Yeung Leung Cheng

The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo3

The naturally‐occurring compound, n‐butylidenephthalide (BP), which is isolated from the chloroform extract of Angelica sinensis (AS‐C), has been investigated with respect to the treatment of angina. In this study, we have examined the anti‐tumor effects of n‐butylidenephthalide on glioblastoma multiforme (GBM) brain tumors both in vitro and in vivo. In vitro, GBM cells were treated with BP, and the effects of proliferation, cell cycle and apoptosis were determined. In vivo, DBTRG‐05MG, the human GBM tumor, and RG2, the rat GBM tumor, were injected subcutaneously or intracerebrally with BP. The effects on tumor growth were determined by tumor volumes, magnetic resonance imaging and survival rate. Here, we report on the potency of BP in suppressing growth of malignant brain tumor cells without simultaneous fibroblast cytotocixity. BP up‐regulated the expression of Cyclin Kinase Inhibitor (CKI), including p21 and p27, to decrease phosphorylation of Rb proteins, and down‐regulated the cell‐cycle regulators, resulting in cell arrest at the G0/G1 phase for DBTRG‐05MG and RG2 cells, respectively. The apoptosis‐associated proteins were dramatically increased and activated by BP in DBTRG‐05MG cells and RG2 cells, but RG2 cells did not express p53 protein. In vitro results showed that BP triggered both p53‐dependent and independent pathways for apoptosis. In vivo, BP not only suppressed growth of subcutaneous rat and human brain tumors but also, reduced the volume of GBM tumors in situ, significantly prolonging survival rate. These in vitro and in vivo anti‐cancer effects indicate that BP could serve as a new anti‐brain tumor drug.

Acetone extract of Bupleurum scorzonerifolium inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing telomerase activity

Bupleuri radix, a traditional Chinese herb, has been widely used to treat liver diseases such as hepatitis and cirrhosis. The acetone extract of Bupleurum scorzonerifolium (AE-BS) showed a dose-dependently antiproliferative effect on the proliferation of A549 human lung cancer cells. The IC(50) of AE-BS, i.e., the concentration required to inhibit proliferation of A549 cells, was 59 +/- 4.5 microg/ml on day 1. The IC(50) of AE-BS for WI38 human normal lung fibroblast cells, however, was significant higher than that for A549 cells (150 +/- 16 microg/ml, p< 0.01). After 72 hours of exposure, AE-BS (60 microg/ml) significantly reduced A549 cell proliferation to 33 +/- 3.2% of control. In TUNEL assay, A549 cells treated with AE-BS showed typical morphologic features of apoptosis, and the percentage of apoptotic cells was approximately 38 % on day 1. In the TRAP assay, AE-BS-treated cells demonstrated significantly lower telomerase activity on day 3. This result indicates that the AE-BS could suppress the proliferation of lung cancer cells via inhibition of telomerase activity and activation of apoptosis.

Activation of Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 via Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase Revealed a Isochaihulactone-Triggered Apoptotic Pathway in Human Lung Cancer A549 Cells

The novel lignan isochaihulactone inhibits cell proliferation and is an effective inducer of apoptosis in a variety of carcinoma cell lines. To determine the mechanisms underlying these effects, we examined isochaihulactone-induced changes in gene expression using oligodeoxynucleotide-based microarray screening of a human lung carcinoma cell line, A549. Isochaihulactone-inducible genes included the early growth response gene-1 (EGR-1) and nonsteroidal anti-inflammatory drug-activated gene (NAG-1). Isochaihulactone increased EGR-1 and then NAG-1 mRNA and protein expression. Pure isochaihulactone induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Isochaihulactone-induced increases in EGR-1 and NAG-1 expression were reduced by the mitogen-activated protein kinase kinase 1/2 inhibitor 2′-amino-3′-methoxyflavone (PD98059), and this effect was not blocked by the phosphatidylinositol 3-kinase/protein kinase B pathway inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002). Inhibition of isochaihulactone-induced NAG-1 expression by EGR-1 small interfering RNA blocked isochaihulactone-induced apoptosis in A549 cells, suggesting that induction of EGR-1 expression decreases survival of A549 cells. RNA interference using double-stranded RNA specific for NAG-1 also inhibited isochaihulactone-induced apoptosis, and cells transfected to increased NAG-1 expression had a greater apoptotic response to isochaihulactone and reduced colony formation efficiency. In addition, treatment of nude mice with isochaihulactone increased the in vivo NAG-1 expression as examined by immunohistochemistry from tumor biopsy. Isochaihulactone treatment increased the luciferase activity of NAG-1 in A549 cells transfected with the NAG-1 promoter construct. This induction increased expression of NAG-1 that was p53-independent and Sp1-dependent. Our findings suggest that NAG-1 expression is up-regulated by isochaihulactone through an ERK-dependent pathway involving the activation of EGR-1.

The impact of smoking in primary spontaneous pneumothorax.

BACKGROUND The crucial role of cigarette smoking in the development of pneumothorax is unclear because nonsmokers can also develop primary spontaneous pneumothorax. The purpose of this study was to clarify the pathophysiologic effects of cigarette smoking and its clinical correlations in primary spontaneous pneumothorax. METHODS Included were 115 specimens of lung tissue from patients with primary spontaneous pneumothorax who underwent video-assisted thoracoscopic surgery from January 2001 to December 2002. We reviewed the clinical features of 56 smokers and 59 nonsmokers with an average follow-up of 67 months. The pathologic findings of resected lung specimens were analyzed retrospectively. RESULTS There were no statistical differences in sex, age, body height, body weight, body mass index, or the presence of blebs/bullae on computed tomography scans of the lung or under thoracoscopy between the 2 groups. In the smoking group, patients had more extensive respiratory bronchiolitis (P < .001), a high prevalence of tobacco pigmentation (P < .001), and a higher recurrence rate without or after surgery than the nonsmoking group (57% vs 22%, P = .001 and 8.9% vs 1.7%, P = .02, respectively). Patients with extensive respiratory bronchiolitis had significantly higher nonoperative and postoperative recurrences than patients with nonextensive respiratory bronchiolitis (P = .004 and P < .001, respectively). CONCLUSION Cigarette smoking is associated with the pathophysiologic consequences of extensive respiratory bronchiolitis, which had a significant impact on the recurrence rates of primary spontaneous pneumothorax.

Simultaneous bilateral primary spontaneous pneumothorax

Objective:  While primary spontaneous pneumothorax (PSP) is common in adolescents and young adults, simultaneous bilateral PSP (SBPSP) is rare and can be life‐threatening if it progresses to tension pneumothorax. This study reviewed cases of PSP to identify the clinical features of SBPSP.

Middle mediastinal thymoma

Abstract:  Thymoma is a common primary neoplasm of the anterior mediastinum. However, it can also arise in other locations, including the neck, the posterior mediastinum, the lung, base of the skull and the pleural cavity. There are only three previous case reports of thymoma located in the middle mediastinum. This report describes a patient together with a review of the literature on middle mediastinal thymoma.

Usefulness of chest images for the assessment of pectus excavatum before and after a Nuss repair in adults

OBJECTIVES The aim of this study was to evaluate whether chest radiographs could offer useful information for the assessment of pectus excavatum (PE) before and after Nuss repair in adults. METHODS A total of 154 adults, with a mean age of 24.0 ± 5.0 years (range, 18-44 years), who underwent a Nuss repair of PE, with a mean follow-up of 42 months (range, 14-71 months), were included in this retrospective study. Sixty-two of these patients were also evaluated after the pectus bar removal, with a mean follow-up of 13 months (range, 6-44 months). The preoperative and postoperative imaging modalities were compared. RESULTS The preoperative mean Haller indices measured on computed tomography (CT) and chest radiographs were 4.61 ± 1.58 (range, 2.6-11.9) and 3.82 ± 1.17 (range, 2.0-10.2), respectively. The Pearson correlation coefficient between the two parameters was 0.757. The postoperative mean Haller index measured on chest radiographs was 2.86 ± 0.56 (range, 1.7-5.4) and showed statistically significant improvement compared with the preoperative index (P < 0.001). The mean sternovertebral (SV) distances detected on preoperative and postoperative (>6 months after surgery) lateral chest radiographs were 7.67 ± 1.89 cm (range, 2.5-12.9 cm) and 9.89 ± 1.80 cm (range, 4.6-15.0 cm), respectively, showing statistically significant improvement (P < 0.001). The mean sternovertebral (SV) distance in patients after the bar removal detected on lateral chest radiographs was 9.25 ± 2.14 cm, also showing statistically significant improvement compared with the preoperative value (P < 0.001). CONCLUSIONS Haller indices measured using chest radiographs and CT showed a strong correlation. Therefore, chest radiographs can be used as an alternative tool for the preoperative evaluation of PE. The Nuss operation significantly improved SV distances detected on lateral chest radiographs. Lateral chest radiographs can be used as a simple modality for the objective quantitative assessment of the anatomic results and follow-up of the Nuss operation in adults.

Standard uptake value of positron emission tomography in clinical stage I lung cancer: clinical application and pathological correlation

OBJECTIVES The aim of this study was to assess the standard uptake value in clinical stage I non-small cell lung cancer (NSCLC) and its correlation with pathological status and prognosis. METHODS We retrospectively reviewed 674 patients diagnosed with NSCLC between January 2002 and June 2005. Patients with clinical stage I diseases undergone a preoperative positron emission tomography-computed tomography scan followed by anatomic resection. We reviewed the clinical features of 152 patients with an average follow-up of 87 months. RESULTS We analysed the clinical features of 108 patients with stage I NSCLC and 44 patients with non-stage I NSCLC. There were no statistical differences in age, histological type, location or tumour differentiation between the two groups. In the Stage I group, the patients had lower maximum standard uptake value (SUVmax; 3.80 ± 3.17 vs 5.73 ± 3.65, P = 0.001), lower carcinoembryonic antigen (CEA) levels (2.86 ± 4.80 vs 9.11 ± 17.21 ng/ml, P = 0.027) and smaller tumour size (2.39 ± 0.98 vs 3.73 ± 2.04 cm, P < 0.001). The patients with higher SUVmax had a more advanced pathological stage, poorer tumour differentiation and larger tumour size. A higher SUVmax was an independent factor predicting an advanced pathological stage (SUVmax ≥ 3.3, odds ratio 3.246). The median survival of patients with SUVmax ≥ 3.3 and SUVmax <3.3 were 64.32 and 53.08 months, respectively (P = 0.654). CONCLUSIONS Higher preoperative 18-fluorodeoxyglucose uptake by a tumour was significantly associated with an advanced pathological stage but not correlated with a poorer prognosis. An aggressive preoperative work-up for occult N2 disease should be emphasized, avoiding inappropriate thoracotomy.

Intrathoracic Displacement of a Fractured Humeral Head due to Blunt Trauma

The incidence of a fractured humeral head penetrating into the thoracic cavity is extremely rare. A 46-year-old woman presented with moderate respiratory distress at the emergency department after being involved in a motor vehicle accident. Radiographic examinations revealed fractures of the second to fifth ribs on the left side along with hemopneumothorax and fracture-dislocation of the humeral head into the thoracic cavity. After initial stabilization, video-assisted thoracic surgery (VATS) was performed to remove the fractured humeral head, and this was followed by a hemiarthroplasty. In this case report, we have discussed significant aspects of this uncommon finding in order to alert surgeons of the potential risks associated with intrathoracic displacement of the fractured humeral bone in trauma patients.

Longstanding Tracheobronchial Foreign Body in an Adult

Foreign body aspiration in adults usually occurs in the elderly or in patients with underlying neurological impairment, excessive alcohol consumption, psychiatric diseases, Alzheimer disease, or head trauma.[1][1] Foreign body aspiration in young adults without these risk factors is rare, and