A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor
prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex AZD5363 in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition. (C) 2011 Wiley Periodicals, Inc.”
“The phosphine-bis-arenesulfonate ligand PPh((2)-SO(3)Li-4-Me-Ph)(2) (Li(2)[OPO]) coordinates as a kappa(2)-P,O chelator
in Li[(Li-OPO)PdMe(Cl)] (2a) and (Li-OPO)PdMe(L) (L = pyridine (2b); MeOH (2d); 4-(5-nonyl)pyridine) (py’, 3)). 2a reacts with AgPF(6) to form (Li-OPO)PdMe}(n) (2c). Photolysis of 2d yields (OPO)Pd(2) (5) in which the [OPO](2-) ligand coordinates as a kappa(3)-O P,O pincer. 3 self-assembles into a tetramer in which four (Li-OPO)PdMe(py’) units are linked by Li-O bonds that form a central Li(4)S(4)O(12) cage. The Pd centers are equivalent but are spatially separated into two identical pairs. The Pd-Pd distance within each pair is 6.04 angstrom. IR data (nu(ArSO(3))region) suggest that the see more solid state structures of 2a-c are similar to that of 3. 3 reacts with the cryptand Krypt211 to form [Li(Krypt211)][(OPO)PdMe(py')] (4). 3 is in equilibrium with a monomeric (Li-OPO)PdMe(py’) species (3′) in solution. 2a-c and 3 produce polyethylene (PE) with high molecular weight and a broad molecular weight Blasticidin S cell line distribution, characteristic of multisite catalysis. Under conditions where the
tetrameric structure remains substantially intact, the PE contains a substantial high molecular weight fraction, while, under conditions where fragmentation is more extensive, the PE contains a large low molecular weight fraction. These results suggest that the tetrameric assembly gives rise to the high molecular weight polymer. In contrast, the monomeric complex 4, which contains a free pendant sulfonate group that can bind to Pd, oligomerizes ethylene to a Schultz-Flory distribution of C(4)-C(18) oligomers.”
“Background: Tramadol, a monoaminergic reuptake inhibitor, is hepatically metabolized to an opioid agonist (M1). This atypical analgesic is generally considered to have limited abuse liability. Recent reports of its abuse have increased in the U.S., leading to more stringent regulation in some states, but not nationally.