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胸苷激酶

維基百科,自由的百科全書
胸苷激酶
Crystal structure of a tetramer of thymidine kinase from U. urealyticum (where the monomers are color cyan, green, red, and magenta respectively) in complex with thymidine (space-filling model, carbon = white, oxygen = red, nitrogen = blue).[1]
識別碼
EC編號 2.7.1.21
CAS號 9002-06-6
數據庫
IntEnz IntEnz瀏覽
BRENDA英語BRENDA BRENDA入口
ExPASy英語ExPASy NiceZyme瀏覽
KEGG KEGG入口
MetaCyc英語MetaCyc 代謝路徑
PRIAM英語PRIAM_enzyme-specific_profiles 概述
PDB RCSB PDB PDBj PDBe PDBsum
基因本體 AmiGO / EGO
胸苷激酶
鑑定
標誌TK
PfamPF00265舊版
Pfam宗系CL0023舊版
InterPro英語InterProIPR001267
PROSITE英語PROSITEPDOC00524
胸苷激酶1,可溶
識別
符號 TK1
Entrez 7083
HUGO 11830
OMIM 188300
RefSeq NM_003258
UniProt P04183
其他資料
EC編號 2.7.1.21
基因座 17 q23.2-25.3
胸苷激酶2,線粒體
識別
符號 TK2
Entrez 7084
HUGO 11831
OMIM 188250
RefSeq NM_004614
UniProt O00142
其他資料
EC編號 2.7.1.21
基因座 16 [1]

胸苷激酶(英語:thymidine kinase)是一種磷酸轉移酶(激酶):2』-脫氧胸苷激酶,三磷酸腺苷-胸苷 5』-磷酸轉移酶,EC 2.7.1.21[2][3]存在於大部分活體細胞中。它以兩種同工酶的形式存在於哺乳動物細胞中,TK1和TK2。某些病毒同樣含有病毒性胸苷激酶表達的遺傳信息。

胸苷激酶催化以下反應:

•Thd + ATP → TMP + ADP

Thd是脫氧胸苷,ATP是5』-三磷酸-腺苷,TMP是5』-一磷酸-脫氧胸苷,ADP是5』-二磷酸-腺苷。

胸苷激酶的主要作用體現在細胞分裂過程中的DNA合成期,是介導脫氧胸苷進入DNA合成的旁路途經的一部分。脫氧胸苷存在於體液中,是食物細胞或機體細胞死亡後,DNA凋亡退化的產物。很多抗病毒藥物的反應都需要胸苷激酶的參與。

胸苷激酶可用於在生產單克隆抗體過程中,篩選雜交瘤細胞。臨床醫學中,胸苷激酶作為一種細胞增殖標誌物,用於惡性腫瘤的輔助診斷,治療監控和跟蹤隨訪。最近也有研究報道提出,胸苷激酶在早期癌症預防中的應用價值。

歷史

胸苷參與DNA合成的途經是在1950年前後發現的[4],後來進一步明確,這一途經始於胸苷的磷酸化[5];在1960年左右,參與此過程的激酶(胸苷激酶)被首次純化出來並進行了鑑定[6][7]


分類

目前已得到鑑別的胸苷激酶可分為兩大類[8][9]

一類存在於疱疹病毒細胞胸苷激酶類似;

一類廣泛存在於脊椎動物,細菌,T4噬菌體,痘病毒,非洲豬瘟病毒(ASFV)和魚淋巴囊腫病毒(FLDV)。昆蟲虹彩病毒衣殼蛋白也屬於此類。

目前只確認了細胞胸苷激酶的蛋白位點模型。

生化特點

高等生物胸苷激酶以兩種同工酶形式存在,TK1和TK2,具有很大的化學差異性。

前一種最初在胎兒組織中發現,後一種大量存在於成人組織,所以最初,被分別命名為胎兒胸苷激酶和成人胸苷激酶。不久之後發現,TK1僅於細胞分裂初期(與細胞周期相關)存在於細胞質中[10][11],而TK2定位於線粒體中,與細胞周期無關[12][13]

1970年代中期定位了兩種酶的基因[14][15],TK1基因的克隆和測序完成[16],其所對應蛋白的分子量為25kD;通常以二聚體的形式出現在組織中,能夠被ATP激活;激活後,轉化為四聚體。重組後的TK1無法被激活也無法轉化為四聚體,表明這種存在於細胞中的激酶在合成後性狀已經發生了改變[17][18][19]

細胞中TK1的合成發生在細胞分裂周期的S期。細胞分裂完成後,TK1在細胞內部降解,因此在正常細胞分裂中,TK1一般不會進入體液[20]。細胞中胸苷激酶的反饋調節作用機理:三磷酸胸苷(TTP:胸苷磷酸化後的終產物)扮演着胸苷激酶抑制劑的角色[21][22][23][24]。這一機制確保了核酸合成所需的TTP量維持在平衡狀態,而不會出現過飽和。5'-氨基胸苷是一種無毒性的胸苷類似物,能夠干擾這一調控機理,因此,胸苷類似物作為一種細胞毒性物質被應用於很多抗腫瘤藥物[25][26][27][28][29][30][31]

一些病毒的特殊胸苷激酶基因也已經得到了鑑別,如單純疱疹病毒,水痘帶狀疱疹病毒和EB病毒(一種疱疹病毒)[32][33][34][35][36][37][38]

生理學背景

胸苷激酶催化反應的產物——一磷酸脫氧胸苷,會繼續被胸苷酸激酶催化生成二磷酸脫氧胸苷,之後再被二磷酸核苷激酶催化生成三磷酸脫氧胸苷。在互補DNA和DNA聚合酶的催化作用下(或是逆轉錄過程中,在RNA和逆轉錄酶的作用下),三磷酸脫氧胸苷進入了DNA分子。

一磷酸脫氧胸苷可由兩種不同的反應得到——一種是前文所述的脫氧胸苷磷酸化反應得到;還有一種是在不動用胸苷的情況下,通過胸苷酸磷酸酶催化其他代謝途徑產生的脫氧尿苷甲基化反應得到。細胞在正常情況下(非細胞分裂狀態)採用第二種途徑為DNA修復提供充足的一磷酸脫氧胸苷。但當細胞準備分裂時,需要構建一組全新的DNA,對組成DNA的材料,如三磷酸脫氧胸苷的需求也增加了。在準備細胞分裂的過程中,一些細胞分裂所必需的酶開始產生。

這些酶平時不存在於細胞中,當細胞分裂完成後,在調控下濃度降低,最終降解。這一類酶被稱為補救酶。胸苷激酶1(TK1)就是一種補救酶,但胸苷激酶2(TK2)卻與細胞周期不相關[39][40][41][42][43][44][45][46][47]

用途

鑑別處於分裂期的細胞

胸苷激酶在生化研究中的第一種直接應用是聯合放射性標記的胸苷和後繼用來測定放射活性的放射自顯影技術來鑑別處於分裂期的細胞。為了達到此目的,氚化的胸苷需保存在培養基中。[48] 儘管技術上存在缺陷,該技術仍被用來測定惡性腫瘤細胞的增殖比例和研究免疫過程中淋巴細胞的活性。

PET 掃描活體腫瘤

3』-脫氧-3』-[氟18]氟化胸苷是一種胸苷類似物。它由胸苷激酶1調控,被迅速增殖的腫瘤組織優先攝取。同位素氟18是一種在正電子發射型斷層顯像技術(PET)中常用的正電子發射體。這種標記物和另一常用的標記物2-[氟18]氟基-2-脫氧-D-葡萄糖相比,在對增殖狀態的活體腫瘤的PET成像方面更有優勢[49][50][51][52][53]

篩選雜交瘤細胞

雜交瘤細胞是腫瘤細胞(具有無限分裂能力)和B淋巴細胞融合後獲得的。雜交瘤細胞能夠持續、大量地產生具有專屬特異性的免疫球蛋白(單克隆抗體)。但問題是如何在細胞融合後,從大量的多餘的未融合細胞中,挑選出雜交瘤細胞。

一種解決該問題的方法就是使用胸苷激酶陰性(TK-)的腫瘤細胞系進行融合。在增殖的腫瘤細胞系中加入胸苷類似物,將殺死胸苷激酶陽性(TK+)細胞,如此就得到了胸苷激酶陰性細胞。然後,這些陰性細胞用來與胸苷激酶陽性的(TK+)B淋巴細胞進行融合。融合之後,細胞需在添加了氨甲蝶呤[54]或氨基蝶呤[55]的培養基中培養,以防止二氫葉酸還原酶阻礙一磷酸胸苷的重新合成。培養基一般選用HAT培養基(含有次黃嘌呤,氨基蝶呤,胸腺嘧啶脫氧核苷)。 胸苷激酶陰性細胞系中的未融合細胞將由於一磷酸胸苷的斷供而死亡。而未融合淋巴細胞的死亡則是由於它們不是「不朽」的(不具備腫瘤細胞的無限分裂能力)。只有雜交瘤細胞由於同時繼承了腫瘤細胞系的「不朽」和B淋巴細胞的胸苷激酶得以倖存。這樣,可以用於生產所需抗體的雜交瘤細胞就篩選出來了,在培養後用於生產單克隆抗體。[56][57][58][59][60]

不過,採用相同原理,也可以通過篩選另一種次黃嘌呤-鳥嘌呤磷酸核糖轉移酶(HGPRT)細胞系來達到篩選雜交瘤細胞的目的從而替代胸苷激酶,該酶在補救合成途經中調控鳥嘌呤核苷酸合成所必須的次黃嘌呤的合成。

應用案例

臨床應用

胸苷激酶是一種補救酶,僅在細胞分裂前出現。由於細胞具有特殊的調控機制能夠降解細胞分裂後不再需要的酶和蛋白,所以在正常的細胞分裂後,胸苷激酶不會從細胞釋放。[61]因此一般條件下,血清或血漿中的胸苷激酶含量很低。腫瘤細胞釋放胸苷激酶進入循環系統,可能是與已經死亡或即將死亡的腫瘤細胞的瓦解有關。因此,血清胸苷激酶水平能夠用來評估腫瘤的增殖程度,並可以此來直接評估腫瘤的攻擊力。有一個令人關注的情況,存在於循環系統中的胸苷激酶與基因編碼的酶並不一致:基因編碼的酶分子量為25kD。二聚體分子量為50kD,被ATP激活轉化為四聚體後,分子量為100kD。[62]而循環系統中具有活性的酶的分子量為730kD,很有可能是與其他蛋白綁定形成了複合物[63]

目前胸苷激酶檢測在臨床應用中的價值主要體現在以下幾點:

1、評估放化療效果:由於胸苷激酶水平與腫瘤細胞惡性增殖程度具有相關性,治療前後的胸苷激酶水平變化情況能為治療評估提供輔助參考;

2、評估手術效果:通過比較腫瘤患者手術前後腫瘤細胞的增殖情況,為手術效果評價提供參考;

3、評估腫瘤復發風險:對腫瘤患者手術及治療恢復期的殘留腫瘤細胞的增殖狀態進行動態評估,較影像學更早發現復發轉移風險。[64]

不同腫瘤類別的胸苷激酶應用案例:

1、血液學惡性腫瘤中胸苷激酶的增長具有規律性。例如,胸苷激酶1(TK1)用於監控非霍奇金淋巴瘤。這種腫瘤的攻擊性差別很大,有些屬於慢速增殖,很難覺察難以及時治療;還有一些屬於快速增殖,具有高攻擊性需要緊急治療。這些差異可以在血清胸苷激酶的水平高低上得以體現,與正常水平相近的對應慢速增殖腫瘤,具有很高水平的對應快速增殖腫瘤。[65][66][67][68][69][70][71][72] 淋巴瘤患者血清TK1水平升高,可能預示着腫瘤具有高活性和高攻擊性,因此通過監測血清TK1水平的變化,適合於腫瘤的治療評估。[73]

該模型也使用於其他類型血液惡性腫瘤中(白血病[74][75][76],漿細胞骨髓瘤[77][78],骨髓增生異常綜合症)。需要關注的是在骨髓增生異常綜合症中:有一部分病例會迅速轉變為進行白血病,但是還有一些在很長一段時間內進展緩慢。那如果能夠鑑別出是否有進展為白血病的趨勢將對治療非常重要。

2、實體腫瘤中胸苷激酶的升高往往也與腫瘤惡性增殖程度,治療效果,復發情況具有相關性[79][80][81][82]。有報告指出在前列腺癌症中,胸苷激酶能夠如同PSA(前列腺特異抗原,目前前列腺癌中使用最頻繁的腫瘤標誌物)一樣提供輔助參考。PSA提示腫瘤大小,而TK提示腫瘤增殖速度[83][84][85][86]。對於其他實體腫瘤,如小細胞肺癌[87][88][89]乳腺癌[90][91][92]胃癌[93]腎癌[94]膀胱癌[95]等都有應用價值。

非惡性腫瘤而造成血清胸苷激酶升高的原因有維生素B12缺乏引起的惡性貧血,[96][97]病毒感染(部分由於疱疹病毒)[97][98][99] 或正處於創傷、手術恢復期[100]

惡性增殖風險評估

由於胸苷激酶1與細胞增殖的相關性,近些年來,有關於胸苷激酶1對於進展期癌前病變的檢測意義,及在癌症預防體檢中的應用價值的探討。

有研究指出胸苷激酶1水平高低與不同年齡結構,及所處不同生活、工作環境的腫瘤發生風險具有相關性,在進行長期跟蹤後,TK1水平的持續升高與所患癌前病變的惡性進程具有相關性,在早期惡性腫瘤病變預防中能夠發揮一定作用。[101][102]

治療

有些藥物專門針對分裂期細胞有效。一般被用來治療腫瘤和病毒性疾病(同時作用於逆轉錄病毒和其他病毒),這是由於病變細胞比正常細胞複製更快更頻繁,同時也會殺死一些複製迅速地非惡性腫瘤細胞。

有不同種類的藥物可以控制細胞分裂過快,能夠直接作用於胸苷代謝也因此與胸苷激酶有關聯[103][104][105][106]

胸苷類似物作為DNA鏈終止物進入DNA鏈複製,但是由於結構已經改變所以抑制了DNA鏈的延長。作為胸苷類似物,更容易磷酸化生成5』-一磷酸複合物。一磷酸複合物進一步磷酸化生成三磷酸複合物參與到DNA鏈的複製。但類似物結構有所變化,一般不具有DNA鏈複製所必須的3』端羥基。如:疊氮胸苷(AZT;ATC:J05AF01)的3』端羥基被疊氮基替代;[107][108] 雙脫氧胸苷(ATC:J05AF04)能夠競爭性抑制胸苷。[109][110] AZT在一種檢測血清胸苷激酶的方法中被用做底物。[111] 這意味着AZT會干擾這一步驟或是作為一種抑制劑: AZT是針對HIV(艾滋病病毒)感染的HAART(Highly Active Antiretroviral Therapy 高活性抗逆轉錄病毒療法)療法的組分之一。AIDS的最終結果一般是淋巴癌,而胸苷激酶檢測的一項最重要的診斷應用就是監控淋巴癌。

酶底物類似物的化學結構

其他胸苷類似物,如碘苷(ATC:J05AB02)能夠在隨後的複製循環中阻礙基礎配對,最終導致DNA合成鏈缺陷。[112]此物質結合化療能夠達到促使惡性腫瘤細胞凋亡的目的。[113]

一些抗病毒藥物,如阿昔洛韋(ATC:J05AB01)和更昔洛韋(ATC:J05AB06)與其他一些研究成功的核酸類似物一樣,[114]則是利用了對病毒胸苷激酶而非對人胸苷激酶的專屬特異性。[115]這些藥物機理如同前體藥物,本身不具有毒性,但是被病毒胸苷激酶磷酸化後,會轉變為細胞毒性藥物。感染了病毒的細胞由於產生出高細胞毒性的三磷酸核苷最終導致細胞的凋亡。而相反的,人胸苷激酶由於其專屬特異性,不會磷酸化而激活前體藥物。因此,只有感染了病毒的細胞對藥物敏感。這些藥物僅對具有特異的疱疹病毒類胸苷激酶的病毒有效。[116]

自1979年12月,WHO宣布天花病毒已經根除之後,牛痘接種項目也已經終止了。該病毒如果由於意外事故或被作為生化武器重新出現,將會在毫無防備的人群中爆發性傳播而難以控制。接種牛痘似乎是不道德的,因為唯一對天花有效的疫苗本身就含有用於刺激機體產生免疫效果反應的活性牛痘病毒。但出於安全問題考慮,有大量的疫苗需要長期儲備,其中以高效的抗天花葯物最為優先。一種可能的方式是利用痘病毒胸苷激酶的特異性來達到目的,作用機理與抗疱疹病毒類藥物類似。有一個難點是痘病毒胸苷激酶與人胸苷激酶屬於同一家族譜系,化學結構相似。目前痘病毒的結構已經探明並正在尋找潛在的抗病毒藥物。[117]但有效的抗痘病毒藥物研究尚無結果。

疱疹病毒胸苷激酶基因也當做「自殺基因」作為基因治療實驗中的安全系統,誘導細胞表達該基因後被更昔洛韋殺死。此種方法適用於通過重組基因誘發突變而最終導致的細胞增殖失控(誘導突變)。這些突變細胞產生的胸苷激酶擴散入周圍細胞中,會導致周圍細胞同樣對更昔洛韋敏感,該現象稱為「旁觀者效應」。此方法已用於動物體的腫瘤治療,有10%的惡性腫瘤細胞表達該基因並會被有效殺死。[118][119]利用一些腫瘤所特有的物質(腫瘤標誌物)也能實現類似的胸苷激酶應用。這些腫瘤標誌物,如CEA(癌胚抗原)和AFP(甲胎蛋白)。將這些腫瘤標誌物的基因作為胸苷激酶的啟動基因。胸苷激酶將在表達腫瘤標誌物基因的細胞中被激活,在正常細胞中則不會,因此使用更昔洛韋治療只會殺死腫瘤細胞。[120][121][122][123][124][125]儘管如此,這些基因治療方法仍在實驗階段,一些與基因轉移相關的問題,還未完全解決。

一種含硼元素的胸苷類似物已經被建議並用於BNCT法(硼-中子交互放射療法)治療腦部腫瘤的動物實驗。[126][127][128][129][130][131][132][133][134][135][136]

檢測方法

血清學

血清胸苷激酶檢測主要是檢測胸苷激酶1(TK1),檢測方法目前主要有兩類,一種是酶活性測定法;一種是酶濃度測定法。

使用酶活性測定法,一般通過將血清樣本和底物類似物共同培養來實現。最初的商業可行性技術是使用碘代脫氧尿苷,即使用放射性碘替代了胸苷的一個甲基。[137][138][139]該底物能夠被酶很好的識別。一磷酸化的碘代脫氧尿苷被添加在培養基中的氧化鋁所吸附。在傾倒和洗脫後,氧化鋁的放射性可換算出樣本中胸苷激酶的量。應用此原理的商業試劑盒由貝克曼公司和索靈公司提供。

此外索靈公司還研究出一種非放射性分析方法。在該技術中3』-疊氮-2』,3』-脫氧胸苷(AZT:疊氮胸苷)首先被樣本中的TK1磷酸化生成5』-一磷酸-AZT(AZTMP:疊氮胸苷一磷酸)。AZTMP通過免疫學方法測定,使用抗-AZTMP抗體為AZTMP標記上過氧化物。測定需在索靈公司提供的封閉式實驗工作系統內進行。[140][111]

另一種新研發的技術是使用胸苷類似物——溴化尿苷,作為酶底物。反應產物(在微量滴定板中)吸附在滴定板各孔的底部。再通過ELISA方法測定:在各孔中加入抗溴化尿苷的單克隆抗體溶液。單克隆抗體上結合有鹼性磷酸酶。洗脫掉過量的結合有鹼性磷酸酶的抗體,加入含有鹼性磷酸酶底物——4-硝基苯酚的溶液。反應產物4-硝基酚在磷酸pH環境中是黃色能夠通過光度法測定。[141]此種分析方法能夠進行更加靈敏的檢測。商業試劑盒由Biovica公司提供。

使用酶濃度測定法,一般對抗TK1抗體的靈敏度要求很高,之前很長一段時間內沒有突破。20世紀末至21世紀初,瑞典karolinska醫學院利用鳥類特異性IgY抗體,開發出一種新型多克隆抗體——抗人TK1-IgY抗體,並申請了國際專利,此抗體具有很高的靈敏度和特異性,能夠識別人血清中低濃度TK1。[142]此抗體在結合化學發光檢測技術後,進一步提高了檢測靈敏度。商用試劑盒由SSTK公司(中國,深圳)提供。

組織學

從組織提取物樣本中能夠檢測到胸苷激酶。但尚沒有標準的組織提取或分析方法,組織和細胞提取物中的TK檢測與實際臨床問題的相關性也未得到證實。見Romain等[143]和Arnér等[144]。有一種方法使用5』-溴-2』-脫氧尿苷作為底物類似物特異性檢測細胞提取物中的TK2。[145]但在使用此方法的其他研究中,報告的結果差異很大方法可行性不佳。

處於發展階段的胎兒組織的TK1水平比之後要高。[146][147][148]

某些非惡性腫瘤細胞和組織中的TK1水平也會出現明顯升高:如存在單核細胞增多症時的周圍淋巴細胞,[149]和存在惡性貧血是的骨髓細胞。[150][151]

由於TK1存在於處於分裂期的細胞中,因此有理由認為惡性腫瘤組織中的TK活性應比正常組織中的要高。這已在大部分的研究中得到證實。腫瘤組織中TK活性比一般組織要高[146][152][153][154],如腦瘤[155],血液系統惡性腫瘤[156],結腸癌和結腸息肉[157][158][159][160][161][162],乳腺癌[163][164][165][166][167][168],肺癌[169][170][171],胃癌[172],卵巢癌[173],間皮瘤[174],黑色素瘤[175],和甲狀腺腫瘤[176][177]

對於白血病[178][179]和乳腺癌[180],治療對細胞增殖速率的影響與對TK值的影響是由相關性的。

免疫組織化學染色

抗胸苷激酶抗體可以用於免疫組化檢測。[181]胸苷激酶染色就是一種可靠的用於鑑別2期乳腺癌患者的技術。胸苷激酶和Ki-67染色技術的聯合使用已經使相當多的患者得到了診斷。[182][183]

該技術對肺癌[182][184],結直腸癌[185],非小細胞肺癌[186]和腎癌[187]具有同樣價值。

標籤

胸苷激酶1;疱疹病毒胸苷激酶;胸苷酸激酶;二磷酸核苷激酶;胸苷酸合成酶

參考文獻

  1. ^ PDB 2B8T; Kosinska U, Carnrot C, Eriksson S, Wang L, Eklund H. Structure of the substrate complex of thymidine kinase from Ureaplasma urealyticum and investigations of possible drug targets for the enzyme. FEBS J. December 2005, 272 (24): 6365–72. PMID 16336273. doi:10.1111/j.1742-4658.2005.05030.x. 
  2. ^ Kit S (December 1985). "Thymidine kinase". Microbiol. Sci. 2 (12): 369–75.
  3. ^ Wintersberger E (February 1997). "Regulation and biological function of thymidine kinase". Biochem. Soc. Trans. 25 (1): 303–8.
  4. ^ Reichard P, Estborn B (February 1951). "Utilization of desoxyribosides in the synthesis of polynucleotides". J. Biol. Chem. 188 (2): 839–46.
  5. ^ Kornberg A, Lehman IR, Simms ES (1956). "Polydeoxyribonucleotide synthesis by enzymes from Eschrichia coli". Fed. Proc. 15: 291–2.
  6. ^ Bollum FJ, Van Potter R (August 1958). "Incorporation of thymidine into deoxyribonucleic acid by enzymes from rat tissues". J. Biol. Chem. 233 (2): 478–82.
  7. ^ Weissman SM, Smellie RMS, Paul J (December 1960). "Studies on the biosynthesis of deoxyribonucleic acid by extracts of mammalian cells. IV. The phosphorylation of thymidine". Biochim. Biophys. Acta 45: 101–10.
  8. ^ Boyle DB, Gibbs AJ, Seigman LJ, Both GW, Coupar BE (1987). "Fowlpox virus thymidine kinase: nucleotide sequence and relationships to other thymidine kinases". Virology 156 (2): 355–365.
  9. ^ Lopez-Otin C, Blasco R, Vinuela E, Munoz M, Simon-Mateo C, Bockamp EO (1990). "Sequence and evolutionary relationships of African swine fever virus thymidine kinase". Virology 178 (1): 301–304.
  10. ^ Littlefield JW (February 1966). "The periodic synthesis of thymidine kinase in mouse fibroblasts". Biochim. Biophys. Acta 114 (2): 398–403
  11. ^ Bello LJ (December 1974). "Regulation of thymidine kinase synthesis in human cells". Exp. Cell Res. 89 (2): 263–74.
  12. ^ Berk AJ, Clayton DA (April 1973). "A genetically distinct thymidine kinase in mammalian mitochondria. Exclusive labeling of mitochondrial deoxyribonucleic acid". J. Biol. Chem. 248 (8): 2722–9.
  13. ^ Berk AJ, Meyer BJ, Clayton DA (February 1973). "Mitochondrial-specific thymidine kinase". Arch. Biochem. Biophys. 154 (2): 563–5.
  14. ^ Elsevier SM, Kucherlapati RS, Nichols EA, Creagan RP, Giles RE, Ruddle FH, Willecke K, McDougall JK (October 1974). "Assignment of the gene for galactokinase to human chromosome 17 and its regional localisation to band q21-22". Nature 251 (5476): 633–6.
  15. ^ Willecke K, Teber T, Kucherlapati RS, Ruddle FH (May 1977). "Human mitochondrial thymidine kinase is coded for by a gene on chromosome 16 of the nucleus". Somatic Cell Genet. 3 (3): 237–45
  16. ^ Flemington E, Bradshaw HD, Traina-Dorge V, Slagel V, Deininger PL (1987). "Sequence, structure and promoter characterization of the human thymidine kinase gene". Gene 52 (2–3): 267–77.
  17. ^ Welin M, Kosinska U, Mikkelsen NE, et al. (December 2004). "Structures of thymidine kinase 1 of human and mycoplasmic origin". Proc. Natl. Acad. Sci. U.S.A. 101 (52): 17970–5.
  18. ^ Munch-Petersen B, Cloos L, Jensen HK, Tyrsted G (1995). "Human thymidine kinase 1. Regulation in normal and malignant cells". Adv. Enzyme Regul. 35: 69–89.
  19. ^ Li CL, Lu CY, Ke PY, Chang ZF (January 2004). "Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site". Biochem. Biophys. Res. Commun. 313 (3): 587–93.
  20. ^ Zhu C, Harlow LS, Berenstein D, Munch-Petersen S, Munch-Petersen B (2006). "Effect of C-terminal of human cytosolic thymidine kinase (TK1) on in vitro stability and enzymatic properties". Nucleosides Nucleotides Nucleic Acids 25 (9–11): 1185–8.
  21. ^ 引用錯誤:沒有為名為pmid7572355的參考文獻提供內容
  22. ^ null Van Potter. FEEDBACK INHIBITION OF THYMIDINE KINASE BY THYMIDINE TRIPHOSPHATE. Experimental Cell Research. 1963, 24: SUPPL9:259–262 [2019-05-26]. ISSN 0014-4827. PMID 14046233. 
  23. ^ E. S. Severin, A. V. Itkes, O. N. Kartasheva, V. L. Tunitskaya, K. T. Turpaev, C. A. Kafiani. Regulation of 2-5 A phosphodiesterase activity by cAMP-dependent phosphorylation: mechanism and biological role. Advances in Enzyme Regulation. 1985, 23: 365–376 [2019-05-26]. ISSN 0065-2571. PMID 3000146. 
  24. ^ Nils Egil Mikkelsen, Kenth Johansson, Andreas Karlsson, Wolfgang Knecht, Gorm Andersen, Jure Piskur, Birgitte Munch-Petersen, Hans Eklund. Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase. Biochemistry. 2003-05-20, 42 (19): 5706–5712 [2019-05-26]. ISSN 0006-2960. PMID 12741827. doi:10.1021/bi0340043. 
  25. ^ P. H. Fischer, A. W. Phillips. Antagonism of feedback inhibition. Stimulation of the phosphorylation of thymidine and 5-iodo-2'-deoxyuridine by 5-iodo-5'-amino-2',5'-dideoxyuridine. Molecular Pharmacology. 1984-5, 25 (3): 446–451 [2019-05-26]. ISSN 0026-895X. PMID 6727866. 
  26. ^ P. H. Fischer, M. A. Vazquez-Padua, C. A. Reznikoff. Perturbation of thymidine kinase regulation: a novel chemotherapeutic approach. Advances in Enzyme Regulation. 1986, 25: 21–34 [2019-05-26]. ISSN 0065-2571. PMID 3812083. 
  27. ^ P. H. Fischer, M. A. Vazquez-Padua, C. A. Reznikoff, W. J. Ratschan. Preferential stimulation of iododeoxyuridine phosphorylation by 5'-aminothymidine in human bladder cancer cells in vitro. Cancer Research. 1986-9, 46 (9): 4522–4526 [2019-05-26]. ISSN 0008-5472. PMID 3731105. 
  28. ^ P. H. Fischer, T. T. Fang, T. S. Lin, A. Hampton, J. Bruggink. Structure-activity analysis of antagonism of the feedback inhibition of thymidine kinase. Biochemical Pharmacology. 1988-04-01, 37 (7): 1293–1298 [2019-05-26]. ISSN 0006-2952. PMID 3355601. 
  29. ^ M. A. Vazquez-Padua, K. Kunugi, P. H. Fischer. Enzyme regulatory site-directed drugs: study of the interactions of 5'-amino-2', 5'-dideoxythymidine (5'-AdThd) and thymidine triphosphate with thymidine kinase and the relationship to the stimulation of thymidine uptake by 5'-AdThd in 647V cells. Molecular Pharmacology. 1989-1, 35 (1): 98–104 [2019-05-26]. ISSN 0026-895X. PMID 2536472. 
  30. ^ M. A. Vazquez-Padua, P. H. Fischer, B. J. Christian, C. A. Reznikoff. Basis for the differential modulation of the uptake of 5-iododeoxyuridine by 5'-aminothymidine among various cell types. Cancer Research. 1989-05-01, 49 (9): 2415–2421 [2019-05-26]. ISSN 0008-5472. PMID 2706629. (原始內容存檔於2016-10-01). 
  31. ^ M. A. Vázquez-Padua. Modulation of thymidine kinase activity: a biochemical strategy to enhance the activation of antineoplastic drugs. Puerto Rico Health Sciences Journal. 1994-3, 13 (1): 19–23 [2019-05-26]. ISSN 0738-0658. PMID 8016290. 
  32. ^ McKnight SL. The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Res. December 1980, 8 (24): 5949–64. PMC 328064可免費查閱. PMID 6258156. doi:10.1093/nar/8.24.5949. 
  33. ^ Halliburton IW, Morse LS, Roizman B, Quinn KE. Mapping of the thymidine kinase genes of type 1 and type 2 herpes simplex viruses using intertypic recombinants. J. Gen. Virol. August 1980, 49 (2): 235–53. PMID 6255066. doi:10.1099/0022-1317-49-2-235. 
  34. ^ McDougall JK, Masse TH, Galloway DA. Location and cloning of the herpes simplex virus type 2 thymidine kinase gene. J. Virol. March 1980, 33 (3): 1221–4 [2012-03-01]. PMC 288658可免費查閱. PMID 6245273. (原始內容存檔於2011-08-07). 
  35. ^ Kit S, Kit M, Qavi H, Trkula D, Otsuka H. Nucleotide sequence of the herpes simplex virus type 2 (HSV-2) thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide and its comparison with the HSV-1 thymidine kinase gene. Biochim. Biophys. Acta. November 1983, 741 (2): 158–70. PMID 6317035. doi:10.1016/0167-4781(83)90056-8. 
  36. ^ Sawyer MH, Ostrove JM, Felser JM, Straus SE. Mapping of the varicella zoster virus deoxypyrimidine kinase gene and preliminary identification of its transcript. Virology. February 1986, 149 (1): 1–9. PMID 3004022. doi:10.1016/0042-6822(86)90081-4. 
  37. ^ Littler E, Zeuthen J, McBride AA, Trøst Sørensen E, Powell KL, Walsh-Arrand JE, Arrand JR. Identification of an Epstein-Barr virus-coded thymidine kinase. EMBO J. August 1986, 5 (8): 1959–66. PMC 1167064可免費查閱. PMID 3019675. 
  38. ^ Kit S, Dubbs DR. Acquisition of thymidine kinase activity by herpes simplex-infected mouse fibroblast cells. Biochem. Biophys. Res. Commun. April 1963, 11: 55–9. PMID 14033128. doi:10.1016/0006-291X(63)90027-5. 
  39. ^ Schlosser CA, Steglich C, deWet JR, Scheffler IE. Cell cycle-dependent regulation of thymidine kinase activity introduced into mouse LMTK- cells by DNA and chromatin-mediated gene transfer. Proc. Natl. Acad. Sci. U.S.A. February 1981, 78 (2): 1119–23. PMC 319958可免費查閱. PMID 6940130. doi:10.1073/pnas.78.2.1119. 
  40. ^ Coppock DL, Pardee AB. Control of thymidine kinase mRNA during the cell cycle. Mol. Cell. Biol. August 1987, 7 (8): 2925–32 [2012-03-01]. PMC 367911可免費查閱. PMID 3670299. (原始內容存檔於2011-09-27). 
  41. ^ Stewart CJ, Ito M, Conrad SE. Evidence for transcriptional and post-transcriptional control of the cellular thymidine kinase gene. Mol. Cell. Biol. March 1987, 7 (3): 1156–63 [2012-03-01]. PMC 365188可免費查閱. PMID 3561412. (原始內容存檔於2011-09-27). 
  42. ^ Piper AA, Tattersall MH, Fox RM. The activities of thymidine metabolising enzymes during the cell cycle of a human lymphocyte cell line LAZ-007 synchronised by centrifugal elutriation. Biochim. Biophys. Acta. December 1980, 633 (3): 400–9. PMID 6260157. 
  43. ^ Pelka-Fleischer R, Ruppelt W, Wilmanns W, Sauer H, Schalhorn A. Relation between cell cycle stage and the activity of DNA-synthesizing enzymes in cultured human lymphoblasts: investigations on cell fractions enriched according to cell cycle stages by way of centrifugal elutriation. Leukemia. March 1987, 1 (3): 182–7. PMID 3669741. 
  44. ^ Sherley JL, Kelly TJ. Regulation of human thymidine kinase during the cell cycle. J. Biol. Chem. June 1988, 263 (17): 8350–8 [2012-03-01]. PMID 3372530. (原始內容存檔於2005-01-26). 
  45. ^ Gross MK, Kainz MS, Merrill GF. The chicken thymidine kinase gene is transcriptionally repressed during terminal differentiation: the associated decline in TK mRNA cannot account fully for the disappearance of TK enzyme activity. Dev. Biol. August 1987, 122 (2): 439–51. PMID 3596017. doi:10.1016/0012-1606(87)90308-3. 
  46. ^ Kauffman MG, Kelly TJ. Cell cycle regulation of thymidine kinase: residues near the carboxyl terminus are essential for the specific degradation of the enzyme at mitosis. Mol. Cell. Biol. May 1991, 11 (5): 2538–46 [2012-03-01]. PMC 360023可免費查閱. PMID 1708095. (原始內容存檔於2011-09-27). 
  47. ^ Sutterluety H, Bartl S, Karlseder J, Wintersberger E, Seiser C. Carboxy-terminal residues of mouse thymidine kinase are essential for rapid degradation in quiescent cells. J. Mol. Biol. June 1996, 259 (3): 383–92. PMID 8676376. doi:10.1006/jmbi.1996.0327. 
  48. ^ Johnson HA, Rubini JR, Cronkite EP, Bond VP. Labeling of human tumor cells in vivo by tritiated thymidine. Lab. Invest. 1960, 9: 460–5. PMID 14407455. 
  49. ^ Barthel H; Cleij MC; Collingridge DR; et al. 3'-deoxy-3'-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res. July 2003, 63 (13): 3791–8. PMID 12839975. 
  50. ^ Chao KS. Functional imaging for early prediction of response to chemoradiotherapy: 3'-deoxy-3'-18F-fluorothymidine positron emission tomography--a clinical application model of esophageal cancer. Semin. Oncol. December 2006, 33 (6 Suppl 11): S59–63. PMID 17178290. doi:10.1053/j.seminoncol.2006.10.011. 
  51. ^ Salskov A, Tammisetti VS, Grierson J, Vesselle H. FLT: measuring tumor cell proliferation in vivo with positron emission tomography and 3'-deoxy-3'-[18F]fluorothymidine. Semin Nucl Med. November 2007, 37 (6): 429–39. PMID 17920350. doi:10.1053/j.semnuclmed.2007.08.001. 
  52. ^ de Langen AJ; Klabbers B; Lubberink M; et al. Reproducibility of quantitative (18)F-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography. Eur. J. Nucl. Med. Mol. Imaging. October 2008, 36 (3): 389–95. PMID 18931838. doi:10.1007/s00259-008-0960-5. 
  53. ^ Shields AF; Lawhorn-Crews JM; Briston DA; et al. Analysis and reproducibility of 3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging in patients with non-small cell lung cancer. Clin. Cancer Res. July 2008, 14 (14): 4463–8. PMID 18628460. doi:10.1158/1078-0432.CCR-07-5243. 
  54. ^ Methotrexate - Compound Summary. [2012-03-01]. (原始內容存檔於2014-03-10). 
  55. ^ Aminopterin - Compound Summary. [2012-03-01]. (原始內容存檔於2014-03-10). 
  56. ^ Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. August 1975, 256 (5517): 495–7. Bibcode:1975Natur.256..495K. PMID 1172191. doi:10.1038/256495a0. 
  57. ^ Köhler G, Howe SC, Milstein C. Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines. Eur. J. Immunol. April 1976, 6 (4): 292–5. PMID 825374. doi:10.1002/eji.1830060411. 
  58. ^ Köhler G, Milstein C. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur. J. Immunol. July 1976, 6 (7): 511–9. PMID 825377. doi:10.1002/eji.1830060713. 
  59. ^ Köhler G, Pearson T, Milstein C. Fusion of T and B cells. Somatic Cell Genet. May 1977, 3 (3): 303–12. PMID 305123. doi:10.1007/BF01538748. 
  60. ^ Milstein C, Adetugbo K, Cowan NJ, Kohler G, Secher DS. Expression of antibody genes in tissue culture: structural mutants and hybrid cells. Natl Cancer Inst Monogr. May 1978, (48): 321–30. PMID 107455. 
  61. ^ 引用錯誤:沒有為名為pmid4223355的參考文獻提供內容
  62. ^ 引用錯誤:沒有為名為pmid15611477的參考文獻提供內容
  63. ^ Karlström AR, Neumüller M, Gronowitz JS, Källander CF. Molecular forms in human serum of enzymes synthesizing DNA precursors and DNA. Mol. Cell. Biochem. January 1990, 92 (1): 23–35. PMID 2155379. doi:10.1007/BF00220716. 
  64. ^ 劉秀菊,周際,李遠等。TK1——一種新的腫瘤生長相關標誌物的應用新進展。《中國藥理學與毒理學雜誌》2010年12月。
  65. ^ Ellims PH, Van der Weyden MB, Medley G. Thymidine kinase isoenzymes in human malignant lymphoma. Cancer Res. February 1981, 41 (2): 691–5. PMID 7448815. 
  66. ^ Hagberg H, Glimelius B, Gronowitz JS, Killander A, Källander CFR, Schröder T. Biochemical markers in non-Hodgkin's lymphoma stages III and IV and prognosis: a multivariate analysis. Scand J Haematol. July 1984, 33 (1): 59–67. PMID 6379852. doi:10.1111/j.1600-0609.1984.tb02211.x. 
  67. ^ Gronowitz JS, Hagberg H, Källander CFR, Simonsson B. The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin's lymphoma. Br. J. Cancer. April 1983, 47 (4): 487–95. PMC 2011337可免費查閱. PMID 6849793. doi:10.1038/bjc.1983.78. 
  68. ^ Hallek M, Wanders L, Strohmeyer S, Emmerich B. Thymidine kinase: a tumor marker with prognostic value for non-Hodgkin's lymphoma and a broad range of potential clinical applications. Ann. Hematol. July 1992, 65 (1): 1–5. PMID 1643153. doi:10.1007/BF01715117. 
  69. ^ Bogni A, Cortinois A, Grasselli G; et al. Thymidine kinase (TK) activity as a prognostic parameter of survival in lymphoma patients. J. Biol. Regul. Homeost. Agents. 1994, 8 (4): 121–5. PMID 7660854. 
  70. ^ Rehn S, Gronowitz JS, Källander C, Sundström C, Glimelius B. Deoxythymidine kinase in the tumour cells and serum of patients with non-Hodgkin lymphomas. Br. J. Cancer. May 1995, 71 (5): 1099–105. PMC 2033808可免費查閱. PMID 7734308. doi:10.1038/bjc.1995.213. 
  71. ^ Suki S, Swan F, Tucker S; et al. Risk classification for large cell lymphoma using lactate dehydrogenase, beta-2 microglobulin, and thymidine kinase. Leuk. Lymphoma. June 1995, 18 (1–2): 87–92. PMID 8580834. doi:10.3109/10428199509064927. 
  72. ^ Hallek M, Wanders L, Ostwald M; et al. Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leuk. Lymphoma. August 1996, 22 (5–6): 439–47. PMID 8882957. doi:10.3109/10428199609054782. 
  73. ^ Zhu-Lin Pan, Xing-Ying Ji, Yan-Min Shi, et al.(2010). " Serum thymidine kinase 1 concentration as a prognostic factor".J Cancer Res Clin Oncol.136:1193-1199.
  74. ^ Källander CFR, Simonsson B, Gronowitz JS, Nilsson K. Serum deoxythymidine kinase correlates with peripheral lymphocyte thymidine uptake in chronic lymphocytic leukemia. Eur. J. Haematol. April 1987, 38 (4): 331–7. PMID 3609253. doi:10.1111/j.1600-0609.1987.tb00007.x. 
  75. ^ Källander CFR, Simonsson B, Hagberg H, Gronowitz JS. Serum deoxythymidine kinase gives prognostic information in chronic lymphocytic leukemia. Cancer. December 1984, 54 (11): 2450–5. PMID 6498737. doi:10.1002/1097-0142(19841201)54:11<2450::AID-CNCR2820541123>3.0.CO;2-R. 
  76. ^ A. Rivkina, G. Vitols, M. Murovska, S. Lejniece. Identifying the stage of new CLL patients using TK, ZAP-70, CD38 levels. Experimental Oncology. 2011-6, 33 (2): 99–103 [2019-05-26]. ISSN 1812-9269. PMID 21716207. (原始內容存檔於2019-09-05). 
  77. ^ Simonsson B, Källander CFR, Brenning G, Killander A, Gronowitz JS, Bergström R. Biochemical markers in multiple myeloma: a multivariate analysis. Br. J. Haematol. May 1988, 69 (1): 47–53. PMID 3289607. doi:10.1111/j.1365-2141.1988.tb07601.x. 
  78. ^ Simonsson B, Källander CFR, Brenning G, Killander A, Ahre A, Gronowitz JS. Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma. Br. J. Haematol. October 1985, 61 (2): 215–24. PMID 4041368. doi:10.1111/j.1365-2141.1985.tb02820.x. 
  79. ^ Yan Chen, MinGang Ying, YanSong Chen, et al. (2010). 「Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings」. Int J Clin Oncol.
  80. ^ Zhishan Li, Yinghong Wang, Jie He, Jie Ma, et al. (March 2010). 「Serological thymidine kinase 1 is a prognostic factor in oesophageal, cardial and lung carcinomas」. European Journal of Cancer Prevention 19:313-318.
  81. ^ Qimin He, PingGN Zhang, Li Zou, et al. (May 2005). 「Concentration of thymidine kinase 1 in serum(S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity". Oncology Reports 14: 1013-1019.
  82. ^ Zhenxin Wang, Bin Zhang, Bin Ni, Jin Zang. (September 2011). 「Value of serum thymidine kinase 1 in evaluating the efficacy of malignant tumor treatment」. Jiangsu Med J, September 2011, Vol37, No.18:2174-2175.
  83. ^ Larson A, Fritjofsson A, Norlén BJ, Gronowitz JS, Ronquist G. Prostate specific acid phosphatase versus five other possible tumour markers: a comparative study in men with prostatic carcinoma. Scand. J. Clin. Lab. Invest. Suppl. 1985, 179: 81–8. PMID 2417306. 
  84. ^ Letocha H, Eklöv S, Gronowitz S, Norlén BJ, Nilsson S. Deoxythymidine kinase in the staging of prostatic adenocarcinoma. Prostate. July 1996, 29 (1): 15–9. PMID 8685050. doi:10.1002/(SICI)1097-0045(199607)29:1<15::AID-PROS2>3.0.CO;2-H. 
  85. ^ Lewenhaupt A, Ekman P, Eneroth P, Nilsson B. Tumour markers as prognostic aids in prostatic carcinoma. Br J Urol. August 1990, 66 (2): 182–7. PMID 1697204. doi:10.1111/j.1464-410X.1990.tb14900.x. 
  86. ^ Ekman P, Lewenhaupt A. Serum tumour markers in human prostatic carcinoma. The value of a marker panel for prognostic information. Acta Oncol. 1991, 30 (2): 173–5. PMID 2029401. doi:10.3109/02841869109092345. 
  87. ^ Gronowitz JS, Bergström R, Nôu E; et al. Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis. Cancer. August 1990, 66 (4): 722–32. PMID 2167141. doi:10.1002/1097-0142(19900815)66:4<722::AID-CNCR2820660421>3.0.CO;2-J. 
  88. ^ Gronowitz JS, Steinholtz L, Källander CF, Hagberg H, Bergh J. Serum deoxythymidine kinase in small cell carcinoma of the lung. Relation to clinical features, prognosis, and other biochemical markers. Cancer. July 1986, 58 (1): 111–8. PMID 3011236. doi:10.1002/1097-0142(19860701)58:1<111::AID-CNCR2820580120>3.0.CO;2-K. 
  89. ^ H.X.Li, S Zhang, D.S Lei, X.Q Wang, et al. (August 2005). 「Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with non-small cell lung cancer」. Oncology Reports 13: 145-149.
  90. ^ Benjamin Nisman, Tanir Allweis, Luna Kaduri, Bella Maly, Simon Gronowitz, Tamar Hamburger, Tamar Peretz. Serum thymidine kinase 1 activity in breast cancer. Cancer Biomarkers: Section A of Disease Markers. 2010, 7 (2): 65–72 [2019-05-26]. ISSN 1875-8592. PMID 21178264. doi:10.3233/CBM-2010-0148. (原始內容存檔於2019-09-05). 
  91. ^ Q. He, L. Zou, P.A Zhang, et al. (2000) 「The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TK1 antibody」. J.Biol.Marker, 15:139-146
  92. ^ Qimin He, Tommy Fornander, Hemming Johansson, et al. (2006) 「Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breast cancer」. Anticancer Research 26: 4753-4760.
  93. ^ L. Zou, P.G Zhang, S. Zou, et al.(2002) 「The half-life of thymidine kinase 1 in serum measured by ECL dot blot: a potential marker for monitoring the response to surgery of patients with gastric cancer」. The international Journal of biological Markers, Vol. 17 No. 2:135-140.
  94. ^ Benjamin Nisman, Vladimir Yutkin, Hovav Nechushtan, Ofer N. Gofrit, Tamar Peretz, Simon Gronowitz, Dov Pode. Circulating tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell carcinoma after nephrectomy. Urology. 2010-8, 76 (2): 513.e1–6 [2019-05-26]. ISSN 1527-9995. PMID 20573390. doi:10.1016/j.urology.2010.04.034. (原始內容存檔於2019-09-05). 
  95. ^ Jie Zhang, Quanan Jia, Shan Zou, et al. (August 2006). 「Thymidine kinase 1: A proliferation marker of determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients」. Oncology Reports 15:455-461.
  96. ^ P. H. Ellims, R. J. Hayman, M. B. Van der Weyden. Expression of fetal thymidine kinase in human cobalamin or folate deficient lymphocytes. Biochemical and Biophysical Research Communications. 1979-07-12, 89 (1): 103–107 [2019-05-26]. ISSN 0006-291X. PMID 475797. 
  97. ^ 97.0 97.1 M. Neumuller, C. F. Källander, J. S. Gronowitz. Detection and characteristics of DNA polymerase activity in serum from patients with malignant, viral, or B12-deficiency disease. Enzyme. 1989, 41 (1): 6–16 [2019-05-26]. ISSN 0013-9432. PMID 2543552. 
  98. ^ G. Tufveson, T. H. Tötterman, C. F. Källander, A. Hagström, J. S. Gronowitz. Serum thymidine-kinase and cytomegalovirus-specific antibodies after renal transplantation. Transplantation Proceedings. 1988-6, 20 (3): 405–407 [2019-05-26]. ISSN 0041-1345. PMID 2837850. 
  99. ^ C. F. Källander, J. S. Gronowitz, E. Olding-Stenkvist. Rapid diagnosis of varicella-zoster virus infection by detection of viral deoxythymidine kinase in serum and vesicle fluid. Journal of Clinical Microbiology. 1983-2, 17 (2): 280–287 [2019-05-26]. ISSN 0095-1137. PMC 272623可免費查閱. PMID 6339548. 
  100. ^ Zhishan Li, Yinghong Wang, Jie Ma, et al. (2010). 「Transient increase in serum thymidine kinase 1 within one week after surgery of patients with carcinoma」. Anticancer Research 30: 1295-1300.
  101. ^ ZhiHeng Chen, Hui Zhou, ShengLan Li, et al. (2008). 「Serological Thymidine Kinase 1 (STK1) indicates an elevated risk for the development of malignant tumors」. Anticancer Research 28:3897-3908.
  102. ^ Shouqing Huang, Jianzh Lin, Na Guo, et al. (2011). 「Elevated serum thymidine kinase 1 predicts risk of pre/early cancerous progression」. Asian Pacific J Cancer Prev, 12, 497-505.
  103. ^ Lin TS, Neenan JP, Cheng YC, Prusoff WH. Synthesis and antiviral activity of 5- and 5'-substituted thymidine analogs. J. Med. Chem. April 1976, 19 (4): 495–8. PMID 177781. doi:10.1021/jm00226a009. 
  104. ^ Helgstrand E, Oberg B. Enzymatic targets in virus chemotherapy. Antibiot Chemother. 1980, 27: 22–69. PMID 6996606. 
  105. ^ Shannon WM, Schabel FM. Antiviral agents as adjuncts in cancer chemotherapy. Pharmacol. Ther. 1980, 11 (2): 263–390. PMID 7001501. doi:10.1016/0163-7258(80)90034-0. 
  106. ^ Hirsch MS. Chemotherapy of human immunodeficiency virus infections: current practice and future prospects. J. Infect. Dis. May 1990, 161 (5): 845–57. PMID 1691243. doi:10.1093/infdis/161.5.845. 
  107. ^ Shiau GT, Schinazi RF, Chen MS, Prusoff WH. Synthesis and biological activities of 5-(hydroxymethyl, azidomethyl, or aminomethyl)-2'-deoxyuridine and related 5'-substituted analogues. J. Med. Chem. February 1980, 23 (2): 127–33. PMID 6244411. doi:10.1021/jm00176a005. 
  108. ^ Mitsuya H, Weinhold KJ, Furman PA; et al. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl. Acad. Sci. U.S.A. October 1985, 82 (20): 7096–100. PMC 391317可免費查閱. PMID 2413459. doi:10.1073/pnas.82.20.7096. 
  109. ^ Baba M, Pauwels R, Herdewijn P, De Clercq E, Desmyter J, Vandeputte M. Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. Biochem. Biophys. Res. Commun. January 1987, 142 (1): 128–34 [2012-03-13]. PMID 3028398. doi:10.1016/0006-291X(87)90460-8. (原始內容存檔於2020-05-29). 
  110. ^ Hamamoto Y, Nakashima H, Matsui T, Matsuda A, Ueda T, Yamamoto N. Inhibitory effect of 2',3'-didehydro-2',3'-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus. Antimicrob. Agents Chemother. June 1987, 31 (6): 907–10. PMC 284209可免費查閱. PMID 3039911. 
  111. ^ 111.0 111.1 Ohrvik A, Lindh M, Einarsson R, Grassi J, Eriksson S. Sensitive nonradiometric method for determining thymidine kinase 1 activity. Clin. Chem. September 2004, 50 (9): 1597–606. PMID 15247154. doi:10.1373/clinchem.2003.030379. 
  112. ^ Prusoff WH. Synthesis and biological activities of iododeoxyuridine, an analog of thymidine. Biochim. Biophys. Acta. March 1959, 32 (1): 295–6. PMID 13628760. doi:10.1016/0006-3002(59)90597-9. 
  113. ^ Morgenroth A, Deisenhofer S, Glatting G; et al. Preferential Tumor Targeting and Selective Tumor Cell Cytotoxicity of 5-[131/125I]Iodo-4'-Thio-2'-Deoxyuridine. Clin. Cancer Res. November 2008, 14 (22): 7311–9. PMID 19010846. doi:10.1158/1078-0432.CCR-08-0907. 
  114. ^ Graciela Andrei, Robert Snoeck. Emerging drugs for varicella-zoster virus infections. Expert Opinion on Emerging Drugs. 2011-9, 16 (3): 507–535 [2019-05-26]. ISSN 1744-7623. PMID 21699441. doi:10.1517/14728214.2011.591786. (原始內容存檔於2011-07-03). 
  115. ^ Johnson VA, Hirsch MS. New developments in antiretroviral drug therapy for human immunodeficiency virus infections. Ganciclover is a 5' monophosphate that does not require thymidine kinase activation and thus expresses higher toxicity to host enzymes due to a decrease in selectivity. AIDS Clin Rev. 1990: 235–72. PMID 1707295. 
  116. ^ Mar EC, Chiou JF, Cheng YC, Huang ES. Inhibition of cellular DNA polymerase alpha and human cytomegalovirus-induced DNA polymerase by the triphosphates of 9-(2-hydroxyethoxymethyl)guanine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine. J. Virol. March 1985, 53 (3): 776–80. PMC 254706可免費查閱. PMID 2983088. 
  117. ^ Black ME, Hruby DE. Quaternary structure of vaccinia virus thymidine kinase. Biochem. Biophys. Res. Commun. June 1990, 169 (3): 1080–6 [2012-03-13]. PMID 2114104. doi:10.1016/0006-291X(90)92005-K. (原始內容存檔於2015-09-24). 
  118. ^ Nicholas TW, Read SB, Burrows FJ, Kruse CA. Suicide gene therapy with Herpes simplex virus thymidine kinase and ganciclovir is enhanced with connexins to improve gap junctions and bystander effects. Histol. Histopathol. April 2003, 18 (2): 495–507 [2012-03-13]. PMID 12647801. (原始內容存檔於2020-07-23). 
  119. ^ Ellen Preuss, Alexander Muik, Kristoffer Weber, Jürgen Otte, Dorothee von Laer, Boris Fehse. Cancer suicide gene therapy with TK.007: superior killing efficiency and bystander effect. Journal of Molecular Medicine (Berlin, Germany). 2011-11, 89 (11): 1113–1124 [2019-05-26]. ISSN 1432-1440. PMID 21698427. doi:10.1007/s00109-011-0777-8. (原始內容存檔於2019-01-06). 
  120. ^ Hart IR. Tissue specific promoters in targeting systemically delivered gene therapy. Semin. Oncol. February 1996, 23 (1): 154–8. PMID 8607025. 
  121. ^ Wills KN, Huang WM, Harris MP, Machemer T, Maneval DC, Gregory RJ. Gene therapy for hepatocellular carcinoma: chemosensitivity conferred by adenovirus-mediated transfer of the HSV-1 thymidine kinase gene. Cancer Gene Ther. September 1995, 2 (3): 191–7. PMID 8528962. 
  122. ^ Ido A, Nakata K, Kato Y; et al. Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter. Cancer Res. July 1995, 55 (14): 3105–9. PMID 7541712. 
  123. ^ Kanai F, Shiratori Y, Yoshida Y; et al. Gene therapy for alpha-fetoprotein-producing human hepatoma cells by adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene. Hepatology. June 1996, 23 (6): 1359–68. PMID 8675152. doi:10.1002/hep.510230611. 
  124. ^ Garver RI, Goldsmith KT, Rodu B, Hu PC, Sorscher EJ, Curiel DT. Strategy for achieving selective killing of carcinomas. Gene Ther. January 1994, 1 (1): 46–50. PMID 7584059. 
  125. ^ Hart IR. Transcriptionally targeted gene therapy. Curr. Top. Microbiol. Immunol. 1996, 213 (3): 19–25. PMID 8815006. 
  126. ^ {{cite journal |author=Byun Y, Thirumamagal BT, Yang W, Eriksson S, Barth RF, Tjarks W |title=Preparation and biological evaluation of 10B-enriched 3-[5-{2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl]thymidine (N5-2OH), a new boron delivery agent for boron neutron capture therapy of brain tumors |journal=J. Med. Chem. |volume=49 |issue=18 |pages=5513–23 |pmid=16942024 |doi=10.1021/jm060413w |url=|date=September 2006}}
  127. ^ Thirumamagal BT, Johnsamuel J, Cosquer GY; et al. Boronated thymidine analogues for boron neutron capture therapy. Nucleosides Nucleotides Nucleic Acids. 2006, 25 (8): 861–6. PMID 16901817. doi:10.1080/15257770600793844. 
  128. ^ Narayanasamy S, Thirumamagal BT, Johnsamuel J; et al. Hydrophilically enhanced 3-carboranyl thymidine analogues (3CTAs) for boron neutron capture therapy (BNCT) of cancer. Bioorg. Med. Chem. October 2006, 14 (20): 6886–99. PMID 16831554. doi:10.1016/j.bmc.2006.06.039. 
  129. ^ Byun Y, Narayanasamy S, Johnsamuel J; et al. 3-Carboranyl thymidine analogues (3CTAs) and other boronated nucleosides for boron neutron capture therapy. Anticancer Agents Med Chem. March 2006, 6 (2): 127–44. PMID 16529536. doi:10.2174/187152006776119171. [永久失效連結]
  130. ^ Byun Y, Yan J, Al-Madhoun AS; et al. Synthesis and biological evaluation of neutral and zwitterionic 3-carboranyl thymidine analogues for boron neutron capture therapy. J. Med. Chem. February 2005, 48 (4): 1188–98. PMID 15715485. doi:10.1021/jm0491896. 
  131. ^ Barth RF, Yang W, Al-Madhoun AS; et al. Boron-containing nucleosides as potential delivery agents for neutron capture therapy of brain tumors. Cancer Res. September 2004, 64 (17): 6287–95. PMID 15342417. doi:10.1158/0008-5472.CAN-04-0437. 
  132. ^ Al-Madhoun AS, Johnsamuel J, Barth RF, Tjarks W, Eriksson S. Evaluation of human thymidine kinase 1 substrates as new candidates for boron neutron capture therapy. Cancer Res. September 2004, 64 (17): 6280–6. PMID 15342416. doi:10.1158/0008-5472.CAN-04-0197. 
  133. ^ Johnsamuel J, Lakhi N, Al-Madhoun AS; et al. Synthesis of ethyleneoxide modified 3-carboranyl thymidine analogues and evaluation of their biochemical, physicochemical, and structural properties. Bioorg. Med. Chem. September 2004, 12 (18): 4769–81. PMID 15336255. doi:10.1016/j.bmc.2004.07.032. 
  134. ^ Byun Y, Yan J, Al-Madhoun AS; et al. The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position. Appl Radiat Isot. November 2004, 61 (5): 1125–30. PMID 15308203. doi:10.1016/j.apradiso.2004.05.023. 
  135. ^ Yan J, Naeslund C, Al-Madhoun AS; et al. Synthesis and biological evaluation of 3'-carboranyl thymidine analogues. Bioorg. Med. Chem. Lett. August 2002, 12 (16): 2209–12 [2012-03-13]. PMID 12127539. doi:10.1016/S0960-894X(02)00357-8. (原始內容存檔於2018-07-02). 
  136. ^ Barth RF, Yang W, Wu G; et al. Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors. Proc. Natl. Acad. Sci. U.S.A. November 2008, 105 (45): 17493–7. PMC 2582264可免費查閱. PMID 18981415. doi:10.1073/pnas.0809569105. 
  137. ^ Gronowitz JS, Källander CF. Optimized assay for thymidine kinase and its application to the detection of antibodies against herpes simplex virus type 1- and 2-induced thymidine kinase. Infect. Immun. August 1980, 29 (2): 425–34. PMC 551136可免費查閱. PMID 6260651. 
  138. ^ Gronowitz JS, Källander FR, Diderholm H, Hagberg H, Pettersson U. Application of an in vitro assay for serum thymidine kinase: results on viral disease and malignancies in humans. Int. J. Cancer. January 1984, 33 (1): 5–12. PMID 6693195. doi:10.1002/ijc.2910330103. 
  139. ^ Gronowitz JS, Källander CF. A sensitive assay for detection of deoxythymidine kinase and its application to herpesvirus diagnosis. Curr. Top. Microbiol. Immunol. 1983, 104: 235–45. PMID 6307593. 
  140. ^ 引用錯誤:沒有為名為pmid16140350的參考文獻提供內容
  141. ^ Gronowitz, JS (24.2.2006) A method and kit for determination of thymidine kinase activity and use thereof. International patent application PCT/SE2006/000246
  142. ^ Chuanjing Wu, Rong-jiang Yang, Ji Zhou, et al. (February 2003). 「Production and characterization of a novel chicken IgY antibody raised against C-terminal peptide from human thymidine kinase 1」. Journal of Immunological Methods 277:157-169.
  143. ^ Romain S, Spyratos F, Guirou O, Deytieux S, Chinot O, Martin PM. Technical evaluation of thymidine kinase assay in cytosols from breast cancers. EORTC Receptor Study Group Report. Eur. J. Cancer. 1994, 30A (14): 2163–5. PMID 7857717. doi:10.1016/0959-8049(94)00376-G. 
  144. ^ Arnér ES, Spasokoukotskaja T, Eriksson S. Selective assays for thymidine kinase 1 and 2 and deoxycytidine kinase and their activities in extracts from human cells and tissues. Biochem. Biophys. Res. Commun. October 1992, 188 (2): 712–8. PMID 1359886. doi:10.1016/0006-291X(92)91114-6. 
  145. ^ Wang L, Eriksson S. 5-Bromovinyl 2'-deoxyuridine phosphorylation by mitochondrial and cytosolic thymidine kinase (TK2 and TK1) and its use in selective measurement of TK2 activity in crude extracts. Nucleosides Nucleotides Nucleic Acids. June 2008, 27 (6): 858–62. PMID 18600552. doi:10.1080/15257770802146510. 
  146. ^ 146.0 146.1 Herzfeld A, Greengard O. Enzyme activities in human fetal and neoplastic tissues. Cancer. November 1980, 46 (9): 2047–54. PMID 6253048. doi:10.1002/1097-0142(19801101)46:9<2047::AID-CNCR2820460924>3.0.CO;2-Q. 
  147. ^ Machovich R, Greengard O. Thymidine kinase in rat tissues during growth and differentiation. Biochim. Biophys. Acta. December 1972, 286 (2): 375–81. PMID 4660462. doi:10.1016/0304-4165(72)90273-5. 
  148. ^ Herzfeld A, Raper SM, Gore I. The ontogeny of thymidine kinase in tissues of man and rat. Pediatr. Res. December 1980, 14 (12): 1304–10. PMID 7208144. doi:10.1203/00006450-198012000-00006. 
  149. ^ Schollenberger S, Taureck D, Wilmanns W. [Enzymes of thymidine and thymidylate metabolism in normal and pathological blood and bone marrow cells] [Enzymes of thymidine and thymidylate metabolism in normal and pathological blood and bone marrow cells]. Blut. November 1972, 25 (5): 318–34. PMID 4508724. doi:10.1007/BF01631814 (德語). 
  150. ^ Nakao K, Fujioka S. Thymidine kinase activity in the human bone marrow from various blood diseases. Life Sci. April 1968, 7 (8): 395–9. PMID 5649653. doi:10.1016/0024-3205(68)90039-8. 
  151. ^ Wickramasinghe SN, Olsen I, Saunders JE. Thymidine kinase activity in human bone marrow cells. Scand J Haematol. September 1975, 15 (2): 139–44. PMID 1059244. doi:10.1111/j.1600-0609.1975.tb01065.x. 
  152. ^ Gordon HL, Bardos TJ, Chmielewicz ZF, Ambrus JL. Comparative study of the thymidine kinase and thymidylate kinase activities and of the feedbach inhibition of thymidine kinase in normal and neoplastic human tissue. Cancer Res. October 1968, 28 (10): 2068–77. PMID 5696936. 
  153. ^ Stafford MA, Jones OW. The presence of "fetal" thymidine kinase in human tumors. Biochim. Biophys. Acta. August 1972, 277 (2): 439–42. PMID 4672678. 
  154. ^ Maehara Y, Nakamura H, Nakane Y; et al. Activities of various enzymes of pyrimidine nucleotide and DNA syntheses in normal and neoplastic human tissues. Gann. April 1982, 73 (2): 289–98. PMID 6288502. 
  155. ^ Persson L, Gronowitz SJ, Källander CF. Thymidine kinase in extracts of human brain tumours. Acta Neurochir (Wien). 1986, 80 (3–4): 123–7. PMID 3012969. doi:10.1007/BF01812286. 
  156. ^ Filanovskaia LI, Togo AV, Shcherbakova EG, Blinov MN. [Thymidine kinase activity in leukocytes from patients with chronic myeloid leukemia at various periods in the disease] [Thymidine kinase activity in leukocytes from patients with chronic myeloid leukemia at various periods in the disease]. Vopr. Med. Khim. 1994, 40 (1): 29–32. PMID 8122406 (俄語). 
  157. ^ Lipkin M. Proliferation and differentiation of normal and neoplastic cells in the colon of man. Cancer. July 1971, 28 (1): 38–40. PMID 5110642. doi:10.1002/1097-0142(197107)28:1<38::AID-CNCR2820280108>3.0.CO;2-W. 
  158. ^ Lipkin M, Deschner E, Troncale F. Cell differentiation and the development of colonic neoplasms. CA Cancer J Clin. 1970, 20 (6): 386–90 [2012-03-13]. PMID 4992499. doi:10.3322/canjclin.20.6.386. (原始內容存檔於2016-03-04). 
  159. ^ Weber G, Lui MS, Takeda E, Denton JE. Enzymology of human colon tumors. Life Sci. September 1980, 27 (9): 793–9. PMID 7412505. doi:10.1016/0024-3205(80)90333-1. 
  160. ^ Sagara T, Tsukada K, Iwama T, Mishima Y, Sakamoto S, Okamoto R. [Thymidine kinase isozymes in human colon polyps] [Thymidine kinase isozymes in human colon polyps]. Nippon Gan Chiryo Gakkai Shi. August 1985, 20 (7): 1312–6. PMID 4078430 (日語). 
  161. ^ Sakamoto S, Sagara T, Iwama T, Kawasaki T, Okamoto R. Increased activities of thymidine kinase isozymes in human colon polyp and carcinoma. Carcinogenesis. June 1985, 6 (6): 917–9. PMID 4006080. doi:10.1093/carcin/6.6.917. 
  162. ^ Sakamoto S, Okamoto R. Thymidine kinase activity in familial adenomatous polyposis. Tohoku J. Exp. Med. October 1992, 168 (2): 291–301. PMID 1339104. doi:10.1620/tjem.168.291. (原始內容存檔於2012-12-19). 
  163. ^ Galloux H, Javre JL, Guerin D, Sampérez S, Jouan P. [Prognostic value of fetal thymidine kinase measurements in breast cancer] [Prognostic value of fetal thymidine kinase measurements in breast cancer]. C. R. Acad. Sci. III, Sci. Vie. 1988, 306 (3): 89–92. PMID 3126994 (法語). 
  164. ^ O'Neill KL, Hoper M, Odling-Smee GW. Can thymidine kinase levels in breast tumors predict disease recurrence?. J. Natl. Cancer Inst. December 1992, 84 (23): 1825–8. PMID 1433372. doi:10.1093/jnci/84.23.1825. 
  165. ^ O'Neill KL, McKelvey VJ, Hoper M; et al. Breast tumour thymidine kinase levels and disease recurrence. Med Lab Sci. December 1992, 49 (4): 244–7. PMID 1339926. 
  166. ^ Romain S, Javre JL, Samperez S; et al. [Prognostic value of thymidine kinase in cancer of the breast] [Prognostic value of thymidine kinase in cancer of the breast]. Bull Cancer. 1990, 77 (10): 973–83. PMID 2249017 (法語). 
  167. ^ Romain S, Chinot O, Guirou O, Soullière M, Martin PM. Biological heterogeneity of ER-positive breast cancers in the post-menopausal population. Int. J. Cancer. October 1994, 59 (1): 17–9. PMID 7927897. doi:10.1002/ijc.2910590105. 
  168. ^ Sakamoto S, Iwama T, Ebuchi M; et al. Increased activities of thymidine kinase isozymes in human mammary tumours. Br J Surg. April 1986, 73 (4): 272–3. PMID 3697655. doi:10.1002/bjs.1800730409. 
  169. ^ Greengard O, Head JF, Goldberg SL, Kirschner PA. Enzyme pathology and the histologic categorization of human lung tumors: the continuum of quantitative biochemical indices of neoplasticity. Cancer. February 1982, 49 (3): 460–7. PMID 6277448. doi:10.1002/1097-0142(19820201)49:3<460::AID-CNCR2820490312>3.0.CO;2-Y. 
  170. ^ Greengard O, Head JF, Goldberg SL, Kirschner PA. Biochemical measure of the volume doubling time of human pulmonary neoplasms. Cancer. April 1985, 55 (7): 1530–5. PMID 2983858. doi:10.1002/1097-0142(19850401)55:7<1530::AID-CNCR2820550720>3.0.CO;2-V. 
  171. ^ Yusa T, Tamiya N, Yamaguchi Y; et al. [A study of thymidine kinase activity in lung cancer tissue] [A study of thymidine kinase activity in lung cancer tissue]. Nihon Kyobu Shikkan Gakkai Zasshi. March 1994, 32 (3): 211–5. PMID 8189640 (日語). 
  172. ^ Konishi T, Miyama T, Sakamoto S; et al. Activities of thymidylate synthetase and thymidine kinase in gastric cancer. Surg Oncol. June 1992, 1 (3): 215–21. PMID 1341254. doi:10.1016/0960-7404(92)90067-U. 
  173. ^ Look KY, Moore DH, Sutton GP, Prajda N, Abonyi M, Weber G. Increased thymidine kinase and thymidylate synthase activities in human epithelial ovarian carcinoma. Anticancer Res. 1997, 17 (4A): 2353–6. PMID 9252646. 
  174. ^ Greengard O, Head JF, Chahinian AP, Goldberg SL. Enzyme pathology of human mesotheliomas. J. Natl. Cancer Inst. April 1987, 78 (4): 617–22. PMID 2882044. 
  175. ^ Borovanský J, Stríbrná J, Elleder M, Netíková I. Thymidine kinase in malignant melanoma. Melanoma Res. October 1994, 4 (5): 275–9. PMID 7858409. doi:10.1097/00008390-199410000-00001. 
  176. ^ Sakamoto S, Murakami S, Sugawara M, Mishima Y, Okamoto R. Increased activities of thymidylate synthetase and thymidine kinase in human thyroid tumors. Thyroid. 1991, 1 (4): 347–51. PMID 1841732. doi:10.1089/thy.1991.1.347. 
  177. ^ Pikner R, Ludvíkova M, Ryska A; et al. TPS, thymidine kinase, VEGF and endostatin in cytosol of thyroid tissue samples. Anticancer Res. 2005, 25 (3A): 1517–21. PMID 16033053. 
  178. ^ Wilms K, Wilmanns W. [Effects of dauno-rubidomycin and adriamycin on enzymes of DNA synthesis in leukocytes in vivo and in culture] [Effects of dauno-rubidomycin and adriamycin on enzymes of DNA synthesis in leukocytes in vivo and in culture]. Klin. Wochenschr. September 1972, 50 (18): 866–70. PMID 4507472. doi:10.1007/BF01488943 (德語). 
  179. ^ Wilmanns W, Wilms K. DNA synthesis in normal and leucemic cells as related to therapy with cytotoxic drugs. Enzyme. 1972, 13 (1): 90–109. PMID 4507104. 
  180. ^ Zhang HJ, Kennedy BJ, Kiang DT. Thymidine kinase as a predictor of response to chemotherapy in advanced breast cancer. Breast Cancer Res. Treat. 1984, 4 (3): 221–5. PMID 6487823. doi:10.1007/BF01806488. 
  181. ^ Kuroiwa N, Nakayama M, Fukuda T; et al. Specific recognition of cytosolic thymidine kinase in the human lung tumor by monoclonal antibodies raised against recombinant human thymidine kinase. J. Immunol. Methods. July 2001, 253 (1–2): 1–11 [2012-03-13]. PMID 11384664. doi:10.1016/S0022-1759(01)00368-4. (原始內容存檔於2018-06-14). 
  182. ^ 182.0 182.1 He Q, Mao Y, Wu J; et al. Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas. Int. J. Oncol. October 2004, 25 (4): 945–53. PMID 15375544. 
  183. ^ Mao Y, Wu J, Wang N; et al. A comparative study: immunohistochemical detection of cytosolic thymidine kinase and proliferating cell nuclear antigen in breast cancer. Cancer Invest. 2002, 20 (7–8): 922–31. PMID 12449723. doi:10.1081/CNV-120005905. 
  184. ^ Mao Y, Wu J, Skog S; et al. Expression of cell proliferating genes in patients with non-small cell lung cancer by immunohistochemistry and cDNA profiling. Oncol. Rep. May 2005, 13 (5): 837–46. PMID 15809747. 
  185. ^ Wu J, Mao Y, He L; et al. A new cell proliferating marker: cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma. Anticancer Res. 2000, 20 (6C): 4815–20. PMID 11205225. 
  186. ^ Li HX, Lei DS, Wang XQ, Skog S, He Q. Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with non-small cell lung cancer. Oncol. Rep. January 2005, 13 (1): 145–9. PMID 15583816. 
  187. ^ Stephan Kruck, Joerg Hennenlotter, Ulrich Vogel, David Schilling, Georgios Gakis, Joachim Hevler, Ursula Kuehs, Arnulf Stenzl, Christian Schwentner. Exposed proliferation antigen 210 (XPA-210) in renal cell carcinoma (RCC) and oncocytoma: clinical utility and biological implications. BJU international. 2012-2, 109 (4): 634–638 [2019-05-26]. ISSN 1464-410X. PMID 21711439. doi:10.1111/j.1464-410X.2011.10392.x. (原始內容存檔於2016-06-07). 

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