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The Biochemical Journal Nov 1959
Topics: Dactinomycin; Fabaceae; Glycine; Sarcosine; Streptomyces
PubMed: 14404788
DOI: 10.1042/bj0730458 -
The Canadian Veterinary Journal = La... Jan 2006In this retrospective study, a 6-drug (prednisone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and actinomycin-D) chemotherapy protocol with extended...
In this retrospective study, a 6-drug (prednisone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and actinomycin-D) chemotherapy protocol with extended maintenance for the treatment of lymphoma was evaluated for efficacy and toxicity in 39 dogs. The complete remission rate was 97%, with a median progression-free survival (PFS) of 331 d. The median overall survival (OS) was 461 d. Of the variables evaluated for prognostic significance, only immunophenotype and sex were found to be prognostic. Dogs with T-cell lymphoma had shorter PFS and OS than dogs with B-cell lymphoma. Castrated male dogs had a shorter PFS and OS than spayed female dogs. Although the majority of dogs experienced one or more episodes of chemotherapy associated toxicity, the majority of these episodes were mild and self-limiting. The results of this study warrant further investigation into the value of extended maintenance therapy and inclusion of actinomycin-D in combination chemotherapy protocols for canine lymphoma.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Disease-Free Survival; Dog Diseases; Dogs; Female; Lymphoma; Male; Prognosis; Remission Induction; Retrospective Studies; Sex Factors; Time Factors; Treatment Outcome
PubMed: 16536229
DOI: No ID Found -
The Journal of Cell Biology Jan 1971Nucelolar morphology was studied by electron microscopy in control and actinomycin D-treated populations of Tetrahymena pyriformis (W) during the cultural growth cycle....
Nucelolar morphology was studied by electron microscopy in control and actinomycin D-treated populations of Tetrahymena pyriformis (W) during the cultural growth cycle. Nucleoli exhibit an "aging" cycle concomitant with the cultural growth cycle, but independent of the individual cell cycle. Four different stages in the course of this aging process have been defined. Stage 1 occurs upon inoculation (low number of cells per milliliter) and lasts through lag and accelerating growth phases. In this stage, many small nucleoli are found at the nuclear periphery. In stages 2 and 3, nucleolar fusion begins. Stage 2 dominates the first half of logarithmic growth, and stage 3 dominates the second half. In late decelerating growth phase, the nucleoli enter stage 4. In this stage, only a few large nucleoli are present and these are apparently inactive in ribosome production. In stationary phase, where total RNA remains constant, only stage 4 nucleoli are present. The relative preponderance of granular vs. fibrous components in the nucleoli changes during this cycle, the granular component dominating stage 1 nucleoli and the fibrillar, stage 4 nucleoli. There is a shortening of the intermediate nucleolar stages in the treated cultures; fusion occurs early and is now pronounced. Not enough ribosomes accumulate to carry the treated cultures through the number of generations equivalent to those of the control, which produces a premature stationary phase.
Topics: Animals; Cell Nucleolus; Culture Media; Dactinomycin
PubMed: 5545100
DOI: 10.1083/jcb.48.1.143 -
Journal of Virology Feb 1995Data showing that an apoptotic reaction (the exit into the cytoplasm and nucleolytic internucleosomal degradation of chromosomal DNA, compaction and fragmentation of...
Data showing that an apoptotic reaction (the exit into the cytoplasm and nucleolytic internucleosomal degradation of chromosomal DNA, compaction and fragmentation of chromatin, cellular shrinkage, and cytoplasmic blebbing) developed in a subline of HeLa-S3 cells upon nonpermissive poliovirus infection with either a guanidine-sensitive poliovirus in the presence of guanidine, a guanidine-dependent mutant in the absence of guanidine, or certain temperature-sensitive mutants at a restrictive temperature are presented. Essentially, no apoptotic reaction occurred upon permissive infection of these cells. Both permissive and nonpermissive infections resulted in the inhibition of host protein synthesis. Actinomycin D or cycloheximide also elicited a rapid apoptotic reaction in uninfected cells. However, preinfection or coinfection with poliovirus prevented the apoptotic response to the addition of actinomycin D, and preinfection blocked cycloheximide-induced apoptosis as well. These data fit a model in which the cells used are prepared to develop apoptosis, with their viability due to the presence of certain short-lived mRNA and protein species. Poliovirus infection turns on two oppositely directed sets of reactions. On the one hand, the balance is driven toward apoptosis, probably via the shutoff of host macromolecular synthesis. On the other hand, viral protein exhibits antiapoptotic activity, thereby preventing premature cell death. To our knowledge, this is the first description of an antiapoptotic function for an RNA virus.
Topics: Apoptosis; Cycloheximide; Dactinomycin; HeLa Cells; Humans; Poliovirus; Protein Biosynthesis; RNA
PubMed: 7529330
DOI: 10.1128/JVI.69.2.1181-1189.1995 -
Cytometry. Part a : the Journal of the... Feb 2008The accurate determination of cell cycle, immunophenotypes and morphology at single-cell level is not fully achieved by current flow cytometry protocols. Acetone, a...
The accurate determination of cell cycle, immunophenotypes and morphology at single-cell level is not fully achieved by current flow cytometry protocols. Acetone, a coagulant fixative/permealizing agent, is widely used in static cytometry, but is impractical in flow cytometry because of its shrinking effect. We sought for conditions of acetone treatment that could permit the simultaneous analysis of physical parameters, surface and intracellular immunostaining, and DNA content. We evaluated different experimental conditions (concentration, duration of fixation, temperature, presence of proteins) to test the capacity of acetone fixation/permeabilization to preserve cell physical parameters (forward and side scatters, FSC, and SSC) and immunophenotyping while allowing stoichiometric DNA staining. The commonly used ethanol fixation technique was used as reference method. To detect phenotypes and DNA content simultaneously, we employed 7-aminoactinomycin D (7-AAD) as "intercalating" dye for DNA in spite of, or just for, its controversial ability in stoichiometric DNA staining. Cells were resting peripheral blood monucleated cells (PBMCs), T- and B-cell blasts obtained by PBMCs stimulation, and the human cell lines Ramos and Shep. Acetone fixation, preserving both the recovery and the physical parameters of cells, is drastically influenced by temperature of treatment and is practicable only when the protocol is realized at 8 degrees C. Under this condition, acetone maintains the immunophenotypic fluorescences (realized before or after the fixation) better than ethanol. Stoichiometric DNA staining of acetone processed cells, the variation coefficients (CV) of frequency distributions of G1/G0 and G2/M phases, the modes ratio of these distributions and doublets generation are at least comparable to those obtained with ethanol treatment. The assay developed in the present study, that we called flow acetone-staining technique (FAST), accurately analyzes cell cycle, physical parameters and immunophenotypes in heterogenous cell populations, and thus provides a useful tool for cytomics.
Topics: Acetone; Cell Cycle; Cell Line; Cell Size; DNA; Dactinomycin; Fixatives; Flow Cytometry; Humans; Monocytes; Staining and Labeling
PubMed: 18189284
DOI: 10.1002/cyto.a.20521 -
Biophysical Journal Jul 2018A growing amount of experimental evidence shows that the local elastic field acting on cells governs their spatial organization and polarity in a tissue. Interestingly,...
A growing amount of experimental evidence shows that the local elastic field acting on cells governs their spatial organization and polarity in a tissue. Interestingly, experiments on wound healing reveal a universal formation of thick actomyosin bundles around the margins of epithelial gaps. Although the forces involved in this process have been measured, the mechanisms governing cellular alignment and contractile ring formation are still not fully understood. To theoretically investigate this process, we have carried out a self-consistent calculation of the elastic field that is actively generated around a circular gap in a contractile cell monolayer that is adhered to an elastic substrate, taking into account the responsiveness of actomyosin activity to the locally generated stress. We model actomyosin contractility by a radial distribution of point force dipoles that may alter in magnitude and orientation in response to the local elastic stress. In addition, the model takes into account the forces exerted by leader cells on the margins of the cell monolayer. Our model suggests that the presence of a hole in the center of a contractile cell monolayer creates a mechanical tendency for actomyosin forces to polarize tangentially around the hole margin. In addition, it predicts that this tendency optimizes with substrate rigidity, thickness, and strength of cell adhesion to the substrate. Our calculations support the view that the universal formation of a peripheral contractile ring is a consequence of actomyosin contractility in the bulk and its inherent responsiveness to the local stress.
Topics: Biomechanical Phenomena; Cell Polarity; Cell Shape; Cytoskeleton; Dactinomycin; Epithelium; Models, Biological; Stress, Mechanical; Wound Healing
PubMed: 30021114
DOI: 10.1016/j.bpj.2018.06.011 -
Journal of Biochemistry Jun 1980Actinomycin D allowed 3.6% of spore formation and 4.9% of dipicolinic acid synthesis of control cultures when added at 0.4 microM at late stage (T6.5) during sporulation...
Actinomycin D allowed 3.6% of spore formation and 4.9% of dipicolinic acid synthesis of control cultures when added at 0.4 microM at late stage (T6.5) during sporulation process of Bacillus subtilis although the drug inhibited sporulation almost completely when added at log phase and early stages. Daunorubin added at log phase, on the other hand, did not inhibit either growth and sporulation of the bacteria up to a concentration of 2.9 microM. The joint use of both antibiotics at late stages decreased the levels of spore formation and the synthesis of dipicolinic acid allowed by the use of actinomycin D alone to 0.9% and 2.1% respectively, and also inhibited the synthesis of spore coat protein in a cooperative manner.
Topics: Bacillus subtilis; Dactinomycin; Daunorubicin; Dose-Response Relationship, Drug; Drug Synergism; Spores, Bacterial
PubMed: 6772636
DOI: 10.1093/oxfordjournals.jbchem.a132905 -
The Canadian Veterinary Journal = La... Feb 2014In this retrospective study, a chemotherapy protocol using dexamethasone, melphalan, actinomycin D, and cytosine arabinoside (DMAC) was evaluated for efficacy and... (Clinical Trial)
Clinical Trial
In this retrospective study, a chemotherapy protocol using dexamethasone, melphalan, actinomycin D, and cytosine arabinoside (DMAC) was evaluated for efficacy and adverse event profile as a first line rescue protocol in 86 client-owned dogs previously treated with a CHOP-based protocol. Forty-three dogs (43%) achieved remission (16% complete remission, 27% partial remission), and 57% were non-responders. The median overall progression-free survival (PFS) was 24 days. Adverse events included thrombocytopenia in 41% of dogs, neutropenia in 17% of dogs, and gastrointestinal toxicity in 13% of dogs. Overall, 16% (13/79) dogs experienced grade III to IV thrombocytopenia, 8% (6/74) dogs grade III to IV neutropenia and 1% (1/79) dogs grade III to IV gastrointestinal toxicity. The efficacy of the DMAC protocol is similar to that of other rescue protocols in dogs with relapsed lymphoma but is associated with shorter PFS. The main toxicity is thrombocytopenia, which may limit treatment.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Dactinomycin; Dexamethasone; Dog Diseases; Dogs; Female; Lymphoma; Male; Melphalan; Recurrence; Retrospective Studies
PubMed: 24489398
DOI: No ID Found -
Cancer Sep 2006The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low-risk gestational trophoblastic...
BACKGROUND
The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low-risk gestational trophoblastic neoplasia (GTN) who failed methotrexate therapy.
METHODS
Eligible patients had persistent/recurrent low-risk GTN defined by changes in serum human chorionic gonadotropin (hCG) levels (<10% fall over 3 consecutive weekly titers, >20% rise over the previous value, or a rise after attaining institutional normal [>5 mu/mL]); World Health Organization (WHO) score 2-6; Gynecologic Oncology Group (GOG) performance status 0-1; and previous treatment restricted to methotrexate. Dactinomycin administration was 1.25 mg/m2 intravenous (i.v.) every 2 weeks until documented complete response (CR) or treatment failure. CR was defined as an institutional normal serum hCG level sustained for >or=4 consecutive weeks; treatment failure was a <10% fall (3 assays over 4 weeks) or >20% rise (over previous value) in hCG serum level. Levels were monitored biweekly x 8 weeks beyond the first normal value, then monthly x 10.
RESULTS
Five of 44 enrolled patients were ineligible due to choriocarcinoma and normal pretreatment serum hCG level (2 each), no history of methotrexate (1), and 1 patient with documented phantom hCG syndrome was unevaluable. In all, 28 of 38 (74%) evaluable patients attained CR. The median number of cycles was 4 (range, 2-10). Severe toxicity was minimal, causing no patient to discontinue therapy. All treatment failures achieved a CR after receiving subsequent chemotherapy; 3 patients also underwent hysterectomy.
CONCLUSION
Pulse dactinomycin is an active regimen for patients with low-risk GTN who fail previous methotrexate therapy.
Topics: Adult; Antibiotics, Antineoplastic; Chorionic Gonadotropin; Dactinomycin; Drug Administration Schedule; Female; Gestational Trophoblastic Disease; Humans; Injections, Intravenous; Nausea; Neutropenia; Pregnancy; Pulse Therapy, Drug; Risk Factors; Salvage Therapy; Treatment Outcome; Vomiting
PubMed: 16900525
DOI: 10.1002/cncr.22118 -
Analytical Biochemistry May 2014Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological...
Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological lymphangiogenesis, particularly in tumor metastasis, making it an attractive therapeutic target. Members of two families of cell surface receptors transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2 is a promising target for inhibition because it is highly expressed in lymphatic vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2 inhibitors. We optimize this assay for use in screening an inhibitor library and identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes of Health (NIH) Clinical Collection small molecule library.
Topics: Dactinomycin; Dose-Response Relationship, Drug; Drug Discovery; High-Throughput Screening Assays; Humans; Indoles; National Institutes of Health (U.S.); Neuropilin-2; Phenanthridines; Phenylcarbamates; Protein Binding; Small Molecule Libraries; Structure-Activity Relationship; Sulfonamides; Tosyl Compounds; United States; Vascular Endothelial Growth Factor C
PubMed: 24583243
DOI: 10.1016/j.ab.2014.02.017