • We also report that GSH interacts with CMMDC to form a stable conjugate, 7-(glutathionylmethyl)-10,11-methylenedioxy-20( S )-camptothecin (GSMMDC), which is formed spontaneously in buffered solutions and in MCF-7 cells treated with CMMDC. (
  • Alkaloid accumulation by cells under various treatments (heavy metal ions, UV-B), methyl-jasmonate, abscisic acid, salicylic acid and hydrogen peroxide was examined, and the most notable effects appeared in the cells induced by UV-B light (which showed an 11-fold increase in camptothecin concentration) and by salicylic acid (which showed a 25-fold increase in 10-hydroxycamptothecin concentration). (
  • We propose a mechanistic-driven approach to sensitize the cells to camptothecins. (
  • In vitro treatment of human HepG2 cells with 5-20 μM (S)-10-hydroxy-camptothecin results in cell cycle arrest at the G2/M phase. (
  • Reduced apoptotic response to camptothecin in CHO cells deficient in XRCC3. (
  • Camptothecin" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (