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Biomedical subjects

Ang Yuan

Publications and source records attributed to Ang Yuan.

At least 19 recordsLinked to original sources
PubMed2007

A five-gene signature and clinical outcome in non-small-cell lung cancer.

BACKGROUND: Current staging methods are inadequate for predicting the outcome of treatment of non-small-cell lung cancer (NSCLC). We developed a five-gene signature that is closely associated with survival of patients with NSCLC. METHODS: We used computer-generated random numbers to assign 185 frozen specimens for microarray analysis, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, or both. We studied gene expression in frozen specimens of lung-cancer tissue from 125 randomly selected patients who had undergone surgical resection of NSCLC and evaluated the association between the level of expression and survival. We used risk scores and decision-tree analysis to develop a gene-expression model for the prediction of the outcome of treatment of NSCLC. For validation, we used randomly assigned specimens from 60 other patients. RESULTS: Sixteen genes that correlated with survival among patients with NSCLC were identified by analyzing microarray data and risk scores. We selected five genes (DUSP6, MMD, STAT1, ERBB3, and LCK) for RT-PCR and decision-tree analysis. The five-gene signature was an independent predictor of relapse-free and overall survival. We validated the model with data from an independent cohort of 60 patients with NSCLC and with a set of published microarray data from 86 patients with NSCLC. CONCLUSIONS: Our five-gene signature is closely associated with relapse-free and overall survival among patients with NSCLC.

Aged↗
PubMed2006

Successful treatment of intractable hemothorax with recombinant factor VIIa in a nonhemophilic patient.

Recombinant factor VIIa (rFVIIa) was developed for the treatment of bleeding in hemophilic patients with inhibitors. It has also been used to stop bleeding in nonhemophilic patients who fail to respond to conventional treatment. We report a case of catastrophic hemothorax in which bleeding was stopped by administration of rFVIIa. A 68-year-old woman with chronic hepatitis C-related liver cirrhosis was admitted due to pneumonia and parapneumonic effusion. The patient developed hemothorax and hypovolemic shock after thoracentesis. Conventional therapies including tube thoracostomy and transarterial embolization failed to stop the life-threatening bleeding. The bleeding stopped after administration of rFVIIa 100 microg/kg/BW at 2-hour intervals for a total of two doses on the 3rd day of hospitalization. Despite intensive care, however, the patient died due to nosocomial infection and multiple organ failure on the 12th day of hospitalization. Hemothorax in a nonhemophilic patient can be successfully treated with rFVIIa.

Aged↗
PubMed2005

Transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma.

PURPOSE: In a previous genome-wide gene expression profiling analysis using an invasion cancer cell lines model, we have identified Slug as selectively overexpressed in the highly invasive cancer cells. Here, we investigated the clinical significance of Slug in lung adenocarcinoma and the role of Slug in the process of cancer cell invasion and metastasis. EXPERIMENTAL DESIGN: Real-time quantitative reverse transcription-PCR was used to investigate Slug mRNA in surgically resected lung adenocarcinoma of 54 patients and its correlation with survival. We overexpressed Slug in a lung adenocarcinoma cell line with very low Slug levels and investigated the in vitro and in vivo effects of Slug expression. RESULTS: High expression of Slug mRNA in lung cancer tissue was significantly associated with postoperative relapse (P = 0.03) and shorter patient survival (P < 0.001). The overexpression of Slug enhanced xenograft tumor growth and increased microvessel counts in angiogenesis assay. Both inducible and constitutive overexpression of Slug suppressed the expression of E-cadherin and increased the in vitro invasive ability. Zymography revealed increased matrix metalloproteinase-2 activity in Slug overexpressed cells. ELISA, reverse transcription-PCR, and immunohistochemistry confirmed the increase of matrix metalloproteinase-2 proteins and mRNA in Slug overexpressed cells and xenograft tumors. CONCLUSIONS: Slug expression can predict the clinical outcome of lung adenocarcinoma patients. Slug is a novel invasion-promoting gene in lung adenocarcinoma.

Adenocarcinoma↗
PubMed2005

Total cyclooxygenase-2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non-small cell lung cancer patients.

Interaction between cancer cells and adjacent stromal cells is important to promote tumor development. Our aim was to study total COX-2 mRNA expression in both cancer cells and surrounding stromal cells and its association with angiogenic factor VEGF mRNA expression, tumor angiogenesis and prognosis in patients with NSCLC. COX-2 mRNA expression in both cancer cells and stromal tissue was analyzed using real-time quantitative (RTQ) RT-PCR in 60 NSCLC surgical specimens. Immunohistochemistry (IHC) was used to localize COX-2 protein in tumor specimens. Correlations between tumoral total COX-2 mRNA expression and VEGF mRNA expression (measured by RTQ RT-PCR), intratumoral microvessel counts (evaluated by IHC), other clinicopathologic variables, survival and relapse were tested. COX-2 protein expression was found in cancer as well as the surrounding stromal cells (including infiltrating inflammatory cells and endothelial cells of tumor-associated microvessels). VEGF protein expression was mainly located in cancer cells. There was a significant association between high tumoral total COX-2 mRNA expression and high VEGF mRNA expression (p = 0.01) or high intratumoral MVC (p < 0.001) but not other clinicopathologic variables, including tumor status and lymph node metastasis. Patients with higher tumoral total COX-2 mRNA expression had a statistically shorter survival time (median 15.0 +/- 2.61 months) and relapse time (median 5.0 +/- 1.37 months) than those with lower tumoral total COX-2 mRNA expression (median 40.0 +/- 3.12 and 34.0 +/- 3.11 months; p < 0.0001 and p < 0.0001, respectively, log-rank test). A significant difference in survival and relapse time was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low intratumoral MVC (p = 0.0046 and p = 0.0038, respectively). After stratification by disease stage or histologic subtype, the prognostic significance of high total COX-2 mRNA expression was still apparent in both stage I and stage II-IV and in both squamous cell carcinoma and adenocarcinoma (p < or = 0.01 for all). Multivariate analysis using the Cox regression model with backward elimination showed that tumoral total COX-2 mRNA expression and lymph node status were the 2 most important independent prognostic predictors for survival and disease relapse. We report that total COX-2 mRNA expression in cancer cells and surrounding stromal cells correlates strongly and positively with VEGF mRNA expression, intratumoral MVC and adverse prognosis in NSCLC patients. This implies that COX-2 expression in both cancer cells and stromal cells within the tumor microenvironment may play an important role in upregulating the expression of the angiogenic factor VEGF and tumor angiogenesis in NSCLC and explains, in part, the adverse prognostic effect of COX-2 overexpression in patients with NSCLC.

Adenocarcinoma↗
PubMed2005

Infections in the survivors of out-of-hospital cardiac arrest in the first 7 days.

OBJECTIVE: To evaluate the incidence, risk factors, foci, isolated organisms, and outcomes of infections in the survivors of out-of-hospital cardiac arrest (OHCA) within the first 7 days after resuscitation. DESIGN AND SETTING: Retrospective cohort study in the intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: We enrolled 117 survivors of adult nontraumatic OHCA victims who survived more than 24 h between January 1999 and May 2004. We collected patients' demographics, the causes and initial electrocardiographic rhythm of cardiac arrest, and the process of cardiopulmonary resuscitation. The incidence, clinical presentations and outcomes of infections occurring in the first 7 days after resuscitation were evaluated. Variables were compared between the infected and noninfected patients. MEASUREMENTS AND RESULTS: Among our OHCA survivors asystole was the most common initial rhythm (66%). Eighty-three patients (71%) were found to have infection. Pneumonia was the most common infection (61%) followed by bacteremia (13%). Although the Gram-negative bacteria were responsible for most infections, the most commonly isolated organism was Staphylococcus aureus. The infection group had more patients with dementia and noncardiac causes of OHCA. The survival curves did not differ significantly between infection and non-infection groups. CONCLUSIONS: Infections were common in OHCA survivors during the first 7 days. The most common responsible organisms were Gram-negative bacteria, and the most commonly isolated organism was S. aureus. Infections in the early stage after return of spontaneous circulation did not change the hospital mortality and hospitalization duration.

Aged↗
PubMed2005

The role of interleukin-8 in cancer cells and microenvironment interaction.

Abstract Interleukin (IL)-8, a cytokine of the CXC chemokine family that was originally classified as a neutrophil chemoattractant, is now reported to play an important role in tumor progression and metastasis in a variety of human cancers, including lung cancers. IL-8 biologic activity in tumors and the tumor microenvironment may contribute to tumor progression through its potential function in the regulation of angiogenesis, cancer cell growth and survival, tumor cell motion, leukocyte infiltration and modification of immune responses. Recently, infiltrating macrophages in tumor stroma have been considered to be able to stimulate cancer growth, enhance angiogenesis and promote metastasis, and has prognostic significance in several human cancers. Accumulating evidence also shows that cancer cells and stromal cell interaction can stimulate cancer cells, as well as stromal cells in the expression of IL-8 and other growth factors. Here, we summarize current information about IL-8 biology in human lung cancers and focus on its effect on tumor angiogenesis, regulation of IL-8 expression in tumors, its prognostic significances, the role of tumor infiltrating macrophages in the production of IL-8 in cancer cells and the tumor microenvironment, gene expression profiles after cancer cell-stromal cell interaction, and the effect of a variety anti- inflammatory drugs on the modification of IL-8 and other gene expressions in cancer cells and the tumor microenvironment in lung cancers.

Anti-Inflammatory Agents↗
PubMed2005

Sialyl Lewis antigens: association with MUC5AC protein and correlation with post-operative recurrence of non-small cell lung cancer.

Sialyl Lewis antigens (sLe(x/a)) are cancer-associated carbohydrate determinants, serve as ligands of the selectin family and are associated with hematogenous metastasis of cancer. So far, the clinicopathologic values of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) in lung cancer have remained controversial. Using immunohistochemistry, the expressions of sLe(x) and sLe(a) antigens, and an airway mucin (MUC5AC) protein, which was supposed to be the major carrying protein of sialyl Lewis moieties, were studied in surgically resected tumor tissues of 61 patients with stages I or II NSCLC. Thirty-two (52.5%) of the 61 studied subjects were found to be positive for expression of sLe(a), 40 (65.6%) were positive for expression of sLe(x), and 16 (26.2%) were positive for MUC5AC protein. Both the expression of sLe(x) and MUC5AC were associated with adenocarcinoma subtype. Patients bearing tumors with MUC5AC and/or sLe(x) expression had a higher probability of post-operative distant metastasis. Survival analysis demonstrated that patients bearing tumors with expression of sLe(x) antigen or MUC5AC had shorter overall survival. The multivariate logistic regression showed that age >65 years old (OR = 0.207, 95% CI = 0.075-0.569, P = 0.002), nodal status (OR = 6.575, 95% CI = 2.459-17.583, P < 0.001), and MUC5AC (OR = 5.545, 95% CI = 1.998-15.386, P = 0.001) were independent factors affecting survival. We concluded that the expression of sLe(x) was related to MUC5AC protein, while patients with tumors co-expressing both MUC5AC and sLe(x) antigen had the worst survival.

Adult↗
PubMed2004

Tumor-associated macrophages: the double-edged sword in cancer progression.

PURPOSE: Inflammation plays a critical role in cancer progression. In this study we investigate the pro-tumorigenic activities and gene expression profiles of lung cancer cells after interaction with macrophages. MATERIALS AND METHODS: We measured intratumoral microvessel counts and macrophage density in 41 lung cancer tumor specimens and correlated these with the patients' clinical outcome. The interaction between macrophages and cancer cell lines was assessed using a transwell coculture system. The invasive potential was evaluated by in vitro invasion assay. The matrix-degrading activity was assayed by gelatin zymography. The microarray was applied to a large-scale analysis of the genes involved in the interaction, as well as to monitor the gene expression profiles of lung cancer cells responding to anti-inflammatory drugs in cocultures. RESULTS: The macrophage density positively correlated with microvessel counts and negatively correlated with patient relapse-free survival (P < .05). After coculture with macrophages, lung cancer cell lines exhibited higher invasive potentials and matrix-degrading activities. We identified 50 genes by microarray that were upregulated more than two-fold in cancer cells after coculture. Northern blot analyses confirmed some gene expression such as interleukin-6, interleukin-8, and matrix metalloproteinase 9. The two-dimensional hierarchical clustering also demonstrated that the gene expression profiles of lung cancer cells responding to various anti-inflammatory drugs in cocultures are distinct. CONCLUSION: The interaction of lung cancer cells and macrophages can promote the invasiveness and matrix-degrading activity of cancer cells. Our results also suggest that a great diversity of gene expression occurs in this interaction, which may assist us in understanding the process of cancer metastasis.

Adenocarcinoma↗
PubMed2004

Tracheal rupture complicating emergent endotracheal intubation.

Tracheal rupture is rare in clinical practice. We present 2 female patients with tracheal rupture after emergent endotracheal intubation from different injury mechanisms; penetrating injury of using stylet during intubation in one case and overinflation of cuff of the endotracheal tube under rapid sequence intubation in another. The lesions of rupture could be detected by bronchoscopy and reconstructive 3-dimensional computed tomography. Both cases received surgical repair without complication. In our report, reconstructive 3-dimensional computed tomography scrupulously detected the rupture sites and provided the noninvasive modality for diagnosis. We review the literature of tracheal rupture after emergent endotracheal intubation in respects of the diagnosis, the possible mechanisms of the injury, and suggest strategies of management.

Aged↗
PubMed2004

Cardiac troponin I levels are a risk factor for mortality and multiple organ failure in noncardiac critically ill patients and have an additive effect to the APACHE II score in outcome prediction.

Cardiac troponin I (cTnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). Recent studies have shown that cTnI levels can also be elevated in patients without ACS, such as in sepsis and trauma patients, and that this is associated with an adverse prognosis. We have evaluated the clinical implications and prognostic significance of serum cTnI levels in noncardiac critically ill patients in a prospective observational study in a general medical intensive care unit at a tertiary-level hospital. A total of 108 consecutive patients without ACS or other cardiac disease was enrolled. Serum cTnI levels were measured on admission using enzyme-linked immunoabsorbant assay kits. Clinical laboratory parameters and outcome were compared between patients with elevated and normal cTnI levels. The prognostic significance of cTnI levels and the Acute Physiology And Chronic Health Evaluation (APACHE) II score was also analyzed. Forty-nine patients (45%) had elevated cTnI levels and 59 (55%) had normal levels. Compared with patients with normal cTnI levels, patients with elevated levels had a higher incidence of new failure of two or more organs, had a lower left ventricular ejection fraction during admission, were more likely to be associated with bacteremia, and had a higher intensive care unit mortality; they also had a significantly shorter survival over a 180-day follow up, before and after stratification by the APACHE II score. Multiple organ failure was the leading cause of mortality in patients with elevated cTnI levels. By multivariate analysis, elevated cTnI levels, a high APACHE II score, and underlying cancer were the three most important independent predictors for a shorter survival. Combination analysis showed a shorter survival in patients with a high APACHE II score plus elevated cTnI levels than in patients with a high APACHE II score or elevated cTnI levels alone. In conclusion, elevated serum cTnI levels is a risk factor for multiple organ failure and mortality in noncardiac critically ill patients, and the cTnI levels and APACHE II score have an additive effect in outcome prediction.

Aged↗
PubMed2003

Clinical and microbiological characteristics of Rhizobium radiobacter infections.

Data obtained from 1996 to 2002 on 13 patients with Rhizobium radiobacter infections were analyzed. Ten patients (76%) had underlying hematological malignancy or solid-organ cancer. Six patients (46%) had febrile neutropenia during the course of R. radiobacter infection. The majority (54%) of infections were catheter-related bacteremia, and 92% of infections were hospital acquired. All the patients survived. Eighteen isolates were recovered from the 13 patients, and each isolate was susceptible to cefepime, piperacillin-tazobactam, carbapenems, and ciprofloxacin. The pulsed-field gel electrophoresis profiles differed among the isolates recovered from different patients, indicating the absence of nosocomial spread of the organism.

Adolescent↗