3. 4. 5.



所有跟贴·加跟贴·新语丝读书论坛http://www.xys.org/cgi-bin/mainpage.pl

送交者: Yush 于 2006-4-16, 06:16:01:

回答: 真不好翻译。刚弄出来1和2: 由 Yush 于 2006-4-16, 04:10:05:

3. 第三篇引用魏的结果的论文发表于2004年(Okaji, Y. et al. 2004, Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity. Cancer Sci. 95:85-90}。引述如下:
根据魏的假说,“克服对{自体血管生成内皮细胞}{autologous angiogenic endothelial cells }的免疫耐受性,是一种治疗癌症的有用途径。然而,以自体或同源内皮细胞或其蛋白质为疫苗对{血管??}{angiogenic vessels}进行免疫在临床上可能有难度,这是因为免疫耐受性是在{免疫系统的发展过程中}{during the development of the immune system}获得的,”用自身的内皮细胞产生抗肿瘤活性是不太可能的。

很不幸,该论文直接与魏的假说相冲突,表明了用同源内皮细胞进行接种具有超强的抗肿瘤活性,与HUVES相比(图2)产生了更强的抗肿瘤活性。此外,免疫球蛋白也没有特异性。引述如下:
{“虽然免疫球蛋白的血清浓度增加程度小,在ELISA化验中,抗体显示出与内膜抗原的强化合力。另外,HSE接种过的小鼠血清中的抗体,不但与HSE内膜蛋白强力结合,而且也与HUVEC内膜蛋白强力结合(图4A),反之亦然(图4A)。因此,内皮疫苗产生的抗体与鼠类和人类抗原都是可交叉反应的。另外,两组小鼠的血清都不与肿瘤细胞的膜蛋白发生反应(图4C),这与流动血细胞计数分析相符。”
”}{“Although the increase in serum concentration of immunoglobulins was small, in the ELISA assay, the antibodies showed a strong affinity for endothelial membrane antigens. In addition, the antibodies present in the sera of HSE-vaccinated mice strongly bound not only proteins of HSE membranes, but also those of HUVEC membranes (Fig. 4A), and vice versa (Fig. 4B). Thus, the antibodies induced by endothelial vaccines were cross-reactive with both murine and human antigens. Furthermore, the sera of mice of both groups did not react with membrane proteins of tumor cells (Fig. 4C), in accordance with the flow-cytometry analysis.” }

看看他们引用了魏的论文的那些内容。引述如下:
{“魏等人报告过,异种而非自体内皮细胞免疫,在诱导抑制血管生成的免疫力和保护小鼠避免肿瘤生长方面在是有效的……然而,在诱导特定体液和细胞对肿瘤内皮的免疫力方面,本研究中的自体内皮免疫比异种内皮免疫更有活性。”}{“Wei et al have reported that immunization with xenogeneic, but not autologous, endothelial cells, was effective in inducing an antiangiogeneic immunity and protecting mice from tumor growth... The present study, however, autologous endothelial vaccines were more active than the xenogeneic ones in inducing specific humoral and cellular immunities against tumor endothelium, and they consequently provided greater tumor inhibition.”}

因此,两篇论文的差异是非常明显的,这篇论文直接挑战了魏的结果,至少挑战了魏的以异种抗原克服自身免疫系统的耐受性这个假说的基础。此外,这篇论文同样不能辨别具有抗肿瘤活性的特异抗原,更辨别不了VEGFR II和alpha v integrin。


4. 寻找以蛋白质或小分子作为新的抑制血管生成的靶标以用于治疗,这一直是研究人员的广泛兴趣所在。{以下这篇论文试图建立抗菌素陈列技术以在内皮细胞中找到特定标识,以找出一个新治疗靶标。}{The following paper was an attempt to identify new therapeutic target by establishing phage display technique in order to identify specific markers in endothelial cells.}该文由Mutuberria等人于2004年发表(Mutuberria, R. et al. 2004, Isolation of human antibodies to tumor associated endothelial cell markers by in vitro human endothelial cell selection with phage display libraries. Journal of Immunological Methods, 287:31-47.)。首先,他们是这样评价魏的工作的:{“用确定的增生HUVEC作为疫苗的肿瘤的免疫治疗已经导致抑制血管生成和实体肿瘤的退化(魏等,2000)”}{“Immunotherapy of tumors using fixed proliferating HUVEC as a vaccine has resulted in the inhibition of angiogenesis and regression of solid tumors (Wei et al., 2000)”. }整篇文章仅在此处提到魏的工作。由于与魏使用了同样的细胞(HUVEC)、研究了同样的{抗原分子基础}{molecular basis of antigens},将他们的结果与魏进行对照是合情合理的 。此外,{抗菌素陈列}{phage display}是{检测特定缩氨酸在抗原中的部位}{probe specific peptide regions in the antigens}的有力工具。任何重要的抗原,例如魏论文图7中所示的VEGFR-2 和alpha v integrin,都应当能被检出。然而,在Mutuberria的这篇论文的结果部分,引述如下:

{“我们采用过市面上找得到的抗体,来比较这些抗原与CD31 (PECAM)、Tie-1、Tie-2、VEGFR-1和VEGFR-2等可能的靶标抗原的分子量。这些商业抗体都不能检测出与所选择的抗菌素抗体完全相同的分子量(图2b及未标出来的数据)。”}{
“We have used commercially available antibodies to compare these antigens with the molecular weights of possible target antigens such as CD31 (PECAM), Tie-1, Tie-2, VEGFR-1 and VEGFR-2. None of the those commercial antibodies detected the exact same molecular weights as the selected phage antibodies (Fig. 2b and data not shown).”}

实际上,他们观察到的条带,其分子量为175 kDa和110-125 kDa。因此,根据本文,可以得出结论:要么是荷兰的研究人员错了,要么是魏院士错了,二者必有一错。

5. 最后,我们查看一下2002年Mittleman发表的{分析基于缩氨酸相似性的免疫反应}{analysis of immune responses based on peptide similarity}的另一篇论文(Mittleman, A. et al. 2002, Monoclonal and polyclonal humoral immune response to EC Her-2/neu peptides with low similarity to the host’s proteome. International Journal of Cancer, 98:741-747)。该文的目的是阐释{缩氨酸序列与蛋白质序列的关系}{relationship between peptide sequences and host’s proteome},来更好地预测{抗原决定缩氨酸序列}{epitopic peptide sequence}及相应的{免疫原}{immunogeneicity}。文中讨论部分引用了魏的论文:“为了提高预测与疾病相关的抗原决定缩氨酸的能力,本文考虑了TAA的自特征,以及免疫耐受性阻碍了有效免疫识别和消灭人类癌症的事实。 30-32。”{“In an effort to improve the ability of predicting disease relevant epitopic peptides, the present work has taken into consideration the self-character of TAAs and the matter of fact that immune tolerance appears as the main obstacle to an effective immune recognition and destruction of human cancers. 30-32”.} 他们的结果表明,{疾病相关抗原决定基与受体蛋白质序列之间存在联系,}{there is a relationship between disease associated epitopes and the host proteome, }{但人类乳房/前列腺癌血清与合成的、与病人相似程度低/中的HER-2/neu缩氨酸优先进行反应。}{
but human brest/prostate cancer sera preferentially react with synthetic HER-2/neu peptides having low/medium level of similarity to human patients.}另外,{缩氨酸中显示的最高水平的缩氨酸免疫原与人类蛋白质序列根本没有相似性。}{the highest level of peptide immunogeneicity was shown in the peptides with no similarity at all to human proteome.}他们的结论是:{“我们建议,与受体蛋白质序列的低水平相似性在确定缩氨酸免疫原方面有可能承担重要角色。”}{“We suggest that a low level of similarity to the host’s proteome might play a significant role in determining peptide immunogeneicity.”}. {与此相反,魏在其论文中所描述的、选择缩氨酸来合成与测试其活性的理论基础是:“用SwissPort database in NCBI进行的序列比较分析表明,小鼠和人类的VEGFR II和alpha v integrin主序列是同源的,在氨基酸水平上分别有82%和89%是相同的。另外,我们从最相同的小鼠和人类氨基酸序列中选择了缩氨酸用于分析。”在魏的事例中,人类缩氨酸是免疫原,而小鼠的序列表达了受体蛋白质序列。因此,魏的理论基础和Mittleman的论文中的实验数据有明显的差异。}{In contrast, what Wei described in his paper and his theoretical basis of choosing peptides for synthesis and test their activity was “Sequence comparison analysis using the SwissPort database in NCBI indicated that the primary sequences of VEGFR II and alpha v integrin of mice and humans were homologs that were 82% and 89% identical, respectively, at amino-acid level. Next, we selected pairs of peptides for synthesis from the regions that shared the most-identical amino-acid sequences between humans and mice”. In his case, human peptides are immunogens whears mouse sequences represent the host proteome. Therefore, there is an obvious discrepancy between Wei’s theoretical basis and this paper’s experimental data. }

总之,迄今为止,文献从来没有报告过从接种动物的内皮细胞产生的抗原中检测和辨别出VEGFR-II和alpha v integrin。可以不冤枉地说,魏院士在其2000年发表于Nature Medicine的论文的实际引用方面误导同行和公众。至今,没有人能够在任何学术论文中重复过他的工作;事实是,有不少论文观察到了十分不同的结果,并得到了相反的结论。如果有可能来重复或验证他的工作,我建议使用他论文中列出的缩氨酸来观察其抗肿瘤活性。这是最简单最方便的办法,以确定他是否在其最重要的论文中假冒伪造了数据。

In conclusion, to date, there has been no report on the detection and identification of VEGFR-II and alpha v integrin as antigens from endothelial cells when they were vaccinated in animals in literature. It’s fair to say that Professor Wei has mislead colleagues and the public on the actual citations of his paper published at Nature-Medicine in 2000. Nobody has been able to repeat his work in any scholastic publications so far, and the truth is that there are some publications that observed very different results and made opposite conclusions. If it were possible to repeat or verify his work, I would suggest to use his peptides listed in the paper to observe their antitumor activity, which is the simplest and most convenient way to draw a conclusion to determine whether he faked or manipulated the data in this very important publication.




所有跟贴:


加跟贴

笔名: 密码(可选项): 注册笔名请按这里

标题:

内容(可选项):

URL(可选项):
URL标题(可选项):
图像(可选项):


所有跟贴·加跟贴·新语丝读书论坛http://www.xys.org/cgi-bin/mainpage.pl