No abstract

The present study investigated expression profiles of the potential CSC markers including CD133, CD44, ALDH1, and β-catenin, and evaluated their prognostic value in lung adenocarcinomas. One-hundred-and-seventy-seven tumors (stage I) were immunohistochemically examined for the expression of these markers, and thresholds to subdivide expression levels were determined using receiver operating characteristics curves. Tumors with high levels of CD133 (adjusted hazard ratio (HR) 4.55 (95% confidence interval (CI) 1.26-16.40, P = 0.021), CD44 (HR 3.73, 95% CI 1.20-11.58, P = 0.023) or ALDH1 (HR 3.61, 95% CI 1.09-12.3, P = 0.036), but not β-catenin (HR 2.43, 95% CI 0.59-10.8, P = 0.220), showed a significantly higher risk of recurrence than the corresponding low expressers. In conclusion, levels of CD133, CD44, and ALDH1 had independent prognostic value to predict the recurrence of lung adenocarcinoma.

Wide coverage of the staple line with absorbable mesh is effective in preventing postoperative air leak and in decreasing the recurrence rates of PSP.

A new classification of adenocarcinoma (ADC) was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) in 2011. The present study evaluates its prognostic value in stage I disease of Japanese cases. One-hundred-and-seventy-nine cases with pathological stage I ADC were classified according to the new classification system and their association with disease recurrence was analyzed. Eighteen (10.1%) and 24 (13.4%) cases were adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), respectively. One-hundred-and-thirty-seven cases (76.5%) were invasive adenocarcinoma (IVA), in which 43 (24.0%) were lepidic (LEP), 59 (33.0%) were acinar (ACN), 16 (8.9%) were papillary (PAP), 1 (0.6%) was micropapillary (MPAP), 12 (6.7%) were solid predominant subtypes (SOL), and 6 (3.4%) were invasive mucinous adenocarcinoma (MUC). The5-year disease-free survivals (DFS) of patients with AIS and MIA were 100%. Those of LEP, ACN, PAP, SOL and MUC were 93.5%, 83.7%, 75.0%, 44.4% and 62.5%, respectively. Multivariate analysis showed that high-histological grade (SOL, MPAP, MUC) had an independent prognostic value to predict post-operative recurrence (HR 3.661, 95% CI 1.421-9.437, P = 0.007). In conclusion, the present study demonstrates a prognostic value of the 2011 IASLC/ATS/ERS classification of ADC in Japanese cases.

Vascular endothelial growth factor-A (VEGF-A

Abstract. Idiopathic interstitial pneumonia (IIP) is considered to be one of the risk factors for lung cancer (LC). However, therapeutic options for patients with LC complicated by IIP are not well established. In this study, we investigated the feasibility and efficacy of chemotherapy for patients with non-small cell lung cancer (NSCLC) complicated by IIP (NSCLC-IIP). We retrospectively analyzed 22 NSCLC-IIP patients who received chemotherapy. To determine how IIP affected the clinical outcomes in NSCLC, they were compared with 276 NSCLC patients without IIP, who were treated with chemotherapy alone. The response rate (partial response + stable disease) was 72.3% (17/22), whereas the incidence of acute exacerbation (AE) was 13.6% (3/22) in NSCLC-IIP patients treated with chemotherapy. NSCLC-IIP patients had significantly shorter survival compared with NSCLC patients without IIP (P<0.001) following chemotherapy, although the response rates to chemotherapy were not significantly different between the two groups. Multivariate analysis demonstrated that, in NSCLC patients receiving chemotherapy, IIP was a significantly unfavorable factor for progression-free and overall survival. Despite similar response rates to chemotherapy, NSCLC-IIP patients showed poorer prognosis than NSCLC patients without IIP, possibly due to the natural course of IIP. Chemotherapy may be a feasible option for NSCLC-IIP, if the risks of adverse effects are acceptable.

Our preliminary studies revealed that oncogenic KRAS (KRAS/V12) dramatically suppressed the growth of immortalized airway epithelial cells (NHBE-T, with viral antigen-inactivated p53 and RB proteins). This process appeared to be a novel event, different from the so-called premature senescence that is induced by either p53 or RB, suggesting the existence of a novel tumor suppressor that functions downstream of oncogenic KRAS. After a comprehensive search for genes whose expression levels were modulated by KRAS/V12, we focused on DUSP6, a pivotal negative feedback regulator of the RAS-ERK pathway. A dominant-negative DUSP6 mutant, however, failed to rescue KRAS/V12-induced growth suppression, but conferred a stronger anchorage-independent growth activity to the surviving subpopulation of cells generated from KRAS/V12-transduced NHBE-T. DUSP6 expression levels were found to be weaker in most lung cancer cell lines than in NHBE-T, and DUSP6 restoration suppressed cellular growth. In primary lung cancers, DUSP6 expression levels decreased as both growth activity and histological grade of the tumor increased. Loss of heterozygosity of the DUSP6 locus was found in 17.7% of cases and was associated with reduced expression levels. These results suggest that DUSP6 is a growth suppressor whose inactivation could promote the progression of lung cancer. We have here identified an important factor involved in carcinogenesis through a comprehensive search for downstream targets of oncogenic KRAS.

here is increasing awareness of the clinical importance of incidentally detected interstitial lung abnormalities (ILAs) on non-contrast-enhanced chest CT images (1). Large cohort studies (2-5) of lung cancer screening have reported that ILAs are present in 8%-10% of participants. ILAs have been associated with a greater risk of all-cause mortality (l,2). Miller et al ( 6) recently reported that some subclinical ILAs at CT represent an early stage or a mild form of pulmonary fibrosis. Moreover, ILAs influence survival in patients with advanced lung cancer (7). Outcomes are reported to be poorer in patients with lung cancer with idiopathic pulmonary fibrosis (IPF) than in patients without IPF (8-10). However, quantitative evaluation of ILAs in patients with lung cancer and their influence on survival have not yet been fully investigated.Many computer-aided detection (CAD) systems have been developed to quantify diffuse lung abnormalities at . Subpleural abnormalities at CT, as measured by using the Gaussian histogram normalized correlation (GHNC) system, correspond to a histologic usual interstitial pneumonia (UIP) pattern of fibrosis in patients with interstitial lung diseases (ILDs) (15).Thus, we hypothesized that the volume of ILAs at CT measured using a GHNC-CAD system would be associated with the UIP CT pattern and worse prognosis in patients with lung cancer. The purpose of this study was to quantify ILAs at preoperative CT by using a GHNC-CAD system and to evaluate the extent of ILAs as a predictor of disease-free survival (DFS) in patients with lung cancer. We also evaluated the