Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiotherapy is considered mandatory for breast cancer patients undergoing conservative surgery and for women at high risk of recurrence. However, relapse due to radio-resistance affects the success of radiotherapy. Ascertaining the fractionated radiation (FIR) modulated molecular targets is important to make tumors more susceptible to molecular targeted therapy. Accordingly, we investigated the (i) expression of 84 genes representing six functional pathways; (ii) NFkappaB DNA binding activity and; (iii) expression of radio-responsive molecules after single dose (10Gy) radiation (SDR) and FIR (2Gyx5). MCF-7 cells exposed to SDR or FIR were analyzed for alterations in gene expression using QPCR-profiling. NFkappaB DNA binding activity was analyzed using EMSA and pIkappaB using immunoblotting. Expression of TNFalpha, IL-1alpha, pAKT, IAP1, IAP2, XIAP, survivin, MnSOD, BID and Bak were determined using QPCR and/or immunoblotting. Compared to SDR, FIR significantly induced 60 genes and completely suppressed 14 genes. Furthermore, FIR induced NFkappaB-DNA binding activity and IkappaBalpha phosphorylation. Like-wise, FIR induced the expression of IAP1, IAP2, XIAP Survivin, MnSOD, TNFalpha, pAKT and IL-1alpha. The results of the study clearly show distinct differences in the molecular response of cells between SDR and FIR exposures. We identified several potential targets that may affect radio-resistance following FIR.
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PMID:NFkappaB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation. 1939 60

Radiotherapy has been used as an adjunctive local-control modality for high-risk neuroblastoma. However, relapse due to radioresistance affects the success of radiotherapy. Ascertaining the fractionated radiation (FIR) modulated molecular targets is imperative in targeted molecular therapy. Accordingly, we investigated the (i) expression of genes representing six functional pathways; (ii) NFkappaB DNA-binding activity and (iii) expression of radioresponsive molecules after single dose (10 Gy) radiation (SDR) and FIR (2 Gy x 5) in human neuroblastoma cells. Alterations in gene expression were analyzed using QPCR-profiling, NFkappaB activity using electrophoretic mobility shift assay (EMSA) and pIkappaBalpha using immunoblotting. Modulations in TNFalpha, IL-1alpha, pAKT, IAP1, IAP2, XIAP, survivin, MnSOD, BID, Bak, MyD88 and Vegfc were determined using quantitative real-time PCR (Q-PCR) and immunoblotting. Compared to SDR, FIR significantly induced the expression of 25 genes and completely suppressed another 30 genes. Furthermore, FIR induced NFkappaB-DNA-binding activity and IkappaBalpha phosphorylation. Similarly, we observed an induced expression of IAP1, IAP2, XIAP, Survivin, IL-1alpha, MnSOD, Bid, Bak, MyD88, TNFalpha and pAKT in cells exposed to FIR. The results of the study clearly show distinct differences in the molecular response of cells between SDR and FIR. We identified several potential targets confining to NFkappaB signaling cascade that may affect radio-resistance after FIR.
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PMID:NFkappaB signaling related molecular alterations in human neuroblastoma cells after fractionated irradiation. 1943 49