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Gefitinib is an essential drug for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. The approved dosage is 250mg/body/day without adjustment for physical size such as body surface area (BSA), and the impact of physical size on the efficacy of gefitinib has not been evaluated. Here, we sought to clarify this issue using a retrospective cohort. We reviewed the medical records of patients with consecutive advanced NSCLC harboring EGFR mutations who underwent gefitinib monotherapy at Okayama University Hospital. In total, 101 patients were included in this study, and the median BSA in this cohort was 1.5m 2 . The median progression-free survival (PFS) of the patients with higher BSA (≥1.5m 2 ) was significantly worse than that of those with lower BSA ( 2 ) (10.4 vs. 18.0 months; p =0.019, log-rank test). Multivariate analysis also showed a significant impact of BSA on PFS (hazards ratio, 2.34; 95% confidence interval, 1.78–2.89; p =0.002). By contrast, no significant association between BSA and PFS was observed in those undergoing cytotoxic chemotherapy (4.0 vs. 5.1 months; p =0.989, log-rank test), suggesting that BSA is a predictive, rather than a prognostic, marker for gefitinib therapy in EGFR -mutated NSCLC. In conclusion, BSA affected PFS in patients with EGFR -mutated NSCLC who underwent gefitinib monotherapy, suggesting the need for appraisal of BSA-based dose adjustment, even for this molecular target-based therapy.

Regulation of cytotrophoblast differentiation toward extravillous trophoblasts (EVTs) is critical for establishing successful pregnancy. Previous studies have focused primarily on the factors promoting the differentiation, while inhibitory regulators except hypoxia have been less documented. In this study, to test our hypothesis that angiotensin II (Ang II) would inhibit EVT differentiation, we investigated the effects of Ang II on trophoblast outgrowth and the expression of molecules associated with the proliferation and invasion of trophoblasts using human first trimester villous explant cultures. Ang II increased EVT outgrowth and the number of cells in cell columns. Moreover, Ang II-treated explants exhibited increased Ki67 and integrin alpha5 immunoreactivity in EVTs as well as matrix metalloproteinase-2 activity in the conditioned media, and decreased alpha1 integrin immunoreactivity, which are compatible with the features of the proliferative phenotype EVTs. These effects of Ang II were similar to those of hypoxia (3% O(2)). Ang II stimulated the expression of hypoxia inducible factor-1alpha at both mRNA and protein levels, and also enhanced the expression of plasminogen activator inhibitor-1 (PAI-1). Data presented herein suggest a possible role for Ang II in impairing trophoblast differentiation toward an invasive phenotype, which might be associated with shallow invasion in preeclamptic placentas.

normalized platelet number. IL-6 and IL-10 levels did not show differences between L-NAME and silibinin groups. Histopathologic lesions in liver of the L-NAME group showed loss of polyedric shape of hepatocyte and acinar architecture. Intense mononuclear inflammatory infiltrate and thickening of muscle tunica of arterial vessel were observed mainly in periportal area. Silibinin treatment produced significant attenuation of the periportal inflammatory infiltrate observed in the L-NAME group, showing an association between inflammatory infiltrate and TNF-alpha, IL-1 and IFN-gamma levels. Conclusion: The silibinin treatment in different periods of pregnancy showed that this flavonoid displays anti-inflammatory and immunomodulatory actions that may contribute to its hepatoprotective effects. FAPESP: Grant no. 2006/07095-3