p53 Target Gene SMAR1 Is Dysregulated in Breast Cancer: Its Role in Cancer Cell Migration and Invasion

Tumor suppressor SMAR1 interacts and stabilizes p53 through phosphorylation at its serine-15 residue. We show that SMAR1 transcription is regulated by p53 through its response element present in the SMAR1 promoter. Upon Doxorubicin induced DNA damage, acetylated p53 is recruited on SMAR1 promoter that allows activation of its transcription. Once SMAR1 is induced, cell cycle arrest is observed that is correlated to increased phospho-ser-15-p53 and decreased p53 acetylation. Further we demonstrate that SMAR1 expression is drastically reduced during advancement of human breast cancer. This was correlated with defective p53 expression in breast cancer where acetylated p53 is sequestered into the heterochromatin region and become inaccessible to activate SMAR1 promoter. In a recent report we have shown that SMAR1 represses Cyclin D1 transcription through recruitment of HDAC1 dependent repressor complex at the MAR site of Cyclin D1 promoter. Here we show that downmodulation of SMAR1 in high grade breast carcinoma is correlated with upregulated Cyclin D1 expression. We also established that SMAR1 inhibits tumor cell migration and metastases through inhibition of TGFβ signaling and its downstream target genes including cutl1 and various focal adhesion molecules. Thus, we report that SMAR1 plays a central role in coordinating p53 and TGFβ pathways in human breast cancer

New opportunities for research in coal derived chemicals

1051-1058Some specialty chemicals are monomers for new variety of aromatic engineering plastics. Some of these monomers can be prepared from 1-4 ring aromatics (alkylated benzenes, biphenyl, anthracene, phenanthrene, pyrene, phenol and carbazole). Among these, 2, 6-dialkyl naphthalenes, 4, 4’- dialkyl benzenes assume greater importance. By oxidation of coal and lignite using alkaline group I metal oxide, it is possible to isolate phenolic acids and naphthalene di-carboxylic acid, which are also important monomers for engineering plastics. By developing critical aromatic chemicals from coal, carbo-chemical resources could contribute to high technology development leading to reduction in the cost of basic monomers. Markets with large volume of carbo-chemicals can be further stimulated through high performance industrial carbons such as graphite, carbon fibre as also by developing processes for manufacture of adsorbents for environmental applications such as air and water purification

Multicenter urethroplasty outcomes for urethral stricture disease for patients with neurogenic bladder or bladder dysfunction requiring clean intermittent catheterization.

BackgroundOur objective is to better comprehend treatment considerations for urethral stricture disease (USD) in patients requiring long-term clean intermittent catheterization (CIC). Patient characteristics, surgical outcomes and complications are unknown in this population.MethodsSix members of the Trauma and Urologic Reconstruction Network of Surgeons (TURNS) participated in a prospective (2009 to present) and retrospective (prior to 2009) database recording patient demographics, surgical approach and outcomes. We included all patients undergoing urethroplasty who perform CIC. Descriptive statistics were used to analyze results.ResultsA total of 37 patients with 39 strictures were included. Bladder dysfunction was characterized as detrusor failure in 35% and neurogenic etiology in 65%. Median stricture length was 3 cm (IQR: 1.5-5.5) with 28% repaired with dorsal onlay buccal mucosal graft, 26% excision and primary anastomosis, 8% dorsal inlay, 8% ventral and dorsal, 8% flap based 8% non-transecting and 15% other. Functional success was 90%: 4 patients required DVIU or dilation due to recurrence, with 2 of those ultimately requiring repeat urethroplasty. 86% of patients returned to CIC; no patients reported new pad use for urinary leakage after urethroplasty. During a median follow-up period of 3.1 years (IQR: 1.0-5.3), no patients underwent urinary diversion.ConclusionsUrethroplasty is suitable, safe and effective for patients dependent on CIC suffering from USD. The effect of continual CIC on long-term outcomes remains uncertain