Expression of PD1 and BTLA on the CD8+ T Cell and γδT Cell Subsets in Peripheral Blood of Non-Small Cell Lung Cancer Patients / 中国医学科学杂志(英文版)

Objective To investigate the expression and regulation of programmed cell death protein 1 (PD1), B lymphocyte and T lymphocyte attenuator (BTLA) in peripheral blood of patients with non-small cell lung cancer (NSCLC); to examine the correlation of the mRNA levels between PD and BTLA in NSCLC. Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8+ T cells and γδ+ T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals. We compared the expression of PD1 and BTLA on the surfaces of γδ+ T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid. The correlations of PD1 and BTLA, as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform. Results The frequency of PD1 on the surfaces of CD8+ T cells was significantly higher than that of the γδT cells in both healthy controls (t=2.324, P=0.024) and NSCLC patients（t=2.498, P=0.015). The frequency of PD1 on CD8+ T cells, rather than on γδ+ T cells, was significantly upregulated in advanced NSCLC patients compared with that in healthy controls (t=4.829, P<0.001). The PD1+ BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients (t=2.422, P=0.0185). No differences in percentage of PD1+γδ+ and BTLA+γδ+ T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment. PD1 was positively correlated with BTLA in both lung adenocarcinoma (r=0.54; P<0.05) and lung squamous cell carcinoma (r=0.78; P<0.05). Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8+ T cells and γδT cells in advanced NSCLC, suggesting that these molecules were involved in regulating the inactivation of CD8+ T cells and γδ+ T cells, immune escape and tumor invasion.

Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice

Objective Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity.Materials and methods NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-α, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples.Results All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent.Conclusion In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress. Arch Endocrinol Metab. 2015;59(3):202-9.

Papel da imuno-histoquímica no diagnóstico do câncer de pulmão: [revisão] / Role of immunohistochemistry in the diagnosis of lung cancer: [review]

O propósito da imuno-histoquímica é reconhecer antígenos e assim identificar e classificar células específicas dentro de uma população celular morfologicamente heterogênea (ou aparentemente homogênea). A visualização do complexo antígeno-anticorpo é possível pela adição de um fluorocromo conjugado ao anticorpo, que pode então ser observado ao microscópio, ou alternativamente uma enzima, cujo produto de reação pode igualmente ser visualizado. A imuno-histoquímica pode ser aplicada na rotina diagnóstica complementar do câncer de pulmão para a identificação de marcadores biológicos diagnósticos e prognósticos. Os painéis imuno-histoquímicos mínimos necessários para a complementação diagnóstica serão discutidos nesta revisão.

The role of immunohistochemistry is to recognize antigens and, consequently, to identify and classify specific cells within a cell population whose morphology is heterogenous or apparently homogenous. The visualization of the antigen-antibody complex is made possible through the addition of either a fluorochrome conjugate or an enzyme to the antibody, which is then viewed under microscopy. Immunohistochemistry can be used in the routine diagnosis of lung cancer, in order to identify biological markers (diagnostic and prognostic). The essential immunohistochemistry panels will be discussed in this review.

Clinical significance of insulin-like growth factor-1 receptor expression in stage I non-small-cell lung cancer: immunohistochemical analysis

BACKGROUND/AIMS: The insulin-like growth factor (IGF) system has been implicated in tumor growth, invasion, and metastasis. However, reports on the IGF-1 receptor (IGF-1R) based on radioimmunoassays are conflicting, and its prognostic implications in non-small-cell lung cancer (NSCLC) are still controversial. METHODS: Seventy-one paraffin-embedded tissue sections from stage I NSCLC patients were stained using a mouse monoclonal antibody against human IGF-1R. RESULTS: The intensity and frequency of IGF-1R expression on the membrane and cytoplasm of cancer cells was evaluated and scored using a semiquantitative system. IGF-1R expression was detected in nine of 71 (12.7%) cases. No significant relationship was found between clinical/histopathological parameters and IGF-1R expression. None of the patients whose tumor expressed IGF-1R had experienced distant metastasis or cancer-related death, although the difference did not reach statistical significance. CONCLUSIONS: We conclude that IGF-1R expression may not be a major prognostic factor for stage I NSCLC.

Detection of Malignant Cells in Pleural Fluid or Ascites by CD44v8-10/CD44v10 competitive RT-PCR

BACKGROUND: CD44 is a cell surface adhesion molecule which has been implicated in various biologic functions as lymphocyte homing and activation, cellular migration and extracellular matrix adhesion. Over-expression of CD44v8- 10 has been found in several cancers and is considered to be associated with tumor progression and metastasis. Recently, a novel molecular method, CD44v8- 10/CD44v10 competitive reverse transcription-polymerase chain reaction(RT-PCR) has been developed for detecting cancer cells over-expressing CD44v8-10. METHODS: We analyzed from benign and malignant pleural effusion and ascites by CD44 competitive RT-PCR and compared to the conventional cytology. RESULTS: The CD44 competitive RT-PCR analysis showed that all the 24 samples associated with benign disease presented a predominant expression of the CD44v10 transcript (v8-10/v10 ratio: 0.126-0.948), whereas 6 of 7 malignant pleural samples associated with cytology positive cancer expressed the CD44v8-10 transcript (v8-10/v10 ratio > 1.00). CONCLUSION: These results indicate that CD44 competitive RT-PCR assay is a useful and adjunct to cytological examination in cancer diagnosis, especially in detecting exfoliated cancer cells in pleural effusion.