We present evidence here that abundantly expressed b-catenin-triggered NF-kB-dependent upregulation of inducible nitric oxide synthase(iNOS) found in hepatoma Mahlavu cells (RT-resistant variant designated as RR-Mal),...We present evidence here that abundantly expressed b-catenin-triggered NF-kB-dependent upregulation of inducible nitric oxide synthase(iNOS) found in hepatoma Mahlavu cells (RT-resistant variant designated as RR-Mal), but not in Hep 3B cells (RT-sensitive variant designated as RS-3B) is a key element contribrting to the radioresisitance through the activation of two prominent radioprotective pathways. First, high iNOS expression found in RR-Mal, but not in RS-3B cells was found to perturb calcium homeostasis that triggered ER stress response leading to the overproduction of ER chaperone GRP-78 via robust generation of cleaved ATF-6a (50 kDa) subunits and their nuclear translocation. Meanwhile, both abundantly expressed NF-κB and COX-2 found in RR-Mal cells could also provoke an increased production of PGE2 resulting in robust production of Bcl-2. Interestingly, when RR-Mal cells were treated with PDTC (a NF-κB inhibitor) or celecoxib (a COX-2 inhibitor), a concentration-dependent downregulation of Bcl-2 could be demonstrated implying that Bcl-2 overexpression was indeed mediated through NF-κB/Cox-2/PGE2 pathway. Importantly, we also unveiled that siRNA-mediated silencing of survivin in RR-Mal cells could result in a concomitant downregulation of GRP-78 due to a severe inhibition of ATF-6a (50 kDa) expression. Taken together, our data demonstrate that constitutively overexpressed b-catenin/NF-κB/iNOS and NF-κB/COX-2/PGE2 pathways that overproducing GRP-78, survivin and Bcl-2 expressions are responsible for radioresistance acquisition in RR-Mal cells. Thus, both pathways could be served as potential targets for overcoming radioresistance.展开更多
MRI provides a highly sensitive technique for early detection of abnormal breast tissue. It is useful for identifying a status of proliferation, angiogenesis, and microvascular permeability, which may indicate early b...MRI provides a highly sensitive technique for early detection of abnormal breast tissue. It is useful for identifying a status of proliferation, angiogenesis, and microvascular permeability, which may indicate early breast neoplasm formation. We retrospectively studied 2005 breast MRI images from Taiwan Residents women and classified them as either healthy or unhealthy according to BI-RADS categories. A subgroup of our study patients had received estrogen supplements, containing estrogen components or phytoestrogen, for at least 3 months. These patients’ images were also classified into the healthy and unhealthy groups. These two groups were compared and a significant difference was found between them (P < 0.002). Comparison of the MRI images also identified certain cases that demonstrated a typical estrogen/phytoestrogen effect or a withdrawal effect. The overuse of estrogen or phytoestrogen supplements can increase breast glandular tissue proliferation, as reflected on MRI images. Such proliferation may increase the patient’s risk of future breast cancer.展开更多
文摘We present evidence here that abundantly expressed b-catenin-triggered NF-kB-dependent upregulation of inducible nitric oxide synthase(iNOS) found in hepatoma Mahlavu cells (RT-resistant variant designated as RR-Mal), but not in Hep 3B cells (RT-sensitive variant designated as RS-3B) is a key element contribrting to the radioresisitance through the activation of two prominent radioprotective pathways. First, high iNOS expression found in RR-Mal, but not in RS-3B cells was found to perturb calcium homeostasis that triggered ER stress response leading to the overproduction of ER chaperone GRP-78 via robust generation of cleaved ATF-6a (50 kDa) subunits and their nuclear translocation. Meanwhile, both abundantly expressed NF-κB and COX-2 found in RR-Mal cells could also provoke an increased production of PGE2 resulting in robust production of Bcl-2. Interestingly, when RR-Mal cells were treated with PDTC (a NF-κB inhibitor) or celecoxib (a COX-2 inhibitor), a concentration-dependent downregulation of Bcl-2 could be demonstrated implying that Bcl-2 overexpression was indeed mediated through NF-κB/Cox-2/PGE2 pathway. Importantly, we also unveiled that siRNA-mediated silencing of survivin in RR-Mal cells could result in a concomitant downregulation of GRP-78 due to a severe inhibition of ATF-6a (50 kDa) expression. Taken together, our data demonstrate that constitutively overexpressed b-catenin/NF-κB/iNOS and NF-κB/COX-2/PGE2 pathways that overproducing GRP-78, survivin and Bcl-2 expressions are responsible for radioresistance acquisition in RR-Mal cells. Thus, both pathways could be served as potential targets for overcoming radioresistance.
文摘MRI provides a highly sensitive technique for early detection of abnormal breast tissue. It is useful for identifying a status of proliferation, angiogenesis, and microvascular permeability, which may indicate early breast neoplasm formation. We retrospectively studied 2005 breast MRI images from Taiwan Residents women and classified them as either healthy or unhealthy according to BI-RADS categories. A subgroup of our study patients had received estrogen supplements, containing estrogen components or phytoestrogen, for at least 3 months. These patients’ images were also classified into the healthy and unhealthy groups. These two groups were compared and a significant difference was found between them (P < 0.002). Comparison of the MRI images also identified certain cases that demonstrated a typical estrogen/phytoestrogen effect or a withdrawal effect. The overuse of estrogen or phytoestrogen supplements can increase breast glandular tissue proliferation, as reflected on MRI images. Such proliferation may increase the patient’s risk of future breast cancer.
