ABSTRACT
COPD, characterized by long-term poorly irreversible airway limitation and persistent respiratory symptoms, has resulted in enormous challenges to human health worldwide, with increasing rates of prevalence, death, and disability. Although its origin was thought to be in the interactions of genetic with environmental factors, the effects of environmental factors on the disease during different life stages remain little known. Without clear mechanisms and radical cure for it, early screening and prevention of COPD seem to be important. In this review, we will discuss the etiologic origins for poor lung function and COPD caused by specific adverse effects during corresponding life stages, as well as try to find new insights and potential prevention strategies for this disease.
Subject(s)
Air Pollutants/adverse effects , Air Pollution/adverse effects , Environmental Exposure/adverse effects , Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/etiology , Smoking/adverse effects , Age Factors , Epigenesis, Genetic , Female , Gene-Environment Interaction , Genetic Predisposition to Disease , Humans , Pregnancy , Prenatal Exposure Delayed Effects , Prognosis , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/prevention & control , Risk Assessment , Risk Factors , Smoking/physiopathology , Tobacco Smoke Pollution/adverse effectsABSTRACT
AIM: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an immune inhibitory receptor which is expressed within most types of hematopoietic cells and negatively regulates immune responses. Recently, we found LAIR-1 expression to be present within tumors of nonhematopoietic lineages. However, the roles of LAIR-1 in hepatocellular carcinoma (HCC) have yet to be examined. The purpose of this study was to investigate the expression of LAIR-1 in HCC tissue and assess its clinical significance at this site. MATERIALS AND METHODS: Expression levels of LAIR-1 within HCC samples collected from 90 patients and compared with that of slides of normal liver tissue collected from 9 non-HCC patients were measured by immunohistochemistry using tissue microarrays. A semiquantitative score was assigned, as was based on staining intensity and percent of positive cells and a Spearman Rank correlation test was used to assess any potential significant correlations between LAIR-1 expression and clinicopathological factors. Overall survival analysis was performed using the Kaplan-Meier and Log Rank statistical test. RESULTS: LAIR-1 expression was detected in cancer tissue and adjacent tumor tissue, but not in normal liver tissue. The percent of LAIR-1-positive expression in cancer tissue of HCC samples was 97.78% (88/90) while that in adjacent tumor tissue was 96.67% (87/90). Significantly greater expression levels of LAIR-1 were obtained from cancer tissue (Mean⯱â¯SDâ¯=â¯5.722⯱â¯2.145) than that in adjacent tumor tissue (4.141⯱â¯1.486). In addition, LAIR-1 expression was found to be significantly correlated with pathological grade of HCC, T stage, and age. Expression levels of LAIR-1 were related with worse overall survival rates of HCC patients, especially in HCC patients with hepatic cirrhosis. CONCLUSION: Results of this study show that LAIR-1 is expressed in HCC tissues and that high levels of LAIR-1 expression are associated with the poor cancer differentiation. In addition, overexpression of LAIR-1 was significantly associated with worse overall survival in the patients with HCC. These data suggest that LAIR-1 may be an independent predictor for clinical outcomes in patients with HCC.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/secondary , Liver Neoplasms/pathology , Receptors, Immunologic/metabolism , Adolescent , Adult , Aged , Carcinoma, Hepatocellular/metabolism , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Liver Neoplasms/metabolism , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young AdultABSTRACT
Previous studies have shown that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on most types of hamatopoietic cells and negatively regulate immune response, but the roles of LAIR-1 in tumor of the non-hematopoietic lineage have not been determined. Despite advances in therapy of epithelial ovarian cancer (EOC), many questions relating to EOC pathogenesis remain unanswered. The aim of this study was to investigate the clinical significance of LAIR-1 expression in EOC and explore the possible association between LAIR-1 and cancer. In this study, a tissue microarray containing 78 ovarian cancer cases was stained following a standard immunohistochemical protocol for LAIR-1 and the correlation of LAIR-1 expression with clinicopathologic features was assessed. LAIR-1 was detected to express in tumor cells of ovarian cancer tissues (73.1%) and EOC cell lines COC1 and HO8910, not in normal ovarian tissues. In addition, LAIR-1 expression correlates significantly with tumor grade (p = 0.004). Furthermore, down-regulation of LAIR-1 in HO8910 cells increased cell proliferation, colony formation and cell invasion. These data suggest that LAIR-1 has a relevant impact on EOC progression and may be helpful for a better understanding of molecular pathogenesis of cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Neoplasms, Glandular and Epithelial/metabolism , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Receptors, Immunologic/metabolism , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Grading , Neoplasm Invasiveness/pathologyABSTRACT
Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34(+)CD41a(+) and CD41a(+)CD42b(+) cells. LAIR-1 is also detectable in a fraction of human cord blood CD34(+) cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34(+) cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.
