Expression and localization of the MMP inhibitor RECK in a rat model of COPD: its involvement in the development of COPD.

OBJECTIVE: To unravel the potential function of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as the matrix metalloproteinase (MMP) inhibitor in the development of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Twelve specific pathogen-free Sprague Dawley rats were randomly assigned to the control cohort (n = 6) or the COPD cohort (n = 6). COPD model was developed by tobacco smoke exposure. Functional residual capacity (FRC), static lung compliance (Cchord), ratio of forced expiratory volume in 0.1 s to forced vital capacity (FEV0.1/FVC), and peak expiratory flow (PEF) were detected by respiratory function tests. Immunohistochemistry was performed to determine the pathological changes as well as the expression and localization of RECK in pulmonary tissue. RECK expression was further quantified by real-time polymerase chain reaction (PCR) and Western blot assays. RESULTS: COPD rats had significantly reduced FEV0.1/FVC% and PEF values but increased FRC and Cchord levels, as compared to the control cohort (p < 0.05). Hematoxylin and eosin (HE) staining indicated typical COPD pathological changes, including leukocyte infiltration, airway thickening, alveoli fusion, etc., in the COPD rats. IHC indicated reduced expression of RECK in the COPD cohort, which was mainly expressed on the epithelium and partly expressed on subepithelial cells and inflammatory cells. Real-time PCR and Western blot assays further revealed the significantly lower expression of RECK in lung tissue from the COPD cohort. CONCLUSIONS: RECK is mainly expressed on airway epithelial cells. COPD rats expressed significantly lower RECK levels, indicating that RECK exhibits a protective function in the development of COPD.

Continued EGFR-TKIs treatment promotes the survival of elderly patients with acquired resistance to EGFR-TKIs therapy.

OBJECTIVE: Continued EGFR-TKIs treatment is still controversial for NSCLC patients with activating EGFR mutations, who acquire resistance to the drug. Of these patients, elderly ones were worth to be investigated to further examine efficacy of continued EGFR-TKIs treatment. PATIENTS AND METHODS: A total of 232 NSCLC patients (≥ 70-year-old) were recruited from the Chinese People's Liberation Army General Hospital between January 1, 2009, and July 31, 2014. And 44 patients were qualified for further retrospectively investigated, which were divided into dramatic and non-dramatic progression groups based on the characteristics of progression during first-line EGFR-TKIs treatment. And they were also divided into two groups: continued EGFR-TKIs group and discontinued EGFR-TKIs group. Subsequently, progression-free survival (PFS), post-progression survival (PPS), and overall survival (OS) of these groups were investigated by multivariate analysis. RESULTS: Median OS (28.9 months vs. 23.2 months, p = 0.46) and median PPS (16.9 months vs. 4.4 months, p = 0.216) were both not significantly different between continued EGFR-TKIs groups and discontinued ones. However, when focusing on patients with non-dramatic progression, the median OS (29.0 months vs. 23.2 months, p = 0.039) and median PPS (21.3 months vs. 3.9 months, p = 0.001) were significantly longer in the continued EGFR-TKIs patients than discontinued ones. DISCUSSION: Continued EGFR-TKIs beyond PD may be a good option for elderly patients with non-dramatic progression. The characteristic of progression after first-line EGFR-TKIs treatment should be taken into account to determine which part of patients is suitable for continued EGFR-TKIs treatment, especially for the speed of progression. CONCLUSION: Continued EGFR-TKIs treatment promotes the survival of elderly patients with acquired resistance to EGFR-TKIs therapy.

Propofol suppresses invasion and induces apoptosis of osteosarcoma cell in vitro via downregulation of TGF-ß1 expression.

OBJECTIVE: Osteosarcoma (OS) is the most common malignant tumor of the bone, with a high mortality rate and poor prognosis. Propofol has been proposed to play a role of antitumor in various cancers. However, the functions and mechanisms of propofol in OS is still not clear. MATERIALS AND METHODS: The different concentrations of propofol were co-incubated with osteosarcoma MG-63 lines for 72 hrs. Cell proliferation, apoptosis, and invasion were detected by MTT assay, Flow cytometry analysis, and Matrigel invasion assay. Western blot was used to detect the TGF-ß1 protein levels. MG-63 cells were treated with human recombinant TGF-ß1 (rh TGF-ß1) to assess the role of TGF-ß1 in propofol-induced anti-tumor activity. RESULTS: Propofol significantly inhibited cell proliferation and invasion and promoted apoptosis of MG-63 lines cells. Propofol also efficiently reduced TGF-ß1 expression. Moreover, restoration of TGF-ß1 by rhTGF-ß1 treatment reversed the effects of propofol on the biological behavior of OS cells. CONCLUSIONS: Propofol can effectively inhibit proliferation and invasion and induce apoptosis of OS cells through, at least partly, downregulation of TGF-ß1 expression.

Propofol suppresses invasion, angiogenesis and survival of EC-1 cells in vitro by regulation of S100A4 expression.

OBJECTIVE: Propofol possess anticancer properties in several cancers. In the present study, we investigate the effect of propofol on the human esophageal squamous cell carcinomas (ESCC) EC-1 cells in vitro and its molecular mechanisms of action. MATERIALS AND METHODS: EC-1 cells were explored to 10-100 µmol/L propofol for 72 h or 100 µmol/L/mL propofol for 24-72 h. EC-1 cells were explored to 100 µmol/L propofol for 24 h, then was transiently transfected into PcDNA3.1-S100A4 cDNA or PcDNA3.1 plasmid for 48 hrs. MTT, TUNEL, ELISA, migration, tube formation and immunoblotting were analized. RESULTS: Propofol inhibits invasion, angiogenesis, proliferation and induces apoptosis in a dose and time-dependence manner, followed by deseased S100A4 expression by Western blot assay. Pre-transfection of PcDNA3.1-S100A4 cDNA inhibits propofol-induced apoptosis and promotes invasion and angiogenesis in EC-1 cells in vitro. CONCLUSIONS: Propofol inhibited invasion, angiogenesis and induces apoptosis of human EC-1 cells in vitro through regulation of S100A4 expression. It not only can be an anesthesia agent, but also plays a important role of inhibiting the migration and angiogenesis of ESCC cells in the therapy of ESCC patients.

Anatomical information for intercostobrachial nerve preservation in axillary lymph node dissection for breast cancer.

This study aimed to provide additional anatomical information for axillary lymph node dissection (ALND) through in vivo anatomy studies of intercostobrachial nerve (ICBN) preservation in order to provide theoretical and practical experience for clinicians. A total of 156 patients with breast cancer underwent ALND at the Department of Gynecology of Baotou Tumor Hospital between June 2009 and March 2010. The origin, destination, main source, length, branch type, and direction of ICBN in axilla were observed, as well as its relationship with adjacent major blood vessels and nerves within the axilla. There were 120 cases of single trunk, 23 cases of double trunks, 9 cases of multiple trunks, and 4 cases without trunks in 156 patients with ICBN preservation. The transverse diameter at the origin of the ICBN was 1.89 ± 0.44 mm with a length of 94.45 ± 12.08 mm; the distances were 77.19 ± 21.04 mm, 29.34 ± 6.73 mm, 90.04 ± 13.13 mm, and 28.63 ± 13.01 mm from origin to the inferior margin at the midpoint of the clavicle, inferior margin of the axillary vein, the bottom of axilla, and branch point, respectively. The identification, dissection, and preservation of ICBN was simple and easy in a modified radical mastectomy for breast cancer and breast-conserving surgery, which only took 10-20 min, but effectively reduced the incidence of post-mastectomy pain syndrome and significantly improved the quality of life for patients after surgery.

Overweight, obesity and thyroid cancer risk: a meta-analysis of cohort studies.

OBJECTIVE: This meta-analysis examined the relationship between excess body weight or body mass index (BMI) and risk of thyroid cancer. METHODS: PubMed(®), MEDLINE(®), EMBASE™ and Academic Search™ Premier databases were searched to identify cohort studies examining the effect of being overweight or obese on the risk of thyroid cancer. RESULTS: The inclusion criteria were met by seven cohort studies (total number of thyroid cancer cases, 5154). The pooled relative risk (RR) of thyroid cancer was 1.13 (95% confidence interval [CI] 1.04, 1.22) for overweight. Obesity was also linked with increased thyroid cancer risk in males and females, the strength of the association increasing with increasing BMI. The combined RR of thyroid cancer was 1.18 (95% CI 1.11, 1.25) for excess body weight (overweight and obesity combined). Being overweight was associated with a significant increase in thyroid cancer risk among non-Asians, but not among Asians. Overweight, obesity and excess body weight were all associated with papillary thyroid carcinoma risk. CONCLUSIONS: The association between overweight/obesity/excess body weight and thyroid cancer risk was confirmed.

Epidemiological prediction of the distribution of insects of medical significance: comparative distributions of fleas and sucking lice on the rat host Rattus norvegicus in Yunnan Province, China.

Determining the distribution patterns of ectoparasites is important for predicting the spread of vector-borne diseases. A simple epidemiological model was used to compare the distributions of two different taxa of ectoparasitic insects, sucking lice (Insecta: Siphonaptera) and fleas (Insecta: Anoplura), on the same rodent host, Rattus norvegicus Berkenhout (Rodentia: Muridae), in Yunnan Province, China. Correlations between mean abundance and prevalence were determined. Both fleas and sucking lice were aggregated on their hosts, and sucking lice showed a higher degree of aggregation than fleas. The prevalence of both fleas and sucking lice increased with log-transformed mean abundance and a highly linear correlation and modelling efficiency of predicted prevalence against observed prevalence were obtained. The results demonstrate that prevalence can be explained simply by mean abundance.

Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms.

BACKGROUND AND PURPOSE: Recent studies have shown that resveratrol increased endothelial progenitor cells (EPCs) numbers and functional activity. However, the mechanisms remain to be determined. Previous studies have demonstrated that increased EPC numbers and activity were associated with the inhibition of EPC senescence, which involves activation of telomerase. Therefore, we investigated whether resveratrol inhibits the onset of EPC senescence through telomerase activation, leading to potentiation of cellular activity. EXPERIMENTAL APPROACH: After prolonged in vitro cultivation, EPCs were incubated with or without resveratrol. The senescence of EPCs were determined by acidic beta-galactosidase staining. The bromo-deoxyuridine incorporation assay or a modified Boyden chamber assay were employed to assess proliferative or migratory capacity, respectively. To further examine the underlying mechanisms of these effects, we measured telomerase activity and the phosphorylation of Akt by western blotting. KEY RESULTS: Resveratrol dose dependently prevented the onset of EPCs senescence and increased the proliferation and migration of EPCs. The effect of resveratrol on senescence could not be abolished by eNOS inhibitor or by an oestrogenic receptor antagonist. Resveratrol significantly increased telomerase activity and Akt phosphorylation. Pre-treatment with the PI3K inhibitor, LY294002, significantly attenuated resveratrol-induced telomerase activity. CONCLUSIONS AND IMPLICATIONS: Resveratrol delayed the onset of EPC senescence and this effect was accompanied by activation of telomerase through the PI3K-Akt signalling pathway. The inhibition of EPCs senescence by resveratrol might protect EPCs against dysfunction induced by pathological factors in vivo and improve EPC functional activities in a way that may be important for cell therapy.

High frequency occurrence of 1-OPRD variant of PRNP gene in gastric cancer cell lines and Chinese population with gastric cancer.

The prion protein gene PRNP encodes PrPc and PrPsc, causing a number of neurological disorders. Approximately 10-15% of human prion disease is inherited and more than 20 pathogenic mutations have been found. Most of the genetic alterations are point mutations, with the exception of genetic insertions of one to nine extra octapeptide repeats occurring in the important octapeptide-coding region. Our previous work showed that PrPc was overexpressed in gastric cancer. We wondered whether mutations of PrPc existed in human gastric cancer. DNA sequencing and gel electrophoresis were used to determine the possible mutation of PrPc in patients and cell lines of gastric cancer. We found that 1-OPRD (one octapeptide-repeat deletion) homozygosity or heterozygosity exists in several gastric cancer cell lines, e.g. MKN28 and KatoIII are homozygous for 1-OPRD, and SGC7901 and BGC-823 are heterozygous for 1-OPRD. The mutation frequency in tissues of gastric cancer cases is significantly higher than that in the common population (p<0.05). All positive cases in gastric cancer were found to be heterozygous for 1-OPRD. Further study of the variant may be helpful in understanding the mechanisms of occurrence and development of clinical gastric carcinoma as well as the biology of the mysterious gene PRNP.

Single-stage laryngotracheal reconstruction: the Great Ormond Street experience and guidelines for patient selection.

OBJECTIVES: To review all patients undergoing single-stage laryngotracheal reconstruction and to determine guidelines to predict successful outcomes and prevent the necessity of tracheotomy following laryngotracheal reconstruction. DESIGN: Chart review. SETTING: Tertiary care children's hospital. PATIENTS: A retrospective chart review was performed at our institution involving all patients who underwent single-stage laryngotracheal reconstruction from 1993 through 1996. A total of 28 patients were reviewed. RESULTS: Based on this chart review, a statistically higher incidence of extubation complications (P = .045), ie, bleeding, reintubation, or subcutaneous emphysema, occurred in children who weighed less than 4 kg. Although not statistically significant (P>.99), the relative risks of failure, defined as tracheotomy dependent or significant airway compromise following single-stage laryngotracheal reconstruction, were 3.43 if the child's weight was less than 4 kg at the time of surgery and 2.31 if the gestational age was less than 30 weeks at the time of surgery. Length of time for intubation did not appear to have any effect on outcome. CONCLUSIONS: Patients' gestational age and weight at the time of surgery appear to have the most impact on successful outcome. Children weighing more than 4 kg and those with gestational age of greater than 30 weeks appear to have a greater chance at successful extubation and eventual patent airway. Duration of intubation following single-stage laryngotracheal reconstruction does not appear to affect outcome.