We were specifically enthusiastic about possible correlation and coexpression in between these markers. Major neuroendocrine tumors from the lung were chosen from your archives from the Methodist Hospital, Houston, TX, such as 38 TC, 6 AC, 34 SCLC and 11 LCNEC.
Briefly, 5 micron sections of TMA were very first deparaffinized and rehydrated, followed by antigen retrieval by heating the sections in ethylenediaminetetraacetic acid buffer at pH 9 for 15 minutes.
Slides were then formulated with 3,3 diaminobenzidine chromogen and counterstained with hematoxylin.The expression levels from the four markers are summarized in Table 1. Photomicrographs of representative circumstances, one from each tumor form, are shown in Figure 1.
In reality, all tumors integrated in this study expressed at the least HSP certainly one of these two proteins, and more than 80% of them strongly expressed at the least certainly one of these two proteins. Nevertheless, the expression of PAX5 varied significantly in between distinct tumor types, lower in TC than in AC, SCLC and LCNEC. Paxillin also showed significantly distinct expression levels, highest in TC and lowest in LCNEC.
The semi quantitative staining intensities from the four Survivin markers were also compared with each other by Pearsons correlation coefficient. Correlation in between other markers was weak and did not show statistical significance. All four types of neuroendocrine tumors from the lung showed frequent expression of c Met and p c Met.
A vast majority of these tumors had strong expression, supporting the role played by c Met in tumor biology as well as the likely utilization of c Met like a therapeutic target, particularly in SCLC and LCNEC for Survivin which you'll find presently only restricted and largely unsuccessful remedy possibilities. That is in maintaining with the previous observation that there was no correlation in between c Met mutations and its expression level in SCLC.
As a result, it can be possible that the final results were biased. Much more importantly, PAX5 appeared to immediately advertise the transcription of c Met; and knocking down PAX5 had a synergizing effect with c Met inhibitors in killing SCLC cells. 9 This observation brought up the possibility of co targeting both proteins for the remedy of lung cancers.
Paxillin is one of the downstream molecules from the HGF/c Met signaling pathway. We could not come across any evidence within the literature that suggests an intrinsic linkage in between the expression manage mechanisms of these two proteins.
Whether it can be basically a coincidence or intrinsically associated with the biology of TGF-beta these tumors would be an exciting topic for future investigation. Carcinoid, then again, is quite distinct both clinically and biologically compared to SCLC and LCNEC.
Monday, December 17, 2012
Twelve TGF-beta Topoisomerase related proteins Dialogue Recommendations
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