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发布于:2018-12-6 22:42:06  访问:39 次 回复:0 篇
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BMC Cell Biology 2009, 10:http://www.biomedcentral.com/1471-2121/10/Figure four Induction of
Danirixin Immunology/Inflammation untreated acini (panels a, c and e) and salubrinal treated acini (panels b, d and f). (B) Graph displaying distribution with the percentage of wt-ErbB2 cells per acinus that stained positively for Ki-67 at days 6, eight and ten (left panel) or phospho-H3 at day 6 (appropriate panel); horizontal red line indicates the median. Statistical significance was determined utilizing the unpaired t-test with p < 0.05 defined as statistically significant. N.S - not significant. Salubrinal treatment significantly decreases the percentage of Ki-67 positive cells in WT-ErbB2 acini only early at day 6.(C) Graph showing distribution of the percentage of cells per acinus that stained positively for Ki-67 cells; mean ?SEM. Statistical significance was determined using the unpaired t-test with p < 0.05 defined as statistically significant. N.S - not significant. Note the increase in percentage of Ki-67 positive cells in untreated CA-ErbB2 expressing acini compared to vector controls. Salubrinal treatment significantly decreases the percentage of Ki-67 positive cells in CA-ErbB2 acini. many positively stained cells (Fig. 4A-dinset, DAPI channel and 4C). In contrast, a statistically significant decrease in Ki-67 staining was observed in CA-ErbB2 acini (Fig. 4C). Thus, it appears that both wt-ErbB2 and CA-ErbB2 are susceptible to salubrinal inhibition of proliferation, except that this effect is only observed during early phases of acinar development in wt-ErbB2 cells and throughout the growth phases for CA-ErbB2 cells. In Wt-ErbB2 acini decreased acinar size could only be partially explained by reduced proliferation in response to salubrinal treatment. Thus, we tested whether apoptosis was being modulated by sustained eIF2 phosphorylation. In this case cleaved caspase-3 staining was used as a marker of apoptosis [22]. Our results revealed that sustained treatment with salubrinal resulted in a significant increase in cleaved caspase-3 positive cells that localizedPage 7 of(page number not for citation purposes)BMC Cell Biology 2009, 10:http://www.biomedcentral.com/1471-2121/10/mainly to the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28212752 central luminal space in vector control and Wt-ErbB2 acini (Fig. 5A, panels b, d) and at a reduce frequency along the periphery in CA-ErbB2 acini (Fig. 5A, panel f). Quantification of your percentage of cleaved caspase-3 positive cells per acinus revealed that vector and Wt-ErbB2 acini displayed similar rates of apoptosis below basal untreated circumstances although constitutively active ErbB2 signaling displayed about 1.5-fold less cell death further highlighting the stronger potency of this mutant ErbB2 receptor (Fig. 5B). Salubrinal remedy.BMC Cell Biology 2009, ten:http://www.biomedcentral.com/1471-2121/10/Figure 4 Induction of eIF2 phosphorylation by salubrinal inhibits ErbB2-induced hyperproliferation Induction of eIF2 phosphorylation by salubrinal inhibits ErbB2-induced hyperproliferation. (A) Representative confocal pictures of equatorial cross-sections by means of day 10 vector handle, wild type and constitutively active ErbB2 acini stained for Ki-67 (red) or the corresponding pictures stained with DAPI (blue). Untreated acini (panels a, c and e) and salubrinal treated acini (panels b, d and f). Note Ki-67-positive cells within the outer basal layer of cells in untreated vector handle acini (outlined in dotted lines in some structures exactly where PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29072704 edges will not be clear) compared to those occupying the central luminal space in untreated ErbB2-over-expressing acini. Scale bars = 40 m.
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