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The Medical Letter on Drugs and... May 1965
Topics: Choriocarcinoma; Dactinomycin; Female; Humans; Male; Pregnancy; Rhabdomyosarcoma; Testicular Neoplasms; Wilms Tumor
PubMed: 4283937
DOI: No ID Found -
Annals of Internal Medicine Feb 1983
Topics: Dactinomycin; Humans
PubMed: 6824271
DOI: 10.7326/0003-4819-98-2-262_3 -
Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress.EMBO Molecular Medicine May 2020Chemotherapy still constitutes the standard of care for the treatment of most neoplastic diseases. Certain chemotherapeutics from the oncological armamentarium are able...
Chemotherapy still constitutes the standard of care for the treatment of most neoplastic diseases. Certain chemotherapeutics from the oncological armamentarium are able to trigger pre-mortem stress signals that lead to immunogenic cell death (ICD), thus inducing an antitumor immune response and mediating long-term tumor growth reduction. Here, we used an established model, built on artificial intelligence to identify, among a library of 50,000 compounds, anticancer agents that, based on their molecular descriptors, were predicted to induce ICD. This algorithm led us to the identification of dactinomycin (DACT, best known as actinomycin D), a highly potent cytotoxicant and ICD inducer that mediates immune-dependent anticancer effects in vivo. Since DACT is commonly used as an inhibitor of DNA to RNA transcription, we investigated whether other experimentally established or algorithm-selected, clinically employed ICD inducers would share this characteristic. As a common leitmotif, a panel of pharmacological ICD stimulators inhibited transcription and secondarily translation. These results establish the inhibition of RNA synthesis as an initial event for ICD induction.
Topics: Antineoplastic Agents; Artificial Intelligence; Dactinomycin; Humans; Immunogenic Cell Death; Neoplasms
PubMed: 32323922
DOI: 10.15252/emmm.201911622 -
Pharmacology & Toxicology Dec 1993Dactinomycin has recently been shown to be a competitive neurokinin-2 receptor antagonist in addition to its inhibiting action on DNA replication. We investigated in the...
Dactinomycin has recently been shown to be a competitive neurokinin-2 receptor antagonist in addition to its inhibiting action on DNA replication. We investigated in the isolated guinea-pig bronchi the action of 3 Dactinomycin analogues on the contractions evoked by the selective neurokinin-2 receptor agonist [Nle10] neurokinin A(4-10). These analogues included 4,4'-Gly-Dactinomycin and the single peptide lactone of dactinomycin which are inactive on DNA replication and 5,5'-MeLeu-Dactinomycin, which has potent antitumour activity. Independently of their known effect on DNA replication, the three analogues showed neurokinin-2 antagonistic activity which was lower than for Dactinomycin.
Topics: Animals; Bronchi; DNA Replication; Dactinomycin; Female; Guinea Pigs; In Vitro Techniques; Male; Muscle Contraction; Receptors, Neurokinin-2
PubMed: 8153053
DOI: 10.1111/j.1600-0773.1993.tb01357.x -
Journal of Surgical Oncology Jul 1989Alternating 5-day chemotherapy with methotrexate and dactinomycin as primary therapy for nonmetastatic gestational trophoblastic disease was studied in nine patients....
Alternating 5-day chemotherapy with methotrexate and dactinomycin as primary therapy for nonmetastatic gestational trophoblastic disease was studied in nine patients. The complete response rate was 100% with follow-up of a median of 80 months. Stomatitis was universal but rarely prevented oral alimentation or delayed therapy. Overall, 94% of toxicity was mild or moderate in severity and all toxicity was reversible. This alternating non-cross resistant regimen, reported in a total of 40 patients in the literature, is the only regimen to result in a 100% response rate. This response rate is statistically improved when compared to historical controls receiving methotrexate/folinic acid or pulse dactinomycin. No patients required hysterectomy for disease control. Cooperative prospective phase III studies are needed to determine the efficacy and toxicity of current regimens.
Topics: Adult; Dactinomycin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Methotrexate; Pregnancy; Time Factors; Trophoblastic Neoplasms; Uterine Neoplasms
PubMed: 2545973
DOI: 10.1002/jso.2930410304 -
Gynecologic Oncology Dec 1999The search for effective systemic chemotherapy for endometrial cancer is ongoing. Complete responses to current drugs or regimens are infrequent, and overall survival... (Clinical Trial)
Clinical Trial
OBJECTIVES
The search for effective systemic chemotherapy for endometrial cancer is ongoing. Complete responses to current drugs or regimens are infrequent, and overall survival for patients with disease not amenable to surgery or radiation therapy is poor. Dactinomycin has proven activity against a wide variety of solid tumors but has not been tested against endometrial cancer. Using pharmacokinetic data supporting an intermittent, single-dose schedule, this Phase II Gynecologic Oncology Group study was conducted to determine the antitumor activity and toxicity of dactinomycin in patients with persistent or recurrent endometrial adenocarcinoma.
METHODS
Eligibility was limited to patients with measurable disease, adequate renal, hepatic, and bone marrow function, and no more than one prior chemotherapy regimen. Treatment consisted of 2 mg/m(2) slow intravenous push of dactinomycin over 15 min with courses repeated every 4 weeks.
RESULTS
A total of 27 patients were entered in this study between April 1996 and September 1996; all were evaluable for toxicity and 25 were evaluable for response. Overall, 12/25 (48%) patients had received prior radiation therapy and all had received prior chemotherapy. Sites of measurable disease were pelvis (9 patients) and distant (16 patients). There was 1 complete response and 2 partial responses for an overall objective response rate of 12%. Aside from emesis (grade 3, 2 patients; grade 4, 2 patients) significant nonhematologic toxicity was rare. The most common toxicity was neutropenia (grade 3, 2 patients; grade 4, 10 patients).
CONCLUSION
Toxicity was deemed acceptable but the limited effectiveness of dactinomycin precludes further clinical development in this patient population.
Topics: Adult; Aged; Antibiotics, Antineoplastic; Dactinomycin; Endometrial Neoplasms; Female; Humans; Middle Aged; Neoplasm Recurrence, Local
PubMed: 10600310
DOI: 10.1006/gyno.1999.5652 -
Progress in Nucleic Acid Research and... 1964
Review
Topics: Animals; Dactinomycin; In Vitro Techniques; Nucleic Acids
PubMed: 4157816
DOI: 10.1016/s0079-6603(08)60742-4 -
Lancet (London, England) Jan 1989
Topics: Chemical and Drug Induced Liver Injury; Child; Dactinomycin; Drug Administration Schedule; Humans; Prognosis; Wilms Tumor
PubMed: 2563091
DOI: 10.1016/s0140-6736(89)91192-6 -
Cytometry. Part a : the Journal of the... Aug 2018The use of formamide for the study in flow cytometry of cell cycle phases, by DNA content measurement in human cancer cell lines, was recently published. In this...
The use of formamide for the study in flow cytometry of cell cycle phases, by DNA content measurement in human cancer cell lines, was recently published. In this manuscript, we verify the possibility of extending the procedure to simultaneous analysis of other parameters. The results obtained, here reported, show that the treatment of samples by formamide is compatible with the simultaneous detection of DNA content and surface phenotypes, with quantification of replicating DNA and with measurement of cells with fractional content of DNA. For each of these three applications, we have adapted the procedure to gain simple, reproducible and above all advantageous protocols. Regarding the simultaneous analysis of DNA content and phenotyping the use of formamide achieves optimal DNA stoichiometric staining (C.V. < 3; G2/G1 ratio = 2 ± 0.05) and sufficient maintenance of physical parameters and membrane fluorescence. In the study of duplicating DNA labeled with click chemistry, our procedure eliminates paraformaldehyde (PFA) fixation improving the DNA stoichiometric staining and allows the use of 7-aminoactinomycin D (7-AAD) preserving the Alexa Fluor 488 quantum efficiency. Concerning the detection of cells with fractional content of DNA, permeabilization and fixation by formamide gives the advantage of resolve on linear scale sub-G1 cells from debris and to allow optimal sample recovery (>90%) which is essential in the study of cell necrobiology. Cells treatment by formamide, suitably modified for different applications, can be used to prepare cell samples for flow cytometry analyses that go far beyond stoichiometric staining of DNA.
Topics: Cell Cycle; Cell Line; Cell Tracking; Click Chemistry; DNA; Dactinomycin; Fixatives; Flow Cytometry; Formamides; Humans; Staining and Labeling; Surface Properties
PubMed: 30110133
DOI: 10.1002/cyto.a.23491 -
Nature Sep 1970
Topics: Dactinomycin; Lactones; Magnetic Resonance Spectroscopy; Models, Structural; Peptides
PubMed: 5452813
DOI: 10.1038/2271239a0