[The diagnostic value of flexible bronchoscopy in tracheobronchopathia osteochondroplastica].

OBJECTIVE: To enhance the knowledge of tracheobronchopathia osteochondroplastica (TO), and to describe the value of flexible bronchoscopic diagnosis and treatment for the disease. METHODS: The clinical data, bronchoscopic findings, histological results and the methods and effect of bronchoscopic treatment in 10 patients with TO admitted to Xiangya Hospital between June 2006 and July 2007 were retrospectively analyzed. RESULTS: There were 8 males and 2 females (mean age 46 +/- 16, range 33-76 years). The bronchoscopic appearance of TO was multiple whitish, hard nodules projecting into the tracheal lumen (mostly from the anterior and less from the lateral walls). The lesions were found most frequently in the trachea and major bronchi, and lobar and segmental bronchi were involved less frequently. Nodules were restricted to the anterolateral walls in 7 cases. The distribution of the lesions was diffuse in 5, confluent in 2 and scattered in 3 cases. Six patients received bronchoscopic management, including radiofrequency treatment for 2 patients and argon ion laser treatment for the other 4. The lesions in the airways were reduced and clinical symptoms improved to some extent after treatment. No severe complications occurred during and after the procedures. CONCLUSIONS: The diagnosis of TO can be easily underdiagnosed or misdiagnosed. Flexible bronchoscopy with histological examination is the main method for the diagnosis of TO. Radiofrequency and argon ion laser treatment are safe and effective.

[Medical thoracoscopy in the diagnosis of complicate pleural effusion].

OBJECTIVE: To evaluate the role of medical thoracoscopy in the diagnosis of the pleural effusion of unknown etiology. METHODS: The results of 36 patients with the pleural disease of unknown etiology diagnosed by medical thoracoscopy were retrospectively analyzed, including the pathologic results and the complications. RESULTS: Among the 36 patients, 35 were determined with positive rate of 97.2%, and no serious complications was found. CONCLUSION: Medical thoracoscopy is an important method of diagnosing complicate pleural effusion, and has high positive rate. It is a simple operation, with no serious complication, and fast recovery.

Multinodule abnormalities of the tracheobronchus: bronchoscopy findings and clinical diagnosis.

BACKGROUND AND AIMS: Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear. OBJECTIVES: The aim of this study was to describe the clinical characteristics of multiple nodule tracheobronchial abnormalities found under bronchoscopy caused by different diseases. METHODS: Eighty-seven patients with multiple tracheobronchial nodules were enrolled in this study. The characteristics of the multinodule lesions and the patient were diagnosed based on the pathology findings in our hospital. Chest computed tomography images were retrospectively reviewed by pulmonologists and radiologist. RESULTS: In 55 patients with definite pathological diagnosis, 16 (29%) patients were diagnosed as tuberculosis (TB) granuloma; 23 (41.8%) cases were diagnosed as malignant disease; 12 (21.8%) cases were diagnosed as tracheobronchopathia osteochondroplastica; 2 (3.6%) cases were diagnosed as sarcoidosis; and one case (1.8%) was diagnosed as lymphoma and one case (1.8%) as fungal infection. There were 32 cases of chronic inflammation. There was no relationship between nodule distribution and the pathological diagnosis. Malignant nodules usually smaller with a pale outlook, while nodules with larger size and smooth and intact mucosa usually turn out to be granuloma of unknown reason. CONCLUSION: The major causes of mutinodule lesions observed using bronchoscopy are tumor and TB. The presence of multiple endotracheobronchial nodules suggest that pulmonary lesion is present, and biopsy should be performed. Malignant nodules can be diagnosed by appearance and biopsy. Pathology results of TB, sarcoidosis and fungal infection can turn out to be granuloma of unknown reason. Further diagnosis needs other clinical materials.

EGCG induces lung cancer A549 cell apoptosis by regulating Ku70 acetylation.

Lung cancer is the leading cause of cancer-related death worldwide. (-)-Epigallocatechin-3-gallate (EGCG) is a potential chemopreventive and therapeutic agent for lung cancer. Induction of apoptosis was examined using Annexin V/PI double staining flow cytometry. Western blot analysis detected the protein expression of cleaved caspase-3, Bax and Bcl-xL. Co-immunoprecipitation was used to detect the interaction of Ku70-Bax and the acetylation status of Ku70. Treatment of A549 cells with EGCG-induced apoptosis via increased expression of cleaved caspase-3 and Bax, but decreased expression of Bcl-xL. EGCG upregulated the K70 acetylation status of A549 cells and downregulated the interaction of Bax-Ku70 in a concentration- and time-dependent manner. The apoptosis-promoting effect of EGCG on A549 cells was obviously weakened, along with strengthening of the Bax-Ku70 interaction, after pCDNA3.1(+)-Ku70 plasmid and pCDNA3.1(+)-Ku70539/542R plasmid transfection. Our results established a role of EGCG in inducing cell apoptosis by suppressing Bax activity. Regulating Ku70 acetylation by EGCG, that block the interaction between Ku70 and Bax, will result in lung cancer cell apoptosis.

Myelomatous pleural effusion as an initial sign of multiple myeloma-a case report and review of literature.

OBJECTIVE: Discuss and improve the understanding of the clinical characters and diagnostic methods of myelomatous pleurisy, particularly of the patients with pleural effusion as an initial manifestation. BACKGROUND: A 53-year-old male, who had been misdiagnosed as tuberculous pleurisy in a local hospital, was diagnosed as multiple myeloma (MM) with pleural infiltration. We reviewed the literature on clinical manifestations, serum and pleural effusion characters, treatment and diagnostic options of this exceptionally rare presentation of MM. METHODS: We conducted a search of the published medical literature since 2000 in MEDLINE and PubMed using search criteria [("pleural effusion" and "MM") or "myelomatous pleural effusions"]. The search led to 64 case reports, and 16 cases with pleural effusion as an initial manifestation were included in this review. We have also searched for recent advances in diagnosis. RESULTS AND CONCLUSIONS: Myelomatous pleurisy is a rare complication of MM. Its clinical and laboratory findings are non-specific. Definitive diagnosis relies on the histopathology of pleural biopsy or pleural effusion. Thoracoscopic pleural biopsy is reliable, safe and effective. Chemotherapy is the mainstay of treatment for myelomatous pleural effusion. However, the response rate is low with an overall median survival time of 4 months.

Biological characteristics and epidermal growth factor receptor tyrosine kinase inhibitors efficacy of EGFR mutation and its subtypes in lung adenocarcinoma.

Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be present in lung adenocarcinoma (LAC). In this study, we extensively investigated the impact of patients' biological characteristics on EGFR mutation and the impact of EGFR mutation subtypes on targeted therapy of advanced LAC. We examined EGFR exons18to21status in169 LAC patients by direct sequencing to study the impact of patients' biological characteristics on the EGFR mutational spectrum. And then, 59 patients with advanced LAC harboring EGFR exon 19 deletions(del 19) or exon 21 point mutation(L858R) mutations received first-line treatment of gefitinib or erlotinib, the efficacy of treatment, and the progression-free survival (PFS) of these patients were recorded. The frequency of the EGFR mutation and its subtypes and the variables associated with the EGFR mutation after removing the confound factors were investigated by the logistic analysis using all samples (n = 169). The EGFR mutation was significantly associated with well-differentiated tumor and excessive household cooking fumes(P < 0.05). The deletions in exon 19 were more frequently associated with well-differentiated tumor (P < 0.05). The overall frequency of the EGFR mutation was 49 %. Then the impact of EGFR mutation subtypes on targeted therapy were investigated by the retrospective analysis on 59 advanced LAC patients with del 19 or L858R mutations and treated first-line with erlotinib or gefitinib. The deletions in exon 19 got longer PFS (P < 0.05). But there were no differences in PFS between erlotinib therapy and gefitinib therapy. EGFR mutations were more frequently in high tumor differentiation and excessive household cooking fumes LAC. The del 19 mutation rate is relatively high with a high differentiation degree in advanced lung adenocarcinoma. The deletions in exon 19 may benefit more from first-line targeted therapy of advanced LAC compared with exon 21 point mutation L858R. There was no significant difference between the efficacy of gefitinib and erlotinib treatments associated with EGFR mutation and its subtypes.

Treatment with EGCG in NSCLC leads to decreasing interstitial fluid pressure and hypoxia to improve chemotherapy efficacy through rebalance of Ang-1 and Ang-2.

AIM: Microvasculature and microenvironment play important roles in proliferation, invasion, metastasis and prognosis in non-small cell lung cancer (NSCLC), which might be altered by many anti-angiogenic drugs. Epigallocatechin-3-gallate (EGCG), a natural anti-angiogenesis agent refined from green tea, was defined to have multiple effects on angiogenesis factors, such as endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and angiopoietins (ANGs). Hypothesizing that EGCG might regulate microvasculature and microenvironment in NSCLC, the effects of EGCG on microvessel density (MVD), expression of Ang-1 and Ang-2, interstitial fluid pressure (IFP), tumor hypoxia, and chemotherapy sensitivity were examined. METHODS AND RESULTS: EGCG treatment of A549 cells in mice bearing xenografts in vivo led to a significant decrease of MVD detected by CD31, and of Ang-2 expression detected by quantum dots double-label immunofluorescence assessment, while Ang-1 decreased with no significance. Decreased IFP was measured by the Wink-in-needle method, while hypoxia was assessed by polarographic electrode and pimonidazole (PIMO) immunohistochemistry. Assuming that these changes would increase response to chemotherapy, tumor growth studies were p[erformed in nude mice with xenografts, which were then treated with EGCG and the chemotherapeutic agent cisplatin. EGCG therapy combined with cisplatin led to synergistic inhibition of tumor growth, compared with administration of each treatment separately (P < 0.001). According to linear regression analysis, IFP was positively correlated with PIMO staining (R(2) = 0.618, P = 0.002), Ang-2 was correlated with MVD (R(2) = 0.423, P = 0.022), IFP (R(2) = 0.663, P = 0.01) and PIMO staining (R(2) = 0.694, P = 0.01). CONCLUSION: IFP and delivery of oxygen might be improved by rebalance of Ang-1/Ang-2 under the treatment of EGCG in NSCLC, which also acts as a sensitizer of chemotherapy. These studies established a new mechanism for using EGCG as an adjuvant chemotherapy agent through modifying microvasculature and microenvironment.

Role of Ku70 and Bax in epigallocatechin-3-gallate-induced apoptosis of A549 cells in vivo.

EGCG (epigallocatechin-3-gallate), the major catechin found in green tea, has been demonstrated to inhibit proliferation and induce apoptosis in a number of types of tumors. Recent studies reveal that EGCG has various anticancer effects. This study investigated a further possible molecular mechanism of the anticancer effects of EGCG in murine lung cancer xenografts. In the study, A549 human lung cancer cells were injected into nude mice. Tumor volume was used to measure cancer cell growth. The weight of the animals was used to assess the toxicity of the drugs. The expression of protein and mRNA was assayed by western blot analysis and RT-PCR, respectively. The interaction between Bax and Ku70 was determined by immunoprecipitation. Our results suggest that EGCG induced A549 lung cancer cell apoptosis in vivo, and had less toxic effects compared to classical anticancer drugs. EGCG may inhibit the surrogate markers of proliferation and apoptosis (caspase 3) in A549 tumor xenografts in vivo. In addition, EGCG downregulated the expression of Bcl-xl and upregulated the expression of Bax mRNA and protein. Further experiments indicated that EGCG downregulated the protein expression of Ku70 and interrupted the binding of Ku70 and Bax. This is the first study demonstrating that the induction of apoptosis by EGCG may be caused by the downregulation of Ku70 and that EGCG disrupts the interaction between Ku70 and Bax in lung cancer.