Clinical significance in the number of involved lymph nodes in patients that underwent surgery for pathological stage III-N2 non-small cell lung cancer

<p>Abstract</p> <p>Purpose</p> <p>This study investigated whether the number of involved lymph nodes is associated with the prognosis in patients that underwent surgery for pathological stage (p-stage) III/N2 NSCLC.</p> <p>Subjects</p> <p>This study evaluated 121 patients with p-stage III/N2 NSCLC.</p> <p>Results</p> <p>The histological types included 65 adenocarcinomas, 39 squamous cell carcinomas and 17 others. The average number of dissected lymph nodes was 23.8 (range: 6-55). The average number of involved lymph nodes was 5.9 (range: 1-23). The 5-year survival rate of the patients was 51.0% for single lymph node positive, 58.9% for 2 lymph nodes positive, 34.2% for 3 lymph nodes positive, and 30.0% for 4 lymph nodes positive, and 20.4% for more than 5 lymph nodes positive. The patients with either single or 2 lymph nodes positive had a significantly more favorable prognosis than the patients with more than 5 lymph nodes positive. A multivariate analysis revealed that the number of involved lymph nodes was a significant independent prognostic factor.</p> <p>Conclusion</p> <p>Surgery appears to be preferable as a one arm of multimodality therapy in p-stage III/N2 patients with single or 2 involved lymph nodes. The optimal incorporation of surgery into the multimodality approach therefore requires further clinical investigation.</p

Emerging ethnic differences in lung cancer therapy

Although global clinical trials for lung cancer can enable the development of new agents efficiently, whether the results of clinical trials performed in one population can be fully extrapolated to another population remains questionable. A comparison of phase III trials for the same drug combinations against lung cancer in different countries shows a great diversity in haematological toxicity. One possible reason for this diversity may be that different ethnic populations may have different physiological capacities for white blood cell production and maturation. In addition, polymorphisms in the promoter and coding regions of drug-metabolising enzymes (e.g., CYP3A4 and UGT1A1) or in transporters (e.g., ABCB1) may vary among different ethnic populations. For example, epidermal growth factor receptor (EGFR) inhibitors are more effective in Asian patients than in patients of other ethnicities, a characteristic that parallels the incidence of EGFR-activating mutations. Interstitial lung disease associated with the administration of gefitinib is also more common among Japanese patients than among patients of other ethnicities. Although research into these differences has just begun, these studies suggest that possible pharmacogenomic and tumour genetic differences associated with individual responses to anticancer agents should be carefully considered when conducting global clinical trials

Interactome Analyses Identify Ties of PrPC and Its Mammalian Paralogs to Oligomannosidic N-Glycans and Endoplasmic Reticulum-Derived Chaperones

The physiological environment which hosts the conformational conversion of the cellular prion protein (PrPC) to disease-associated isoforms has remained enigmatic. A quantitative investigation of the PrPC interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrPC paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrPC and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrPC with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrPSc. A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrPC organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins