The loss-of-function of DNA methyltransferase 1 by siRNA impairs the growth of non-small cell lung cancer with alleviated side effects via reactivation of RASSF1A and APC in vitro and vivo.

Hypermethylation of tumor suppressor genes (TSGs) promoters by DNA methyltransferase (DNMT) can be observed in almost all cancers which represent a hallmark of carcinogenesis, including lung cancer. DNMT inhibitors (e.g.5-Aza-CR/CdR) reactivate TSGs to exert anti-cancer activity and have been applied into the clinical. However, it is cytotoxic even at low concentrations, which might be not directly related to DNA methylation. We here investigated an alternative strategy in the lung cancer therapy and aimed to estimate and compare its efficiency and side effects of knockdown of DNMT1 in vitro and in vivo. Lung cancer tissues (n=20) showed enhanced expression of DNMT1 than corresponding non-neoplastic tissues. Similar results were found in lung cancer cell lines A549 and H538. The treatment of 5-Aza-CR or knockdown of DNMT1 in vitro could inhibit the expressions of DNMT1 but restore the TSGs expressions including the Ras association domain family 1A (RASSF1A) and the adenomatous polyposis coli (APC) via the demethylation of its promoter region, which results in the decreased proliferation, increased apoptosis and impaired ability of migration. Importantly, knockdown of DNMT1 by siRNA in vivo also effectively demethylated the RASSF1A and APC promoter, elevated their expressions and limited tumor growth, which functioned like 5-Aza-CR but with alleviated side effects, suggesting that knockdown of DNMT1 might be potential strategy for the treatment of lung cancer with better tolerability.

Activation of the HMGB1­TLR4­NF­κB pathway may occur in patients with atopic eczema.

High mobility group protein B1 (HMGB1) has been reported to serve important roles in various pathological conditions. Toll­like receptor 4 (TLR4), as one of the HMGB1 receptors, has been reported to be involved in the development of certain inflammatory diseases by activating nuclear factor NF­κ­B (NF­κB). However, there are few studies investigating the effects of HMGB1, TLR4 and NF­κB on human inflammatory dermatoses. In the present study, the distribution and characteristics of HMGB1, TLR4 and NF­κB p65 expression in psoriasis and atopic eczema (AE) were investigated. In addition, immunohistochemical analysis was performed to evaluate their expression and distribution in normal skin, and in patients with AE or psoria-sis. Spearman's correlation analysis was used to predicate their relevancy. The present study identified that the p65 level in epithelial nuclei in AE skin was increased compared with normal and psoriasis skin (P<0.01). The level of extracellular HMGB1 in AE skin was also increased compared with normal and psoriasis skin (P<0.01). Meanwhile, TLR4 expression on the epithelial membranes of AE skin was increased compared with psoriasis skin (P<0.01). Furthermore, the level of extracellular HMGB1 was positively correlated with epithelial membrane TLR4 (r=0.3856; P<0.05) and epithelial nuclear p65 (r=0.5894; P<0.01) in AE skin. These results indicated that the HMGB1­TLR4­NF­κB signaling pathway is activated in AE and may account for its pathogenesis, but not in psoriasis. Therefore, HMGB1, TLR4 and NF­κB p65 have the potential to be targets for the treatment of human inflammatory dermatoses, including AE.

Upregulation of colonic and hepatic tumor overexpressed gene is significantly associated with the unfavorable prognosis marker of human hepatocellular carcinoma.

Colonic hepatic tumor overexpressed gene (ch-TOG), a member of the highly conserved XMAP215 family of microtubule-associated proteins (MAPs), plays a crucial role in bipolar mitotic spindle assembly. Here, we performed proof-of-principle studies targeting ch-TOG for the development of HCC and further compared its prognostic significance with the clinicopathologic features of HCC. Quantitative real-time PCR was used to measure the expression level of ch-TOG mRNA in 207 cases of paired HCC and adjacent noncancerous liver tissues (ANLT). Additionally, immunohistochemistry was employed to identify ch-TOG protein in 71 HCC tissues. All HCC patients were divided into two groups according to the expression level of ch-TOG. Cumulative progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method, and the prognostic value of ch-TOG was further evaluated using the Cox proportional hazards regression model. Our studies suggested that ch-TOG is overexpressed in HCC tissues compared with ANLT. The ch-TOG level was correlated with other prognostic factors, including the hepatitis B surface antigen (HBsAg) (p = 0.030), median size (p = 0.008), clinical tumor-node-metastasis (TNM) stage (p = 0.002), and alpha-fetoprotein (AFP) level (p = 0.030). Kaplan-Meier survival analysis showed that increased ch-TOG was associated with reduced PFS (p = 0.002) and OS (p = 0.004). Multivariate Cox proportional hazards analysis identified ch-TOG as an independent prognostic factor for the PFS (hazard ratio [HR] = 1.479, 95% confidence interval [CI] = 1.028-2.127, p = 0.035) and OS (HR = 1.609, 95% CI = 1.114-2.325, p = 0.011) of the HCC patients. Increased ch-TOG represents a powerful marker for predicting poorer prognosis in the clinical management of HCC, and may serve as a potential molecular target for HCC therapies in the future.

Rabbit model of radiation-induced lung injury.

OBJECTIVE: To explore the feasibility of establishing an animal model of chronic radiation-induced lung injury. METHODS: Twenty-eight New Zealand white rabbits were randomly divided into 3 groups (the right lung irradiation group, the whole lung irradiation group and the control group). Animal model of radiation-induced lung injury was established by high-does radiotherapy in the irradiation groups, then all rabbits underwent CT and pathological examinations at 1, 2, 4, 8, 12, 16 weeks, respectively after radiation. RESULTS: Within 4 weeks of irradiation, some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis. At 8-12 weeks after irradiation, CT scanning showed ground glass samples signs, patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. CONCLUSIONS: The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

[Surgical treatment of primary malignant tumors of the trachea and main bronchus].

OBJECTIVE: To explore the clinical experience of surgical treatment of primary malignant tumors of the trachea and main bronchus. METHODS: The clinicopathological data of 18 patients with primary malignant tumors of the trachea and main bronchus surgically treated from February 1994 to August 2007 were reviewed retrospectively. The surgical management included sleeve tracheal resection in 8 cases, lower trachea and carina resection with carina reconstruction in 4 cases, local enucleation of the tumor in 4 cases, left or right carino-pneumonectomy and carina reconstruction in 2 cases, and resection of the tracheal or bronchial tumor and reconstruction of the airway under cardiopulmonary bypass in 6 cases. RESULTS: Among the 18 cases, there were 7 adenoid cystic carcinomas, 9 squamous cell carcinomas, 1 lymphoepithelial-like carcinoma and 1 follicular non-Hodgkin lymphoma. All the cases recovered well except one who died of endotracheal bleeding and asphyxia at the 10(th) postoperative day. CONCLUSION: Surgical resection is the most effective treatment for primary malignant tumors of the trachea and main bronchus. The selection of operation modes should be individualized according to patients' condition. Both complete resection and safety should be taken into consideration simultaneously.

[Perioperative management for primary tracheal malignant tumors resected under cardiopulmonary bypass].

OBJECTIVE: To retrospectively review the perioperative management for primary tracheal malignant tumors resected under cardiopulmonary bypass. METHODS: The data of 6 patients with primary tracheal malignant tumors who underwent surgery under cardiopulmonary bypass from December 1999 to August 2003 were reviewed. Cardiopulmonary bypass was established through right femoral vessels in 2 patients for emergency operation, through right atrium and ascending aorta in 4 patients. Sleeve tracheal resections in 3 patients, carinal resections and carina reconstructions in 2, and local enucleation in 1 were performed. Respiratory airway was kept patent by coughing and expectorating sputum. RESULTS: All patients' dyspnea were relieved remarkably. The postoperative mechanic ventilation assistance lasted from 10 hours to 7 days. There was no perioperative mortality. CONCLUSION: Resection of primary tracheal malignant tumors with severe tracheal obstruction under cardiopulmonary bypass is practicable. Keeping respiratory airway patent perioperatively is very important and helpful to postoperative recovery.

[Experimental study of myocardial protective effect of cardiac arrest versus beating heart during open heart surgery].

OBJECTIVE: To investigate the myocardial protective effects of beating heart versus heart arrest in goats undergoing open heart surgery with cardiopulmonary bypass (CPB). METHODS: Eighteen healthy and homologous goats were randomly divided into three groups: groupI (n=6), with intermittent cold crystalloid cardioplegia; group II (n=6), with continuous warm blood cardioplegia; group III (n=6), with beating heart. Animals in group II and group III were operated with mild hypothermic CPB. The changes in malondialdehyde (MDA) in the myocardium of the right ventricles and atrial natriuretic peptide (ANP) in venous blood were measured respectively. The myocardial tissues were examined for ultrastructural changes. RESULTS: In group I, contents of MDA and ANP rose significantly during CPB, especially when blood was reperfused routinely. While in group II and group III, the levels were lower than those in group I at the same time points. There was no difference in the values between group II and group III. Ultrastructural changes were distinctly seen in group I, while they were mild in group II and group III. CONCLUSION: Continuous warm blood cardioplegia to keep the heart beating during operation can prevent ischemia-reperfusion injury and protect heart better.