(c) 2007 Elsevier Inc. All rights reserved.”
“Introduction: Peroxisome proliferator-activated receptor gamma (PPAR gamma) transcriptionally modulates fat metabolism and also plays a role in pathological conditions
such as cancer, neurodegenerative disease and inflammation. PPAR gamma imaging agents are potential tools for investigating these diseases.
Methods: Four analogs of GW9662, a PPAR gamma antagonist, with different fluorine-containing substituents at the para-position of the aniline ring were synthesized and evaluated using two different receptor binding assays for measuring PPAR gamma affinity. Micro-positron emission tomography (PET) imaging studies were performed in a transgenic mouse model having a heart-specific overexpression
of PPAR gamma.
Results: All four analogs were found to have binding affinities that were comparable to or better than the reference antagonist, GW9662, using a scintillation proximity assay (SPA). However, only the chloro-based analogs (compounds 3 and 4) had activity in a whole-cell assay measuring activation of the PPAR gamma/retinoid X receptor complex. The microPET imaging studies in an MHC-PPAR gamma transgenic mouse model showed high uptake and PPAR gamma-specific binding for the irreversible antagonist [F-18]3, whereas the corresponding reversible methoxy analog ([F-18]5) displayed only nonspecific uptake in heart.
Conclusions: The results of this preliminary study show that the irreversible antagonist [F-18]3 may represent a novel strategy for imaging PPAR gamma in vivo with PET. (C) 2012 Elsevier Inc. All rights reserved.”
“Objective: This study examined the impact of neoadjuvant chemotherapy and concurrent high-dose radiation therapy on survival in patients
with node-negative T3 and T4 non-small cell lung cancer.
Methods: A total of 110 consecutive patients underwent surgical resection for invasive T3N0M0 (94 patients) and T4N0M0 (16 patients) non-small cell lung cancer between 1979 and 2008. Forty-seven patients received neoadjuvant chemotherapy and concurrent high-dose (5940 cGy) radiation therapy before resection (Chemo-RT group). Sixty-three patients underwent surgical resection without receiving induction chemoradiotherapy (Surg group), of whom 21 received neoadjuvant radiation, 19 received adjuvant radiation, 17 received surgery alone, 2 received adjuvant chemotherapy, 2 received adjuvant chemoradiotherapy, and 2 received brachytherapy. Survival of the Chemo-RT and Surg groups was compared using both crude and adjusted Cox proportional hazards models.
Results: The 5-year, 10-year, and median survivals were 61%, 50%, and 90 months, respectively, in the Chemo-RT group versus 22%, 14%, and 22 months, respectively, in the Surg group.