C-Myc protein expression indicates unfavorable clinical outcome in surgically resected small cell lung cancer.

BACKGROUND: By being highly involved in the tumor evolution and disease progression of small cell lung cancer (SCLC), Myc family members (C-Myc, L-Myc, and N-Myc) might represent promising targetable molecules. Our aim was to investigate the expression pattern and prognostic relevance of these oncogenic proteins in an international cohort of surgically resected SCLC tumors. METHODS: Clinicopathological data and surgically resected tissue specimens from 104 SCLC patients were collected from two collaborating European institutes. Tissue sections were stained by immunohistochemistry (IHC) for all three Myc family members and the recently introduced SCLC molecular subtype-markers (ASCL1, NEUROD1, POU2F3, and YAP1). RESULTS: IHC analysis showed C-Myc, L-Myc, and N-Myc positivity in 48%, 63%, and 9% of the specimens, respectively. N-Myc positivity significantly correlated with the POU2F3-defined molecular subtype (r = 0.6913, p = 0.0056). SCLC patients with C-Myc positive tumors exhibited significantly worse overall survival (OS) (20 vs. 44 months compared to those with C-Myc negative tumors, p = 0.0176). Ultimately, in a multivariate risk model adjusted for clinicopathological and treatment confounders, positive C-Myc expression was confirmed as an independent prognosticator of impaired OS (HR 1.811, CI 95% 1.054-3.113, p = 0.032). CONCLUSIONS: Our study provides insights into the clinical aspects of Myc family members in surgically resected SCLC tumors. Notably, besides showing that positivity of Myc family members varies across the patients, we also reveal that C-Myc protein expression independently correlates with worse survival outcomes. Further studies are warranted to investigate the role of Myc family members as potential prognostic and predictive markers in this hard-to-treat disease.

Lymphocyte-to-monocyte ratio is an independent prognostic factor in surgically treated small cell lung cancer: An international multicenter analysis.

INTRODUCTION: The prognostic value of lymphocyte-to-monocyte ratio (LMR) has already been evaluated in a wide range of malignancies including patients with non-surgically managed small cell lung cancer (SCLC). However, the impact of LMR on survival in surgically treated SCLC patients has not yet been assessed. The aim of this study was to determine the clinical role of LMR in patients undergoing surgical resection for SCLC. MATERIALS AND METHODS: In this retrospective study, individuals receiving radical surgery for SCLC between January 2000 and December 2019 from three participating European institutions were included. LMR was calculated from the most recent blood test prior to surgery. Optimal cut-off values for LMR were determined and correlated with clinical data and survival outcomes. RESULTS: In total, 101 patients underwent surgical resection for SCLC during the study period. 76 (75.2%) received anatomic lung resection (defined as lobectomy or pneumonectomy), 63 (62.4%) were male and the median age was 63 (range 41-80) years. LMR > 2.50 significantly associated with improved overall survival (OS) (35.3 vs. 20.7 months, p = 0.032) and disease-free survival (DFS) (25.8 vs 18.5 months, p = 0.011). Moreover, multivariate Cox proportional hazard model identified LMR > 2.50 as an independent prognostic factor of longer OS (hazard ratio (HR) 0.617; 95% confidence interval (CI) 0.383-0.993; p = 0.047) and DFS (HR 0.505; 95% CI 0.266-0.959; p = 0.037). CONCLUSION: Preoperatively elevated LMR is a robust prognostic factor associated with improved OS and DFS in patients undergoing surgery for SCLC. Further studies are warranted to better understand the overall impact of LMR when applying surgery in these patients.

Autotrophic sulfide removal by mixed culture purple phototrophic bacteria.

Current H2S treatment methods for sour gases require considerable amounts of chemicals and energy, or in case of biological treatment, unwanted diluents such as oxygen or nitrogen may be introduced. In order to reduce those requirements, the viability of an anaerobic biological H2S removal process using purple phototrophic bacteria (PPB) was investigated in this study. PPB can use sunlight, and centrate as nutrient source, thus potentially reducing energy and chemical requirements. An added benefit is the production of biomass with potential uses, such as single cell protein. An inoculum of PPB enriched from domestic wastewater was grown photoautotrophically with sulfide as the electron donor and inorganic carbon in a mixed culture. Additionally, synthetic medium and centrate as well as high (56 ±â€¯11 Wm-2) and low (27 ±â€¯3 Wm-2) IR irradiation were trialled. Finally, a process model was developed to study biomass specific removal rates and yield. The results showed that a mixed culture of PPB removed sulfide completely in synthetic media (121 ±â€¯9 mg-S.L-1) at a maximum rate of 1.79 ±â€¯0.16 mg-S(Lh)-1 (low irradiance) and 2.9 mg-S(Lh)-1 (high irradiance). The pH increased in both experiments from about 8.5 to 9. Sulfide removal rates using centrate and low irradiance were similar. However Fe and Mn were found to be limiting growth and sulfide removal. In all experiments, Chromatiaceae (purple sulfur bacteria) were most abundant at the end of the experiment, while at the start purple non-sulfur bacteria were most abundant (from the inoculum). Process modelling and experimental work identified the sulfide oxidation to be a multi-step process with accumulation of intermediates. Specific rates were directly dependent on light input, doubling at high irradiance. Sulfide oxidation was estimated at 0.100 ±â€¯0.014 h-1 (0.085 ±â€¯0.012 g-S(g-VS.h)-1) at low irradiance, and the biomass yield at 0.86 ±â€¯0.05 mg-COD.mg-COD-1. This process model enables the virtual evaluation of autotrophic sulfide removal by PPB in a continuous scaled-up process. Overall, the photoautotrophic removal of sulfide seems to be a viable option, especially because of the possibility of using sunlight as an energy source and centrate as a nutrient source.