Prognostic Value of LC3B and p62 Expression in Small Intestinal Adenocarcinoma

Autophagy, a mechanism that maintains cellular homeostasis, is involved in tumor cell growth and survival in cancer, and autophagy inhibitors have been tested clinical trials for anticancer therapy. To elucidate the clinical and prognostic implications of autophagy in small intestinal adenocarcinoma (SIAC), we assessed the expression of autophagy markers, LC3B and p62, in 171 surgically resected primary SIACs using automated quantitative analysis. Positive LC3B, p62 nuclear (p62Nu), and p62 cytoplasmic (p62Cy) expression was observed in 23 (13.5%), 52 (30.4%), and 43 (25.1%) carcinomas, respectively. LC3B+ expression was correlated with undifferentiated carcinoma (p < 0.001) and high histologic grade (p = 0.029). The combined expression of LC3B and p62Nu (LC3+/p62Nu+) was related to the older age of patients (p = 0.017), undifferentiated carcinoma (p < 0.001), and high grade (p = 0.031). LC3B+ (p = 0.006), p62Cy+ (p = 0.041), or p62Nu+ (p = 0.006) expression were associated with worse survival. In addition, SIAC patients with either LC3B+/p62Nu+ (p = 0.001) or LC3B+/p62Cy+ (p = 0.002) expression had shorter survival times. In multivariate analysis, LC3B expression remained an independent prognostic factor (p = 0.025) for overall survival. In conclusion, autophagy may play a role in the tumorigenesis of SIACs, and LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for SIACs.

The Correlation Between Potential “Anti- Cancer” Trace Elements and the Risk of Breast Cancer: A Case-Control Study in a Chinese Population

BackgroundsBreast cancer is a heterogeneous disease without clear pathogenesis and effective primary prevention. The “anti-cancer” effects of several trace elements have received increasing attention in recent years. The main purpose of current study is to explore the differences of three potential “anti-cancer” trace elements selenium (Se), molybdenum (Mo), and strontium (Sr) between patients with malignant breast tumors and healthy controls.MethodsWe conducted a case–control study in 45 patients with malignant breast tumors as cases and 95 healthy volunteers as controls from Peking University Third Hospital, Beijing, China. The serum concentrations of trace elements were evaluated by using inductively coupled plasma mass spectrometry (ICP-MS).ResultsThe cases may have a lower Se levels when compared with controls (cases: 106.22 ng/ml, SD: 20.95 ng/ml; controls: 117.02 ng/ml, IQR: 22.79 ng/ml, p = 0.014). High levels of Se were a protective factor from breast cancer after adjusting the potential confounders of age, BMI, smoking, drinking, and menopause status (OR = 0.395, 95% CI, 0.178, 0.877, p = 0.023). The levels of Sr were lower in cases with high histologic grade when compared to low histologic grade (low histologic grade: 49.83 ng/ml, IQR: 41.35–62.60 ng/ml; high histologic grade: 40.19 ng/ml, IQR: 39.24–47.16 ng/ml, p &lt; 0.05).ConclusionsOur findings herein supported that Se has protective effects to avoid malignant breast tumors and Sr has protective effects to avoid poorly differentiated malignant breast tumors. Exploring “anti-cancer” related trace elements and their associations with breast cancer will assist for the early prevention and intervention for the disease.

Ameliorative Effect of Heat-Killed Lactobacillus plantarum L.137 and/or Aloe vera against Colitis in Mice

Inflammatory bowel disease (IBD) is one of the predominant intestinal diseases associated with chronic inflammation and ulceration of the colon. This study explored the ameliorative effect of Aloe vera extract (Aloe) and/or heat-killed Lactobacillus plantarum L.137 (HK L.137) on dextran sodium sulfate (DSS)-induced colitis in mice. Aloe and/or HK L.137 were supplied for 9 days and the mice were challenged with DSS for 7 days. The DSS group demonstrated bloody diarrhea, colitis of high histologic grade, increased nuclear factor-kappa B (NF-κB) p65, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α, and decreased IL-10 expression. These alterations were dwindled in DSS-induced mice treated with Aloe and HK L.137 separately. Aloe and HK L.137 together have augmented the therapeutic effect of each other. In conclusion, our findings demonstrated that Aloe and/or HK L.137 ameliorated DSS-induced colitis by promoting the secretion of anti-inflammatory cytokines and suppressing pro-inflammatory mediators. This study indicated that A. vera may function synergistically with HK L.137 to confer an effective strategy to prevent colitis.

Programmed Death Ligand-1 (PD-L1) Expression in Either Tumor Cells or Tumor-Infiltrating Immune Cells Correlates With Solid and High-Grade Lung Adenocarcinomas

Context.— Programmed death ligand-1 (PD-L1) expression in non–small cell lung carcinoma (NSCLC) is heterogeneous and known to be underestimated on small biopsies. Correlation of PD-L1 expression with clinicopathologic features may provide additional useful information. To our knowledge, the clinicopathologic features of NSCLC have not been reported for subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Objective.— To investigate the clinicopathologic characteristics of NSCLC subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Design.— PD-L1 immunohistochemistry with the SP142 clone was performed on whole-tissue sections and given semiquantitative scores (0/1/2/3) according to percent of PD-L1+ tumor cells (TCs) and percent tumor area with PD-L1+ tumor-infiltrating immune cells (ICs). Results.— Adenocarcinoma cases that were scored either TC 1/2/3 or IC 1/2/3 included most (22 of 34; 65%) high–histologic grade cases and most (25 of 36; 69%) solid subtype cases. Compared with the adenocarcinoma TC 0 and IC 0 subset, the TC 1/2/3 or IC 1/2/3 subset correlated with higher histologic grade (P = .005, χ2 test for trend) and solid subtype (P &lt; .001, Fisher exact test). Compared with the adenocarcinoma TC 0/1 or IC 0/1 subset, the TC 2/3 or IC 2/3 subset correlated with higher histologic grade (P = .002, χ2 test for trend), solid subtype (P &lt; .001, Fisher exact test), and higher smoking pack-years (P = .01, Mann-Whitney test). Conclusions.— Lung adenocarcinoma subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells correlated with high histologic grade, solid subtype, and high smoking pack-years.

A High Ki67/BCL2 Index Could Predict Lower Disease-Free and Overall Survival in Intestinal-Type Gastric Cancer

Background: The heterogeneity of gastric cancer makes the identification of potential prognostic indicators particularly important. The Ki67 and BCL2 proteins are known prognostic markers for different types of cancer. Ki67 is associated with cell proliferation, whereas BCL2 has antiproliferative roles. A combined marker based on these opposite functions might provide improved prognostic information in gastric cancer. Method: Ki67 and BCL2 expression was assessed in 276 gastric adenocarcinoma tissue microarrays. A Ki67/BCL2 index based on the relative expression of each protein was divided into low- and high-risk groups using receiver operating characteristic curves. Results: A high Ki67/BCL2 index significantly correlated with advanced stage, recurrence, intestinal type, high histologic grade, and lymphatic and perineural invasion (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between disease-free or overall survival and the Ki67/BCL2 index in intestinal-type gastric cancer (all p < 0.05). Conclusions: A combined marker using Ki67 and BCL2 could be a useful indicator for predicting survival in patients with intestinal-type gastric cancer.