1.A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone.
Li-jun LING ; Shui WANG ; Xiao-an LIU ; En-chao SHEN ; Qiang DING ; Chao LU ; Jian XU ; Qin-hong CAO ; Hai-qing ZHU ; Feng WANG
Chinese Medical Journal 2008;121(20):1980-1986
BACKGROUNDA satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.
METHODSHuman breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1 x 10(5), 1 x 10(6) human breast cancer stem-like cells, and 1 x 10(6) parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1 x 10(6) MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR).
RESULTSOur results demonstrated that cells in implanted human bones of group B, which received 1 x 10(6) cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P = 0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest.
CONCLUSIONSIn the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.
Animals ; Bone Neoplasms ; secondary ; Breast Neoplasms ; pathology ; CD24 Antigen ; analysis ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Hepatocyte Growth Factor ; pharmacology ; Humans ; Hyaluronan Receptors ; analysis ; Immunohistochemistry ; Mice ; Neoplastic Stem Cells ; pathology ; Osteopontin ; analysis ; Phenotype ; Receptors, CXCR4 ; analysis
2.Changes of NO2-/NO3- and nitration tyrosine concentrations in induced sputum of silicosis patients.
Kun WANG ; Rui WANG ; Zheng-liang LIU ; Jin-long MEN ; En-guang WAN ; Ling-min KONG ; Jin-peng WANG ; Chao SHEN ; Yang LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2009;27(1):30-33
OBJECTIVETo analyze the change in nitration tyrosine, NO(2)(-)/NO(3)(-)level in induced sputum of silicosis patients and dust exposure workers and to evaluate the approach and feasibility of nitric oxide (NO) metabolites as early detection indicators of silicosis.
METHODSNitration tyrosine, NO(2)(-)/NO(3)(-)concentration in induced sputum of 80 dust exposure workers, 84 silicosis patients, 30 logistic personnel with no history of exposure to silica dust were determined and the relationship among Nitration tyrosine, NO(2)(-)/NO(3)(-)level and dust exposure years as well as pulmonary function tests were analyzed.
RESULTSNO(2)(-)/NO(3)(-)level among exposed group [60.30 (46.58) micromol/l] was significantly higher than the control group [36.90 (22.28) micromol/l], (P < 0.05), and the level of NO(2)(-)/NO(3)(-)among the cases [79.65 (89.10) micromol/l] was significantly higher than exposed group as well as the control group (P < 0.05). Compared with control, the level of nitration tyrosine in exposed group [3.51 (0.46) nmol/l] and the cases [3.48 (0.49) nmol/l] was significantly higher (P < 0.05). NO(2)(-)/NO(3)(-)level and dust exposure years were positively correlated (r = 0.3733 and 0.3830 respectively P < 0.05); NO(2)(-)/NO(3)(-)level and pulmonary function tests (FVC%, FEV1.0%, PEF%, MEF25%, MEF50%) were negatively correlated (r = 0.1540, 0.1723, 0.1535, 0.1485, 0.1643 respectively, P < 0.05). There was no correlation between nitration tyrosine and dust exposure years (P > 0.05), no correlation between nitration tyrosine and pulmonary function test (P > 0.05).
CONCLUSIONThe level of NO(2)(-)/NO(3)(-)level in induced sputum has a positive correlation with exposure to dust, suggesting that there will be a certain feasibility of the NO(2)(-)/NO(3)(-)as indicators of early detection of silicosis.
Adult ; Humans ; Middle Aged ; Nitrates ; metabolism ; Nitrites ; metabolism ; Silicosis ; metabolism ; Sputum ; metabolism ; Tyrosine ; metabolism
3.Predictors of mortality in critically multiple trauma patients after damage control surgery.
Xiao-jun SHEN ; Xu-chao XUE ; Yao WANG ; Hao ZHANG ; Kang-kang ZHI ; Jian-wei BI ; Guo-en FANG
Chinese Journal of Surgery 2009;47(10):755-757
OBJECTIVETo investigate the efficiency of damage control surgery (DCS) and predictors of mortality in critically multiple trauma patients.
METHODSFrom May 1998 to February 2007, DCS were carried out in 27 patients with critically multiple trauma. Of the patients 15 cases survived (survival group) and 12 cases died (dead group). The surgical complications, causes of death, demographic, physiologic and medical parameters were collected and compared between the two groups. Multiple logistic regression analysis were performed to identify possible predictors of mortality.
RESULTSThe incidence of surgical complications was 37.0 percent, and the intra-abdominal infections was the most frequent (18.5%). The overall mortality rate was 44.4 percent. The most common causes of death was multiple organ dysfunction syndrome (50.0%). With respect to predicting mortality, statistically significant differences was found in parameters as age, injury severity score (ISS), initial temperature and base excess (BE), estimated blood loss, initial ICU temperature and length of hospital stay. Older age, increased absolute value of initial BE and lower initial ICU temperature were determined as independent predictors of mortality on multiple logistic regression analysis.
CONCLUSIONSThere is a comparable high morbidity and mortality rate in severely injured patients managed with DCS. Increased age, a larger absolute value of initial BE and lower initial ICU temperature could independently predict death of the patients.
Adolescent ; Adult ; Age Factors ; Aged ; Female ; Humans ; Injury Severity Score ; Logistic Models ; Male ; Middle Aged ; Multiple Trauma ; mortality ; surgery ; Multivariate Analysis ; Postoperative Complications ; Prognosis ; Temperature ; Young Adult