維基百科

電脈衝化療

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電脈衝化療是一種通過施加局部電脈衝，增加細胞通透性，將通常情況下無法進入細胞內部的藥物送入細胞內，從而達到殺死癌細胞目的的治療癌症的療法[1][2]。配合博萊黴素和順鉑使用電脈衝化療治療皮內和皮下腫瘤的研究已經進入臨床階段。[3][4][5][6][7][8][9][10][11][12]第一次伯萊黴素電脈衝化療於1991年在法國Gustave Roussy研究所實現[13]，第一次順鉑電脈衝化療則於1995年在斯洛文尼亞盧布爾雅那腫瘤研究所實現[14]。其後，來自全球多個國家（愛爾蘭、澳洲、奧地利、比利時、保加利亞、丹麥、德國、法國、美國、墨西哥、尼加瓜拉、波蘭、葡萄牙、日本、瑞士、斯洛文尼亞、西班牙、希臘、匈牙利、意大利、英國）的4000多名患者接受了電脈衝化療。最近，為了治療體內腫瘤，開發了通過外科手術、內窺鏡、皮下穿刺等方法到達患處的新的電脈衝化療方法。[15][16]

物理原理

當細胞暴露在足夠強的電場中時，跨膜電位（細胞膜內外的電勢差）將會增加，這會引發細胞膜結構重排[17][18][19][20][21][22]，從而導致細胞膜通透性增加，進而允許通常無法穿過細胞膜的分子進入細胞[13][23][24]。這一被稱為電穿孔（英語：electroporation）或電通透（英語：electropermeabilization）的現象，正被廣泛應用到抗腫瘤治療中。這種治療方案就是廣為熟知的電脈衝化療。電脈衝化療只採用短暫但強勁的單級直流電，儘管在體外培養的細胞和細菌中可以用電場強度隨時間衰減的脈衝。在生物體內完整組織中，脈衝的電場強度依不同組織和電極的形狀和位置而不同。在一般的腫瘤治療中，電脈衝強度需要在腫瘤範圍內達到400V/cm。通常每次連續施加8個持續100微秒[25]的脈衝。在最初的試驗中，施加脈衝的頻率為1Hz，而現在通常採用5000Hz，因為這可以大大降低患者的不適感和治療的持續時間[26][27]。而在治療靠近心臟的腫瘤時，脈衝應和心肌的絕對不應期同步，從而儘可能降低電脈衝影響心臟正常功能的可能性。[28]

治療說明

電脈衝治療首先需要對全身或局部引入不通透或低通透的細胞毒素藥物。然後，當腫瘤區域藥物濃度達到峰值時直接對該區域施加脈衝電場[12]。脈衝電場可以在細胞膜上產生納米級缺陷，從而方便藥物進入細胞。在施加電場期間以及電場消失後的一段時間內，藥物分子可以自由擴散進入細胞質，從而實現抗腫瘤效果。如果藥物濃度足夠，可以通過在不同的地方插入電極和施加多次電場來治療整個腫瘤。[25]如果首次治療時因腫瘤太大而無法對整個腫瘤施加電脈衝化療，也可以在幾周或幾個月後繼續治療。

療效和相關性

一些二期臨床實驗證明，使用博萊黴素和順鉑的電脈衝化療對皮內或皮下肉瘤的客觀應答率超過80%。[4][29]電脈衝化療在縮小皮膚腫瘤和皮下腫瘤的大小上比化療更快更有效。電脈衝化療對黑色素瘤、Kaposi肉瘤、鱗狀細胞癌、基底細胞癌、腺癌、乳腺癌均有療效。[4][5][6][7][9][10][30]初步表明也很有希望可以利用電脈衝療法治療內部腫瘤（例如肝轉移腫瘤）。

安全性

電脈衝化療所使用的藥物濃度比普通化療所使用的更低，因此沒有常規化療所引起的不良反應。適當的麻醉可以減輕電脈衝引起的不適症狀，從而可以把疼痛感控制在病人可以接受的範圍內。除去電脈衝引起的疼痛以外，脈衝期間的肌肉收縮是患者唯一的不適。[4][31]脈衝同時會引起短暫的缺血。在治療區域內，正常組織內的血液循環會被打斷幾分鐘[32][33]，但是由於時間短暫，所以並不會產生缺血反應；相反地，腫瘤組織內部的缺血時間會更長，從而對抑制腫瘤也有一定幫助。在一項以建立歐洲電脈衝化療標準手術程序為目的的醫療實驗中，大部分接受調查患者表示如果需要，願意再次接受電脈衝化療[4]，因此可以推斷電脈衝化療並不特別令人痛苦或者緊張。[4][34]

獸醫應用

電脈衝化療同樣可以應用於犬類、貓和馬的腫瘤治療。巴西、法國、意大利、愛爾蘭、斯洛文尼亞、英國及台灣的一些醫療中心可以提供針對各種腫瘤的治療。[34]

評論

電脈衝化療在多個歐盟國家（波蘭、丹麥、德國、葡萄牙、斯洛文尼亞、希臘、意大利和英國）都已經獲得認可和醫療補貼。意大利Carpy Igea, s.r.l.生產的Cliniporator儀被認證為醫療器具並和歐洲電脈衝化療標準手術程序一起向市場推廣。[4]

參考資料

  1. ^ Mir LM, Orlowski S, Belehradek J, Paoletti C (1991). "Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses". Eur. J. Cancer 27 (1): 68–72. PMID 1707289.
  2. ^ Sersa G, Cemazar M, Miklavcic D (August 1995). "Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice". Cancer Res. 55 (15): 3450–5. PMID 7614485.
  3. ^ Gehl, J. & Geertsen, P.F. Palliation of haemorrhaging and ulcerated cutaneous tumours using electrochemotherapy. Eur J Cancer Suppl 4, 35-37 (2006).
  4. ^ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Marty, M. et al. Electrochemotherapy - An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. Eur J Cancer Suppl 4, 3-13 (2006).
  5. ^ 5.0 5.1 Larkin JO, Collins CG, Aarons S, et al. (March 2007). "Electrochemotherapy: aspects of preclinical development and early clinical experience". Ann. Surg. 245 (3): 469–79. doi:10.1097/01.sla.0000250419.36053.33. PMC 1877027. PMID 17435555.
  6. ^ 6.0 6.1 Sersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoj M (February 2008). "Electrochemotherapy in treatment of tumours". Eur J Surg Oncol 34 (2): 232–40. doi:10.1016/j.ejso.2007.05.016. PMID 17614247.
  7. ^ 7.0 7.1 M?ller MG, Salwa S, Soden DM, O'Sullivan GC (November 2009). "Electrochemotherapy as an adjunct or alternative to other treatments for unresectable or in-transit melanoma". Expert Rev Anticancer Ther 9 (11): 1611–30. doi:10.1586/era.09.129. PMID 19895245.
  8. ^ Campana, L.G. et al. Electrochemotherapy: clinical outcome and predictive factors from a single institution experience on 50 melanoma patients. Ann Surg Oncol 17, S106-S106 (2010).
  9. ^ 9.0 9.1 Testori A, Tosti G, Martinoli C, et al. (2010). "Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach". Dermatol Ther 23 (6): 651–61. doi:10.1111/j.1529-8019.2010.01370.x. PMID 21054709.
  10. ^ 10.0 10.1 Hampton T (February 2011). "Electric pulses help with chemotherapy, may open new paths for other agents". JAMA 305 (6): 549–51. doi:10.1001/jama.2011.92. PMID 21304073.
  11. ^ Mu?oz Madero V, Ortega Pérez G (January 2011). "Electrochemotherapy for treatment of skin and soft tissue tumours. Update and definition of its role in multimodal therapy". Clin Transl Oncol 13 (1): 18–24. PMID 21239351.
  12. ^ 12.0 12.1 Sersa G, Miklavcic D (2008). "Electrochemotherapy of tumours". J Vis Exp (22). doi:10.3791/1038. PMC 2762922. PMID 19229171.
  13. ^ 13.0 13.1 Mir LM, Belehradek M, Domenge C, et al. (1991). "Electrochemotherapy, a new antitumor treatment: first clinical trial (in French). C. R. Acad. Sci. III, Sci. Vie 313 (13): 613–8. PMID 1723647.
  14. ^ Rudolf, Z. et al. Electrochemotherapy with bleomycin. The first clinical experience in malignant melanoma patients. Radiol Oncol 29, 229-35 (1995).
  15. ^ Soden DM, Larkin JO, Collins CG, et al. (February 2006). "Successful application of targeted electrochemotherapy using novel flexible electrodes and low dose bleomycin to solid tumours". Cancer Lett. 232 (2): 300–10. doi:10.1016/j.canlet.2005.03.057. PMID 15964138.
  16. ^ Miklavcic, D. et al. Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. BioMed Eng OnLine 9, 10 (2010).
  17. ^ Weaver, J.C. & Chizmadzhev, Y.A. Theory of electroporation: A review. Bioelectrochemistry Bioenerg 41, 135-160 (1996).
  18. ^ Kotnik, T., Bobanovic, F. & Miklavcic, D. Sensitivity of transmembrane voltage induced by applied electric fields - a theoretical analysis. Bioelectrochemistry Bioenerg 43, 285-291 (1997).
  19. ^ Weaver, J.C. Electroporation of cells and tissues. IEEE Trans Plasma Sci 28, 24–33 (2000).
  20. ^ Chen C, Smye SW, Robinson MP, Evans JA (March 2006). "Membrane electroporation theories: a review". Med Biol Eng Comput 44 (1-2): 5–14. doi:10.1007/s11517-005-0020-2. PMID 16929916.
  21. ^ Puc M, Kotnik T, Mir LM, Miklavcic D (August 2003). "Quantitative model of small molecules uptake after in vitro cell electropermeabilization". Bioelectrochemistry 60 (1-2): 1–10. PMID 12893304.
  22. ^ Puc M, Corovi? S, Flisar K, Petkovsek M, Nastran J, Miklavcic D (September 2004). "Techniques of signal generation required for electropermeabilization. Survey of electropermeabilization devices". Bioelectrochemistry 64 (2): 113–24. doi:10.1016/j.bioelechem.2004.04.001. PMID 15296784.
  23. ^ Cemazar M, Sersa G (December 2007). "Electrotransfer of therapeutic molecules into tissues". Curr. Opin. Mol. Ther. 9 (6): 554–62. PMID 18041666.
  24. ^ Sersa G, Stabuc B, Cemazar M, Jancar B, Miklavcic D, Rudolf Z (July 1998). "Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients". Eur. J. Cancer 34 (8): 1213–8. PMID 9849482.
  25. ^ 25.0 25.1 Zupanic, A., Corovic, S. & Miklavcic, D. Optimization of electrode position and electric pulse amplitude in electrochemotherapy. Radiol Oncol 42, 93-101 (2008).
  26. ^ Pucihar G, Mir LM, Miklavcic D (September 2002). "The effect of pulse repetition frequency on the uptake into electropermeabilized cells in vitro with possible applications in electrochemotherapy". Bioelectrochemistry 57 (2): 167–72. PMID 12160614.
  27. ^ Zupanic A, Ribaric S, Miklavcic D (2007). "Increasing the repetition frequency of electric pulse delivery reduces unpleasant sensations that occur in electrochemotherapy". Neoplasma 54 (3): 246–50. PMID 17447858.
  28. ^ Mali B, Jarm T, Corovic S, et al. (August 2008). "The effect of electroporation pulses on functioning of the heart". Med Biol Eng Comput 46 (8): 745–57. doi:10.1007/s11517-008-0346-7. PMC 2491703. PMID 18415132.
  29. ^ Sersa, G. The state-of-the-art of electrochemotherapy before the ESOPE study; advantages and clinical uses. Eur J Cancer Suppl 4, 52-59 (2006).
  30. ^ Heller R, Gilbert R, Jaroszeski MJ (January 1999). "Clinical applications of electrochemotherapy". Adv. Drug Deliv. Rev. 35 (1): 119–129. PMID 10837693.
  31. ^ Sersa G, Jarm T, Kotnik T, et al. (January 2008). "Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma". Br. J. Cancer 98 (2): 388–98. doi:10.1038/sj.bjc.6604168. PMC 2361464. PMID 18182988.
  32. ^ Jarm T, Cemazar M, Miklavcic D, Sersa G (May 2010). "Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases". Expert Rev Anticancer Ther 10 (5): 729–46. doi:10.1586/era.10.43. PMID 20470005.
  33. ^ Cemazar M, Tamzali Y, Sersa G, et al. (2008). "Electrochemotherapy in veterinary oncology". J. Vet. Intern. Med. 22 (4): 826–31. doi:10.1111/j.1939-1676.2008.0117.x. PMID 18537879.
  34. ^ 34.0 34.1 Mir, L.M. et al. Standard operating procedures of the electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes. Eur J Cancer Suppl 4, 14-25 (2006).

參考

取自 "https://zh.wikipedia.org/w/index.php?title=电脉冲化疗&oldid=69107365"