12月20日,，據(jù)《每日科學(xué)》報(bào)道,，ScienceDaily (Dec. 20, 2011)許多癌癥療法靶向于癌細(xì)胞外的特定蛋白質(zhì)，但這些療法是不完善的而且并不總是有效。既然能盡快讓醫(yī)生知道治療對(duì)癌癥的影響是有利的,，Vanderbilt大學(xué)的研究人員正努力設(shè)計(jì)一些能迅速,、準(zhǔn)確且經(jīng)濟(jì)有效的測(cè)試方法用于評(píng)估治療的反應(yīng)。該研究小組已證明了一種新的方法,，利用光學(xué)測(cè)試培養(yǎng)的癌細(xì)胞對(duì)一個(gè)特定抗癌藥物的反應(yīng),。
這項(xiàng)結(jié)果發(fā)表于Biomedical Optics Express 12期上。
某些特定的癌細(xì)胞呈現(xiàn)高于正常數(shù)值的蛋白,，即一種稱(chēng)之為人類(lèi)表皮生長(zhǎng)因子受體2(HER2),。在正常細(xì)胞中，HER2有助于調(diào)解細(xì)胞的生長(zhǎng),，但過(guò)度表達(dá)的HER2卻標(biāo)志著一種極具侵略性形式的乳腺癌,。一些能結(jié)合和阻斷生長(zhǎng)因子受體的藥物已被證明能夠延長(zhǎng)一些癌癥患者的生命，但是約有30%的HER2過(guò)度表達(dá)的腫瘤對(duì)藥物沒(méi)有響應(yīng),。能夠在早期確定這些非響應(yīng)腫瘤的測(cè)試方法,，將幫助醫(yī)生做出重要的治療決策，以改善患者的預(yù)后,。
為了設(shè)計(jì)這種測(cè)試方法,，Vanderbilt團(tuán)隊(duì)利用了這樣一個(gè)事實(shí)，就是一些癌細(xì)胞優(yōu)先利用一種不同于正常細(xì)胞的代謝途徑,。研究人員通過(guò)使用各種頻率的光照射細(xì)胞，使2種不同的代謝分子發(fā)出自然的熒光,，從而可視化了2種不同代謝途徑的相對(duì)使用情況,。隨后，他們計(jì)算了這2種水平的熒光的比率,，稱(chēng)之為光光氧化還原率,。他們發(fā)現(xiàn)，在測(cè)試的不同的細(xì)胞系中,，HER2過(guò)表達(dá)的細(xì)胞有最高的光氧化還原率,。他們還發(fā)現(xiàn)，當(dāng)用一種HER2阻斷藥物作用HER2癌細(xì)胞時(shí),，光氧化還原率降低了,。然而，在對(duì)這種藥物有抗性的癌細(xì)胞中卻沒(méi)有觀察到光氧化還原率的降低,。這些發(fā)現(xiàn)為未來(lái)的體內(nèi)研究奠定了基礎(chǔ),，具有通過(guò)光學(xué)測(cè)量獲知腫瘤對(duì)治療的實(shí)時(shí)響應(yīng)的潛力。（生物谷bioon.com）
doi:10.1364/BOE.3.000075
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Optical imaging of metabolism in HER2 overexpressing breast cancer cells
Alex Walsh, Rebecca S. Cook, Brent Rexer, Carlos L. Arteaga, Melissa C. Skala
Abstract： The optical redox ratio (fluorescence intensity of NADH divided by that of FAD), was acquired for a panel of breast cancer cell lines to investigate how overexpression of human epidermal growth factor receptor 2 (HER2) affects tumor cell metabolism, and how tumor metabolism may be altered in response to clinically used HER2-targeted therapies. Confocal fluorescence microscopy was used to acquire NADH and FAD auto-fluorescent images. The optical redox ratio was highest in cells overexpressing HER2 and lowest in triple negative breast cancer (TNBC) cells, which lack HER2, progesterone receptor, and estrogen receptor (ER). The redox ratio in ER-positive/HER2-negative cells was higher than what was seen in TNBC cells, but lower than that in HER2 overexpressing cells. Importantly, inhibition of HER2 using trastuzumab significantly reduced the redox ratio in HER2 overexpressing cells. Furthermore, the combinatorial inhibition of HER2 and ER decreased the redox ratio in ER+/HER2+ breast cancer cells to a greater extent than inhibition of either receptor alone. Interestingly, trastuzumab had little impact upon the redox ratio in a cell line selected for acquired resistance to trastuzumab. Taken together, these data indicate that the optical redox ratio measures changes in tumor metabolism that reflect the oncogenic effects of HER2 activity within the cell, as well as the response of the cell to therapeutic inhibition of HER2. Therefore, optical redox imaging holds the promise of measuring response and resistance to receptor-targeted breast cancer therapies in real time, which could potentially impact clinical decisions and improve patient outcome.
