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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 source | edit]

Tubulin is a structural protein that polymerizes to microtubules. The cell cytoskeleton and mitotic spindle, among other things, are made of microtubules. Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures. Disruption of the microtubules arrests mitosis in metaphase. Therefore, the vinca alkaloids affect all rapidly dividing cell types including cancer cells, but also those of intestinal epithelium and bone marrow.

Uses[edit source | 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, and in treatment for nephroblastoma (Wilms tumor, a kidney tumor most common in young children). It is also used to induce remission in ALL with Dexamethasone and L-Asparaginase. Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP). It is used in combination with prednisone to treat childhood leukemia.

Side-effects[edit source | edit]

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

Peripheral neuropathy 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.^[2]

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; a handful of survivors were left with devastating neurological damage with no hope of recovery. Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications.^[3] 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.^[4]

History[edit source | 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.^[5]

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 source | edit]

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

References[edit source | edit]

^ "Pharmacognosy of Vinca Alkaloids".
^ 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.
^ 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 source | 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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1. 非プラチナ製剤ベースの癌化学療法の神経学的合併症の概要 overview of neurologic complications of non platinum cancer chemotherapy
2. 成人における抗癌剤の投与 dosing of anticancer agents in adults
3. 成人における再発性および難治性の急性リンパ芽球性白血病の治療 treatment of relapsed or refractory acute lymphoblastic leukemia in adults
4. 進行性（ステージIII～IV）の古典型ホジキンリンパ腫の初期治療 initial treatment of advanced stage iii iv classical hodgkin lymphoma
5. 成人の古典的ホジキンリンパ腫生存者に対するアプローチの概要 overview of the approach to the adult survivor of classical hodgkin lymphoma

English Journal

Induction of thyroid neoplasm following plant medicine marine algae (sargassum): a rare case and review of the literature.

Zhu G, Musumeci F, Byrne P1.Author information 1Institute of Oncology of George Zhu, 422407, Beijing, China. sansan4240732@163.com.AbstractIn this study induction of neoplasm in thyroid gland of one postoperative patient with breast cancer was conducted by marine algae (also seaweed, sargassum), which is presented here. A 41-year-old women was diagnosed as her right breast cancer complicated with lymph node metastasis in her right axilla on February, 1999. In June 19, 1999 she was given the combination chemotherapy of vincristine, cyclophosphamide, 5-Fluorouracil and cinobufacini drugs due to two lymph nodes on her right superclavicular following radical mastectomy. During chemotherapy she was also taken the adjuvant treatment of traditional medicine. Traditional medicine consisted of seaweed plant drugs (containing iodine 362,400 ug/kg). As to intermittent maintance treatment the total dosage of seaweed herb was at least exceeded 500 gram. Induction of thyroid tumor (thumb size) was found in June, 2001. A thyroidectomy due to thyroma was successfully performed. Histologically there revealed thyroid tissue without the evidence of metastasis of breast cancer. She had a 5-year survivor. The data indicated oncogenic function of some traditional herbs, and further experience of traditional medicine in treating thyroid disease especially in thyroid cancer.
Current pharmaceutical biotechnology.Curr Pharm Biotechnol.2014 Oct;14(9):859-63.
In this study induction of neoplasm in thyroid gland of one postoperative patient with breast cancer was conducted by marine algae (also seaweed, sargassum), which is presented here. A 41-year-old women was diagnosed as her right breast cancer complicated with lymph node metastasis in her right axil
PMID 24433506

Cost minimization analysis of two treatment regimens for low-risk rhabdomyosarcoma in children: A report from the Children's Oncology Group.

Russell H1, Swint JM, Lal L, Meza J, Walterhouse D, Hawkins DS, Okcu MF.Author information 1Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas; University of Texas School of Public Health, Division of Management, Policy and Community Health, Houston, Texas.AbstractBACKGROUND: Recent Children's Oncology Group trials for low-risk rhabdomyosarcoma attempted to reduce therapy while maintaining excellent outcomes. D9602 delivered 45 weeks of outpatient vincristine and dactinomycin (VA) for patients in Subgroup A. ARST0331 reduced the duration of therapy to 22 weeks but added four doses of cyclophosphamide to VA for patients in Subset 1. Failure-free survival was similar. We undertook a cost minimization comparison to help guide future decision-making.
Pediatric blood & cancer.Pediatr Blood Cancer.2014 Jun;61(6):970-6. doi: 10.1002/pbc.24950. Epub 2014 Jan 22.
BACKGROUND: Recent Children's Oncology Group trials for low-risk rhabdomyosarcoma attempted to reduce therapy while maintaining excellent outcomes. D9602 delivered 45 weeks of outpatient vincristine and dactinomycin (VA) for patients in Subgroup A. ARST0331 reduced the duration of therapy to 22 week
PMID 24453105

A unique composite follicular lymphoma and mantle cell lymphoma with a mixed cell pattern and aggressive course.

Liu Y1, Li P, Guo Y, Fan L, Wang L, Zhu J, Huang G, Yan Q, Wang Z.Author information 1Dept of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China; zhwang@fmmu.edu.cn or yanqg@fmmu.edu.cn.AbstractObjectives There are a limited number of reports of composite follicular lymphoma (FL) and mantle cell lymphoma (MCL) in the literature, and all previous cases report that FL and MCL components are separated, even within a single lymph node. Here we report a case of a patient with a distinctive composite FL and MCL with a mixed cell pattern. Methods A 34-year-old man presented with left supraclavicular lymphadenopathy for one month. The lymph node contained closely packed nodules of lymphocytes. Immunostaining and fluorescence in situ hybridization demonstrated the FL nature of the Bcl-2- and CD10-positive tumor cells, as well as the scattered cyclin D1-positive MCL tumor cells in the nodules. Double immunohistochemical staining showed an unusual mixed pattern of both types of tumor cells. Results The patient received a regimen of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and achieved partial remission following four cycles of chemotherapy but relapsed 1 month after the last treatment and died of meninges involvement 8 months after the first presentation. Conclusions To our knowledge, this is the first report of composite FL and MCL with a mixed pattern. A mixture of grade IIIb FL and MCL may explain the poor prognosis of the patient.
American journal of clinical pathology.Am J Clin Pathol.2014 May;141(5):737-41. doi: 10.1309/AJCPAWDDYO5OQYCD.
Objectives There are a limited number of reports of composite follicular lymphoma (FL) and mantle cell lymphoma (MCL) in the literature, and all previous cases report that FL and MCL components are separated, even within a single lymph node. Here we report a case of a patient with a distinctive comp
PMID 24713749

Japanese Journal

小腸穿孔をきたしたII型腸管症関連T細胞リンパ腫の1例

崎村千恵,河本真大,呉幸枝,阿古英次,藤田茂樹,妙中直之
日本臨床外科学会雑誌 75(8), 2229-2233, 2014
症例は59歳の男性．持続する発熱と貧血の精査で当院を受診，CT検査で7cm大の腹腔内腫瘤を認め悪性リンパ腫が疑われた．手術を予定していたが突然の腹痛にて当施設を受診，腹部MRI検査にて，腹水・腹腔内ガス像を認め穿孔性腹膜炎を疑い緊急手術を行った．手術では回腸に穿孔した腫瘍を認め，腫瘍を含む小腸を切除した．病理検査ではCD8，CD56陽性でtype II enteropathy associated …
NAID 130004901362

乳糜腹水を合併した限局期の胃原発非ホジキンリンパ腫の1例

山本宜和,久米井伸介,小倉武司,大西裕,前田光雄,松野寧子
日本消化機病學會雜誌. 乙 110(10), 1790-1796, 2013
症例は87歳男性．食欲不振・腹部膨満を主訴に受診した．上部消化管内視鏡検査で，胃全体にびらんと粘膜の結節状腫大を認め，生検で非ホジキンリンパ腫と診断した．同時に認めた腹水は乳糜腹水を呈していた．画像検査では腹腔内への腫瘍の進展は指摘されなかった．治療はR-CHOP療法を施行したが完全寛解となり，腹水はほぼ消失した．限局期の胃悪性リンパ腫が乳糜腹水の原因となりうることを示したまれな症例である．
NAID 130004776820

CHOP-Rが著効した食道原発悪性リンパ腫の1例 : 本邦報告38例についての考案

中谷雅美,藤原靖弘,永見康明,亀田夏彦,町田浩久,岡崎博俊,渡辺俊雄,富永和作,大澤政彦,荒川哲男
日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy 51(12), 3070-3077, 2009-12-20
… 部CT検査，PET検査にて病変の主座は食道にあり，左鎖骨上，縦隔リンパ節に転移をみとめた．以上より，原発性食道悪性リンパ腫，Musshoff分類Stage II E2と診断した．標準的CHOP-R（Cyclophosphamide，Hydroxydau-norubicin，Oncovin，Prednisone and Rituxi-mab）を6クール施行し，完全寛解を得た．13カ月経過した現在も再発や転移なく，経過順調である．<BR>今回，われわれは比較的稀な化学療法が奏功した食道悪性リンパ腫を経験したので …
NAID 10026909164

Related Pictures

★リンクテーブル★

リンク元	「絨毛癌」「vincristine sulfate」
関連記事	「oncovin」

「絨毛癌」

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	Exclusively 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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