The exact mechanism by which SRT501 and SRT1720 increase transcriptional activa

Go down

 The exact mechanism by which SRT501 and SRT1720 increase transcriptional activa Empty The exact mechanism by which SRT501 and SRT1720 increase transcriptional activa

Post  jy9202 on Mon Jun 23, 2014 7:47 am

STAT3 rep resents a critical regulator of keratinocytes in response to UVB irradiation. After UVB irradiation, STAT3 is rapidly downregulated in keratinocytes, which leads to decreased cell cycle progression and increased sensitivity to UVB induced apoptosis. It has also been reported that UV specifically decreases ABT-888 912444-00-9 the DNA binding activity of STAT3. Furthermore, UV triggers the activation of members of the MAPK family, including Erk1 2, JNK, and p38 MAPK. UV irradiation can enhance MAPK activ ity and lead to a greater phosphorylation of STAT3 at Ser727 in the presence of everolimus. These re sults suggest that the dermatological side effects induced by molecular target drugs can be increased potentially by UV irradiation, with repression of STAT3 activity mediat ing greater phosphorylation of Ser727.

However, add itional studies are Afatinib BIBW2992 necessary to clarify this potency. Conclusions In conclusion, STAT3 activation may be a key factor in everolimus induced keratinocyte cytotoxicity. More over, p38 MAPK and Erk mediated between mTOR signaling and STAT3 signaling may also play an im portant role of everolimus induced dermatological side effects. Skin reactions caused by everolimus or other molecular target drugs may cause significant physical discomfort, thus decreasing the quality of life of pa tients or leading to the discontinuation of drug ther apy. Therefore, a mechanism based approach, and not just clinical experience based treatment strategies, to assess dermatological toxicity should be proposed to overcome this uncomfortable reaction.

We advocate that cutaneous localized treatment aimed at the main tenance of the homeostasis of STAT3 activity may be an effective strategy. AG-1478 EGFR 阻害剤 Incision associated with surgery causes acute pain and surgery has been identified as a potential major cause of chronic pain conditions. Between 10 and 50% of patients develop chronic pain following surgical proce dures such as groin hernia repair, breast and thoracic surgery, leg amputation, or coronary artery bypass surgery. Despite improvements in post surgical pain treatment strategies, the incidence of moderate to severe pain after surgery is still high in several patient popula tions. Moreover, the exact mechanisms involved in the development of persistent pain following surgery have not been elucidated.

Interleukin 6, a pro inflammatory cytokine, is a significant mediator of noci ceptive plasticity in pre clinical pain models and is implicated in several human pain conditions. Serum IL 6 levels increase significantly in patients immediately after surgery and circulating IL 6 levels are pro portional to the extent of tissue injury during an operation, rather than being proportional to the dura tion of the surgical procedure itself. Furthermore, IL 6 levels have been shown to be elevated in skin around incision sites and it has been implicated in preclinical incision induced pain models. Although these reports are suggestive of involvement of IL 6 in post surgical pain, the precise mechanisms by which IL 6 drives post surgical pain are poorly under stood. However, IL 6 has been implicated as an impor tant player in many preclinical pain models and elegant genetic studies have demonstrated that IL 6s pain pro moting qualities are mediated by IL 6 receptors expressed by nociceptors.

jy9202

Posts : 509
Join date : 2013-12-18

View user profile

Back to top Go down

Back to top


 
Permissions in this forum:
You cannot reply to topics in this forum