Neoadjuvant chemotherapy, as an addition of surgery, would significantly improve the overall survival of operable NSCLC patients, including patients with stage III NSCLC.

No abstract

Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) has been linked to carcinogenesis. However, the role of FHL1 in lung cancer remains unclear and the detailed mechanism underlying its tumor suppressive role is poorly understood. The purpose of this study was to examine FHL1 expression in lung cancer patients and to investigate how it was associated with lung cancer cell growth. Immunoblotting and immunohistochemistry showed that FHL1 protein was downregulated in over 90% of 80 lung cancer patients. FHL1 expression was strongly correlated with tumor histological types (p < 10 24 ) and the differentiation of the tumor (p 5 0.002). FHL1 inhibited anchorage-dependent and -independent growth of human lung cancer cell lines. The inhibitory effects of FHL1 on lung cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest concomitant with a marked inhibition of cyclin A, cyclin B1 and cyclin D as well as the induction of the cyclin dependent kinase inhibitors p21 (WAF1/CIP1) and p27 (Kip1). Direct intratumoral injection of an adenovirus expressing FHL1 dramatically suppressed the growth of A549 lung cancer cells in nude mice. Our data suggest that reduced expression of FHL1 may play an important role in the development and progression of lung cancer and that FHL1 may be a useful target for lung cancer gene therapy.

EESS for patients with CRSwNP and with asthma may help to improve the subjective olfaction and endoscopic appearance.

This study was designed to evaluate the distribution of Tregs/Th17/Th1 cells in type 2 diabetic patients with foot disease before and after human umbilical cord blood mesenchymal stem cell (hUCB-MSCs) transplantation. Fifteen diabetic patients with foot disease under insulin therapy received hUCB-MSC transplantation. The hUCB-MSCs were directly injected into the quadriceps thigh muscles in patients with foot disease (cell quantity at 2 x 10⁶ per point). Physical attributes, blood cytokines, blood glucose and insulin dosage were evaluated before treatment and 1, 2, 4, 8, and 12 weeks thereafter. The ratios of Treg/Th17, Treg/Th1, and Th17/Th1 cells were measured using flow cytometry and their correlation with various cytokines (FoxP3, IL-17, INF-γ, C-RP, TNF-α, and VEGF) was scrutinized. Levels of blood glucose and insulin dosage were significantly reduced in all 15 patients following hUCB-MSC transplantation. The ratios of CD4⁺CD25(hi)FoxP3⁺ Treg/Th17 and CD4⁺CD25(hi)FoxP3⁺ Treg/Th1 cells were significantly increased 4 weeks after transplantation (p < 0.01), while the ratio of Th17/Th1 cells remained unchanged. Serum levels of VEGF peaked at 4 weeks following transplantation. Levels of C-RP and TNF-α were significantly reduced 4 weeks after transplantation. Intriguingly, the ratios of Treg/Th17 were positively correlated with VEGF levels, and were inversely correlated with plasma IL-6 levels. Our data indicated that immune disorders are associated with the development of type 2 diabetes and its complications. Levels of blood glucose and required insulin dosage were reduced after hUCB-MSC transplantation accompanied with improved clinical profiles in diabetic patients. These data favor a role for Treg cells in the onset and progression of T2D.

The epidermal growth factor receptor (EGFR) activates downstream mTOR phosphorylation to promote the progression of many different tumor types, thus making it a prime therapeutic target. However, the role of DEP domain-containing mTORinteracting protein (DEPTOR), a natural mTOR inhibitor, remains unclear in this process. Here, it is reported that EGFR expression is significantly increased in tumors of lung adenocarcinoma patients and is negatively correlated with the expression of DEPTOR. Activation of EGFR signaling, by EGF, in A549 lung adenocarcinoma cells (overexpressing EGFR) significantly enhanced the function of the mTOR autoamplification loop, consisting of S6K, mTOR, CK1a, and bTrCP1, which resulted in downregulation of DEPTOR expression. Gefitinib, a specific EGFR inhibitor, stimulated DEPTOR accumulation by downregulating the function of the mTOR autoamplification loop. Furthermore, a series of assays conducted in DEPTOR knockout or ectopic expression in A549 cells confirmed that DEPTOR inhibited proliferation, migration, and invasion as well as the in vivo tumor growth of lung adenocarcinoma. Importantly, tumor progression mediated by EGFR ectopic expression was diminished by transfection with DEPTOR. This study uncovers the important inhibitory role of DEPTOR in lung adenocarcinoma progression and reveals a novel mechanism that EGFR downregulates DEPTOR expression to facilitate tumor growth.Implications: DEPTOR acts as a tumor suppressor by limiting EGFR-driven lung adenocarcinoma progression.

The surrogate markers for subclassifying eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS remain elusive. We herein performed a cross-sectional study to assess the clinical implication of clinical symptoms, CT findings, blood eosinophil (EOS) examination based on histological examination of tissue eosinophilia in 105 adult CRS patients (including 72 with nasal polyps and 33 without nasal polyps) in southern China. We found the mean score of smell loss was significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05), whereas the average ethmoid osteitis index in non-ECRS subgroup was significantly higher than that in ECRS subgroup (p < 0.05). Moreover, we found both the mean blood EOS number and ratio were significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05). By applying receiver operating characteristic (ROC) curve analysis, we found blood EOS number had a sensitivity of 84.9 % and specificity of 84.4 % [area under the curve (AUC): 0.873] at the cutoff level of 0.16 × 10(9)/L, and blood EOS ratio had a sensitivity of 89.0 % and specificity of 84.4 % (AUC: 0.863) at the cutoff level of 2.05 % in this cohort. Our findings indicated that smell loss score, ethmoid osteitis index and blood EOS number and ratio may be used for the differential diagnosis of ECRS as the surrogate markers.

Objectives: To clarify the utility of a safe and effective endoscopic procedure for closing frontal sinus cerebrospinal fluid (CSF) leaks. Methods: A retrospective review of all 15 patients seen at our hospital from 2002 to 2008 whose CSF leak originated within the frontal sinus or frontal recess. A transnasal endoscopic or combined transfrontal endoscopic approach was used to repair the CSF leak. Results and Surgical Outcomes: Four defects originated in the frontal recess and 11 involved the posterior wall of the frontal sinus. Nine patients were repaired by a direct endoscopic approach and 4 patients were repaired after widening the frontal recess endoscopically. Two patients were repaired using the combined transfrontal and transnasal approach. The leak was stopped in 14 cases (93%) after the first operation. One patient (7%) required a second repair 1 month after initial surgery and has remained well after 27 months. Complications included a frontal lobe abscess and a frontal sinus obstructive mucocele. These 2 patients were successfully treated without further complications. Patient follow-up ranged from 4 to 44 months (mean 30 months). Conclusions: Most frontal CSF leaks can be successfully closed by an endoscopic surgical approach.