硫酸ビンクリスチン

関: Oncovin、vincristine

WordNet

convert into a sulfate
a salt or ester of sulphuric acid (同)sulphate
periwinkle plant derivative used as an antineoplastic drug (trade name Oncovin); used to treat cancer of the lymphatic system (同)Oncovin

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/28 00:03:23」(JST)

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This article is about the cancer chemotherapy drug vincristine. It should not be confused with vinblastine, a chemotherapy drug with a different chemical formula.

Vincristine (brand name, Oncovin), formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus (Madagascar periwinkle), formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy. Vincristine is created by the coupling of indole alkaloids vindoline and catharanthine in the vinca plant.^[1]

Mechanism[edit]

Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures and arresting mitosis in metaphase. Because vincristine's mechanism of action targets all rapidly dividing cell types, it not only inhibits cancerous cells but can also affect the intestinal epithelium and bone marrow.

Uses[edit]

Vincristine is delivered via intravenous infusion for use in various types of chemotherapy regimens. Its main uses are in non-Hodgkin's lymphoma as part of the chemotherapy regimen CHOP, Hodgkin's lymphoma as part of MOPP, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen in acute lymphoblastic leukemia (ALL), and in treatment for nephroblastoma. It is also used to induce remission in ALL with dexamethasone and L-Asparaginase, and in combination with prednisone to treat childhood leukemia. Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP).

Side-effects[edit]

The main side-effects of vincristine are chemotherapy-induced peripheral neuropathy, hyponatremia, constipation, and hair loss.

Chemotherapy-induced peripheral neuropathy, a progressive, enduring, often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs,^[2] can be severe, and hence a reason to avoid, reduce, or stop the use of vincristine. One of the first symptoms of peripheral neuropathy is foot drop: A person with a family history of foot drop and/or Charcot-Marie-Tooth disease (CMT) should avoid the taking of vincristine.^[3]

Accidental injection of vinca alkaloids into the spinal canal (intrathecal administration) is highly dangerous, with a mortality rate approaching 100 percent. The medical literature documents cases of ascending paralysis due to massive encephalopathy and spinal nerve demyelination, accompanied by intractable pain, almost uniformly leading to death. Several patients have survived after aggressive and immediate intervention. Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications.^[4] Children may do better following this injury. One child, who was aggressively treated at the time of the injection, recovered almost completely with only mild neurological deficits.^[5] A significant series of inadvertent intrathecal vincristine administration occurred in China in 2007 when batches of cytarabine and methotrexate (both often used intrathecally) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine.^[6]

History[edit]

Having been used as a folk remedy for centuries, studies in the 1950s revealed that C. roseus contained 70 alkaloids, many of which are biologically active. While initial studies for its use in diabetes mellitus were disappointing, the discovery that it caused myelosuppression (decreased activity of the bone marrow) led to its study in mice with leukemia, whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skelly-B defatting agent and an acid benzene extract led to a fraction termed "fraction A". This fraction was further treated with aluminium oxide, chromatography, trichloromethane, benz-dichloromethane, and separation by pH to yield vincristine.^[7]

Vincristine was approved by the United States Food and Drug Administration (FDA) in July 1963 as Oncovin. The drug was initially discovered by a team led by Dr. J.G. Armstrong, then marketed by Eli Lilly and Company.

Suppliers[edit]

Three generic drug makers supply vincristine in the United States - APP, Mayne, and Sicor (Teva).

References[edit]

^ "Pharmacognosy of Vinca Alkaloids".
^ del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010;7(4):6.
^ Graf, W. D.; Chance, P. F.; Lensch, M. W.; Eng, L. J.; Lipe, H. P.; Bird, T. D. (1996). "Severe Vincristine Neuropathy in Charcot-Marie-Tooth Disease Type 1A". Cancer 77 (7): 1356–1362. doi:10.1002/(SICI)1097-0142(19960401)77:7<1356::AID-CNCR20>3.0.CO;2-#. PMID 8608515.
^ Qweider, M.; Gilsbach, J. M.; Rohde, V. (2007). "Inadvertent Intrathecal Vincristine Administration: A Neurosurgical Emergency. Case Report". Journal of Neurosurgery: Spine 6 (3): 280–283. doi:10.3171/spi.2007.6.3.280. PMID 17355029.
^ Zaragosa, M.; Ritchey, M.; Walter, A. (1995). "Neurological Consequences of Accidental Intrathecal Vincristine: A Case Report.". Medial and Pediatric Oncology 24: 61–62. PMID 7968797.
^ Jake Hooker and Walt Bogdanich (January 31, 2008). "Tainted Drugs Tied to Maker of Abortion Pill". New York Times.
^ Johnson, I. S.; Armstrong, J. G.; Gorman, M.; Burnett, J. P. (1963). "The Vinca Alkaloids: A New Class of Oncolytic Agents" (pdf). Cancer Research 23 (8 Part 1): 1390–1427. PMID 14070392.

External links[edit]

Vincristine chemotherapy
Vincristine and vinblastine
Description and Natural History of the Periwinkle
The Boger Route to (-)-Vindoline
U.S. National Library of Medicine: Drug Information Portal - Vincristine

UpToDate Contents

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English Journal

Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway.

Lu Y1, Zhao X1, Luo G1, Shen G1, Li K1, Ren G1, Pan Y1, Wang X2, Fan D3.
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Modification of sphingolipid metabolism by tamoxifen and N-desmethyltamoxifen in acute myelogenous leukemia-Impact on enzyme activity and response to cytotoxics.

Morad SA1, Tan SF2, Feith DJ3, Kester M4, Claxton DF5, Loughran TP Jr3, Barth BM5, Fox TE6, Cabot MC7.
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PMID 25769964

Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms?

Carozzi VA1, Canta A2, Chiorazzi A2.
Neuroscience letters.Neurosci Lett.2015 Jun 2;596:90-107. doi: 10.1016/j.neulet.2014.10.014. Epub 2014 Oct 22.
Cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib are some of the most effective drugs successfully employed (alone or in combinations) as first-line treatment for common cancers. However they often caused severe peripheral neurotoxicity and neuropathic pain. Structural deficits in Dors
PMID 25459280

Japanese Journal

プロプラノロールが有効であった鼻腔乳児血管腫の１例

赤木祐介,丸中秀格,折田頼尚
小児耳鼻咽喉科 36(1), 27-30, 2015
尾翼腫脹・反復性鼻出血が主訴の 3 カ月男児の鼻腔乳児血管腫に β–blocker の一種であるプロプラノロールを使用し縮小効果が得られた症例を経験したので報告する。本症例は生後 2 カ月頃より鼻出血を反復し，3 カ月になった頃から右鼻翼が膨隆してきたため当科紹介となった。右鼻前庭部に乳児血管腫を認めたため，プロプラノロールを 1 mg/kg/日で開始し，治療開始後 7 日目で 2 mg/kg …
NAID 130005078711

Erratum: 侵襲性肺炎球菌感染症を発症した腎臓移植レシピエントの2例[移植 2014: 49(6): 423-427]

伊藤健太,後藤憲彦,西平守邦,二村健太,岡田学,山本貴之,辻田誠,平光高久,鳴海俊治,冨永芳博,渡井至彦
移植 50(1), e1-e1, 2015
… 訂正前：R-CHOP：rituximab＋CyA＋doxorubicin hydrochloride＋vincristine sulfate＋PSL，MMF：mycophenolate mofetil，EVL：everolimus，CyA：cyclisporin，PSL：prednisolone※「CyA」ではなく，正しくは「cyclophosphamide」となります。 … 訂正後：R-CHOP：rituximab＋cyclophosphamide＋doxorubicin hydrochloride＋vincristine sulfate＋PSL，MMF：mycophenolate mofetil，EVL：everolimus，CyA：cyclosporin，PSL：prednisolone …
NAID 130005002828

Clinical Pharmacokinetics and Effects of Vincristine Sulfate in Dogs with Transmissible Venereal Tumor (TVT)

HANTRAKUL Supannika,KLANGKAEW Narumol,KUNAKORNSAWAT Sunee [他],TANSATIT Tawewan,POAPOLATHEP Ammart,KUMAGAI Susumu,POAPOLATHEP Saranya
Journal of Veterinary Medical Science 76(12), 1549-1553, 2014
… This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). … Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m2 of body surface area. … The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). …
NAID 130004780992

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リンク元	「ビンクリスチン」
関連記事	「sulfate」「sulfated」「sulfa」

「ビンクリスチン」

Vincristine
Systematic (IUPAC) name
	(3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-ethyl-9-((5S,7S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-6-formyl-5-hydroxy-8-methoxy-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682822
Pregnancy cat.	D (AU) D (US)
Legal status	℞ Prescription only
Routes	intravenous
Pharmacokinetic data
Bioavailability	n/a
Protein binding	~75%
Metabolism	Hepatic
Half-life	19 to 155 hours
Excretion	Mostly biliary, 10% in urine
Identifiers
CAS number	57-22-7
ATC code	L01CA02
PubChem	CID 5978
DrugBank	DB00541
ChemSpider	5758
UNII	5J49Q6B70F
KEGG	D08679
ChEBI	CHEBI:28445
ChEMBL	CHEMBL303560
Chemical data
Formula	C46H56N4O10
Mol. mass	824.958 g/mol
	SMILES O=C(OC)[C@]4(c2c(c1ccccc1n2)CCN3C[C@](O)(CC)C[C@@H](C3)C4)c5c(OC)cc6c(c5)[C@@]89[C@@H](N6C=O)[C@@](O)(C(=O)OC)[C@H](OC(=O)C)[C@@]7(/C=C\CN([C@@H]78)CC9)CC;
	InChI InChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28) ; Key:OGWKCGZFUXNPDA-XQKSVPLYSA-N ;
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　　[★]

英: vincristine, VCR
同: 硫酸リューロクリスチン leurocristine sulfate
化: 硫酸ビンクリスチン vincristine sulfate　
商: ONCO-TCS、ONCOVIN、VINCASAR PFS、オンコビン oncovin
関

first aid step1 2006 p.84,310

特徴

ビンカアルカロイドの一つで、チューブリンに結合して微小管の重合(紡錘体の形成を含む)を阻害して細胞増殖を抑制する。　⇔ (パクリタキセルは微小管の脱重合を阻害)

構造

ビンカアルカロイド

作用機序

M-phase-specific alkaloids that bind to tubulin and block polymerization of microtubules so that mitotic spindle cannot form (first aid step1 2006 p.310)

適応

part of the MOPP (Oncovin [vincristine]) regimen for lymphoma, Wilms' tumor, choriocarcinoma(first aid step1 2006 p.310)
MAPP regimen for Hodgkin disease, ALL lymphoma, CNS tumer, sarcoma, Wilms tumor