関: actinomycin、actinomycin D、dactinomycin

WordNet

any of various red antibiotics isolated from soil bacteria

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/09 21:06:20」(JST)

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Actinomycin D (also known generically as Actinomycin or Dactinomycin), is the most significant member of actinomycines, which are a class of polypeptide antibiotics isolated from soil bacteria of the genus Streptomyces.^[1] As one of the older chemotherapy drugs, it has been used for many years.

History[edit]

Actinomycin D was the first antibiotic shown to have anti-cancer activity.^[1] It was first isolated by Selman Waksman and his co-worker H. B. Woodruff in 1940.^[2] It was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1964 and launched by Merck Sharp and Dohme under the trade name Cosmegen.

Mechanism[edit]

In cell biology, Actinomycin D is shown to have the ability to inhibit transcription. It does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase.^[3]

Clinical use[edit]

Actinomycin is a clear, yellow liquid administered intravenously and most commonly used in treatment of a variety of cancers, including:

Gestational trophoblastic neoplasia^[4]
Wilms' tumor^[5]
Rhabdomyosarcoma^[6]
Ewing's sarcoma^[7]
Malignant hydatidiform mole^[8]

Sometimes it will be combined with other drugs in Chemotherapy regimens, like the VAC regimen (with Vincristine and Cyclophosphamide) for treating rhabdomyosarcoma and Ewing's Sarcoma.

It is also used as a radiosensitizer in adjunct to radiotherapies, since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation.^[9]

Side effects[edit]

Common adverse drug reaction includes bone marrow suppression, fatigue, hair loss, mouth ulcer, loss of appetite and diarrhea. Actinomycin is a vesicant, if extravasation occurs.

Research use[edit]

Because Actinomycin can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis.

Actinomycin D and its fluorescent derivative, 7-aminoactinomycin D (7-AAD), are used as stains in microscopy and flow cytometry applications. The affinity of these stains/compounds for GC-rich regions of DNA strands makes them excellent markers for DNA. 7-AAD binds to single stranded DNA; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones.^[10]

References[edit]

^ ^a ^b Hollstein, U. (1974). "Actinomycin. Chemistry and mechanism of action". Chemical Reviews 74 (6): 625–652. doi:10.1021/cr60292a002.
^ Waksman S A, Woodruff H B (1940). "Bacteriostatic and bacteriocidal substances produced by soil actinomycetes". Proc Soc Exper Biol 45: 609–614.
^ Sobell H (1985). "Actinomycin and DNA transcription". Proceedings of the National Academy of Sciences of the United States of America 82 (16): 5328–31. doi:10.1073/pnas.82.16.5328. PMC 390561. PMID 2410919.
^ Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M (2006). "Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia". Int J Gynecol Cancer 16 (3): 1432–8. doi:10.1111/j.1525-1438.2006.00606.x. PMID 16803542.
^ Abd El-Aal H, Habib E, Mishrif M (2005). "Wilms' Tumor: The Experience of the Pediatric Unit of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK)". J Egypt Natl Canc Inst 17 (4): 308–11. PMID 17102824.
^ Khatua S, Nair C, Ghosh K (2004). "Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues". J Pediatr Hematol Oncol 26 (11): 777–9. doi:10.1097/00043426-200411000-00020. PMID 15543019.
^ Jaffe, N.; Paed, D.; Traggis, D.; Salian, S.; Cassady, J. R. (1976). "Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy". Cancer 38 (5): 1925–1930. doi:10.1002/1097-0142(197611)38:5<1925::AID-CNCR2820380510>3.0.CO;2-J. PMID 991106.
^ Uberti, E. M. H.; Fajardo, M. D. C.; Ferreira, S. V. V. R.; Pereira, M. C. V.; Seger, R. C.; Moreira, M. A. L. R.; Torres, M. D.; De Nápoli, G.; Schmid, H. (2009). "Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy". Gynecologic Oncology 115 (3): 476–481. doi:10.1016/j.ygyno.2009.09.012. PMID 19818481.
^ Hagemann, R. F.; Concannon, J. P. (1973). "Mechanism of intestinal radiosensitization by actinomycin D". British Journal of Radiology 46 (544): 302–308. doi:10.1259/0007-1285-46-544-302. PMID 4720744.
^ Toba, K.; Koike, T.; Watanabe, K.; Fuse, I.; Takahashi, M.; Hashimoto, S.; Takahashi, H.; Abe, T.; Yano, T.; Shibazaki, Y.; Itoh, H.; Aizawa, Y. (2000). "Cell kinetic study of normal humanbone marrow hematopoiesis andacute leukemia using 7AAD/PY". European Journal of Haematology 64 (1): 10–21. doi:10.1034/j.1600-0609.2000.09005.x. PMID 10680701. edit

External links[edit]

MedlinePlus DrugInfo medmaster-a682224

UpToDate Contents

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1. 低リスク妊娠性絨毛腫瘍の初期マネージメント initial management of low risk gestational trophoblastic neoplasia
2. 抵抗性または再発性の妊娠性絨毛腫瘍のマネージメント management of resistant or recurrent gestational trophoblastic neoplasia
3. ユーイング肉腫ファミリーの腫瘍の治療 treatment of the ewing sarcoma family of tumors
4. 高リスク妊娠性絨毛腫瘍の初期マネージメント initial management of high risk gestational trophoblastic neoplasia
5. 肝疾患を有する患者における化学療法による肝毒性および用量調整 chemotherapy hepatotoxicity and dose modification in patients with liver disease

English Journal

Effects of Single-Agent and Combination Chemotherapy for Gestational Trophoblastic Tumors on Risks of Second Malignancy and Early Menopause.

Savage P1, Cooke R2, O'Nions J2, Krell J2, Kwan A2, Camarata M2, Dancy G2, Short D2, Seckl MJ2, Swerdlow A2.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.J Clin Oncol.2014 Dec 29. pii: JCO.2014.57.5332. [Epub ahead of print]
PURPOSE: To assess the risks of second malignancy and early menopause in a large cohort of patients with gestational trophoblastic tumor who were treated with chemotherapy.PATIENTS AND METHODS: A survey of patients treated at Charing Cross Hospital between 1958 and 2000 was performed in 2006 to asse
PMID 25547507

Inflammatory myofibroblastic tumor as a second neoplasm after Wilms tumor.

Ortiz MV1, Rossi CT, Hill DA, Guzzetta PC, Qureshi F, Dome JS.
Pediatric blood & cancer.Pediatr Blood Cancer.2014 Dec 11. doi: 10.1002/pbc.25345. [Epub ahead of print]
We report two survivors of Wilms tumor (WT) who developed inflammatory myofibroblastic tumor (IMT). The first patient had IMT in the mainstem bronchus 1 year after WT therapy that included vincristine, dactinomycin, doxorubicin (VDA) and whole lung radiation therapy (XRT). The second patient had IMT
PMID 25504840

Knockdown of Sec8 enhances the binding affinity of c-Jun N-terminal kinase (JNK)-interacting protein 4 for mitogen-activated protein kinase kinase 4 (MKK4) and suppresses the phosphorylation of MKK4, p38, and JNK, thereby inhibiting apoptosis.

Tanaka T1, Iino M, Goto K.
The FEBS journal.FEBS J.2014 Dec;281(23):5237-50. doi: 10.1111/febs.13063. Epub 2014 Oct 13.
The exocyst complex, also called the Sec6/8 complex, is important for targeting exocytic vesicles to specific docking sites on the plasma membrane in yeast and mammalian cells. In addition to these original findings, recent results of studies suggest that Sec8 is also involved in oncogenesis, althou
PMID 25244576

Japanese Journal

A CASE OF PRIMARY GASTRIC CHORIOCARTINOMA WITH EXTRAMURAL GROWTH

岡田秀司,内田雄三,友成一英,村上信一,久保宣博,葉玉哲生,横山繁夫
日本臨床外科医学会雑誌 52(3), 578-582, 1991
… Though a total of 3 courses of postopertive VAC regimen (oncovine, cosmegen, and endoxan) was carried out, be patient died of hepatic metastasis about 6 months after surgery.A total of 14 cases of primary malignant ciliated epithelioma of the stomach, including this case in Japanese women has been reported up to now. …
NAID 130003431803

陰茎の原発性細網肉腫の1例ならびに原発性陰茎肉腫の文献的考察

三国友吉 [他],田端運久,田倉弘
泌尿器科紀要 19(9), 761-783, 1973-09
… As the second operation, total penectomy with perineal urethrostomy was done, and postoperative chemotherapy with 5 FU (250mg×30) and Cosmegen (1mg×3) and tele-CO6o irradiation (41167) to the region of penile root were performed again. …
NAID 120002232727

Actinomycin D, Vincristine sulfate, CO^<60> 照射および Cyclophosphamide の併用療法による Rhabdomyosarcoma の長期生存例

沢田淳 [他],今宿晋作,高田洋,乾明彦,好地衛
日本小児外科学会雑誌 8(2), 241-245, 1972-08
… Actinomycin D, Vincristine, CO^<60>照射, Cyclophosphamideによる併用療法を行ったところ, 急速に腫瘤は縮少し, 2年3カ月経過した現在, 再発の徴候なく, 健康に通学している症例を報告した.このような強力な治療は予後不良な本症に対して, 今後さらに多くの症例に用いられるべきであると思われる.「Actinomycin Dはlyovac Cosmegen(日本メルク万有), Vincristine sulfateはOnchovin(塩野義製薬KK), CyclophosphamineはEndoxan(塩野義製薬KK)を用いた」 …
NAID 110002120271

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★リンクテーブル★

リンク元	「アクチノマイシンD」

「アクチノマイシンD」

Actinomycin D
Systematic (IUPAC) name
	2-Amino-N,N′- bis[(6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide
Clinical data
Trade names	Cosmegen
AHFS/Drugs.com	monograph
MedlinePlus	a682224
Pregnancy cat.	D
Legal status	℞ Prescription only
Routes	IV
Pharmacokinetic data
Protein binding	5%
Half-life	36 hours
Identifiers
CAS number	50-76-0
ATC code	L01DA01
PubChem	CID 2019
DrugBank	DB00970
ChemSpider	10482167
UNII	1CC1JFE158
KEGG	C06770
ChEBI	CHEBI:27666
ChEMBL	CHEMBL1554
NIAID ChemDB	009885
Synonyms	2-Amino- 4,6-dimethyl- 3-oxo- 3H-phenoxazine- 1,9-dicarboxylic acid bis- [(5,12-diisopropyl- 9,13,16-trimethyl- 4,7,11,14,17-pentaoxo- hexadecahydro- 10-oxa- 3a,6,13,16-tetraaza- cyclopentacyclohexadecen- 8-yl)- amide]
Chemical data
Formula	C62H86N12O16
Mol. mass	1255.42 g/mol
	InChI InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1 ; Key:RJURFGZVJUQBHK-IIXSONLDSA-N ;
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　　[★]

英: actinomycin D　actinomycin-D ACT-D
同: アクチノマイシン actinomycin、ダクチノマイシン dactinomycin DACT、Cosmegen
商: コスメゲン Cosmegen

first aid step1 2006 p.307,309,326

分類

抗悪性腫瘍薬

抗生物質

構造

作用機序

intercalates in DNA

適応

Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma(first aid step1 2006 p.309) ← 子供の腫瘍

副作用

myelosuppression

[gen-1] Hollstein, U. (1974). "Actinomycin. Chemistry and mechanism of action". Chemical Reviews 74 (6): 625–652. doi:10.1021/cr60292a002.

[2] Waksman S A, Woodruff H B (1940). "Bacteriostatic and bacteriocidal substances produced by soil actinomycetes". Proc Soc Exper Biol 45: 609–614.

[3] Sobell H (1985). "Actinomycin and DNA transcription". Proceedings of the National Academy of Sciences of the United States of America 82 (16): 5328–31. doi:10.1073/pnas.82.16.5328. PMC 390561. PMID 2410919.

[4] Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M (2006). "Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia". Int J Gynecol Cancer 16 (3): 1432–8. doi:10.1111/j.1525-1438.2006.00606.x. PMID 16803542.

[5] Abd El-Aal H, Habib E, Mishrif M (2005). "Wilms' Tumor: The Experience of the Pediatric Unit of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK)". J Egypt Natl Canc Inst 17 (4): 308–11. PMID 17102824.

[6] Khatua S, Nair C, Ghosh K (2004). "Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues". J Pediatr Hematol Oncol 26 (11): 777–9. doi:10.1097/00043426-200411000-00020. PMID 15543019.

[7] Jaffe, N.; Paed, D.; Traggis, D.; Salian, S.; Cassady, J. R. (1976). "Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy". Cancer 38 (5): 1925–1930. doi:10.1002/1097-0142(197611)38:5<1925::AID-CNCR2820380510>3.0.CO;2-J. PMID 991106.

[8] Uberti, E. M. H.; Fajardo, M. D. C.; Ferreira, S. V. V. R.; Pereira, M. C. V.; Seger, R. C.; Moreira, M. A. L. R.; Torres, M. D.; De Nápoli, G.; Schmid, H. (2009). "Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy". Gynecologic Oncology 115 (3): 476–481. doi:10.1016/j.ygyno.2009.09.012. PMID 19818481.

[9] Hagemann, R. F.; Concannon, J. P. (1973). "Mechanism of intestinal radiosensitization by actinomycin D". British Journal of Radiology 46 (544): 302–308. doi:10.1259/0007-1285-46-544-302. PMID 4720744.

[10] Toba, K.; Koike, T.; Watanabe, K.; Fuse, I.; Takahashi, M.; Hashimoto, S.; Takahashi, H.; Abe, T.; Yano, T.; Shibazaki, Y.; Itoh, H.; Aizawa, Y. (2000). "Cell kinetic study of normal humanbone marrow hematopoiesis andacute leukemia using 7AAD/PY". European Journal of Haematology 64 (1): 10–21. doi:10.1034/j.1600-0609.2000.09005.x. PMID 10680701. edit

匿名

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案内

案内

Cosmegen